Scientific Program

Lecture Summaries
FULL TEXT CONGRESS BOOK Oral Presentations
Poster Presentations
1
 11 March Thursday 12 March Friday 13 March Saturday 14 March Sunday
09:00-09:15 OPENING SPEECH & LECTURE 09:00-09:50 INFECTIVE SKIN DISEASES 09:00-10:10 DERMATOSCOPY SESSION-2 09:00-10:40 SESSION:
ADVANCED TECHNOLOGIES IN
DERMATOLOGY
09:30-11:10 ERCIN OZUNTURK SESSION 10:05-11:45 INVESTIGATIVE DERMATOLOGY-2 10:25-10:45 TRICHOSCOPY COURSE 10:55-12:25 SESSION: GENERAL
(AESTHETIC DERMATOLOGY)-1 DERMATOLOGY 3
11:25-12:45 INVESTIGATIVE DERMATOLOGY-1 12:00-13:00 DEBATABLE TOPICS FOR 11:00-12:00 SESSION: ORPHAN DISEASES IN 12:25-12:55 LUNCH
DERMATOLOGIC THERAPY DERMATOLOGY
12:45-13:15 LUNCH 13:00-13:30 LUNCH 12:15-12:45 LUNCH 12:55-14:05 INVESTIGATIVE DERMATOLOGY-3

13:15-14:25 DERMATOSCOPY SESSION-1 13:30-14:50 SESSION: SYSTEMIC TREATMENT 12:45-14:15 TOPICAL TREATMENT IN 14:20-15:30 DIET AND ALTERNATIVE
IN DERMATOLOGY-1 DERMATOLOGY THERAPY FOR DERMATOLOGIST
14:40-15:40 SATELLITE 15:05-16:05 SATELLITE 14:30-15:30 SATELLITE 15:35-16:35 BREAK
Pfizer PFE İlaçları
15:55-17:35 ERCIN OZUNTURK SESSION 16:20-17:50 ERCIN OZUNTURK SESSION 15:45-16:25 NAIL SURGERY SESSION 16:40-17:20 PSORIASIS
(AESTHETIC DERMATOLOGY)-2 (AESTHETIC DERMATOLOGY)-3
17:50-18:40 SESSION: SUN, LIGHT, VITAMIN D 18:05-19:05 SESSION: ALLERGY AND 16:40-17:40 PSORIASIS 17:35-18:35 SESSION: PSYCHODERMATOLOGY
AND THE SKIN PRURITUS-1
18:55-19:25 ATOPIC DERMATITIS 19:20-20:00 DERMATOLOGIC SURGERY 17:55-18:35 SESSION: UCARE 18:50-19:50 HOW CAN WE TREAT
SESSION CHALLENGE CASES? (4
DIFFICULT/CHALLENGE CASES)

19:40-21:10 SESSION: PIGMENTATION 20:15-21:25 POPULAR 18:50-19:50 SEBACEOUS GLAND DISEASES: 20:05-20:45 HIGHLIGHTS OF THE CURRENT
DISORDERS AND SKIN CANCERS DEBATABLE ISSUES FOR TOPICAL ANTIBIOTIC GUIDE
DERMATOLOGIST
20:05-21:55 ERCIN OZUNTURK SESSION 20:45 CLOSING SPEECH AND LECTURE
(AESTHETIC DERMATOLOGY)-4 WHAT’S NEW IN VITILIGO 2020
 11 March Thursday
09:00 - 09:15 OPENING SPEECH & LECTURE
A new era in Integrative Dermatology / Katlein Franca
09:30 - 11:10 ERCIN OZUNTURK SESSION (AESTHETIC DERMATOLOGY)-1
Chairs: Pertevniyal Bodamyalı, Sadiye Kuş
Survivin in dermatology Elif Cömert
Exosoms in dermatology Sevda Önder
Microneedling combined procedures in aesthetic dermatology Mehmet Can Emeksiz
Inflamm-aging in skin: Update Sadiye Kuş
Liquid collagen: Where are we now for dermatology? Semahat Alp
Ceramides and skin Semahat Alp
Beta-carotene/Astaxanthin/CoenzymeQ10 and dermatology Seray Külcü Çakmak
Zinc/Selenium and skin Deniz Demirseren
Shock waves in aesthetic dermatology Pertevniyal Bodamyalı
HIFEM in aesthetic dermatology Pertevniyal Bodamyalı
11:25-12:45 INVESTIGATIVE DERMATOLOGY-1
Chairs: Özgür Gündüz, Habibullah Aktaş
Mitochondrial DNA and dermatology Özgür Gündüz
Aquaporins in dermatology Özgür Gündüz
Integrins / HIF1alpha / VEGF / PAI1 in dermatology Yasemin Yuyucu Karabulut
Cytokines and chemokines in dermatology Birgül Özkesici Kurt
Differences between B and T cells Seçil Vural
Nod2: The intestinal gate keeper in dermatology Büşra Altun Deniz
Transepidermal elimination in dermatology Gökşen Ertuğrul
Nobel Prize of Aziz Sancar and Dermatology Habibullah Aktaş
12:45-13:00 RATIONAL USES OF MEDICINE Özgür Gündüz
13:00-13:15 LUNCH
13:15-14:25 DERMATOSCOPY SESSION-1
Chairs: Mustafa Turhan Şahin, Fezal Özdemir
Inflamoscopy: Basics and beyond Paweł Pietkiewicz
Dermoscopy in acral lesions Fezal Özdemir
Facial pigmented lesions: Make it simple! Ömer Faruk Elmas
Dermoscopy in melanoma: What’s new? Tuğba Kevser Uzunçakmak
Mucoscopy: What we know ? Mustafa Turhan Şahin
Dermoscopy in adnexal lesions Aylin Türel Ermertcan
Onychoscopy in non-pigmented nail lesions Herman Mayısoğlu

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 11 March Thursday
14:40-15:40 SATELLITE SYMPOSIUM
How AWARE are we about chronic urticaria treatment?
Moderators: Emek Kocatürk, Kemal Özyurt

24-month outcomes from the multicenter observational study AWARE Marcus Maurer
Real world outcomes with omalizumab treatment in CSU from Turkey Nida Kaçar
15:55-17:35 ERCIN OZUNTURK SESSION (AESTHETIC DERMATOLOGY)-2
Chairs: Gaye Sarıkan, Filiz Kuşak
Face shapes and cosmetical approaches Gökçe Işıl Kurmuş
Off-label uses of HA fillers in aesthetic dermatology Hilal Gökalp
Ageism in aesthetic dermatology Ayşe Ferzan Aytuğ
Diet and aesthetic dermatology Gaye Sarıkan
BDDA: Myths and facts in aesthetic dermatology Pelin Üstüner
Botulinum toxins for nasel area problems Filiz Kuşak
The skin aging exposome Selda Pelin Kartal
Epidemiology of cosmetic procedures in dermatology Selda Pelin Kartal
A Holistic approach to skin aging Şükran Sarıgül Güdük
Periorbital hyperpigmentation: Etiology, medical evaluation and Filiz Kuşak
treatment
17:50-18:40 SESSION: SUN, LIGHT, VITAMIN D AND THE SKIN
Chairs: Işıl İnanır, Mustafa Tunca
Sunscreens: What’s new? Işıl Bulur
Do sunscreens prevent vitamin D sythesis? Armağan Kutlay
New vitamin D analogues in dermatology Mustafa Tunca
Does phototherapy cause cancer? Algün Polat Ekinci
What’s new in phototherapy? Işıl İnanır
Discussion
18:55-19:25 ATOPIC DERMATITIS
Chairs: Marcus Maurer, Kemal Özyurt
Type II inflammation and its role in atopic dermatitis and beyond Marcus Maurer
Emerging treatments of atopic dermatitis Torsten Zuberbier
The role of allergens in atopic dermatitis Maryam Khoshkhui
19:40-21:10 SESSION: PIGMENTATION DISORDERS AND SKIN CANCERS
Chairs: Rafet Koca, Emine Çölgeçen
Integrative approaches of vitiligo Abdullah Demirbaş
Integrative approaches of melasma Emel Hazinedar
Integrative approaches of skin cancers Mahmut Sami Metin
Lipoma: Causes, symptoms, diagnosis and treatment Gözde Emel Gökçek
Piezogenic pedal papules: Etiology and treatment Emine Müge Acar
Xanthelasma: What is new? Gözde Emel Gökçek
Bowen disease: Update Aslı Şahin
Novel modalities in keloid and hypertrophic scars Pelin Ertop Doğan
Discussion
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 12 March Friday
09:00-09:50 INFECTIVE SKIN DISEASES
Chairs: Bengü Gerçeker Türk, Belkız Uyar
COVID-19 and skin Bengü Gerçeker Türk
COVID-19 and urticaria Emek Kocatürk
Molluscum contagiosum: What’s new? Ayşin Köktürk
Integrative approaches of superficial fungal infections Belkız Uyar
Discussion
10:05-11:45 INVESTIGATIVE DERMATOLOGY-2
Chairs: Ömer Kutlu, Betül Şereflican
Mechanoreceptors in dermatology: An overview Emin Gündüz
Skin aging and epigenetics (Anti-aging genes)/SIRT1: As antiaging Emin Gündüz
Cellular oxygen sensor systems in skin Begüm Ünlü
Follistatin/activin a and skin/hair Begüm Ünlü
Biological rhythms in the skin Pelin Ertop Doğan
Human 3D skin models Neslihan Fişek İzci
ELISA in dermatology Betül Şereflican
Free fatty acids in dermatology Hülya Süslü
TGF-beta and Dermatology Ömer Kutlu
CCR-5 in dermatology Ömer Kutlu
12:00-13:00 DEBATABLE TOPICS FOR DERMATOLOGIC THERAPY
Chair: Arzu Kılıç
How long should biologics treatments be used? Zeynep Topkarcı
Do biologics cause cancer? Nida Kaçar
Whats the new approach for antifungal therapy? Arzu Kılıç
If superbugs are monster, how can we prevent them when using
Melek Aslan Kayıran
antibiotics?
Discussion
13:00-13:30 LUNCH
13:30-14:50 SESSION: SYSTEMIC TREATMENT IN DERMATOLOGY-1
Chairs: Özlem Su Küçük, Didem Didar Balcı
Postmodern treatments in dermatology Tuğba Özkök Akbulut
Does metformin really works in dermatology? Asude Kara Polat
Adaptive immunotherapy in dermatology Sibel Doğan
Immun checkpoint inhibitors and dermatology Didem Didar Balcı
EGFR inhibitors and skin Sezgi Sarıkaya Solak
Dupilumab in dermatology: Indications and adverse events Özlem Su Küçük
Discussion

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 12 March Friday
15:05-16:05 SATELLITE SYMPOSIUM Pfizer PFE İlaçları
A Comprehensive Approach to Superficial Fungal Infections İlteriş Oğuz Topal

16:20-17:50 ERCIN OZUNTURK SESSION (AESTHETIC DERMATOLOGY)-3

Chairs: Zehra Aşiran Serdar, Berna Aksoy
Periorbital wrinkles: Etiology and treatment Zehra Aşiran Serdar
Acoustic waves in aesthetic dermatology Zahide Eriş
Low-level laser treatment in dermatology Zahide Eriş
Cryolipolysis: What is new? Hasan Mete Aksoy
Smoking and skin aging Berna Aksoy
Endermologie in aesthetic dermatology Hasan Mete Aksoy
Alpha-and beta-hydroxy acids in dermatology Aslı Tatlıparmak
Fractional photothermolysis in aesthetic dermatology Filiz Canpolat
Hyaluronon and skin Filiz Canpolat
18:05-19:05 SESSION: ALLERGY AND PRURITUS-1
Chairs: Ümit Şahiner, Oktay Taşkapan
Nocturnal pruritus in children Ümit Şahiner
Nocturnal pruritus in elder Oktay Taşkapan
Integrative approaches of pruritus Zafer Türkoğlu
Integrative approaches of urticaria and drug allergy Murat Türk
Integrative approaches of atopy Murat Türk
Discussion
19:20-20:00 DERMATOLOGIC SURGERY SESSION
Chairs: Emel Fetil, Amor Khachemoune
Skin biopsy techniques Tamer İrfan Kaya
Advanced surgical suturation techniques in dermatological surgery Eckart Haneke
Basics of flaps and grafts in dermatological surgery Amor Khachemoune
Cryosurgery and electrosurgery: Widen your horizon Tuğrul Dereli
20:15-21:25 POPULAR
Chairs: Emel Erdal, Meltem Önder
Physician burnout and mental stress in pandemia Emel Erdal
Panel or manel/sex discrimination in dermatology congress Meltem Önder
Predatory publishing and congress in dermatology Vildan Manav
Myths and facts in dermatology Müge Göre Karaali
Pioneers in dermatology Mahmut Can Koska
Financial toxicity in dermatology Gonca Saraç
Discussion

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 13 March Saturday
09:00-10:10 DERMATOSCOPY SESSION-2
Chairs: Şirin Yaşar, Ercan Arca
Dermoscopy in non-melanoma skin cancers: What’s new? Ercan Arca
Black, red and green: Siascopy Ahmet Metin
Dermoscopy: widen your horizon! Cüneyt Soyal
Dermoscopy: A game changer in management of multiple nevi Gamze Erfan
Onychoscopy in pigmented nail lesions Şirin Yaşar
Dermoscopy in infectious skin diseases Ersoy Acer
Discussion
10:25-10:45 TRICHOSCOPY COURSE
Chairs: Ömer Faruk Elmas, Haitham Donia
Trichoscpy of patchy alopecia (clues & algorithms) Haitham Donia
11:00-12:00 SESSION: ORPHAN DISEASES IN DERMATOLOGY
Chairs: Deniz Yücelten, Aslı Kaptanoğlu
Syndromes associated with palmoplantar keratoderma Deniz Yücelten
Syndromes associated with ichthyosis Deniz Akkaya
Orphan drugs in dermatology Nazan Emiroğlu
Orphan tests and diagnostic approaches in dermatology Aslı Kaptanoğlu
Syndromes associated with hair and nail problems Aslı Bilgiç
Discussion
12:15-12:45 LUNCH
12:45-14:15 SESSION: TOPICAL TREATMENT IN DERMATOLOGY
Chairs: Aslı Hapa, Göknur Kalkan
Topical “jump start” therapies in dermatology Pelin Eşme
Are they immortality formulas: Resveratrol and rapamycin Şule Güngör
Hypericin-the facts about a controversial agent Gülşen Tükenmez Demirci
Topical brimonidine in dermatology Burçe Can
Vinegar in dermatology İlteriş Oğuz Topal
5-FU in dermatology Esra Ağaoğlu
Topical timolol and nifedipine in dermatology Hasan Aksoy
Topical JAK inhibitors and skin Aslı Hapa
Discussion
14:30-15:30 SATELLITE SYMPOSIUM
Görüneniṅ Ötesindeki
̇ ̇ Güçlü Seçenek Beksar JEL
Moderator: Dilek Bayramgürler
İlkin Zindancı
Dilek Bayramgürler
15:45-16:25 NAIL SURGERY SESSION
Chairs: Eckart Haneke, Necmettin Akdeniz
Ingrown nail: Non-surgical approach Gülru Erdoğan
Ingrown nail: Surgical approach Necmettin Akdeniz
Biopsy in nail disorders: When and how? Fatih Göktay
Surgical principles in nail unit tumors Eckart Haneke
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 13 March Saturday
16:40-17:40 PSORIASIS-1
Chairs: Sibel Alper, Tomasz Hawro
Psoriasis and itch Tomasz Hawro
Stigmatization in patients with psoriasis Tomasz Hawro
Social and psychological impacts of psoriasis Sibel Alper
Psoriasis and alopecia Filiz Topaloğlu Demir
Nail-lacquers in dermatology Mahmut Sami Metin
Discussion
17:55-18:35 SESSION: UCARE
Chairs: Luis Felipe Ensina, Kemal Özyurt
Emerging therapies in urticaria: What’s new? Emek Kocatürk
Urticaria and comorbidities: What's new? Luis Felipe Ensina
Biologic markers in urticaria: What’s new? Andaç Salman
Following the latest guideline in 2021: What’s new? Ragıp Ertaş
18:50-19:50 SEBACEOUS GLAND DISEASES: DEBATABLE ISSUES FOR DERMATOLOGIST
Chairs: Bodo Melnik, Ayşe Serap Karadağ
Which came first? The chicken or the egg?: The rosacea or the Seray Külcü Çakmak
demodex situation
Which is better for HS: The surgery or the medical treatment Algün Polat Ekinci
Is diet important for acne? Sezgi Sarıkaya Solak
What is discussed in 2021 on isotretinoin therapy Ayşe Serap Karadağ
The role of FoxO1-GATA6 signaling in acne pathogenesis and Bodo Melnik
treatment
Discussion
20:05-21:55 ERCIN OZUNTURK SESSION (AESTHETIC DERMATOLOGY)-4
Chairs: Ahu Birol, Ömür Tekeli
Laser, HIFU and RF treatments in hyperhidrosis Ahu Birol
Inflammatory skin diseases (psoriasis, acne and seborrhea) and
Melike Kibar Öztürk
botulinum toxins
Understanding the differences of emollient, moisturizer and
Melike Kibar Öztürk
humectant in dermatology
Picosecond lasers in dermatology Ömür Tekeli
Gummy smiles and treatment Hüray Hügül
Visual loss in aesthetic dermatology Hüray Hügül
Tears trough problems and fillers Hüray Hügül
Retaining ligamants of face in aesthetic dermatology Filiz Kuşak
Fat pads of face and aesthetic dermatology Zekai Kutlubay
Can we analyse skin aging by blood markers? Mehmet Melikoğlu
Blepharoplasty for dermatologist Alp Kayıran

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 14 March Sunday
09:00-10:40 SESSION: ADVANCED TECHNOLOGIES IN DERMATOLOGY
Chairs: Tamer İrfan Kaya, Emin Özlü
Simulation models in dermatology education Emin Özlü
eHealth technologies in dermatology Duygu Erdil
Best dermatology software Ozan Erdem
Industry 4.0/5.0 and dermatology Cahit Yavuz
Flow-cytometry in dermatology Emine Müge Acar
Blue light and skin health Cahit Yavuz
Elastography in dermatology İlkin Zindancı
Continuous-wave laser hyperthermia in dermatology
Abdullah Demirbaş
(thermotherapy)
Thermography in dermatology Ozan Erdem
Confocal, USG, imaging methods in dermatology Sümeyre Seda Ertekin
10:55-12:25 SESSION: GENERAL DERMATOLOGY-3
Chairs: Aylin Türel Ermertcan, Zennure Takcı
Colours in dermatology (white, black, brown, purple, yellow, green,
Aylin Türel Ermertcan
redness)
Diagnostic criteria in dermatology Ayşenur Botsalı
Hypo/hyper/absence (A)-conditions in dermatology Banu Taşkın
Red scrotum syndrome and male genital dysaesthesia Amr Abdelhamed
Jolly roger sign in dermatology Bachar Memet
Intestinal bacterial overgrowth in dermatology Amr Abdelhamed
Cutibacterium in dermatology Elif Cömert
Black box sigs for dermatologic therapies Zennure Takcı
Discussion
12:25-12:55 LUNCH
12:55-14:05 INVESTIGATIVE DERMATOLOGY-3
Chairs: Emel Bülbül Başkan, Kansu Büyükafşar
IGF in dermatology Ufuk Kavuzlu
Ghrelin in dermatology Ufuk Kavuzlu
Histopathologic features of aesthetic applications on rats Recep Dursun
Ultrastructural and histopathological changes after cosmetic
Özge Aşkın
procedures in humans
Microchimerism and skin diseases Ahmet Metin
MRGPRX-2 and allergy Kansu Büyükafşar
AI in dermatology Emel Bülbül Başkan

9
 14 March Sunday
14:20-15:30 DIET AND ALTERNATIVE THERAPY FOR DERMATOLOGIST
Chairs: Erdem Yeşilada, Hilal Kaya Erdoğan
Healing plants for skin diseases Erdem Yeşilada
Ketogenic diet in dermatology Emine Ünal
Do vitamins work for skin diseases? Hilal Kaya Erdoğan
Does pyhtotheraphy real or not for skin therapy? Hatice Kaya Özden
Discussion
15:35-16:35 BREAK

16:40-17:20 PSORIASIS-2
Chairs: Kemal Özyurt, Zafer Türkoğlu
When? & which one? Biologics for psoriasis Leon Kırcık
Management of difficult to treat psoriasis Omid Zargari
Integrative approaches of psoriasis and psoriatic arthritis Şule Ketenci Ertaş
Discussion
17:35-18:35 SESSION: PSYCHODERMATOLOGY
Chairs: İlknur Kıvanç Altunay, Mohamad Jafferany
How do we look at the skin and read the brain? Anthony Bewley
Management approach to psychocutaneous disorders Mohamad Jafferany
Tattoo and psychology Ezgi Özkur
How liyezon psychiatry works for dermatology? İlknur Kıvanç Altunay
Personality disorders in dermatology Mohamad Jafferany
Discussion
18:50-19:50 HOW CAN WE TREAT CHALLENGE CASES? (4 DIFFICULT/CHALLENGE CASES)
Chairs: Serap Öztürkcan, Ayşe Serap Karadağ
Bullous diseases Ayşe Akman
Psoriasis Ayşe Serap Karadağ
Skin cancer Fatma Pelin Cengiz
Vasculitis Sibel Doğan
Pruritus Esra Pancar Yüksel
Discussion
20:05-20:45 HIGHLIGHTS OF THE CURRENT TOPICAL ANTIBIOTIC GUIDE
Chairs: Ayşe Serap Karadağ, Ümit Türsen, Belma Türsen
In infection diseases Göknur Kalkan
In inflammatory diseases Andaç Salman
For cosmetologic and surgical and wounds Bengü Gerçeker Türk
Discussion
20:45 CLOSING SPEECH AND LECTURE WHAT’S NEW IN VITILIGO 2020
Chairs: Torello Lotti
10
 LECTURE
SUMMARIES

11
 SURVIVIN IN DERMATOLOGY
Elif Cömert-Özer
Marmara University Pendik Research Hospital, Istanbul, Turkey

Survivin is smallest member of the inhibitor of apoptosis (IAP) protein family. Survivin has antiapoptotic functions and
also regulates the cell cycle. Survivin is highly expressed in cancer cells, but it is expressed at a low level in normal adult
tissues, including skin. It is mostly located in the nucleus of keratinocyte stem cells (KSCs), but it is also expressed in
melanocytes and fibroblasts. Survivin has an important role in the regulation of cell cycle in keratinocytes, it protects
these cells from anoikis and UV-induced apoptosis and low levels of survivin might be necessary to preserve the regen-
erative potential of epidermal stem cells. In the skin, surviving has been implicated in several pathological conditions
such as psoriasis and tumors of melanocytic and epithelial origin. In both, melanocytic and epithelial skin tumors, sur-
vivin expression has further been associated with tumor aggression, decreased patient survival and metastasis.
Survivin is a small protein with multifunctional domains. Its N-terminal two-thirds comprise a globular baculovirus
inhibitor of apoptosis repeat (BIR) domain and it is defines survivin as an IAP. Although IAPs are generally considered
antiapoptotic proteins, survivin not only inhibits apoptosis but also regulates cell division. And also, unlike other IAPs
survivin is not able to inhibit apoptosis by directly binding to caspases. Under apoptotic stimuli involving mitochondria,
surviving forms a complex with X-linked inhibitor of apoptosis protein (XIAP), thus increasing the stability of XIAP
and its inhibitory activity against caspases. The gene encoding for survivin, named BIRC5 located on the long arm of
chromosome 17 (q25). BIRC5 encodes ten splice variants by alternative splicing, six with known function: wild-type
(WT)-survivin, survivin-2B, survivin-DEx3, survivin-3B, and survivin-2a, survivin-3a. It is not yet fully known how
these different variants are regulated and how they function in comparison with the WT-survivin. Survivin is the only
member of IAP family that can interact with the mitotic apparatus, by binding to microtubules, thus ensuring correct
cell division.
Survivin is expressed in normal human skin, and it is mostly localized in the few cells located in the basal layer of the
epidermis. It is thought that survivin is protecting the viability of epidermal stem cells. Various studies have confirmed
that survivin expression in a subpopulation of keratinocytes in the basal cell layer of normal human interfollicular epi-
dermis where stem cells reside. Survivin is markedly upregulated during UVB-induced keratinocyte cell cycle arrest
and protects human keratinocytes against UVB-induced apoptosis. Together, these data provide evidence that survivin
is important for both cell cycle progression and resistance to apoptosis of human keratinocytes. In human melanocytes,
survivin expression and functions are controversial. In some reports, melanocytes do not seem to express survivin. In
contrast, some studies detected survivin in normal melanocytes in culture. Survivin is also detected in skin endothelial
cells. It is expressed in capillaries of normal epithelium, while it is upregulated in endothelial cells of granulation tissue.
Survivin was also found to be expressed in sebocytes of normal human sebaceous glands, mainly in reserve cells Hence,
survivin might have a similar pro-survival role in sebocytes. Consequently, survivin is important for both resistance to
apoptosis and cell cycle progression of keratinocytes.
Clearly, with roles in mitosis, apoptosis suppression, autophagy, migration, metabolism and angiogenesis, survivin can
promote tumor cell survival and cancer metastasis. Mitochondrial survivin seems to have an important role in cancer
biology, it protects cancer cells from apoptosis and promotes tumor formation. In cutaneous tumors, both nonmelanoma
and melanoma skin cancers, survivin is overall highly expressed compared with normal skin. In addition to cancer, sur-
vivin has been implicated in psoriasis, acne and acne scars, alopesia areata, vitiligo, lichen planus, rheumatoid arthritis
and multiple sclerosis.
In human cutaneous tumors, survivin is expressed in both premalignant and malignant neoplasms, as well as in some
benign tumors. Survivin is overexpressed in human SCCs as compared with normal skin, and it is levels correlates with
tumor aggressiveness and lymph node metastasis. Also, in head and neck SCCs, survivin overexpression correlates with
tumor progression and resistance to therapy. Survivin is expressed both in precancerous lesions, such as actinic kera-
tosis, and in the SCC, although in SCCs its expression is more pronounced. In contrast, basal cell carcinomas weakly

12
express surviving. Merkel cell carcinoma, a rare and highly aggressive malignant tumor, recent studies showed that
survivin expression is upregulated in this tumor and it is expression correlate with tumor recurrence and metastasis.
Survivin is overexpressed in melanoma cells as compared with normal melanocytes, and this seems to be a promoting
factor for early-step melanoma formation and prognostic factor for metastasis.
A role of survivin in inflammatory skin disorders has also been studied. Survivin is expressed in 70–80% of psoriatic le-
sions, and it is overexpressed in lesional skin than normal epidermis. Although in normal human skin survivin is located
only in few cells of the basal layer, in psoriasis survivin is expressed in nearly all layers of epidermis. In psoriatic skin,
survivin thought to role in prolonged keratinocyte survival as well as in angiogenesis, which are the key pathogenetic
events in this disease.
In conclusion, further studies are needed to better understand the exact functions of survivin in healthy skin. In skin
pathologies, survivin is proposed to be a useful cancer biomarker, as well as a reliable predictive marker of skin tumors
with a direct correlation with resistance to radio- and chemotherapy. Although different treatment strategies targeting
survivin have been studied, more research are needed at the skin level to develop new treatments for inflammatory and
neoplastic skin diseases.

References
1. Wheatley, Sally P., and Dario C. Altieri. “Survivin at a glance.” Journal of Cell Science 132.7 (2019).
2. Dallaglio, Katiuscia, Alessandra Marconi, and Carlo Pincelli. “Survivin: a dual player in healthy and diseased
skin.” Journal of Investigative Dermatology 132.1 (2012): 18-27.
3. Bongiovanni, Laura, Eliane J. Müller, and Leonardo Della Salda. “Survivin in skin pathologies.” Experimental
dermatology 20.6 (2011): 457-463.
4. Khan, Zakir, et al. “Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma.” Cellular
& molecular biology letters 22.1 (2017): 1-32.
5. Ding, Yiling, et al. “Nuclear expression of the antiapoptotic protein survivin in malignant melanoma.” Cancer: In-
terdisciplinary International Journal of the American Cancer Society 106.5 (2006): 1123-1129.
6. Salem, Ahmed, et al. “Role of vascular endothelial growth factor, survivin, and inducible nitric oxide synthase
expression in psoriasis: an immunohistochemical study.” Egyptian Journal of Dermatology and Venerology 34.1
(2014): 21.
7. El-Tahlawi, Samar, et al. “Survivin and insulin-like growth factor-I: potential role in the pathogenesis of acne and
post-acne scar.” Scars, burns & healing 5 (2019): 2059513118818031.
8. Marie, R. E. M., et al. “Assessment of survivin levels in serum in patients with vitiligo: A case-control study.” The
Australasian Journal of Dermatology (2020).
9. Marie, Radwa El‐Sayed Mahmoud, Noha M. Abd El‐Fadeal, and Lina M. Atef. “Expression of survivin and p53
genes in patients with alopecia areata: A case–control study.” Australasian Journal of Dermatology (2020).
10. Park, Hye‐Rim, et al. “Expression profiles of p63, p53, survivin, and hTERT in skin tumors.” Journal of cutaneous
pathology 31.8 (2004): 544-549.

13
 EXOSOMES IN DERMATOLOGY
Sevda Önder

Cell to cell interaction is vital for human life and development. Although the intercellular interaction is regulated with
many hormones, mediators, cytokines or direct cellular interactions, the important roles of extracellular vesicles (EVs)
have attracted the attention of researchers in recent years. EVs have been divided into three categories; exosomes,
microvesicles and apoptotic bodies. They include specific cargos like messengerRNAs (mRNA) microRNAs, long
noncoding RNAs, mitochondrial DNAs, DNA, protein ligands, receptors and transcription factors (1).
What are exosomes?
Exosomes are nano-vesicles with sizes ranging from 30 to 150 nm, released by all known cells. These vesicles can be
obtained from all body fluids (such as serum, plasma, urine, amniotic fluid, synovial fluid, breast milk, saliva, cerebrospinal
fluid) in both healthy and diseased conditions. Studies have shown that they play important roles in many biological
functions such as intercellular communication, signal transmission, genetic material transfer and regulation of immune
response (2). Understanding that exosomes have such functions has led to the different uses of these nanoparticles (1).
Structure and Cargo of Exosomes
Exosomes are formed when the endosome membrane folds into itself during the maturation of the endosomes. This
formation, which contains many nanovesicles, is called multivesicular bodies (MVB). Exosomes spread to body fluids
as this MVB combines with the cell membrane of the endosome and releases the cargo inside. Studies show that the
exosome content varies from cell to cell and according to the current state of the cell (1-2). However different cell
origin exosomes also express certain common proteins. Among these proteins, CD9, CD37, CD53, CD63, CD81 and
CD82 stand out. Exosomes also express Alix and TSG101 (tumor susceptibility gene 101), Rab11, HSP70 (heat shock
proteins 70) and 90, Annexin 1 and 2 and ICAM-1 (intercellular adhesion molecule 1) proteins that play a role in the
formation of MVB. Cholesterol, phosphatidylcholine, phosphatidylserine and diglycerides in lipid barrier that are found
in the membrane structure of exosomes are common lipid molecules found in all exosomes. What makes exosomes
so popular is that they contain mRNA, miRNA and sometimes DNA (3). This functional mRNA and miRNA can be
transferred from cell to cell via exosomes. Exosomes play an important role in the pathogenesis of diseases due to their
very different functions. Considering all these functions, exosomes can be used both for diagnosis as a biomarker and
for the treatment of diseases due to their specific properties in many branch of medicine
Exosomes in dermatology
In recent years there is increasing literature about exosomes roles in the dermatology field. It is known that exosomes
have important roles in skin homeostazis, pathology and repair. Recent studies showed that exosomes play roles in the
physiological processes of the skin and have pathological roles in the process of skin diseases. Among the pathologic
process of the skin diseases exosomes regulate the secretion of pro-inflammatory cytokines , promote angiogenesis,
deposite collagen in skin defects and regulate the proliferation and differentiation of skin fibroblasts in the cutaneous tissue.
Exosomes regulate microenvironment of skin by releasing their spesific cargos and thus they promote the occurrence of
skin diesases such as psoriasis, atopic dermatitis, melanoma and some other skin diseases (4,5,6). Thus, exosomes may
act as potent drug carriers that can selectively infiltrate skin lesions for the treatment of various skin diseases. Exosomes
have important physiological roles in skin homeostazis, such as inflammatory response, cutaneous wound healing,
the immune response, and skin immunity (7). The specific contents carried by the exosomes reflect the physiological
or pathological conditions of the cells from which they originate. Many studies have reported that the RNA profile of
exosomes derived from pathological cells or diseases is different from exosomes derived from healthy cells, therefore,
exosomes are potential candidates for diagnostic biomarkers and treatments for a variety of diseases (1,7).
Exosomes have also become an area of ​​interest in cosmetic dermatology in recent years (8) Exosomes can originate
from many different tissues, both immune and non-immune. According to the tissues they originate from, their contents
and therefore their functions may also change. In cosmetic dermatology, there is increasing literatur about the roles of
the adipose tissue-derived exosomes. Adipose tissue has important functions in immune modulation, wound healing,

14
and tissue regeneration. Removing stromal cells from the adipose tissue can create complex application possibilities.
Thus, adipose-derived stem cells(ASCs) and ASC-derived exosomes (ASC-exos) become important derivatives of fat
tissue. The ASC-exos can be used as tools for repairing and regenerated activation of damaged cells, have roles on skin
regeneration, skin homeostazis, anti-inflammation and immune function (9).
As a result, the increasing literature knowledge of exosomes shows us they will continue to be the focus of researchers
in the field of dermatology in such as pathogenesis, diagnosis and treatment of many diseases and cosmetic dermatology
in the coming years.

References
1- McBride JD, Rodriguez-Menocal L, Badiavas EV. Extracellular Vesicles as Biomarkers and Therapeutics in
Dermatology: A Focus on Exosomes. J Invest Dermatol. 2017 ;137:1622-1629.
2- Théry C. Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep. 2011;3:15.
3- Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013; 200:373-83.
4- Jiang M, Fang H, Shao S, et al. Keratinocyte exosomes activate neutrophils and enhance skin inflammation in
psoriasis. FASEB J. 2019 ;33:13241-13253.
5- Guo D, Lui GYL, Lai SL, et al. RAB27A promotes melanoma cell invasion and metastasis via regulation of pro-
invasive exosomes. Int J Cancer. 2019 ;144:3070-3085.
6- Kim YJ, Yoo SM, Park HH, et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells
stimulates rejuvenation of human skin. Biochem Biophys Res Commun. 2017 ;493:1102-1108.
7- Wong PM, Yang L, Yang L, et al. New insight into the role of exosomes in vitiligo. Autoimmun Rev. 2020; 19:102664.
8- Xiong M, Zhang Q, Hu W, et al. Exosomes From Adipose-Derived Stem Cells: The Emerging Roles and Applications
in Tissue Regeneration of Plastic and Cosmetic Surgery. Front Cell Dev Biol. 2020;8:574223.
9- Qiu H, Liu S, Wu K, et al. Prospective application of exosomes derived from adipose-derived stem cells in skin
wound healing: A review. J Cosmet Dermatol. 2020;19:574-581.

15
 MICRONEEDLING COMBINED PROCEDURES IN AESTHETIC DERMATOLOGY
Emeksiz MC
Ufuk University, Department of Dermatology, Ankara,Turkey

Orentreich first described the use of a skin needling as “subcision” in In 1994.

Furthermore, the first modern dermaroller was introduced in 2006. Main devices using microneedling technology can
be summarized as 1. Dermaroller, 2. Derma pen 3. Fractional radiofrequency microneedling 4. Superficial home-care
rollers 5. Devices combining microneedling and vacuum-assisted infusion such as DermaFracTM (Genesis Biosystems,
Lewisville, TX, USA) 6. LED microneedling rollers 7. Others such as Fluzone® Intradermal influenza virus vaccine
(Sanofi Pasteur, Swiftwater, PA, USA)1
The basis of microneedling relies on physical trauma which penetrates the dermis to a uniform depth, creating a con-
trolled skin injury. The natural wound healing cascade is induced as platelets and neutrophils are recruited to release
growth factors such as TGF-alpha, TGF-beta, and platelet-derived growth factor (PDGF). This ultimately results in the
deposition of collagen by fibroblasts. This controlled skin injury induces rapidly-healing micropunctures with subse-
quent stimulation of collagen and elastin fiber production, resulting in skin remodelling.1,2
Microneedlng is a non-ablative alternative for many cosmetic procedures. Although initially developed as a tool for skin
rejuvenation, it is now being used for many indications, such as scars, acne, melasma, photodamage, skin rejuvenation,
hyperhidrosis, alopecia, and facilitation of transdermal drug delivery.1,2
Despite its common use and a wide variety of indications, strong evidence for the efficacy of microneedling is not still
evident in the literature.1,2
Although being used as a routine in near and middle-east countries for a longer time, it has gained popularity in the USA
and other western countries in the last few years.2
Microneedling can be used alone and combined with many procedures. At least two different and unrelated modalities,
which can be combined depending on the patient’s condition, needs, and goals are employed to consider as a combina-
tion treatment.2
Some microneedling combined procedures are:1-8
1.Platelet-rich plasma (PRP): for facial rejuvenation, androgenetic alopecia, alopecia areata, stria, atrophic acne scars,
also telogen effluvium, pigmentation, melasma, skin laxity, wrinkles etc.
2.TCA 15% peeling: for pigment tx, or facial rejuvenation,
3. Minoxidil treatment: alopecia
4. Mesotherapy: for facial rejuvenation, alopecia, stria, melasma, periorbital melanosis
5. Lasers: such as 1927 nm thulium laser and fractional Er:YAG laser for facial rejuvenation; 1064-nm Q-switched
Nd:YAG laser for hyperpigmentation.
6. Radiofrequency (RFMN): for facial rejuvenation, aging, acne scars, inflammatory acne, axillary hyperhidrosis, cellu-
lite, stria, alopecia, rosacea, postinflammatory erythema etc.
7. Chemical peeling (glycolic acid, Jessner’s solution) for atrophic acne scars
8. Stem cell: amniotic fluid mesenchymal stem cell-derived conditioned media (AF-MSC-CM): for facial ageing
9. BotulinumtoxinA: post-operative facial scars, mesobotox
10. Drug delivery: lidocaine for local anaesthesia, 5-fluorouracil (5-FU) and bleomycin for SCC and warts; Topical
glycopyrrolate for eccrine hidrocystomas, and vitamin C, tranexamic acid for melasma etc.

16
11. Photodynamic therapy (PDT) utilizing the photosensitizers aminolevulinic acid (ALA) or methyl aminolevulinate
(MAL) for actinic keratosis, superficial BCC, SCCs, and other sun-related skin damage.
Advantages:1,3
Easy application
Low cost, a relatively short recovery period (two to three days) and
A very low risk for postinflammatory hyperpigmentation that is a potential side effect of other collagen remodeling
treatments.
Disadvantages:1,3
A bit painful
Mild transient erythema and edema is expected
Scar formation, very rare
Risk of granuloma formation (if combined with topicals)
Although, microneedling is generally a well-tolerated, safe procedure. Contraindications are limited, but include the
following:2
1. Active acne, especially inflammatory lesions
2. Active herpes labialis or other localized infection in the treatment area, including warts.
3. Moderate-to-severe chronic skin diseases such as eczema or psoriasis
4. Patients with extreme keloidal tendencies
5. Immunosuppressed patients, including patients on chemotherapy
6. Care should also be taken in patients near concomitant chemodenervation (botulinum toxin) injection sites to avoid
unwanted toxin diffusion
Adverse effects:
The use of topical medications with or immediately after a microneedling procedure may increase the incidence of ad-
verse effects because of the creation of channels within the epidermis and dermis that acts as a gateway into the body
allowing for the development of an immune response to immunogenic particles. Avoidance of non-prescribed skincare
products for the first week after the microneedling procedure as these may potentially induce a local or systemic hyper-
sensitivity reaction.1,4
Since the microneedling procedure is often used in combination with other treatments such as injections of hyaluronic
acid filler and chemical peels and various dermatologic lasers, no “wash out” period is necessary before initiation of
treatment. However, it is recommended the order of treatments be applied from deep to superficial (e.g., injectables
before micro-needling and/or laser irradiation) to maintain visual landmarks and prevent diffusion of injectables caused
by tissue edema or bleeding. 1,4,5
What’s new?
Nanofat micro-needling:9
Nanofat is prepared by a 2-step emulsification technique followed by filtration. It is a highly concentrated solution of
progenitor cells and has no viable adipocytes with no filling capacity. Grafting can be performed by a microneedling
delivery pump system called Hydra Needle 20 microneedling device (Guangzhou Ekai Electronic Technology Co Ltd,
Guangzhou, China).
Meso-botox by microneedling9,10

17
Botox can be applied through a very superficial and uniform injection technique into the dermis via the same micronee-
dling delivery system. The botulinum toxin acts by decreasing sweat, oil, and sebum production and superficial wrinkles.
Skin booster (as a combination of all) 9,10
The mixture with nanofat, botulinum toxin, and vitamin C can be delivered in the same session. Striking improvement
on the skin quality is perceived 6 to 8 months after nanofat grafting. Association of hyaluronic acid, botulin toxin, and
vitamin C provides shorter-term enhancement of skin quality.
In conclusion, microneedling is a safe, minimally invasive, and effective aesthetic treatment modality for numerous der-
matologic conditions, including acne and other scars, rhytides, and striae. With its fast post-treatment recovery, limited
side effect profile, and impressive clinical results, microneedling is a valuable alternative to more invasive procedures
such as laser skin resurfacing and deep chemical peeling. Moreover, the combination of microneedling with another
procedure is found to increase the success, and decrease the complication risk in the recent literature.

Referances
1. Litchman G, Nair PA, Badri T, Kelly SE. Microneedling. In: StatPearls. Treasure Island (FL): StatPearls Publishing;
September 27, 2020.
2. Alster TS, Graham PM. Microneedling: A Review and Practical Guide. Dermatol Surg. 2018;44(3):397-404.
doi:10.1097/DSS.0000000000001248
3.Long T, Gupta A, Ma S, Hsu S. Platelet-rich plasma in noninvasive procedures for atrophic acne scars: A systematic
review and meta-analysis. J Cosmet Dermatol. 2020;19(4):836-844. doi:10.1111/jocd.13331
4. Dhurat R, Mathapati S. Response to microneedling treatment in men with androgenetic alopecia who failed to re-
spond to conventional therapy. Indian J Dermatol. 2015;60(3):260-3.
5. Sahni K, Kassir M. Dermafrac™: an innovative new treatment for periorbital melanosis in a dark-skinned male pa-
tient. J Cutan Aesthet Surg. 2013;6(3):158-160. doi:10.4103/0974-2077.118420
6. Karadağ Köse Ö, Borlu M. Efficacy of the combination of Q-switched Nd:YAG laser and microneedling for melasma
[published online ahead of print, 2020 Jul 22]. J Cosmet Dermatol. 2020;10.1111/jocd.13629. doi:10.1111/jocd.13629
7. El-Domyati M, Moftah NH, Nasif GA, Ameen SW, Ibrahim MR, Ragaie MH. Facial rejuvenation using stem cell
conditioned media combined with skin needling: A split-face comparative study. J Cosmet Dermatol. 2020;19(9):2404-
2410. doi:10.1111/jocd.13594
8. Wan M, Lin J. Current evidence and applications of photodynamic therapy in dermatology. Clin Cosmet Investig
Dermatol. 2014;7:145-63.
9. Weiner SF. Radiofrequency Microneedling: Overview of Technology, Advantages, Differences in Devices, Studies,
and Indications. Facial Plast Surg Clin North Am. 2019;27(3):291-303. doi:10.1016/j.fsc.2019.03.002
10. Casabona GR, Giacomo TB. Improving the Appearance of Surgical Facial Scars With IncobotulinumtoxinA and
Microneedling. J Drugs Dermatol. 2020;19(6):611-615. doi:10.36849/JDD.2020.10.36849

keywords: collagen induction therapy, microneedling, dermarolling, or skin needling

18
 LIQUID COLLAGEN: WHERE ARE WE NOW FOR DERMATOLOGY?
Semahat Alp Erdal

Collagen is the one of an essential components of connective tissue and present abundant in various fibrous tissues,
such as skin, bones, ligaments, tendons, blood vessels, muscle, cornea and dentin. This fibrous protein composed of the
characteristic triple helix of three polypeptide α chains containing repetitive triplets of the amino acids glycine, proline,
and hydroxyproline accounts for ~30% of total protein mass in the mammals body, and may constitute >70% of the dry
weight of the normal human skin dermis.
Having the same basic amino acid building blocks collagens differe in according to their α-chain composition, and there
are 28 different unique types of collagen. The skin contains mostly Type I, and Type III collagen ( Natural ratio of type
I:III collagen is 4:1). Collagen type II is mainly present in the cartilages. Collagen loss in the body starts about 29 years
of age, after 40 years the human body can lose around 1% per year.
According to 2019 industry reports, with rising of collagen demand in the healthcare area and medical industry, Colla-
gen Market size has exceeded USD 3.5 Billion, globally in 2019 and it is antipicated to register more than 8% CAGR
between 2020 and 2026. We see that it is common to use collagen supplements in population through advice or ad-
vertising without dermatologist advice. It is no wonder that rising globally coronavirus issues and improvements in
health awareness among people have led to increasing nutraceuticals demand to boost immunity and to remain healthy.
For these and similar reasons oral collagen supplements have recently become more popular due to various beneficial
effects, such as improving muscle strength, bone density, and skin health. Though widely marketed to consumers via
alleged benefits, these expected effects have still not precisely elucidated in the literature. However, data regarding its
affirmative effects on wrinkle reduction, skin rejuvenation, skin aging reversal, besides data directed to its possible long
term adverse impacts on body are not yet enough. According to common opinion of supporters, based on their in vitro/
in vivo experimental or clinical trials, orally intaking protein peptides can maintain and increase the collagen in the skin.
They claim that these products induce fibroblast migration and increasing hyaluronic acid production of dermal fibro-
blasts, promote stronger collagen fibrils, increase the water content of the stratum corneum, and additionally protect the
skin against UV induced melasma.
Collagen has long been used in food supplements and pharmaceutical industry. It can be isolated from several sources,
mainly bovine (because of its availability and biocompatibility), porcine byproducts, which they have a difference in
its chemical and thermal properties. Collagen extraction can be carried out from their different tissues such as tendons,
bones, lung tissue, or even connective tissue. Alternative sourche of collagen are fish tissue such as bones, skin, and
scales, ovine tendon and skin, jellyfishes or sponges or others sources such as chicken, duck, and rabbit skin. Collagen
peptides obtained these sourches, are offered in pill, powder, liquid or topical forms on market.
Oral collagen supplementation is usually in the form of hydrolyzed collagen (HC, collagen peptides). Collagen is con-
sidered to be an antioxidant in its hydrolyzed form. HC is composed of small peptides with low molecular weight 3-6
KDa. There have been different types of extraction of HC. It can be obtained by thermal treatment with/without pres-
sure, enzymatic reaction by use of chemical products, or by use of high intensity ultrasound. Low-molecular-weight
collagen hydrolysates are generally thought to perform better bioactivities than their larger counterparts. Many clinical
studies performed to show benefits, such as bioavailability, rapid absorption in the digestive tract, passage into the
bloodstream as small peptides and accumulation in the skin. Hydrolyzed collagen has to cross the intestinal barrier and
to enter the bloodstream to be reach to the skin. The rate of transport across the intestinal barrier is an controlling factor
that affects these compounds bioavailability in the skin. For this reason, it is important to determined better absorbed in
what quantity and form of collagen peptides. It is claim that beverages with HC have more advantage of easy digestion,
high assimilation (about 80%), and good absorption at the intestinal level.
Digestion process involving in several proteases consists of degradation of hydrolyzed collagen to form dipeptides and
tripeptides or free amino acids. However, before they are absorbed, peptides are hydrolyzed in the gastrointestinal tract,
in order to predominantly free amino acids can enter the circulation. Hydroxyproline is absorbed in two forms, with an

19
amino acid form and a peptide form. The free amino acids provide building blocks for the formation of collagen and
elastin fibers. Collagen oligopeptides stimulates the production of new collagen, elastin, and hyaluronic acid. Most of
oral collagen peptide supplementation products also include vitamins like A, C, E, biotin to provide bioactivity in these
process.
Some studies have shown, by histological analysis, that the structural architecture of dermal collagen fibers and stratifi-
cation of epidermal layers improves when HC supplements are taken orally. Common alleged benefits include wrinkle
reduction, skin rejuvenation, skin aging reversal, and skin fullness. Hydrolyzed collagen has been presumed to be safe
and non toxic. It has generally mild advers effects including diarrhea, heaviness in the stomach, and rashes, yet there
have been reported high levels of cadmium, a toxic heavy metal in all collagen products. In 2016 the FDA prohibited the
use of bovine products in dietary supplements to avoid bovine spongiform encephalopathy, except gelatin.
Despite claims of manufacturers, many benefits of liquid collagen seems to be anecdotal. Most of research are performed
about HC. Persuasive scientific research with high level of evidence is needed to say that oral collagen supplement is the
best way to get collagen. The best way to boost collagen seems to be dietary intake of protein-rich foods such as beef,
poultry, fish for now.

References;
1. Hong H, Fan H, Chalamaiah M, Wu J. Preparation of low-molecular-weight, collagen hydrolysates (peptides):
Current progress, challenges, and future perspectives. Food Chem. 2019 Dec 15;301:125222. doi: 10.1016/j.food-
chem.2019.125222. Epub 2019 Jul 22. PMID: 31382108.
2. Kim DU, Chung HC, Choi J, Sakai Y, Lee BY. Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hy-
dration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients.
2018 Jun 26;10(7):826. doi: 10.3390/nu10070826. PMID: 29949889; PMCID: PMC6073484.
3. Jo Ann Summitt Marrs. Collagen Supplements: Benefits, Uses and Side Effects. On J Complement & Alt Med. 5(2):
2020. OJCAM.MS.ID.000607. DOI: 10.33552/OJCAM.2020.05.000607
4. Jhawar N, Wang JV, Saedi N. Oral collagen supplementation for skin aging: A fad or the future? J Cosmet Dermatol.
2019;00:1–3. https ://doi.org/10.1111/ jocd.13096
5. Aguirre-Cruz G, León-López A, Cruz-Gómez V, Jiménez-Alvarado R, Aguirre-Álvarez G. Collagen Hydrolysates
for Skin Protection: Oral Administration and Topical Formulation. Antioxidants (Basel). 2020 Feb 22;9(2):181. doi:
10.3390/antiox9020181. PMID: 32098294; PMCID: PMC7070905.
6. https://www.gminsights.com/industry-analysis/collagen-market
7. Jafari, H., Lista, A., Siekapen, M. M., Ghaffari-Bohlouli, P., Nie, L., Alimoradi, H., & Shavandi, A. (2020). Fish
Collagen: Extraction, Characterization, and Applications for Biomaterials Engineering. Polymers, 12(10), 2230. https://
doi.org/10.3390/polym12102230
8. León-López, A., Morales-Peñaloza, A., Martínez-Juárez, V. M., Vargas-Torres, A., Zeugolis, D. I., & Aguirre-Álva-
rez, G. (2019). Hydrolyzed Collagen-Sources and Applications. Molecules (Basel, Switzerland), 24(22), 4031. https://
doi.org/10.3390/molecules24224031
9. Lupu MA, Gradisteanu Pircalabioru G, Chifiriuc MC, Albulescu R, Tanase C. Beneficial effects of food supplements
based on hydrolyzed collagen for skin care (Review). Exp Ther Med. 2020 Jul;20(1):12-17. doi: 10.3892/etm.2019.8342.
Epub 2019 Dec 17. PMID: 32508986; PMCID: PMC7271718.
10. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J
Surg. 1998;176(2A Suppl):26S–38S.

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 BETA-CAROTENE/ASTAXANTHIN/COENZYME Q10 AND DERMATOLOGY
BETA-CAROTENE
Seray Külcü Çakmak
University of Health Sciences, Ankara City Hospital, Dermatology Clinic, Turkey

Beta-carotene is a yellow pigment found in chlorophyll-containing plants, bacteria, and food. It is the most abundant
and most efficient precursor of vitamin A and most nutritionally active carotenoid. Its’ consumption does not lead to
hypervitaminosis A because of a feedback mechanism in the mucosa of the gut.
Beta-carotene is derived from natural dietary sources such as carrots, pumpkin, spinach, sweet potatoes, other yellow
and green vegetables and fruits.
Besides direct light-absorbing properties, carotenoids provide endogenous photoprotection and contribute to the
prevention of UV damage in humans mostly by their well-known antioxidant effects. It prevents UV-induced erythema,
increases minimal erythema dose (MED) and decreases the rate of mitochondrial mutation in human dermal fibroblasts
after UV irradiation. Systemic photoprotective effects of beta-carotene depend both on the dose and the duration of
treatment. In most of the interventional studies with carotenoids, photoprotection was observed only after a minimum of
10 weeks of dietary intake or supplementation, with doses >12 mg/day. It was found especially useful in the treatment
and prevention of some photodermatoses, like erythropoietic protoporphyria and polymorphic light eruption.
It has also been shown to prevent and repair effects of photoaging; improve facial wrinkles and elasticity by O2 quenching
and decrease in MMP5 -1, -3, and MMP-10 and MMP-9.
There are also some studies on mice showing the effectiveness of beta-carotene in atopic dermatitis.
Though protective effects of beta carotene from some cancers like esophagial and breast cancer has been shown, long-
term beta-carotene supplementation has been associated with an increased risk of lung cancer in smokers and also a
higher beta-carotene status may increase risk of prostate cancer. So further studies are needed to determine the optimal
daily allowance for supplementation.

ASTAXANTHIN
Astaxanthin (ASX) is a ketocarotenoid first isolated by Kuhn and Sorensen from a lobster. It is found extensively in
the aquatic environment primarly in the microalgae Haematococcus pluvialis and multiple marine species, as an orange
pigment.
Astaxanthin is related to other carotenoids, however, it is more bioactive than zeaxanthin, lutein, and beta-carotene.
ASX is not converted into vitamin A. It has a higher antioxidant activity than other carotenoids.
Recently, ASX has attracted considerable interest because of its potential pharmacological effects, including anticancer,
antidiabetic, anti-inflammatory, and antioxidant activities as well as neuro-, cardiovascular, ocular, and skin-protective
effects.
The mechanisms involved in the protection of skin are antioxidant and antiinflammatory activities and altering the DNA
repair kinetics. The effects of ASX on hyperpigmentation suppression, photoaging inhibition, and wrinkle formation
reduction have been reported in several clinical studies. The reported effects of astaxanhine in skin are; decrease in fine
wrinkles, increase in moisture content, improvement in skin elasticity, reduction in visible signs of aging, improvement
of skin elasticity, antioxidant effect leading to facial rejuvenation, suppression of inflammatory response on UV-B–
exposed skin, decrease in corneocyte desquamation and microbial presence in skin, increase in MED andimprovement
in skin texture. Benefical effects of ASX also have been reported in wound healing, atopic and contact dermatitis.
FDA has approved ASX from H. pluvialis for direct human consumption dosages up to 12 mg per day and up to 24 mg
per day for no more than 30 days. Researches have also shown that astaxanthin is a safe compound, without adverse
effects.

21
COENZYME Q10
Coenzyme Q10 (CoQ10) is an essential compound found naturally in virtually every cell in the human body. It is necessary
for cellular respiration and ATP production. It also functions as an intercellular antioxidant and recognized to have an
effect on gene expression that might account for its effects on overall tissue metabolism.
It is naturally found in dietary sources, with large amounts present in heart, chicken leg, herring and trout.
In the skin CoQ10 acts as an antioxidant with 10-fold higher levels in the epidermis than in the dermis. The amount of
coenzyme Q10 in skin decreases with age. Additionally, UV-irradiation, which leads to oxidative damage, significantly
reduces skin’s Q10 levels. Therefore, in the cosmetic industry the antioxidant CoQ10 is widely used in anti-aging products.
Topical application of coenzyme Q10 to human skin was found to be effective in reducing the depth of wrinkles. Daily
supplementation with 50 and 150 mg of CoQ10 has also been shown to significantly reduce wrinkles and microrelief
lines and improve skin smoothness. CoQ10 is able to suppress the UVR- or IL-1-induced inflammatory response in
dermal fibroblasts. It can block the UVR induction of the matrix-eroding enzyme, MMP-1.
Other effects in dermatology are; suppression severity of dermatitis in mice and cutaneous healing effects in vivo.
CoQ10 dosage guidelines, which appeared to be safe and well tolerated, were suggested for adults (up to 1,200 mg/day)
and for children (up to 10 mg/kg/day).
Drug-nutrient interactions may be observed with cholesterol-lowering drugs, beta blockers, propranolol and metoprolol,
phenothiazines and tricyclic antidepressants, antiplatelet drugs, warfarin and antihypertensive drugs.
Gastrointestinal effects such as abdominal discomfort, nausea, vomiting, diarrhea, and anorexia may occur and CoQ10’s
antiplatelet effect may increase the risk of bleeding.

References
1) Black HS, Boehm F, Edge R, Truscott TG. The Benefits and Risks of Certain Dietary Carotenoids that Exhibit both
Anti- and Pro-Oxidative Mechanisms-A Comprehensive Review. Antioxidants (Basel). 2020 Mar 23;9(3):264.
2) Huang ZR, Lin YK, Fang JY. Biological and pharmacological activities of squalene and related compounds: potential
uses in cosmetic dermatology. Molecules. 2009;14(1):540-54.
3) Bayerl Ch. Beta-carotene in dermatology: Does it help? Acta Dermatovenerol Alp Pannonica Adriat. 2008;17(4):160-
2, 164-6.
4) Balić A, Mokos M. Do We Utilize Our Knowledge of the Skin Protective Effects of Carotenoids Enough?
Antioxidants (Basel). 2019;8(8):259.
5) Davinelli S, Nielsen ME, Scapagnini G. Astaxanthin in Skin Health, Repair, and Disease: A Comprehensive Review.
Nutrients. 2018;10(4):522.
6) Singh KN, Patil S, Barkate H. Protective effects of astaxanthin on skin: Recent scientific evidence, possible
mechanisms, and potential indications. J Cosmet Dermatol. 2020;19(1):22-27.
7) Garrido-Maraver J, Cordero MD, Oropesa-Avila M, Vega AF, de la Mata M, Pavon AD, Alcocer-Gomez E, Calero
CP, Paz MV, Alanis M, de Lavera I, Cotan D, Sanchez-Alcazar JA. Clinical applications of coenzyme Q10. Front
Biosci (Landmark Ed). 2014 ;19:619-33.
8) Garrido-Maraver J, Cordero MD, Oropesa-Ávila M, Fernández Vega A, de la Mata M, Delgado Pavón A, de Miguel
M, Pérez Calero C, Villanueva Paz M, Cotán D, Sánchez-Alcázar JA. Coenzyme q10 therapy. Mol Syndromol.
2014;5(3-4):187-97.

22
 ZINC / SELENIUM AND SKIN
Düriye Deniz Demirseren
Ankara City Hospital, Dermatology Department, Turkey

Zinc is a nutritionally essential trace element. It plays an important role in the regulation of lipid, pro-tein and nucleic
acid metabolism .It supports healthy immunologic system and plays an important role in wound repair. Zinc, has
antioxidant eect and prevents ultraviolet damage. Unfortunately, no ideal method exists to measure the body zinc level.
Measurements of zinc in serum, plasma, erythrocyte , hair and urine can be done. Normal plasma zinc level range is
considered as 70-250 mg/dL. Daily zinc is 5-9 mg for females and 7-14 mg for males. There is no standard regiment for
the dosage and period. The main source of zinc taken in diet is meat. As we all know, acrodermatitis enteropathica is an
autosomal recessive disease characterised by a deffect in zinc absorbtion. Symptoms start with the delactation. In contrast
to severe deficiency, there is no evidence of the effect of moderate zinc defici-ency on wound repair. There are studies
showing that serum zinc level in patients with Behçet Disea-se and recurrent aphthous stomatit is low. Consequently;
despite contradictory studies; zinc therapy; can be considered as encouring in recurrent aphtous stomatitis and Behçet
diseases. There are studies showing a positive correlation between zinc deficiency and hair loss. Al-Refu K. suggested
that zinc deficiency might be the reason of cronic hair loss in children. However, there are studies not binding alopecia
and zinc deficiency. Harrison and Sinclair claimed that zinc deficiency in telogen effluvium couldn’t be the reason of
alopecia without other dermotological signs. In the systematic review of Cochrane database in 2012, it is noted that
there are not a convincing evidence about the effective-ness of dietary supplements in atopic dermatıtıs about the
effectiveness of of dietary supplements in atopic dermatıtıs .As a conclution; there are studies about zinc deficiency
in dermotological diseases, there is not enough scientific evidence for recommending its therapatic usage. In order to
prove its efficacy in dermotological diseases, more plecebo controlled, double blind and randomized studies should be
done with large group of patients and then, treatment algoritms should be prepared. For now, it can be recommended
as adjuvant medications in addition to current approved therapies.
Selenium is an essential trace element in human nutrition being the component of selenoproteins which have antioxidant
functions in cardiovascular disease and cancer prevention. Selenium, though present in meat, may be found in higher
values in seafood. Selenium has an important role in glutathi-one peroxidise activity, a crucial enzyme in detoxification
processes.
Basic research has further clarified the role of selenium in skin aging. Selenium preserves keratinocyte stemness and
delays senescence by maintaining epidermal adhesion . Besides, after oxidative damage to keratinocytes by ultraviolet
A, young keratinocytes treated with low doses of selenium attenuate the cytotoxicity of ultraviolat A by promoting
DNA repair of 8-oxoguanine. Nevertheless, for aged kerati-nocytes, a higher concentration of selenium is needed ,
suggesting that selenium supplementation strengthens the DNA repair activities of keratinocytes to fight aging and
prevent photoaging in skin tissue. As a conclusion, there are many beneficial effects of selenium on human skin health
involving its antioxidant properties along with various other biochemical actions.
References:
1.Patel M, Harrison S, Sinclair R. Drugs and hair loss. Dermatol Clin. 2013 Jan;31(1):67-73. doi: 10.1016/j.det.2012.08.002.
2. Al-Refu K. Stem cells and alopecia: a review of pathogenesis. Br J Dermatol. 2012 Sep;167(3):479-84.
3. Pereira PM, Vicente AF. Meat nutritional composition and nutritive role in the human diet. Meat Sci. 2013 Mar;93(3):586-92. doi:
10.1016/j.meatsci.2012.09.018.
4. Richelle M, Sabatier M, Steiling H, Williamson G. Skin bioavailability of dietary vitamin E, carote-noids, polyphenols, vitamin C, zinc
and selenium. Br J Nutr. 2006 Aug;96(2):227-38. doi: 10.1079/bjn20061817.
5. Cai Z, Zhang J, Li H. Selenium, aging and aging-related diseases. Aging Clin Exp Res. 2019 Aug;31(8):1035-1047. doi: 10.1007/
s40520-018-1086-7.
6. Rayman MP. The importance of selenium to human health. Lancet. 2000 Jul 15;356(9225):233-41. doi: 10.1016/S0140-6736(00)02490-9.
7. Bath-Hextall FJ, Jenkinson C, Humphreys R, Williams HC. Dietary supplements for established atopic eczema. Cochrane Database Syst
Rev. 2012 Feb 15;2:CD005205.
8. Vollmer DL, West VA, Lephart ED. Enhancing Skin Health: By Oral Administration of Natural Compounds and Minerals with
Implications to the Dermal Microbiome. Int J Mol Sci. 2018 Oct 7;19(10):3059. doi: 10.3390/ijms19103059.

23
 Mitochondrial DNA and Dermatology
Özgür Gündüz
Kırıkkale University Faculty of Medicine Hospital, Kırıkkale, Turkey

Mitochondrium (pl. mitochondria); is an double membrane-surrounded organelle, which is, with a few exceptions (i.e.,
erythrocytes), found in most of the eukaryotic cells.1 Number, shape, and form of mitochondria may differ from cell to
cell.2 Hundred to thousands of mitochondria can be found in most human cells, depending on their metabolic activity.
Mitochondria generate most of the much-needed cellular energy in the form of ATP through a process called oxidative
phosphorylation (OXPHOS), which takes place in its inner membrane. In addition to that, mitochondria play essential
roles in Ca homeostasis, heme synthesis, steroid synthesis, heat generation.
Recent mitochondrial genetic and ultrastructural studies showed that the functions of mitochondria are not limited
to biosynthetic processes, energy generation. New data indicate that mitochondria possibly have a crucial role in the
regulation of cellular proliferation and apoptosis. A good example is the discovery of the mitonucleon. Although mi-
tochondrium has initially been believed to be an individual, isolated organelle, in recent years, it has been found out
that mitochondria may fuse into the superstructures, called mitonucleons, which are thought to take part in endometrial
differentiation, spermatogenesis, and also synthesis and excretion of steroid hormones.3
Mitochondrial DNA
Mitochondrial functions are regulated by mitochondrial (mtDNA) and nuclear genomes (nDNA). mtDNA includes
16,569 base pairs and encodes 13 proteins.4 Unlike diploid nDNA, mtDNA is a multi-copy genome transmitted and ma-
ternally inherited through oocyte. Point mutations or rearrangements of mtDNA may lead to mitochondrial dysfunction
and multisystem diseases through compromising OXPHOS function.5 The multi-copy nature of mtDNA easily causes
the heteroplasmy as a unique aspect of mtDNA, making mitochondrial diseases more complex and heterogeneous. mtD-
NA-, and nDNA-associated mitochondrial dysfunction play a critical role in the development of multisystemic primary
mitochondrial diseases, neurodegeneration, and various cancers.5
Mitochondrial Diseases
Mitochondrial diseases are genetic disorders, which are caused by mutations in the nuclear DNA (nDNA) and mitochon-
drial DNA (mtDNA) encoding the structural mitochondrial proteins or proteins participating in mitochondrial function,
and which usually lead to defective oxidative phosphorylation. These disorders may manifest in childhood or later in
life. While some mitochondrial disorders may manifest as a single organ disease (e.g., the eye in Leber hereditary
optic neuropathy [LHON]), others may affect multiple organ systems and are often characterized by neuromuscular
symptoms. Mitochondrial diseases may manifest at any age. Many individuals with a mutation of mtDNA may pres-
ent with typical clinical features of a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic
progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like
episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retini-
tis pigmentosa (NARP), or Leigh syndrome (LS). But, considerable clinical variability exists, and many patients can
not be classified easily into one particular category, which is well-illustrated by the overlapping spectrum of disease
phenotypes (including mitochondrial recessive ataxia syndrome (MIRAS) resulting from mutation of the nuclear gene
POLG, which has emerged as a major cause of mitochondrial disease. Common clinical features of mitochondrial
disease are ptosis, external ophthalmoplegia, proximal myopathy, exercise intolerance, cardiomyopathy, sensorineural
deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. Common central nervous system findings are
encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. A high incidence of mid-and
late pregnancy loss is a common occurrence that often goes unrecognized.
The prevalence of childhood-onset mitochondrial disorders is reported to range from 5 to 15 cases per 100,000 indi-
viduals. With a prevalence of 2,5 cases per 100000 births, Leigh syndrome is the common mitochondrial disease of
childhood. Adult-onset mitochondrial diseases are estimated to have a prevalence of 20 cases per 100000 individuals
globally. mtDNA mutations seem to be more frequent in adult-onset mitochondrial disorders (about 80% of all cases),
where they are observed only in 20-25% of childhood mitochondrial diseases.6
Dermatology and Mitochondrial Genetics
As the outermost layer of the human body, the skin is continuously in contact with numerous environmental stimuli,
many of which can be quite detrimental. Constant mitosis at the level of stratum basale, the passage of keratinocytes
directed to the skin surface from basal layer to the stratum corneum, and transformation of basal keratinocytes into the

24
corneocytes, presenting antigenic structures to immune cells are some of the crucial means by which our skin deals with
these harmful stimuli. Each one of these processes requires a constant energy flow, which is supplied by numerous mito-
chondria. Recent research show that, in addition to acting as power generators, mitochondria play more critical roles in
the metabolism and differentiation of keratinocytes7,8. It is reasonable to speculate that any disturbance in mitochondrial
functions may also manifest as skin problems.
Skin manifestations such as poikiloderma, acrocyanosis, vitiligo, hair abnormalities, hirsutism, petechiae with cutis
marmorata, brownish discoloration of skin were reported in 16 of 271 patients with mtDNA disorders.9 Moreover,
mutations in mtDNA have been detected in specific dermatological diseases. Powers et al. reported mtDNA3895 and
mtDNA4977 deletions in sun-exposed human skin.10 Berneberg et al. reported 10-fold 5000bp deletion in the mtDNA of
photodamaged skin compared to sun-protected skin cells. Singh et al. observed that ubiquitous depletion of mtDNA in
mice results in skin wrinkling and hair loss and speculated that restoration of mtDNA could reverse these conditions.11
Another research group, Villavicencio et al., studied the pigmentation changes in mtDNA depleted mice’s ears and
observed cutaneous and pigmentary changes similar to age-related cutaneous changes in humans such as senile lentig-
ines.12 Various research groups also found out that radiation and other carcinogenic stimuli damage mtDNA directly,
indicating the possible role of mtDNA damage in cutaneous carcinogenesis. Furthermore, dose-dependent changes in
mitochondrial membrane potential and function in SLE and pemphigus Vulgaris patients treated with glucocorticoids
have been observed.
All things considered, mitochondrial dysfunction seems to play a crucial role more than imagined before. New thera-
peutic approaches targeting the defective or dysfunctional mitochondria may prove effective in various dermatological
conditions, particularly in skin-aging, pigmentary problems.
References
1. (2011) Mitochondrium. In: Schwab M. (eds) Encyclopedia of Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-
3-642-16483-5_3768
2. Griparic L, van der Bliek A. The Many Shapes of Mitochondrial Membranes. Traffic, 2001:2; 235-244. https://doi.org/10.1034/
j.1600-0854.2001.1r008.x
3. Fleming, H. Mitochondrial/Nuclear Superstructures Drive Morphological Changes in Endometrial Epithelia by Pressure Exert-
ed when Gas Vacuoles Form and Coalesce within Superstructures. Advances in Bioscience and Biotechnology, 2018: 9; 224-42.
DOI: 10.4236/abb.2018.95016.
4. Schon, E., DiMauro, S. & Hirano, M. Human mitochondrial DNA: roles of inherited and somatic mutations. Nat Rev Genet 13,
878–890 (2012). https://doi.org/10.1038/nrg3275
5. Zhu Z, Wang X. Significance of Mitochondria DNA Mutations in Diseases. Adv Exp Med Biol. 2017;1038:219-230. DOI:
10.1007/978-981-10-6674-0_15. PMID: 29178079.
6. Gorman, G., Chinnery, P., DiMauro, S. et al. Mitochondrial diseases. Nat Rev Dis Primers 2016: 2, 16080. https://doi.
org/10.1038/nrdp.2016.80
7. Hamanaka RB, Chandel NS. Mitochondrial reactive oxygen species regulate cellular signaling and dictate cellular outcomes.
Trends Biochem Sci 2010; 35:910-3.
8. Hamanaka RB, Chandel NS. Mitochondrial metabolism as a regulator of keratinocyte differentiation. Cell Logist 2013;3:e25456.
http://dx.doi.org/10.4161/cl.25456
9. Flynn MK, Wee SA, Lane AT. Skin manifestations of mitochondrial DNA syndromes: case report and review. J Am Acad Der-
matol. 1998 Nov;39(5 Pt 2):819-23. doi: 10.1016/s0190-9622(98)70356-1. PMID: 9810906.
10. Powers JM, Murphy G, Ralph N, O’Gorman SM, Murphy JE. Mitochondrial DNA deletion percentage in sun-exposed and
non-sun-exposed skin. J Photochem Photobiol B. 2016 Dec;165:277-282. DOI: 10.1016/j.jphotobiol.2016.10.030. Epub 2016
Oct 29. PMID: 27829204.
11. Singh, B., Schoeb, T.R., Bajpai, P. et al. Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function. Cell
Death Dis 9, 735 (2018). https://doi.org/10.1038/s41419-018-0765-9
12. Villavicencio KM, Ahmed N, Harris ML, et al. Mitochondrial DNA-depleter mouse as a model to study human pigmentary skin
disorders. Pigment Cell Melanoma Res 2020 Aug 16. DOI: 10.1111/pcmr.12921. Online ahead of print.
13. Sreedhar, A., Aguilera-Aguirre, L. & Singh, K.K. Mitochondria in skin health, aging, and disease. Cell Death Dis 11, 444
(2020). https://doi.org/10.1038/s41419-020-2649-z
14. Sreedhar, A., Aguilera-Aguirre, L. & Singh, K.K. Mitochondria in skin health, aging, and disease. Cell Death Dis 11, 444
(2020). https://doi.org/10.1038/s41419-020-2649-z

25
 AQUAPORINS IN DERMATOLOGY
Özgür Gündüz
Kırıkkale University Faculty of Medicine Hospital, Kırıkkale, Turkey

Aquaporin(AQP)s, also known as water channels, are a group of intrinsic membrane proteins that form pores in biological
cells’ membranes, mainly facilitating water transport between cells.1Aquaporins possess six membrane-spanning alpha-
helical domains with both carboxylic and amino terminals on the cytoplasmic side. Due to their diminutive size, water
molecules can pass through the cell membrane through simple diffusion. However, simple diffusion is relatively slow
because of the polarity of water molecules, and the majority of water passes through aquaporin.2 In recent years, it has
been found out that, in addition to water, AQPs also transport other molecules, such as glycerol.
The first aquaporin, ‘aquaporin-1’ (known initially as CHIP 28), was reported by Peter Agre of Johns Hopkins University
in 1992, who also won The 2003 Nobel Prize in Chemistry for his discovery.3,4 Further studies using supercomputer
simulations identified the pathway of water as it moved through the channel and demonstrated how a pore could allow
water to pass without the passage of small solutes.5
Aquaporins in Humans
Thirteen aquaporin types have been identified (AQP0-12) in humans and divided into three subgroups according
to the primary sequences: water selective AQPs (AQP0, 1, 2, 4, 5, 6, 8), aquaglyceroporins (AQP3, 7, 9, 10), and
superaquaporins (AQP11, 12 - aquaporins found inside the mammalian cells). Due to the lack of specific inhibitors,
functions of AQPs are hypothesized from the observations of AQP null mice and humans. Abnormal water metabolism
was observed with AQP1, 2, 3, 4, 5 null mice, particularly with AQP2 null mice: leading to death at neonatal period
due to diabetes insipidus. Abnormal glycerol transport was detected in AQP3, 7, 9 null mice, despite their normal
phenotypes. Ctaracts are observed in AQP0 null mice suffer. AQP11 null mice are reported to die from uremia as a result
of polycystic kidneys. AQP6, 8, 10, 12 null mice are healthy. AQP null humans have been reported with AQP0, 1, 2, 3,
7. Among them, AQP2 null humans manifest diabetes insipidus.6
Dermatology and Aquaporins
AQP3 is of particular interest to dermatologists. Aquaporin-3 (AQP3) is a membrane transporter of water and glycerol
expressed in plasma membranes in the basal layer keratinocytes of the epidermis in normal skin.7 Altered expression
of AQP3 has been detected in atopic eczema, erythema toxicum neonatal, squamous cell carcinoma, indicating their
possible roles in inflammation and carcinogenesis.

REFERENCES
1. Agre P (2006). “The aquaporin water channels.” Proc Am Thorac Soc. 3 (1): 5–13. doi:10.1513/pats.200510-109JH.
PMC 2658677. PMID 16493146.
2. Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence (2000). Molecular Cell Biology (4th ed.). New York: W. H.
Freeman. ISBN 9781464183393. Retrieved May 20 2020.
3. Agre P, Preston GM, Smith BL, Jung JS, Raina S, Moon C, Guggino WB, Nielsen S (Oct 1 1993). “Aquaporin CHIP:
the archetypal molecular water channel.” Am. J. Physiol. 265 (4 Pt 2): F463–76. doi:10.1152/ajprena l.1993.265.4.F463.
PMID 7694481
4. Knepper MA, Nielsen S (2004). “Peter Agre, 2003 Nobel Prize winner in chemistry”. J. Am. Soc. Nephrol. 15 (4):
1093–5. doi:10.1097/01.ASN.0000118814.47663.7D. PMID 15034115.
5. de Groot BL, Grubmüller H (2005). “The dynamics and energetics of water permeation and proton exclusion in
aquaporins.” Curr. Opin. Struct. Biol. 15 (2): 176–83. doi:10.1016/j.sbi.2005.02.003. hdl:11858/00-001M-0000-0012-
E99D-E. PMID 15837176.
6. Ishibashi K, Hara S, Kondo S. Aquaporin water channels in mammals. Clin Exp Nephrol. 2009 Apr;13(2):107-117.
doi: 10.1007/s10157-008-0118-6. Epub 2008 Dec 16. PMID: 19085041.
7. Hara-Chikuma M, Verkman AS. Roles of Aquaporin-3 in the Epidermis, Journal of Investigative Dermatology, 2008;
128(9): 2145-51.

26
 INTEGRINS / HIF1 ALPHA / VEGF/PAI1 IN DERMATHOLOGY
Yasemin Yuyucu Karabulut
Mersin Üniversity, Medical School, Department of Pathology, Mersin, Turkey

Integrins
Integrins are heterodimeric proteins composed of noncovalently associated ɑ and β subunits. Different combinations
of 18 ɑ and 8 β subunits make up the 24 integrin heterodimers encountered in mammals. The integrin structure is
depicted as a molecule with a head and two tails. The head is the ligand-binding extracellular component made up of the
ectodomains of the ɑ and β subunits; intracellular domains represent the legs anchoring to cytoskeletal proteins, with
other domains traversing the transmembrane region in between (1).
Integrins therefore function bidirectionally, meaning information can be transmitted from the outside environment
to inside the cell and vice versa.This bidirectional signaling capability of integrins provides the cell with important
information on its immediate extracellular environment and informs decisions on proliferation, apoptosis, or the
remodeling of the ECM to facilitate metastasis (1, 2).
Integrins also are important for angiogenesis, providing both blood supply to the rapidly growing tumor cells and a
pathway for hematogenous spread to distant organs. Integrins mediate angiogenesis by interacting with the tumor-
secreted growth factors, specifically by promoting endothelial cell migration and survival. Integrins may contribute to
signal transduction that promotes angiogenesis (3).
Hypoxia-inducible factor-1α (HIF-1α)
Skin, the first barrier against invading microorganisms, is hypoxic, even under baseline conditions. The transcription
factor hypoxia-inducible factor-1α (HIF-1α, the principal regulator of cellular adaptation to low oxygen, is strongly
expressed in skin epithelium. HIF-1α is now understood to play a key role in the bactericidal capacity of phagocytic cells
such as macrophages and neutrophils (4).
More recently, HIF-1α has emerged as a critical regulator of immune cell function that couples shifts in cellular
metabolism to cell type-specific transcriptional outputs. Activation of macrophages with inflammatory stimuli leads
to induction of the metabolic program aerobic glycolysis and to HIF-1α stabilization, which reinforce one another in
a positive feedback loop that helps drive macrophage activation. This activation of aerobic glycolysis and HIF-1α is
important both for production of inflammatory cytokines, such as IL-1β, and for cell intrinsic control of infection (5).
Chronic infections are often associated with inflammation and tissue disruption. Inflamed tissues are characterized by low
levels of oxygen and glucose, a microenvironment that triggers the stabilization of the hypoxia-inducible transcription
factor HIF-1α. HIF-1α is the master regulator of the response to hypoxia (6).
Plasminogen activator inhibitor-1 (PAI-1)
PAI-1, also known as SERPINE1 (serpin peptidase inhibitor, clade E), is a member of the serpin family of protease
inhibitors (7).
Fibrosis is defined as a fibroproliferative or abnormal fibroblast activation-related disease. Deregulation of wound
healing leads to hyperactivation of fibroblasts and excessive accumulation of extracellular matrix (ECM) proteins in the
wound area, the pathological manifestation of fibrosis. The accumulation of excessive levels of collagen in the ECM
depends on two factors: an increased rate of collagen synthesis and or decreased rate of collagen degradation by cellular
proteolytic activities (7). The urokinase/tissue type plasminogen activator (uPA/tPA) and plasmin play significant roles
in the cellular proteolytic degradation of ECM proteins and the maintenance of tissue homeostasis. The activities of uPA/
tPA/plasmin and plasmin-dependent MMPs rely mostly on the activity of a potent inhibitor of uPA/tPA, plasminogen
activator inhibitor-1 (PAI-1). Under normal physiologic conditions, PAI-1 controls the activities of uPA/tPA/plasmin/
MMP proteolytic activities and thus maintains the tissue homeostasis. During wound healing, elevated levels of PAI-1
inhibit uPA/tPA/plasmin and plasmin-dependent MMP activities, and, thus, help expedite wound healing. In contrast to

27
this scenario, under pathologic conditions, excessive PAI-1 contributes to excessive accumulation of collagen and other
ECM protein in the wound area, and thus preserves scarring. While the level of PAI-1 is significantly elevated in fibrotic
tissues, lack of PAI-1 protects different organs from fibrosis in response to injury-related profibrotic signals. Thus, PAI-
1 is implicated in the pathology of fibrosis in different organs including the heart, lung, kidney, liver, and skin (7, 8).
Vascular endothelial growth factor (VEGF)
Vascular endothelial growth factor (VEGF, also referred to as VEGF-A), which plays a key role in normal and pathological
angiogenesis, is a homodimeric, heparin-binding glycoprotein, with at least five isoforms of 121, 145, 165, 189, and 206
amino acids due to alternative splicing (9)
VEGF secreted by the cutaneous cells plays an important role in sustaining the skin development and maintenance and
in wound healing . Overexpression of VEGF in skin could lead to pathologic angiogenesis observed in psoriasis and
other chronic inflammatory skin diseases (10).

References
1. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 2002; 110: 673– 687.
2. Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev
Cancer 2010; 10: 9– 22.
3. Suzette M. Arias-Mejias BA at al. The role of integrins in melanoma: a review. International journal of dermathology,
2020.
4. M.H. Braff, R.L. Gallo. Antimicrobial peptides: an essential component of the skin defensive barrier Curr Top
Microbiol Immunol, 306 (2006), pp. 91-110
5. Matthew Knight , Sarah Stanley, HIF-1α as a central mediator of cellular resistance to intracellular pathogens Cell
Immunol. 2016
6. Tania Charpentier , Akil Hammami Simona Stäger Hypoxia inducible factor 1α: A critical factor for the immune
response to pathogens and Leishmania Cell Immunol. 2016.
7. Ghosh AK, Rai R, Park KE, Eren M, Miyata T, Wilsbacher LD, Vaughan DE. 2016. A small molecule inhibitor of
PAI-1 protects against doxorubicin-induced cellular senescence. Oncotarget 7(45): 3– 72457.
8. Reyhaneh R, Maryam B, at al. Plasminogen Activator Inhibitor Type-1 as a Regulator of Fibrosis. Journal of cellular
biyochemistry, 2017.
9. Trompezinski S, Pernet I, Mayoux C, Schmitt D, Viac J. Transforming growth factor-beta1 and ultraviolet A1
radiation increase production of vascular endothelial growth factor but not endothelin-1 in human dermal fibroblasts.
Br J Dermatol 143(3):539-545, 2000.
10. Liu JH, Wu HH, Zhao YK, Wang F, Gao Q, Luo DQ. Thalidomide Improves Psoriasis-like Lesions and Inhibits
Cutaneous VEGF Expression without Alteration of Microvessel Density in Imiquimod-induced Psoriatic Mouse
Model. Curr Vascular Pharmacol, 2017.

28
 CYTOKINES AND CHEMOKINES IN DERMATOLOGY
Birgül Özkesici Kurt
Clinic of Dermatology, Adıyaman University Training and Research Hospital, Adıyaman, Turkey

The skin is the largest organ in the human body and forms a barrier against the entry of physical agents, chemicals
and microbes. To maintain this function, keratinocytes undergo a differentiation (also called cornification) process. It
is a highly complex process under the control of cytokines and intercellular signaling molecules. This differentiation
program requires well-regulated cell communication processes. Alterations and disorganization of the differentiation
process lead to weakening of the skin barrier (1). Atopic dermatitis and psoriasis are examples of immunologically well-
defined inflammatory skin diseases that involve defects in skin barrier formation (2,3). Clarifying key pathogenic factors
has changed our therapeutic practice (4-6).
Cytokines and chemokines are responsible for the control of cellular communication and trafficking. Cytokines are
messenger substances that can be secreted by almost any cell type. They can act in an autocrine, paracrine or endocrine
manner. Cytokines exert their biologic activities by binding to specific cell surface receptors (7). Cytokines and
their receptors can be classified based on the three-dimensional structure of the receptors. Besides, due to structural
similarities, some cytokines are grouped into families, e.g. the IL-10 family (IL-10, IL-19, IL-20, IL-22, IL-24, IL-26),
and the IL-12 family (IL-12, IL-23, IL-27) (1). Cytokines influence the proliferation, differentiation, and activation of
cells. Chemokines are a large superfamily of small cytokines that have chemoattractant activity. CC, CXC, C, and CX3C
chemokines are the four main subfamilies (8). They play a crucial role in leukocyte migration. Advances in this area
have provided clinical relevance. I will give this lecture in the light of current dermatological advances.
References
1. Hänel KH, Cornelissen C, Lüscher B, et al. Cytokines and the Skin Barrier. Int J Mol Sci 2013; 14: 6720-45.
2. Rerknimitr P, Otsuka A, Nakashima C et al. The etiopathogenesis of atopic dermatitis: barrier disruption, immunological
derangement, and pruritus. Inflammation and Regeneration 2017; 37: 14.
3. Bai F, Zheng W, Dong Y, et al. Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and
meta-analysis. Oncotarget, 2018; 9: 1266-78.
4. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.
N Engl J Med 2016; 375: 2335-48.
5. Pavel AB, Song T, Kim HJ, et al. Oral Janus kinase/SYK inhibition (ASN002) suppresses inflammation and improves
epidermal barrier markers in patients with atopic dermatitis. J Allergy Clin Immunol 2019; 144: 1011-24.
6. Bai F, Li GG, Liu Q, et al. Short-Term Efficacy and Safety of IL-17, IL-12/23, and IL-23 Inhibitors Brodalumab,
Secukinumab, Ixekizumab, Ustekinumab, Guselkumab, Tildrakizumab, and Risankizumab for the Treatment of
Moderate to Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis of Randomized Controlled
Trials. J Immunol Res 2019; 2019: 2546161.
7. Thomson AW. The cytokine handbook. 2nd ed. London: Academic Press; 1996.
8. Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 2015; 7: a016303.

29
 NOD2: THE INTESTINAL GATE KEPER IN DERMATOLOGY
Büşra Altun Deniz

Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular protein recognition receptor and this
intracellular surveillance protein detect bacterial peptidoglycan and stimulates host immune response.
There are hundreds of NOD2 gene mutations associated with diseases such as Crohn’s disease, Blau syndrome, and
NOD2-associated autoinflammatory disease (NAID). Its relationship with graft-versus-host-disease is controversial.
NOD2 gene mutations are associated with several diseases and shapes the gut commensal microbiota and pathogens. In
this presentation, we present about the structure of NOD2, relationship with diseases and role of NOD2 in dermatology.

References
1.Nabhani Z A, Dietrich G, Hugot J-P. Nod2: The intestinal gate keper. Plos Pathog. 2017 Mar 2;13(3):e1006177.
2. Yao Q MD. Nucleotide-binding oligomerization domain containing 2: Structure, function, and diseases, Semin.
Arthritis Rheum., 43 (2013), pp. 125-130
3. R. Caruso, N. Warner, N. Inohara, G. Nunez NOD1 and NOD2: signaling, host defense, and inflammatory disease
Immunity, 41 (2014), pp. 898-908
4. Caso, P. Galozzi, L. Costa, P. Sfriso, L. Cantarini, L. Punzi Autoinflammatory granulomatous diseases: from Blau
syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn’s disease RMD Open, 1 (2015), Article
e000097

30
 TRANSEPIDERMAL ELIMINATION IN DERMATOLOGY
Gökşen Ertuğrul

Tranepidermal elimination (TE) is a mechanism whereby foreign or altered constituents can be removed from the
dermis. There are 3 mechanisms whereby dermal foreign material can be transported to the surface of the skin. In type 1;
nonmotile cells (eg,erytrocytes) or small inert particles (eg,hemosiderin) carried upward to the surface during epidermal
turnover. In type 2; larger, motile cells (eg,leukocytes) or organisms such as Treponema pallidum may actively migrate
into the epidermal spaces. Type 1 and 2 have been termed as “transmigration”. In type 3; there is varying degrees of
pseudoepitheliomatous hyperplasia of the epidermis or follicular epithelium. İrritant material partially or completely
taken into the prolifering epithelium and moved upward by the force of maturing keratinocytes. As a result, transepithelial
perforating channels are formed (1,2).
Perforating disorders of the skin are group of uncommon diseases which are histopathologically characterised by
transepidermal elimination of material from the upper dermis. Perforating dermatoses have a common clinical
appearance; umbilicated papules with hyperkeratotic plug and unigue histopathologic findings (1). Due to the fact that
perforating dermatoses are quite rare, little is known about their pathogenesis.
Perforating dermatoses may be divided into in primary and secondary forms. In primary perforating dermatoses, the
main disease process consists of perforation of the dermoepidermal junction and transepidermal elimination of collagen
or elastic fibers. In secondary perforating dermatoses, perforation and elimination of connective tissue fibers or other
materials is an occasional phenomenon which occurs in another dermatosis with a different pathogenesis (3).
Primer Perforating Diseases;
1. Elastosis perforans serpiginosa (EPS)
2. Reactive perforating collagenosis (RPC)
3. Kyrle disease (Hyperkeratosis follicularis et parafollicularis in cutem penetrans) (KD)
4. Perforating folliculitis (PF)
Secondary Perforating Dermatoses
Non-infective granulomatous disorders; Granuloma annulare, Necrobiosis Iipoidica diabeticorum, Rheumatoid
nodule, Sarcoid
Dermatoses with calcification; Pseudoxanthoma elasticum, Calcified tumor of hair follicle origin (pilmatricoma),
Calcinosis cutis, Osteoma cutis
Infectious agents; Botryomycosis, Schistosomiasis, Chromoblastomycosis, Tuberculosis, Leishmaniasis,
Rhinosporidiosis, Lobomyosis, Histoid leprosy
Others; Chondrodermatitis nodularis chronica helicis, Collogenome perforant verruciforme, Lichen nitidus,
Papular mucinosis, Melanoma, Amyloidosis, Vitiligo, Nevocellular nevus, Porokeratosis of Mibelli, Hidradenitis
Suppurativa, Eruptive vellus hair cyst, Gout crystals, Tattoo pigment
Rapini et al suggested in 1989 that perforating dermatosis seen in people with diabetes mellitus (DM) or kidney disease
should be named ‘acquired perforating dermatosis’. However, many literature still use other terms such as acquired
reactive perforating dermatosis, acquired perforating disorders, and perforating dermatoses (4).
Elastosis perforans serpiginosa
Elastosis perforans serpiginosa is a rare skin disease characterized by transepidermal elimination of abnormal elastic
fibers. This condition classically presents as small papules arranged in serpiginous or annular patterns on the neck,
face, arms, or other flexural areas (5). We can distinguish three subtypes of EPS. The first one, known as reactive
one, is associated with connective tissue diseases such as Ehlers-Danlos syndrome, cutis laxa, Marfan syndrome,
acrogeria, Rothmund-Thomson syndrome, osteogenesis imperfecta, Down’s syndrome and pseudoxanthoma elasticum.
The second form of the disease is a drug-induced one which is caused by treatment with D-penicillamine. The last

31
subtype, idiopathic one, may be associated with genetic basis of the autosomal dominant type of inheritance (6). It is
believed that 90% of EPS cases are patients before the age of 30. EPS more often affects men and only 25% of cases
are women. The prevalence of the disease is not known exactly (6). EPS etiopathogenesis has not been fully elucidated.
Differential diagnosis should include granuloma annulare, dermatophyte infections, sarcoidosis, skin calcinosis, Mibelli
porokeratosis (5).
In the biopsies an increased amount of elastic fibers can be found. There is no ‘gold standard’ therapy. Numerous treatment
modalities have been described. The pinhole method using a carbon dioxide laser showed complete clearing in one case.
Topical tazarotene and topical imiquimod therapy is reported to improve EPS skin lesions. Discontinuing penicillamine
therapy does not guarantee preventing further development of EPS lesions in patients undergoing penicillamine therapy (5).
Reactive perforating collagenosis
Reactive perforating collagenosis is a rare skin disease that has transepidermal elimination of altered collagen through
the epidermis. While there is epidermal hyperplasia in new lesions, degenerated basophilic collogen fibers and
invagination of the epidermis with keratin plug will be observed in advanced lesions (7). The inherited form begins
in infancy as papules located on the extensor surfaces of the hands, elbows and knees, most likely after superficial
trauma to the area. Fewer than 50 cases have been reported in the literature so far (7). Reactive perforating collogenous
lesions gradually turn into larger, umbilicated papulonodules with central adherent keratin plugging. The acquired form
found in adults is more common and a underlying systemic disease mostly detected (8). DM, chronic renal failure
and hyperuricemia are the most common diseases associated with acquired RPC. Other rare reasons are; thyroid and
liver diseases, myeloproliferative and solid malignant neoplasms and some drugs (eg, clopidogrel, indinavir, sirolimus)
(8). Acquired RPC is most common between the 3rd and 5th decades (7). Acquired form predilection sites are; trunk,
shoulder girdle, gluteal region and extensor aspects on the upper and lower extremities (8). Lesions can often be itchy
and heal within 6-8 weeks with hypopigmentation or scarring. Koebner phenomenon of the lesions can ocur. The sex
distribution is generally considered to be equal. Most patients will experience a relapsing and remitting course of the
disease throughout their life (7). At the pathophysiological level, RPC is characterized by hyaline degeneration of
collagen fibers. The metabolic products obtained remain in proteins with a long half-life and change their physical /
biochemical properties. Elimination of metabolites is impaired in chronic renal failure. The microtrauma to the skin may
trigger the elimination of altered collagen fibers (8).
The treatment of ARPD is primarily the treatment of internal or oncological diseases with which it is associated. This
includes the treatment of metabolic disorders, optimal management of diabetes mellitus, effective dialysis, and, if
possible, the curative treatment of existing solid or hematopoietic neoplasms (8). Avoiding trauma is important. In
topical treatment, first the application of keratolytic agent (5-7% concentration of salicylic acid, 10-15% urea and 0.01-
0.1% tretinoin in Vaseline) after which the detacment of crusts and curettage is performed. Topical corticosteroids,
antiseptic agents can be added to the treatment. Intralesional injections of the triamcinolone suspension can be tried. In
addition, corticosteroids and retinoids can be used as systemic therapy. Systemic antihistamines and phototherapy are
used to treat pruritus. Different responses have been reported regarding allopurinol treatment (8).
Perforating folliculitis
In perforating folliculitis; necrotic and modified dermal material is incorporated into the follicular lumen and slowly
eliminated to the surface. Here, a dilated follicular infundibulum filled with a parakeratotic plug and a basophilic nuclear
debris is seen (1). PF lesions are characterized by erythematous follicular papules with a central keratotic plug, several
millimeters in diameter (3). PF persists for years with periods of remission, age of onset is between 2nd and 4th decades
(1). Perforating folliculitis is usually associated with underlying conditions such as chronic renal failure, diabetes
mellitus, arterial hypertention, primer sclerosing cholangitis, vitamin A deficiency, juvenile acanthosis nigricans , human
immunodeficiency virus and drugs. Drugs which are reported to be associated with perforating folliculitis include
infliximab, etanercept, bendamustine nilotinib, sorafenib and vemurafemid.

32
Kyrle disease
Histopathologically there is characteristic transepidermal elimination of abnormal keratin. Kyrle disease usually
manifests as multiple, discrete, eruptive papules with a central keratotic plug on the lower extremities. Although few
hereditary cases have been reported, most of the cases develops secondary to systemic chronic diseases (10). Kyrle
disease typically occurs between the age of 30 and 50 years. Female-to-male ratio of up to 6:1. Kyrle disease is most
commonly associated with chronic renal disease and diabetes mellitus. In rare cases, it has been seen in tuberculosis,
pulmonary aspergillosis, scabies, atopic dermatitis, AIDS, neurodermatitis, malignancy, hepatic disorders, congestive
heart failure, and endocrinological disorders. There are also authors who consider kyrle disease as a variant of prurigo
nodularis representing end-stage excoriated folliculitis(10).

References;
1) Shah H, Tiwary AK, Kumar P. Transepidermal elimination: Historical evolution, pathogenesis and nosology. Indian J
Dermatol Venereol Leprol. 2018 Nov-Dec;84(6):753-757. doi: 10.4103/ijdvl.IJDVL_396_17. PMID: 30073986.
2) Woo TY, Rasmussen JE. Disorders of transepidermal elimination. Part 1. Int J Dermatol. 1985 Jun;24(5):267-79. doi:
10.1111/j.1365-4362.1985.tb05781.x. PMID: 3160676.
3) Wagner G, Sachse MM. Acquired reactive perforating dermatosis. J Dtsch Dermatol Ges. 2013 Aug;11(8):723-9,
723-30. English, German. doi: 10.1111/ddg.12131. Epub 2013 May 29. PMID: 23718268.
4) Harbaoui S, Litaiem N. Acquired Perforating Dermatosis. [Updated 2020 May 16]. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539715/
5) Lee SH, Choi Y, Kim SC. Elastosis perforans serpiginosa. Ann Dermatol. 2014;26(1):103-106. doi:10.5021/
ad.2014.26.1.103
6) Polańska A, Bowszyc-Dmochowska M, Żaba RW, Adamski Z, Reich A, Dańczak-Pazdrowska A. Elastosis perforans
serpiginosa: a review of the literature and our own experience. Postepy Dermatol Alergol. 2016;33(5):392-395.
doi:10.5114/ada.2016.62849
7) Mullins TB, Sickinger M, Zito PM. Reactive Perforating Collagenosis. [Updated 2020 Sep 29]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/
NBK459214/
8) Wagner G, Sachse MM. Acquired reactive perforating dermatosis. J Dtsch Dermatol Ges. 2013 Aug;11(8):723-9,
723-30. English, German. doi: 10.1111/ddg.12131. Epub 2013 May 29. PMID: 23718268
9) SHIRAISHI K, MASUNAGA T, TOHYAMA M. A Case of Perforating Folliculitis Induced by Vemurafenib. Acta
Derm Venereol 2019; 99: 230–231
10) Rice AS, Zedek D. Kyrle Disease. 2020 Jun 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2020 Jan–. PMID: 30422481.

33
 Nobel Prize of Aziz Sancar and Dermatology
Habibullah Aktaş
Karabük Üniversitesi Tıp Fakültesi, Dermatoloji Anabilim Dalı, Türkiye

Aziz Sancar won the 2015 Nobel Prize in Chemistry for his research mapping how cells repair damaged DNA and
preserve their genetic information.
The DNA structure is faced with the attack of thousands of toxic internal and external agents every day. In response
to these attacks, human cells have tried to develop many repair pathways to maintain their integrity. Absence
or insufficiency of these repair mechanisms led to many diseases including cancer and genetic disorders.Some types
of colon and breast cancer along with several genetic disorders including Ataxia Telangiectasia , Bloom and Werner
syndrome have been reported in individuals with repair defects in cells (1).
Skin cancer is the most common form of cancer across the world. The main cause of this cancer is DNA damage induced
by the ultraviolet component of sunlight. Ultraviolet radiation produces major lesions in DNA, which are mutagenic
and carcinogenic in animal model systems and are thought to be the primary cause of skin cancer in humans (2).
Exposure of cells to ultraviolet light from the sun causes the formation of pyrimidine dimers in DNA that have the
potential to lead to mutation and cancer.In humans, the single way for removing pyrimidine dimers from the genome is
nucleotide excision repair (3).
Aziz Sancar studied the first DNA repair pathways, an enzymatic photoreactivation which is the process of converting
ultraviolet-induced pyrimidine dimers back to monomers by photolyase enzyme (4).
Photolyase is a member of cryptochrome/photolyase protein family which perform different functions such as DNA
repair, circadian photoreceptor, and transcriptional regulation. This enzyme repairs DNA photoproducts formed due to
ultraviolet exposure through the absorption of blue light (5).
Several products are now commercially available that contain the specific ingredient, photolyase, one of the DNA
repairing enzymes shown to have clinical effect on human skin.
Ultraviolet-induced skin cancers are caused by mutagenic replication of epidermal keratinocyte DNA. The same
ultraviolet dose is more carcinogenic in early morning hours compared to exposure in the early evening hours.Sancar et
al found that maximum repair capacity was in the morning hours. Thereby, restricting ultraviolet exposure to morning
hours would reduce the risk of skin cancer in humans (6).
Besides skin cancers, there are many other diseases characterized by hypersensitivity to ultraviolet and are often
precipitated or exacerbated by exposure to sunlight.So, excision repair is really an important issue for human health.

References
1.Saini N. The journey of DNA repair. Trends Cancer. 2015 Dec 1;1(4):215-216
2. Cadet J , Douki T . Formation of UV-induced DNA damage contributing to skin cancer development. Photochem
Photobiol Sci. 2018 Dec 5;17(12):1816-1841.
3.Kemp MG, Sancar A. DNA excision repair: where do all the dimers go? Cell Cycle. 2012 Aug 15;11(16):2997-3002
4.Sancar A, Rupert CS. Cloning of the phr gene and amplification of photolyase in Escherichia coli. Gene. 1978;4:295–308
5. Kavakli IH, Ozturk N, Gul S. DNA repair by photolyases. Adv Protein Chem Struct Biol. 2019;115:1-19)
6. Gaddameedhi S, Selby CP, Kaufmann WK, Smart RC, Sancar A. Control of skin cancer by the circadian rhythm. Proc
Natl Acad Sci U S A. 2011 Nov 15;108(46):18790-5.

34
 THE RATIONAL USE OF DRUGS
Özgür Gündüz
Kırıkkale University Faculty of Medicine Hospital, Kırıkkale, Turkey

The Irrational Use of Drugs (IUD) is an ever-growing global problem. Due to non-compliance to the rules of rational
use of drugs (RUD), many formerly unencountered economic and health-related problems have begun to arise, and the
consequences of “irrational drug usage” make themselves more evident with each passing day. According to WHO,
more than 50% of all medicines are incorrectly prescribed, dispensed, and sold, and more than 50% of patients take their
drugs incorrectly.1
Rational Use of Drugs is defined by the World Health Organisation (WHO) ‘s experts as “Patients receive medications
appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time,
and at the lowest cost to them and their community.”, in a meeting in Nairobi in 1985.2
The most common factors that may contribute to the incorrect use of medicines are indicated as follows;
1. Prescriptions based on the information from pharmaceutical companies rather than on evidence-based clinical
guidelines;
2. Mis- or incomplete diagnosis of a patient’s disease
3. Patients’ budget limitations leading them to seek affordable but not-quality-assured versions of drugs on the internet.
CONSEQUENCES OF IRRATIONAL DRUG USE
One of the most well-known consequences of irrational drug use is the emergence of antibiotic-resistant bacteria.
Overuse of antibiotics has led to the appearance of drug-resistant forms of various infectious diseases (e.g., multidrug-
resistant forms of tuberculosis and staph. aureus). Other negative results of misuse include exhaustion of national health
budgets, depletion of drug stocks, and increased drug prices. In addition to these global problems, incorrect use of drugs
may also cause serious individual risks for patients, i.e., adverse events which may increase the illness period, cause
death or reduce their faith in health-care providers.3
A PERSONAL EXPERIENCE
Like our many other colleagues, I have also experienced the effects of irrational use of drugs firsthand. At this point,
I would like to present one of the cases followed-up in my clinic to emphasize the effects of “irrational use of drugs”
on patients and doctors, to show how harder our lives are made by these antibiotic-resistant bacteria, the so-called
“superbugs” by the mainstream media.
An 80-year man was referred to our clinic. This man was diagnosed with erysipelas and treated for 25 days with
sulbactam + ampicillin combination (first ten days with tablet form and the remaining 15 days with iv form). Despite the
worsening of the clinical situation, the patient’s medications were not reviewed and changed. At the end of the 25 days,
due to lack of clinical improvement, he was referred to our clinic. At the time of admission, the patient’s right leg was
edematous, covered with erythema, and painful to touch. After the admission and hospitalization, we performed multiple
biopsies for cultures. Systemic antibiotherapy was started with tazobactam and teicoplanin without any further delay.
All the bacterial cultures were negative, but there was a marked elevation in the Antistreptolysin O levels. After 30 days,
there was a marked improvement in the patient’s condition: to be precise in the condition of his right leg. However,
during these days, we first had to struggle with the impaired renal function tests. Due to the persistent elevations in blood
urea nitrogen and creatinine levels, we had to extend the intervals between the teicoplanin doses, leading to extended
hospitalization and immobilization. On the 10th day (about after 40 days of immobilization), a deep vein thrombosis
in the right leg manifested with intensified erythema and pain. The patient was heparinized (impaired renal function
test), which was followed by gastrointestinal bleeding. Heparin dose was lowered, but then atrial fibrillation occurred,
possibly due to thromboembolism. We had found ourselves in a situation similar to a “Mexican Standoff.” We could

35
neither increase nor decrease the heparin doses safely. Finally, heparin doses were increased with closeup monitoring
and with more intense gastrointestinal protective therapy.
As you can see, all the clinical and laboratory clues were pointing out to a streptococcal infection. Theoretically, this
patient should be able to recover with simple aminopenicillins in 10 – 14 days. But it took him 60 days to heal, and
during this period, he experienced many serious complications.

Probably, many of us have experienced similar situations and are familiar with this aspect of irrational drug use,
antibiotic-resistant bacteria. World Health Organisation’s 2014 surveillance report for global antimicrobial resistance
(AMR) shows us that we are not alone, and the situation is far more critical.4
CONCLUSION
Irrational use of medicines is a global and multifaceted problem with severe consequences. Physicians may contribute
to RUD by staying up to date with therapeutical guidelines.

REFERENCES
1. World Health Organization. World Medicines Situation Report 2011. World Health Organization; Geneva,
Switzerland: 2011
2. World Health Organization Rational use of drugs: A review of major issues; Proceedings of the Conference of
Experts; Nairobi, Kenya. 22–29 November 1985.
3. Vincent Rajkumar S. The high cost of prescription drugs: causes and solutions. Blood Cancer J. 2020;10(6):71.
Published 2020 Jun 23. doi:10.1038/s41408-020-0338-x
4. https://www.who.int/antimicrobial-resistance/publications/surveillancereport/en/

36
 INFLAMMOSCOPY: BASICS AND BEYOND
Paweł Pietkiewicz
General and Oncological Surgery Clinic I, Greater Poland Cancer Center, Poznan, Poland
Polish Dermatoscopy Group

Even though the primary idea behind the introduction of dermatoscopy was an early skin cancer diagnosis, the method
has become widely used in a number of situations. Considering how common are inflammatory diseases in everyday
dermatology practice, inflammoscopy becomes an integrative part of the dermatologic clinical examination, along
with taking medical history, visual inspection and palpation. The rudimentary knowledge on the origins of colours and
vascular patterns in dermatoscopy, and the ability to combine all the clues is pivotal for making the diagnosis and to
interpret the inflammoscopic images during the follow-up to monitor the outcomes of the treatment (monitoroscopy)
[1]. This powerful auxiliary tool is not only potent to rule out many clinical differentials, confirm the tentative diagnosis
or introduce new, dermatoscopic ones. This method limits the costs of care (unnecessary laboratory tests and medical
procedures), saves patient’s money, stress and time till the final diagnosis. Moreover, it may prevent the consequences
of diagnostic error and subsequent therapeutic side-effects. The dermatoscope creates an invisible bond between the
patient and the physician, and familiarizes him with the idea that the physician cares about the patient’s well-being, is
precise and eager to help, and has a broad knowledge on what he sees. International Dermoscopy Society consensus
on inflammoscopy (2019) distinguished 5 parameters important for the diagnosis: vascular clues (morphology and
arrangement), scale (colour and distribution), follicular clues, other clues and specific clues (unique to particular
diagnoses) [2,3]. 4 clinical groups of inflammatory diseases were selected for this lecture (papulosquamous and
maculopapular diseases, papulokeratotic diseases, erythematous facial diseases and granulomatous diseases) either due
to their prevalence or for the presence of specific clues [4,5].
Keywords: dermatoscopy, inflammoscopy, monitoroscopy, inflammatory diseases

References:
1. Errichetti E. Dermoscopy in Monitoring and Predicting Therapeutic Response in General Dermatology (Non-Tumoral
Dermatoses): An Up-To-Date Overview. Dermatol Ther (Heidelb). 2020 Dec;10(6):1199-1214.
2. Errichetti E, Zalaudek I, Kittler H, et al. Standardization of dermoscopic terminology and basic dermoscopic parameters
to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International
Dermoscopy Society. Br J Dermatol. 2020 Feb;182(2):454-467.
3. Errichetti E, Stinco G. The practical usefulness of dermoscopy in general dermatology. G Ital Dermatol Venereol.
2015;150(5):533–546.
4. Lallas A, Zalaudek I, Argenziano G, et al. Dermoscopy in general dermatology. Dermatol Clin. 2013 Oct; 31(4):679-94.
5. Errichetti E. Dermoscopy of Inflammatory Dermatoses (Inflammoscopy): An Up-to-Date Overview. Dermatol Pract
Concept. 2019 Jul; 9(3): 169–180.

37
 FACIAL PIGMENTED LESIONS: MAKE IT SIMPLE!
Ömer Faruk Elmas
Kırıkkale University, Department of Dermatology, Kırıkkale, Turkey

Dermoscopy significantly enhances the diagnostic accuracy of pigmented and non-pigmented cutaneous lesions.
Nevertheless, the dermoscopic differential diagnosis of facial lesions may be challenging, due to the specific anatomic
and histologic characteristics of facial skin. Solar lentigo, pigmented actinic keratosis, lichen planus like keratosis
and lentigo maligna are the common pigmented flat facial lesions. The presence of four dermoscopic criteria has high
sensitivity and specificity for the diagnosis of lentigo maligna when compared to solar lentigo or early seborrheic
keratosis. These criteria include asymmetric pigmented follicular openings, dark rhomboidal structures, gray globules,
and gray dots. Every single criterion can also be observed in solar lentigo or seborrheic keratosis but the presence of all
four features together is indicative of lentigo maligna. In contrast, light brown curved lines, milia like cysts, scalloped
borders and sharp demarcation have been linked with the diagnosis of seborrheic keratosis or solar lentigo. Recent
studies showed that lentigo maligna and pigmented actinic keratosis show strikingly similar dermoscopic patterns.
Any of the established criteria of lentigo maligna can be also observed in pigmented actinic keratosis. However; black
blotches within the follicular opening, namely obliterated follicles appear quite specific to lentigo maligna while obvious
follicular openings are indicative of pigmented actinic keratosis. The differential diagnosis between the two entities may
be even histopathologically challenging when it is not clear whether the pigmented atypical cells in the basal layer are
keratinocytes or melanocytes. Dermoscopic differentiation between lichen planus like keratosis and lentigo maligna is
also not straightforward and can be made only if areas of the preexisting benign solar lentigo and seborrheic keratosis
are yet preserved. Completely or nearly completely regressed lichen planus like keratosis is distinguished by diffuse
brownish-gray granules, which may coalescence to create globules, streaks, or even structures similar to rhomboids.
Because lentigo maligna may display the same dermoscopic features, a biopsy should constantly be done in a lesion
exhibiting dermoscopic hints of regression.

References
1.Tschandl P, Gambardella A, Boespflug A, Deinlein T, de Giorgi V, Kittler H, Lallas A, Malvehy J, Moscarella E, Puig
S, Scalvenzi M, Thomas L, Zalaudek I, Alfano R, Argenziano G. Seven Non-melanoma Features to Rule Out Facial
Melanoma. Acta Derm Venereol. 2017 Nov 15;97(10):1219-1224. doi: 10.2340/00015555-2759. PMID: 28761960.
2. Ozbagcivan O, Akarsu S, Ikiz N, Semiz F, Fetil E. Dermoscopic Differentiation of Facial Lentigo Maligna from
Pigmented Actinic Keratosis and Solar Lentigines. Acta Dermatovenerol Croat. 2019 Sep;27(3):146-152. PMID:
31542057.
3. Fensterseifer GS, Lodi AP, Dantas ML, Boff AL, Lovatto L. Lentigo Maligna of the Face: The Importance of
Clinical, Dermoscopic, and Histological Correlation. Dermatol Pract Concept. 2019 Oct 31;9(4):292-294. doi: 10.5826/
dpc.0904a08. PMID: 31723463; PMCID: PMC6830558.
4. Micantonio T, Neri L, Longo C, Grassi S, Di Stefani A, Antonini A, Coco V, Fargnoli MC, Argenziano G, Peris K. A
new dermoscopic algorithm for the differential diagnosis of facial lentigo maligna and pigmented actinic keratosis. Eur
J Dermatol. 2018 Apr 1;28(2):162-168. doi: 10.1684/ejd.2018.3246. PMID: 29620004.
5. Kelati A, Baybay H, Moscarella E, Argenziano G, Gallouj S, Mernissi FZ. Dermoscopy of Pigmented Actinic Keratosis
of the Face: A Study of 232 Cases. Actas Dermosifiliogr. 2017 Nov;108(9):844-851. English, Spanish. doi: 10.1016/j.
ad.2017.05.002. Epub 2017 Jul 11. PMID: 28705516.

38
 DERMOSCOPY IN MELANOMA: WHAT’S NEW?
Tugba Kevser Uzuncakmak
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Department of Dermatology, Turkey

Melanoma is one of the most aggressive skin cancers and accounts for the vast majority of skin cancer deaths. Due to
the rising incidence of cutaneous melanoma clinicians may need new diagnostic techniques and clues as well as the
improvement of those that are already well known, such as dermoscopy. Since early detection and a proper technique
for excising the tumor are crucial for patients’ survival, early staging of the tumor is very important.
Multicomponent global pattern, including atypical network, regression, irregular dots/globules, irregular bloch,
irregular streaks/pseudopods, shiny white streaks, blue white veil and atypical vessels is the most common and classical
dermoscopic feature of melanoma. Most of the features above have been described in advanced melanoma cases and
recently there are some new dermoscopic features that are described especially in diagnosis of melanoma in situ and
small melanomas. Of course, classical features may be found in these tumors but irregular hyperpigmented areas,
prominent skin markings, polygons/angulated lines and rhomboids or zig-zag lines may be the main clues of early
melanoma. In nonpigmented thin melanomas the irregular blue structureless areas, shiny white lines, dotted vessels and
serpentine vessels may be the clues for melanoma.
The presence of such dermoscopic structures should alert the examining clinician. From this point of view, dermoscopic
examination is a very important method in the early diagnosis of cutaneous melanoma, especially in regard to early,
non- metastatic tumors.

References
1. Lallas A, Longo C, Manfredini M, Benati E, Babino G, Chinazzo C, Apalla Z, Papageorgiou C, Moscarella E,
Kyrgidis A, Argenziano G. Accuracy of Dermoscopic Criteria for the Diagnosis of Melanoma In Situ. JAMA Dermatol.
2018 Apr 1;154(4):414-419.
2. Ramji R, Oakley A, Rademaker M. Morphological evolution in melanoma in situ using revised pattern analysis.
Pigment Cell Melanoma Res. 2020 Aug 29. doi: 10.1111/pcmr.12923.

39
 MUCOSCOPY: WHAT WE KNOW?
Prof. Dr. Mustafa Turhan Sahin
Celal Bayar University, Medical Faculty, Dept. of Dermatology, Manisa, Turkey

Dermoscopy is a noninvasive technique, which is widely used for the examination of pigmented and nonpigmented
lesions of the skin, scalp, nails, palms, and soles. By using dermoscopy, the clinician’s diagnostic accuracy increases,
and may allow the recognition of malignant skin tumors at an early, curable stage. There is increasing evidence that
dermoscopy may also be helpful to differentiate benign from malignant or suspicious lesions arising in the mucosa.
Lips, oral cavity, and genital skin (perianal, penil, vulvar) are mucosal areas. Pigmented or non-pigmented lesions of
these areas are rarely seen. Dermoscopic examination of mucosal lesions, namely Mucoscopy, reveals structural, color
and pattern characteristics of these lesions. This presentation will review the dermoscopic features of pigmented and
nonpigmented mucosal lesions and the dermoscopic criteria for differentiating benign from malignant tumors.

40
 DERMOSCOPY IN ADNEXAL NEOPLASMS
Aylin Türel Ermertcan
Manisa Celal Bayar University, Faculty of Medicine, Department of Dermatology, Manisa, Turkey

Introduction
Cutaneous adnexal tumors are classified to their adnexal differentiation as sebaceous, follicular, ecrine and apocrine.
They often cause diagnostic difficulty. Dermoscopy is a noninvasive technique improves diagnostic accuracy of skin
tumors.
Sebaceous tumors
They are classified as sebaceous nevus, sebaceous hyperplasia, sebaceous adenoma, sebaceoma and sebaceous carcinoma.
Sebaceous nevus; complex hamartoma presents at birth and commonly affects head and neck, particularly scalp. The
natural history is divided into 3 stages: childhood, puberty and postpubertal stage. At the third stage 10-20% may be
complicated by benign or malignant epidermal, adnexal or mesenchymal tumors (trichoblastoma, syringocystadenoma
papilliferum and BCC).
Sebaceous hyperplasia; most common proliferative abnormality of sebaceous glands. It most often presents on the face
of older adults, particularly men and characterized as whitish-yellow or skin colored, soft umblicated papules.
Sebaceous adenoma; solitary or multiple skin-colored, yellowish or reddish nodules, sometimes with multilobulated
surface, particularly seen on head and neck area. Two patterns are observed on dermoscopy. One of them is opaque
structureless ovoid white-yellow centre and embracing elongated radial telangiectasias (crown vessels) with central
crater. The other one is branching but unfocussed arborizing vessels over a white-yellow bacground and few yellow
comedolike globules without central crater.
Sebaceous carcinoma; a rare adenocarcinoma with variable degrees of sebaceous differentiation. Classified into
periocular and extraocular subtypes. Clinical presentation is varied. It has a 30-40% for local recurrence, 20-25% distant
metastases and 10-20% mortality. Dermoscopic pattern described only sporadically. It is composed of polymorphous
atypical vessels, homogeneous yellowish background and ulceration.
Follicular tumors
These are a large and heterogeneous group neoplasms. They are classified as nevus comedonicus, basaloid follicular
hamartoma, trichilemmoma, inverted follicular keratosis, pilomatricoma, trichofolliculoma, trichoblastoma,
trichoepithelioma and fibrofolliculoma.
Nevus comedonicus; clinically characterized by multiple, grouped dilated follicular openings with dark keratin plugs
resembling comedones. Dermoscopically, multiple, well-defined, light and dark brown, circular or barrel-shaped
homogeneous areas with keratin plugs have been observed.
Basaloid follicular hamartoma; a rare acquired or hereditary benign adnexal tumor. Asymptomatic small lesion (macule,
papule, nodüle, plaque) located on the head. Dermoscopically, structureless bluish macule or as a lesion with globular
pattern; white, pink and gray areas; and the presence of comedolike openings and milialike cysts are seen.
Trichilemmoma; well-defined, asymptomatic, flesh-colored papules or verrucous growths located on head. On
dermoscopy, radial linear vessels (occasionally hairpin vessels) with distal thickening adopting a triangular form in the
periphery of lesion (red irislike structure), white shiny areas surrounding vessels, a whitish keratin mass, maybe with a
central hyperkeratotic crust are seen.
Inverted follicular keratosis; a rare tumor originates from follicular infundibulum. Asymptomatic, solitary, white-pink
nodular or verrucous lesion (small than 1 cm) located on head of older men. Dermoscopically, there are 2 main patterns:
the most common «keratoacanthomalike pattern». Central keratin surrounded by hairpin vessels with a white halo in a

41
radial arrangement is seen. The other pattern is characterized by a yellowish-white,
homogeneous, amorphous central area surrounded by hairpin vessels with a white halo in a radial arrangement.
Arborizing vessels, glomerular vessels, corkscrew vessels and milky-red globules may be seen. Vascular structures are
commonly monomorphic.
Pilomatricoma; a benign tumor with tendency toward calcification that usually presents as a single, firm, dermal nodule,
often on the head or neck of children or adolescents. White and/or yellow homogeneous areas shaped and distributed
irregularly (calcification), white streaks, reddish homogeneous areas, hairpin vessels and linear irregular vessels are
common. Ulceration, dotted vessels, structureless blue-gray areas are additional findings.
Trichofolliculoma; uncommon, benign hair follicle hamartoma of adults. Solitary facial or scalp papule with a central
dilated pore with a small tuft of hairs. On «firework» pattern; central brown zone with radial, dark brown projections
are observed. Pinkish papule with a central disruptor and fine peripheral serpiginous vascularization with centripetal
disposition was described by Jegou-Penouil et al. Garcia-Garcia et al described a well-defined, firm, bluish nodule with
a white-pink central area, shiny white structures, dotted vessels and a central scale.
Trichoblastoma; a benign tumor of rudimentary hair follicles characterized by solitary, skin-colored papule on the scalp
or face. It developes in isolation or arise in sebaceous nevus. It is difficult to differentiate BCC by dermoscopy. Both have
blue-gray ovoid nests, leaflike structures, and arborizing vessels. Arborizing vessels in trichoblastoma less branching
than in BCC. Blue-gray globules and ovoid nests more frequent in BCC. Trichoblastomas are symmetric (BCC mainly
asymmetric) and have large blue-gray ovoid nests.
Trichoepithelioma; considered as a superficial trichoblastoma with prominent infundibulocystic differentiation
(cribriform trichoblastoma). There are skin-colored papules on the central face. Dermoscopically; small, thin, infocus
arborizing vessels, shiny white areas/background and milialike cysts are observed.
Fibrofolliculoma; benign, clinically indistinguishable connective tissue tumors. Small (2-4 mm), white to flesh colored
papules are seen on the head, neck and upper trunk. Dermoscopically, fibrofolliculomas show whitish globules with a
central yellowish-brown spot and may present a prominent vascular component, such as curvilinear vessels connecting
red dots and globules. Trichodiscomas reveal whitish globuler structures, blue-gray nests and blurred linear vessels.
Others
Pilar sheath acanthoma; benign tumor as an asymptomatic facial (upper lip) papule with a central opening. On
dermoscopy: papillomatous projections toward the center of the lesion, linear vessels on the periphery, depressed central
area with rests of yellowish keratin are observed.
Trichilemmal carcinoma; a rare malignant tumor frequently appears on the face and ears of elderly patients.
Dermoscopically polymorphous vascular pattern, white-yellowish areas and ulceration have been observed.
Eccrine and Apocrine Tumors
Apocrine and ecrine hidrocystomas, syringocystadenoma papilliferum, nodular hidradenoma, cylindroma and
spiradenoma, syringoma, poroma, hidroacanthoma simplex, porocarcinoma
Apocrine hidrocystomas are benign cystic lesions of apocrine sweat glands. Intradermal translucent nodule on the head
and neck is seen. Dermoscopically; a central homogeneous area, translucent to opaque, occupied the whole lesion is
observed. That area may be skin-colored, yellowish, blue, less frequently pinkish-blue or gray. Vascular structures
usually as arborizing vessels and whitish structures may be observed.
Ecrine hidrocystomas are benign tumors of the ecrine sweat glands. Translucent, skin-colored vesicular-papular lesions,
mainly localized on the face. Dermoscopically; a central homogeneous area with a skin-colored or bluish hue sometimes
surrounded by a pale halo is seen.
Syringocystadenoma papilliferum; a benign sweat glandular tumor frequently seen in association with other adnexal
tumors. Second most common benign neoplasm occuring in sebaceous nevus after trichoblastoma. Quite symmetric,

42
erythematous lesion with exophytic papillary structures, ulceration and vessels are observed. Flatter lesions have pinkish-
white or yellowish structureless central area with irregular vessels were reported by Zaballos et al.
Nodular hidradenoma; is a benign, slowly growing benign tumor of mostly apocrine origin. It is characterized by
solitary, nodular, cystic or pedunculated lesion. Serrano et al reported homogeneous area occupying the whole lesion
with vascular and white structures on dermoscopy. Homogeneous area is pinkish in nonpigmented hidradenomas, bluish
in pigmented hidradenomas and pink-bluish in the rest. Highly vascular; 3 most common
vascular structures are arborizing telangiectasias, polymorphous atypical vessels and linear irregular vessels. It is
confused with BCC, melanoma, dermatofibroma.
Cylindroma; benign tumor of the head, characterized with slowly growing solitary pink or red dermal nodule.
Spiradenoma; solitary blue or pink dermal nodule. Dermoscopy of both are similar, homogeneous pink or pink-orange
area with arborizing telangiectasias, sometimes blue globules and ovoid nests are seen.
Syringoma; common tumors present as multiple small papules on the lower eyelids, less frequently on other locations.
Homogeneous pinkish or light brownish central area with multiple round yellow-whitish structures are seen.
Poroma; uncommon benign tumors clinically simulate other neoplasms. Solitary reddish nodule is seen on the soles or
palms with a collarette. Multiple lesions, pigmented variants and different localizations have been described. It is called
as «great dermoscopic imitator». Dermoscopic features associated with poromas are white interlacing areas around
vessels, yellow structureless areas, milky-red globules. Vessels are poorly visualized.
Hidroacanthoma simplex; is a benign intraepidermal neoplasm derived from acrosyringium. It is usually misdiagnosed
as a seborrheic keratosis, BCC or Bowen disease. As epidermal, special dermoscopic findings are pinkish, whitish or
brownish background with black dots/globules, black lines, whitish globular structuress, scales and dotted vessels.
Porocarcinoma; most frequent malignant sweat gland neoplasm of elderly individuals commonly localized on lower
extremities. It is characterized by pink nodule with occasional ulceration. Dermoscopically; pink, whitish, or brown
background and vascular structures have been seen. White-pink halos around the vascular structures, round or oval
structureless areas, hemorrhage and ulceration are seen.
Others
Accessory nipples; resemble dermatofibroma, peripheral delicate pigment network and a central white scarlike area.
Hidradenoma papilliferum; benign tumor with apocrine differentiation usually localized on anogenital area, diffuse
homogeneous blue pigmentation.
Nipple adenoma; resembles mammary Paget disease, light red background with irregular vessels.
Tubular apocrine adenoma; red to brownish nodule of the scalp, oval bluish areas with short fine telangiectasias and
large blue-gray ovoid nests very similar to BCC.
Microcystic adnexal carcinoma; locally aggressive malignant adnexal tumor of the head and neck, white or orange
background with arborizing vessels and white small dots.
Malignant nodular hidradenoma (hidradenocarcinoma); only one dermoscopic description about a fast-growing facial
nodule; whitish pink background and scattered around, pinpoint, linear irregular, hairpin and glomerular vessels. It
resembles amelanotic melanoma, poroma or porocarcinoma.
Conclusion
Dermoscopy of adnexal neoplasms and the other skin cancers usually resembles to each other. So, excisional biopsy and
histopathological examination is still gold standard for the distinct diagnosis.

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References
1) Zaballos P, Gomez-Martin I, Martin JM, Banuls J. Dermoscopy of adnexal tumors. Dermatol Clin 2018; 36: 397-412.
2) Zalaudek I, Kreusch J, Giacomel J, Ferrara G, Catricala C, Argenziano G. How to diagnose nonpigmented skin
tumors: A review of vascular structures seen with dermoscopy. J Am Acad Dermatol 2010; 63: 377-386.
3) Sawaya JL, Khachemoune A. Poroma: a review of eccrine, apocrine, and malignant forms. Int J Dermatol 2014; 53:
1053-1061.
4) Papageorgiou V, Apalla Z, Sotiriou E, Papageorgiou C, Lazaridou E, Vakirlis S, Ioannides D, Lallas A. The limitations
of dermoscopy: false-positive and falsenegative tumours. JEADV 2018; 32: 879-888.
5) Sgouros D, Piana S, Argenziano G, Longo C, Moscarella E, Kilinc Karaarslan I, Akalin T, Özdemir F, Zalaudek I.
Clinical, dermoscopic and histopathological features of eccrine poroid neoplasms. Dermatology 2013; 227: 175–179.

44
 FACE SHAPES AND COSMETICAL APPROACHES
Gökçe Işıl Kurmuş
Yüksek İhtisas University Department of Dermatology and Venereology, Ankara, Turkey

Abstract
The concept of facial aesthetic has changed over time, for this reason it seems difficult to define ideal aesthetic
characteristics and beauty. The face is the most important factor affecting the physical appearance. The most important
factors of facial attractiveness are averageness, sexual dimorphism, youthfulness and symmetry.
In facial aesthetics, there is a specific mathematical proportion which is called golden proportion (GP). The GP is used
to evaluate the aesthetic appearance of face in aesthetic surgery. Many authors have used the GP tool to measure and
analyse facial aesthetic qualities in their own countries.
Facial analysis typically begins with examining the skeletal framework of the face for symmetry and proportion. This is
traditionally done by dividing the face into horizontal thirds and vertical fifths. The horizontal thirds are measured from
the hairline to the glabella, the glabella to the subnasale, and the subnasale to the menton. Each of these heights is exactly
one-third of the facial height. Studies about facial height proportions reported that there is only 50% of equality. Facial
height is higher in males than in females in all races. The face is also divided into vertical fifths, in which each part is
equal to the width of the eye. Classically, the nose fits perfectly within the middle fifth, and the lateral fifth extends from
the lateral canthus to the lateral most visible point of the helix of the ear on frontal view.
Although cosmetic interventions commonly are described based on a single anatomical unit, it is important to figure
out the relationships between facial structures. Clinicians should be mindful of facial ratios when considering the
introduction of filler materials. Augmentation procedures at the temples, zygomatic arch, jaw, chin, and lips all have
the possibility to alter facial ratios. Changes should therefore be considered in the context of improving overall facial
harmony, with the clinician’s knowledge of the ideal vertical and horizontal divisions of the face. Understanding such
concepts and communicating them to patients can help in addressing all target areas, thereby leading to greater patient
satisfaction.

References
1. Kaya KS, Türk B, Cankaya M, Seyhun N, Coşkun BU. Assessment of facial analysis measurements by golden
proportion.Braz J Otorhinolaryngol. 2019;85:494-50.
2. Lambros V, Amos G. Facial Shape, Size, and Gender. Plast Reconstr Surg. 2020;146:1012-1014.
3. Bueller H. Ideal Facial Relationships and Goals. Facial Plast Surg. 2018;34:458-465.
4. Hashim PW, Nia JK, Taliercio M, Goldenberg G. Ideals of facial beauty. Cutis. 2017;100:222-224.
5. Goodman GJ. The Oval Female Facial Shape- A Study in Beauty. Dermatol Surg. 2015;41:1375-83.

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 OFF-LABEL USES OF HA FILLERS IN AESTHETIC DERMATOLOGY
Hilal Gökalp
Hilal Gökalp Clinic, Istanbul, Turkey

Injectable soft tissue filler procedures are becoming increasingly important for rejuvenating the aging face. Hyaluronic
acid (HA) fillers appear to be ideal due to their low immunogenic potential.1 They are medical device implants approved
by the FDA for use in helping to create a smoother and/or fuller appearance in the face, including nasolabial folds cheeks,
chin, lips, and back of the hands. However, glabella, nose, periorbital area, forehead, and neck have not been approved
by the FDA. The FDA also recommends against using dermal fillers or any injectable filler for body contouring and
enhancement to breast augmentation, size of the buttocks, fullness of the feet and bone, tendon, ligament, or muscle.2,3
As with any medical procedure, there are risks involved with the use of HA-fillers. It is important to understand their
limits and possible risks. Any dermal filler can cause temporary side effects, permanent side effects, or both. Most side
effects associated with HA fillers occur shortly after injection and many of them resolve in a couple of days. Swelling
and pain after hand treatment may last a month or longer. In some cases, side effects may be lethal.4-6
Common risks include; bruising, redness, swelling, pain, tenderness, itching, rash and difficulty in performing activities
(after hand filler).
Less common risks include; raised bumps in or under the skin (nodules or granulomas that may need to be treated
with injections, oral antibiotics, or surgically removed), infection, open or draining wounds, a sore at the injection site,
allergic reaction and vascular occlusion-necrosis.
Rare risks include; anaphylactic shock that requires immediate emergency medical assistance, late allergic reactions,
filler migration, leakage or rupture of the filler material, chronic inflammation and infection, biofilm, hypertrophic or
keloid scars, telangiectasia, the formation of permanent hard nodules, loss of function (Vascular occlusion, resulting in
necrosis, vision abnormalities including blindness, stroke, or even death).3-6
It is crucial to manage complications of both approved or off-label uses of dermal fillers. Safety should be the first
and most important consideration. Hyaluronic acid fillers can be delivered safely and efficaciously by either cannula
or needle if used appropriately. However, the panel recommended that needles be used with caution in areas prone to
vascular complications. Product selection is important, as the safety profiles of dermal fillers may vary. Importantly, the
physical and rheologic properties of the filler should fit the intended intervention. For example, products with a higher
elastic modulus (G′) are not recommended in delicate areas such as the tear trough. Appropriate injection techniques
help to limit the risk of adverse reactions and contour irregularities.7-8
Insufficient experience is a contributory factor in the development of complications. Clinicians should seek appropriate
product selection and practice proper techniques to minimize adverse reactions. Clinicians performing injections should
have a thorough knowledge of injection-related anatomy and before treatment, elicit a full history of previous cosmetic
procedures to determine whether relative or absolute contraindications exist. Vascular complications are statistically
rare following the injection of dermal fillers, but these complications are still prevalent in the population because dermal
filler products are used so often. The risk is higher for these events when large bolus injections are sent deeper into
tissues for volume enhancement and when smaller needles are used. Treatment begins with diagnosis of the event and
should continue with administration of hyaluronidase, aspirin, and topical nitropaste, along with the application of warm
compresses and massage of the affected area. After initial treatment, if ischemia is still present, evidence, although weak,
suggests that hyperbaric oxygen therapy may benefit some patients.6-10

46
References
1. Bertucci V, Lynde CB. Current Concepts in the Use of Small-Particle Hyaluronic Acid. Plast Reconstr Surg. 2015
(136):132-8.
2. Huynh A, Priefer R. Hyaluronic acid applications in ophthalmology, rheumatology, and dermatology. Carbohydr
Res. 2020 (489):107950.
3. FDA, “Dermal fillers (Soft-tissue fillers)” September 2020. https://www.fda.gov/medical-devices/aesthetic-
cosmetic-devices/dermal-fillers-soft-tissue-fillers
4. Vanaman M, Fabi SG, Carruthers J. Complications in the Cosmetic Dermatology Patient: A Review and Our
Experience (Part 1). Dermatol Surg. 2016;42(1):1-11.
5. DeLorenzi C. Complications of injectable fillers, part I. Aesthet Surg J. 2013;33(4):561-75.
6. DeLorenzi C. Complications of injectable fillers, part 2: vascular complications. Aesthet Surg J. 2014;34(4):584-600.
7. Da Costa A. Minimally invasive aesthetic procedures. 2020. Brazil: Springer
8. Signorini M, Liew S, Sundaram H, De Boulle KL, Goodman GJ, et al. Global Aesthetics Consensus: Avoidance and
Management of Complications from Hyaluronic Acid Fillers-Evidence- and Opinion-Based Review and Consensus
Recommendations. Plast Reconstr Surg. 2016;137(6):961-71.
9. De Boulle K. Management of complications after implantation of fillers. J Cosmet Dermatol. 2004;3:2-15.
10. Mansouri Y, Goldenberg G. Update on hyaluronic acid fillers for facial rejuvenation. Cutis. 2015;96(2):85-8.

47
 AGEISM IN AESTHETIC DERMATOLOGY
Ayşe Ferzan Aytuğ
Acıbadem International Hospital Dermatology, Turkey

Growing elderly population referred to as gray or silver tsunami are an increasingly serious health and socioeconomic
concern for modern societies. Aging societies are no longer an interesting phenomenon but rather an inevitable fact1.
Age discrimination is a widespread and insidious global issue with far reaching ramifications. But the tide is turning2.
Ageism against individuals due to age negatively affects older adults, particularly women. Age discrimination has been
shown to negatively affect self-esteem, cognition, behaviour, physiological function, health, willingness to live, and
even mortality. This stress of rejection increases risk for psychological distress and physical health problems. Negative
stereotypes of older adults as being incompetent may lead to different forms of social exclusion3.
Such exclusion is also present in research, specifically in clinical research and randomised clinical trials. Many studies
use upper age limits as an unjustified exclusion criterion4.
Aging is a prominent factor in motivating patients to seek cosmetic treatments. A significant proportion of cosmetic
surgery patients seek antiaging procedures due to negative societal views about aging and the appearence of aging signs3.
84% of adults who undergo minimally invasive cosmetic procedures, and 81% of adults undergoing any cosmetic
procedure, are ages 35 years and older!3
However, few studies have investigated experiences of ageism and their relationship to health among patients seeking
these and other cosmetic procedures3.
‘Looking younger’ and ‘as young as i feel’ were among the main reasons reported by patients for seeking their cosmetic
procedure. patients reported seeking cosmetic treatment to look younger, but not to ‘conceal’ their age!3
Perceived age discrimination was associated with poorer self-rated health, lower self-esteem, and greater anticipation of
age discrimination in the future3,5.
More research is needed to understand how older adults’ use of anti-aging procedures, and the public’s knowledge of
these procedures, may or may not affect experiences of age-based discrimination. Also further studies are required to
understand the relationship between cosmetic procedures and anticipated and perceived age based discrimination in
aging patients to optimize patient outcomes3.
Referrences
1 Stjepan Oreskovic. No Country for old men: five prevalent stereotypes affecting the life of the elderly. Croat Med
J, 2020;61: 184-8.
2 Doug O’Neill. Riding the Wave: Boomers Defy Ageism. Diversity Featured, August 29, 2018
3 Rebecca L. Pearl, Ivona Percec. Ageism and Health in Patients Undergoing Cosmetic Procedures. Research.
Aesthetic Surgery Journal 2018, Vol 39; 7, NP288-NP292.
4 Mannheim I, Schwartz E, Xi W, Buttigieg SC, McDonnell-Naughton M, Wouters E JM\ Zaalen Y. Inclusion of
Older Adults in the Research and Design of Digital Technology. Int.J.Environ.Res.Public Health 2019, 16, 3718.
5 Sabik NJ. Is social engagement linked to body image and depression among aging women? J Women Aging. 2017;
29(5): 405-416

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 BDDA: MYTHS AND FACTS IN AESTHETIC DERMATOLOGY
Pelin Ustuner
BHT Clinic Tema Hospital, Istanbul, Turkey

A myth is a popular belief or tradition that has grown up around something or someone. Besides, a fact is something
that has actual existence. As acne vulgaris, skin aging problems and pigmentation disorders are the most common
dermatological diagnostic skin disorders in the past year in my clinic, I would like to talk about the basic myths in these
three popular topics. The myths and misconceptions about acne causation, exacerbating factors and treatment efficacies
are common not just among the patients, but also among some family physicians (1). It was also seen that there is still
a lack of knowledge about acne course, treatment outcomes, recurrences and isotretinoin therapy (1). The myth that
“acne is just a teenager disease that will improve spontaneously” may have already caused some people refuse to go
to a dermatologist (2). However, acne vulgaris is a chronic disease, that often starts at puberty and lasts long time after
puberty. “Acne is not caused by cosmetics” is another common misconception, as some of the oily comedogenic make
up products are the well known causes of a mild comedogenic acne known as “acne cosmetica” seen especially among
young women (2). Besides, “acne doesn’t affect psychosocial life, it’s just only a skin disease” is another common myth
(3). We have to accept that acne’s psychological impact may affect social relationships, success in business life, sexual
affair and friendship situations (4). Open comedones are thought to be blackheads that are made up of dirt. However,
comedones are consist of oxidized sebum and keratin (2). Face wash with harsh soaps has just very little to do with
acne and does not stop acne or cloging of the pores. Patients need to avoid frequently washing face because it will
cause sebaceous gland hyperactivity to compensate skin lipid loss (2). Some people believe that sun exposure helps to
eliminate acne vulgaris (2). In fact; although there is a little evidence that sunlight has a positive effect on acne, we also
have to consider the possible long term carcinogenic effects of sun exposure (2).
Secondly when we have a look at the myths about skin aging; we may notice some people think that “Only genetic and
age play a role in the formation of wrinkles” (4). But, in fact skin aging includes both intrinsic and extrinsic factors.
Extrinsic factors include enviromental and behavioral factors such as sun exposure, smoking, dietary nutrients, body
mass index, menopausal status (4). The myth that “skin aging can not be prevented by consistent skin regimen” is just a
false belief (5). Retinoic acid, anti-oxidants, estrogens, growth factors and cytokines are some of the secondary measures
against skin aging (5). Besides, cosmetic procedures such as chemical peels, microdermabrassion, laser, botulinum toxin
and filler injections are the tertiary antiaging treatments that reduces and treats the signs of skin aging. While retinoids
such as tretinoin and tazarotene are some of the evidence level A antiaging treatments, aminoacids, minerals, anti-
oxidants such as vitamin C, vitamin E and Coenzyme Q10, alpha-Lipoic acid may also act with a level of evidence that
differ from A to C (5).
There are also numerous other misconceptions regarding the use of botulinum toxin for aesthetic indications that have
arisen (6). Botulinum toxin neurotoxin/protein complexes are irrelevant to the toxins’s therapeutic indications. BONTA
neurotoxin/protein complexes do not influence movement from injection site or immunogenecity (6). Any relationship
between neutralizing antibody formation and clinical response is complex and clinicians should consider other factors
that may induce an appereant loss of clinical response (6). Diffusion appears predominantely, perhaps exclusively, dose
dependent (6). Careful placement and correct dosing optimizes likelihood of good outcomes. Manufacturers recommend
reconstriction of products with sterile non-preserved saline. However, compelling evidence suggests that reconstriction
using preserved saline dramatically improves patient comfort without compromising efficacy (7). Several posttreatment
instructions/restrictions are widely used despite the lack of evidence, but muscle activity after injection may be beneficial
(6). Cooling the treatment area might hinder BONTA translocation and should probably be abandoned (6).
Facial fillers that are used only for the elimination of wrinkles make the face look like frozen and they act exactly the
same as botox are some of the common myths arisen about fillers. Besides, there are still lots of different myths and
misconceptions about the aims, application protocols, treatment outcomes, patient expectations and adverse effects
of cool sculpting, radiofrequency (RF), Thermage, high intensity focus ultrasound (HIFU) and laser hair removal
treatments (7-8).

49
If we consider the most popular myths about the use of sunscreens, the myth that the higher SPF is better is not heard
rarely (9). Besides, applying sunscreens with SPF 15 and SPF 30 will result in SPF45 is another common myth. There
are also some other misconceptions about the use of sunscreens in cloudy weather and rainy seasons such as the sun
exposure is not dangerous during winter (9). Moreover, some popular myths about skin pigmentation include darker
complexion individuals are not likely to develop disorders of hyperpigmentation, using a skin-lightening treatment will
permanently remove skin pigmentation and applying skin lightening products long term is safe (10).

References
1) Ines Brajac, Lidija Bilić-Zulle, Mladenka Tkalcić, Karmen Loncarek, Franjo Gruber. Acne vulgaris: myths and
misconceptions among patients and family physicians. Patient Educ Couns 2004;54(1):21-5.
2) Greg Goodman. Acne--natural history, facts and myths. Aust Fam Physician 2006;35(8):613-6.
3) Brigitte Dreno, Edileia Bagatin, Ulrike Blume-Peytavi, Marco Rocha, Harald Gollnick. Female type of adult acne:
Physiological and psychological considerations and management. J Dtsch Dermatol Ges 2018;16(10):1185-1194.
4) Makrantonaki E, Bekou V, Zouboulis CC. Genetics and skin aging. Dermatoendocrinol 2012; 4(3): 280–284.
5) Guyatt GH, Sackett DL, Sinclair JC, Hayward R, Cook DJ, Cook RJ. Users’ guides to the medical literature. IX. A
method for grading health care recommendations. Evidence-Based Medicine Working Group. JAMA 1995;274(22):1800-4.
6) Dover JS, Monheit G, Greener M, Pickett A. Botulinum Toxin in Aesthetic Medicine: Myths and Realities. Dermatol
Surg 2018;44(2):249-260.
7) Weiss RA. Noninvasive radio frequency for skin tightening and body contouring. Semin Cutan Med Surg 2013;32(1):9-17.
8) Fritz K, Salavastru C. Ways of Noninvasive Facial Skin Tightening and Fat Reduction. Facial Plast Surg 2016;32(3):276-82.
9) Kullavanijaya P, Lim HW. Photoprotection. J Am Acad Dermatol 2005;52(6):937-58; quiz 959-62.
10) Kooyers TJ, Westerhof W. Toxicological aspects and health risks associated with hydroquinone in skin bleaching
formula. Ned Tijdschr Geneeskd 2004;148(16):768-71.

50
 HOLISTIC APPROACH TO SKIN AGING
Şükran Sarıgül Güdük
Dermatologist, Private Practice, Istanbul, Turkey

Skin aging has two components. Intrinsic aging stands for the “normal” decay of the skin, associated with chronological
age. Extrinsic aging is incurred through environmental causes of cell damage (exposome) and overlaps intrinsic aging.
Both intrinsic and extrinsic inflammatory processes combine to manifest in the skin aging as fine wrinkles, loss of
elasticity, dryness, and sallowness. Cosmetic dermatologists use many procedural interventions to diminish signs of
aging. However the procedures alone are not enough for a successful antiaging treatment. A complete anti-aging treatment
can consist of many strategies or combinations of them, such as avoiding exogenous factors of aging, changing one’s
lifestyle and habits (i.e. smoking, UV radiation, nutrition, physical activity, stress), and using topical cosmeceutical
agents and/or oral nutraceuticals.

51
 SUNSCREENS: WHAT’S NEW?
Işıl Bulur
Memorial Sisli Hospital, Turkey

Sunscreens are used to protect the skin against harmful effects of ultraviolet (UV) radiation. The history of sunscreen
can be traced back to the Egyptians, they used ingredients such as rice bran, jasmine, and lupine to avoid the tanning
effects of the sun.1 Modern sunscreens were initially developed with the sole purpose of minimizing erythema after
1930s.2 Nowadays, new sunscreens have the combination of a filter system (UVB, UVA, long-UVA) and antioxidant
protection against infrared and pollution.2
The primary effect of sunscreens includes physical barriers that reflect and scatter light and chemical barriers that absorb
light. Secondary factors include antioxidants, osmolytes, and DNA repair enzymes, which help to limit skin damage by
disturbing the photochemical cascade that takes place by UV sunlight.
Antioxidants, photolyases or photoreactivation enzymes, and polyphenols or plant-derived aromatic compounds have
been the newest area of research due to their anti-inflammatory and anticancer properties.3, 4 Beside newest compounds
delivery methods are also newly research area. Nanostructured lipid carriers (NLCs) have been highlighted for topical
application due to their biocompatibility, owing to the presence of non-irritating and non-toxic lipids. They can provide
controlled release for prolonged time and thus can potentially reduce systemic exposure. More importantly, these lipid
nanoparticles present physical stability and produce the stabilization of labile substances against degradation. Addition-
ally, the concentration of the incorporated sunscreen can be decreased, and the sunscreen effect is kept, which reduces
the risks associated with high concentrations administered.5
In conclusion, together with the newly developed substances, sunscreens provide anti-inflammatory, anti-tumor, and
antioxidant effects and the systemic side effect profile of sunscreens is reduced.

References:
1- Aldahan AS, Shah VV, Mlacker S, et al. The history of sunscreen. JAMA Dermatol. 2015;151(12):1316.
2- Bennett SL, Khachemoune A. Dispelling myths about sunscreen.J Dermatolog Treat. 2020;7:1-5.
3- Afaq F, Katiyar SK. Polyphenols: skin photoprotection and inhibition of photocarcinogenesis. Mini Rev Med
Chem. 2011;11(14):1200-15.
4- Bhatia N, Berman B, Ceilley RI, Kircik LH. Understanding the role of photolyases: photoprotection and beyond. J
Drugs Dermatol. 2017;16(5 Suppl):61-6.
5- Do Prado AH, Araújo VHS, Eloy JO, Fonseca-Santos B, Pereira-da-Silva MA, Peccinini RG, Chorilli M. Synthesis
and Characterization of Nanostructured Lipid Nanocarriers for Enhanced Sun Protection Factor of Octyl p-me-
thoxycinnamate. AAPS PharmSciTech . 2020; 21(4):125.

52
 DO SUNSCREENS PREVENT VITAMIN D SYTHESIS?
Armağan Kutlay
Istanbul Faculty of Medicine, Turkey

Solar ultraviolet (UV) radiation contains UVB and UVA. While UVB makes up ~5% of solar radiation, it is responsible
for most of the damaging effects of the sun. However, UVB also initiates cutaneous vitamin D synthesis, providing the
mechanism responsible for ~80% of all the synthesized in the body (1). Sunscreen use is widely advocated to prevent
the unwanted effects of sun exposure, such as skin aging, sunburns, and skin cancer. There are concerns that widespread
use of sunscreens may lead to vitamin D deficiency.
In theory, effective use of sunscreens should limit UVB-dependent conversion of 7-dehydrocholesterol in the skin to
pre-vitamin D3, which is later hydroxylated in the liver to form 25 hydroxyvitamin (25-OH-D), the primary circulating
form of vitamin D. However, vitamin D production is dependent on various factors, such as the surface area of the body
exposed to sun, exposure time, and previous vitamin D status.
Several experimental studies reported a reduction in vitamin D synthesis with sunscreen use (2,3). These studies utilized
artificial UV radiation sources with spectra different from sunlight and measured the change in vitamin D levels in a
short time span. On the other hand, large field trials with longer periods of observation reported that sunscreen use was
not associated with lower levels of circulating 25-OH-D. However, the sunscreens used in these studies had a moderate
sun protection factor (SPF) (4,5). There are not any field trials with high SPF sunscreens used. Most abundant data on
the subject is present in observational studies, with discrepant results. In a systematic review, it was found that 65% of
observational studies reported no association between sunscreen use and serum 25-OH-D levels, while 25% reported an
increase and 10% reported a decrease (6).
In summary, it can be concluded that there is insufficient evidence that sunscreen use decreases 25-OH-D levels. There is
still a need for large field studies with high SPF sunscreens. Considering the importance of sun protection in preventing
skin cancers, and the low likelihood of sunscreens causing reduced 25-OH-D levels, their benefits seem to outweigh
their risks.

References:
1. Macdonald HM, Mavroeidi A, Fraser WD et al. Sunlight and dietary contributions to the seasonal vitamin D status
of cohorts of healthy postmenopausal women living at northerly latitudes: a major cause for concern? Osteoporos Int
2011; 22:2461–72.
2. Libon F, Courtois J, Le Goff C et al. Sunscreens block cutaneous vitamin D production with only a minimal effect on
circulating 25-hydroxyvitamin D. Arch Osteoporos 2017; 12:66.
3. Faurschou A, Beyer DM, Schmedes A et al. The relation between sunscreen layer thickness and vitamin D production
after ultraviolet B exposure: a randomized clinical trial. Br J Dermatol 2012; 167:391–5.
4. Jayaratne N, Russell A, van der Pols JC. Sun protection and vitamin D status in an Australian subtropical community.
Prev Med 2012; 55:146–50. Marks R, Foley PA, Jolley D et al. The effect of regular sunscreen use on vitamin D levels
in an Australian population. Results of a randomized controlled trial. Arch Dermatol 1995; 131:415–21.
5. Marks R, Foley PA, Jolley D et al. The effect of regular sunscreen use on vitamin D levels in an Australian population.
Results of a randomized controlled trial. Arch Dermatol 1995; 131:415–21.
6. Neale RE, Khan SR, Lucas RM, Waterhouse M, Whiteman DC, Olsen CM. The effect of sunscreen on vitamin D: a
review. Br J Dermatol. 2019 Nov; 181(5):907-915.

53
 DOES PHOTOTHERAPY CAUSE CANCER?
Algün Polat Ekinci
İstanbul University, Faculty of Medicine, Department of Dermatology and Venereology, İstanbul, Turkey

Phototherapy, ultraviolet (UV) light-based therapy, is characterized by controlled administration of non-ionizing

radiation to the skin. Phototherapy is widely used in the treatment of various skin diseases including, psoriasis, mycosis
fungoides, atopic dermatitis, vitiligo, pityriasis lichenoides chronica, eczema, chronic pruritus, lichen planus, and
polymorphous light eruption.1-3
The commonly used phototherapy types are ultraviolet A-1 (UVA-1) spectrum, UVA spectrum with a photosensitizing
agent (psoralenes) (PUVA), and ultraviolet B (UVB) spectrum as broad-band (BB)-UVB or narrow-band (NB)-UVB.4
Being the most often used phototherapy type, UVB phototherapy shows anti-inflammatory, immunosuppressive, and
cytotoxic effects through of cis-urocanic acid induction, Langerhans cell depletion, decreased activity of natural killer
cells, and apoptosis of both T lymphocytes and keratinocytes.4 NBUVB therapy is known to be more effective and less
carcinogenenic as compared with BBUVB therapy.
PUVA phototherapy shows its efficacy by forming the cross-linking of deoxyribonucleic acid (DNA), thus inhibiting
DNA replication. Increased production of reactive oxygen species via PUVA leads to cell membrane damage followed
by cell death. The other effects are depletion of Langerhans cells and suppression of T-lymphocyte functions and
migration.4
UVA-1 phototherapy penetrates into the deeper parts of the dermis. Its mechanism of action occurs via inducing
interstitial collagenase and cytokines, which provides softening of the sclerotic skin.4
Along with therapeutic effects of ultraviolet light, various damages to the skin, including mutations in the DNA of
keratinocytes and fibroblasts, chronic oxidation and inflammation, and changes in the expression of tumor suppressor
genes may result in carcinogenic skin lesions. 2
The risk of nonmelanoma skin cancers (NMSC) with PUVA in patients with psoriasis has been well investigated in
the literature. A systemic review by Archier1 et al. showed controversial results of PUVA therapy concerning the risk
for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in patients with psoriasis. Overall, the majority
of large-scaled studies showed that the risk of SCC was significantly higher for patients exposed to more than 200
sessions or 2000J/cm2 of PUVA than those exposed to less than 100 sessions or 1000J/cm2 of PUVA. Moreover, SCC
may develop in non-exposed skin areas such as the genital region. SCC risk increases linearly with cumulative UV dose.
Moreover, despite to cessation of treatment, the risk continues to persist.1 The risk of BCC was also found to be increased
in patients exposed to very high doses of PUVA. The risk of melanoma among psoriatic patients treated with PUVA was
reported to be increased, particularly in patients who were exposed to at least 200 sessions of PUVA treatments and after
15 years of time from the first treatment. Merkel cell carcinoma (MCC), a rare type of skin cancer, was investigated in
only one study, which showed an increased risk in PUVA-exposed skin sites in patients with psoriasis.
NB-UVB related skin cancers were evaluated in fewer studies compared to PUVA therapy. A recent population-based
retrospective cohort study investigated the risks of skin cancers and precancerous lesions among patients who had
undergone NBUVB to treat vitiligo.5 The authors reported that the risks of Bowen disease, nonmelanoma skin cancers,
and melanoma did not increase even after more than 200 sessions of NBUVB. However, the risks of actinic keratosis
increased significantly in patients who received 200 or more sessions of NBUVB phototherapy.5
There is not a large-scale study evaluating the risk of skin cancers following UVA1 phototherapy. Only two cases
were reported with the development of skin cancers like melanoma and MCC after UVA1 phototherapy. But these two
patients also had other risk factors as follows; concomitant bath PUVA therapy in the first case and immunosuppressive
comorbidities in the second case.6
In conclusion, the increased risk of skin cancers particularly NMSC is well-documented in patients undergone more than

54
200 sessions of PUVA. On the other hand, NBUVB seems to be not associated with the increased risk of skin cancers.
There is the lack of data on carcinogenic risks of UVA-1 and other phototherapy types.

References
1. Archier E, Devaux S, Castela E, et al. Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy
in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol 2012;26:22-31.
2. Hofbauer G. Phototherapie und karzinogenese [Phototherapy and carcinogenesis]. Hautarzt 2013;64:349-53. doi:
10.1007/s00105-013-2587-0.
3. Elmets CA, Lim HW, Stoff B, et al. Joint American Academy of Dermatology-National Psoriasis Foundation
guidelines of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol
2019;81:775-804.
4. Rathod DG, Muneer H, Masood S. Phototherapy. [Updated 2020 Oct 28]. In: StatPearls [Internet]. Treasure Island
(FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563140/
5. Bae JM, Ju HJ, Lee RW, et al.; Korean Society of Vitiligo. Evaluation for Skin Cancer and Precancer in Patients
With Vitiligo Treated With Long-term Narrowband UV-B Phototherapy. JAMA Dermatol 2020;156:529-37. doi:
10.1001/jamadermatol.2020.0218.
6. Thompson KG, Kim N. Distinguishing Myth from Fact: Photocarcinogenesis and Phototherapy. Dermatol Clin
2020;38:25-35. doi: 10.1016/j.det.2019.08.003.

55
 WHAT’S NEW IN PHOTOTHERAPY?
Işıl İnanir
Celal Bayar University, Dept of Dermatology, Manisa, Turkey

Phototherapy has been widely used in dermatology since early 20th century. Conventional phototherapy modalities
are UVA, broadband UVB, narrowband UVB and UVA1. The disadvantages such as frequent clinic visits, difficulty
in some areas, risk of photoaging and carcinogenesis, caused development of newer targeted therapies. Most targeted
phototherapy devices (laser/nonlaser ones) emit radiation in the narrowband UVB range, but UVA emitting machines
also exits.
Excimer laser
The device uses a mixture of a gas and a halogene, predominantly 308-nm xenon-chloride in dermatology. Besides
psoriasis and vitiligo, effectivity was reported in oral lichen planus, alopecia areata, atopic dermatitis, morphea, prurigo
nodularis, mycosis fungoides, and lymphomatoid papulosis. Bulky expensive machines and blistering reaction are
disadvantages.
Monocromatic Excimer light (MEL)
Less bulky and cheaper machines with Xenon-Chloride lambs emitting monochromatic 304 or 308 nm are used.
Relatively larger treatment areas are possible in comparison with excimer laser. Responsive dermatoses are similar.
Targeted NB-UVB/UVA
Devices with high-pressure burner and fibre-optic cable transmit energy directly to the lesion. They irradiate both UVA
and NB-UVB. There are also handheld home therapy devices with the possibility of inproper administration.
Low level laser therapy ( LLLT)
It is also known as photobiomodulation, cold laser and soft laser. Low doses of various light sources (inert gas lasers and
semiconductor laser diodes) are insufficent for ablation, cutting and coagulating. LTTT serves to supress inflammation
and to increase antioxydants. It is found to be beneficial in cutaneous conditions of acne, psoriasis, vitiligo, dermatitis,
herpes, hair loss, keloids and skin aging.
Light emitted diode (LED)
LED is a safe, nonthermal, nontoxic and noninvasive technology. LEDs provide a peak energy output, a less harmful
result and greater body application compared to lasers. They are used for inflammatory acne, wound healing, sunburn,
hair loss, skin photoaging, scar preventation and postinflammatory hyperpigmentation. Since they reach the sebaceous
glands, red and blue LEDS are alsoeffective for acne and rosacea. Visible-near IR (NIR) spectrum is found to be
effective for atopic dermatitis and cellulitis. The antimicrobial effect of 405 nm LED had also been shown. In addition,
LED technology enhances the activity of PDT.
Photodynamic therapy (PDT)
PDT uses photosensitizing agents to augmentate the effects of visible light or lasers. The absorbation of light by the
target cells causes formation of reactive oxygen species, and thereafter apoptosis. PDT is effective in acne, seborrhea,
psoriasis, morphea, verruca, molluscum, leischmaniasis and photodamage in addition to cutaneous malignities as actinic
keratosis, Bowen’s disease and superficial BCC. Fractional laser or microneedle assisted drug delivery of photosensitizers
enhances the activity of PDT

56
Phototermal therapy (PTT)
PTT is the thermal ablation of tumours using photosensizers activated by pulsed laser irradiation at near-infrared (NIR).
It has a limited penetration and less harmful to surrounding tissues. Unlike PDT, oxygen has not any role for the
destruction of malign cells. It can also be combined with PDT for synergistic affects. Nanomaterials such as carbon
nanotube, graphene, gold nanoparticles and quantum nanorods are used in PTT. Not only for cutaneous ones including
melanoma, PTT is an advanced and adjuvant procedure in the treatment several malign tumours in general oncology.
Except malignities, PTT is also reported to be beneficial in warts, wound healing, candidal granuloma etc.
These targeted therapies obtain quick delivery of energy providing less treatment time, less frequent clinic visits, ability
to use in difficult areas as scalp, nails, oral mucosa, palmoplantar and intertriginous and genital regions, and minimizing
side effects. But they are already expensive and appropriate for only small areas. Development of simple, smaller and
cheaper devices in the light of nanotechnology will obtain less harmful and more effective therapies in dermatology.

References
1. Bhole R, Bonde C, Kadam C, Waywale R. Comprehensive Review on PDT and PTT for Cancer Treatment. Turkish
J Oncol 2021 ;36(1):125–32
2. Mehraban S, Feily A. 308nm Excimer Laser in Dermatology. J Lasers Med Sci 2014;5(1):8-12
3. Mysore V. Targeted phototherapy. Indian J Dermatol Venereol Leprol 2009;75:119-25.
4. Sundaram P, Abrahamse H. Phototherapy combined with carbon nanomaterials (1D and 2D) and their applications in
cancer therapy. Materials (Basel). 2020 Oct 28;13(21):4830.
5. Paasch U, Grunewald S. Update on dermatologic laser therapy II - advances in photodynamic therapy using laser-
assisted drug delivery. .J Dtsch Dermatol Ges. 2020 Dec;18(12):1370-1377
6. Ablon G. Phototherapy with Light Emitting Diodes: Treating a Broad Range of Medical and Aesthetic Conditions in
Dermatology. J Clin Aesthet Dermatol. 2018 Feb;11(2):21-27
7. Zhang P, Wu MX. A clinical review of phototherapy for psoriasis. Lasers Med Sci. 2018 Jan;33(1):173-180
8. Elmets CA, Lim HW, Stoff B, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines
of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol. 2019 Sep;81(3):775-804
9. Paasch U, Schwandt A, Seeber N, Kautz G, Grunewald S, Haedersdal M. New lasers and light sources - old and new
risks? J Dtsch Dermatol Ges. 2017 May;15(5):487-496
10. Glass GE. Photobiomodulation: The Clinical Applications of Low-Level Light Therapy. Aesthet Surg J. 2021 Jan
20:sjab025

57
 TYPE II INFLAMMATION AND ITS ROLE IN ATOPIC DERMATITIS AND BEYOND
Marcus Maurer
Dermatological Allergology, Allergie-Centrum-Charité Department of Dermatology and Allergology
Charité – Universitätsmedizin Berlin, Germany

Type II inflammation underlies inflammatory diseases in a range of organs, including the skin. Type II inflammation is
characterized by the action of type II cytokines such as interleukin (IL)-4, IL-13, but also alarmins such as IL-33 and
TSLP. These cytokines contribute to the pathogenesis of atopic dermatitis and various other dermatological diseases,
where they are key drivers of chronic itch and inflammation. In atopic dermatitis, IL-4 is held to sensitize sensory
nerves in the skin and to contribute to itch directly. Type II inflammation is also a key feature of chronic spontaneous
urticaria where type I and type II autoimmunity are underlying causes. Type I autoimmunity is IgE-mediated, and IgE-
mediated inflammation is linked strongly to type II inflammation. IL-4 is increased in chronic spontaneous urticaria,
drives IgE production and is pruritogenic. Ongoing studies in chronic spontaneous urticaria as well as cholinergic
urticaria and cold urticaria with dupilumab, which inhibits IL-4 and IL-13, will characterize the benefit of this approach.
TSLP (thymic stromal lymphopoietin) plays a pivotal role in allergy and inflammation and drives TH2-mediated
immunity. It is produced by keratinocytes and activates mast cells and basophils. Mast cells express TSLP receptors and
make TSLP, and TSLP increases mast cell proliferation and prolongs mast cell survival by interfering with apoptosis.
TSLP is increased in the lesional and non-lesional skin of patients with chronic spontaneous urticaria. In addition to
atopic dermatitis and chronic spontaneous urticaria several other inflammatory skin diseases show features of type II
inflammation. These include chronic prurigo and bullous pemphigoid. In summary, type II inflammation plays a key role
in the pathogenesis of several dermatological diseases. Type II cytokines, pruritus, a role for IgE and mast cells are all
shared pathophysiological features of type II inflammatory skin diseases.

58
 THE ROLE OF ALLERGENS IN ATOPIC DERMATITIS
Maryam Khoshkhui
Allergist and Clinical Immunologist, Mashhad University of Medical Sciences, Mashhad, Iran

Atopic dermatitis (AD) is an important and chronic skin condition that has recently been the subject of enormous
volumes of basic science, clinical, and epidemiologic research.
Clinical associations with AD have greatly expanded in recent years. Current concepts are well beyond thinking solely
of the “atopic march”:
• Eczema and food allergies as an infant • Asthma as a child • Hay fever as an adult
Well controlled studies suggest that allergens can impact the course of this disease.
Two important allergen group are: A) foods B) Aeroallergens
A) Food allergens:
Approximately 33% of infants and young children with AD will show clinically relevant reactivity to a food allergen.
The most concerning reaction is an immediate immunoglobulin E (IgE)-mediated reaction leading to anaphylaxis. Some
patients, instead have a delayed eczematous flare in response to food ingestion.
The NIAID recommendation states: Consideration of limited food allergy testing (ie, cow’s milk, egg, wheat, soy,
peanut) if a child < 5 years of age has moderate to severe AD and the following:
• Persistent disease in spite of optimized management and topical therapy
• A reliable history of an immediate allergic reaction after ingestion of a specific food
Identification of allergens involves taking a careful history and doing selective immediate-hypersensitivity skin tests
or in vitro tests when appropriate. The gold standard for diagnosis of immunoglobulin E (IgE)-mediated food allergy
remains the oral food challenge, with serum IgE testing and skin prick testing serving as acceptable alternatives.
Skin prick test: Negative skin tests with proper controls have a high predictive value for ruling out a suspected allergen.
Positive skin tests have a lower correlation with clinical symptoms in suspected food allergen–induced AD and should
be confirmed with double-blind placebo-controlled food challenge, unless the patient has a history of anaphylaxis to the
suspected food. More importantly, avoidance of foods implicated in controlled challenges results in clinical improvement.
Specific IgE concentrations: In response to four food allergens measured by the Phadia ImmunoCAP assay—egg, 7
kUA/L (2 kUA/L age ≤2 years); milk, 15 kUA/L (5 kUA/L age ≤2 years); peanut, 14 kUA/L; and fish, 20 kUA/L—have
been shown to be associated with a greater than 95% probability of clinical reaction . However, these levels do not
identify the type or severity of reaction.
The atopy patch test: It has revealed sensitization in some patients with AD but remains an investigational tool.
It is important that extensive elimination diets, which can be both burdensome and nutritionally unsound, are almost
never warranted, because even patients with multiple positive allergy tests are rarely clinically sensitive to more than
three foods on challenge.
B) Aeroallergens:
The evidence supporting a role for aeroallergens in AD includes the finding of both allergen-specific IgE antibodies and
allergen-specific T cells. Contact reactions from aeroallergens have been associated in patients with eczema. Lesions
tend to be on exposed areas of the body such as the neck and face. Dust mite has been the most implicated aeroallergen,

59
with positive patch tests in up to 40% of patients.
Environmental control measures aimed at reducing dust mite load may improve AD in patients who demonstrate specific
IgE to dust mite allergen.

References:
1) Middleton’s ALLERGY, principles and practice Ninth Edition 2020
2) Robert Sidbury, Samantha Kodama. Atopic dermatitis guidelines: Diagnosis, systemic therapy, and adjunctive care.
Clinics in Dermatology (2018) 36, 648–652
3) Bergmann MM, Caubet J-C, Boguniewicz M, et al. Evaluation of food allergy in patients with atopic dermatitis. J
Allergy Clin Immunol Pract 2013;1:22–8.
4) Rekha Raveendran. Tips and Tricks for Controlling Eczema. Immunol Allergy Clin North Am. 2019 Nov;39(4):521-533
5) Boyce JA, Assa’ad A, Burks W, et al. Guidelines for the diagnosis and management of food allergy in the United
States: Report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010
6) Hammond C, Lieberman JA. Unproven Diagnostic Tests for Food Allergy Immunol Allergy Clin North Am. 2018

60
 INTEGRATIVE APPROACHES OF VITILIGO
Abdullah Demirbaş
Department of Dermatology, Evliya Çelebi Training and Research Hospital, Kütahya Health Sciences
University, Kütahya, Turkey

Introduction
Vitiligo is an acquired skin disease characterized by depigmented macules with the loss of functional melanocytes in
the skin . The worldwide incidence varies between 0.1 and 2%. Although the average age of onset is around 20 years,
it can occur at any age . The etiopathogenesis of the entity is clearly unknown but it has been reported to be associated
with various factors including genetic factors, autoimmune factors, oxidative stress, neuro-humoral, and auto-cytotoxic
mechanisms . Vitiligo can be subdivided according to the morphological presentation, the extent of the disease and the
evolution of the disease.
• Segmental Vitiligo (SV); One or more vitiliginous patches, in a linear or flag-like pattern of mosaicism, with a
unilateral dermatomal distribution.
• Nonsegmental vitiligo (NSV); Heterogeneous group of pigmentary disorders with different localization,
usually in a symmetric pattern.
• Unclassified or indeterminate
According to the extent of involvement, severity and distribution of the depigmentation, vitiligo has been classified in
different clinical classes. This classification is very useful to evaluate different therapeutics regimens.
Based on severity vitiligo can be divided into 4 stages ;
1. Limited (10%) involvement
2. Moderate (10–25%)
3. Moderately severe (26–50%)
4. Severe disease (50%) depigmentation
Prognosis and Clinical Course: The course of vitiligo cannot be predicted. Initial clinical sub-type of vitiligo does
not predict future anatomical sites of involvement or activity of disease. Complete and stable repigmentation is rare.
Spontaneous repigmentation - 10–20% of patients, most frequently in sun-exposed areas and in younger patients.
Spontaneous repigmentation poliosis does not occur.
Treatment: Treatment of Vitiligo has two main objectives: the first is to stop the progression of the disease, the second
is to induce repigmentation of the lesions and to achieve an acceptable cosmetic result. Essential is the psychological
support for Vitiligo patients and the awareness of the social community that Vitiligo is not a contagious stigma.
Vitiligo treatment options are divided into 6 main branches: medical, physical, surgical, depigmentation, camouflage,
and psychological support.
Medical treatments are divided into 3 as topical, systemic and phototherapy.
Complementary Treatments: Herbal products of different nature and effects have been used for the treatment of
vitiligo since ancient times.
Polypodium leucotomos: P. leucotomos is a tropical fern native to Central and South America, which tends to have
beneficial skin properties due to the presence of various compounds with antioxidant and photoprotective properties

61
within the extract. The P. leucotomos extract has been studied for treating various skin conditions like vitiligo, psoriasis,
melasma. Oral intake of P. leucotomos has helped prevent photoaging effects of sunlight, such as hyperpigmentation
and textural changes.
Green Tea: The antioxidant activity of green tea is due to catechins, secondary metabolites that are present in the tea.
Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active compound in green tea. EGCG is a
good scavenger of ROS/RNS and an anti-inflammatory, which has the potential to control the immune response.
Ginkgo biloba: Ginkgo biloba is a unique species of tree found in China, widely cultivated and used in traditional
medicines. Although a specific mechanism of action is not known for ginkgo, it appears to have anti-inflammatory,
immunomodulatory, and antioxidant properties all of which could potentially help in vitiligo which may have an
oxidative stress component. In addition, GB can further inhibit the development of vitiligo via its anxiolytic properties
as psychological stress has been shown to intensify vitiligo.
Curcumin : Curcumin, also called diferuloylmethane, is the main natural lipophilic polyphenol found in the rhizome of
Curcuma longa (turmeric). Clinical trials demonstrated that curcumin has high antioxidant function, modulating directly
and indirectly the antioxidant system and suppressing intracellular sources of ROS development.
Khellin: Khellin is an extract from the Mediterranean fruit Ammi visnaga. Since khellin is structurally similar to
psoralens used in PUVA, interest has arisen in the use of khellin as a safer alternative to psoralens known to crosslink
DNA and to be mutagenic. On the other hand, khellin does not produce DNA crosslinks when exposed to UVA in vitro
or inside mammalian cells.
Punica granatum & Phyllanthus emblica L: Both Punica granatum L. and P. Emblica L. are polyphenolic compounds
with high anti-oxidant activity. Studies have shown that anti-oxidant mixtures administered after phototherapy in vitligo
patients increase the repigmentation rate.
Conclusions: While a number of studies have shown benefit associated with the use of these alternative treatments,
larger, well-controlled trials are warranted to firmly establish the place of these agents in the therapeutic hierarchy. The
use of these alternative treatments can be considered as a supplement to the treatment regimen of interested or treatment
refractory patients as they appear to be relatively safe and may provide additional benefit in outcomes and patient
satisfaction.

References
1. Ortonne JP, Bahadoran P, Fitzpatrick TB, Mosher DB, Hory Y (2003) Hypomelanoses and hypermelanoses. In:
Freedberg IM, Eisen AZ, Wolf K, et al. (eds) Fitzpatrick’s dermatology in general medicine, 6th edn. The McGraw-
Hill Companies Inc, USA, pp 836–881.
2. Alikhan A, Felsten LM, Daly M, Petronic-Rosic V (2011) Vitiligo: a comprehensive overview: part I. Introduction,
epidemiology, quality of life, diagnosis, diferential diagnosis, associations, histopathology, etiology, and work-up. J
Am Acad Dermatol 65:473–491. https://doi.org/10.1016/j.jaad.2010.11.061.
3. Ezzedine K, Lim H, Suzuki T, Katayama I, Hamzavi I, Lan C et al (2012) Revised classifcation/nomenclature of
vitiligo and related issues: the vitiligo global issues consensus conference. Pigm Cell Melanoma R 25:E1–E13.
https://doi.org/10.1111/j.1755- 148X.2012.00997.x.
4. Njoo MD, Westerhof W (2001) Vitiligo: pathogenesis and treatment. Am J Clin Dermat 2(3):167–181. https://doi.
org/10.2165/00128071-200102030-00006.
5. Nestor M, Bucay V, Callender V, Cohen JL, Sadick N, Waldorf H. Polypodium leucotomos as an Adjunct Treatment
of Pigmentary Disorders. J Clin Aesthet Dermatol. 2014 Mar;7(3):13-7. PMID: 24688621.

62
6. Ning, W., Wang, S., Liu, D., Fu, L., Jin, R., & Xu, A. (2016). Potent effects of peracetylated (-)-epigallocatechin-
3-gallate against hydrogen peroxide-induced damage in human epidermal melanocytes via attenuation of oxidative
stress and apoptosis. Clinical and experimental dermatology, 41(6), 616-624.
7. Ude C, Schubert-Zsilavecz M, Wurglics M. Ginkgo biloba extracts: a review of the pharmacokinetics of the active
ingredients. Clin Pharmacokinet. 2013 Sep;52(9):727-49. doi: 10.1007/s40262-013-0074-5.
8. Prignano F, Pescitelli L, Becatti M, Di Gennaro P, Fiorillo C, Taddei N, Lotti T. Ultrastructural and functional
alterations of mitochondria in perilesional vitiligo skin. J Dermatol Sci. 2009 Jun;54(3):157-67. doi: 10.1016/j.
jdermsci.2009.02.004.
9. Morliere P, Hönigsmann H, Averbeck D, Dardalhon M, Hüppe G, Ortel B, Santus R, Dubertret L. Phototherapeutic,
photobiologic, and photosensitizing properties of khellin. J Invest Dermatol. 1988 May;90(5):720-4. doi:
10.1111/1523-1747.ep13083852.
10. Di Nardo V, Barygina V, França K, Tirant M, Valle Y, Lotti T. Functional nutrition as integrated approach in vitiligo
management. Dermatol Ther. 2019 Jul;32(4):e12625. doi: 10.1111/dth.12625.

63
 INTEGRATIVE APROACHES OF MELASMA
Emel Hazinedar
Bülent Ecevi̇ t University, Turkey

Melasma, is a common chronic, acquired hyperpigmentation of the skin that typically affects the sun-exposed areas of
the face. Patients with melasma present with irregularly shaped, hyperpigmented macules on the face but can also rarely
be seen on the neck, chest, and forearm. The color varies from light brown to dark brown or ash/blue, depending upon
the site of melanin deposition in the skin. Melasma affects millions of people worldwide. It is commoner in women,
especially in their reproductive years, but about 10% cases occur in men(1).
Melasma’s complex pathology and recurring nature make it difficult to target therapeutically. Management of melasma
is highly challenging, especially because it is prone to frequent relapse despite successful clearance. Melasma has a
signifcant efect on quality of life due to its disfguring appearance, chronic course, and recalcitrance to treatment (2, 3).
A better understanding of the pathological findings is key to developing novel and successful treatment options.
Several factors such as genetics, sunlight, cosmetics, pregnancy, hormonal treatments, thyroid dysfunction, and drugs
have been implicated in the pathogenesis of melasma . Constitutive pigmentation reflects the genetically determined
level of melanin and can be changed by several regulatory factors (4). Although earlier classified as epidermal and
dermal, melasma is now thought to be a complex interaction between epidermal melanocytes, keratinocytes, dermal
fibroblasts, mast cells, and vascular endothelial cells. It is known now that all melasma is “mixed” with the dermis
often showing solar elastosis and increased vascularity as well. Factors influencing melasma may include inflammation,
reactive oxygen species, ultraviolet radiation, genetic factors, and hormones (5, 6).
The pathology of melasma is complex although it was initially thought to involve only melanocytes. Evolving research
points to a more heterogeneous pathogenesis involving an interplay of keratinocytes, mast cells, gene regulation
abnormalities, increased vascularization, and basement membrane disruption (2). Although the melanocyte number is
similar in lesional and perilesional skin, melanocytes in the affected skin are larger, contain more melanosomes, and
show more and very prominent dendrites. In lesional skin, keratinocytes also show an increased number of melanosomes
compared with healthy skin (7).
Most of the effects of UVB on melanogenesis are mediated by the keratinocytes through the secretion of several cytokines
and hormones that stimulate not only the melanogenesis but also dendritogenesis, melanosome transfer and melanocyte
proliferation). The main mechanism is mediated by UVB-induced DNA damage that activates the p53 protein. Then,
p53 binds the Pro-Opiomelanocortin (POMC) promoter and induces the production of αMSH, which is the main pro-
pigmenting hormone (8). The impact of ultraviolet (UV) radiation as a triggering factor of melasma has been known for
decades. However, even when using potent UVB and UVA protection during the summer season , most patients have
a worsening of their lesions. The shorter wavelengths of visible light (blue -violet light) have recently been shown to
induce a hyperpigmentation through a specific sensor in melanocytes called opsin 3. (8, 9). Passeron’s group detected
higher levels of opsin3 (also called encephalopsin or panopsin) relative to other opsins in both primary melanocytes and
skin prototypes III to VI, suggesting a role for opsin3 in skin pigmentation (9).
Solar elastosis refers to the accumulation of abnormal elastic tissue in the dermis resulting from chronic sun exposure
or photoaging. Melasma patients have been found to have high levels of solar elastosis in affected skin. In addition,
histological analysis shows that melasma skin tends to have thicker and more curled and fragmented elastic fibers
when compared to normal skin. UVR also enhances reactive oxygen species (ROS) formation in keratinocytes and
melanocytes, with consequent DNA damage (10).
Numbers of mast cells are higher in melasma skin than in unaffected skin (4). UV exposure triggers the release of
histamine from these mast cells, leading to downstream effects. Histamine binding at the H2 receptor activates the
tyrosinase pathway and induces melanogenesis. This finding may help elucidate the link between the inflammatory

64
process in UV radiation and the hyperpigmentation that follows. In addition, UV radiation also increases the production
of mast cell tryptase, which activates matrix metalloproteinase (MMP) precursors. These active enzymes then go on
to degrade type IV collagen and damage the basement membrane. Mast cells induce hypervascularization (2, 9). The
number of blood vessels, vessel size and vessel density are greater in lesional melasma skin than in perilesional skin.
Elevated levels of cytokines that could affect vascularization have been demonstrated in melasma skin, such as vascular
endothelial growth factor (VEGF), stem cell factor (SCF) and inducible nitric oxide synthase (iNOs). Endothelin-1 (ET-
1) released from endothelial cells stimulates the pigmentation through endothelin receptor B activation at the surface of
melanocytes. Sebocytes have been hypothesized to contribute to the development of melasma (1).
Prolonged UV radiation causes dermal inflammation and activates fibroblasts. These cells then secrete SCF, which may
diffuse into and induce melanogenesis in the overlying epidermis. Likewise, levels of stem cell growth factor receptor,
also known as c-kit, are also upregulated in melasma lesions. When c-kit binds to SCF, it activates the tyrosine kinase
pathway responsible for melanogenesis. Therefore, trauma induced by lasers or any therapies that further aggravate the
basement membrane may worsen the disease. Similarly, restoration of the basement membrane may limit recurrence (2).
Current melasma therapies include topical agents, chemical peels, laser and light treatments, and systemic agents (2).
Regardless of the treatment modality chosen, sun protection is crucial to prevent new lesions and avoid worsening
existing melasma. The current recommendation is that patients use a broadspectrum UVA/UVB sunscreen with at least
SPF30 daily, preferably with a physical blocking agent such as zinc oxide or titanium dioxide. Sunscreens that contain
iron oxide, which blocks shorter wavelength of visible light and broad-spectrum UVA/ UVB filters, significantly lowered
the relapse of melasma during summer when compared with broad-spectrum UVA/UVB protection alone Behavioral
measures such as wearing wide-brimmed hats or avoiding peak sunlight hours may also help (2, 10).
Traditionally, melasma has been treated with topical agents, including hydroquinone (which inhibits tyrosinase), tretinoin,
corticosteroids, and combination creams with varying formulations. Hydroquinone (HQ) has long been the conventional
treatment, but the concern over its side effects have prompted the use of potentially safer alternatives. Safety issues
for HQ have been raised, including exogenous ochronosis, permanent depigmentation andpotential carcinogenic risk
(2) .4-n-butylresorcinol, niacinamide, ascorbic acid, resveratrol, azelaic acid, kojic acid and newer agents including
arbutin, deoxyarbutin, aloesin, rucinol, topical flavonoids, ellagic acid, gentisic acid, topical linoleic acid are considered
alternative topical agents that have been reported to exhibit depigmenting properties without severe adverse effects (10).
However, topical depigmenting agents alone cannot restore photoaged skin condition in melasma. Thus, antiageing
approaches should be combined with topical depigmenting agents because melasma frequently relapses without the
correction of other photoaging-related conditions that affect melanogenesis. A triple combination cream (TCC) containing
4% HQ, 0.05% tretinoin and 0.01% flucinolone acetonide is the only HQ-containing drug approved by the United States
Food and Drug Administration (FDA) to treat melasma. Tretinoin exhibits not only a hypopigmentary effect, but also
an anti-ageing property. Steroids inhibit the secretion of ET-1 and granulocyte macrophage colony-stimulating factor
(GM-CSF) that act against mild inflammation associated with photodamage and melanogenesis (10). The chemical peel
is a well-known modality for treating melasma. It causes controlled epidermal dyscohesion and subsequent regeneration
to remove epidermal melanin and suspend the transfer of melanosomes. However, the result is unsatisfactory, especially
in Asian patients with Fitzpatrick skin types III-IV due to high risk of post-inflammatory hyperpigmentation (PIH) (10).
Systemic tranexamic acid (TXA), an antifibrinolytic agent, have been shown to inhibit UV-induced melanogenesis
and neovascularization by hindering the plasminogen activator and plasmin activity. A histologic analysis revealed
significant improvement not only in the level of epidermal pigmentation, but also in the number of mast cells and
vessels. The expression of ET-1 was significantly decreased after TXA administration (10, 5)
Topical liquorice extract and oral and proanthocyanidin have significant antioxidant action and have been shown to be
beneficial in melasma. Polypodium leucomatous extracts act by inhibition of UV induced ROS generation, including
superoxide anions. AsA and alpha tocopherol are strong anti inflammatory agents with a marked antioxidant mechanism
(5).

65
There are five major categories of light therapy and lasers used for the treatment of melasma: intense pulse light (IPL),
Q switched lasers, ablative fractional resurfacing lasers, non-ablative fractional resurfacing lasers, and picosecond
lasers. The major side effects of using lasers and light sources for the treatment of melasma include post-inflammatory
hyperpigmentation (PIH) and recurrence. The thulium laser targets water instead of pigment molecules, and has less
risk of PIH compared to traditional lasers. The 1927 nm wavelength delivers energy up to 200 µm into the papillary
dermis. Therefore, it is generally used for epidermal lesions (11). Kurmuş and colleagues treated 100 melasma patients
with a 1927 nm thulium fiber fractional laser. They reported that thulium laser is effective and safe in the treatment of
melasma(11).

References
1. Kang HY, Ortonne JP. What should be considered in treatment of melasma. Ann Dermatol. 2010;22(4):373-8.
2. Rajanala S, Maymone MBC, Vashi NA. Melasma pathogenesis: a review of the latest research, pathological findings,
and investigational therapies. Dermatol Online J. 2019;25(10).
3. McKesey J, Tovar-Garza A, Pandya AG. Melasma Treatment: An Evidence-Based Review. Am J Clin Dermatol.
2020;21(2):173-225.
4. Videira IF, Moura DF, Magina S. Mechanisms regulating melanogenesis. An Bras Dermatol. 2013;88(1):76-83.
5. Sarkar R, Bansal A, Ailawadi P. Future therapies in melasma: What lies ahead? Indian journal of dermatology,
venereology and leprology. 2020;86(1):8-17.
6. Young Kang H, Ortonne JP. Melasma update. Actas dermo-sifiliograficas. 2009;100 Suppl 2:110-3.
7. Grimes PE, Yamada N, Bhawan J. Light microscopic, immunohistochemical, and ultrastructural alterations in patients
with melasma. Am J Dermatopathol. 2005;27(2):96-101.
8. Regazzetti C, Sormani L, Debayle D, Bernerd F, Tulic MK, De Donatis GM, et al. Melanocytes Sense Blue Light and
Regulate Pigmentation through Opsin-3. J Invest Dermatol. 2018;138(1):171-8.
9. Passeron T, Picardo M. Melasma, a photoaging disorder. Pigment Cell Melanoma Res. 2018;31(4):461-5.
10. Kwon SH, Hwang YJ, Lee SK, Park KC. Heterogeneous Pathology of Melasma and Its Clinical Implications. Int J
Mol Sci. 2016;17(6).
11. Kurmuş G, Tatlıparmak A, Aksoy B, Koç E, Aşiran Serdar Z, Ergin C. Efficacy and safety of 1927 nm fractional
Thulium fiber laser for the treatment of melasma: a retrospective study of 100 patients. Journal of cosmetic and laser
therapy : official publication of the European Society for Laser Dermatology. 2019;21(7-8):408-11.

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 INTEGRATIVE APPROACHES OF SKIN CANCERS
Mahmut Sami̇ Meti̇ n
Kozan State Hospital, Dept of Dermatology, Turkey

Introduction
Modern medicine can take credit for tremendous achievements and advances in the understanding of human health and
the prevention and treatment of disease. Antibiotics, vaccination, hygiene improvements, and modern pain control and
anesthesia are just some examples of developments that have changed the world and, in some ways, have eclipsed the
accomplishments of the first several thousand years of recorded medicine. But if modern medicine is so great, why are
people so interested in alternatives? In reviewing studies and talking to many patients over the years, three major reasons
seem to surface: when diseases are not curable, when our explanations are unsatisfying, and when our treatments are
thought to be unsafe, questionable, and/or only “symptomatic.” An unspoken reason also seems to be that the experience
of seeing a modern doctor can often feel rushed, overly-focused, and impersonal, where many alternative practitioners
pride themselves on having a slower pace, listening carefully to the patient, and generally being more “holistic” in con-
sidering the patient and his or her health issues. A provocative study approached this from a slightly oblique angle, but
nicely demonstrates some of these principles in action.
Skin Cancer
Skin Cancer incidence is increasing at 3.1% per year [1]. Skin cancer spread over the body with the help of lymphatic
and blood vessels. Thus, early detection of skin cancer is very important for proper diagnosis of the disease.Melanoma
and Non-Melanoma are two major categories of skin cancers. Malignant melanoma is of several sub-types. Basal cell
carcinoma and Squamous-cell carcinomas are two main types of non-melanoma skin cancers. Each type of skin cancers
has different characteristics from other skin cancers.
Treatment of non-melanoma skin cancers has increased by 77% between 1992 and 2006 leading to continual reassess-
ment of treatment. Morbidity has been minimized with techniques such as Mohs Micrographic surgery, and excellent
cure rates have been reported. For malignant melanoma, by far the most dangerous of these three skin cancers, the
outcomes are far less rosy, with good cure rates for thin tumors, but poor rates for thicker, invasive lesions. Importantly,
options for metastatic melanoma are limited, with modest life prolongation at best. In fact, patients with visceral metas-
tases have medial survival rates of only 4 months .Nonetheless, newer immunotherapies such as ipilimumab and PD1
inhibitors now offer hope to melanoma patients with advanced disease . Some skin cancer patients find the cost and/
or resultant excision scar unsatisfactory, or fear surgery altogether. Perhaps surprisingly, complementary and alterna-
tive (CAM) therapy options are being increasingly sought out and utilized by skin cancer patients. In one survey, the
prevalence of CAM use among adults reporting skin problems was nearly 50% As patients seek alternative options to
conventional therapy for skin cancer, the use of ‘natural products’ cannot be assumed to mean ‘safe’. Health providers
need to be aware of several specific alternative therapies for skin cancer, some promising and others plainly dangerous.
Some of these natural products have lead to major discoveries in skin cancer research (cyclopamine) or have proven effi-
cacy (ingenol mebutate). However, randomized controlled trials (RCT) demonstrating efficacy and safety of alternative
therapies are necessary before they can be considered viable options in the management of skin cancer. It is important
to stress that invasive basal and squamous cell cancers, as well as all melanomas can metastasize and cause significant
morbidity and even mortality. Failing to use proven techniques to properly diagnose (i.e., biopsy) and to surgically resect
or debulk these tumors greatly increases the risk for poor outcomes, and may increase the medicolegal risk in such cases.
Because of the inherent dangers of skin cancer, only adjuvants to conventional care should be considered until sufficient
evidence displaces current standards of care.

67
Top Considerations
Treatment How administered Notes

Ingenol Topically as 0.05% gel FDA-approved and effective

mebutate for the body (applied for AKs, easy to apply for
once daily for 2 days) short duration; local reactions
and 0.015% for the face common, but relatively mild
and scalp (once daily for
3 days)

Solasodine Topically as 0.005% Limited data for AK, SCC, and

glycosides cream (BID × 7–60 days) BCC; no data for melanoma.
(BEC) Perhaps could be used in special
circumstances as an adjunct to
surgery or alternative trial for
low- risk lesions under close
supervision
Vitamin D Daily or weekly Some studies suggest protective
supplementation effect and survival advantage for
Optimal dosing is melanoma; Safe and inexpensive
unclear

Coenzyme 200 mg PO BID May reduce risk of metastasis

Q10 and potentiate efficacy of
adjuvant therapies; data is very
limited
Not Recommended
*The escharotics (i.e., bloodroot, sanguinarine, and related compounds) should be avoided for known malignancies as
they are unpredictable and have not reliably been shown to be a viable treatment without concomitant surgery.
*Gossypin (an extract from cotton and hibiscus plants) has some promising data in mice and in vitro for melanoma, but
is simply too experimental for clinical use at this time.

References
1- Lio, P. A., Patel, T., Peters, N. T., & Kasprowicz, S. (2015). Handbook of integrative dermatology: An evidence-based
approach. Springer International Publishing. https://doi.org/10.1007/978-3-319-17816-5
2- R. Maurya, A. Singh, V. Srivastava, R. Yadav, (2017). A Comparative Review of Various Approaches for Skin Cancer
Detection. International Journal of Computer Sciences and Engineering, 5(10), 146-152.
3- Clark CM, Furniss M, Mackay-Wiggan JM. Basal cell cancer: an evidence based treatment update. Am J Clin Der-
matol. 2014;15:197–216.
4- Fox MC, Lao CD, Schwartz JL, Frohm ML, Bichakjian CK, Johnson TM. Management options for metastatic mela-
noma in the era of novel therapies: a primer for the practicing dermatologist. Part II. Management of Stage IV Disease.
JAAD. 2013;68(1):13e.1–13.
5- Smith N, Shin DB, Brauer JA, Mao J, Glefand JM. Use of complementary and alternative medicine among adults
with skin disease: results from a national survey. JAAD. 2010;60(3):419–25.

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 PIEZOGENIC PEDAL PAPULES
Emine Müge Acar

Piezogenic pedal papules (PPP) are described as herniations of subcutaneous tissue of medial aspect of heels which is
characterized by soft, round, skin colored papules measuring 0.2-1 cm. The term “Piezogenic” refers to the generation
of the lesions by pressure. 1 Lesions can be seen in infancy and adulthood. Infantil variant occurs in nonweight bearing
infants and lesions are seen as large nodules. 2
Etiology.
A specific etiology has not been identified for piezogenic pedal papules and development of PPP can also be seen in an
otherwise healthy individual. 3 Obesity may lead to large PPP which can present as nodules rather than plaques. Reports
of cases in successive generations in the same family is also suggestive of a possible hereditary cause. 4 However
hereditary transmission is not observed in the vast majority of the patients.
Piezogenic pedal papules appear during weight bearing in up to 60% of the population, 10% of the patients describe
pain which may be possibly related to neurovascular anoxia. 1 The lesions can be triggered by jumping, running and
standing long periods. Most of the cases occur spontaneously 5 No direct association has been observed between a
specific connective tissue defect and piezogenic pedal papules. 6 Ehlers Danlors and Prader Willi syndrome have been
anecdotally associated with PPP. 7,8
Piezogenic pedal papules can also be one of the manifestations of GATA2 deficiency, which is a zinc finger transcription
factor that plays a critical role in hematopoietic lineage commitment. 9 The development of PPP has been reported in
patients with rheumatoid arthritis and rheumatic heart disease 10 A patient with mitral valve prolapse with PPP has also
been reported in the literature suggesting a detailed systemic especially cardiologic examination is necessary in the
patients with PPP. 11
A high frequency ultrasonography can be used in the diagnosis. Biopsy can be considered in the presence of alternative
diagnosis. Histopathological examination reveals dermal fibrosis and herniation of subcutaneous fat tissue from the
papillary dermis.
Treatment
In asymptomatic lesions no treatment is necessary. Weight loss, avoidance of prolonged standing and reduced foot
trauma are recommended in the presence of painful lesions. Compression stockings, heel cups and orthotics can be
used.1 In refractory cases invasive treatments can be considered. Intralesional betamethasone and bupivakaine injections
have been reported to be benefical in patients with Ehler Danlors syndrome. 12 A good clinical response and pain control
was obtained in a female case treated with a course of electroacupuncture. 13 Deoxycholic acid injection has been
reported to be successful in one case. 5 Pulsed diod soft laser caused significant improvement in PPP lesions in another
case. 14 Surgical excision can be performed in the case of severe pain.

References
1. Jiang ZX, Tan GZ., Li, BY, Wang L, Li XQ. Painful piezogenic pedal papules in a female baby sitter: a case-
basedreview. The American Journal of Dermatopathology, 2019; 41(6): 463-4.
2. Falon, B, Cook C “Piezogenic Pedal Papule.” StatPearls 2019.
3. Mai Y, Nishie W, Sugai T, Imafuku K, Arita K, Shimizu H. Disappearing subcutaneous papules and nodules:
Characteristic features of muscle herniation and piezogenic pedal papules. J Dermatology 2017; 44(12): e361-e362.
4. Gibney MD, Glaser DA. Piezogenic pedal papules in two family members. Cutis 1996 ;57(4):260-2.

69
5. Turkmani, Mohammed G. Piezogenic pedal papules treated successfully with deoxycholic acid injection. JAAD case
reports 4.6 (2018): 582.
6. Laing VB, Fleischer AB. Piezogenic wrist papules: a common and asymptomatic finding J Am Acad
Dermatol 1991;24(3):415-7.
7. Kahana M, Feinstein A, Tabachnic E, Schewach-Millet M, Engelberg S. Painful piezogenic pedal papules in patients
with Ehlers-Danlos syndrome. J Am Acad Dermatol 1987;17:205–9.
8. Schepis C, Greco D, Siragusa M, Romano C. Piezogenic pedal papules during Prader-Willi syndrome. J Eur Acad
Dermatol Venereol 2005; 19:136–7.
9. Amarnani AA, Poladian KR, Marciano BE, Daub JR, Williams SG, Livinski AA et al A panoply of Rheumatological
Manifestations in patients with GATA2 Deficiency. Scientific reports, 2020;10(1): 1-9.
10. Ronnen M, Suster S, Huszar M, Schewach-Millet M. Solitary painful piezogenic pedal papule in a patient with
rheumatoid arthritis. Int J Dermatol, 1987;26(4): 240-1.
11. Altin C, Askin U, Gezmis E, Muderrisoglu H. Piezogenic pedal papules with mitral valve prolapse. Indian J Dermatol
2016; 61(2): 234.
12. Doukas DJ, Holmes J, and Leonard JA. A nonsurgical approach to painful piezogenic pedal papules. Cutis 2004:
339-340.
13. Woodrow SL, Brereton-Smith G and Handfietd-Jones S. “Painful piezogenic pedal papules: response to local etectro-
acupuncture.” Br J Dermatol 1997; 136.4 :628-630.
14. Singh SK, Tehseen M, Kalam A. Painless piezogenic pedal papules in a patient with rheumatic heart disease. Indian
J Dermatol Venereol Leprol 2002; 68:107-8.

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 NOVEL MODALITIES IN KELOID AND HYPERTROPHIC SCARS
Dr. Pelin Ertop Doğan
Zonguldak Bülent Ecevit University, Department of Dermatology, Turkey

Wound healing is a dynamic process which leads to regeneration or tissue repair. It consists of three main stages including
inflammatory, proliferative and remodelling stages that happen consecutively. Dysregulation of these stages may lead
to scar formation.
Keloids and hypertrophic scars are fibroproliferative disorders of the skin that result from abnormal healing of injured
or irritated skin. Genetic predisposition, systemic and local factors may contribute to these disorders(1).
There are both clinical and pathological differences between keloid and hypertrophic scar. Hypertrophic scars usually
occur after a definite injury within 4 to 8 weeks. These scars are firm and raised within the site of injury and do not
extend beyond the borders. Although it takes years, there is a possibility of spontaneous regression for hypertrophic
scars. Keloids may appear many years later and can develop from minute wounds such as a mosquito bite, vaccination
or hair folliculitis. Unlike hypertrophic scars, keloids extend beyond the wound margins and spontaneous regression
never occurs(2).
Pathologically in hypertrophic scar collagen is arranged in a wavy pattern parallel to the epidermis whereas in keloids
collagen is seen haphazardly in a random pattern(2).
Although there are many differences between hypertrophic scars and keloid, increasing evidence support that hypertrophic
scars and keloids are actually different stages of the same fibroproliferative disorder.
Various treatment modalities have been proposed for hypertrophic scars and keloid up to now. First line treatment
modality is steroid either in steroid-impregnated tape form or as intralesional injection(3). Other treatment modalities
include silicone gel or sheating, intralesional 5-Fluorouracil (5-FU) or intralesional combination of 5-FU and steroid,
cryotherapy, Pulse dye laser (PDL), ablative lasers and surgical excision with adjuvant steroid, 5-FU, radiotherapy,
bleomycin or mitomycin. However because no therapy has yet proven to be curative, novel approaches or combination
therapies are being researched(3). Novel treatment modalities include botulinum toxin-A, hyaluronidase, hyaluronic
acid, stem cell therapy, verapamil, and angiotensin converting enzyme (ACE) inhibitors(3, 4).
Botulinum toxin A (BoNT-A) is a widely used product for many medical conditions. In case of hypertrophic scars and
keloid, intralesional BoNT-A is one of the promising methods. Mechanism of action on keloid and hypertrophic scar
is not yet clearly understood. Alleviation of the scar tension, modulation of fibroblast cell cycle and collagen level and
decreasing the level of TGF-β, are proposed mechanisms. Positive clinical effects of BoNT-A is shown by most of the
studies. In addition to the clinical efficacy, the most favorable feature of BoNT-A is absence of side effects such as skin
atrophy and telangiectasia which may occur with intralesional steroid injections(5).
Hyaluronidase is an enzyme which is used in dermatology mostly for the correction of complications related to hyaluronic
acid fillers. There are various other dermatological conditions in which hyaluronidase is used. One of these conditions
is keloid and hypertrophic scar. In these diseases hyaluronidase facilitates penetration of other treatment agents into
tissue(6). Also combination of hyaluronidase with triamcinolone resulted in reduced side effect profile including
atrophy together with increased efficacy(6). Hyaluronidase can also be used alone as an alternative treatment modality
by modulating inflammatory response. It was suggested that the product of hyaluronidase degradation action, low
molecular weight hyaluronans, stimulate angiogenesis and activates mesenchymal stem cells(7). However mechanism
of its actions is poorly understood. Most side-effects of hyaluronidase are minor and transient and consist of post-
enjection pruritus, bruising and swelling. The risk of anaphylaxis is reportedly increased in those with wasp allergies(6).
Mesenchymal stem cell therapy (MSCT) is one of the promising treatment modalities for hypertrophic scar and
keloid. Mesenchymal stem cells (MSC) are involved in wound healing by increasing migration, angiogenesis and re-
epithelisation. In addition to that MSCs secrete growth and differentiation factors that modulate inflammatory and

71
immune responses during wound healing. There isn’t any human clinical trial that investigate the potential of MSCs
in hypertrophic scars and keloid yet. However, it was shown that MSC have antifibrotic properties through paracrine
signaling in vitro studies and and murine models(4, 8).
Verapamil is a calcium channel blocker which can alter fibroblast shape, induce TGF-beta apoptosis and reduce ECM
production by inducing procollagenase secretion. According to the clinical studies, verapamil could improve keloid
and hypertrophic scars either alone or as a part of combination therapies with fewer side effects. However there is
still controversial results about this agent and further more qualified studies are needed to elucidate exact effect of
verapamil(2, 4, 9).
Local renin-angiotensin system has been shown to involve in wound healing, collagen synthesis and fibrosis. There are
some small clinical studies and a few case reports propose the beneficial effects of ACE inhibitors and Angiotensin
receptor blockers on keloid and hypertrophic scars. It was shown that these modalities may involve in the treatment by
decreasing collagen synthesis, fibroblast proliferation and reducing expression of TGF-beta(10).
There are various modalities which are currently available and new treatment modalities are being investigated for
hypertrophic scar and keloid. None of these treatment modalities is accepted as gold standart. Each of the treatment
modalities has its own benefits and side effect profile. Best treatment option can be decided by comprehensive clinical
assessment and patients medical history. Further elucidation of the pathogenesis and finding new treatment modalities
will lead to better patient outcomes and treatment options for these pathological scars.

References
1. Tsai CH, Ogawa R. Keloid research: current status and future directions. Scars, burns & healing.
2019;5:2059513119868659.
2. Berman B, Maderal A, Raphael B. Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2017;43 Suppl 1:S3-
S18.
3. Limmer EE, Glass DA, 2nd. A Review of Current Keloid Management: Mainstay Monotherapies and Emerging
Approaches. Dermatology and therapy. 2020;10(5):931-48.
4. Ojeh N, Bharatha A, Gaur U, Forde AL. Keloids: Current and emerging therapies. Scars, burns & healing.
2020;6:2059513120940499.
5. Kasyanju Carrero LM, Ma WW, Liu HF, Yin XF, Zhou BR. Botulinum toxin type A for the treatment and prevention
of hypertrophic scars and keloids: Updated review. Journal of cosmetic dermatology. 2019;18(1):10-5.
6. Searle T, Ali FR, Al-Niaimi F. Hyaluronidase in Dermatology: Uses Beyond Hyaluronic Acid Fillers. Journal of drugs
in dermatology : JDD. 2020;19(10):993-8.
7. Tabola R, Augoff K, Grabowski K, Cirocchi R. Role of Hyaluronidase in the Treatment of Hypertrophic Scars.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2018;44(8):1155-7.
8. Bojanic C, To K, Hatoum A, Shea J, Seah KTM, Khan W, et al. Mesenchymal stem cell therapy in hypertrophic and
keloid scars. Cell Tissue Res. 2021.
9. Wang R, Mao Y, Zhang Z, Li Z, Chen J, Cen Y. Role of verapamil in preventing and treating hypertrophic scars and
keloids. Int Wound J. 2016;13(4):461-8.
10. Hedayatyanfard K, Haddadi NS, Ziai SA, Karim H, Niazi F, Steckelings UM, et al. The renin-angiotensin system in
cutaneous hypertrophic scar and keloid formation. Exp Dermatol. 2020;29(9):902-9.

72
 MOLLUSCUM CONTAGIOSUM: WHAT’S NEW?
Ayşın Köktürk
Mersin University Faculty of Medicine, Mersi̇ n, Turkey

Molluscum contagiosum (MC) is a common, contagious viral skin disease that often affects children and adolescents.
The virus is transmitted by close physical contact, autoinoculation, and fomites. Typically, molluscum contagiosum
presents as usually asymptomatic, discrete, smooth, flesh-colored, dome-shaped papules with central umbilication.
Sometimes an inflammation may be seen in molluscum contagiosum which represents a host response that often precedes
resolution of the viral disease, rather than secondary bacterial superinfection.This phenomenon has been termed as the
“beginning of the end (BOTE) sign” and this does not require additional antibacterial treatment.
Although MC lesions usually resolve spontaneously in 6–12 months, many authors suggest active treatment of lesions
for cosmetic reasons or concerns of transmission and autoinoculation. There is no consensus for the optimal treatment
of MC. The choice of treatment method should depend on the physician’s comfort level with the various treatment
options, the patient’s age, the number and severity of lesions, location of lesions, the preference of the patients/parents,
and patient’s immune status.
The diagnosis of MC is usually made on clinical grounds, but unclear cases may be confirmed by histopathological
examination, polymerase chain reaction or electron microscopy.Molluscum bodies can also be identified by
immunohistochemistry on paraffin-embedded, formalin-fixed material, and a cross-reactivity of molluscum bodies with
Melan A, a melanocytic marker, has been recently reported.
Dermoscopy and in vivo confocal microscopy may be very useful to aid diagnosis. Dermoscopy may facilitate diagnosis
by revealing a central polylobular white-yellow structureless area, surrounded by vessels in a crown pattern. Extraction
dermoscopy was recently described as a new method for the diagnosis of MC.
Confocal microscopy shows a round, well-circumscribed lesion with central round cystic areas filled with brightly
refractile material that correlates with the characteristic molluscum bodies seen on histopathological analysis.
Active treatments of MC may be mechanical (e.g. cryotherapy, curettage, pulsed dye laser therapy) chemical (e.g.
cantharidin, potassium hydroxide, podophyllotoxin, benzoyl peroxide, tretinoin, trichloroacetic acid, lactic acid,
glycolic acid, salicylic acid), immune-modulating (e.g. imiquimod, interferon-alpha, cimetidine) and anti-viral (e.g.
cidofovir). Currently, intralesional immunotherapy (candida, combined measles, mumps, rubella vaccine, tuberculin
purified protein derivative, vitamin D3, interferon α, and Streptococcal substrain OK-432) has been proposed as a
beneficial treatment in MC infection. It creates a delayed-type hypersensitivity reaction that results in a virus-directed
immune response by stimulating of the T helper (Th1) cytokine response, activating cytotoxic T cells to eradicate virally
infected cells.
The other treatments which may be useful in patients with multiple resistant lesions are local hyperthermia, occlusion
with adhesive tape, and the topical application of Polypodium leucotomos extract, immunoferon, zinc oxide,azelaic
acid, and certain natural products such as essential oil of Australian lemon myrtle leaves, tea tree oil, sandalwood album
oil and sinecatechins.

References
1. Gerlero, Á. Hernández-Martín. Update on the Treatment of molluscum Contagiosum in children. Actas Dermosifiliogr.
2018 Jun;109(5):408-415. doi: 10.1016/j.ad.2018.01.007. Epub 2018
2. Sil A, Bhanja DB, Chandra A, Biswas SK. BOTE sign in molluscum contagiosum.BMJ Case Rep. 2020 Sep
16;13(9):e239142. doi: 10.1136/bcr-2020-239142

73
3. Sanober Burzin Daruwalla et al.Extraction Dermoscopy”: Expanding the Utility of Epiluminescence Microscopy.
Skin Appendage Disord. 2020 Jul;6(4):220-223. doi: 10.1159/000508518. Epub 2020 Jun 25.
4. Badri T, Gandhi GR.Molluscum Contagiosum. 2020 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2020 Jan
5. Edwards S, Boffa MJ, Janier M, Calzavara-Pinton P, Rovati C, Salavastru CM, Rongioletti F, Wollenberg A, Butacu
AI, Skerlev M, Tiplica GS.2020 European guideline on the management of genital molluscum contagiosumJ Eur
Acad Dermatol Venereol. 2020 Sep 2. doi: 10.1111/jdv.16856.
6. Wells A, Saikaly SK, Schoch JJ.Intralesional immunotherapy for molluscum contagiosum: A review. Dermatol
Ther. 2020 Nov;33(6):e14386. doi: 10.1111/dth.14386. Epub 2020 Oct 20.

74
 INTEGRATIVE APPROACHES OF SUPERFICIAL FUNGAL INFECTIONS
Belkız Uyar
Department of Dermatology and Venereology, Ahi Evran University Faculty of Medicine, Kırşehir, Turkey

Superficial fungal infections are among the most common infections worldwide and limited to the stratum corneum,
hair, nails and the surface of mucous membranes.
They are caused by yeasts (e.g., Candida species and Malassezia species), dermatophytes, and non–dermatophyte spe-
cies of filamentous fungi (dermatomycoses). Although dermatophytosis, tinea versicolor and candidiasis are widely
distributed over of the world, tinea nigra and piedra are rarely seen.
Mycosis is a public health problem, particularly in tropical and subtropical developing countries.
Topical antifungals are sufficient for many patients with tinea corporis, tinea cruris, and tinea pedis. Systemic antifungal
therapy, although associated with both a higher incidence of side effects including potentially severe adverse reactions
and the potential for drug–drug interactions, is typically required to cure tinea manuum, capitis, and onychomycosis (1).
In general, oral treatment is also needed for infections involving extensive areas of skin, in hairy areas other than the
scalp (e.g. tinea barbae), or associated with excessive inflammatory reactions(1). Furthermore, in recent years, there
are increasing antifungal drugs resistance. These infections are prone to recurrence. This drives the need to pursue for
alternatives to conventional antimicrobial therapy.
Medicinal plants and chemical constituents isolated from herbs include essential oils, phenolic compounds, alkaloids
and terpenoids and they display various levels of antifungal activity.
Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years in China and Eastern Asia
(2). One of the most successful studies in this field was conducted by Bing Chen Jiang et al. They evaluated a total of 163
TCM herbs for antifungal activity against four strains of fungi and a hyphal growth inhibition effects against Candida
albicans by using consistent methods and standards. Among these, active herbs were tested against six additional fungal
strains. Their individual and synergistic antifungal activities in combination with fluconazole were evaluated against a
fungicide-resistant Candida albicans strain (FLC-resistant C. Albicans). In this study, Rosa chinensis was found to be
the most potent antifungal herb. The main antifungal constituents of Rosa chinensis were gallic acid and flavonoids.
These compounds exhibited synergistic and additive antifungal effects. Rosa chinensis, Neopicrorhiza scrophulariiflora,
Phellodendron chinense and Syzygium aromaticum displayed the strongest antifungal effects. The hyphal growth inhi-
bition assay demonstrated that extracts from six herbs completely inhibited hyphal growth. However, only three of these
(Macleaya cordata, Anethum graveolens and Veratum nigrum) showed antifungal activities (2).
Juanjuan Liu et al. demonstrated the anti-Candida effect and the cell wall remodeling induction potential of the five
traditional herbal monomers (Sodium houttuyfonate, berberine, palmatine, iatrorrhizine, cinnamaldehyde) and their
associated combinations (3).
In the literatüre, some studies examined the therapy potential of phenolic compounds in different plant extracts on fun-
gal infections (4). Piper betle L., (Piperaceae) is a widely distributed plant in the tropical and subtropical regions of the
world. The leaves of this plant have been used for a long time in many Asian countries to prepare traditional herbal re-
medies. Hydroxychavicol, the active component of P. Betle L., is a major phenolic component which has broad spectrum
fungicidal effects against clinically significant cutaneous human pathogenic fungi (5).
Geraniol (C10H18O) is present in several types of flowers, and presents a characteristic odor and flavor. This natural or-
ganic acyclic compound is part of the constitution of various volatile oils. The antifungal activity of the terpene geraniol
was also focused by many studies (6).
The essential oils of Mentha and Thymus albicans have been extensively studied for their antifungal activity against
different species (7,8).

75
Bee products have been used in folk medicine since antiquity. Propolis is a resinous substance that bees collect from
exudates of plants. Its chemical analysis has pointed to the presence of at least 300 compounds, mainly composed of
resin, wax, essential oils, pollen, and other organic compounds such as phenolic compounds and flavonoids. Several in
vitro studies have highlighted the antifungal activity of propolis and honey (9,10).

References
1. Boni E Elewski, Lauren C. Hughey, Katherine Marchiony Hunt, Roderick J Hay. Fungal Disease. In Dermatology ,
Edited by Jean L. Bolognia , Julie V. Schaffer , Lorenzo Cerroni Fourth edition , Elsevier, 2018.
2. Bing-Chen Jiangb, Jia-Ying Shenc, Jing Wu et al. In vitro antifungal activity of 163 extracts from traditional Chine-
se medicine herbs. European Journal of Integrative Medicine, Volume 39, October 2020, 101213.
3. Juanjuan Liu, Qianqian Li, Changzhong Wang et al. Antifungal evaluation of traditional herbal monomers and their
potential for inducing cell wall remodeling in Candida albicans and Candida auris. Bıofoulıng. 2020, VOL. 36, NO.
3, 319–331
4. Magdalena Działo, Justyna Mierziak, Urszula Korzun et al. The Potential of Plant Phenolics in Prevention and The-
rapy of Skin Disorders. Int. J. Mol. Sci. 2016, 17, 160; doi:10.3390/ijms17020160
5. Intzar Ali, Naresh Kumar Satti, Prabhu Dutt. et al. Hydroxychavicol: A phytochemical targeting cutaneous fungal
infections. Scientific Reports | 6:37867 | DOI: 10.1038/srep37867
6. Maria Helena Pereira de Lira, Francisco Patricio de Andrade Júnior, Gustavo Fernandes Queiroga Moraes, et al.
Antimicrobial activity of geraniol: an integrative review, Journal of Essential Oil Research, 2020, 32:3, 187-197,
DOI: 10.1080/10412905.2020.1745697
7. Annarita Stringaro , Marisa Colone, Letizia Angiolella. Antioxidant, Antifungal, Antibiofilm, and Cytotoxic Activi-
ties of Mentha spp. Essential Oils. Medicines 2018, 5, 112; doi:10.3390/medicines5040112.
8. Roxo, M., Zuzarte, M., Gonçalves, M.J. et al. Antifungal and anti-inflammatory potential of the endangered aroma-
tic plant Thymus albicans. Sci Rep 10, 18859 (2020). https://doi.org/10.1038/s41598-020-75244-w
9. Zubaidah Hamid, Irfan Mohamad1, Azian Harun et al. Antifungal Effect of Three Local Malaysian Honeys on Se-
lected Pathogenic Fungi of Otomycosis: An in vitro Evaluation. Young Pharm, 2018; 10(4):414-417
10. Nlandu Roger Ngatu a, Takao Saruta b, Ryoji Hirota Antifungal efficacy of Brazilian green propolis extracts and
honey onTinea capitis and Tinea versicolor. European Journal of Integrative Medicine 3 (2011) e281–e287

76
 BIOLOGICAL RHYTHMS IN THE SKIN
Dr. Pelin Ertop Doğan
Zonguldak Bülent Ecevit University, Department of Dermatology, Turkey

In humans virtually all aspects of physiology is rhythmic. Most physiological oscillations occur in 24 hour periodicity
but additionally periods of less than or greater than 24 hour also exist. Circadian rhythm refers to body’s endogenous
24-hour physiologic, metabolic and behavioral rhythms to meet environmental stimuli associated with solar day and
optimize cellular responses. It is an ancient evolutionary system to adapt to changes stemming from rotation of earth.
Circadian rhythm is controlled by the master or central clock of the body which is suprachiasmatic nucleus (SCN)
located in the anterior hypothalamus. Visible light enters the retina and then via retinohypothalamic tract it modulates
suprachiasmatic nucleus. SCN initiates hormonal and neuronal signals that coordinate oscillations throughout the body.
In the body, the core molecular clock system consist of an autoregulatory gene expression feedback loop. Clock and
Bmal1 transcription factors form a heterodimer and stimulate genes termed clock controlled genes. At the same time
Clock and Bmal1 induce expression of their own inhibitors, which are Period (Per) and Cryptochrome (Cry) leading
to an approximately 24 hour oscillatory rhythm. Circadian rhythm of the skin is regulated both by the SCN and by the
intrinsic regulators of the skin(1).
Skin is the largest organ in the body. Morphologically, skin contains various cell types and structures. There are evidences
that there is a functional clock in the regulation of skin, if not all, of its cell types. Both the central clock, suprachiasmatic
nucleus (SCN) and endogenous rhytmicity of the skin have impact on the activities of the skin. The peripheral clock
in the skin is not a single entity rather it is composed of multiple independent clocks yet most likely work coordinated
that function within distinct anatomical compartments of the skin. These clocks lead to formation of rhythmicity in the
activities. Most known rhythmic activities of skin are epidermal turn over cycle and hair cycle(2).
In the skin circadian variations can be observed in keratinocyte proliferation, DNA synthesis and repair, sebum
production, skin blood flow, transepidermal water loss, and skin temperature. Circadian variation of these functions, also
any disruption of this rhythmicity may have impact on disease formation, cancer development or treatment strategies(3).
Circadian rhythm influences cutaneous blood flow and properties of skin barrier function, such as transepidermal water
loss (TEWL). At night, blood flow to the skin and TEWL increase, sebum production and skin hydration decrease. In
atopic dermatitis, high TEWL and low hydration at night contribute to nocturnal itching(4). Cortisol levels also fluctuate
throughout the day which have a natural decrease during the evening. This could be also a contributing factor to increased
pruritus at night seen in inflammatory dermatoses including atopic dermatitis and psoriasis. Increased inflammation and
skin permability at night could be important clinically. Thus, to maximize effectiveness of the treatments, topical steroid
and moisturizers might be used in the evening hours(3).
Circadian disruption may be more important for skin diseases than previously recognized. For example in a study
increased psoriasis incidence was observed in shift workers. Also in a murine study it was shown that Clock transcription
factor may modulate psoriasis like inflammation via Interleukin-23 pathway(1).
Relation of circadian dysrhythmia and skin carcinogenesis, is another topic which is under investigation. Disrupted
melatonin synthesis, is one of the proposed reasons for this association(5). Melatonin has been associated with wound
healing, antititumor and antioxidant effects and supression of ultraviolet damage in skin cells. It is mostly synthesized
in pineal gland and also it can be synthesized in the skin. Melatonin levels fluctuate with the circadian rhythm and
are typically high at night. Exposure to light leads to an acute drop in melatonin levels(6). Due to its antioxidant and
antitumorogenic effect, any disruption in this rhytmicity of melatonin secretion may lead to cancer formation, however
further studies are required for clarification of this association. It was shown that clock genes were down-regulated in
melanoma as compared to normal adjacent tissue. Also reduced clock gene expression was associated with increased
tumor thickness and mitotic level in melanoma(7).
Circadian rhythm of the skin has importance in many aspects of the skin functions including aging, regeneration of
human skin and hair precursor cells as well as inflammatory disease occurence, cancer development and progression

77
and deciding effective treatment modalites. Future studies and further examination of these mechanisms would create
new perspectives.

References
1. Matsui MS, Pelle E, Dong K, Pernodet N. Biological Rhythms in the Skin. Int J Mol Sci. 2016;17(6).
2. Plikus MV, Van Spyk EN, Pham K, Geyfman M, Kumar V, Takahashi JS, et al. The circadian clock in skin: implications
for adult stem cells, tissue regeneration, cancer, aging, and immunity. J Biol Rhythms. 2015;30(3):163-82.
3. Lyons AB, Moy L, Moy R, Tung R. Circadian Rhythm and the Skin: A Review of the Literature. J Clin Aesthet
Dermatol. 2019;12(9):42-5.
4. Vaughn AR, Clark AK, Sivamani RK, Shi VY. Circadian rhythm in atopic dermatitis-Pathophysiology and implications
for chronotherapy. Pediatr Dermatol. 2018;35(1):152-7.
5. Gutierrez D, Arbesman J. Circadian Dysrhythmias, Physiological Aberrations, and the Link to Skin Cancer. Int J Mol
Sci. 2016;17(5).
6. Slominski AT, Hardeland R, Zmijewski MA, Slominski RM, Reiter RJ, Paus R. Melatonin: A Cutaneous Perspective
on its Production, Metabolism, and Functions. J Invest Dermatol. 2018;138(3):490-9.
7. de Assis LVM, Moraes MN, Castrucci AML. The molecular clock in the skin, its functionality, and how it is disrupted
in cutaneous melanoma: a new pharmacological target? Cell Mol Life Sci. 2019;76(19):3801-26.

78
 HUMAN 3D SKIN MODELS
Neslihan Fişek İzci
Bahçeşehir University, Dermatology Departman, Turkey

Tissue engineering is used to fabricate 3-dimensional (3D) artificial scaffolds to create a microenvironment that mimics
human tissue. Bioprinting uses biomaterials, cells, and/or bioink to fabricate prospective scaffolds to mirror the structural,
compositional, and functional aspects of the skin (1). The relevance for in vitro three-dimensional (3D) tissue culture
of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic
full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era
(2) . The 3D Skin Model is a highly physiological, three-dimensional cellular system of keratinocytes, fibroblasts, and
melanocytes for in vitro studies, suggesting an excellent tool to examine aspects of epithelial function and disease,
particularly those related to skin biology and toxicology (3).
Threedimensional (3D) skin equivalents have been established as a valuable tool in dermatological research because
they contain a fully differentiated epidermal barrier that reflects the morphological and molecular characteristics of
normal human epidermis (4). Herein, we will summarize 3D skin bioprinting techniques, applications and approaches.

References:
1. Ishack , Lipner SR. A Review of 3-Dimensional Skin Bioprinting Techniques: Applications, Approaches, and
Trends. Dermatol Surg 2020 Dec;46(12):1500-1505.
2. Randall MJ, Jüngel A, Rimann M, Wuertz-Kozak K. Advances in the Biofabrication of 3D Skin in vitro: Healthy
and Pathological Models. Frontiers in bioengineering and biotechnology 2018; 6: 15.
3. Eun HC, Num C. Alternative Methods for Evaluating Skin Irritation Using Three-Dimensional Cultures. Exog
Dermatol 2003;2:1–5
4. Rademacher F, Simanski M, Gläser R, Harder J. Skin microbiota and human 3D skin models. Experimental
Dermatology 2018; (27):5.

79
 ELISA IN DERMATOLOGY
Betül Şereflican
Bolu Abant İzzet Baysal Üniversitesi İzzet Baysal Eğitim ve Araştırma Hastanesi Deri ve Zührevi
Hastalıkları Anabilim Dalı, Türkiye

Anamnesis and clinical features of skin lesions are very important in the diagnosis of skin diseases. Dermatological
examination findings may need to be supported by some laboratory tests and special examination methods. In some
dermatological diseases, the demonstration of autoantibodies stored in the tissue and /or circulating in the serum is used
in diagnosis and follow-up. One of the methods for this purpose is Enzyme Linked Immunosorbent Assay (ELISA). It is
a test used to determine antigen or antibody in patient samples (serum, saliva, etc.). In dermatology practice this method
is used especially in autoimmune bullous disorders, autoimmune connective tissue diseases, some viral and bacterial
diseases.
A variety of highly sensitive and specific ELISA systems has become commercially available within the last two de-
cades. These ELISAs identify autoantibodies against specific autoantigens, also make it possible to quantify serum
autoantibody levels (1). In addition to clinical, histopathological and immunofluorescent methods, ELISA is used as a
confirmation test in the diagnosis of autoimmune bullous disorders. Compared to other traditional diagnostic methods, it
has advantages such as being faster, easier to apply, better standardized and that many samples can be studied simultane-
ously (2). ELISA is the most accurate diagnostic test for the diagnosis of pemphigus vulgaris and pemphigus foliaceus,
separately measuring anti-Dsg3 and anti-Dsg1 (3). An ELISA for autoantibodies against envoplakin in paraneoplas-
tic pemphigus has recently been developed. For pemphigoid diseases, ELISAs applying recombinant BP180 NC16A,
BP230, and type VII collagen are available (1).
In autoimmune connective tissue disorders, autoantibodies occur secondary to autoimmunity. The presence of autoanti-
bodies shown serologically in autoimmune connective tissue diseases can provide important information to the clinician
in terms of disease diagnosis, activity and treatment follow-up. ELISA method is mostly used for anti-dsDNA measure-
ment. dsDNA antibodies are associated with systemic lupus, but not subacute cutaneous lupus or discoid lupus; dsDNA
antibodies increase in active disease and in the progression of lupus nephritis. dsDNA antibody assays can be negative
after treatment, in clinical remission. Around 50–80% of patients with SLE have antihistone antibodies detectable by
ELISA (4). Anti-neutrophil cytoplasmic antibodies are useful diagnostic markers for primary vasculitis, wegener gran-
ulomatosis, microscopic polyangiitis, and churg-strauss syndrome. Consensus has been developed regarding the admin-
istration of ELISA to detect autoantibodies against proteinase 3 and myeloperoxidase in indirect immunofluorescence
positive sera (5).
An enzyme immunoassay (EIA, Captia Syphilis-G) for detecting IgG antibodies against Treponema pallidum was im-
proved as a screening test for syphilis (6). Captia syphilis M test has been used for detection of congenital syphilis in
the newborn. Infected infants can produce IgM in utero after 3 months of gestation. Ig M ELISA test is based on using
anti-human IgM antibody to capture IgM in the patient’s serum, followed by the addition of a purified T.pallidum anti-
gen to detect those IgM antibodies in the patient’s serum (7).

References
1. Van Beek N, Zillikens D, Schmidt E. Diagnosis of autoimmune bullous diseases. J Dtsch Dermatol Ges.
2018;16(9):1077-1091.
2. Özkesici B, Karakaş Aa. Otoimmün Büllöz Hastalıkların Serolojik Tanısı. Turk J Dermatol 2016;10:1-8.
3. Harrell J, Rubio XB, Nielson C, Hsu S, Motaparthi K. Advances in the diagnosis of autoimmune bullous dermato-
ses. Clin Dermatol. 2019;37(6):692-712.
4. Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol. 2000;53(6):424-432.
5. Ramponi G, Folci M, De Santis M, Damoiseaux JGMC, Selmi C, Brunetta E. The biology, pathogenetic role,
clinical implications, and open issues of serum anti-neutrophil cytoplasmic antibodies. Autoimmun Rev. 2021 Jan
18:102759.
6. Young H, Moyes A, McMillan A, Robertson DH. Screening for treponemal infection by a new enzyme immunoas-
say. Genitourin Med. 1989;65(2):72-8.
7. Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol
Rev. 1995;8(1):1-21.

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 FREE FATTY ACIDS IN DERMATOLOGY
Hülya Süslü
Istanbul Haseki Research and Training Hospital, Turkey

The skin is an effective barrier that protects the organism from harmful physical and chemical effects from the external
environment and prevents the loss of water and other fluids from the body. The stratum corneum, the outermost layer of
the epidermis, consists of corneocytes that emerge from the stratum basal, mature and rise, and then lose their nuclei.
Lipid matrix found between these cells; It consists of approximately equal molar proportions of ceramides (CERs),
cholesterol, and free fatty acids (FFAs) (1). The SC structure is defined as similar to the bricks and mortar structure,
the corneocyte being the bricks and the intercellular lipids the mortar. Intercellular lipids are assembled in two lamellar
phases. Within the lamellae, most of the SC lipids prefer a dense orthorhombic lateral packing at skin temperature
(30−32°C), while some of the lipids adopt the less dense hexagonal packing. The ordered lipid packing in SC is induced
by the FFAs with predominantly saturated chains, carbon chain lengths ranging from 12 to 30 (mostly chain lengths of
22, 24 or 26 carbon atoms) and the CERs with a long hydrocarbon tail and small headgroups(1,2). The CERs may vary
in headgroup structure and chain length. Currently, 18 subclasses of CERs have been defined in human SC.
Changes in SC lipid composition have been reported in one of the most common chronic inflammatory skin diseases
called atopic dermatitis (AD). The etiology of AD is multifactorial and involves the interaction of immunological, genetic
and environmental factors. Damaged skin barrier characterized by increased water loss through SC is characteristic of
patients with AD. There are studies showing that impaired skin barrier is associated with changes in lipid composition.
In a study; a reduction FFA chain length, an increase in mono-unsaturated FFAs (MUFAs) and a decrease in hydroxy
FFA have been shown in non-lesional and lesional SC of AD patients (3). FFA chain length reduction increased the
formation of less densely packed hexagonal lipid organization, while the increased level of MUFA observed in SC of
AD patients was also reported to increase a hexagonal lipid organization in in vitro studies. All changes were more
pronounced in lesional SC than in non-lesional skin. Again, in this study, no relationship was observed between lipid
changes and filaggrin mutations, which are an important predisposing factor for AD development (3).
In the skin of AD patients compared to healthy skin; a reduction in the levels of the CER NP, CER NH, CER EO classes,
an increase in the levels of CER NS and AS (4-7), a decrease in the chain length of CERs have been reported. As these
changes in lipid composition occur simultaneously, it has not yet been determined which of them is the underlying factor
of the impaired skin barrier. In another study investigating the role of various anarmolytics in the composition of CERs
and FFAs (palmitic acid (C16), stearic acid (C18), arachidic acid (C20), behenic acid (C22), in AD on model membrane
systems, it was shown that the increased level of short-chain FFAs caused a greater reduction in barrier function than the
compositional changes of CERs (8).
Another disease in which FFAs are investigated in pathogenesis is acne vulgaris. In the pathogenesis of acne vulgaris,
it has been defined as abnormal ductal keratinization, increased sebum production resulting in seborrhea, excessive
Propionibacterium increase. FFAs are formed from sebum triglycerides (TG) with lipase secreted by Propionibacterium
acnes. FFAs are thought to be involved in abnormal ductal keratinization in acne. While there is much more sebum
on the facial skin of a female patient with acne than that of a healthy woman, increased sebum levels do not directly
cause acne development. In a pilot study involving 9 men, no significant difference was observed in the sebum FFA
composition of the subjects in the two groups with and without acne. Free sature FFA composition has been reported to
differ between acne and acne-free women. Furthermore, the diet with low glycemic load reduced the amount of sebum
and these amounts changed the fat composition of TG in men with acne. In a study investigating the effect of fatty acid
composition of sebum on acne vulgaris; the amounts of TGs and FFAs, fatty acid compositions and cutaneous superficial
Propionibacterium acnes were examined.
Samples were taken from the foreheads of 18 female patients, 10 male patients, 10 healthy women and 10 healthy men by
swab method. Significant differences were observed in the amounts of sebum, TG and cutaneous superficial P. acnes as
well as the fatty acid composition of TG and FFA between acne and healthy female subjects. FFA compositions correlated

81
with the amount of TG in both groups. It has been reported that the fatty acid compositions of TG and FFA change with
the amount of TG and that the fatty acid composition does not change with the presence or absence of acne (9).
A study has been carried out on the composition of free fatty acids from the skin surface and the barrier region of free
fatty acids in normal and abnormal kertanization (psoriasis). The presence of substantial amounts of free fatty acids
with chain lengths longer than C20 has been demonstrated, particularly in barrier zone lipids of healthy subjects and
in both the surface and barrier zone of psoriatic individuals. Approximately one-third of the free fatty acids of lipids
from the barrier region of normal healthy subjects have chain lengths longer than C18. Evidence is presented that long-
chain acids from C18 are produced in the epidermis, at or near the barrier, and not by sebaceous glands. These acids
are probably to be incorporated into the keratin or into the glycolipoprotein cementing substance during the normal
keratinization process, so only small amounts are transported to the skin surface and are visible in the surface lipid film.
In psoriasis, almost three-quarters of free fatty acids have longer chain lengths than C18 (10).
In psoriasis, there is probably both the overproduction of these acids and their failure to participate in keratin or glyco-
lipoprotein. Therefore, these acids accumulate in the barrier area and are transported to the skin surface in extremely
large amounts.

References
1. Norlen, L.; Nicander, I.; Lundsjo, A.; Cronholm, T.; Forslind, B. A new HPLC-based method for the quantitative
analysis of inner stratum corneum lipids with special reference to the free fatty acid fraction. Arch. Dermatol. Res. 1998,
290 (9), 508−16.
2. van Smeden, J.; Boiten, W. A.; Hankemeier, T.; Rissmann, R.; Bouwstra, J. A.; Vreeken, R. J. Combined LC/MS-
platform for analysis of all major stratum corneum lipids, and the profiling of skin substitutes. Biochim. Biophys. Acta,
Mol. Cell Biol. Lipids 2014, 1841 (1), 70−79. (15) t’Kindt
3. van Smeden, J.; Janssens, M.; Kaye, E. C.; Caspers, P. J.; Lavrijsen, A. P.; Vreeken, R. J.; Bouwstra, J. A. The
importance of free fatty acid chain length for the skin barrier function in atopic eczema patients. Exp. Dermatol. 2014,
23 (1), 45−52.
4. (22) Ishikawa, J.; Narita, H.; Kondo, N.; Hotta, M.; Takagi, Y.; Masukawa, Y.; Kitahara, T.; Takema, Y.; Koyano, S.;
Yamazaki, S.; Hatamochi, A. Changes in the ceramide profile of atopic dermatitis patients. J. Invest. Dermatol. 2010,
130 (10), 2511−4.
5. Di Nardo, A.; Wertz, P.; Giannetti, A.; Seidenari, S. Ceramide and cholesterol composition of the skin of patients with
atopic dermatitis. Acta Derm-Venereol. 1998, 78 (1), 27−30.
6. Imokawa, G.; Abe, A.; Jin, K.; Higaki, Y.; Kawashima, M.; Hidano, A. Decreased level of ceramides in stratum
corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J. Invest. Dermatol. 1991, 96 (4), 523−6.
7. Janssens, M.; van Smeden, J.; Gooris, G. S.; Bras, W.; Portale, G.; Caspers, P. J.; Vreeken, R. J.; Hankemeier, T.;
Kezic, S.; Wolterbeek, R.; Lavrijsen, A. P.; Bouwstra, J. A. Increase in shortchain ceramides correlates with an altered
lipid organization and decreased barrier function in atopic eczema patients. J. Lipid Res. 2012, 53 (12), 2755−66.
8. Uche LE, Gooris GS, Bouwstra JA, Beddoes CM. Barrier Capability of Skin Lipid Models: Effect of Ceramides and
Free Fatty Acid Composition. Langmuir. 2019 Nov 26;35(47):15376-15388. doi: 10.1021/acs.langmuir.
9. Akaza N, Akamatsu H, Numata S, Matsusue M, Mashima Y, Miyawaki M, Yamada S, Yagami A, Nakata S, Matsunaga
K. Fatty acid compositions of triglycerides and free fatty acids in sebum depend on amount of triglycerides, and do not
differ in presence or absence of acne vulgaris. J Dermatol. 2014 Dec;41(12):1069-76. doi: 10.1111/1346-8138.12699.
10. Coon wm, Wheatley Vr, Herrmann F, Mandol l. Free fatty acids of the skin surface and barrier zone in normal and
abnormal keratinization. J Invest Dermatol. 1963 nov; 41:259-64.

82
 TGF- BETA IN DERMATOLOGY
Ömer Kutlu
Tokat Gaziosmanpaşa University, School of Medicine,
Department of Dermatology and Venereology, Turkey

Cytokines are signaling water-soluble non-immunoglobulin proteins and glycoproteins released by a wide variety of
cells especially, immune cells. Cytokines play an important role in cellular communication and their function may be
autocrine, paracrine or endocrine. In this lecture, we will talk about TGF- β in Dermatology.
Cytokines use several downstream pathways including JAK-STAT, NF-kβ, and serine/threonine kinase pathways. TGF-
β mainly use the last pathway. There are three isoforms of TGFβ (TGFβ1, 2 and 3). The activation of these cytokins may
lead to following factors:
• Cell proliferation
• Differantiation
• Immun response
• Angiogenesis
• Tissue repair
So far, TGF-β has been studied certain dermatological diseases such as hair loss (basically alopecia areata), psoriasis,
wound healing, malignancies (squameous cell carcionoma, basal cell carcinoma), lipogenesis, hypertrophic scar, keloids,
and vitiligo.
The activated TGF-β receptor I (RI) subsequently induces the signal intracellularly by phosphorylating SMAD2 and
SMAD3. Upon phosphorylation, SMAD2 and SMAD3 make a complex with SMAD4, accumulate in the DNA and
act as transcription factors. However, the actions of the TGF-β receptors are inhibted by Smad7. Smad7 interacts with
the activated TGF-β RI to prevent activation of Smad2 and Smad3, hence interrupting TGF-β induced signaling. It has
been shown that UVB exposure may induce rapid and transiet gene expression of Smad-7 which subsequently may
inactivate TGF- β related pathways. These effect may be benefical for numerous TGF- β related dermatological diseases
as it mentioned above. Furthermore, there are certain anti-TGF- β drugs such as kaempferol and galagin thath inhbitis
fibroblast collagen synthesis and hypertrophic scar formation. These drug shed light on dermatological diseases in which
TGF- β plays an important role.
To incrase knowledge of pathophysiological mechanism of TGF-β in certain dermatologic diseases such as alopecia
areata, psoriasis, keloids, vitiligo etc. may lead to new treatment methods in the future.

83
 CCR-5 IN DERMATOLOGY
Ömer Kutlu
Tokat Gaziosmanpaşa University, School of Medicine,
Department of Dermatology and Venereology, Turkey

To date, we discovered over two hundreds cytokines including approximately 50 chemokines in our body.CCR-5 is a
chemokine receptor that is mainly expressed on cytotoxic T cells and T helper 1 cells. Natural ligands for CCR5 consist
of CCL-3, CCL-4, CCL-5 (RANTES), CCL-8, CCL-11 (eotaxin), CCL-14, and CCL-16.
CCR-5 is the among the most popular mediator in HIV patogenesis. CCR-5 acting as a co-receptor along with CXCR-4
for HIV entry into the CD-4 T cell. In recent years, CCR-5 has been started to be investigated in the field of dermatology.
Psoriasis, pannicullitis, melanoma, mycosis fungoides, wound healing and alopcia area are the main diseases that has
been studied on CCR-5. It has also been shown that CCR-5 has the effect on the edema and hemorrhage in the cutaneous
reverse passive Arthus reaction.
The current studies on malignancy particularly mycosis fungoides revealed that the expression of chemokin receptors
including CCR-5 contributes to the migration of tumour cells.
RANTES which is the one of the ligand of CCR-5 receptors has been found to have higher expression on lesional psoriatic
skin. The increased mRNA expression of CCR-5 was also reported. These result provided to perform a new randomized
placebo controlled study in order to see the effect of CCR5 antagonism on psoriasis. Interestingly, the study reported 50
mg twice daily CCR5 inhibitor does not have effect on the established study but rather may be a preventive effect.
In another study, genetic distrubition of CCR-5 has been found to associated with delayed skin wound healing and
decreased neovascularization. However, it has no effect on macrophage recruitment in wound healing.
The previous studies on CCR-5 in dermatology imply that CCR-5 has considerable effect on the infammatory based
dermatologic diseases. Therefore, CCR-5 antagonism may be adjuvant treatment in some dermatologic diseases. Further
studies required in order to see the exact effect of CCR-5 antagonism in certain skin diseases.

84
 WHAT’S NEW APPROACH FOR ANTIFUNGAL THERAPY?
Arzu Kılıç
Balıkesir University School of Medicine, Balıkesir, Turkey

Cutaneous fungal infections are classified as superficial and deep mycoses. Most mycotic infections are superficial
and are limited to stratum corneum, hair and nails. The main groups of fungi causing superficial fungal infections
are; dermatophytes (tinea), nondermatophyte molds and yeasts (Candida including non albicans candida species, and
dimorphic fungus as Malassezia).
Herein, new approaches in the management of superficial fungal infections and antifungal therapy will be mentioned
shortly.
Dermatophytes (Trichophyton, Epidermophyton, and Microsporum genera) are one of the most common cause of
superficial fungal infections. Despite the progress in medicine, the prevalence of dermatophyte infections is increasing
from year to year. These infections lead to a variety of clinical manifestations, such as tinea pedis, tinea corporis, tinea
cruris, Majocchi’s granuloma, tinea capitis, and tinea unguium. For patients with limited tinea pedis, tinea corporis,
or tinea cruris, treatment with a topical antifungal drug applied once or twice daily is recommended. Tinea capitis and
onychomycosis require systemic antifungal treatment.
A variety of topical antifungal agents are available including azoles (clotrimazole, econazole, ketoconazole, miconazole,
sulconazole), allylamines (terbinafine), butenafine, naftifine, and ciclopirox . The most important development in the
treatment is the approval of new drugs. Some of the newer topical antifungal drugs are listed below.
1. Azoles: Sertaconazole, luliconazole and efinaconazole
2. Oxaborole: Tavabarole
Sertaconazole 2 % cream is FDA approved for treatment of tinea pedis in individuals 12 years of age and older and is
approved in the EU for the treatment of tinea corporis/tinea cruris. It has broadspectrum antifungal activity against all
three genera of dermatophytes, Candida and Cryptococcus. In addition, it is also effective against Grampositive cocci.
Luliconazole is approved by FDA for the treatment of tinea pedis, tinea cruris, and tinea corporis onca a day for a
week. Luliconazole has a broad-spectrum activity against a variety of etiologic fungi in skin infections including
dermatophytes, Candida, Malassezia subspecies, and Aspergillus.
Efinaconazole 10 % solution was approved for the treatment of onychomycosis. It has a greater nail bed penetration
and efficacy than previous topical antifungal treatments. It is mainly indicated for the treatment of T.rubrum and
T. mentagrophytes. However, it exhibits activity toward other dermatophytes and nondermatophytes including
Microsporum, Epidermophyton, molds, Aspergillus, Cryptococcus, Trichosporon, and Candida genera fungi.
Tavaborole is an oxaborole antifungal drug approved for toenail onychomycosis. It has a broad-spectrum activity
against a variety of fungi, including the dermatophytes T. rubrum, T. mentagrophytes, T. tonsurans, and E. floccosum.
In addition to new drugs, in order to enhance the dermal delivery and skin retention of the drug, the development of new
formulated drugs such as water-soluble formulation of ciclopirox, ciclopirox8 % HPCH (P-3051) is another innovation.
Another issue apart from the development of new antifungal drugs is the increased awareness of drug resistance.
Although generally considered easy to treat, recalcitrant infections, presenting as extensive and difficult dermatophyte
infections are on the rise in some parts of the world especially in India.
Our frequent and prophylactic use of antifungal agents has led to the increased frequency of development of resistance
to current antifungal drugs. Azole and terbinafine resistance have been recently emphasized. This high levels of
resistance reveals warranting antifungal susceptibility testing in rcalcitrant cases.
The last issue to be mentioned is the approach to the treatment of onychomycosis. Systemic medications are widely used

85
because of their accessibility, low cost, and high efficacy. Oral terbinafine, itraconazole and fluconazole (fluconazole
not approved by FDA) are approved for the treatment of onychomycosis. Because of higher cure rates with terbinafine
and fewer drug interactions, terbinafine is usually preferred over itraconazole and fluconazole. Table 1 reveals the
indications for oral and topical treatment of onychomycosis (Table 1).
Topical treatment with amorolfine, ciclopirox, tavaborole, or efinaconazole is appropriate for cases of mild to moderate
toenail onychomycosis due to dermatophyte or mixed dermatophyte/Candida infection. In a study, in cases with the
involvement of matrix; using amorolfine and systemic terbinafine has been found to be superior to using only systemic
terbinafine.
Nail debridement may be preferred as an another treatment option. Avulsion with urea in combination with bifonazole
is also a treatment option and is more attractive than undergoing surgical nail removal.
Photodynamic and plasma therapies have been explored, but larger randomized trials are needed to determine their
efficacy in the clinical setting.
Laser treatment is approved by the FDA for onychomycosis. It is not recommended as a first line treatment since cure
rates are lower than those for oral and topical antifungal treatment. Short, long pulsed, and Q-switched neodymium-
doped yttrium aluminum garnet lasers, near infrared and dual wavelength diode lasers and fractional CO2 lasers have
been used for the treatment of fungal nail infections with mixed results.

Table 1. Indications for oral and topical therapy in onychomycosis

Indications for both oral and topical
Indications for oral therapy Indications for topical therapy
therapy
Proximal subungual onychomycosis Superficial onychomycosis Contraindications to oral therapy

DLSO affecting >50% of the surface

DLSO affecting <50% of the surface area of
area of the nail plate with matrix For prevention of recurrences or
the nail plate without matrix involvement and
involvement and nail plate thickness reinfection
nail plate thickness <2 mm
>2 mm
>3 or 4 nails affected Up to 3 or 4 nails affected
Poor compliance and prognostic
factors

References
1. Sahni K,Singh S, Dogra S. Newer Topical Treatments in Skin and Nail Dermatophyte Infections. Indian Dermatol
Online J 2018;9(3):149-58.
2. Gnat S, Łagowski D, Nowakiewicz A. Major challenges and perspectives in the diagnostics and treatment of
dermatophyte infections. J Appl Microbiol 2020 Aug;129(2):212-2.
3. Saunders J, Maki K, Koski R, Nybo SE. Tavaborole, Efinaconazole, and Luliconazole:Three New Antimycotic
Agents for the Treatment of Dermatophytic Fungi. J Pharm Pract 2017;30(6):621-630.
4. Lipner SR, Scher RK. Onychomycosis. Treatment and prevention of recurrence. J Am Acad Dermatol 2019;80:853-67.
5. Revie NM, Iyer KR, Robbins N, Cowen LE. Antifungal drug resistance: evolution, mechanisms and impact. Curr
Opin Microbiol 2018;45:70-6.

86
 IF SUPERBUGS ARE MONSTER, HOW CAN WE PREVENT THEM WHEN USING
ANTIBIOTICS?
Melek Aslan Kayıran
Department of Dermatology, İstanbul Medeniyet University,
Göztepe Prof. Dr. Süleyman Yalçın City Hospital, Turkey

The antibiotic use began with the discovery of penicillin by Sir Alexander Fleming in 1928.1 Simple infections resulted
in death or serious sequelae for centuries due to lack of antibiotics. While helping to extend average human life from
56.4 at 1920s to around 80 by the end of 20th century, it is impossible to consider antibiotics so innocent and life-
saving.2 Although the antibiotics saved the past and our generation from death, the antibiotic resistant bacteria, so called
superbugs, will be one of the major causes of death in next generations.
Causes of the occurrence of superbugs
The infections caused by superbugs were listed among the top ten human life threading topics in 2019.3 Superbugs are
bacteria which are resistant to most antibiotics and other medications that are commonly used to cure the infections they
cause. The main reason behind the existence of superbugs is the misuse of the antibiotics. The main headlines if this
misuse are as follows.
Overuse of the antibiotics: 30% of the antibiotics are prescribed unnecessarily and the number of prescribed antibiotic
units is increasing by millions in every year.4 Over-prescribing of the antibiotics has led to the development of a number
of protective mechanisms of the bacteria. The bacteria are clever microorganisms. They have the capacity to transfer
their genes of antibiotic resistance mechanisms not only to their offspring, but also to other bacteria by gene transfer
elements such as plasmids. In addition, antibiotic resistance may occur with various mutations.4
Inappropriate Prescribing: Sub-inhibitory and sub-therapeutic doses or unnecessary use of antibiotics may cause
genetic changes such as mutations and gene expressions which may increase the virulence and also the increasing
resistance in bacteria may help to spread.1
Extensive use in animals and plants: The antibiotics are added to animal feeds and the water of plants as preservatives
in some countries. In addition, fruits are sprayed with water containing antibiotics in some regions. Thus, humans may
inadvertently ingest antibiotics or antibiotic resistant bacteria with food.1
Lack of new antibiotics: The discovery of new antibiotics are very rare today. Drug industry developed 13 classes of
antibiotics in thirty years till 1968, but only three since then. One reason for this is the main focus of the pharmaceutical
companies shifted to the more profitable biological agents, drugs for neuromuscular diseases or cancer. Research on
COVID-19, the major pandemic of the latest years, naturally proceeded all drug research. In addition, as with other
drugs, years long phase studies are required for new antibiotics before marketing.
Over the counter use: The life saving properties of antibiotics have made them the most prescribed and used drug group
in the world.5 However, the only reason for the superbugs is not the prescribing habits of the physicians.6 It is reported
that one of the main causes of superbugs is the use of antibiotics without prescription in many countries.7
Measures should be taken to prevent antibiotic resistance4,9,10
· Both physicians and public should be trained on the conscious use of antibiotics.
· Over the counter antibiotic sales should be prevented.
· The antibiotics should not be prescribed for the viral or parasitic infections.
· Broad-spectrum antibiotics should not be used in infections that can be treated with narrow-spectrum antibiotics.
· Prescribing multiple antibiotics should be avoided while a single antibiotic is enough for therapy.
· Antibiotics should be used in appropriate doses and duration; neither long nor short time intervals.

87
· Auxiliary tests such as Gram staining and culture antibiogram should be carried out before prescribing antibiotics,
if possible.
· These measures should be taken not only for humans but also for animals. Antibiotic use for prevention infections
in animal feed or plant water should be avoided worldwide.
· More attention should be paid to discovery of new antibiotics and pharmaceutical companies should be encouraged
in this respect and their work on this subject should be facilitated.
· Rapid diagnostic tests should be established to confirm bacterial infection, resulting in a few hours or even minutes.
· Superbugs can be transmitted by contact. Attention should be payed to the use of common item at home and
healthcare professionals should wash their hands or apply disinfectant before and after each examination and use
disposable gloves.
· In cases of possible non-antibiotic treatments such as acne vulgaris, other treatment options should be considered.
The addition of topical benzoyl peroxide or retinoids to the antibiotics in acne vulgaris treatment should be done in
case of prevent superbugs to form biofilms.
Conclusion
All life forms tend to adapt to changing environmental conditions in order to survive. This is the case for bacteria, too.
Although superbugs are defined as monsters, it should kept in mind that human beings created these monsters by their
own. The widespread and misuse of antibiotics has led bacteria to adapt to changing conditions. Necessary precautions
must be taken against these monsters by humans. If we do not improve our antibiotic use habits, it seems that the next
years will be tough for all humanity.

References
1.Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015;40(4):277-283.
2. Arias E, Rostron BL, Tejada-Vera B. United States life tables, 2005. Natl Vital Stat Rep. 2010:3;58(10):1-132.
3. Jacome MPO, Gonzales-Zubiate FA. How to stop the spreading of super bacteria? Brasil Para Todos-Revista
Internacional 2019;7(1):10–14
4. Aslan Kayiran M, Karadag AS, Al-Khuzaei S, Chen W, Parish LC. Antibiotic Resistance in Acne: Mechanisms,
Complications and Management. Am J Clin Dermatol. 2020;21(6):813-819.
5. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, et al. Global antibiotic consumption 2000
to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742–750.
6. Torres NF, Chibi B, Kuupiel D, Solomon VP, Mashamba-Thompson TP, Middleton LE. The use of non-prescribed
antibiotics; prevalence estimates in low-and-middle-income countries. A systematic review and meta-analysis. Arch
Public Health. 2021;79(1):2.
7. Aslam B, Wang W, Arshad M, Khurshid M, Muzammil S, Rasool M, et al. Antibiotic resistance: a rundown of a global
crisis. Infect drug resist. 2018;11:1645–1658.
8. WHO. Antimicrobial resistance: Global report on surveilla. https://www.who.int/drugresistance/documents/
surveillancereport/en/
9. Karadag AS, Aslan Kayıran M, Wu CY, Chen W, Parish LC. Antibiotic resistance in acne: changes, consequences and
concerns. J Eur Acad Dermatol Venereol. 2020. doi: 10.1111/jdv.16686. (ahead of print)
10. Ventola CL. The antibiotic resistance crisis: part 2: management strategies and new agents. P T. 2015;40(5):344-352.

88
 POSTMODERN TREATMENTS IN DERMATOLOGY
Tuğba Özkök Akbulut
Haseki Training and Research Hospital, Turkey

Postmodern medicine, in other words complementary and alternative medicine, has been the focus of attention worldwide
in recent years. It has been defined as a group of health care practices and products, which is usually not considered part
of traditional western medicine.
It is called “alternative medicine” when used instead of traditional medicine, and it is also called “complementary
medicine” when used with traditional medicine.
Complementary and alternative medicine categories include,
· dietary supplements and herbals
· manipulations,
· body-based practices,
· mind-body interventions.
An increasing number of dermatology patients are using complementary and alternative medicine. During lifetime, the
rate of using complementary and alternative medicine is estimated to be between 35-69% of adults in USA, and 42-70%
in adults in Turkey.1,2 It is claimed that approximately 84.5% of people who report skin problems use complementary
and alternative medicine.
It has been reported that the demographic profile of patients using TCAM applications for skin diseases in the United
States of America (USA) is mostly white women aged 26-50 with at least a high school diploma.3
In one study, the most common TCAM modalities used among adults with skin disease were found as supplements
containing vitamins, minerals or herbs.4 In a study was performed in Turkey, in which 1610 people attended; TCAM use,
such as henna, cologne, moisturizing cream, prayer, and herbal therapy, was common among 43.7% of the participants.5
Complementary and alternative medicine is often chosen in chronic dermatologic conditions, such as atopic dermatitis
(AD), psoriasis, rosacea, acne.6

Atopic dermatitis
The most common complementary and alternative treatment among patients with AD was dietary intervention (42%),
homeopathy (34%), followed by herbalism and supplements (19% and 18%, respectively).6 Patients with atopic
dermatitis due to inconsistent evidence with respect to the guidelines for the treatment of atopic dermatitis, borage
oil, evening primrose oil, fish oil, probiotics / prebiotics, multivitamin supplements, vitamin E, vitamin D, zinc, and
vitamins B12 and B6 are not recommended.

Psoriasis
There are several randomized controlled studies on the efficacy and safety of complementary and alternative medicine
for psoriasis.6 Talbott and Duffy reported that there is a strong evidence in favor of climatotherapy and the use of Qing-
Dai, also referred to as Indigo Naturalis, fish oil and herbs such as Mahonia aquifolium, in the treatment of psoriasis.7 No
evidence was found for herbs, vitamins, minerals such as vitamin D, zinc, or selenium. In a study, evidence of efficacy
was found for inositol in the group of psoriatics taking lithium. One study demonstrated that the plants including neem
and M aquifolium had a evidence of effect for psoriasis. There is a conflicting evidence for aloe vera, fish oil in the
literature. In only one study found an evidence of effect on psoriasis treatment with Chinese medicine. Acupuncture had
no efficacy on psoriasis treatment.

89
Rosacea
Evidence based on the efficacy and safety of complementary and alternative medicine for rosacea is composed of several
methodologically non-strict clinical studies.6 Some studies have noted that various herbal treatments can be promising
for rosacea symptoms.8 It has been showed that several phytochemicals and herbal extracts improved facial erythema
and number of papule and pustule related to rosacea.

Acne
Recently, there is very restricted data on its efficacy and safety to recommend the use of herbal extracts and other
complementary treatments for acne.6 In a RCT, oral barberry extract showed better results in patients with moderate to
severe acne.9

Conclusion
Despite the increasing popularity of complementary and alternative medicine in recent years, further studies are needed
on its efficacy and especially its safety in dermatoses.

Keywords: complementary and alternative medicine, postmodern

References:
1- Ernst E, Pittler MH, Stevinson C. Complementary/alternative medicine in dermatology: evidence-assessed efficacy
of two diseases and two treatments. Am J Clin Dermatol. 2002;3(5):341-8.
2- Tıbbın Alternatifi Olmaz! Geleneksel Alternatif ve Tamamlayıcı Tıp Uygulamaları Türk Tabipler Birliği. Kasım
2017, Ankara Türk Tabipleri Birliği Yayınları. ISBN 978-605 9665-25-4
3- Landis ET, Davis SA, Feldman SR, et al. Complementary and alternative medicine use in dermatology in the United
States. J Altern Complement Med. 2014;20(5):392–398.
4- Fuhrmann T, Smith N, Tausk F. Use of complementary and alternative medicine among adults with skin disease:
Updated results from a national survey. J Am Acad Dermatol. 2010;63(6):1000–1005.
5- Bilgili SG, Ozkol HU, Karadag AS, et al. The use of complementary and alternative medicine among dermatology
outpatients in Eastern Turkey. Hum Exp Toxicol. 2014; 33(2):214–221.
6- National Center for Complementary and Alternative Medicine. Available at: nccam.nih.gov [accessed on February
2021].
7- Talbott W, Duffy N. Complementary and Alternative Medicine for Psoriasis: What the Dermatologist Needs to
Know. Am J Clin Dermatol. 2015;16(3):147–165.
8- Fisk WA, Lev-Tov HA, Clark AK, Sivamani RK. Phytochemical and Botanical Therapies for Rosacea: A Systematic
Review. Phytother Res. 2015 Oct;29(10):1439-51.
9- Fouladi RF. Aqueous extract of dried fruit of Berberis vulgaris L. in acne vulgaris, a clinical trial. J Diet Suppl. 2012
Dec;9(4):253-61.

90
 DOES METFORMIN REALLY WORKS IN DERMATOLOGY
Asude Kara Polat
Department of Dermatology, University of Health Sciences, Istanbul Training and Research Hospital,
Istanbul, Turkey

Metformin (dimethylbiguanide) has been used for years as a traditional herbal therapy in the treatment of type 2 diabetes.
This hypoglycaemic drug was derivated from a herbal source from Galega officinalis (also known as galega, French
lilac, goat’s rue, Italian fitch) (1).
Drug shows its effect by increasing peripheral tissue sensitivity to insulin and peripheral glucose uptake. It inhibits
gluconeogenesis, decreases hepatic glucose, and thus blood glucose decreases. Metformin also has a lipid lowering
effect, such as reducing serum triglyceride and low-density lipoprotein (LDL) cholesterol levels, and increasing serum
high-density lipoprotein (HDL) cholesterol levels (2).
Due to its wide effect mechanisms and properties, it is a suitable drug to be used in the treatment of many diseases
other than diabetes mellitus. The spectrum of dermatological diseases is also quite wide such as psoriasis, hidradenitis
suppurativa, acanthosis nigricans, polycystic ovary syndrome (PCOS) related acne, hirsutismus, skin cancer, and among
others (2-4). It has been reported that metformin decreases the frequency or severity of flares in patients with HS (4).
Again, adding to the treatment in patients with psoriasis leads to an improvement in the quality of life (5). Using
metformin alone or as an adjuvant leads to acne recovery in patients with PCOS (6).
Adverse effects are not serious. It can be observed as cutaneous or noncutaneous (7). Metformin-induced lichen planus,
leukocytoclastic vasculitis and bullous pemphigoid had been reported as a cutaneous adverse effect (8-10). Non-
cutaneous adverse effects include indigestion, myalgia, nausea, vomiting, diarrhea, and flu-like symptoms (7).
Metformin is an agent that is thought to be effective in dermatological diseases, such as psoriasis, hidradenitis suppurativa,
acanthosis nigricans, PCOS related acne, and hirsutismus (4). We can safely use this drug in our clinical practice and
increase our experience.

References
1. Bailey CJ. Metformin: historical overview. Diabetologia 2017;60(9):1566-1576.
2. Chang JE, Choi MS. A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory
Skin Disorders. Int J Mol Sci. 2020; 21(23): 8960.
3. Badr D, Kurban M, Abbas O. Metformin in dermatology: an overview. J Eur Acad Dermatol Venereol. 2013;27(11):1329-35.
4. Sung CT, Chao T, Lee A, Foulad DP, Choi F, Juhasz M, Dobry A, Mesinkovska NA. Oral Metformin for Treating
Dermatological Diseases: A Systematic Review. J Drugs Dermatol. 2020 Aug 1;19(8):713-720.
5. Xuan THT, Thi VB, Ngoc AT, Van ED, Dang QT, Van TN, Minh PPT, Thi LP, Huu ND, Gandolfi M, Satolli F,
Feliciani C, Tirant M, Vojvodic A, Lotti T. Quality of Life in Psoriasis Vietnamese Patients Treated with Metformin in
Combination with Methotrexate. Open Access Maced J Med Sci. 2019;7(2):302-303.
6. Yen H, Chang YT, Yee FJ, Huang YC. Metformin Therapy for Acne in Patients with Polycystic Ovary Syndrome: A
Systematic Review and Meta-analysis. Am J Clin Dermatol 2020 Oct 13. doi: 10.1007/s40257-020-00565-5.
7. Bubna AK. Metformin-For the dermatologist. Indian J Pharmacol. 2016; 48(1): 4–10.
8. Azzam H, Bergman R, Friedman-Birnbaum R. Lichen planus associated with metformin therapy. Dermatology.
1997;194:376.
9. Czarnowicki T, Ramot Y, Ingber A, Maly A, Horev L. Metformin-induced leukocytoclastic vasculitis: A case report.
Am J Clin Dermatol. 2012;13(1):61–3.
10. Skandalis K, Spirova M, Gaitanis G, Tsartsarakis A, Bassukas ID. Drug-induced bullous pemphigoid in diabetes
mellitus patients receiving dipeptidyl peptidase-IV inhibitors plus metformin. J Eur Acad Dermatol Venereol.
2012;26(2):249–53.

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 EGFR INHIBITORS AND SKIN
Sezgi Sarıkaya Solak
Trakya University, Faculty of Medicine, Department of Dermatology, Edirne, Turkey

Epidermal growth factor receptor inhibitors (EGFRIs) are anti-cancer agents targeting specific oncogenic pathways.
They are approved for use in various malignancies including squamous cell carcinoma of the head and neck, colorectal
carcinoma, non-small cell lung cancer, pancreatic cancer and breast cancer. The agents in the EGFRI group are as
following; cetuximab, panitumumab, erlotinib, gefitinib and lapatinib. These treatments are often associated with similar
cutaneous adverse effects (AE).(1, 2)
EGFRs are widely expressed in epidermis and skin appendages. As a result, cutaneous adverse effects are commonly
observed among patients receiving EGFRIs.(3) In addition to EGFR blockade in skin, altering IL-1, TNF-alfa and IL-8
levels is another mechanism causing EGFRI-related cutaneous AEs.(1) Cutaneous toxicities occur in skin, mucosa and
adnexal structures in the majority of the patients treated with EGFRIs. Therefore, it is essential for dermatologists to know
the signs and management of EGFRI-related cutaneous AEs.(2) The most frequently seen reactions are; papulopustular
rash, xerosis, pruritus, hair changes and paronychia.(1, 2, 4)
Papulopustular rash in a seborrheic distribution is the most common (>75%) and earliest cutaneous AE of EGFRIs. It
occurs one or two weeks after initiation of treatment.(2) Pruritic follicular papules evolving into pustules is the main
clinical sign. The severity of eruption and/or discomfort of patient determine the management. Topical antibiotics,
topical corticosteroids, topical calcineurin inhibitors, oral tetracyclines and low-dose oral isotretinoin are the treatment
options.
Xerosis and pruritus appear approximately in one third and half of the patients, respectively.(1, 4) Typically, xerosis is
prominently seen in the extremities during the first months of the treatment.(1) Due to the xerosis; pruritus, fissuring,
eczema and secondary skin infections can occur. Symptomatic treatment of xerosis with moisturizing agents is beneficial.
(2) Oral antihistamines, pregabalin, gabapentin, doxepin and topical anti-inflammatory agents can be considered in case
of severe and disturbing pruritus.(4, 5)
Paronychia is one of the most frequent AEs of EGFRIs occurring in the first to third month of the treatment.(4) The
nail of the thumb or toe is commonly affected. Patients should be advised to avoid tight, uncomfortable shoes before
treatment starts.(2) Antibacterial soaks, topical corticosteroids, warm compress and oral tetracyclines may be used to
reduce inflammation.(1, 2, 4)
Hair changes include; slow growth of hair, finer, more brittle, curlier and kinky hair and mild alopecia. These changes
occur in the second or third month of treatment. Trichomegaly of eye lashes or facial hypertrichosis may be observed.
(2) Patient should be informed that the hair changes are reversible after the cessation of treatment.(1, 4)

References
1. Macdonald JB, Macdonald B, Golitz LE, LoRusso P, Sekulic A. Cutaneous adverse effects of targeted therapies: Part I:
Inhibitors of the cellular membrane. J Am Acad Dermatol. 2015;72(2):203-18; quiz 19-20.
2. Balagula Y, Garbe C, Myskowski PL, Hauschild A, Rapoport BL, Boers-Doets CB, et al. Clinical presentation and
management of dermatological toxicities of epidermal growth factor receptor inhibitors. Int J Dermatol. 2011;50(2):129-46.
3. Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6(10):803-12.
4. Reyes-Habito CM, Roh EK. Cutaneous reactions to chemotherapeutic drugs and targeted therapy for cancer: Part II.
Targeted therapy. J Am Acad Dermatol. 2014;71(2):217.e1-.e11; quiz 27-8.
5. Lacouture ME, Anadkat MJ, Bensadoun RJ, Bryce J, Chan A, Epstein JB, et al. Clinical practice guidelines for the
prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19(8):1079-95.

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 PERIORBITAL WRINKLES AND HYPERPIGMENTATION ETIOLOGY AND TREATMENT
Zehra Aşiran Serdar
İstanbul Yeni Yüzyıl University of Dermotology Department, Turkey

The periorbital region serves as a barometer of chronologic and environmental age and, as such, patients often seek its
cosmetic rejuvenation(1). Maintaining a youthful appearance is a priority for many people. Global eye rejuvenation is
sought more frequently and at a younger age than other treatments.
Periorbital Wrinkles and Hyperpigmentation Etiology
Main causes and mechanisms associated with the three major aging concerns of the periorbital area:
· Periorbital hyperpigmentation (dark circles and upper-eyelid discoloration),
· Puffiness,
· Lines and wrinkles(2).
· All these conditions are triggered by a variety of factors and therefore require a multi-factorial approach.
Skin aging, regardless of whether its origin is chronological or environmental, results in visible deterioration of the
skin’s condition and loss of its functionality. Periorbital wrinkles are formed with repetitive muscle contraction over
time, and they contribute to the appearance of age. However, treatment of the periorbital area is difficult because of its
delicate nature and important function(3).
Proper patient selection and assessment of aging severity are critical to determine the best therapeutic option(1).
Periorbital Wrinkles and Hyperpigmentation Treatment
Treatment modalities
• Ablative and Non-Ablative Lasers,
• Radiofrequency (RF) devices
• Chemical peels
• Platelet-Rich Plasma(PRP),
• Mesotherapy
• Botulinum Toxin
• Filler
Ablative and Non-Ablative Lasers; For patients seeking non-surgical options to improve the appearance of photoaged
skin, several laser-based ablative resurfacing and non-ablative rejuvenation technologies have been employed. Although
these systems have proven efficacy and good safety profiles, there are associated limitations. Certain ablative laser tech-
nologies, such as carbon dioxide and erbium:yttrium–aluminum–garnet lasers, are more effective but result in prolonged
downtime and have greater potential for complications, including dyspigmentation, scarring, infection and prolonged
healing. Non-ablative laser technologies are associated with shorter downtime, but the outcome often seems limited, and
many treatment sessions are necessary.
Radiofrequency (RF) devices; Radiofrequency (RF) devices for skin rejuvenation have also been introduced. This
technology produces volumetric heating via tissue impedance and subsequent heat diffusion, and it affects deeper tissue
layers than laser-based methods.3 Recently, a novel minimally invasive bipolar RF device, the fractionated microneedle
electrode system, has become available for clinical use(4). Collagen remodeling stimulated by this device may result
from combined effects of dermal heating by RF and physical stimulation by microneedling. Radiofrequency is elec-
trical current that can produce thermal effects via tissue resistance. These effects stimulate initial collagen contraction

93
and a wound healing response, which induces remodeling of dermal collagen and tightens skin tissues over a period of
time(5). This neocollagenesis induces deep tissue tightening and thus improves periorbital wrinkles.
Chemical peels; The most commonly used alpha hydroxy acids (AHA) are glycolic 20% and lactic acid 15% which
reduce periorbital pigmentation. Vavouli et al reported an improvement of up to 90% in dark circles following treatment
with 3.75% trichloroacetic acid and 15% lactic acid(6).
Platelet-Rich Plasma(PRP); PRP can be used to treat aesthetic problems in the periorbital regions like wrinkles, pig-
mentation, erythema, xerosis, skin elasticity, and firmness. The best response was observed after three monthly injec-
tions and that is being recommended(7).
Mesotherapy; Mesotherapy, commonly known as “biorejuvenation” a technique used to rejuvenate the skin by means
of a transdermal injection of a multivitamin solution and natural plant extracts that are thought to improve the signs of
skin aging. The efficacy, treatment protocols, pharmacokinetics, and safety of mesotherapy are still of concern and under
debate. Improvements in wrinkles, increased elasticity, and enhanced skin texture have been attributed to mesotherapy
injection but have not been rigorously proven(8).
Botulinum Toxin; Neuromodulator, specifically botulinum toxin A (BoNT-A) is nonsurgical treatment that is frequently
used to address signs of aging in the periocular area(9). Botulinum toxin can be injected in the lower eyelid in a dose of
2-4 units safely along with lateral orbital lines to give a synergistic response and eye widening(10).
Hyaluronic Acid Dermal Fillers; The use of hyaluronic acid fillers has become common nowadays. High patient
satisfaction and low morbidity of these fillers have led to an increase in the acceptance to fillers(11). Fillers are used to
restore age-related periocular volume loss, which is most pronounced in the lower eyelid as well as the superior sulcus.
Injectables such as fillers and botulinum toxin can be combined with skin-tightening devices for a synergistic effect(9).
References
1.Periorbital Rejuvenation: A Review of Dermatologic Treatments.RMP Manaloto, TS Alster - Dermatologic surgery,
2001.
2. Global periorbital skin rejuvenation by a topical eye cream containing low molecular weight heparan sulfate (LMW-
HS) and a blend of naturally derived extracts.Colvan L, Fleck T, Vega VL.J Cosmet Dermatol. 2019 Apr;18(2):530-538.
3.JK Kim, MR Roh, G PARK, YJ Kim. Fractionated microneedle radiofrequency for the treatment of periorbital wrin-
kles. J Dermatol. 2013 Mar;40(3):172-6.
4.Hantash BM, Renton B, Berkowitz RL, Stridde BC, Newman J. Pilot clinical study of a novel minimally invasive
bipolar microneedle radiofrequency device. Lasers Surg Med 2009; 41: 87–95.
5.Elsaie ML, Choudhary S, Leiva A, Nouri K. Nonablative radiofrequency for skin rejuvenation. Dermatol Surg 2010;
36: 577–589.
6.Vavouli C, Katsambas A, Gregoriou S, et al. Chemical peeling with trichloroacetic acid and lactic acid for infraorbital
dark circles. J Cosmet Dermatol. 2013;12(3):204-209.
7.Kassir M, Kroumpouzos G, Puja P, Katsambas A, Galadari H, Lotti T, Abdelmaksoud A, Grabbe S, Juchems E, Gol-
dust M.Update in minimally invasive periorbital rejuvenation with a focus on platelet-rich plasma: A narrative review. J
Cosmet Dermatol. 2020 May;19(5):1057-1062.
8.El-Domyati M, El-Ammawi TS, Moawad O, El-Fakahany H, Medhat W, Mahoney MG, Uitto .Efficacy of mesothera-
py in facial rejuvenation: a histological and immunohistochemical evaluation. J.Int J Dermatol. 2012 Aug;51(8):913-9.
9.Park JY, Byun EJ, Kim HS. Rejuvenation of periocular region in Koreans: A multimodal approach combining bot-
ulinum toxin, fillers, and micro-focused ultrasound with visualization for optimal results. Dermatol Ther. 2020
Jan;33(1):e13159.
10. Flynn TC, Carruthers JA, Carruthers JA, Clark RE 2nd. Botulinum A toxin in lower eyelid: dose finding study. Der-
matol Surg. 2003;29(9):943–950.
11.Goldberg RA, Fiaschetti D. Filling the periorbital hollows with hyaluronic acid gel: initial experience with 244 injec-
tions. Ophthal Plast Reconstr Surg. 2006;22:335-34.

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 ACOSUTIC WAVES IN AESTHETIC DERMATOLOGY
Zahide Eris
Gayrettepe Florence Nightingale Hospital, Dermatology Department, Turkey

Ultrasonography with frequency higher than 7 MHz allows the observation of the skin and its appendages, subcutaneous
tissue and deep structures (muscles, tendons, bone margins and regional lymph nodes).
The era of ultrasounds in dermatology started in 1979, when pioneering use of 15 MHz by Alexander and Miller in
measuring the skin thickness was introduced. Since then, some new applications of high-frequency ultrasonography
(HF-USG) have emerged providing the clinicians with an extra hand in their everyday practice. The main advantages
of HF-USG include the possibility of real-time imaging, measurements of morphological and physiological aspects of
the skin, safety associated with the use of non-ionizing media as well as the lack of contraindications to its performance.
Currently the main clinical use of HF-USG in dermatology regards preoperative assessment of the depth of invasion in
melanomas and basal cell carcinomas.
High-intensity focused ultrasound is the result of the evolution of ultrasound from a simple diagnostic procedure to a
therapeutic modality with broader potential. Ultrasound has long been an intriguing medical modality because of its
noninvasive nature, low cost, and relatively low rate of complications.1 Sound is transmitted by mechanical vibrations;
ultrasound technology utilizes vibrations that are outside of the range of human hearing. High-intensity focused
ultrasound, in comparison to typical ultrasound, uses lower frequencies and higher energy levels by several orders of
magnitude.1 As compared to normal ultrasound, where acoustic waves are resorbed and deflected through tissue, HIFU
can target a specific volume (on the order of millimeters) within the body cavity without harming surrounding tissues.2
A major advantage is that the energy is nonionizing and can theoretically be repeated an unlimited number of times.
High-intensity focused ultrasound (HIFU) safely and effectively improves skin elasticity and clinical contouring of the
face and body.

References:
1. Ulrich J, Schwürzer-Voit M, Jenderka KV, Voit C. Sonographic diagnostics in dermatology. J Dtsch Dermatol Ges.
2014;12:1083–1098.
2. Lucas VS, Burk RS, Creehan S, Grap MJ. Utility of High-frequency ultrasound: moving beyond the surface to detect
changes in skin integrity. Plast Surg Nurs. 2014;34:34–38.
3. Wortsman X, Wortsman J. Clinical usefulness of variable-frequency ultrasound in localized lesions of the skin. J Am
Acad Dermatol. 2010;62:247–256.
4. Wortsman X. Common application of dermatologic sonography. J Ultrasound Med. 2012;31:97–111.
5. Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumors. Nat Rev Cancer. 2005;5(4):321–7.
6. Zhou Y-F. High intensity focused ultrasound in clinical tumor ablation. World J Clin Oncol. 2011;2:8–27.

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 LOW-LEVEL LASER TREATMENT IN DERMATOLOGY
Zahide Eris
Gayrettepe Florence Nightingale Hospital, Dermatology Department, Turkey

It has long been known that red or near-infrared laser light promotes tissue repair and regeneration and low-intensity
light called low-level laser therapy (LLLT) stimulates cellular activity [1]. The most commonly used devices have
wavelengths in the range 500–1,100 nm and they deliver fluences of 1–10 J/cm2 with a power density of 3–90 mW/cm2.
LLLT has shown beneficial effects for a variety of medical conditions such as wound healing, nerve regeneration, joint
pain relief, stroke recovery, and the prevention and treatment of mucositis
Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require
stimulation of healing, relief of pain and inflammation, and restoration of function. Although the skin is the organ that
is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths.
In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT
can reduce UV damage both as a treatment and as a prophylaxis. In pigmentary disorders such as vitiligo, LLLT can
increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity.
Inflammatory diseases such as psoriasis and acne can also benefit. The non-invasive nature and almost complete absence
of side-effects encourages further testing in dermatology.

References:
1. Bjordal JM, Couppe C, Chow RT, Tuner J, Ljunggren EA. A systematic review of low level laser therapy with
location-specific doses for pain from chronic joint disorders. Aust J
2. Brosseau L, Welch V, Wells G, deBie R, Gam A, Harman K, Morin M, Shea B, Tugwell P. Low level laser therapy
(classes I, II and III) in the treatment of rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD002049.
3. Cauwels RG, Martens LC. Low level laser therapy in oral mucositis: A pilot study. Eur Arch Paediatr Dent.
2011;12(2):118–123.
4. Silva GB, Mendonca EF, Bariani C, Antunes HS, Silva MA. The prevention of induced oral mucositis with low-level
laser therapy in bone marrow transplantation patients: A randomized clinical trial. Photomed Laser Surg. 2011;29(1):27–31.

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 CRYOLIPOLYSIS: WHAT IS NEW?
Hasan Mete Aksoy
Plastic, Reconstructive and Aesthetic Surgery Specialist, Kocaeli, Turkey

Cryolipolysis is a non-surgical body sculpting method that uses controlled cooling for localised nonsurgical fat reduction.
Cryolipolysisis is a popular noninvasive treatment method because of its efficacy, convenience, and safety profile;
multiple sessions may have equal efficacy to liposuction.
Cryolipolysis involves placing an applicator over an area containing unwanted excess subcutaneous fat. The applicator
varies in temperatures from +7C to -15C for 25 to 60 minutes. Adipocytes are susceptible to these low temperatures,
whereas the surrounding soft tissues remain unaffected.6 At these temperatures, a combination of fat apoptosis and
necrosis takes place. Apoptosis of fat cells begins after 2 to 3 days, peaks at 2 weeks, and is completed approximately 3
months post-treatment with replacement of adipose tissue by fibrotic tissue.
As this procedure becomes more popular, the wide range of adverse events (AEs) will be well understood.
Concerns of treatment-induced hyperlipidemia following cryolipolysis were initially warranted, however, there is no
evidence of this occurring in practice. A study showed that lipid levels and liver function tests were virtually unchanged
following this procedure.
Most AEs were reported to be mild and transient. The most commonly reported AE was erythema and this was followed
by numbness/paresthesia, bruising, and edema or swelling. There are no reports of permanent loss of sensation following
the procedure. One clinical trial reported that 96% of participants experienced mild procedure-related pain. Severe,
delayed, or persistent pain, and excessive treatment related discomfort were infrequent.
Paradoxical adipose hyperplasia (PAH) is a rare but serious complication of this procedure, presenting as a well-
demarcated hyperplasia of subcutaneous fat, developing months post-treatment. Paradoxical adipose hyperplasia is a
benign growth of adipocytes, however it does not resolve
spontaneously and worries patients who underwent treatment to decrease the adipose tissue. The exact mechanism of
PAH remains unknown, however hypotheses include subapoptotic injury to adipocytes due to inadequate contact with
the cooling applicator, which then stimulates growth of these cells. There are no cases of spontaneous resolution of PAH,
and liposuction is the current mainstay of treatment.
The results of one study revealed incidence rates of PAH between 0.05% and 0.39%, which are slightly higher than
the manufacturer’s quoted rate of 0.025% (1 per 4000 cycles). However, incidence rates at all sites were dramatically
reduced by over 75% with the implementation of newer models of CS units. Of patients who developed PAH, 55% were
male and 77.8% were of European ethnic origin in this study. The majority of PAH cases (76.9%) were associated with
older models of CS units. Thus development of PAH may be related to a combination of factors, including older models
of CS units and applicators, as well as individual characteristics that predispose certain patients to this complication.
Treatment of the submental region can result in injury to throat structures causing swelling and hoarseness and mandibular
nerve palsy may occur after submental treatment. Radial nerve palsy may occur following upper arm treatment. Reported
nerve injuries took place within a range of 1 hour to 6 months after the procedure.
There are some noteworthy contraindications of this procedure. People with conditions exacerbated by cold temperature,
such as paroxysmal cold hemoglobinuria, cryoglobulinemia, and cold urticaria, should not receive this treatment.
Moreover, people with diabetic neuropathy, bleeding disorders (or those using blood thinners), hernias, and active
pacemakers may not be fit for the cryolipolysis procedure.
Severe frostbite complication after cryolipolysis was reported. This case report presents a full-thickness frostbite
complication following cryolipolysis for subcutaneous fat reduction performed in a non-medical esthetic clinic. The
deep and large abdominal wound (15 × 12 cm) required hospitalization and surgical treatment.

97
Clinical research on cryolipolysis has been growing and new evidence is available. The latest systematic review showed
that reduction of the adipose layer can approach 30% per treated region. There are a few clinical trials disclosing that
the reduction of the fat layer can reach 17.4%-20.4% after 2 months and 21.5%-25.5% after 6 months of treatment. In
addition, an epidemiological study showed that two sessions per treatment area were required to obtain some satisfactory
result, with the exception of the abdomen that acquired satisfactory results with only 1 session in 21% of the cases.
Large number of clinical trials rely on tape measures or cutometers to quantify fat loss following treatment; High-
resolution ultrasound and magnetic resonance imaging can also be used to characterize changes in adipose tissue.
However, given the long period over which cryolipolysis results take place and limitations of current quantitative
measurements, it is difficult to monitor treatment response over time. Diffuse optical spectroscopic imaging (DOSI) is
a novel, noninvasive imaging technology that can be used to assess functional and metabolic changes in treated adipose
tissue.
Twenty-seven/28 patients (54 body areas) were considered as treatment ‘responders’ in a clinical trial. In these patients,
mean skinfold thickness decreased from 35.4 ± 9.9 mm pre-treatment to 22.2 ± 7.6 mm at 12 weeks (mean change:
-40%; p<0.001). Mean change in skinfold thickness was greater with ≥ 3 cycles versus 1-2 cycles of CoolSculpting
(p=0.01). Patient satisfaction with treatment was high (n=51/58; 88%). No adverse effects were recorded. This study
shows that multiple cycles/sessions of CoolSculpting can safely improve overall treatment benefit in body contouring,
with greater decreases in skinfold thickness.
In a single-arm intervention study thirty-six subjects underwent one session of cryolipolysis in each area (22 subjects
treated the arms, 20 the submental region and 9 the breast). A mean reduction of 19.1% was observed. So cryolipolysis is
a useful noninvasive tool in reduction of visible localized fat in arms and submental region and of pseudogynecomastia.
Obese subjects are not benefited by this treatment.
Three-dimensional cryolipolysis for submental and lateral neck fat reduction was performed in one study. Posttreatment,
82.05% of patients marked the results of fat reduction as exceptional or very improved,12.82% as improved, 5.13% as
no result, and 0% as worse.
One study investigated cryolipolysis-induced abdominal fat change. Single unilateral cryolipolysis tended to decrease
the cross-sectional areas of visceral adipose tissue, by 8.4 cm2 (9.9%), the waist circumferences, and the percent body
fat, by 2.8 cm2 (0.6%), overall. The cross-sectional area of visceral adipose tissues on the treated side significantly
reduced, by 6.8 cm2 (15.6%; P = 0.003), and that of the untreated side tended to decrease by 1.2 cm2 (3.6%). Split-
body trials have shown that a single unilateral session of noninvasive selective cryolipolysis can be considered as a safe
and effective treatment for reduction of visceral adipose tissue over a period of 12 weeks, which should also result in
metabolic improvement.
Effects of cryolipolysis on lower abdomen fat thickness of healthy women and patient satisfaction were studied in a
randomized controlled trial. The study showed that a single application of the utilized protocol of cryolipolysis does not
produce any significant effect on fat thickness of the lower abdomen of healthy women.
Investigation of systemic effects of cryolipolysis in central obese women was performed in a randomized controlled trial.
In this study there were statistically significant improvements of waist-to-hip ratio, body mass index, total cholesterol,
triglycerides, low-and high-density lipoprotein, as well as liver enzymes in favor of the study group (P < 0.001).
The effect of ultrasound cavitation in combination with cryolipolysis as a non-invasive selective procedure for abdominal
fat reduction was studied. Apart from fat-free mass, the combination therapy significantly reduced body fat mass, weight,
BMI, and abdomen circumference compared to the control group (P < 0.01).
Feasibility Study of Electromagnetic Muscle Stimulation and Cryolipolysis for Abdominal Contouring - with 3 cohorts:
EMMS alone, Cryolipolysis alone, and Cryolipolysis + EMMS in combination was performed. Mean circumferential
reduction measurements were greatest for Cryolipolysis + EMMS cohort group followed by Cryolipolysis only, and then
EMMS only cohort. So a multimodal approach using cryolipolysis and EMMS was safe and demonstrated enhanced
body contouring efficacy for this feasibility study.
A randomized double-blind trial evaluating the efficacy and tolerability of topical body treatment with TriHex

98
Technology® combined with abdomen cryolipolysis or radiofrequency was performed. Nonsurgical fat reduction
procedures using cryolipolysis and radiofrequency are among the most popular noninvasive aesthetic procedures. In
this clinical study, TransFORM Body Treatment (TFB) with TriHex Technology® (ALASTIN® Skincare) improved the
contour and reduced skin laxity following cryolipolysis of the arms. This product is formulated by using a combination
of peptides and other active ingredients designed to stimulate the autophagic breakdown of lipid droplets and expedite
the apoptotic process after fat reduction procedures. In another study, topical application of TFB significantly increased
adipose volume loss and improved clinical outcomes of nonsurgical fat reduction procedures.
To claim that CLL is a noninvasive technique that could be a good alternative to liposuction in patients with moderate
excess fat as claimed by some is not justified after review of literature on this subject. Certainly further research should
be performed to prove positive effects of this treatment modality and to determine categories of patients in whom most
favorable outcomes might be expected.

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 SMOKING AND SKIN AGING
Berna Aksoy
Bahcesehir University, Faculty of Medicine, Department of Dermatology, Istanbul, Turkey

Cigarette smoke is a highly complex aerosol composed of thousands of chemical substances, including carbon monoxide,
reactive oxygen species, and reactive nitrogen species.
Smoking affects several aspects of health and skin. Smoking leads to disruption of the mitochondrial respiratory chain
and induction of reactive oxygen compounds, leading to apoptosis and cellular damage.
Aging in general has been linked to telomere-associated cellular senescence. Oxidative stress contributes to telomere
shortening, and because smoking increases oxidative stress or secondary oxidative events and inhibition of antioxidant
mechanisms it is therefore involved in exogenous aging of the skin. Chemical substances from cigarette smoke increase
transepidermal water loss, degeneration of connective tissue in the skin and upregulation of matrix metalloproteinases‑1
and 3 which degrade collagen and elastic fibers.
Tobacco smoking is an independent risk factor for facial wrinkles as a sign of aging, and extrinsic aging by ultraviolet
irradiation is aggravated also by smoking. Smoking is also a risk factor for eyelid sagging. Smoking causes premature
aging with a characteristic pattern of wrinkling and orange‑purple skin discoloration. Premature facial skin aging in
smokers was defined as smoker’s face. Smoker’s face typically has lines or wrinkles radiating at the right angles from
the corners of the eyes or upper and lower lips, numerous shallow lines on the cheeks and lower jaw, or deep lines on
the cheeks. Smoking was found to be associated with an increased severity of forehead, crow’s feet, and glabellar lines;
under-eye puffiness; tear-trough hollowing; nasolabial folds; oral commissures; perioral lines; and reduced lip fullness
but not midface volume loss or visible blood vessels in a study performed in women. The skin is slightly pigmented
gray with orange, purple and red complexion, and the bony contours become prominent. It has been observed that
wrinkling in a 40‑year‑old heavy smoker resembles that of a 70‑year‑old nonsmoker. Sometimes, large open and closed
comedones with furrows (smoker’s comedones) are seen in the periorbital area. There is yellow discoloration of nails,
yellowish discoloration of the hair and beard (e.g. smoker’s moustache), premature graying and loss of hair, gingival
pigmentation (smoker’s melanosis), leukoplakia of the tongue (smoker’s tongue), oral leukoplakia and a gray‑white
keratinized palate with multiple red umbilicated papules (smoker’s palate/nicotine stomatitis). Smoking contributes to
premature hair graying in men. Smoking is the third most important factor for premature graying after a positive family
history and obesity, but is not related to severity of graying.
Various mechanisms have been postulated for premature aging caused by cigarette smoke.
Particularly owing to nicotine, smoking negatively affects the dermal microvasculature and the healing process. It also
has a toxic effect on keratinocytes and fibroblasts by increasing the expression of metalloproteins and tropoelastin.
Furthermore, smoking increases the expression of small proteoglycans and reduces the synthesis of procollagen. In
mice models, second‑hand smoke, also known as passive smoke caused premature aging by increased cytoplasmic
translocation of high‑mobility group box 1 protein, and hence, the loss of collagen.Transcription of p16INK4a has been
associated with aging, and p16INK4a is a known gerontogen. In murine models, both cigarette smoke and ultraviolet
light have augmented the transcription of p16INK4a. Cigarette smoke extract caused senescence of fibroblasts, possibly
by oxidative stress injury and inhibition of antioxidant defense activity in in vitro studies. Cigarette smoke‑induced early
growth response‑1 induces the expression of cysteine‑rich 61 in human skin dermal fibroblasts. DNA mutations also
result from oxidative effects or direct toxic damage. Smoking can accelerate advanced glycation end-products formation
and increases their deposition in various tissues, including the skin, similarly to UV radiation. Smoking is an important
independent factor in skin aging, observed in an identical twin study, which concluded that 5-year difference in smoking
history is associated with skin changes.

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 ENDERMOLOGIE IN AESTHETIC DERMATOLOGY
Hasan Mete Aksoy
Plastic, Reconstructive and Aesthetic Surgery Specialist, Kocaeli, Turkey

LPG endermologie is a well-tolerated and effective alternative treatment modality for slimming and body contouring. It is
also an alternative treatment of cellulite.
Cellulite is a common phenomenon that gives the skin an orange-peel appearance which is particularly observed on the
thighs and buttocks of post-adolescent women. It is present even in most of the fit women. There are debates on its treatment
methods which, most of the time, lack scientific evidence of efficacy such as liposuction, mesotherapy, subcision, topical
creams, and carboxytherapy.
LPG endermologie is a FDA – approved, non-invasive mechanical massage technique for the treatment of cellulite. LPG
endermologie system consists of a deep tissue mobilization provided by a medical device composed of a treatment chamber
with an aspiration system and two independent motorized rollers that roll and unroll skin folds. The positive pressure from
the rollers combined with the negative pressure from aspiration is believed to cause sublethal damage to the subcutaneous
fat cells. As these damaged fat cells heal, they rebuild with an improved contour of the skin and a better distribution of
subcutaneous fat as a result. Although the fat layer is altered, this mechanical force does not affect the overlying skin, bones,
or muscles.
The scientific evidence of LPG in the literature is inconclusive and has only level-II evidence strength (at least one
controlled study without randomization). Thus, comparing other treatment modalities such as mesotherapy, carboxytherapy,
radiofrequency, and ultrasound should enhance the knowledge of clinicians on the efficiency of LPG treatment on cellulite.
However, LPG endermologie seems to be an effective, well-tolerated and satisfying non-
invasive technique for reducing cellulite grade, BFP, and body circumference measurements.
A study with a porcine model demonstrates that Endermologie treatment does not cause fatty tissues to be broken down,
mobilized, and excreted. A standard regime of Endermologie sessions does not produce an inflammatory or classical wound
healing response. Increased cell proliferation, neovascularity, or injury to the dermis and epidermis do not occur. However,
changes in subdermal tissue architecture result from Endermologie treatment, and these changes are proportional to the
number of Endermologie treatments performed. Although adipocyte injury occurs, there is no net decrease in thickness
of subcutaneous tissue. However, significant accumulation of collagen fibers occurs mainly in the deep subdermal layer,
primarily in the form of dense longitudinal collagen bands. These bands may be largely responsible for the smoothing effect
to the skin that has been reported following Endermologie treatments. The question of whether these changes are temporary
or permanent must be addressed by future long-term experimental studies.
Endermologie (LPG Systems, Miami, FL), or mechanically-assisted deep soft tissue massage, remains a controversial
adjunct to lipoplasty and other forms of body contour surgery.
Endermologie remains an interesting and potentially valuable adjunct to body contouring surgical procedures. However, the
fact that it is so operator dependent may explain some of the variable clinical results that have been reported so far.
Recent laboratory studies have shown that various maneuvers in Endermologie treatment, such as smoothing, kneading,
and bouncing, create unique waveforms. The amount of pressure generated with each maneuver depends more on the
operator’s technique than on the suction setting or the force of the spring-loaded rollers. This observation might explain the
variable clinical results for Endermologie that have been reported.
Endermologie has been used during liposuction surgery, and in some patients after lipoplasty surgery (i.e., Endermologie-
assisted lipoplasty [EAL]).
The technique involves applying Endermologie to a body region just suctioned while another area is being infused. So the
operating time is not prolonged. A palpable difference in the subcutaneous fat can be appreciated because it becomes more
even and pliable after the application of Endermologie ® to the suctioned area. Endermologie applied in this manner also
helps with the even dispersion of the wetting solution during lipoplasty procedure.
Ecchymosis and swelling dissipated quite rapidly in EAL patients and as early as the first dressing change (2 to 4 days after
surgery).
During the long-term follow-up of the patients, it seems that postlipoplasty surface irregularities have been lessened.

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 ALPHA AND BETA HYDROXY ACIDS IN DERMATOLOGY
Aslı Tatlıparmak
İstinye University Faculty of Medicine, Department of Dermatology, İstanbul, Turkey

Hydroxy acids (HAs) represent a class of compounds which have been widely used in a number of cosmetic and
therapeutic formulations in order to achieve a variety of beneficial effects for the skin (1). Αlpha-Has (AHAs) are
carboxylic acids with one hydroxyl group attached to the α-position of the carboxyl group. The simplest representative
of αHA is glycolic acid (chemical name, hydroxyacetic acid), which was the first of this class of compounds to be
introduced into skin care products. Lactic acid, with optimal biologic activity in its L-form, is also used in various
topical formulations to exfoliate the skin and also to provide antiaging properties (1,2). The cosmetic and dermatologic
use of AHAs, i. e. the indication for the treatment with the acids and their salts, depends mainly on concentration, pH,
formulation and application time. The higher the concentration and the lower the pH of the product, the greater is the
exfoliative, toxic, and corrosive action (1,3). Lower concentrations with 5 % up to 20 % of AHAs are formulated in
creams or gels for use prior to peelings and for long-term application in acne as well as in hyperkeratotic or aged skin
(4). Solutions containing free AHAs at concentrations of 20 % up to 70 %, partially neutralized AHA-solutions (30 % to
70 %) as well as gels at 70 % are used for peelings carried out profession- ally by a dermatologist (2).
β-Hydroxy acids (βHAs) are carboxylic acids having one hydroxyl group attached to the β-position of the carboxyl group.
The most common βHA is β-hydroxybutanoic acid. A lipid soluble βHA is tropic acid (2-phenyl-3-hydroxypropanoic
acid). Some βHAs are also considered αHAs as they contain a hydroxyl group in the α-position to one carboxyl group and
in the β-position to the other carboxyl group. Malic acid and citric acid are prominent representa- tives in this category.
Citric acid is widely used in topical formulations as an antioxidant, and its antiaging benefits are well established (1).
In the cosmetic and dermatologic literature, salicylic acid SA is often described as a βHA, but that classification is
incorrect. In SA, both the hydroxyl and the carboxyl groups are directly attached to an aromatic benzene ring and both
exhibit acidic properties. In contrast, the hydroxy groups in αHAs, and βHAs are neutral under the conditions used in
clinical and cosmetic settings. On the basis of knowledge to date, SA does not function physiologically or therapeutically
as a βHA. SA is used in cosmetic formulations for a variety of applications, more specifically, it is fat soluble, which
makes it useful in subjects with oily skin (1).

References
1. Kornhauser A. Applications of hydroxy acids: classification, mechanisms, and photoactivity. Clin Cosmet Investig
Dermatol. 2010 Nov;3:135.
2. Babilas P, Knie U, Abels C. Cosmetic and dermatologic use of alpha hydroxy acids. JDDG J der Dtsch Dermatologischen
Gesellschaft. 2012;
3. Ramos-E-Silva M, Hexsel DM, Rutowitsch MS, Zechmeister M. Hydroxy acids and retinoids in cosmetics. Clin
Dermatol. 2001;19(4):460–6.
4. Dahiya A, Romano JF. Cosmeceuticals: A review of their use for aging and photoaged skin. Cosmetic Dermatology.
2006.

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 FRACTIONAL PHOTOTHERMOLYSIS IN AESTHETIC DERMATOLOGY
Filiz Canpolat
Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Dermatoloji Kliniği, Türkiye

Fractional Photothermolysis (FP) a novel treatment concept that utilizes focused laser beams to create a 3-dimensional
pattern of microscopically small lesions within the skin.1
Ablative lasers (CO2 and Er:YAG) provide the greatest improvement in photoaging, but significant adverse effects limit
their use. Nonablative lasers have reduced adverse effects, but limited efficacy. Fractional photothermolysis produces
arrays of microscopic thermal wounds called microscopic treatment zones (MTZs) at specific depths in the skin without
injuring surrounding tissue. Wounding is not apparent because the stratum corneum remains intact during treatment
and acts as a natural bandage.2 Tissue in the MTZs is typically either thermally damaged in non-ablative FP (nFP),
or physically removed (vaporized) in ablative FP (aFP). Due to the small size of the MTZs—generally in the sub-
millimeter range—and the availability of surrounding unharmed tissue, such lesions can regenerate very quickly with
relatively few side effects as compared to macroscopic lesions extending to similar depth.1 In contrast to ablative
lasers, fractional lasers coagulate only 20 percent of the treated skin, sparing islands of viable epidermis and untreated
dermis that maintain the skin’s barrier function while speeding re-epithelialization. The fractional approach may achieve
comparable results to fullsurface ablative lasers without the associated side effects.3 Downtime is minimal and erythema
is mild, permitting patients to apply cosmetics immediately after treatment. As with other nonablative laser modalities,
multiple treatments are required.2
FP represents an alternative for treatment of dermatologic conditions without the adverse effects of ablative laser
devices and can be used on all parts of the body. FP can be used for the treatment of facial rhytides, acne scars, surgical
scars, melasma, and photodamaged skin.2 A multitude of FP devices employing different wavelengths and exposure
parameters have been developed and are currently used clinically.
The fractional approach of laser delivery offers significant benefits in terms of rapid tissue healing and enables its use in
all skin types and nonfacial areas which greatly expands the treatment capacity for laser resurfacing. The development
of the newer ablative fractional devices may further increase clinical efficacy while minimizing the number of treatment
sessions required to achieve optimal results.

References:
1. Manstein D., Laubach HJ. (2011) Fractional Photothermolysis. In: Nouri K. (eds) Lasers in Dermatology and
Medicine. Springer, London.
2. Geronemus RG. Fractional photothermolysis: current and future applications. Lasers Surg Med. 2006; 38(3): 169-76.
3. Cohen SR, Henssler C, Johnston C. Fractional Photothermolysis for Skin Rejuvenation. Plast Reconstr Surg 2009;
124: 281.

103
 HYALURONON AND SKIN
Filiz Canpolat
Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Dermatoloji Kliniği, Türkiye

Skin aging is a combination of multifactorial mechanisms that are not fully understood. It is the result of two biologically
independent processes. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share
similar molecular pathways. The first is intrinsic or innate aging, an unpreventable process, which affects the skin in the
same pattern as it affects all internal organs. The second is extrinsic aging, which is the result of exposure to external
factors, mainly ultraviolet (UV) irradiation, that is also referred to as photoaging. Intrinsic skin aging is influenced by
hormonal changes that occur with age, such as the gradual decreased production of sex hormones from the mid-twenties
and the diminution of estrogens and progesterone associated with menopause. It is well established that the deficiency
in estrogens and androgens results in collagen degradation, dryness, loss of elasticity, epidermal atrophy and wrinkling
of the skin. 1
Skin aging is also associated with loss of skin moisture. One of the main characteristics of youthful skin is its large
capacity to retain water, and this decreases significantly as we age. The key molecule involved in skin moisture is
hyaluronan or hyaluronic acid (HA), a glycosaminoglycan (GAG) with a unique capacity to bind and retain water
molecules. HA belongs to the extracellular matrix (ECM) molecules. Hyaluronan (HA) is a key component of the extra-
cellular matrix and is involved in several mechanisms of the wound healing process. It is highly hygroscopic and is
involved in the visco-elasticity of the skin.2, 3 It has been proven to modulate via specific HA receptors, inflammation,
cellular migration, and angiogenesis, which are the main phases of wound healing. Degradation of HA by specific
hyaluronidase enzymes produces HA fragments that can help to regulate inflammatory processes. HA is also the most
popular and commonly employed dermal filler.4
Functions of HA include the following: hydration, lubrication of joints, a space filling capacity, and the framework
through which cells migrate. The synthesis of HA increases during tissue injury and wound healing and HA regulates
several aspects of tissue repair, including activation of inflammatory cells to enhance immune response and the response
to injury of fibroblasts and epithelial cells. HA also provides the framework for blood vessel formation and fibroblast
migration, that may be involved in tumor progression. The correlation of HA levels on the cell surface of cancer cells
with the aggressiveness of tumors has also been reported.1
In this presentation, I summarize the role of HA polymers of different molecular weight in tissue regeneration and
provide a short overview of main cellular receptors involved in HA signaling. In addition, the role of HA in 2 major
steps of wound healing is examined: inflammation and the angiogenesis process. Finally, the antioxidative and antiaging
properties of HA are discussed and its possible clinical implication presented.

References:
1. Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: A key molecule in skin aging. Dermatoendocrinol.
2012; 4(3): 253-8.
2. Gall Y. Acide hyaluronique : structure, métabolisme et implication dans la cicatrisation [Hyaluronic acid: structure,
metabolism and implication in cicatrisation]. Ann Dermatol Venereol. 2010; 137 Suppl 1: S30-9.
3. Narurkar VA, Fabi SG, Bucay VW, et al. Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis
With Instant Benefits. J Drugs Dermatol. 2016; 15(1 Suppl 2): s24-37.
4. Mandal P, Gama F. The use of periocular fillers in aesthetic medicine. J Plast Reconstr Aesthet Surg. 2021; 9: S1748-
6815(21)00013-9.

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 INTEGRATIVE APPROACHES OF PRURITUS
Zafer Türkoğlu
Basaksehir City Hospital, Turkey

Pruritus (synonymous with “itch”) can be defined as “an unpleasant sensation that provokes the desire to scratch” It
is a common feature of many inflammatory skin diseases such as atopic dermatitis, irritant and allergic dermatitis,
scabies, and lichen planus, but may also be seen in a large number of systemic conditions, including cholestasis, thyroid
disorders, and kidney failure. Pruritus is a common symptome,which has a negative effect on quality of life. Current
treatments do not fully control the pruritus, these drugs can provide temporary relief but can also cause side-effects and
do not help modulate overactive immune responses or address other underlying factors that cause pruritus.
Thus effective, safe treatments for pruritus are still needed. For many years, integrative medicines have found to be very
active in the treatment of pruritus (1).
Integrative treatments: Possible underlying factors involved in the development of chronic and acute pruritus, toward
which holistic treatments may be targeted, include:
• Intestinal dysbiosis and “leaky gut” related to food allergies
• Chronic inflammation
• Oxidative stress
• Latent infection.
Dietary changes and immune-modulation therapies—Numerous published studies suggest that pruritus can be
related to food allergies.
A gluten-free diet and other antiallergenic diets have successfully reduced inflammation and immune responses in
pruritus as well as in autoimmune conditions.
The foods considered allergenic include fish, shellfish, beef, lamb, egg and spicy foods. Patients choose to eliminate
these possible allergic foods from their diet without further diagnostic procedures (2).
Botanical and herbal therapies— In East Asian regions, by virtue of safety and fewer adverse reaction, a variety of
herbal medicines are used in the treatment of pruritus and they are likely to be a good substitute for Western medicines.
Some herbs or herbal formulae have been shown to be effective when applied alone or combined with antihistamines,
even when antihistamine did not work alone, with low or high evidence.Botanicals that reduce inflammation, combat
oxidative stress, and treat underlying infections, particularly in the intestines, Curcumin (active constituent of Turmuric),
Gingerol (active constituent of Ginger), Aaragawdha, Shirish and few other plants have actively been used for pruritus
since ages (3).There is evidence about sunflower seed oil especially relevant to pruritus. The itch-scratch cycle with its
associated barrier damage and secondary inflammation can occur even in the absence of primary skin disease. Sunflower
(Helianthus annus) seed oil is rich in linoleic acid, and has been used topically in the treatment of essential fatty-acid
deficiency, rapidly reversing the disease (4). These essential fatty acids can also help maintain the skin barrier and
decrease transepidermal water loss, both important features in thinking about the barrier problem in atopic dermatitis
and, presumably, in other situa- tions where the barrier has been damaged. Several studies have also suggested that there
are anti- inflammatory properties of sunflower seed oil, perhaps via the PPAR pathway, which may also be helpful given
that the mechanical act of scratching can contribute to inflammation in the skin (5). Safe and inexpensive, sunflower oil
could play a role in managing itch, regardless of the etiology. Aromatherapy refers to the use of essential oils extracted
from botanical sources to treat diseases . It is commonly administered by massaging into the skin, although can be
vaporized and inhaled, taken orally, or even used in the bath. Aromatherapy often implies a mixture of oils, rather
than a single oil. Because of the wide range of botanicals, their variable concentrations, and the multiple routes of
administration, it is difficult to postulate a single mechanism of action. Clinically, however, several studies sug- gest that
aromatherapy can cause a reduction in anxiety and improves mental status, which could play a role in the perception of
itch (6).
105
Acupuncture /Acupressure— Acupuncture has a long history and been widely used in clinical practice for treating
pruritus in China and other countries. Many clinical studies have reported that acupuncture is effective for the treatment
of pruritus (2).
Acupuncture is based on the idea that energy meridians in the body can become unbalanced and that by stimulating
certain points (acupoints) with needles, pressure, magnets, or even lasers, the flow can be restored and rebalanced.
From a conventional standpoint, there are studies that show clear changes in specific brain areas with acupuncture,
and evidence that there is endorphin production with acupuncture, suggesting a neurocutaneous connection (7). While
formal acupuncture would require a specially-trained practitioner, more limited ver- sions (including the single point
study discussed below) could be performed by nearly anyone, including patients themselves.
Mind–body therapies, Hypnotherapy Biofeedback, and Cognitive Behavioral Therapy:
Allergies can be ameliorated with mind–body exercises, such as mindfulness meditation. Mind–body practices help
to calm an overactive immune system, while supporting greater adaptation and tolerance to one’s environment on all
levels: physical; mental; and psychospiritual. Stress is known to be a significant trigger for atopic dermati- tis, and the
itch-scratch cycle may become a deeply ingrained behavioral response that is elicited more during times of anxiety,
regardless of the cause (6). It follows, then, that techniques to reduce stress could be helpful in the management of itch.
Safe and somewhat holistic, hypnosis and cognitive behavioral techniques do seem to be helpful in both adults and
children, and appear to have a durable response.
Cupping therapy
Cupping therapy is a complementary and alternative medical technique with a long history in China. There are two main
types of cupping therapy: dry cupping and wet cupping . In dry cupping, a vacuum created in the cup exerts tension on
the skin and draws it into the cup. In wet cupping, a small incision is first made on the skin and then the negative pressure
applied to the cup draws out a small volume of blood . In recent years, cupping therapy has been widely used in the
treatment of skin diseases , including pruritus (7).
Probiotics—A preliminary study was conducted to examine the effect of ENDOLAC (Lactobacillus acidophilus, Lacto-
bacillus delbrueckii, and Streptococcus thermophilus) on CD34+ cells in patients with clinical symptoms of asthma and/
or conjunctivitis, rhinitis, urticaria, atopic dermatitis, food allergy, and irritable bowel syndrome. After the treatment,
circulating CD34+ cell values were significantly reduced (8).
Ozone Therapy, autologous whole blood therapy: Ozone, a classic oxidant and sterilizer, has been widely applied
in clinic, which involves in mechanisms of antimicrobial effect, antioxidant defenses, immunoregulation, epigenetic
modification, biosynthesis, analgesics and vasodilation. Ozonated water and oil have been widely used in treatment of
inflammatory and infectious skin conditions because it can quickly relieve symptoms such as pruritus and edema thus
mitigating disease severity. Topical ozone therapy is highly effective for treatment for AD. It can change the proportional
ratio of Staphylococcus and Acinetobacter, thereby restoring the microbiological diversity in AD lesions (9).
Treatment with autohemotherapy has been proposed as a strategy to induce tolerance to circulating histamine-releasing
factors.
Psychiatric medications and psychotherapy
Anxiety, depression and somatoform disorders have been reported as the most prevalent mental disorders in patients
with pruritus. Patients with pruritus had a higher prevalence of psychiatric disorders and psychiatric medication use than
control groups in the general population. Mental health evaluations and management are important elements in pruritus
management (10).
Patients turn to complementary and alternative medicine (CAM) when they are faced with pruritus, particularly when
they experience the ineffectiveness and side-effects of Western medicines used to treat the condition or if their symptoms
are not resolved.
An integrative Eastern and Western medicine approach can be very effective for managing pruritus and the root condition
that causes pruritus.

106
Correct and appropriate applications can be used by trained people in every field of medicine, as treating pruritus.

References
1.Pfab F, Schalock PC, Napadow V, Athanasiadis GI, Yosipovitch G, Ring J. Complementary integrative approach for
treating pruritus. Dermatol Ther. 2013;26(2):149–56.
2.Ohlsen BA. Acupuncture and a gluten-free diet relieve urticaria and eczema in a case of undiagnosed dermatitis
herpetiformis and atypical or extraintestinal celiac disease: A case report. J Chiropr Med 2011;10:294–300.
3.Shah, K., Raole, V., Parikh, N., Engineer, S., Bhrambhatt, R., Chauhan, B. A review on herbal approach towards
urticaria an allergic skin disorder2018;7:1996-2010.
4.Lodén M, Andersson AC. Effect of topically applied lipids on surfactant-irritated skin. Br J Dermatol. 1996;134(2):215–20.
5.Eichenfield LF, McCollum A, Msika P. The benefits of sunflower oleodistillate (SOD) in pediatric dermatology. Pediatr
Dermatol. 2009;26(6):669–75.
6.Shenefelt PD. Biofeedback, cognitive-behavioral methods, and hyp- nosis in dermatology: is it all in your mind?
Dermatol Ther. 2003;16:114–22.
7. Li, X. Clinical Observation on Skin Pruritus Treated by Blood-letting Puncture and Cupping of Auricular and Shu-
back Acupoints. Asia-Pacific Journal of Chinese Medicine
2019; 1(2): 19-21
8. Mastrandrea F, Coradduzza G, Serio G, et al. Probiotics reduce the CD34+ hemopoietic precursor cell increased
traffic in allergic subjects. Eur Ann Al-lergy Clin Immunol 2004;36:118–122.
9. Zeng J, et al. “Topical ozone therapy restores microbiome diversity in atopic dermatitis.” International
immunopharmacology 80 (2020): 106191.
10. Jafferan M, Maryam ED. “Itch and psyche: psychiatric aspects of pruritus.” International journal of dermatology
2019;58: 3-23.

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 INTEGRATIVE APPROACHES OF URTICARIA AND DRUG ALLERGY
Murat Türk
Clinic of Allergic and Immunologic Diseases, Kayseri Şehir Hastanesi, Kayseri, Turkey

Drug hypersensitivity reactions are a prevalent phenomenon and affect more than 7% of the population. Skin is the most
frequently involved organ. Drug hypersensitivity reactions can be immunologically and non-immunologically mediated.
Urticaria is one of the main clinical manifestations in immediate reactions and are usually mediated by specific IgE
binding to the FcɛRI receptor on mast cells and basophils leads to degranulation and release of preformed mediators
that cause the clinical symptoms. Urticaria can also be mediated by a pharmacological mechanism with non-steroidal
anti-inflammatory drugs being the most frequent culprits. Up to 35% of patients with chronic spontaneous urticaria
(CSU) experience exacerbation of skin symptoms when exposed to NSAIDs. Analogous to AERD, the designation
AECD (NERD) has been recently proposed for this condition. Acute urticaria also may develop in some patients who
do not have CSU on exposure to NSAIDs. Serum-specific IgE antibodies specific for the drug have been detected
in tghis condition. Skin test (ST) is the best-validated method in IgE-mediated reactions. It is challenging for the
clinicians to perform skin tests to patient diagnosed with CSU since most patients are unable to withdraw their ongoing
treatments or have comorbid dermographism. Drug provocation test is the gold standard in drug allergy diagnosis and
in non-immunologically mediated reactions, DPT is the only available tool. There is still a gap in the standardization
of procedures of DPT and interpretation of test results. In another perspective, it was shown that prevalence of reported
drug allergy in chronic ut-rticaria patients is dramatically higher in comparison to that of the general population showing
a significant proportion of patients labeled with multiple drug allergies have an underlying, undiagnosed chronic or
recurrent urticaria ultimately leading to overdiagnosis of drug hypersensitivity.Current diagnostic tools to detect drug
allergy in patients diagnosed with chronic urticaria will be discussed in this section.

References
1. Brockow K, Ardern-Jones MR, Mockenhaupt M, Barbaud A, Caubet JC, Spiewak R, et al. EAACI position paper on
how to classify cutaneous manifestations of drug hypersensitivity. Allergy 2019;74:14-27
2. Fernandez J, Doña I. Diagnosing and managing patients with drug hypersensitivity. Expert Rev Clin Immunol
2018;14:29-41
3. Li KL, Lee AY, Abuzeid WM. Aspirin Exacerbated Respiratory Disease: Epidemiology, Pathophysiology, and
Management. Med Sci (Basel). 2019;7(3):45.
4. Soyer O, Sahiner UM, Sekerel BE. Pro and Contra: Provocation Tests in Drug Hypersensitivity. Int J Mol Sci.
2017;18(7):1437.
5. Roxanne C. Oriel, Amanda Innamorato, Blanka M. Kaplan. Underlying Chronic Urticaria in Patients With Multiple
Drug Allergies: A Call For Screening JACI. 2017; 139:2.

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 INTEGRATIVE APPROACH TO ATOPY
Murat Türk
Clinic of Allergic and Immunologic Diseases, Kayseri Şehir Hastanesi, Kayseri, Türkiye

Atopy is a predisposition to respond immunologically to diverse antigens/allergens, leading to CD4+ Th2 differentiation
and overproduction of immunoglobulin E (IgE). The clinical consequence of this is the propensity to develop
hypersensitivity reactions to allergens. Complex genetic, environmental, and site-specific factors contribute to
development of allergies. Prevalance of atopic diseases including asthma, allergic rhinitis and atopic dermatitis are
considered to be rising in world.
The evaluation of immediate hypersensitivity includes both in-vivo (e.g. skin prick test, intradermal test, provocation
tests) and in-vitro (e.g. eosinophil count, spesific IgE, basophil activation test) objective testing. Here, we will discuss
an integrative approach to atopy an allergic diseases.

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 SKIN BIOPSY TECHNIQUES
Tamer İrfan Kaya
Mersin University, Faculty of Medicine, Department of Dermatology, Mersin, Turkey

The skin biopsy is a simple but vital clinical skill of the dermatologist. Skin biopsy for diagnostic and therapeutic
purposes is a central component in the management of skin diseases. When performed properly, it can be quick and
comfortable for the patient, and yield a very high level of diagnostic information. However when performed incorrectly,
it can lead to delays in diagnosis and treatment for the patient. While the technical aspects of performing biopsies are
familiar to most clinicians, a number of other aspects of the skin biopsy pathway are equally important such as optimal
selection of the most characteristic lesion at the most appropriate anatomic location, correct biopsy technique, proper
handling of specimens, and providing detailed clinical information for the dermatopathologist.1-5
The most important skin biopsy techniques are shave (horizontal) biopsy, punch biopsy, incisional and excisional
biopsy. Punch, incisional, or excisional biopsy is suitable for dermal and/or subcutaneous lesions, where as shave biopsy
is preferred for more superficial lesions and haemostasis may be achieved with pressure, 25 % aluminium chloride
solution or electrocautery. Punch biopsy is quick and easy technique performed using a circular blade. Punch blade
sizes range from 2 to 8 mm in diameter, however 3–4 mm punches are often used which usually provides adequate tissue
for pathologic evaluation. Incisional and excisional biopsies are performed with a scalpel. A representative portion of
the lesion can be excised and the defect should be closed with sutures. The shape of the incision should be fusiform,
with angles of 30 degrees at the wound tips. Skin biopsy can be performed with a clean (modified sterile) technique.
For smaller biopsies cleaning the area with alcohol for 10 seconds is the fastest and practical option. Alcohol instantly
denatures the proteins but it has no residual activity. For long lasting operations povidone iodine should be preferred.
When povidone iodine is applied to the skin the dermatologist should wait 2 minutes for the optimum antimicrobial
activity. Skin biopsy will usually be performed using local anesthesia, which usually relates to anesthesia of a small area
of the body. Preferring a dermal injection technique results in quick and long lasting anesthesia but it is more painful
compared to subcutaneous injection technique. When operating on skin, care must be taken not to distort anatomic
structures and it is important to be familiar with Langer’s lines, also known as relaxed skin tension lines when deciding
how to locate an incision to optimize healing and minimize scarring.1-8
The objective of this presentation is to provide basic information about the skin biopsy techniques and to offer practical
advice on the approach to some common skin lesions.

References:
1. Alguire PC, Mathes BM. Skin biopsy techniques for the internist. J Gen Intern Med 1998;13:46–54.
2. Sleiman R, Kurban M, Abbas O. Maximizing diagnostic outcomes of skin biopsy specimens. Int J Dermatol
2013;52:72–78.
3. Sina B, Kao GF, Deng AC, Gaspari AA. Skin biopsy for inflammatory and common neoplastic skin diseases: Optimum
time, best location and preferred techniques. A critical review. J Cutan Pathol 2009;36:505–510.
4. Harvey NT, Chan J, Wood BA. Skin biopsy in the diagnosis of inflammatory skin disease. Aust Fam Physician
2017;46:283–288.
5. Robinson J, Hanke CW, Sengelmann R, Siegel D (editors). Surgery of the skin: Procedural dermatology. Chapter 14:
Skin biopsy techniques. Philadelphia: Elsevier Mosby, 2005; p. 203–212.
6. Nischal U, Nischal Kc, Khopkar U. Techniques of skin biopsy and practical considerations. J Cutan Aesthet Surg
2008;1:107–111.
7. Wark KJ, Smith SD, Sebaratnam DF. How to perform a skin biopsy. Med J Aust. 2020 Mar;212:156-158.
8. Kilic A, Kilic A, Kivanc AE, Sisik A. Biopsy Techniques for Skin Disease and Skin Cancer: A New Approach. J
Cutan Aesthet Surg. 2020;13:251-254.

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 ADVANCED SURGICAL SUTURE TECHNIQUES IN DERMATOLOGICAL SURGERY
Eckart Haneke
Department of Dermatology, Inselspital, University of Berne, Switzerland
Dermatology Practice Dermaticum, Freiburg, Germany
Centro de Dermatología Epidermis, Instituto CUF, Matosinhos, Porto, Portugal
Department of Dermatology, University Hospital Ghent, Belgium

Surgical treatment is the mainstay of cutaneous tumors and some otherwise intractable skin conditions. The remaining
scar is the visible track left behind by the dermatological surgeon. An unsightly scar will soon let the patient forget
what he/she had before and may ruin his/her future life. Sutures are the most common way to close an incisional wound
and a skin defect. This requires sutures in most cases as non-suture wound closures are only available for some special
situations like incisions without tension.
The number of different skin sutures available for closure is vast. The easiest is the simple percutaneous stitch with the
knot outside of the skin. It can be used for virtually all wounds, but its disadvantage is sutures marks after stitch removal.
In order to overcome this adverse result, intradermal sutures of various kinds can be used. The most commonly used
stitch technique is the intradermal suture. The needle is inserted at the undersurface of the dermis and exits just under the
epidermis at the level of border between the papillary and the reticular dermis. This gives good support as it can be tied
firmly because no stitch marks will appear. However, it is crucial not to take subcutaneous fat as this will be resorbed
within a short period of time and the suture will be loose inviting wound dehiscence.
Many textbooks claim that sutures must not be done under tension. This is nonsense as virtually all skin defects will
result in some degree of skin tension. However, there are techniques facilitating suturing under tension by using two or
even three loops for one knot, this kind of pulley suture may be transepidermal or intradermal the latter not leaving stitch
marks. For an intradermal parallel pulley suture, the needle is inserted at the undersurface of the dermis, exits under the
epidermis, is re-inserted at the same level at the oppositie wound margin , exits at the dermis underside and a second loop
like the first is performed 3 – 5 mm lateral from the first throw. The ends of the thread are then pulled towards each other
to close the wound and tied. This suture has double strength while distributing the tension at two suture points, it is easy
to knot as it usually does not slip and therefore does not require help of an assistant. A particular variant of the parallel
pulley suture may be used for the pole of a small defect with a relatively large angle (> 35°) combining the pulley action
with skin sparing. The first throw is performed as described, the second is performed obliquely so that upon tying the
knot the end of the fusiform excision is pulled down preventing the formation of a dog-ear or standing cone. If there is
even more tension, the parallel double stitch can be extended to a triple suture: The first throw is performed as usual,
the second as in the parallel double stitch, the third is parallel to the first and second but on the other side of the first
bite. This triple suture is very versatile for wounds after excision of naevi of the back. The preferred suture material is
polyglactin which remains stable for several months.
Commonly, 3/8 curvature needles are used. They are practical for percutaneous stitches but may not be easy to use for
intradermal stitches as they do not allow the needle to be inserted and exited in the dermis. A half-circle needle is more
practical for intradermal sutures. However, it must be taken with care with the needle holder in order to avoid bending it.
If you can still not exit the needle within the dermis you may exit the needle through the skin approximately 5 mm from
the wound margin and re-enter it through the same exit point to come out at the wound margin at the border between the
papillary and reticular dermis. In a mirror fashion, it may be repeated on the other side of the wound. The knot is tied at
the undersurface of the dermis. A tiny dimple is seen for 24 hours where the exit and re-insertion point was. This suture
can also be performed as a parallel buried pulley suture.
Running intracuticular sutures are usually performed parallel to the skin surface. They give nice results, however, they
cannot hold tension. In contrast, a running intradermal spiral suture is extremely supporting and holds a lot of tension as
it is pulled tight with each new loop.

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In summary, there are many useful alternatives to common suture techniques giving excellent aesthetic results.

References
1. Haneke E. Variationen der Flaschenzugnaht. In: Mahrle G, Schulze H-J, Krieg T: Fortschritte der operativen und
onkologischen Dermatologie 8: Wundheilung - Wundverschluß. Springer, Heidelberg, 1994: 158-164
2. Haneke E. Developments and techniques in general cutaneous surgery. In Dahl MV, Lynch PJ (eds) Current Opinion
in DERMATOLOGY, vol 2, sect. Surgery (WHITAKER DC, ed), Current Science, Philadelphia, 1995: 129-136
3. Mainusch OM, Titzmann T, Haneke E. Intrakutane Nahttechniken. Z ästhet op Dermatol 2001;2/2:6-10
4. Haneke E. Aesthetic suture techniques. In André P, Haneke E, Marini L, Rowland Payne C. Cosmetic Dermatology
and Surgery. Taylor & Francis CRC Press, London 2017:207-218

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 BASICS OF FLAPS AND GRAFTS IN DERMATOLOGICAL SURGERY
Amor Khachemoune
State University of New York, NY & University of Maryland, ABD

A flap is a form of adjacent tissue rearrangement where a unit of the tissue is transferred from one site (donor site)
to another (recipient site) while maintaining its own blood supply. They have different shapes and forms, and are
categorized according to their location, blood supply and the primary tissue movement… How does a flap differ from
a graft?
A graft (autogenous) is a skin transplanted from one location to another on the same individual, they are usually classified
either as full-thickness, split-thickness or composite grafts.
In this presentation, and for the purpose of aiding communication with peers, I will review a simplified “vocabulary
for tissue movements” for the common flaps, and survey the principles and stages of some grafts used in dermatologic
surgery.

References
1. Johnson KS, Blattner CM, Lear W. Simplified approach to the design of rhombic flaps. J Am Acad Dermatol. 2019
Jul;81(1):e7-e8. doi: 10.1016/j.jaad.2018.08.027. Epub 2018 Aug 28. PMID: 30165165.
2. Konofaos P, Alvarez S, McKinnie JE, Wallace RD. Nasal Reconstruction: A Simplified Approach Based on 419
Operated Cases. Aesthetic Plast Surg. 2015 Feb;39(1):91-9. doi: 10.1007/s00266-014-0417-0. Epub 2014 Nov 21.
PMID: 25413009.
3. van Wingerden JJ, Lapid O, van der Horst CM. Bridging phenomenon - Simplifying complex ear reconstructions.
Head Neck. 2014 May;36(5):735-8. doi: 10.1002/hed.23458. Epub 2013 Nov 7. PMID: 23970464.

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 CRYOSURGERY AND ELECTROSURGERY: WIDEN YOUR HORIZON
Tuğrul Dereli
MD, Emeritus Professor of Dermatology of Ege University Medical Faculty, Private Practice, Turkey

Is medicine an art or a craft? In the historical process, medicine is evolving from being an art to being a craft. Guidelines
that must be followed closely are prepared for almost every disease. And physicians are forced to comply with these
guidelines. However, in guidelines, the financial condition of the patient, the mood he is in, the knowledge and skill of
the physician, and the facilities of that country or region are not mentioned. This makes it difficult for physicians to act
according to the situation.
Electrosurgery and cryosurgery are increasingly being pushed out of the guideline. However, it is obvious that very good
results will be obtained if used in the hands of an experienced physician.
Here are a few examples of patients successfully treated with electrotherapy and cryotherapy.

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 PREDATORY PUBLISHING AND CONGRESS IN DERMATOLOGY
Vildan Manav
İstanbul Training and Research Hospital, İstanbul, Turkey

With the increasing use of Internet and electronic facilities together with the globalization of all areas of life including
medicine and science, also medical journals are affected by an increasing ‘flood’ of clinical and scientific material to be
published (1). In particular, young researchers are placed under constant pressure to publish their work to increase their
rating and receive funding (2). So; The past few years have witnessed an emergence of predatory publishers. However,
as the majority of these journals do not conduct proper peer review processes or offer customer service, these journals
have been named ‘predatory journals’ by Jeffrey Beall – a librarian at the University of Colorado.
In 2010, the number of papers published in predatory journals reached 53,000, however, by 2014, 420.000 were
estimated to have been published. By the end of 2016, the number of predatory journals listed on the Beall’s list had
reached approximateyl 10,000, approaching in number the journals found on the Journal Citation Reports and Directory
of Open Access Journals (3).
In 2016, researchers Stefan Eriksson and Gert Helgesson identified 25 signs of predatory publishing (4);
o The publisher is not a member of any recognized professional organisation committed to best publishing
practices (like COPE or EASE)
o The journal is not indexed in well-established electronic databases (like MEDLINE or Web of Science)
o The publisher claims to be a “leading publisher” even though it just got started
o The journal and the publisher are unfamiliar to you and all your colleagues
o The papers of the journal are of poor research quality, and may not be academic at all (for instance allowing for
obvious pseudo-science)
o There are fundamental errors in the titles and abstracts, or frequent and repeated typographical or factual errors
throughout the published papers
o The journal website is not professional
o The journal website does not present an editorial board or gives insufficient detail on names and affiliations
o The journal website does not reveal the journal’s editorial office location or uses an incorrect address
o The publishing schedule is not clearly stated
o The journal title claims a national affiliation that does not match its location (such as “American Journal of ...”
while being located on another continent) or includes “International” in its title while having a single-country
editorial board
o The journal mimics another journal title or the website of said journal
o The journal provides an impact factor in spite of the fact that the journal is new (which means that the
impact cannot yet be calculated)
o The journal claims an unrealistically high impact based on spurious alternative impact factors (such as 7 for
a bioethics journal, which is far beyond the top notation)
o The journal website posts non-related or non-academic advertisements
o The publisher of the journal has released an overwhelmingly large suite of new journals at one occasion or
during a very short period of time
o The editor in chief of the journal is editor in chief also for other journals with widely different focus

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 o The journal includes articles (very far) outside its stated scope
o The journal sends you an unsolicited invitation to submit an article for publication, while making it blatantly
clear that the editor has absolutely no idea about your field of expertise
o Emails from the journal editor are written in poor language, include exaggerated flattering (everyone is a leading
profile in the field), and make contradictory claims (such as “You have to respond within 48 h” while later on
saying “You may submit your manuscript whenever you find convenient”)
o The journal charges a submission or handling fee, instead of a publication fee (which means that you have to
pay even if the paper is not accepted for publication)
o The types of submission/publication fees and what they amount to are not clearly stated on the journal’s website
o The journal gives unrealistic promises regarding the speed of the peer review process (hinting that the journal›s
peer review process is minimal or non-existent)—or boasts an equally unrealistic track-record
o The journal does not describe copyright agreements clearly or demands the copyright of the paper while claiming
to be an open access journal
o The journal displays no strategies for how to handle misconduct, conflicts of interest, or secure the archiving of
articles when no longer in operation
What about predatory journals in Dermatology?
1058 publishers as of July 2016, 76 journals were identified in dermatology, cutaneous surgery and venereology. Due
to the poor quality of the majority of the publishing websites, several were unsearchable, no longer existed, or were
not in the English language. For these reasons, this is not a complete and comprehensive list of predatory journals in
dermatology and it is probable that there are more (5) (Table 1. List of predatory journals in Dermatology).
What about predatory conferences in Dermatology?
The big challenge is how to identify a predatory conference. A few points are worth considering: the organizer holds
low-quality academic meetings with the primary aim of making money and not supporting scholarships; there is no
effective peer review, allowing anyone to purchase a speaking slot; and the organizer employs deceit, the most common
forms being false claims of peer review, hiding the true location of the company headquarters, and concealing the for-
profit nature of the company (6).

References
1. Ring J. Predatory journals abuse the flood of publishable material. J Eur Acad Dermatol Venereol.
2018;32(4):511-2.
2. Richtig G, Berger M, Lange-Asschenfeldt B, Aberer W, Richtig E. Problems and challenges of predatory
journals. Journal of the European Academy of Dermatology and Venereology. 2018;32(9):1441-9.
3. Grzybowski A, Patryn R, Sak J. Predatory journals and dishonesty in science. Clinics in Dermatology.
2017;35(6):607-10.
4. Eriksson S, Helgesson G. The false academy: predatory publishing in science and bioethics. Med Health
Care Philos. 2017;20(2):163-70.
5. Maddy AJ, Tosti A. Predatory journals in dermatology. The British journal of dermatology. 2017;177(1):307-9.
6. Jakhar D, Kaur I. Predatory conferences: a flimflam academic deception. Clinical and Experimental
Dermatology. 2019;44(8):948-9.

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 MYTHS AND FACTS IN DERMATOLOGY
Müge Göre Karaali
Erzincan Binali Yıldırım University, Faculty of Medicine, Mengücek Gazi Training and Research Hospital,
Department of Dermatology, Erzincan, Turkey

In the clinical practice of dermatology, we hear similar questions from our patients and observe that they have similar
beliefs about some diseases. Are there any truth to these beliefs according to the literature?
(Q: Question, A: Answer)
Q1: Are acne related to nutrition?
A1: Nutrition was believed to cause or worsen acne. But it has become a dermatological doctrine that there is no direct
association between diet and acne. > 3 portions of milk consumption per week, excessive intake of dairy products and
hyperglycaemic food were found to be associated with acne. Dairy products are increasing plasma insulin-like growth
factor (IGF)-1 levels. Cow’s milk is available at different fat levels: skimmed milk was associated with higher plasma
IGF-1 levels. IGF-1 stimulates the synthesis of androgens in both ovarian and testicular tissues and inhibits hepatic
synthesis of sex hormone-binding globulin resulting in increased bioavailability of androgens. Skimmed milk also
contains less oestrogen, which is known to reduce acne. Chronic and acute hyperinsulinemia activates a hormonal
cascade that favours unregulated tissue growth by simultaneously elevating the free (IGF-1) level and reducing levels of
insulin-like growth factor binding protein 3 (IGFBP-3). A low-glycaemic-load diet improved acne severity and insulin
sensitivity. IGF-1 have been shown activating the PI3K and Akt pathway which plays a key role in the sebaceous
lipogenesis. Although there are studies showing that alcohol, tea, coffee and salty foods also increase acne, the level of
evidence is low or there are conflicting results.
Patients should be questioned during their first visit about their daily food habits, lifestyle or eating disorders. Should
nutrition be an issue, then patients may be advised to change their food habits or, if necessary, seek the help of a
nutritionist in addition to a pharmacological treatment of their acne, according to the severity of the condition and
current treatment guidelines.
Q2: Is it necessary to pay attention to food for urticaria?
A2: In acute urticaria, a relationship with food can be detected in children. Frequently, a relationship is found with milk,
egg, soy, tree nuts, soy and wheat. Although the nutritional relationship is lower in adults, a relationship can be detected
with fish, shellfish, tree nuts and peanuts. Food is a very rare etiology in chronic urticaria. In one study, a response
to pseudoallergenic diet was observed in 28% of chronic urticaria patients. Pseudo-allergen diet is not recommended
routinely, but can be recommended if the person has a very strong relationship with food.
Q3: Patients with chronic pruritus, urticaria want to have an allergy test?
A3: Prick test and patch test are allergy tests in dermatology and their indications are limited. Atopic dermatitis, total
IgE height, acute urticaria, contact urticaria are indications for prick testing. Atopic dermatitis, mainly allergic contact
dermatitis, and some drug eruptions may be indications for patch testing. Although prick test positivity can be detected
with food in patients with atopy in patients with chronic urticaria, the relationship between food and urticaria induction
cannot be established frequently.
Q4: Does laser hair removal cause skin cancer?
A4: Laser is a technology that uses non-ionizing radiation as a concentrated light source, and the UV wavelengths used
are different from sunlight. Although there are no long-term risk studies yet, changes have been observed in melanocytic
nevi; however, malignant transformation has not yet been reported.

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Q5: If a razor is used in epilation, will darker and black hairs grow?
A5: In epilation, it removes unwanted hair at the level of the skin surface, the trapezoid edge of the cut hair is felt harder
on the skin surface. Hair base is thicker than distal. As the bristles grow, their colors lighten with sunlight, chemical
exposure, and may appear darker when first starting to grow.
Q6: Does performing biopsy from skin cancer increase the risk of metastasis?
A6: In lesions with suspicious melanoma, an excisional biopsy that extends to subdermal adipose tissue with 1-2
mm margin should be performed, if possible; However, punch biopsy may be recommended in large lesions and in
cases where the diagnosis is doubtful. Tumor seeding phenomenon: shown in breast, gastrointestinal, thyroid, hepatic,
urological cancers. However, it has not been detected in skin malignancies.
Q7: Isn’t Lidocaine + epinephrine used in the anesthesia of the end regions?
A7: There are cases reported in the literature about hypoxia and necrosis in the distal regions due to the vasoconstrictor
effect of epinephrine; however, there are no reported cases of necrosis in standard dosage and technique. Although
careful use is recommended in patients with vascular insufficiency, elderly, cardiac disease and using b-blockers,
standard lidechoin + epinephrine is safe in infiltrative and block anesthesia, provides better pain control, less pain and
tourniquet use and less total anesthesia need.
Q8: Does systemic isotretionine cause infertility?
A8: In terms of female patients, although there are studies showing that the results have a significant negative effect on
the contradictory ovarian reserve, there are also studies that do not see a significant effect. However, it has been shown
that female hormone levels may be low. In terms of male patients, although there was no significant change in the
hormonal profile, positive changes were found in the spermiogram after treatment.
Q9: Should we wait 6 months for systemic isotretinoin ablative procedures?
A9: It has been reported that systemic isotretinoin suppresses collagenase and triggers keloid formation with increased
angiogenesis. There is not enough scientific data to support that systemic retinoids impair wound healing or cause
atypical scar formation. A safe time margin is set due to medicolegal problems.
Q10: Is there no cure for psoriasis?
A10: With the understanding of the etiopathogenesis of psoriasis at the molecular level, it is now much easier to reach
PASI90 levels with the use of new biological agents. Patients now think that it is a treatable disease and they apply to
our clinics with this desire. However, a cure without treatment seems not possible yet.
Q11: Does regular sunscreen use cause vitamin D deficiency?
A11: 90% of the daily vitamin D requirement is produced on the skin through UVB. In experimental studies, severe low
vitamin D was found with the proper and continuous use of sunscreen; however, it should be keep in mind that patients
do not use it”ideal and optimized” in daily practice. There is no scientifically proven safe dose and duration of UVB to
synthesize vitamin D without increasing the risk of skin cancer. It makes sense to avoid the sun and to supplement your
vitamin D orally. It is important to recommend simultaneously routine vitamin D supplements in patients with diseases
such as skin malignancy, lupus, rosasea, for which we recommend absolute and continuous sun protection.
Q12: Does verruca vulgaris heal with pray?
A12: Verruca vulgaris regress spontaneously, especially in children. Therefore, it is difficult to understand what is the
main reason for success in treatment. Destructive methods are frequently used in treatment. The immune system plays
an important role in the treatment of the disease. Suggestion, prayer, etc. methods can also affect the immune system
with the effect of psychotherapy. in a placebo-controlled study, there were no significant differences between the plasebo
group and the group which be prayed in terms of healing.

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Q13: Can pruritus be caused by liver pathologies?
A13: Pruritus originates from the liver only in the case of cholestasis. Cholestatic pruritus, which occurs due to the
impaired secretion of bile, is a common symptom in certain forms of liver disease. It is typically generalized and often
begins on palmoplantar regions that are uncommon sites for pruritus in other systemic diseases. Intrahepatic cholestasis
of pregnancy, sclerosing cholangitis, viral hepatitis, drug-induced cholestasis, as well as cases of obstructive jaundice
are cholestatic diseases. Patients with cholestatic pruritus have elevated plasma opioid levels, which may contribute to
itch.

References
1. Smith RN, Mann NJ, Braue A, Mäkeläinen H, Varigos GA. The effect of a high-protein, low glycemic-load diet
versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: a randomized,
investigator-masked, controlled trial. J Am Acad Dermatol. 2007;57(2):247.
2. Claudel JP, Auffret N, Leccia MT, Poli F, Dréno B. Acne and nutrition: hypotheses, myths and facts. J Eur Acad
Dermatol Venereol. 2018 Oct;32(10):1631-1637.
3. Magerl M, Pisarevskaja D, Scheufele R, Zuberbier T, Maurer M. Effects of a pseudoallergen-free diet on chronic
spontaneous urticaria: a prospective trial. Allergy. 2010;65(1):78
4. Lin SW, Kaye V, Goldfarb N, Rawal A, Warshaw E. Melanoma tumor seeding after punch biopsy. Dermatol Surg.
2012 Jul;38(7 Pt 1):1083-5.
5. Aksoy H, Cinar L, Acmaz G, Aksoy U, Aydin T, Vurdem UE, Oz L, Karadag OI, Kartal D. The effect of isotretinoin on
ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with acne. Gynecol
Obstet Invest. 2015;79(2):78-82.
6. Çinar L, Kartal D, Ergin C, Aksoy H, Karadag MA, Aydin T, Cinar E, Borlu M. The effect of systemic isotretinoin on
male fertility. Cutan Ocul Toxicol. 2016 Dec;35(4):296-9.
7. Mysore V, Mahadevappa OH, Barua S, Majid I, Viswanath V, Bhat RM, Talwar S, Thurakkal S, Aurangabadkar SJ,
Chatterjee M, Ganjoo A. Standard Guidelines of Care: Performing Procedures in Patients on or Recently Administered
with Isotretinoin. J Cutan Aesthet Surg. Oct-Dec 2017;10(4):186-194.
8. Faurschou A, Beyer DM, Schmedes A, Bogh MK, Philipsen PA, Wulf HC. The relation between sunscreen
layer thickness and vitamin D production after ultraviolet B exposure: a randomized clinical trial. Br J Dermatol.
2012;167(2):391.
9. Hoşrik EM, Cüceloğlu, AE, Erpolat S. Therapeutic Effects of Islamic Intercessory Prayer on Warts. J Relig Health
56, 2053–2060 (2017).
10. Wang H, Yosipovitch G. New insights into the pathophysiology and treatment of chronic itch in patients with end-
stage renal disease, chronic liver disease, and lymphoma. Int J Dermatol. 2010;49(1):1.

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 PIONEERS IN DERMATOLOGY
Mahmut Can Koska
Artvin State Hospital, Dermatology Clinic, Turkey

Because skin is visible with eyes and skin diseases are very common, the history of Dermatology lies beyond on deep
history. Even, it is very hard to consider initial cornerstones through ancient scripts.1 In one way or another, according to
reliable documents, the very first known written sources of Dermatology belongs to Egypt, The Ebers and Smith Papyri.
Is it surprising? Little bit because roots of European and modern medicine mostly depend on ancient Greek and Roman
sources. However, in the field of Dermatology, Egyptians initially described many conditions and treatments according
to these scripts such as inflammatory reactions, tumors, epidermal cysts and its treatment, ulcers, burns, several rashes,
hair disorders, topical treatments, wound repairing and dressing, cauterization and anti-sepsis. Also, cosmetics, anti-
aging applications and daily skin care was existed in Ebers Papirus. These scripts also demonstrated patient evaluation
depending on history and examination and prediction of prognosis. All of these and of course many more inventions and
definitions were upgraded by Greek physicians.2
Hinduism had also too many inflictions on Dermatology, and for some, they were the most successful in medicine in
antique era. They invented many treatments several of which are still being used such as treatment of pediculosis with
mixture of sulfur and mercury. Also, they were the first who described elephantiasis and acne.3
Like in many fields of medicine Greeks, and of course Hippocrates, had many contributions to Dermatology. Hippocrates,
the father of medicine, was the first who split the human health from religious and philosophic dogmas. He defined many
skin conditions which are under use even today. For example, herpes, ecthyma, erysipelas were just several of these.
Furthermore, although defined as different names; psoriasis, filiform warts, chilblains, carbuncles were first described by
him. Term of “pityriasis”, “sycosis”, “psora”, “erythema” and “exanthema” were also first used by him.3
In Roman era, maybe the most important physician, at least whom works remained until today, Celsus described many
Dermatologic conditions. He treated erysipelas and defined carbuncle and furunculus. He defined impetigo and maybe
firstly reported lichen planus. Another important Roman physician Paulus Aeginata who lived seven centuries after
Celsus reviewed and invented many Dermatologic treatments and firstly reported alopecia areata patients.3
One of the most important steps in Dermatology was getting in order of these scattered knowledge from antique and
medieval era, and of course criticization of these. Robert Willan (1757-1812), an English physician, reviewed and
ordered all of these knowledges in such a clear way. He designed taxonomy and reviewed different terms that had been
used for skin disease including impetigo, lupus, psoriasis, scleroderma, ichtiyosis, sycosis and pemphigus.3 He classified
diseases according to physical signs such as papules, scales, exanthems and bullae.1 Many regarded him as founder of
Dermatology as a specialty. He also described erythema infectiosum and he is the first physician to use word of “lupus”
to describe skin lesions of tuberculosis.3 He also reviewed sources from Arabic medicine and assembled with Greek
and Romans. Even not the first, his textbook was the most important one which impressed many physicians in that era.
Even Hebra, one of the most important pioneers of Dermatology, appreciated his publishments 50 years later.3 Thomas
Bateman was another British Dermatologist who clearly defined Molloscum contagiosum, Purpura Senilis, Alopecia
Areata and Herpes Iris with their exact names.3
At the same time with Willan, Jean-Louis-Marc Alibert of France (1766-1837) independently founded school of
Dermatology at the St. Louis hospital in Paris. He categorized skin disorders through macroscopic view initially and
subsequently in more detailed manner which he called “the tree of dermatoses”. Also, he was the first who defined
Keloids, Mycosis Fungoides patients and gave the disease its name. Laurent-Theodore Biett (1781-1840), who studied
with Willan, Alibert and Bateman, expanded works of Willan and Alibert. Although mostly regarded as the real establisher
of St. Louis school and most of his career was hold there, he preferred classification of Willan rather than Alibert. He
defined the term “Lupus Erythematoides”.3 Another French pioneer Pierre François Rayer (1793-1867) distinguished
true eczema, clearly described exfoliative cheilitis, firstly reported the case with adenoma sebaceum and studied about
glanders.3,4 Marie-Guillaume-Alphonse Devergie (1798-1879), founder of the most famous Dermatology museum in

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St. Louis hospital, described eczema marginatum and pityriasis rubra pilaris. Antoine Pierre Ernst Bazin (1807-1878),
best known for describing of erythema induratum, studied about ringworm, defined acne varioliformis, acne keloid and
hydroa vacciniforme.3
Sir Erasmus Wilson (1809-1884) was the one most important pioneer of Dermatology. According to several resources
daily bath became common habit after him. Also, he tried to establish Turkish bath in Britain. He described lichen planus,
exfoliative dermatitis, erythema nodosum, trichorexis nodosa under the name of trichodasis and punctate bleeding of
psoriasis lesions after scraping the surface which was going to be named Auspitz sign later.3
Joseph Jacob Plenck (1738-1807) described treatment of syphilis with mercury. He categorized 150 types of skin diseases
into 14 groups according to the physical properties of lesions, causes and involvement area.5 Ferdinand Ritter von Hebra
(1816-1880) founder of Vienna School of Dermatology and author of one of the most important atlas of skin disease.
He made classification based on pathological anatomy but, however it was criticized at that era. He defined erythema
multiforme, impetigo herpetiformis, rhinoscleroma, lichen scrofulosorum. He founded the cause of scabies and was
the first who invented skin resurfacing with chemical peel.3 Mortiz Kaposi (1807-1902) was a student of Hebra. He
continued Hebra’s teachings and defined eczema herpeticum, pigmented sarcoma, diabetic dermatitis and lymphoderma
pernisciosa.1,3
Tilbury Fox (1836-1879) wrote the best textbook of its time. He described kerion, lymphangioma and first case of
epidermolysis bullosa.3
Otto Schrön (1837-1917), such a highly talented a histologist and drawer in scientific manner, firstly discovered
desmosomes, tonofilament system and observed cell to cell connections. He also took very important part in studies
under his mentor, Carl Thiersch, to discover epithelial origin of cancer and demonstrate, although under different names,
squamous cell carcinoma and basal cell carcinoma.6
Paul Gerson Unna (1850-1929) had many contributions in Dermatology literature other than Unna boot and Thost-Unna
palmoplantar keratoderma. He reviewed the knowledge about anatomy and physiology of epidermis. He was the first
who correctly demonstrated structure and functions of epidermal layers in his book. He also defined plasma, foam and
balloon cells.6,7
Josef Jadassohn (1863-1936) was the one of the important pioneers of Dermatopathology. He re-classified skin diseases
according to etiology. He was the inventor patch test which is still being used today. He defined many diseases correctly
such as nevus sebaceous, pityriasis lichenoides chronica, granulosis rubra nasi, incontinentia pigmenti, blue nevi,
pachyonychia congenita. He also described borst-jadassohn phenomenon.8
Helen Ollendorff Curth (1899-1982) was the one of the rare women physicians in her era. She was the one of the
leading authors in genodermatoses. With Macklin she described ichtiyosis hystrix which is called ichtiyosis Curth-
Macklin today. She also described dermatofibrosis lenticularis disseminata with Buschke. Today patients with multiple
connective tissue nevi, osteopoikilosis and sclerotic bone disorder in addition to that lesions is called Buschke-Ollendorff
syndrome. She also very clearly demonstrated the association of acanthosis nigricans with malignancies.9
Stephen Rothman (1894-1963), Hungarian pioneer of investigative Dermatology. He influenced new and molecular
sights in Dermatology. He published the “Physiology and Biochemistry of the Skin” in 1954, the first textbook which
reviewed biochemistry and physiology of the skin. The book impressed and inspired many physicians in that times.
With Julius M. Coon, they discovered cholinergic innervations of vessels and eccrine sweat glands. They also identified
pilomotor response and neurophysiology of flushing. He firstly demonstrated molecular effects of UVR on melanogenesis,
suggested para-amino benzoic acid as sunscreen, observed tendency of melanin to bind metal ions, recognized trans-
epidermal water loss and association of its with altered cornification, observed cross reaction between substances that
cause allergic contact dermatitis, skin hardening treatment with UV radiation in solar urticaria. He also investigated
skin surface lipids with Konrad Bloch. The disappearance of tinea capitis that caused by Microsporodium Audouinii
after puberty by increasing levels of free fatty acids in scalp sebum was recognized and explained by him. His works
about skin surface lipids leaded to great insights in skin barrier, antimicrobial defense, regulation of innate immunity.
He also demonstrated that testosterone could induce sebaceous gland hyperplasia. He was also a great teacher. Many

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of students also became one the pioneers of Dermatology too. He was widely considered as the father of investigative
Dermatology.10
Of course, many more important Dermatologists and pioneers existed in history of Dermatology. Even several of them
are still active physicians, academicians and scientists.
In conclusion, one can foresee that history of Dermatology passed through three main paths. First the ancient era
including mostly Egyptians, then Greeks, Romans and Arabs and finally, mostly by efforts of Sir Willan, the modern
era.3 In all that path, too many pioneers have passed and of course, many new leading physicians, authors and scientists
will come. Today our knowledge totally depends on their analyzed, written and published masterful observations, efforts
in clarification of problems in nomenclature and treatments and of course, reviews and classifications that were created
through their visions.

References
1. Copeman PW. The creation of global dermatology. J R Soc Med. 1995;88(2):78-84.
2. Hartmann A. Back to the roots - dermatology in ancient Egyptian medicine. J Dtsch Dermatol Ges.
2016;14(4):389-396.
3. King JM. Historical review of early dermatology by J. M. King, MD, Nashville, Tenn. Originally published
May 1927. South Med J. 1983;76(4):426-436.
4. Beeson BB. Pierre François Rayer 1793-1867. Arch Derm Syphilol. 1930;22(5):893-897.
5. Jackson R. Historical outline of attempts to classify skin diseases. Can Med Assoc J. 1977;116(10):1165-
1168.
6. Weyers W. Otto Schron--an early pioneer in dermatopathology. Am J Dermatopathol. 2011;33(2):177-184.
7. Bhawan J. The evolution of dermatopathology -- the American experience. Am J Dermatopathol.
2006;28(1):67-71.
8. Falto-Aizpurua LA, Griffith RD, Nouri K. Josef Jadassohn: a dermatologic pioneer. JAMA Dermatol.
2015;151(1):41.
9. Burgdorf WH, Hoenig LJ. A female pioneer--doubly recognized. JAMA Dermatol. 2013;149(5):527.
10. Burgdorf WHC, Bickers DR. The scientific legacy of Stephen Rothman. J Invest Dermatol. 2015;135(4):954-
959.

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 FINANCIAL TOXICITY IN DERMATOLOGY
Gonca Saraç

The term “financial toxicity” describes problems a patient experiences related to the cost of medical care. This challenge,
which was first defined for cancer patients, is mainly a result of out-of-pocket costs and indirect costs for diagnosis and
treatment, as well as the intangible costs. The financial distress of medical care can significantly affect quality of life
and treatment compliance.
Exposure to financial toxicity for which there are quite limited studies regarding dermatological diseases, varies widely
depending on the country and health system, the type and severity of the disease. For instance, out-of-pocket expenses
for eczema include all healthcare costs, even moisturizers and topical steroids for uninsured patients from the US,
in Europe extra costs of everyday products such as clothing, washing etc. are included for patients with a healthcare
insurance. In skin cancers, as more expensive drugs and more intensive treatment processes are involved, the financial
burden becomes greater. Most dermatological diseases have a chronic course and long-term treatments, often comprise
of several procedures, produce lifelong and higher costs. New techniques such as laser therapy, which can now be
used for previously untreatable conditions, and expensive but highly effective ‘biologics’ have been used for many
dermatological diseases in recent years. Increase in drug prices, use of new techniques and new drugs expand the
amount of payment by patients for many diseases. On the other hand, while objective financial distress varies by country,
subjective financial distress may be equally high for all patients.
Skin diseases are extremely common and with studies investigating the actual size of financial toxicity in dermatology
in Turkey and worldwide, to which extent the prescribed treatments can be reached by the patients and the sustainability
of these treatments will come to light.

References
1 Rychlik R, Kilburg A. The Basics of Health Economics: An Example from Dermatology. Dermatology Psychosom /
Dermatologie und Psychosom 2000; 1:105–9.
2 Zink A, Arents B, Fink-Wagner A, et al. Out-of-pocket costs for individuals with atopic Eczema: A cross-sectional
study in nine European countries. Acta Derm Venereol 2019; 99:263–7.
3 Basra MKA, Shahrukh M. Burden of skin diseases. Expert Rev Pharmacoeconomics Outcomes Res 2009; 9:271–83.
4 De Souza JA, Yap BJ, Hlubocky FJ, et al. The development of a financial toxicity patient-reported outcome in cancer:
The COST measure. Cancer 2014; 120:3245–53.
5 Jungen D, Augustin M, Langenbruch A, et al. Cost-of-illness of psoriasis – results of a German cross-sectional study.
J Eur Acad Dermatology Venereol 2018; 32:174–80.

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 DERMOSCOPY IN NON-MELANOMA SKIN CANCERS: WHAT’S NEW?
Ercan Arca
Guven Hospital Department of Dermatology, Ankara, Turkey

Nonmelanoma skin cancer (NMSC) is the most common skin cancer affecting both sexes. It includes mostly basal cell
carcinoma (BCC), actinic keratosis (AK), keratoacanthoma (KA), Bowen’s disease (BD) and squamous cell carcinoma
(SCC). And also vascular malignancies such as Kaposi Sarcoma (KS) and angiosarcoma are included in NMSCs. In
most NMSC tumors, diagnosis is easy with morphologic appearance; however, it is sometimes difficult to differentiate
the pigmented-nonpigmented skin lesions. With naked eye, only half-of-pigmented lesions are correctly diagnosed;
dermoscopy increases the diagnostic sensitivity to 95%.
BCC is the most common of all cutaneous malignancy. It is locally invasive and often grows slowly. Up-to date,
dermoscopy has been shown to increase BCC diagnosis by enhancing the differentiation from other skin tumors and
inflammatory skin diseases. Classical dermoscopy algorithm for the diagnosis of BCC, especially for the pigmented
variant, includes the absence of pigmented network and the presence of at least one of the following criteria: multiple
blue/gray ovoid nests, spoke-wheel structures, arborizing vessels and ulceration. However, BCC may reveal a large
variety of dermoscopic features. These non-classical features include some additional criteria more frequently seen
in superficial BCC or Fibroepithelioma of Pinkus such as short-fine superficial telangiectasia, concentric structures,
multiple small erosions, multiple in focus blue/gray dots, shiny white-red structureless areas.
AK has been characterized as“precancerous” or “premalignant” because the atypical keratinocytes within these lesions
are confined to the epidermis. Dermoscopically, facial AKs commonly reveal a red pseudonetwork pattern and white
keratotic hair follicle openings, the “strawberry pattern”, white/yellow surface scales, linear or wavy vessels surrounding
the hair follicles, and yellowish keratotic plugs. The strawberry pattern consists of an erythema forming a marked pink
to-red “pseudonetwork” around the hair follicles. Some special AK subtypes may reveal different patterns. For example,
Bowenoid AK is typified by glomerular vessels, which are regularly distributed and not arranged in clusters, as seen in
classic BD. Hyperkeratotic AK frequently shows surface scale and erythema. Pigmented AK is often characterized by
lack of associated erythema and has a hyperpigmented or reticulated appearance.
BD is a malignant intraepithelial tumor that affects older adults, especially women. Typically, it presents as a slowly
enlarging, flat, pink, scaly patch or plaque on lower extremities, face, and intertriginous areas. Dermoscopy of BD shows
a peculiar pattern characterized by glomerular vessels and a scaly surface. In addition to these clues, pigmented BD may
exhibit irregular pigment globules in a patchy distribution, gray-brown homogeneous pigmentation, and pseudonetwork.
SCC presents with various clinical appearances. Clinical lesions of SCC in situ range from ill-defined, rough, pink
patches similar to AK, to sharply demarcated verrucous papules or plaques. The typical SCC is a skin-colored papule-
nodule-plaque localized on sun-damaged skin. It may be hyperkeratotic with central necrosis or bleeding. The biologic
behavior differs by location, size, depth, and grade of histologic differentiation. There are significant differences in
the dermoscopic patterns of AK, intraepidermal carcinoma, and invasive SCC and these differences may assist in their
clinical diagnosis and subsequent management. Progression of AK into intraepidermal carcinoma and invasive SCC
can be observed on dermatoscopic examination. Initially, AK shows a red pseudonetwork: ‘‘strawberry pattern.” The
first step of progressing toward intraepidermal carcinoma ischaracterized by progressive development of redstarburst
pattern and yellow-white opaque scales.Initially, scales are discrete; however, with further progression to intraepidermal
carcinoma, they become thicker and coalesce to be located in a predominantly central position. Also, increased
neovascularization, the development of clustered dotted/glomerular vessels, can be seen. Further steps toward invasive
SCC are characterized by progressive development of elongated vessels, keratinization, and ulceration.
Dermoscopic features of KS are homogenous with the color ranging from reddish to bluish, pinkish, whitish, or
violaceous. Rainbow-like pattern that characterized by the presence of multicolored areas, compared with the rainbow
spectrum, is the most striking dermoscopic feature of KS. It can be seen with polarized dermoscopy, and can be also seen
in other skin tumors. The other findings in KS are scaly surface, small brown globules, white colarette, rosette sign, and

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vascular structures such as coiled, dotted and curved vessels.
In this presentation, a summary of the dermoscopic features of NMSCs and also the value of dermoscopy for diagnosis
and management of NMSCs will be discussed.

References:
1- Arca E. Keratinositik tümörler. Dermoskopi Atlası’nda. Eds. Özdemir F, Arca E, Karaarslan I, Şahin MT. 1. Baskı.
Dünya Kitapevi, Ankara, 2017, s:169-205.
2- Wozniak-Rito A, Zalaudek I, Rudnicka L. Dermoscopy of basal cell carcinoma. Clin Exp Dermatol 2018;43:241-7.
3- Reiter O, Mimouni I, Gdalevich M, Marghoob AA, Levi A, Emmilia H, Leshem YA. The diagnostic accuracy of
dermoscopy for basal cell carcinoma: a systematic review and meta-analysis. J Am Acad Dermatol 2019;80:1380-8.
4- Zalaudek I, Argenziano G. Dermoscopy of actinik keratosis, intraepidermal carcinoma and squamous cell carcinoma.
Curr Probl Dermatol 2015;46:70-6.
5- Zalaudek I, Giacomel J, Schmid K, et al. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and
invasive squamous cell carcinoma: a progression model. J Am Acad Dermatol 2012:66:589-97.
6- Lallas A, Tschandl P, Kyrgidis A, et al. Dermoscopic clues to differentiate facial lentigo maligna from pigmented
actinic keratosis. Br J Dermatol 2016;174:1079-85.
7- Pyne J, Windrum G, Sapkota D, Wong JC. Keratoacanthoma versus invasive squamous cell carcinoma: a comparison
of dermatoscopic vascular features in 510 cases. Dermatol Pract Concept 2013;4:6:37-41.
8- Rosendahl C, Cameron A, Argenziano G, et al. Dermoscopy of squamous cell carcinoma and keratoacanthoma. Arch
Dermatol 2012;148:1386-92.
9- Lallas A, Pyne J, Kyrgidis A, et al. The clinical and dermoscopic features of invasive cutaneous squamous cell
carcinoma depend on the histopathological grade of differentiation. Br J Dermatol 2015;172:1308-15.
10- Ertürk Yılmaz T, Akay BN, Heper AO. Dermoscopic findings of Kaposi sarcoma and dermatopathological
correlations. Aust J Dermatol 2020;61:e46-e53.

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 BLACK, RED AND GREEN: SIASCOPY
Ahmet Metin
Ankara Yıldırım Beyazıt University, Medical Faculty, Departmant of Dermatology and Venereology, Turkey

SIAscopy (Spectrophotometric Intracutaneous Analysis Scope) is one of the Multispectral digital dermoscopic
examination methods that, used for analytical examination of skin lesions. It is a newly developed modern diagnostic
tool that is non-invasive just like dermoscopy and other multispectral procedures. In a multispectral examination, lights
of different colors and wavelengths are applied to the skin surface. Then, the parts of these lights emitted and reflected on
the skin are processed and recorded on a computer base by an analytical software [1,2]. Three different devices capable
of multispectral examination have been approved recently. Of these, Melafind, SolarScan provides computer-aided fully
automatic diagnostics. The images obtained with the SIAscope require the interpretation of the physicians according to
various algorithms in order to increase the diagnostic accuracy as well as the computer-aided analysis. (Figure 1).

Figure 1: Five different siascans of SIAscopy

In a Siascopic examination, light from 5 different spectra between

400 and 1000 nm is shined into the skin lesions. These are white,
blue, green, red and infrared glows. Siascan images are obtained by
analyzing the part of the light reflected or scattered from the epidermal
and dermal region spectroscopically. Hence, the Siascope is composed
of a combination of contact remittance spectrophotometer with a
dermatoscope and hyperspectral imaging [5] (Figure 2). As a result,
four different images are taken in addition to a dermoscopic view with
SIAscopic examinations. These images contain some valuable data on
structural chromophores from the skin surface (papillary dermis) to a
depth of 2-2.5 mm.
Figure 2. Contact SIAskop V

126
These data include the concentration of melanin, hemoglobin, dermal collagen, and hemoglobin of blood vessels
belonging to epidermal and dermal structures. Thus, qualitative and quantitative digital data on the distribution and
placement of these pigments are obtained. These data are processed with a digital colorimetric analysis technique and
transformed into images used in the diagnosis of pigmented skin lesions [2,3]. The five images obtained consist of a
color dermoscopic image, as well as total melanin, dermal melanin, blood and collagen images [4].
Dermatoscopes, which are widely used in the diagnosis of skin lesions, can be useful when used by physicians with
long-term training and experience in this field. Therefore, it can only be used by dermatologists. The SIAscope device
is also primarily designed for use in primary health care for patients with pigmented skin lesions. Naturally, it has
primarily been used in melanoma screening in primary health care to increase diagnostic accuracy, reduce unnecessary
patient referrals and invasive diagnostic procedures. A computerized scoring algorithm “PCSA”, which is integrated
with the scanner, has been developed to increase diagnostic accuracy. In addition, optional 7-point and 3-point scoring
software has been added to the structure to be used for the same purpose.
It is much easier to learn the characteristics determined for skin lesions in siascopy and to use the device in siascopic
examination. Long-term experience and various agorithms are not required. Two hours is enough for its training. The
color image taken with the SIAscope is evaluated just like the dermotoscopic image. Histological maps and suggestions
provided with the red, blue, green and infrared light spectrum are always more useful.
Some symptoms such as dermal melanin, erythematous appearance, prominence of blood vessels and the presence
of collagen holes are very characteristic in a siascopic examination to be used in the diagnosis of pigmented lesions,
especially melanoma.
In studies performed, its sensitivity in the diagnosis of melanoma has been reported to vary between 79-94% and
specificity ranging from 80.1-84% [6,7] (Table I).

Table I: Melanoma Research via Siascope.

Author Year Lesion Melanoma Sensitivity Spesivity Journal / meeting

Moncrieff 2001 348 52 80.1 82.7 Br J Dermatol 2002, 146(3):448-457
Tomatis 2004 1391 184 80.4 75.6 Physics Med Biol 2005, 50(8):1675-1687
Carrara 2006 1966 287 88.0 80.0 Physics Med Biol 2007, 52(9):2599-2613
Hunter 2006 679 40 94-100 69.0 Br J Dermatol 2007, 156(6):1350-1352
Govindan 2007 886 54 94.4 64.0 J Plast Recon Aest Surg 2007, 60(6):639-45
Haniffa 2007 881 31 87.0 91.0 Br J Dermatol 2007, 156(6):1350-1352
Glud 2009 83 12 100.0 59.0 Melanoma Res 2009, 19(3):176-179
Terstappen 2013 60 42 24.0 84.0 J Biomed Optics 2013, 18(6):061223
Total - 6294 702 85 81 -

Moreover, it has been found useful in the diagnosis of non-melanoma skin cancers [8] (Table II). However, there are
studies that find siascopy less sensitive and specific than dermoscopic examinations. However, all of these were carried
out in advanced research institutions where physicians who have mastered dermoscopy work and where histopathological
examination facilities can also be made.

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Table II: Non-melanoma cancer research via siascopy.

Author Year Patients Lesion Sensitivity Specivity Research Journal or Meeting

Department
Tehrani 2013 250 250 - - PRC Annals of Plastic Surgery 2013
Tehrani 2006 302 363 98.0 95.7 PRC Br J Dermatol 2006,
Tehrani 2007 - 323 97.5 86.7 PRC Ann Plast Surg 2007

Emiroğlu 2018 72 33 93.9 53.8 Dermatology AAD Annual Meeting, 2018

Hacioglu 2013 76 80 55- 93 88-53 Dermatology Clin Exp Dermatol 2013

On the other hand, siascopy is used in various skin diseases and cosmetic problems as well as pigmentation disorder
and malignancy, although it is rare. These; issues such as photoaging, psoriasis, keloid, wound healing, burns, rosacea,
planer warts [9,10]
Considering the present value and condition of the siascopy; “Although it provides a color image equivalent to
dermoscopy, it has remained in the shadow of dermoscopy” and it is possible to say that it has not yet found its rightful
place in dermatological practice. This is probably because the technique is new, the technology is different, the devices
are expensive, the optical principles are complex, and it is difficult for the dermatologist to understand.

References
1. Bhat Y, Zeerak S, Hassan I: The global scenario of melanoma. Pigment International 2017, 4(2).
2. Jalil B: Multispectral image processing applied to dermatology. Université de Bourgogne; 2008.
3. Terstappen K, Suurküla M, Hallberg H, Ericson MB, Wennberg A-M: Poor correlation between spectrophotometric
intracutaneous analysis and histopathology in melanoma and nonmelanoma lesions. Journal of Biomedical Optics
2013, 18(6):061223-061223-061223.
4. Haniffa MA, Lloyd JJ, Lawrence CM: The use of a spectrophotometric intracutaneous analysis device in the real‐
time diagnosis of melanoma in the setting of a melanoma screening clinic. British Journal of Dermatology 2007,
156(6):1350-1352-1352.
5. Matts PJ, Dykes PJ, Marks R: The distribution of melanin in skin determined in vivo. Br J Dermatol 2007,
156(4):620-628.
6. Walter FM, Morris HC, Humphrys E, Hall PN, Kinmonth AL, Prevost AT, Wilson ECF, Burrows N, Norris P,
Johnson M et al: Protocol for the MoleMate™ UK Trial: a randomised controlled trial of the MoleMate system in
the management of pigmented skin lesions in primary care [ISRCTN 79932379]. BMC Family Practice 2010, 11(1).
7. Moncrieff M, Cotton S, Claridge E, Hall P: Spectrophotometric intracutaneous analysis: a new technique for imaging
pigmented skin lesions. British Journal of Dermatology 2002, 146(3):448-457.
8. Tehrani H, Walls J, Morse R, Cotton S: The in-vivo image analysis of tumour vasculature in the diagnosis of non-
melanoma skin cancer. In: The American Academy of Dermatology 2006: 2006; 2006.
9. Cibelik A: Plantarverrülerse spektrofotometrik intrakutanöz analiz bulguları ve karakteristikleri. Research. Ankara:
Yıldırım Beyazıt Üniversitesi 2020.
10. Zübeyde Başar. Rozase ve Sistemik Lupus Eritematozusa Ait Fasiyal Telenjiektazilerin ayrımında SIAskopik
Yöntemle Deri KapillerYapılarının İncelenmesi. Research. Bursa: Uludağ Üniversitesi 2010.

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 DERMOSCOPY: WIDEN YOUR HORIZON!
M. Cüneyt Soyal

In recent years, Artificial intelligence (AI) has been widely used in various fields of medicine, as well as in Dermatology.
Most of the clinical studies on AI use in Dermatology are particularly focused on the diagnosis of skin cancers. Recent
reports have also pointed out that AI has surpassed dermatologists in skin cancer detection. This presentation aims to
present an overview of AI basics and results of AI applications in classification and diagnosis of skin cancers, especially
melanoma.

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 DERMOSCOPY IN INFECTIOUS SKIN DISEASES
Ersoy Acer
Eskişehir Osmangazi University Department of Dermatology Eskişehir, Turkey

Dermoscopy born to be an instrument for early diagnosis of skin cancer, however today, it can be routinely used to support
diagnosis in general dermatology such as cutaneous inflammatory and infectious diseases. In this paper, dermoscopic
features of cutaneous infectious diseases will be told.
The first description of dermoscopic findings among cutaneous infectious diseases has been scabies.1 Then, many
dermoscopic findings of various cutaneous infectious diseases have been published. Before dermoscopy, diagnosis of
scabies is made by direct observation of mite, feces and eggs after skin scraping. But the sensitivity of the the test is
low and depends on the personal experience. Delta-wing jet with contrail sign has been defined for scabies. It indicates
the irregular burrow excavated by the mite. The mite’s anterior part of body is visible at dermoscopy as a small black
arrowhead area at the end of the whitish wavy line. This finding is considered pathognomonic for scabies.1 Currently a
novel dermoscopic sign namely the noodle sign was described in crusted scabies. The sign represents an accumulation
of hundreds of burrows in the same dermoscopic field.2 Human papillomavirus infections are very common in human.
It has very different clinical variants and dermoscopic findings. The most important feature is dotted vessels and/or
hemorrhagic points. It can often found in different kinds of warts. Common warts are the most common type of warts.
It’s dermoscopy demonsrate grouped papillae with dotted or loop vessels and/or hemorrhagic points and lines often
surrounded by a whitish halo, it is likened to a ‘’frogspawn appearance’’.3,4 Dermoscopy of filiform warts demonstrate
the same features as cpmmon warts with more prevalent papillae. Small dotted vessels on a yellowish background
may be seen in dermoscopy of flat warts. Plantar warts show at dermoscopy as small dotted hemorrhagic structures
corresponding to thrombosed vessels, visible in the context of whitish or yellowish paillae which interrupt cutaneous
dermatoglyphics. Genital warts show at dermoscopy grouped dotted or glomerular vessels at center surrounded by a
whitish network. The finding is the so-called mosaic pattern. Dermoscopy of pigmented genital warts demontrate a
cerebriform or seborrheic keratosis-like appearance.3,4 Molloscum contagiosum is a very frequent infection in human. It
shows usually at dermoscopy as the presence of a central pore on a white-yellowish amorphous area, often surrounded by
thin crown vessels.4 Only central amorphous area may be observed without central pore and vessels may have different
patterns radial or dotted except crown. On the other hand, vessels sometimes may be not visible.5 Dermoscopy has an
important role of diagnosis of dermatophytosis especially tinea capitis. Tinea capitis is a frequent dermatophytosis of
the scalp of especially children. The exact diagnosis is made by potassium hydroxide examination and microbiological
culture but dermoscopy plays an important role in differential diagnosis with causes of hair loss such as alopecia areata
and tricchotillomania.3 Tinea capitis may show at dermoscopy comma hair, zig-zag hair, corkscrew hair, Morse code-like
or barcode hairs, black dots, dystrophic hairs and hair casts.6-8 The most common dermoscopic finding is comma hair. It
is a shortened, curved hair resulting from the fungal inasion of the shaft.6 Pediculosis capitis is a common infestation in
world. It’s diagnosis is usually easy. The detection of lice is diffucult in dermoscopic examination. But nits are easily
seen through dermatoscope as ovoid structures anchored to the hair shaft. Pthirus pubis is predominantly a sexually
transmitted disease among adults. Dermoscopy confirms diagnosis of pthirus pubis by direct detection of the Pthirus.
Pthirus adherent to pubic hairs and blood feding. Nits can be detected to.3,4 Cutaneous leishmaniasis is a protozoan
infection, affects people by the vectors sandflies. Dermoscopic examination often shows that generalized erythema
and yellowish White round-to-oval structures. The latter is named as yellow tears. Moreover hyperkeratosis, central
erosion, ulceration, white starburst-like pattern and various vascular structures may be observed.9,10 Dermoscopy has
been suggested in diagnosis of pseudomonas onychopaty, trichomycosis axillaris and common form of folliculitis too.3
Dermoscopy is not a definitive diagnostic method of most cutaneous infectious diseases such as potassium hydroxide
examination, culture and histology. However it is low cost, practical and easy diagnostic method. Consequently, it
should be commonly used in differential diagnosis of cutaneous infectious diseases by dermatologists.

130
References
1. Argenziano G, Fabbrocini G, Delfino M. Epiluminescence micros¬copy: a new approach to in vivo detection of
Sarcoptes scabiei. Arch Dermatol. 1997;133(6):751-753.
2. Chavez-Alvarez S, Villarreal-Martinez A, Argenziano G, Anc¬er-Arellano J, Ocampo-Candiani J. Noodle pattern: a
new der¬moscopic pattern for crusted scabies (Norwegian scabies). J Eur Acad Dermatol Venereol. 2018;32(2):e46-e47.
3. Piccolo V. Update on dermoscopy and infectious skin diseases. Dermatol Pract Concept 2020;10(1):e2020003.
4. Tschandl P, Argenziano G, Bakos R, et al. Dermoscopy and entomology (entomodermoscopy). J Dtsch Dermatol Ges
2009;7(7):589-596.
5. Ianhez M, Cestari Sda C, Enokihara MY, Seize MB. Dermoscopic patterns of molluscum contagiosum: a study of 211
lesions con¬firmed by histopathology. An Bras Dermatol. 2011;86(1):74-79.
6. Slowinska M, Rudnicka L, Schwartz RA, et al. Comma hairs: a dermatoscopic marker for tinea capitis: a rapid
diagnostic meth¬od. J Am Acad Dermatol. 2008;59(5 Suppl):S77-S79.
7. Lacarrubba F, Verzì AE, Micali G. Newly described features resulting from high-magnification dermoscopy of tinea
capitis. JAMA Dermatol. 2015;151(3):308-310.
8. Wang HH, Lin YT. Bar code-like hair: dermoscopic marker of tinea capitis and tinea of the eyebrow. J Am Acad
Dermatol. 2015;72(1 Suppl):S41-S42.
9. Llambrich A, Zaballos P, Terrasa F, Torne I, Puig S, Malve¬hy J. Dermoscopy of cutaneous leishmaniasis. Br J
Dermatol. 2009;160(4):756-761.
10. Serarslan G, Ekiz Ö, Özer C, Sarıkaya G. Dermoscopy in the diagnosis of cutaneous leishmaniasis. Dermatol Pract
Concept. 2019;9(2):111-118.

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 SYNDROMES ASSOCIATED WITH HAIR AND NAIL PROBLEMS
Aslı Bilgiç
Akdeniz University, Department Of Dermatology And Venereology, Antalya, Turkey

Hair loss can represent a broad differential diagnosis. Especially hair loss in children and hair shaft disorders can further
be a therapeutic challenge as it might be an isolated phenomenon or a sign of genetic multisystemic syndromes. Similar
to hair disorders, nail diseases and abnormalities are often with systemic diseases and syndromes.
Thus, physicians should carefully evaluate personal and family history, and examine the hair on the scalp and on all
body areas, also all nails and other ectodermal structures to establish the correct diagnosis. In this oral presentation the
main syndromes associated with hair and nail problems are summarized. I will further discuss the most common clinical
features of hair and nail abnormalities and known associated genetic abnormalities with these abnormalities.

Hair shaft disorders with increased fragility Hair shaft disorders without increased fragility
Acquired Acquired
Bubbled hair Acquired progressive uncombable hair
Acquired Trichorrhexis nodosa
Congenital Congenital
Trichorrhexis nodosa Pilli annulati
Monilethrix Pseudopili annulati
Trichorrhexis invaginata Woolly hair
Pili torti Uncombable hair syndrome (Pili annulati et canalikuli)
Trichoschisis Loose anagen hair syndrome
Pili bifurcati
Pili multigemini

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Hair shaft disorders and associated syndromes
Monilethrix Ectodermal dysplasia syndrome
Trichorrhexis nodosa Argininosuccinicaciduria
Citrullinemia
Trichoschisis Trichothiodystrophy
Trichorrhexis invaginata Netherton syndrome
Pili torti Bjornstad syndrome
Crandall syndrome
Menkes syndrome
Ectodermal dysplasia syndromes
Other syndromes;
Familial acne conglobata
Rapp-Hodgkin syndrome/ankyloblepharon-ectodermal dysplasia-clefting syndrome
Salti-Salem syndrome
Monilethrix
Pseudomonilethrix
Woolly hair
Mitochondrial disorders
Netherton syndrome
Bazex syndrome
Beare syndrome
Condradi-Hünermann syndrome
Longitudinal grooves
Trichorrhexis nodosa
Trichorrhexis invaginata
Citrullinemia
Laron syndrome
Woolly hair Hereditary dominant woolly hair
Familial recessive woolly hair
Woolly hair syndromes with cardiac abnormalities;
Naxos disease
Carvajal syndrome
Naxos-like disease
Woolly hair syndromes without cardiac abnormalities;
Woolly hair and skin fragility syndrome
Diffuse partial woolly hair
Woolly hair nevus
Curly hair Tricho-dento-osseous (TDO) syndrome
CHAND syndrome
Costello syndrome
Noonan syndrome
Lipoatrophic diabetes
Miscellaneous Marie Unna hypotrichosis
Uncombable hair syndrome
Loose anagen syndrome
Pili annulati
Mitochondrial disorders

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Nail disorders and associated syndromes
Hereditary Disorders with Darier–White disease
Secondary Nail Changes Lesh–Nyhan syndrome
Neurofibromatosis type 1 (Recklinghausen)
Pityriasis rubra pilaris
Tuberous sclerosis
Dystrophic nails Ectodermal dysplasia/skin fragility syndrome
Hidrotic ED, Clouston syndrome
Hypohidrotic ectodermal dysplasia (Christ–Siemens– Touraine syndrome)
Focal dermal hypoplasia/Goltz–Gorlin syndrome
Epidermolysis Bullosa
Incontinentia Pigmenti
Pachyonychia congenita
Naegeli–Franceschetti–Jadassohn syndrome
Dyskeratosis congenita
Naxos disease
CHANDS syndrome
Conradi–Hünermann–Happle
Schopf–Schulz–Passarge syndrome
KID syndrome
Meleda syndrome
Thost–Unna syndrome
PIBIDS/IBIDS/ Trichothiodystrophy
Olmsted syndrome
Papillon–Lefevre syndrome
Haim–Munk syndrome
Costello syndrome
Vohwinkel syndrome
Rapp–Hodgkin syndrome
Bart–Pumphrey syndrome
Ankyloblepharon– ectodermal–cleft (AEC) syndrome
Anonychia Zimmerman–Laband syndrome
DOOR syndrome
Glossopalatine ankylosis syndrome
Otoonychoperoneal syndrome
Klein syndrome/ popliteal pterygium syndrome
Nail–patella syndrome/ hereditary osteoonychodysplasia
Dyscephalic–mandibulooculofacial syndrome
References:
1. Ahmed A, Almohanna H, Griggs J, Tosti A. Genetic Hair Disorders: A Review. Dermatol Ther (Heidelb) https://doi.
org/10.1007/s13555-019-0313-2.
2. Cheng AS, Bayliss SJ. The genetics of hair shaft disorders. J Am Acad Dermatol 2008;59:1-22.
3. Atlas of Trichoscopy Dermoscopy in Hair and Scalp Disease. Ed: Rudnicka, Malgorzata Olszewska, Adriana Ra-
kowska. Springer-Verlag London 2012.
4. Baran Dawber’s Diseases of the Nails and their Management. Ed: Robert Baran, David de Berker, Mark Holzberg,
Bianca Maria Piraccini, Bertrand Richert, Luc Thomas. Wiley Blackwell. 5.Edition. 2019 John Wiley & Sons Ltd. UK.
5. Pediatric nail disorders by Robert Baran, Smail Hadj-Rabia, Robert Silverman. Taylor & Francis Group, LLC. 2017.
USA.
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 TOPIC OF THE LECTURE: TOPICAL “JUMP START” THERAPIES IN DERMATOLOGY
Pelin Esme
University of Health Sciences, Gulhane Training and Research Hospital, Department of Dermatology and
Venereology, Ankara, Turkey

Topical treatments provide an alternative modality, bypassing the systemic effects of oral drugs and minimizing drug-
drug interactions. Rapid onset and long duration of action are the most two important factors that increase patient
compliance with treatment. Undoubtedly, patients with dermatological diseases have a higher demand for treatments
with rapid onset of action, because the lesions are easily noticeable by both themselves and other people. For this
reason, many physicians prioritize many topical treatments that provide a ‘jump start’ effect in their clinical practice.
Topical steroids are the best-known example of ‘jump start’ therapies in dermatology with rapid effect in a wide range
of diseases. Topical steroids are used in the relief of many skin eczemas such as psoriasis, atopic dermatitis, burns,
bullous autoimmune diseases, or suppression of inflammation before antimycotic treatment in diaper dermatitis, etc.
They are the first agents that come to mind with rapid activity in many cases. Magistral prescriptions are another
example of topical ‘jumps start’ therapies, for examle eau-borique solution that is very effective in rapidly drying an
irrigated area. However, many other topical treatments can be considered as ‘jump start’ therapies, including topical
antibiotics, moisturizers and many other topicals can show ‘jump start’ efficacy with several physical manipulations
such as occlusion and laser assisted drug delivery.
This lecture primarily aims to discuss 3 main topics that demonstrate successful outcomes of topical ‘jump-start’
therapies: wound healing, superficial peelings, and in the last part, physical manipulations such as occlusion or laser
assisted drug delivery that accelerate the onset of action will be focused on.
A wound is a disruption of the normal structure and function of the epidermis and associated underlying tissues. The
healing process proceeds in four phases: hemostasis, inflammation, proliferation, and remodeling. Wound healing appears
to be the most popular dermatology topic in the literature where the role of topical ‘jump start’ treatments has been
objectively observed. Hyperbaric oxygen, topical supplemental oxygen (1), surgical and mechanic debridements (2),
vacuum-assisted closure devices, topical growth factors, enzymatic debridement dressings and wound care dressings,
platelet-rich plasma (3), platelet-rich fibrin (4) stand out as fast-acting topical therapies that accelerate wound healing.
Chemical peelings are commonly used cosmetic procedures but they also provide an additional therapeutic benefit
to medical management of acne, acne scars, melasma, hyperpigmentation disorders, and photorejuvenation (5,6). In
dermatology, peels are generally used either alone or in combination treatment with other treatments to provide a rapid
onset of action. They are classified based on their depth of skin penetration into superficial, medium, and deep peels.
Due to limited damage to the epidermis, superficial peelings are more preferred for ‘jump start’ therapeutic effect with
significant improvement especially on active acne, acne scars, melasma, and photorejuvenation.
When a topical agent does not have sufficient potency and rapid onset of action, some physical manipulation can
be performed to increase these two drug-related parameters. These methods include conventional methods such as
administration of the drug under occlusion or the more popular one, laser-assisted drug delivery. Laser-assisted drug
delivery (LADD) is an evolving new therapy with many possible applications as a highly targeted customizable method
for the distribution of drugs within the skin. LADD offers the advantages of accessibility and rapid onset of topical
treatment (7).
References:
1. Rodriguez PG, Felix FN, Woodley DT, Shim EK. The role of oxygen in wound healing: a review of the literature.
Dermatol Surg. 2008 Sep;34(9):1159-69.
2. Falanga V, Brem H, Ennis WJ, Wolcott R, Gould LJ, Ayello EA. Maintenance debridement in the treatment of
difficult-to-heal chronic wounds. Recommendations of an expert panel. Ostomy Wound Manage. 2008 Jun;Suppl:2-13;
quiz 14-5.

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3. Houlton JJ, Hom DB. Approaching delayed-healing wounds on the face and neck. Facial Plast Surg Clin North Am.
2013 Feb;21(1):81-93.
4. Kumar RV, Shubhashini N. Platelet rich fibrin: a new paradigm in periodontal regeneration. Cell Tissue Bank. 2013
Sep;14(3):453-63. doi: 10.1007/s10561-012-9349-6.
5. Lee KC, Wambier CG, Soon SL, Sterling JB, Landau M, Rullan P, Brody HJ; International Peeling Society. Basic
chemical peeling: Superficial and medium-depth peels. J Am Acad Dermatol. 2019 Aug;81(2):313-324.
6. Kontochristopoulos G, Platsidaki E. Chemical peels in active acne and acne scars. Clin Dermatol. 2017 Mar-
Apr;35(2):179-182.
7. Zaleski-Larsen LA, Fabi SG. Laser-Assisted Drug Delivery. Dermatol Surg. 2016 Aug;42(8):919-31.

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 ARE THEY IMMORTALITY FORMULAS: RESVERATROL AND RAPAMYCIN
Şule Güngör

Resveratrol is a polyphenol that has three hydroxyl groups which are involved in free radical scavenging and metal
chelation. Food sources of resveratrol include wine, grape, berries, and peanuts. It has antiglycation, antioxidant, anti-
inflammatory, neuroprotection , anticancer activity. It can prevent age-related diseases like diabetes, hypertension,
atherosclerosis, renal disease, metabolic syndrome, nörodejenerative diseases. So it can be considered as an antiaging
medicine.
Rapamycin (sirolimus) is a macrolide targeting the “mechanistic target of rapamycin” (mTOR) complex. It is used
FDA-approved as an immunsupressant following organ transplantation and to reduce proliferation of fibrous, vascular,
muscular tissues in tuberosclerosis. Topical rapamycin is used for the treatment of angiofibroms. Rapamycine acts its
benefical effects by inhibiting mTOR pathway. The mTOR pathway regulates the proliferation, growth, metabolism and
aging. The activation of mTOR pathway leads aging, the inhibiton of mTOR pathway prevents aging. As rapamycine
inhibits mTOR pathway it can be considered as an antiaging medicine. In 2009 it was shown that rapamycin increased
lifespan in mice by lowering the activity of the mTOR pathway. Since then, numerous studies showed that rapamycin
prevents cancer and age-related diseases. It was told that rapamycin will be most effective when administered at the
pre-disease stages of age-related diseases, in other words it is most effective before organ damage and loss of function.
The limitations of using rapamycin as an anti-aging drug is its side effects. It can cause stomatitis, hyperglycemia,
hyperlipidemi, anemia, trombopenia, leukopenia and infections. These side effects are seen in continuous taking of
rapamycin for medical purpose. For anti-aging purpose rapamycin can be used in intermittent administration but there is
not a standard intermittent dose schedule. It was shown that the side effects of rapamycin is due to mTORC2. So, in the
future, new “rapamycin-like” agents should be discovered, similar to rapamycin inhibits mTORC1 leading to anti-aging
effect, but not inhibiting mTORC2.

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 HYPERICIN- THE FACTS ABOUT A CONTRAVERSIAL AGENT
Gülşen Tükenmez Demirci
Acibadem University School of Medicine, İstanbul, Turkey

Hypericin is a naturally occurring substance found in the plant St. Johns Wort (Hypericum species) and can also be
synthesized from the anthraquinone derivative emodin. (1) Hypericin and its derivatives are accumulated in special
morphological structures, so called dark nodules, occurring in the aerial parts of hypericin-producing Hypericum
species. It is also found in some basidiomycetes (Dermocybe spp.) or endophytic fungi (Thielavia subthermophila).
(2) It historically has been used for medicinal application. Today, it is still of remarkable interest and is a main topic
of discussion. Antidepressive, antiviral, antiretroviral, antineoplastic, antitumor, photodynamic and photodiagnostic
activities of hypericin are currently under investigation.(3) On the other hand, several light-independent actions of
hypericin have also been described, eventhough its effects in the dark have not been studied as intensively as those of
photoactivated hypericin. On the contrary, hypericin can induce the expression of some ABC transporters, which are
often associated with the multidrug resistance of cancer cells and the hypericin-mediated attenuation of the cytotoxicity
of some chemotherapeutics was revealed.(4-5) Thus, the chronic usage of St. John’s wort extracts as an antidepressant
by oncological patients undergoing anticancer treatment should be avoided. (2)
Topical application of St. Johns Wort such as oils or tinctures is also very common in some skin diseases in folk medicine
such as minor burns and wounds, sunburn, abrasions, bruises, contusions, decubitus ulcers, keloid scars and many
others. The plant contains a broad spectrum of pharmacologically active substances, but mostly two chemical classes;
the phloroglucinols (hyperforins) and the naphthodianthrones (hypericins) were found to be effective for dermatological
applications. Hypericins show antimicrobial, anti-inflammatory, and anticancer activities, especially when irradiated
with visible light, and their photo-induced cytotoxicity can be used for photodynamic treatment of non-melanoma skin
cancer and also for diagnostic purposes.
Modern clinical research on the role of SJW in dermatology has been scarce compared to the numerous trials with oral
forms in depression and other psychiatric indications. The official 2009 HMPC monograph of the European Medicines
Agency regards none of these topical applications as scientifically well established but accepts the use of topical SJW
preparations for “symptomatic treatment of minor inflammations of the skin (such as sunburn) and as an aid in the
healing of minor wounds” in the context of traditional medicine (6).
Recently, sporadic trials have been conducted in wound healing, atopic dermatitis, psoriasis, and herpes simplex
infections, partly with purified single constituents and modern dermatological formulations. Potential adverse effects
of dermal application may be irritation/ sensitization and unwanted photosensitization, although clinical data available
suggests that the risk is relatively low. (7)

References
1- A Kubin , F Wierrani, U Burner, G Alth, W Grünberger Hypericin--the facts about a controversial agentCurr
Pharm Des2005;11(2):233-53.doi: 10.2174/1381612053382287.
2- Jendželovská Z, Jendželovský R, Kuchárová B, Fedoročko P.Front Plant Sci. 2016
Hypericin in the Light and in the Dark: Two Sides of the Same Coin.
May 6;7:560. doi: 10.3389/fpls.2016.00560. eCollection 2016.
3-Miskovsky P. Hypericin--a new antiviral and antitumor photosensitizer: mechanism of action and interaction with
biological macromolecules. Curr Drug Targets 2002; 3(1): 55-84.

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4-Goey, A. K., Meijerman, I., Rosing, H., Marchetti, S., Mergui-Roelvink, M., Keessen, M., et al. (2014). The effect
of St John’s wort on the pharmacokinetics of docetaxel. Clin. Pharmacokinet. 53, 103–110. doi: 10.1007/s40262-01
3-0102-5
5-Frye, R. F., Fitzgerald, S. M., Lagattuta, T. F., Hruska, M. W., and Egorin, M. J. (2004). Effect of St John’s wort on
imatinib mesylate pharmacokinetics. Clin. Pharmacol. Ther. 76, 323–329. doi: 10.1016/j.clpt.2004.06.007
6- EMEA (European Medicines Agency). HMPC Community herbal mono- graph on Hypericum perforatum L., herba
(Traditional use). EMEA/ HMPC/745582/2009. Wien Med Wochenschr 2010; 160: 557–563
7- Wölfle U, Seelinger G, Schempp CM.Planta Med. Topical application of St. John’s wort (Hypericum perforatum)2014
Feb;80(2-3):109-20.doi: 10.1055/s-0033-1351019. Epub 2013 Nov 8.PMID: 24214835

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 TOPIKAL BRIMONIDINE IN DERMATOLOGY
Burçe Can Kuru
Bakırköy Dr.Sadi Konuk Training and Research Hospital, Department of Dermatology, Istanbul, Turkey

Brimonidine is a alpha-2 selective adrenergic receptor agonist and it has strong vasoconstrictive effects on a2-ARs of
vessels and—to a lesser extent—on a1-ARs.It has anti-inflammatory properties and reduces vasodilation and edema.
It is a medication using to treat open-angle glaucoma for about 20 years. In 2013, FDA approved brimonidine 0.33%
gel for the treatment of persistent facial erythema of rosacea. It can also used for hemostasis in Mohs micrographic
surgery. Brimonidine can reduce the post-treatment erythema of daylight-activated photodynamic therapy. It can be
used in camouflaging redness of immature scars. Brimonidine prevents laser treatment therapy-related erythema and
hyperpigmentation. It can reduce Ipl-induced erythema. And also in the literature it is reported that brimonidine can be
used in treating telangiectasia of dermatomyositis.

References
1. Edward Chen et all. Randomized controlled pilot study of the preoperative use of brimonidine 0.33% topical jel for
hemostasis in Mohs micrographic surgery. J Am Acad Dermatol 2017;77:1114-8.
2. Abigail Cline et all. Medical management of facial redness in rosacea. Dermatol Clin 36(2018):151-159.
3. P.A.Gerber. Topical brimonidine tartrate 0.33% jel effectively reduces the post-treatment erythema of daylight-
activated photodynamic therapy. Br J Dermatol 2016;174:1415-1426.
4. Reinholz M et all. Topical 0.5% brimonidine gel to camouflage redness of immature scars. J Dermatol Case Rep
2015;2:87-88.
5. Sang Ju Lee et all. Topical brimonidine-assisted laser treatment for the prevention of therapy-related erythema and
hyperpigmentation. Journal of Cosmetic and LaserTherapy 2018.

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 VINEGAR IN DERMATOLOGY
İlteris Oğuz Topal
Department of Dermatology and Venereology, University of Health Sciences,
Prof. Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey

Introduction
Vinegar may be defined as a condiment made from various sugary and starchy materials by alcoholic and subsequent
acetic fermentation. The concentration of acetic acid ranges from 4% to 8%. Vinegar was first made from wine, as its
name indicates. It has been produced and sold for thousands of years, dating back to before the 6th century (1).
Use in pediculosis
Several studies have been conducted on the use of vinegar in the treatment of pediculosis. Abdolhosseini et al. evaluated
to efficiency of squill vinegar in 10 patients with head pediculosis. Squill vinegar locally applied to head for one
week after using permethrin shampoo twice. Examinations were done on 2nd, 7th and 14th days. Infestation was not
observed in 4 patients in 7th and 14th days examinations. In two cases, infestation was significantly reduced (75%) in
7th and 14th days. In all cases, the itchiness was gone.
This report stresses the effectiveness of Squill vinegar in the treatment of head Pediculosis resistant to treatment and
recommends its implementation in school health units (2).
In another study, compared to efficiency of 1% permethrin shampoo, 4% dimethicone lotion and (1:1) vinegar wet
combing for the treatment of head pediculosis. At the primary endpoint of day 7 post-treatment, the cure rate were 86%
in dimethicone group, 64.2% in permethrin group and %60.8 in vinegar group (3).
Because none of the pediculicides are 100% ovicidal, manual removal of nits with a fine-toothed nit comb after treatment
with any product is recommended. Some products are available that claim to loosen the “glue” that attaches nits to the
hair shaft, making the process easier. Vinegar or vinegar-based products (Clear Lice Egg Remover Gel) are intended to
be applied to the hair for 3 minutes before combing out the nits (3).
Use in pruritus
In interesting article about Scabies and Pruritus, the authors said Cosimo Bonomo discovered that prolonged antiseptic
baths can eliminate pruritus and vinegar compresses or baths may have also have been used to treat “the itch” (4).
Nakhaee et al. compared the effects Avena sativa, diluted vinegar and hydroxyzine on the reduction of uremic pruritus.
In this crossover randomized clinical trial, 23 hemodialysis patients with uremic pruritus were randomly divided into
3 groups. The first group was treated with Avena sativa lotion, twice a day, for as long as 2 weeks; the second group
received diluted vinegar; and the third group took hydroxyzine tablets for the same time span. The data were collected
by a pruritus scale and a visual analogue scale, which were completed before and after the interventions. Vinegar
solution (30-mL synthetic white vinegar 5% in 500 ml of water) was used on pruritic areas with a vinegar sponge by the
patient twice daily for 2 weeks. Vinegar significantly decreased all of the scores. According to this study, diluted vinegar
reduced all pruritus dimensions and vinegar was more effective than Avena sativa (5).
Use in fungal infection
The use of vinegar (5% acetic acid) to treat fungal infection has also been studied. A randomized controlled trial
was designed to efficacy of apple cider vinegar as an adjunct to 2% ketokonazole shampoo in the treatment of tinea
versicolor. Twenty patients with tinea versicolor were randomly assigned to receive 2% ketoconazole shampoo and apple
cider vinegar or 2% ketoconazole shampoo alone over a 5-day intervention. Efficacy was assessed in terms of clinical
signs and symptoms (pruritus/itchiness, scaling and erythema), and laboratory parameters (Wood’s lamp examination
and 10% KOH Test). A comparison of the measures of effectiveness between the two groups did not yield significant
differences. However, the percentage of treatment success favored the apple cider vinegar-ketoconazole group where

141
the clinical signs and symptoms and laboratory parameters were negative in all the subjects compared to the control
group. In conclusion the authors suggested Apple cider vinegar may be considered as a safe and potential adjunct to 2%
ketoconazole shampoo in the treatment of tinea versicolor (6).
Use in bacterial infection
An another indication is Gram- Negative Bacterial Toe Web Infection (GNBTWI) often accompanied by fungal infection.
The first description of acetic acid as treatment for purulent wounds was made by Taylor at 1916 (Taylor, 1916). Later on,
Aste et al. described systemic treatment of GNBTWI with oral antibiotics such as ciprofloxacin along topical amikacin
treatment and hot compresses of 2–5% acetic acid solution. They reported relatively high rate of success and only 7%
relapse rate, and therefore concluded that acetic acid is effective for treating GNBTWI (7).
Use in leg ulcer and non-healing wounds
As the development of bacterial resistance to antibiotics continues, the need for new antimicrobial agents has led to
reemergence of therapies that have been used for centuries.
Vinegar debridement therapy was used in many hospitals around the world for treating bone and soft-tissue infections
due to its antimicrobial properties, meanwhile, it has been used as an antibiotic for the dressing of wounds as well as
other uses, so that the vinegar has been suggested as a cure or ingredient in a cure for most human and many animal
ailments.
Chronic non-healing wounds have an elevated alkaline environment. Healing occurs more readily in an acid environment.
As a 0.25% to 0.5% solution, white distilled vinegar has bactericidal action against many Gram-positive and Gram-
negative organisms, and is effective in reducing bacterial burden. Vinegar has been used as an adjunctive short-term
treatment for superficial wound infection (8).
A study conducted from Iran to assess the efficacy of vinegar therapy on bacterial growth in the process of treating
diabetic foot ulcers. Total of 30 patients with non-healing ulcers were divided into 3 groups; 10 wounds were treated with
conventional therapy, 10 with vinegar therapy, and 10 with hypertonic saline. After 3 weeks of therapy, conventionally
treated wounds were still covered with necrotic tissue over 41% of their surface and still growth of different pathogens
, whereas after only 3 weeks of therapy vinegar-treated wounds were completely debrided (P = 0.001) and 70% of
cultures were negative. Vinegar therapy was also associated with hastened growth of granulation tissue and grater
wound healing rates.
The author said that vinegar therapy was more effective and efficient in debriding non healing foot and leg ulcers in
diabetic patients than was continued conventional care and associated with lower bacterial growth rates (8).
Use in atopic dermatitis
The acidic pH of the stratum corneum (SC) is important for epidermal permeability barrier homeostasis. Acidification of
the skin surface has been suggested as a therapeutic strategy for skin disorders such as atopic dermatitis (AD).
Lee et al. conducted an animal study to evaluate the usefulness of acidification of SC for inhibition of AD lesions.
Five groups of six oxazolone-treated (Ox)-AD mice were treated for three weeks with creams of different acidity:
vehicle cream alone (pH 5.5), neutralized vinegar cream (pH 7.4), pH 5.0 vinegar cream, pH 3.5 vinegar cream, and
pH 3.5 hydrogen chloride (HCl) cream. Ox-AD mice treated with acidic creams exhibited fewer AD-like lesions, had
significantly lower eczema scores, decreased basal by transepidermal water loss (TEWL), and increased SC hydration
compared to the groups given only vehicle and neutral cream. There was no significant difference between the acidic
vinegar and HCl groups. Between the groups treated with vehicle and pH 5.5 vinegar cream, there was no difference
in eczema score, basal TEWL and SC hydration. Application of topical acids, regardless of their source materials,
inhibits the development of AD lesions by maintenance of skin surface pH and skin barrier function in murine model.
Collectively, maintenance of acidic skin surface pH by topical application of acidic cream could be an effective
therapeutic modality for AD by improvement of skin barrier function (9).
There are also studies that find the opposite of these results. In another study, A total 22 patients with atopic dermatitis
soaked both their forearms for 14 days, with one arm dilute apple cider vinegar (0.5% acetic acid) and other in water 10

142
minutes daily. Transepidermal water loss and pH were measured pre- and post-treatment. In both groups, transepidermal
water loss increased and pH decreased at 0 minutes post-ACV treatment, but these effects were not sustained at 60
minutes. Therefore, although epidermal acidification would theoretically be beneficial in treating AD, results showed
that acidification by way of topical bathing in a 0.5% ACV solution as performed in this study was not useful in AD
treatment (10).
Use in diagnostic procedures
The use of 3% to 5% acetic acid (vinegar) can help in detecting anogenital warts and differentiating warts from other
lesions in genital area.
The lesion or lesions can be soaked in acetic acid, and, if a change occurs in color to a white appearance, the lesions
are most likely HPV lesions. This color change may be seen with the naked eye; magnification may be needed to detect
subtle changes (1).

References
1) Dhivya S, Padma VV, Santhini E. Wound dressings – a review. BioMedicine. 2015;5(4):24-8.
2) Abdolhosseini S, Mokaberinejad R, AlianNezhadi V, Bozorgi M, Nazem E. Evaluation of Treatment with Squill
Vinegar in 10 patients with Head Pediculosis. Asian J Clin Case Rep Trad Alt Med. 2017;1(1):57-64.
3) Tashakori Gh, Dayer MS, Mashayekhi –Ghoyonlo V. Comparative Efficacy of Three Control Protocols of Head Lice
(Pediculus Humanus Capitis) Infesting Schoolchildren in Mashhad City. Int J Pediatr. 2018;6(6):7803-14.
4) Puza CJ, Suresh V. Scabies and Pruritus-A Historical Review. JAMA Dermatol. 2018;154(5):536.
5) Nakhaee S, Nasiri A, Waghei Y, Morshedi J. Avena Sativa, Vinegar, and Hydroxyzine for Uremic Pruritus. Iranian
Journal of Kidney Diseases. 2015;9(4):316-22.
6) Almirañez JE, Almonte SH, Alvarez AD, Alvero EA, Alviz CA, Alzate ZL, et al. Efficacy of apple cider vinegar as an
adjunct to 2% ketoconazole shampoo in the treatment of tinea versicolor: A randomized controlled trial. A randomized
controlled trial UERM Health Sciences Journal. 2015;4(1):10-9.
7) Rozenblat M, Last O, Fisher S, Ziv M. Acetic acid treatment for toe web infection caused by Pseudomonas Aeruginosa
combined with fungal infection: A case series of ten patients. Dermatol Ther. 2019;32(3):e12883.
8) Al-Duboni GI. Effect of Vinegar Therapy on Bacterial Growth in Diabetic Foot Ulcers. Diyala Journal of Medicin.
2015;9(1):15-22.
9) Lee NR, Lee HJ, Yoon NY, Kim D, Jung M, Choi EH. Application of Topical Acids Improves Atopic Dermatitis
in Murine Model by Enhancement of Skin Barrier Functions Regardless of the Origin of Acids. Ann Dermatol.
2016;28(6):690-6.
10) Luu LA, Flowers RH, Kellams AL, Zeichner S, Preston DC, Zlotoff BJ, Wisniewski JA. Apple cider vinegar soaks
[0.5%] as a treatment for atopic dermatitis do not improve skin barrier integrity. Pediatr Dermatol. 2019;36(5):634-9.

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 5-FU IN DERMATOLOGY
Esra Ağaoğlu
Kars Harakani State Hospital Clinic of Dermatology, Kars, Turkey

Topical 5-Fluorouracil (5-FU) is an antimetabolite drug and has been widely used for the treatment of various dermato-
logical conditions. As a structural analogue of thymidine, it hinders thymidylate synthase and interferes with DNA and
RNA synthesis in neoplastic cells, resulting in decreased cell proliferation and apoptosis. Because 5-FU interferes with
DNA replication, rapidly proliferating cells are most sensitive to its cytotoxic effect (1, 2).
5-FU is currently available in topical formulations ranging from 0.5% to 5% concentrations in solutions or creams.
Generally, topical formulations of 5-FU are indicated for twice daily application, while a controlled-release 0.5% mi-
crosphere formulation is indicated for once daily application. During the treatment phase, inflammation and erosion of
the lesions increase and subclinical abnormal lesions become visible (1, 3).
Topical 5-FU is approved by the Food and Drug Administration for the treatment of actinic keratoses and superficial
basal cell carcinomas, however its efficacy is demonstrated in other dermatological diseases such as kerathoacantho-
ma, Bowen’s disease, malignant melanoma, psoriatic nail dystrophies, vitiligo, verruca vulgaris, Darier’s disease and
photoaging. Topical 5-FU offers an alternative to ablative and surgical treatments, which may cause scarring or require
reconstructive procedures. Of the mucocutaneous diseases, topical 5-FU is also effective in the treatment of actinic
cheilitis, condyloma acuminata, anogenital Bowen’s disease and extramammary Paget’s disease. The most common side
effects of topical 5-FU treatment include erythema, pain, pruritus, irritation, erosion, and eczematous reaction. Several
combination treatments, such as cryotherapy, salicylic acid, and photodynamic therapy, may increase the efficacy and
tolerability of 5-FU. Topical 5-FU should not be used in women who are or may become pregnant, since it is teratogenic
and classified as pregnancy category X (1-3,4).

References:
1. Grossberg AL, Gaspari AA. Topical antineoplastic agents in the treatment of mucocutaneous diseases. Curr Probl
Dermatol 2011;40:71-82.
2. Micali G, Lacarrubba F, Dinotta F, Massimino D, Nasca MR. Treating skin cancer with topical cream. Expert Opin
Pharmacother 2010;11:1515-1527.
3. Ceilley RI. Mechanisms of action of topical 5-fluorouracil: review and implications for the treatment of dermatolog-
ical disorders. J Dermatolog Treat 2012;23:83-89.
4. Prince GT, Cameron MC, Fathi R, Alkousakis T. Topical 5-fluorouracil in dermatologic disease. Int J Dermatol
2018;57:1259-1264.

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 TOPICAL TIMOLOL AND NIFEDIPINE IN DERMATOLOGY
Hasan Aksoy
Istanbul Medeniyet University, Göztepe Prof. Dr. Süleyman Yalçın City Hospital, Department of Dermatology,
Kadıköy, Istanbul, Turkey

Topical Timolol
Timolol maleate is a non-selective β-blocker originally used for the treatment of open-angle glaucoma. It is available
in formulations of 0.5% eyedrop and 0.5% ophthalmic gel. TM is also an off-label option for various dermatological
conditions, such as infantile hemangioma (IH), pyogenic granuloma, Kaposi’s sarcoma, or chronic wounds. Herein the
dermatological use of topical timolol is summarized.
Oral propranolol, a non-selective β-blocker, is the first line therapy for IH. Possible mechanisms of action of propranolol
-and also timolol- are: vasoconstriction, supression of genes encoding vascular endothelial growth factor and basic
fibroblast growth factor, and capillary endothelial cell apoptosis. Because of the side effects of propranolol such as
bronchospasm, hypotension, and hypoglycemia, a topical β-blocker, timolol, serves an alternative with a good safety
profile.
In a prospective study conducted on 124 patients with superficial infantile hemangiomas (IHs), “controlled growth”
in 35.6% and “promoted regression” in 56.4% of 101 patients treated by timolol drops (3 times daily, 4 months), were
demonstrated. In another study, 278 patients with superficial IH were divided into three groups: topical ultrapotent
corticosteroid, TM 0.5% solution, and TM 0.5% gel. TM groups were significantly superior to corticosteroid in terms of
size reduction of IHs2. A retrospective study of 731 patients with IH supports that the best responders of topical TM are
those who have IHs <1 mm thickness.
Timolol is also a good adjunct therapy to propranolol. Using topical timolol subsequent to oral propranolol shortens the
duration of propranolol treatment by 2.2 months (9.7 months vs 7.5 months; p=0.006), provides a 1.7 months younger
completion of propranolol treatment (14.0 months vs 12.3 months; p=0.007), and removes the need for propranolol
reinitiation (p=0.036)3. In a meta-analysis including 8 randomized controlled trials with 759 cases, topical timolol had a
similar response rate to oral proplanolol (risk ratio [RR]=0.97; p=0.63), and the combination of timolol and propranolol
was superior to oral propranolol (RR=1.14; p=0.03) or topical timolol (RR=1.36; p=0.01) monotherapies4.
Pyogenic granuloma (PG) is another dermatological condition that can be treated with TM. In a series of 10 patients
with PG who applied TM 0.5% ophthalmic solution 4 times a day, complete response in 4 patients (duration: 3-24 days)
and partial response in 3 patients were demonstrated5. Timolol is a therapeutic option for PG, especially where surgical
procedures are not favorable such as pediatric population, debilitated cases, or critical localizations (face, nail, gum).
Timolol can be used for Kaposi’s sarcoma. There are approximately ten cases in the literature, regarding the use of 0.1%-
0.5% topical timolol in the treatment of radiotherapy-refractory iatrogenic Kaposi’s sarcoma, classic Kaposi sarcoma,
or HIV associated Kaposi’s sarcoma. The remission was achieved in 5 to 24 weeks6. Timolol can act via inhibition of
angiogenesis. Besides, oral propranolol has been shown to suppress Kaposi’s sarcoma-associated herpesvirus infection
and this property may be another mechanism of action of timolol. Topical timolol may be an alternative when surgery,
radiotherapy, or chemotherapy are inappropriate.
Timolol induces keratinocyte migration via β2 blockade and thus supports re-epithelialization in chronic wounds, so
it can be used for the treatment of recalcitrant ulcers. In a retrospective study, of the 55 chronic wounds of varying
etiologies (median duration of wound before treatment: 118 days) treated with timolol, 34 wounds had healed, 15 had
improved, and two had worsened. The median treatment duration of healed group was 89.5 days7.
Topical timolol have also been used for the treatment of EGFR-inhibitor induced paronychia and pseudopyogenic
granuloma, hypergranulation, fissures and erosions of hand eczema, fissures of heels, post-acne erythema, junctional
epidermolysis bullosa, angiofibroma, pyoderma gangrenosum, red scrotum, and scars. Randomized controlled trials are
needed to confirm the efficacy of topical timolol in these conditions.

145
Although timolol is a safer alternative of oral propranolol, it may also cause adverse effects such as bradycardia, AV
block, or local irritation. In infants with IH treated with topical timolol and adults who applied TM 0.5 % gel to their
wounds, serum/plasma levels of timolol were similar to levels seen with adult ophtalmic timolol use. The scarcity of
adverse effects of topical TM in various clinical studies may be due to lack of proper monitoring8.
Topical Nifedipine
Nifedipine is a dihydropyridinic calcium channel antagonist that inhibits the contraction of smooth muscles. It is originally
used to provide internal anal sphincter relaxation in the treatment of anal fissure and acute thrombosed hemorrhoids. It
is available as 0.5% cream form.
In dermatology practice, topical nifedipine cream has been used for facial wrinkles. It is thought to act via inhibiting the
contraction of mimic muscle fibers, and may be an alternative to Botulinum toxin A injections. In a single-arm study
of 64 women with periocular wrinkles, topical 0.5% nifedipine cream (once daily, 90 days) was shown to reduce the
depth of wrinkles. In a randomized controlled trial, 20 women with moderate-moderately severe facial wrinkles were
treated with 0.5% nifedipine based topical formulation or moisturizer twice daily for 90 days. Nifedipine group was
demonstrated a significant decrease in wrinkle severity rating scale (3.85 to 1.84 vs. 3.78 to 3.36) and a significant
increase in skin hydration and lightening, compared to placebo9. Nifedipine has been shown to improve transepidermal
water loss and later this finding has been confirmed by an experimental study.
Topical nifedipine is also used for the treatment of pressure ulcers. Nitric oxide (NO) plays an important role in wound
healing, and is an NO donor. Vasodilatation, collagenation, and antioxidant effects are other potential mechanism of
action of nifedipine in the treatment of ulcers. In a randomized placebo controlled trial of 200 patients with stage I or
II pressure ulcers, patients who treated with topical nifedipine 3% ointment for 2 weeks (n=83) have demonstrated a
significantly higher mean decrease in the stage of ulcers and in the surface area of ulcers10.
The dermatological use of topical nifedipine appears to be safe, and it has no side effects other than local irritation seen
in some patients.
References
1. Yu L, Li S, Su B, et al. Treatment of superficial infantile hemangiomas with timolol: Evaluation of short-term efficacy
and safety in infants. Exp Ther Med. 2013;6(2):388-390.
2. Danarti R, Ariwibowo L, Radiono S, Budiyanto A. Topical Timolol Maleate 0.5% for Infantile Hemangioma: Its
Effectiveness Compared to Ultrapotent Topical Corticosteroids - A Single-Center Experience of 278 Cases. Dermatology.
2016;232(5):566-571.
3. Mannschreck DB, Huang AH, Lie E, Psoter K, Puttgen K. Topical timolol as adjunct therapy to shorten oral propranolol
therapy for infantile hemangiomas. Pediatr Dermatol. 2019;36(3):283-9.
5. Zheng L, Li Y. Effect of topical timolol on response rate and adverse events in infantile hemangioma: a meta-analysis.
Arch Dermatol Res. 2018;310(4):261-9.
6. Gupta D, Singh N, Thappa DM. Is timolol an effective treatment for pyogenic granuloma?. Int J Dermatol.
2016;55(5):592-5
7. Espadafor-López B, Cuenca-Barrales C, Salvador-Rodriguez L, Ruiz-Villaverde R. Iatrogenic Kaposi’s Sarcoma
Successfully Treated with Topical Timolol. Sarcoma de Kaposi iatrogénico tratado con éxito con timolol tópico. Actas
Dermosifiliogr. 2020;111(2):176-178.
8. Cahn BA, Kaur R, Hirt PA, et al. Use of Topical Timolol Maleate as Re-Epithelialization Agent for Treatment of
Recalcitrant Wounds of Varying Etiologies. J Drugs Dermatol. 2020;19(12):1252-1256.
9. Yoon DJ, Kaur R, Gallegos A, et al. Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and
Historical Review of Adverse Events. Am J Clin Dermatol. 2021;22(1):89-99.
10. Calabrò G, De Vita V, Patalano A, Mazzella C, Lo Conte V, Antropoli C. Confirmed efficacy of topical nifedipine in
the treatment of facial wrinkles. J Dermatolog Treat. 2014;25(4):319-325.
11. Zolfagharnezhad H, Khalili H, Mohammadi M, Niknam S, Vatanara A. Topical Nifedipine for the Treatment of
Pressure Ulcer: A Randomized, Placebo-Controlled Clinical Trial. Am J Ther. 2021;28(1):e41-e51.

146
 INGROWN NAIL: NON-SURGICAL APPROACH
Gülru Erdoğan

Ingrown nail is the erythema, edema and pain of the nail folds, usually lateral nail folds.
It is usually the result of an acute irritation on nail fold.
While ingrown nail starts with edema, penetration of nail into the nail fold is not a must. Edema of the toe by securing
the feet closed for long hours especially in hyperhydrotic patients lead to prominent edema together with moist and
sweat accumulation may cause irritation of nail fold and hence pain.
Sometimes erythema, edema and pain on nail fold can be misdiagnosed as bacterial paronychia. This may be the reason
why sometimes local or systemic antibiotics may not help for nail fold pain and edema. Therefore focus on edema,
remove edema so you remove pain.
Usually patients try to cut deep their nails just at this stage which makes the picture worse.

Objectives;
Cease the pain.
Relieve pain ASAP
There are various conservative methods for treating ingrown nails; eg bands, wiring, braces, cotton, dental floss,
lotions,etc. Choosing the correct method is as important as early diagnosis (1,2,3,4,5,6).
Methods usually followed can be classified in three main groups;
1.Put a mechanical barrier between nail and nail bed; most commonly used however nail has to be long enough:nail
braces, nail wiring, etc
2. Soften the nail; just one product. Nail is better long, not in hyperhidrotic feet as nail is already soft in hyperhidrotic feet.
3. Remove edema; Nail may be very short, asymmetrical, all shapesrespond as nail is not treated but rather the nail fold is.
Here we may propose an algorythm to choose the correct method by using three important variables; hyperhydrosis,
overcurvature and nail length.
1.Decide whether there is hyperhidrosis or lateral nail fold hypertrophy; this leads the nail to be soft, therefore wiring or
bracing can break the nail. Choose band, cotton or lotion.
2.Decide whether there is an overcurvature of the nail on the sides; then wiring, bracing or softening the nail can be
appropriate if there is no hyperhidrosis. Lotion may also help remove the edema and pain.
3.Decide whether nail is too short to put on a brace, wire or not; then you can use cotton or lotion or softening gel and
wait till nail side elongates. After then you put on wire or brace if there is overcurvature.
Granulation tissue formation;
Granulation tissue is not infectious. It is a kind of reactive vascular tissue as in the case of foreign body reaction.
Therefore, it bleeds easily and leaves a crust.
Once you see crust on nail fold, it is the sign for a granulation tissue. It is not infection.
Once you see the crust, most probably there is a subungual granulation tissue as well as on the nail fold. Therefore by
applying cream on nail fold, most probably you will not reach the subungual portion and hence be successfull.
This is why we apply an undernail cushion for such cases; to reach subungual granulation tissue. You may pour antibiotic
lotions through it or hyperosmolar, astringent lotons as we prefer.

147
Take home lessons;
1.Recognize ingrown nail ASAP. Erythema, edema on one nail side, not usually covering all sides.
2.Recognize crust ASAP. It is the sign for a granulation tissue, usually with a subungual extension.
3.Edema is the main reason of pain. Remove the edema, you cease the pain.
4.Pay attention to hyperhidrotic feet, cream formulations usually increase mositure and edema!!! It may be better to dry up.
PS: Please prefer conservative methods first, as conservative methods lead to recurrence in previously operated cases (7).
Early diagnosis and commencement of correct conservative treatment increases the success rate and decreases the need
for operations. Please remember conservative means are patient friendly, pain free and cost effective.

References
1. Senapati A. Conservative outpatient management of ingrown toenails. JRSoc Med 1986; 79: 339-340.
2. Manca D. Practice tips. Taping toes. Effective treatment for ingrown toenails. Can Fam Physician 1998; 44: 275.
3. Wallace WA, Milne DD, Andrew T. Gutter treatment for ingrowntoenails. Br Med J 1979; 2: 168-171.
4. Erdogan FG. A simple pain-free treatment for ingrown nails complicated with granulation tissue. Dermatol Surg
2006; 32: 1388-1390.
5. Erdogan FG, Güven M, Elhan A H, Gürler A. Tırnak batmasında tırnak teli tedavisinin etkinliği. Turkderm 2010; 44:
88-91.
6. Erdogan FG, Erdogan G. Long term results of nail brace application in patients ingrown nails. Dermatol Surg 2008;
24: 84-87.
7. Erdogan FG, Guven M, Erdogan BD, Gurler A. Previous nail surgery is a risk factor for recurrence of ingrown nails.
Dermatol Surg 2014; 40: 1152-1154.

148
 SURGICAL PRINCIPLES IN NAIL UNIT TUMORS
Eckart Haneke
Department of Dermatology, Inselspital, University of Berne, Switzerland
Dermatology Practice Dermaticum, Freiburg, Germany
Centro de Dermatología Epidermis, Instituto CUF, Matosinhos, Porto, Portugal
Department of Dermatology, University Hospital Ghent, Belgium

Surgery is the gold standard of nail tumor treatment although there are a few options of conservative therapies; however,
they are not safe with regard to treatment control.
Before considering nail surgery the diagnosis should be made or at least a suspect diagnosis. Then the nature of the
tumor – benign or malignant – has to be assessed. A thorough discussion of the type of surgery with the patient, its
alternatives, possible risks inclusive those of doing nothing follow. After informed consent the surgical technique has
to be explained so as to let the patient know what he/she will have to face in terms of anesthesia, postoperative pain,
healing time, risk of infection, disability to work, etc. Further, the patient must know how to get home after surgery, to
bring wide shoes for toenail surgery, organize transport and pain relief.
The most common nail tumors are viral warts – and they are virtually the only ones that are not treated surgically but
rather by aggressive keratolysis.
Ungual fibrokeratomas may have their origin in the depth of the nail pocket and emerge on the nail from under the
proximal nail fold. An incision is carried around their base, which is the released with pointed curved iris scissors from
the bone. Fibrokeratomas of the mid-matrix grow in the nail plate. The overlying portion of the plate is gently carved
away and the lesion the removed like the epiungual one. Fibrokeratomas of the nail bed cause a rim and their tip is
usually visible under the nail. The overlying nail is separated allowing access to the tumor, which is again cut down to
bone and removed.
Glomus tumors are characteristic for the nail and best known for their typical symptomatology although they are relatively
rare. Inspection, probing and magnetic resonance imaging allow their exact localization. If the tumor is located in the
lateral third, a lateral subungual approach is used whereas central localization requires a transungual technique. For
this, the overlying nail portion is lifted allowing the matrix and nailbed to be observed. The glomus tumor is seen as a
violaceous spot, mostly in the distal matrix and proximal nail bed. A slightly arched shallow transverse incision is made
in the matrix and the tumor usually pops out as a greyish glassy round lesion surrounded by a thin connective tissue
capsule. It is cautiously dissected out and the wound sutured with 6-0 fast resorbing stitches. A nailbed glomus tumor is
dissected after a longitudinal incision has been made.
Subungual exostosis is a characteristic lesion of children and young adults. It is visible as a stone-hard circumscribed
swelling raising the overlying nail plate margin. The exostosis characteristically has an epidermal margin like a collarette
whereas the overlying epidermis is smooth and shiny. An incision is made along the border down to phalanx bone, the
surrounding soft tissue is dissected, and the exostosis finally clipped of the bone. The skin is sutured to close the defect;
however, this is often not completely possible and wound margin adaptation with transungual stitches are recommended.
Longitudinal brown streaks in the nail present a major diagnostic and therapeutic challenge in adults as they may be
the sign of a subungual melanoma. The rule is that an acquired brown streak in the nail of an adult is rather malignant
than benign until otherwise proven. This requires a biopsy for histopathological examination. Several different biopsy
techniques are available, from a small punch to excisional tangential biopsy. A punch is technically easy but may not
contain enough tissue for a reliable diagnosis. Therefore, we have developed a tangential matrix and nailbed biopsy that
allows the whole melanocyte lesion to be remove with sufficient depth but virtually without the risk of postbiopsy nail
dystrophy. Proximal nail fold is incised on both sides, freed from the underlying nail and reclined. The proximal third
of the nail plate is incised transversally and opened so as to allow the melanocyte focus to be seen. A shallow incision is

149
carried around the pigmented lesion with an adequate safety margin, the width of which depends on the clinical suspect
diagnosis, and the lesion is then tangentially removed. The tissue slice should be 0.8 mm thick. This will leave enough
matrix dermis behind so that re-epithelialization will yield matrix epithelium again. The specimen is stretched out on
filter paper, on which a nail schema has been drawn and immersed into the fixative. This technique permits to take
virtually the entire matrix epithelium for diagnosis. The nail plate is then laid back and the proximal nail fold stitched in
place again. Healing is commonly uneventful without nail dystrophy.
Bowen disease and squamous cell carcinoma of the nail are probably the most frequent ungual malignancies. Up to 80%
of the Bowen cases are associated with high-risk human papillomaviruses, particularly HPV 16 and 18, but also many
other high-risk types. Bowen disease may be very extensive and require large excisions. Mohs micrographic surgery
is the treatment of choice. Defect closure depends on the size and particular localization of the defect. Local flaps are
technically demanding but very rewarding. Large defects are gest grafter after guided granulation of the wound.
Nail melanoma is the most serious nail disease. It is not uncommon with approximately 1.5 to 2% of all melanomas in
light-skinned Caucasians, >20% in Blacks and up to 40% in East Asians; however, race is no risk factor as the absolute
number of nail melanomas does not differ. The peak age is between 45 and 60 years, but ungual melanoma has also
been observed in children. The prognosis of nail melanomas is said to be poor as they are often diagnosed and treated
very late. The treatment of choice of early melanoma – in situ and under Breslow 1 mm – is wide local excision with
preservation of the digit. This treatment was described by us 43 years ago and is now adopted world-wide. Large studies
comparing conservative or functional surgery with amputation have demonstrated comparable cure rates and a much
better quality of life for functional surgery. The surgery comprised total extirpation of the whole nail unit with a 6 mm
safety margin around the anatomical borders of the nail apparatus. As so-called field cells may extend for up to 9 mm
around in situ melanoma, we extend the safety margin in case of Hutchinson sign to 10 mm. The defect is usually left
for granulation and may then be grafted with full-thickness skin.
Nail tumor surgery is critical as it has to ensure that the neoplasm has been completely removed but no uninvolved tissue
has been sacrificed. Atraumatic surgery has to be combined with aesthetic and tumor surgery principles.

References
1. Haneke E, Binder D: Subunguales Melanom mit streifiger Nagelpigmentierung. Hautarzt 1978;29: 389-391
2. Haneke E. Epidermoid carcinoma (Bowen’s disease) of the nail simulating acquired ungual fibrokeratoma. Skin Cancer
1991;6: 217-221
3. Haneke E. Morbus Bowen und Plattenepithelkarzinom der Nagelregion - klinisches Spektrum und Therapie. In:
Winter H. Bellmann K-P, eds: Fortschritte der operativen und onkologischen Dermatologie 9: Operative Dermatologie -
Möglichkeiten und Grenzen. Springer, Heidelberg, 1995:187-190
4. Perruchoud DL, Varonier C, Haneke E, Hunger RE, Beltraminelli H, Borradori L, Ehnis Pérez A. Bowen disease of
the nail unit: a retrospective study of 12 cases and their association with human papillomaviruses. J Eur Acad Dermatol
Venereol 2016;30:1503-1506
5. Haneke E. Developments and techniques in general cutaneous surgery. In Dahl MV, Lynch PJ (eds) Current Opinion in
DERMATOLOGY, vol 2, sect. Surgery (WHITAKER DC, ed), Current Science, Philadelphia, 1995: 129-136
6. Haneke E Czerniak podpaznokciowy – rozpoznanie, diagnostyka różnicowa i sposob y leczenia. Dermatol Estet
2008;10:218-223
Melanoma of the nail organ – diagnosis, differential diagnosis and treatment options. Dermatol Estet 2008;10:223-228
7. Duarte AF, Correia O, Barros AM, Azevedo R, Haneke E. Nail matrix melanoma in situ: Conservative surgical
management. Dermatology 2010:220:173-175
8. Haneke E. Ungual melanoma – controversies in diagnosis and treatment. Dermatol Ther 2012;25:510-524
9. Lieberherr S, Cazzaniga S, Haneke E, Hunger RE, Seyed Jafari SM. Melanoma of the nail apparatus: a systematic
review and meta-analysis of current challenges and prognosis. J Eur Acad Dermatol Venereol 2020;34:967-976
10. Haneke E, Jellinek N. Commentary Mohs surgery for nail unit melanoma in situ. Dermatol Surg 2021;47:264-265

150
 PSORIASIS AND ALOPECIA
Filiz Topaloğlu Demir
Istanbul Medipol University, Faculty of Medicine, Department of Dermatology and Venereology, Istanbul, Turkey

Abstract
Psoriasis is a chronic, multi-factorial, immune-mediated skin disease that presents a variety of clinical manifestations.
Scalp involvement in patients with psoriasis is one of the most common manifestations throughout the course of the
disease. Between 50% and 80% of patients have scalp involvement alone or with lesions in other parts of the body.1
Alopecia may accompany patients with scalp involvement more often than thought. It can be a cause of secondary
cicatricial alopecia.
Alopecia and other hair abnormalities that occur in patients with psoriasis were described for the first time in 1972.2
Three types of scalp alopecia have been defined by Shuster: (i) alopecia confined to lesional skin, (ii) generalized telogen
effluvium, and rarely (iii) scarring alopecia.2,3 It may be directly related to psoriasis itself, to the topical therapies or
systemic treatments such as methotrexate, retinoids, and biological agents used to treat it, or to associated autoimmune
conditions. It can affect both the scalp and other psoriatic plaques on the trunk and limbs. Histopathological findings
are similar to those seen in the interfollicular epithelium of psoriasis, which also includes perifollicular lymphocytic
inflammation, atrophy or loss of sebaceous glands, and a marked increase in telogen hairs. 4,5
In most cases, there is regrowth of hair, scarring alopecia is rarely seen. The exact incidence of this complication is
not known. In the largest case series reported, 12% of patients with psoriatic alopecia resulted in permanent scarring
alopecia.6 Psoriatic scarring alopecia was most frequently associated with long duration and higher severity of scalp
psoriasis. Scratching and secondary infections especially staphylococcal infections were thought to be the main drivers
of the cicatricial process. Proper control of psoriasis inflammation is important to avoid progression to scarring alopecia.
Familial cases have also been reported, suggesting that some genetic variants of psoriasis may trigger scarring alopecia. 4
More recent reports describe a wide variety of cutaneous reactions as an adverse effect or paradoxical reaction with
biological agents. One of the rare side effects of treatment with anti-TNF agents is the development of alopecia, often
associated with psoriasiform lesions on the scalp or elsewhere in patients without previous psoriasis. These lesions may
be clinically similar to primary psoriatic alopecia or alopecia areata.7 There are also a few cases of alopecia associated
with IL-17 use in the literature. They were defined as an unexpected ‘’paradoxical reaction’’, as IL-17 inhibitors could
also be used in the treatment of alopecia. It has been reported that the use of IL-17 inhibitors can lead to alopecia by
converting the Th17 / Th1 axis into a Th1 dominant immune state.8 The presence of psoriatic alopecia may affect the
choice of systemic treatment for psoriasis.
References
1. Sola-Ortigosa J, Sánchez-Regaña M, Umbert-Millet P. An update on scalp psoriasis. Actas Dermosifiliogr. 2009;100:536-43.
2. Shuster S. Psoriatic alopecia. Br J Dermatol 1972; 87: 73–7.
3. Shuster S. Psoriatic alopecia. Arch Dermatol 1990; 126: 397.
4. George SM, Taylor MR, Farrant PB. Psoriatic alopecia. Clin Exp Dermatol. 2015 Oct;40(7):717-21
5. Almeida MC, Romiti R, Doche I, Valente NYS, Donati A.An Bras Dermatol. 2013;88(6 Suppl 1):29-31.
6. Runne U, Kroneisen-Wiersma P. Psoriatic alopecia: acute and chronic hair loss in 47 patients with scalp psoriasis. Dermatology
1992; 185: 82–7.
7. Doyle LA, Sperling LC, Baksh S, Lackey J, Thomas B, Vleugels RA, Qureshi AA, Velazquez EF. Psoriatic alopecia/alopecia
areata-like reactions secondary to anti-tumor necrosis factor-α therapy: a novel cause of noncicatricial alopecia.Am J Dermatopathol.
2011 Apr;33(2):161-6.
8. Yajima M, Akeda T, Kondo M, Habe K, Yamanaka K. Alopecia Diffusa while Using Interleukin-17 Inhibitors against Psoriasis
Vulgaris.Case Rep Dermatol. 2019 Mar 28;11(1):82-85.

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 NAIL LACQUERS IN DERMATOLOGY
Mahmut Sami̇ Meti̇ n, MD, Kozan State Hospital, Dept Of Dermatolo
Anatomy of the Nail
*Nail matrix *Nail bed *Cuticle *Nail plate *Nail folds *Lunula

Unlike the skin,

- nails have a low lipid content (around 1%), mainly composed of cholesterol,
-and the water content is higher than in the stratum corneum at around 10–30% (as a protein solvate) in a normal state
Factors Affecting The Nail
Environmental factors (e.g., low relative humidity, winter, etc.) could reduce the water content, leading to nail brittleness.* Constant
use of nail cosmetic products (nail polish) based on a high amount of organic solvents (e.g., butyl acetate, ethyl acetate) could
extract nail water and lipids, leading to progressive dehydration. *Nutritional deficiencies (biotin deficiencies ) *Diseases;microbial
infections, psoriasis, lichen planus, alopecia areata, Darier’s disease, could affect the nail structure
Nail Psoriasis
Psoriasis is a chronic immune disease affecting the skin. Keratinocyte hyperproliferation and inflammation are observed in patients
and the involvement of the nail apparatus happens in around 50% of cases.Nail alterations in psoriasis usually involve-the nail
matrix (pitting, leukonychia or white spots, and crumbling) and the nail bed (onycholysis, hyperkeratosis, and discoloration).
Topical drug delivery systems
Transungual delivery is an effective approach in the treatment of onchomycosis where the drug penetration is influenced by compact
structure of nail. Nail lacquers based on novel formulation approaches are being focused upon to improve the delivery of active
ingredients in a more economical way.The transungual delivery seems to be an attractive approach in the treatment of nail infections
however, the delivery system faces difficulties to reach all the required sites of deep-seated infections due to their limited penetration
into the nail unit. The success of transungual delivery for the effective treatment of nail fungal infection directly depends on
the thickness and compact structure of nail.Transungual drug diffusion across the nail plate depends on a number of factors like
degree of hydration of nail, nature and pH of vehicle, molecular weight, surface charge of drug, hydrophilicity/lipophilicity and its
interaction with keratin matrix of the nail.Hence for an effective penetration into the nail plate, an apparent balance between the
physic-chemical properties of drug and biophysical properties of nail plate is desirable. A drug molecule with high permeability
coefficient, acidic pH, unionized/ undissociated molecule, small size (<300Da) and low keratin affinity permeates the nail barrier.
Nail lacquer and its Potential
Nail lacquer is a varnish applied to nails for the treatment of nail infections namely, onchomycosis and psoriasis. It is a novel
formulation solution to the problem of transungual drug delivery. Nail lacquers consist of solvents, film forming polymers which
improve the adhesion and plasticizers make the nail lacquer flexible. A nail lacquer application to the nail forms an adhesive
polymeric film on evaporation of volatile organic solvent. An active ingredient is incorporated in the nail lacquer for therapeutic
action and is applied by a brush forming a film on evaporation of volatile solvent.Direct application of the nail lacquer onto the nail
plate maintains optimal concentration of drug . The volatile solvent(s) of nail lacquer get evaporated and the drug concentration in
the lacquer film residue thereby increases. The lacquer film residue acts as a drug reservoir since the drug remains with the infected
nail for a longer duration of time. The potential advantages of nail lacquer can be gauged from the fact that they prevent reinfection
in initial step along with the property of occlusion offered by the lacquer film, which further enhances nail plate hydration. The
recurrence rates of infection is reduced as the drug by pass delivery from nail bed via matrix circulation. This is because the nail
bed turnover is high depleting drug concentrations.The polymeric adhesive film formed by the lacquer ensures sufficient adhesion
with the nail for continuous delivery of the drug and longer periods of time. The drug concentration in the film is much higher than
concentration as compared to the nail lacquer.The formation of film has an additional benefit on the nail plate as it reduces water
loss from the nail surface leading to hydration of the upper nail layers. The permeation enhancers present can cause sufficient nail

152
hydration by reducing pores obstructing drug diffusion.The water-insoluble films like methacrylic polymer and vinyl resin provide
sustained drug release and water-soluble films like hydroxypropyl chitosan provide stronger adhesion and facilitate greater drug
partitioning/release into the nail plate .The water-soluble films easily get washed on exposure to water. Hence, to combine the
advantages of adhesion and drug release properties of water-soluble films with the occlusiveness of water-insoluble films.
Components of Nail Lacquer
The components of nail lacquer play a significant role in the transungual delivery.
Nail lacquer usually contains;Volatile solvent to solubilise the drug (65 to 75%)*Film forming polymer (10 to 20%),*Plasticizer
to give flexibility and durability to the film.*Film suspending agents can be added to increase the viscosity of enamel, *Resins
to improve adhesion of the film to nail and surfactants to improve drug’s wettability and solubility (7 to 15%)*Humectants like
sorbitol, glycerol can be added alternatively which on evaporation of alcohol leave a hydrated polymer film, hence; increasing drug
solubility and thus permeation *Titanium oxide, mica, bismuth oxychloride, sedimentation retarders, chelating agents, antioxidants,
silicates, aroma substances, wetting agents, lanolin derivatives, light stabilizers and antibacterial substances can also be added.
Ciclopirox Hydroxypropyl Chitosan (HPCH) Nail Lacquer
Ciclopirox 8% hydroxypropyl chitosan (HPCH) [Marketed in different countries as the following registered (®) brands: Ciclopoli,
Fulcare, Kitonail, Myconail, Niogermos, Niogermox, Onytec, Ony-Tec, Polinail, Privex, Rejuvenail] is the first topical nail lacquer
developed using innovative drug formulation technology. It is indicated for the treatment of mild-to-moderate fungal infections
of the nails that are caused by dermatophytes and/or other ciclopirox-sensitive fungi, without nail matrix involvement. HPCH is
a patented drug formulation technology for the delivery of active principles into the nails based on a hydrosoluble semisynthetic
amino-polysaccharide biopolymer derivative of chitosan. The lacquer acts as a protective barrier against microbiological attack,
physical damage and/or aggressive chemicals. In clinical studies in patients with mild-to-moderate onychomycosis, ciclopirox 8%
HPCH was found to be more effective than the commercial water-insoluble ciclopirox 8% and amorolfine 5% lacquers, as indicated
by higher complete cure, response and mycological cure rates at 48 weeks after treatment initiation. Ciclopirox 8% HPCH has been
found to be generally well tolerated, with no treatment-related adverse events reported in patients using this nail lacquer.
Conclusions
Nail lacquers can be used for the topical treatment of nail fungus and psoriasis.There are only a few products on the market for now.
There are nearly ten products in development phase.We look forward to new products
References
1. Kataria P, Sharma G, Thakur K, Bansal V, Dogra S, Katare OP. Emergence of nail lacquers as potential transungual delivery
system in the management of onchomycosis. Expert Opin Drug Deliv. 2016 Jul;13(7):937-52.
2. Fernández-Campos F, Navarro F, Corrales A, Picas J, Pena E, González J, Otero-Espinar FJ. Transungual Delivery, Anti-
Inflammatory Activity, and In Vivo Assessment of a Cyclodextrin Polypseudorotaxanes Nail Lacquer. Pharmaceutics. 2020 Aug
4;12(8):730.
3. Cutrín-Gómez E, Conde-Penedo A, Anguiano-Igea S, Gómez-Amoza JL, Otero-Espinar FJ. Optimization of Drug Permeation from
8% Ciclopirox Cyclodextrin/Poloxamer-Soluble Polypseudorotaxane-Based Nail Lacquers. Pharmaceutics. 2020 Mar 5;12(3):231.
4. Piraccini BM, Iorizzo M, Lencastre A, Nenoff P, Rigopoulos D. Ciclopirox Hydroxypropyl Chitosan (HPCH) Nail Lacquer: A
Review of Its Use in Onychomycosis. Dermatol Ther (Heidelb). 2020 Oct;10(5):917-929.
5. Monti D, Saccomani L, Chetoni P, et al. Hydrosoluble medicated nail lacquers: in vitro drug permeation and corresponding
antimycotic activity. Br J Dermatol 2010;162:311-7.
6. Monti D, Saccomani L, Chetoni P, et al. In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based,
water-soluble nail lacquer. Drug Dev Ind Pharm 2005;31:11-7.
7. Shivakumar HN, Vaka SR, Madhav NV, et al. Bilayered nail lacquer of terbinafine hydrochloride for treatment of onychomycosis.
J Pharm Sci 2010;99:4267-76.
8. Nogueiras-Nieto L, Begoña Delgado-Charro M and Otero-Espinar FJ. Thermogelling hydrogels of cyclodextrin/poloxamer
polypseudorotaxanes as aqueous-based nail lacquers: application to the delivery of triamcinolone acetonide and ciclopirox olamine.
Eur J Pharm Biopharm 2013;83:370-7.

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 FOLLOWING THE LATEST GUIDELINE IN 2021: WHAT’S NEW?
Ragıp Ertaş
Kayseri City Education and Research Hospital, Kayseri, Turkey

The most used guidelines for managing Chronic Urticaria are; the American Academy of Allergy, Asthma, and
Immunology (AAAAI) and the European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and
Asthma European Network (GA2LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO).
There are some differences between their recommendations however the main recommendations are remaining similar.
The EAACI/GA2LEN/EDF/WAO updated their guideline for chronic urticaria in December 2020. There were many
topics discussed in the 5th Global Urticaria Forum (GUF) and new recommendations were considered. As a UCARE and
ACARE center from Kayseri, Turkey, we have also contributed by voting in the new guideline. However, the guideline
for chronic spontaneous urticaria (CSU) is still under development however, we are waiting for some important changes.
If we summarize the expected suggestions:
1-To including the angioedema control test (ACT) as a tool for the assessment of patients with CSU who have angioedema,
2-To include the total IgE levels and IgG anti-TPO to be assessed by specialists in the workup of CSU,
3- To reduce the guideline algorithm into three steps: antihistamines, omalizumab, cyclosporine, and updosing of
antihistamines and omalizumab will be included in the respective steps for treatment.
However, the core recommendations are expected to be similar. We are looking forward to the official guideline of the
EAACI/GA2LEN/EDF/WAO.

References
1- Bernstein JA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin
Immunol. 2014 May;133(5):1270-7. doi: 10.1016/j.jaci.2014.02.036. PMID: 24766875.
2- Zuberbier T, et al; Endorsed by the following societies: AAAAI, AAD, AAIITO, ACAAI, AEDV, APAAACI, ASBAI,
ASCIA, BAD, BSACI, CDA, CMICA, CSACI, DDG, DDS, DGAKI, DSA, DST, EAACI, EIAS, EDF, EMBRN, ESCD,
GA²LEN, IAACI, IADVL, JDA, NVvA, MSAI, ÖGDV, PSA, RAACI, SBD, SFD, SGAI, SGDV, SIAAIC, SIDeMaST,
SPDV, TSD, UNBB, UNEV and WAO. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification,
diagnosis and management of urticaria. Allergy. 2018 Jul;73(7):1393-1414. doi: 10.1111/all.13397. PMID: 29336054.
3- Ertas R, et al. The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted
by IgE levels and their change. Allergy. 2018 Mar;73(3):705-712. doi: 10.1111/all.13345. Epub 2017 Nov 27. PMID:
29083482.
4- Maurer M, et al. Definition, aims, and implementation of GA2 LEN/HAEi Angioedema Centers of Reference and
Excellence. Allergy. 2020 Aug;75(8):2115-2123. doi: 10.1111/all.14293. Epub 2020 Apr 27. PMID: 32248571.

154
 WHICH CAME FIRST? THE CHICKEN OR THE EGG?: THE ROSACEA OR THE DEMODEX
SITUATION
Seray Külcü Çakmak

Rosacea and demodicosis are common conditions in dermatology practice. While demodicosis is clearly the result of
infestation by the Demodex mite, the etiology of rosacea is unclear.
Rosacea is currently considered by most authors as a disease of the immune system, an inflammatory process including
innate and then adaptive immune responses. There is increasing evidence to suggest that rosacea is an inflammatory
continuum and that there is a key role for the Demodex mite in this inflammatory process.
Individuals with rosacea have been shown to have a higher density of Demodex mites on their facial skin compared to
individuals without rosacea in studies performed with skin surface biopsy specimens, polymerase chain reaction and
reflectance confocal microscopy.
In a metaanalysis of 23 case-control studies with 1513 rosacea patients it was reported that
rosacea patients were more likely to be infested by Demodex mites and had significantly higher Demodex density than
did healthy control patients. Patients with erythemathotelengiectatic rosacea (ETR) and papulopustular rosacea (PPR)
had significantly higher Demodex density (DD) than that healthy control patients, but DD tended to be lower in ETR
than in PPR. It was reported that Demodex mites promoted the development of acute-inflammatory morphological
elements, increased the duration of rosacea and the probability of recurrence.
Also the antiparasitic drug ivermectin, in the form of an external form, at a concentration of 1% has a high therapeutic
efficacy in patients with rosacea associated with Demodex mites.
In rosacea it was proposed that increased numbers of Demodex mites could lead to blockage of the hair follicles and
sebaceous glands resulting in cutaneous barrier disruption and tissue damage. The resulting increase in toll like receptor
expression and recognition of the mite’s chitin exoskeleton could trigger an inflammatory reaction. Disruption of the
epithelium and recognition of exoskeletal chitin may also result in a Th2 and/or Th17 response leading to tissue damage
as a result of neutrophil and macrophage activation. Studies also suggest that mites from rosacea patients harbour
pathogenic bacteria and other microorganisms which drive inflammatory skin responses.
The potential role of the Demodex mite in the development of rosacea and the multiple clinical and histopathological
similarities between demodicosis and rosacea also leads to diagnostic confusion between demodicosis and rosacea.
However most authors still think that proliferation of the Demodex mite in patients with rosacea is a secondary event, in
which the initial inflammation, activation of matrix metalloproteinases, increased size of blood and lymphatic vessels,
reduced levels of long-chain saturated fatty acids in the facial skin of patients with rosacea promotes the proliferation of
Demodex, which then exacerbates the disease.
Also human Demodex mites, as a causative for rosacea, can not fulfill the Koch’s postulates and the causative role of
Demodex mites is limited considering Bradford Hills criteria for casual association including the strength of association
(nearly 100 % prevalence rate of Demodex mites but up to 3% prevalence rate of rosacea in large-scale population
surveys).
It can be thought that Demodex mites may enhance the disease progression in rosacea, leading to an increase in
inflammation and eventually papulopustules.
So, although there are many studies indicating that the Demodex mites may play a significant role in rosacea by
orchestrating the host immune status, more work needs to be done to determine the exact association between Demodex
mites and rosacea.

155
References
1) Ahn CS, Huang WW. Rosacea Pathogenesis. Dermatol Clin. 2018;36(2):81-86.
2) Chen W, Plewig G. Are Demodex mites principal, conspirator, accomplice, witness or bystander in the cause of
rosacea? Am J Clin Dermatol. 2015;16(2):67-72.
3) Forton F, De Maertelaer V. Erythematotelangiectatic rosacea may be associated with a subclinical stage of demodicosis:
a case-control study. Br J Dermatol. 2019;181(4):818-825
4) Chang YS, Huang YC. Role of Demodex mite infestation in rosacea: A systematic review and meta-analysis. J Am
Acad Dermatol. 2017;77(3):441-447.e6.
5) Lacey N, Russell-Hallinan A, Zouboulis CC, Powell FC. Demodex mites modulate sebocyte immune reaction:
possible role in the pathogenesis of rosacea. Br J Dermatol. 2018;179(2):420-430.
6) Moran EM, Foley R, Powell FC. Demodex and rosacea revisited. Clin Dermatol. 2017;35(2):195-200.
7) Forton FMN, De Maertelaer V. Papulopustular rosacea and rosacea-like demodicosis: two phenotypes of the same
disease? J Eur Acad Dermatol Venereol. 2018;32(6):1011-1016.
8) Rosacea pathogenesis. In: Plewig G, Melnik B, Chen W. Plewig and Kligman´s Acne and Rosacea, Switzerland:
Springer; 2019:509-516.

156
 WHICH IS BETTER FOR HIDRADENITIS SUPPURATIVA:
SURGERY OR MEDICAL TREATMENT
Algün Polat Ekinci
İstanbul University, Faculty of Medicine, Department of Dermatology and Venereology, İstanbul, Turkey

Hidradenitis suppurativa (HS) is a chronic progressive disease that primarily affects the apocrine sweat glands. Its
exact prevalence is unclear, ranging from 0.1% to 4%. Young adults and women are most affected from HS. A genetic
background was reported nearly in 30-40% of HS patients.1,2
The disease initially appears around the pilosebaceous-apocrine unit with the obstruction of hair follicles by follicular
hyperkeratosis, subsequently resulting in rupture of hair follicles and inflammation of the perifollicular areas and
apocrine glands.2 At early stages, inflammation is mainly characterized by involvement of proinflammatory cytokines,
lymphohistiocytes, neutrophiles, macrophages, monocytes, and dendritic cells, leading to inflammatory nodules and
abscess formation. During the chronic stage, with additional contribution of histiocytes, B cells, plasma cells, and giant
cells, inflammation is complicated by formation of granulation tissue and granulomas, and subsequently extensive
fibrosis.
Tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 are considered to be the most relevant cytokines, particularly
in moderate-to-severe HS.3.4 In addition, alterations in the cutaneous microbiome are common, with accumulation of
biofilm-forming bacteria in lesional areas, such as Corynebacterium, Porphyromonas, and Peptoniphilus species.1
Depending on disease severity, HS may exhibit a wide variety of manifestations, including comedones (characteristically
paired), papules, pustules, nodules, cysts, abscesses, sinus tracts, fistulae, and bridged scars in the flexural areas, e.g. the
axillary, groin, anal, and breast regions.5,6
Among multiple scoring systems for disease severity, the Hurley Staging System is most common.1 Hurley stage I, II,
and III correspond to mild, moderate, and severe disease, respectively. Stage I is characterized by solitary or multiple
recurrent nodules, abscesses, and minimal scars without formation of sinus tracts. Stage II is characterized by a single
or a few sinus tracts and/or scar tissue as individual lesions. Stage III is characterized by multiple interconnected sinus
tracts, abscesses and/or scar tissues entirely involving a certain area.2,5,6 Progressive, chronic, painful, and debilitating
features of HS inevitably lead to disruptions in the social and occupational lives of patients, and impaired quality of life.
HS may be accompanied by comorbidities, including cardiovascular conditions (myocardial infarction, ischemic
stroke, and CV-associated death), hypertension, obesity, dyslipidemia, metabolic syndrome, smoking, thyroid disorders,
arthropathies, psoriasis, inflammatory bowel disease, psychiatric disorders, and polycystic ovarian syndrome.1
Treatment of HS is designed by consideration of disease severity, comorbidities, and impact of the disease on patients’
quality of life.
Despite the paucity of high-level evidence on optimal treatment of HS, multiple guidelines have been released guidelines
during the past several years aiming to guide the treating physicians, the most relevant of which are the European S1
guideline, HS ALLIANCE working group recommendations, North American Clinical Management guidelines, and
British Association of Dermatologists (BAD).2,6-8
Most guidelines recommend to assess disease severity based on the combined use of the Hurley classification system, a
visual analog scale (VAS), and the Dermatology Life Quality Index (DLQI). After screening associated comorbidities
and providing lifestyle recommendations, appropriate treatment is designed.2,6-8
Medical Therapies
In mild-to-moderate HS, topical treatment, e.g. clindamycin 1% solution, resorcinol 15% cream, chlorhexidine, zinc
pyrithione, or other antibacterial creams or solutions, may prove to be beneficial. Additionally, oral antibiotic treatment
with tetracyclines (doxycycline or lymecycline) over a 12-week course is recommended as the first-line systemic therapy.
As a second-line alternative oral treatment, clindamycin and rifampin combination over 10-12 weeks is recommended.
Another antibiotic option reported to be effective is the combination of moxifloxacin (400 mg daily), metronidazole
(500 mg thrice daily), and rifampin (300 mg twice daily).

157
In cases in which antibiotic therapies are not efficacious, acitretin (0.3–0.5 mg/kg per day) or dapsone (25-100 mg/day)
may be considered.
There are also ongoing experimental studies of hormonal agents to be used for all stages of HS, including estrogen-
containing oral contraceptives, spironolactone, cyproterone acetate, metformin, and finasteride.
In moderate-to-severe HS, initially conventional systemic therapies (antibiotic therapies, acitretin and dapsone) are
recommended. In refractory cases, biologic agents represent the second-line option, adalimumab followed by infliximab.
When using adalimumab, if a reduction (³25%) in the overall count of abscesses and inflammatory nodules is achieved
at 12 weeks, maintenance of adalimumab is recommended. Otherwise, switching to infliximab is considered. Other
treatment modalities such as carbon dioxide laser therapy, laser hair removal, radiation therapy are reported to be
beneficial in sporadic cases.2,6-8
Surgical Alternatives
Currently, data on surgical treatment of HS are sparse and sporadic.2 However, there are quite a large number of
moderate-to-severe cases in which no other alternative exists other than surgery. Various surgical methods have been
reported, including incision and drainage, deroofing, electrosurgery, narrow-margin excision, and wide radical excision
with closure by secondary intention, skin flap, or graft.6-8
In the treatment of painful abscesses and sinus tract formations no medical treatment alone is efficient; therefore, addition
of surgical interventions is mandatory.
Hyperplasia of the follicular epithelium and healing of inflammatory lesions is often complicated by formation of
fibrosis, scarring, hypertrophic tissue, bridging, and sinus tracts, which may facilitate local recurrences of HS and
worsen patients’ quality of life by restricting mobility. A meta-analysis investigating recurrence rates of HS after surgery
reported varying recurrence rates: wide excision, 13.0%; local excision, 22.0%; and deroofing, 27.0%.9 Another meta-
analysis reported the average estimated recurrences as 26.0% for partial excisions and 5.0% for wide excisions.10
In conclusion, HS may require both medical and surgical treatment options depending on the disease severity, the stage of
HS, and types of lesions. Therefore, these two treatment modalities are not alternative to, but complementary to each other.
References
1. Goldburg SR, Strober BE, Payette MJ. Hidradenitis suppurativa: epidemiology, clinical presentation, and pathogenesis. J Am
Acad Dermatol 2020;82:1045-58. doi: 10.1016/j.jaad.2019.08.090.
2. Ingram JR, Collier F, Brown D, et al. British Association of Dermatologists guidelines for the management of hidradenitis
suppurativa (acne inversa) 2018. Br J Dermatol 2019;180:1009-17. doi: 10.1111/bjd.17537.
3. Del Duca E, Morelli P, Bennardo L, et al. Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa.
Int J Mol Sci 2020;21:8436. doi:10.3390/ijms21228436
4. Hoffman LK, Ghias MH, Lowes MA. Pathophysiology of hidradenitis suppurativa. Semin Cutan Med Surg 2017;36:47-54. doi:
10.12788/j.sder.2017.017.
5. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from
the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary
and procedural management. J Am Acad Dermatol 2019;81:76-90. doi: 10.1016/j.jaad.2019.02.067.
6. Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J
Eur Acad Dermatol Venereol 2015;29:619-44. doi: 10.1111/jdv.12966.
7. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication
from the United States and Canadian Hidradenitis Suppurativa Foundations: Part II: Topical, intralesional, and systemic medical
management. J Am Acad Dermatol 2019;81:91-101. doi: 10.1016/j.jaad.2019.02.068.
8. Zouboulis CC, Bechara FG, Dickinson-Blok JL, et al. Hidradenitis suppurativa/acne inversa: a practical framework for treatment
optimization - systematic review and recommendations from the HS ALLIANCE working group. J Eur Acad Dermatol Venereol
2019;33:19-31. doi: 10.1111/jdv.15233.
9. Mehdizadeh A, Hazen PG, Bechara FG, et al. Recurrence of hidradenitis suppurativa after surgical management: a systematic
review and meta-analysis. J Am Acad Dermatol 2015;73:70–7. doi:10.1016/j.jaad.2015.07.044
10. Ovadja ZN, Jacobs W, Zugaj M, van der Horst CMAM, Lapid O. Recurrence Rates Following Excision of Hidradenitis
Suppurativa: A Systematic Review and Meta-analysis. Dermatol Surg. 2020;46:e1-e7. doi: 10.1097/DSS.0000000000002403.
PMID: 32235148.
158
 IS DIET REALLY IMPORTANT FOR ACNE?
Sezgi Sarıkaya Solak
Trakya University, Faculty of Medicine, Department of Dermatology, Edirne, Turkey

The relationship between acne and diet has attracted great attention for many years. The occurrence of acne in populations
who did not historically have acne, after the shift from traditional diets to Western style diet, supports the role of diet in
acne. So far many studies have been conducted on this relationship, however, there is still uncertainty regarding the role
of some food in acne.(1)
In literature, several reports including meta-analysis and reviews focus on various dietary factors that can have positive
or negative effects on the development of acne.(2) Dietary factors worsening acne include high glysemic index (GI)/
glycemic load (GL), dairy products, fat food and chocolate. Dietary factors reducing acne include fatty acids, fruit and
vegetable intake.
Glysemic index (GI)/ glycemic load (GL)
Glysemic index (GI) is a value for foods based on how slowly or quickly foods cause increase in blood glucose levels.
Glycemic load (GL) is the measure of foods’ ability to raise blood glucose levels. Diets that have low GI/ GL include
low carbohydrate, low processed meats and low refined food.(1, 3) Low GI/GL reduces free androgens and insulin like
growth factor-1 (IGF-1) levels which lead to reduction of acne. Evidence from many studies supports the role of food
with high GI/GL in promoting or aggravating acne.(1, 2, 4)
Milk and dairy products
Hormonal components and bioactive molecules of milk and dairy products mainly raise IGF-1 which increases
mammalian target of rapamycin (mTOR) activity and sebaceous lipogenesis resulting with acne development.(5) Many
studies have confirmed that there is an association between acne and milk and dairy products.(2, 5)
Fat food
Fried, oily food, fast food and saturated and trans fatty acids which are under the topic of fat food cause increase of
IGF-1 followed by the well-known pathway of acne pathogenesis. The adverse role of fat food on acne is supported by
several studies.(2, 6)
Chocolate
Consumption of chocolate was found to be associated with acne in various previous literature.(1, 2, 7) However, it is
still uncertain whether chocolate’s acne promoting effect depends on its high GI/GL, milk content or cocoa.(2) Further
studies are needed to understand the impact of chocolate on acne.
Fatty acids
Omega-3 fatty acids have been shown to decrease IGF-1 levels and reduce inflammation.(1) Although beneficial effects
of supplementation with omega-3 fatty acid and gamma-linoleic acid on acne is reported in a randomized-controlled
trial (RCT)(8), further studies are need to confirm their utility.
Fruit and vegetables
There are reports indicating that frequent consumption of fruits and vegetables, more than 3 days a week, has a protective
effect on acne. Their acne reducing effect is due to their anti-inflammatory and anti-oxidant activities.(2) Nevertheless,
there are no RCTs evaluating the role of fruits and vegetables so far.

159
References
1. Baldwin H, Tan J. Effects of Diet on Acne and Its Response to Treatment. Am J Clin Dermatol. 2021;22(1):55-65.
2. Dall’Oglio F, Nasca MR, Fiorentini F, Micali G. Diet and acne: review of the evidence from 2009 to 2020. Int J
Dermatol. 2021.
3. Smith R, Mann N, Mäkeläinen H, Roper J, Braue A, Varigos G. A pilot study to determine the short-term effects of
a low glycemic load diet on hormonal markers of acne: a nonrandomized, parallel, controlled feeding trial. Mol Nutr
Food Res. 2008;52(6):718-26.
4. Matsui MS. Update on diet and acne. Cutis. 2019;104(1):11-3.
5. Aghasi M, Golzarand M, Shab-Bidar S, Aminianfar A, Omidian M, Taheri F. Dairy intake and acne development: A
meta-analysis of observational studies. Clin Nutr. 2019;38(3):1067-75.
6. Burris J, Rietkerk W, Woolf K. Relationships of self-reported dietary factors and perceived acne severity in a cohort
of New York young adults. J Acad Nutr Diet. 2014;114(3):384-92.
7. Caperton C, Block S, Viera M, Keri J, Berman B. Double-blind, Placebo-controlled Study Assessing the Effect of
Chocolate Consumption in Subjects with a History of Acne Vulgaris. J Clin Aesthet Dermatol. 2014;7(5):19-23.
8. Jung JY, Kwon HH, Hong JS, Yoon JY, Park MS, Jang MY, et al. Effect of dietary supplementation with omega-3
fatty acid and gamma-linolenic acid on acne vulgaris: a randomised, double-blind, controlled trial. Acta Derm Venereol.
2014;94(5):521-5.

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 WHAT IS DISCUSSED IN 2021 ON ISOTRETINOIN THERAPY
Ayşe Serap Karadağ
İstanbul Medeniyet Üniversitesi Dahili Tıp Bilimleri, Türkiye

Isotretinoin treatment has been used in acne treatment for over 40 years since 1980s. It is the only medication that
eradicates and has an effect on all mechanisms. Despite an approximately %30 relapse, it comforts the rest of the
patients significantly. It is used with FDA approval from 12 years of age, however, it can also be used in pediatric and
infantile patients with severe acne. Although there have been several studies for many years, there are still some points
that needs to be clarified and it is been discussed among authors. This speech will focus on these issues that are under
discussion in 2021.
What are these issues discussed?
- What is the ideal dose of isotretinoin use? Is disease severity important for dosage?
- Is the completion of cumulative dosing compulsory? Does the severity of disease affect dosage?
- How often should lab examinations be conducted for patients using isotretinoin? What should the progress be like
in case of hyperlipidemia, hepatotoxicity and hyper creatine-kinase emia?
- Is there an association between inflammatory bowel disease and isotretinoin use?
- Is there an increase of depression and suicidal thoughts or attempts in isotretinoin use?
- Can interventional applications and cosmetic treatments be implemented during treatment or right after treatment?
- What kind of an approach should be adopted in case of acne exacerbation or acne fulminans development?
- Does isotretinoin use have a positive or negative effect on rhinoplasty patients?
- Is there an association between Covid and isotretinoin use?
- What should be considered for patients using isotretinoin that will have a refractive surgery or wear contact lenses?

Challenging Cases
Psoriasis:
Psoriasis is a chronic inflammatory disease that can be highly severe. Biological treatments can be used in severe cases.
These treatments respond really well in many patients, but some patients can experience side effects. Here, 4 specific
psoriasis cases will be shared.
1st case: A psoriasis case experiencing erythroderma while using adalimumab treatment. Intact areas were observed in
areas where the medication was used. Adalimumab was stopped and secukinumab treatment commenced. Why sucbutan
injected areas remained intact will be discussed here.
2nd case: Tinea corporis was detected in a patient developing severe itchy plaques under ustekinumab treatment.
Immunosuppressive treatments can lead to the development of several infections. These kinds of fungal lesions can be
mistaken with psoriatic plaques and if corticosteroid is applied, this can cause tinea incognito development and diagnosis
can be harder. Tinea infection should be considered in case of severe itchy lesion presence despite the treatment in
psoriatic patients.
3rd case: Biological treatments, especially anti-TNF agents can lead to very different paradoxical reactions. Paradoxical
alopecia, onycomadesis, an ankylosing spondylitis patient developing psoriasis and his successful response to antiL17
will be told here.
4th case: How long should the treatment be halted in psoriatic patients using biological treatment if operation is planned?
This will be discussed with a case.
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 THE ROLE OF FOXO1-GATA6 SIGNALING IN ACNE PATHOGENESIS AND TREATMENT
Bodo Melnik
Department of Dermatology, Environmental Medicine and Health Theory
University of Osnabrück, Germany

The GATA family of transcription factors is of crucial importance during embryonic development, playing complex and
widespread roles in cell fate decisions and tissue morphogenesis. GATA proteins are essential for the development of
tissues derived from all three germ layers, including the skin. The zinc finger transcription factor GATA6 also known
as GATA-binding factor 6 has gained great attention as a key regulator of the pilosebaceous follicle. Loss of GATA6
from the skin results in dilation of both the hair canal and sebaceous ducts [1]. Recently, Oulès and coworkers [2]
presented fundamental research data demonstrating that the transcription factor GATA6, which is expressed in the upper
pilosebaceous unit of normal human skin, is down-regulated in acne skin. GATA6 marks a population of cells of the
human upper pilosebaceous unit that contributes to both the follicular (lower infundibulum/junctional zone/sebaceous
duct) and upper sebaceous gland compartments [2,3]. GATA6 suppresses keratinocyte and sebocyte proliferation
and reduces the expression of epidermal proteins critically involved in keratinization (comedogenesis) and sebaceous
lipogenesis [2]. GATA6 is co-expressed with infundibular differentiation markers (involucrin and KRT79) and markers
of differentiating sebocytes (FASN, KRT7, PPAR and BLIMP1), but not observed in mature sebocytes [2]. GATA6
controls the identity of the sebaceous duct lineage and specifies a lineage switch between sebocytes and sebaceous duct
cells [3]. Furthermore, GATA6 suppresses androgen receptor expression [3], and controls the expression of inflammatory
molecules such as IL-6, TLR2 and TLR4 [2], which are up-regulated in acne lesions.
Of importance, the transforming growth factor-β (TGFβ) pathway is activated by GATA6 [2]. In particular, GATA6
negatively regulates interfollicular epidermis/upper infundibulum fate through the induction of TGFβ signaling [2]. In
a human sebaceous organoid model, GATA6-mediated down-regulation of the infundibular differentiation program is
mediated by the induction of TGFβ signaling [2]. In addition, activation of the TGFβ signaling pathway is necessary and
sufficient for maintaining sebocytes in an undifferentiated state. The presence of TGFβ ligands decreases the expression
of genes required for the production of characteristic sebaceous lipids and for sebocyte differentiation such as FADS2
and PPARγ, thereby decreasing lipid accumulation through the TGFβ receptor 2/SMAD2-dependent pathway [4]. Of
note, a genome-wide association study identified TGFB2 as a susceptibility locus for severe acne associated with reduced
TGFβ2 expression in lesional acne skin compared to non-lesional skin [5].
It is of critical importance that the expression of GATA6 is induced by the transcription factor FoxO1 [2], which plays
a key role in acne pathogenesis [6]. Three putative FoxO1 binding sites have been detected on the GATA6 promoter and
inhibition of the transcriptional activity of FoxO1 diminishes both GATA6 transcription and GAZA6 protein expression.
Puberty, the major period of highest acne prevalence, is associated with increased insulin-like growth factor 1 (IGF-
1) signaling. In addition, Western diet with excessive intake of hyperglycemic carbohydrates and commercial milk
increases insulin/IGF-1 signaling resulting in AKT-mediated translocation of FoxO1 from the nucleus to the cytoplasm
(Fig. 1A) [6]. In fact, decreased FoxO1 signaling with increased cytoplasmic FoxO1 expression has been demonstrated
in sebaceous glands of acne patients [7,8]. Thus, Western diet with high insulin/IGF-1 signaling, which is superimposed
on increased IGF-1 signaling during puberty, further impairs FoxO1-mediated GATA6 expression and consecutively
GATA6-dependent TGFβ signaling disturbing sebofollicular homeostasis with comedo formation, hyper- and
dysseborrhea.
In contrast, up-regulated GATA6 expression contributes to the therapeutic effects of all-trans retinoic acid (ATRA) [2].
In fact, GATA6 mediates the effects of ATRA on sebocytes [2]. Treatment of acne with isotretinoin, the precursor drug of
ATRA, normalizes infundibular hyperkeratinization (comedo formation) and suppresses sebaceous lipogenesis via p53-
mediated up-regulation of nuclear FoxO1 expression in epidermal keratinocytes, human SZ95 sebocytes and human
sebaceous glands (Fig. 1B) [9,10].

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Experimental and translational evidence supports the view that acne is a disease with diminished FoxO1-GATA6-TGFβ
signaling commonly induced during puberty and aggravated by Western diet as well as genetically impaired TGFβ
signaling. In contrast, treatment of acne with isotretinoin enhances p53-FoxO1-GATA6 expression and augments TGFβ
signaling normalizing infundibular hyperkeratinization and dysseborrhea in acne vulgaris.
Thus, recent progress in the molecular pathology of acne allows a deeper understanding of acne pathogenesis,
pharmacological and dietary intervention converging on the same road of signal transduction: the FoxO1-GATA6-TGFβ
pathway (Fig. 1).

Fig. 1 A Acne pathogenesis: Impaired FoxO1-GATA6-TGFβ signaling during puberty and Western diet. Increased
insulin-IGF-1 signaling decreases nuclear FoxO1 resulting in reduced GATA6 expression and diminished TGFsignaling
disturbing follicular keratinization (comedogenesis) and enhancing sebaceous lipogenesis (hyper- and dysseborrhea).
B Acne treatment: Dietary intervention with reduction of glycemic load and milk intake reduces insulin/IGF-1 signaling
increasing nuclear expression of FoxO1, which induces the expression of GATA6. Isotretinoin via ATRA-mediated
over-expression of p53 augments nuclear FoxO1 expression, thus synergizes with dietary intervention in the treatment
of acne. High GATA6 expression normalizes disturbed follicular keratinization and sebaceous lipogenesis. GATA6
stimulates TGF signaling, which is diminished in acne patients, especially those with gene polymorphisms of TGF
pathway.
Abbreviations: IGF-1: insulin-like growth factor 1; IR: insulin receptor; IGF1R: IGF-1 receptor; PI3K:
phosphatidylinositol 3-kinase; AKT: kinase Akt; FoxO1: forkhead transcription factor O1; GATA6: GATA6 transcription
factor; TGF: transforming growth factor-.

References
1. Swanson JB, Vagnozzi AN, Veniaminova NA, et al. Loss of Gata6 causes dilation of the hair follicle canal and
sebaceous duct. Exp Dermatol 2019; 28:345-9.
2. Oulès B, Philippeos C, Segal J, et al. Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit
and acne pathogenesis. Nat Commun 2020; 11:506
3. Donati G, Rognoni E, Hiratsuka T, et al. Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition
of stem cell properties. Nat Cell Biol 2017; 19:603-13.
4. McNairn AJ, Doucet Y, Demaude J, et al. TGFβ signaling regulates lipogenesis in human sebaceous glands cells.
BMC Dermatol 2013; 13:2.

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5. Navarini AA, Simpson MA, Weale M, et al. Genome-wide association study identifies three novel susceptibility
loci for severe Acne vulgaris. Nat Commun 2014; 5:4020.
6. Melnik BC. FoxO1 - the key for the pathogenesis and therapy of acne? J Dtsch Dermatol Ges 2010; 8:105-14.
7. Mirdamadi Y, Thielitz A, Wiede A, et al. Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-
3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro. Mol Cell Endocrinol 2015; 415:32-44.
8. Agamia NF, Abdallah DM, Sorour O, et al. Skin expression of mammalian target of rapamycin and forkhead box
transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with
diet. Br J Dermatol 2016; 174:1299-307.
9. Shi G, Liao PY, Cai XL, et al. FoxO1 enhances differentiation and apoptosis in human primary keratinocytes. Exp
Dermatol 2018; 27:1254-60.
10. Agamia NF, Hussein OM, Abdelmaksoud RE, et al. Effect of oral isotretinoin on the nucleo-cytoplasmic distribution
of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris. Exp Dermatol 2018; 27:1344-51.

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 LASER, HIFU AND RF TREATMENTS IN HYPERHIDROSIS
Ahu Birol

Hyperhidrosis (HH) is a chronic disorder of excess sweat production that may have a significant adverse effect on quality
of life. Treatment of HH depends on the etiology, localization, severity of the problem. Side effects of the treatment and
the cost of procedure are other important issues.
Topical antiperspirants, oral agents, iontophoresis, botulinum toxin, devices and thoracic symphatectomy are the
treatment options for hyperhidrosis.
Microwave thermolysis, high frequency ultrasound treatment, fractional microneedling, and laser treatments are recently
used devices for axillary hyperhidrosis treatment.
Microwave thermolysis has been approved by the FDA for the treatment of primary axillary HH. It causes permanent
destruction of both eccrine and apocrine sweat glands. The intervention ranged from a single administration to three
times during the course of treatment. Overall efficacy of 90 % persisting for 12 months have been reported. Ultrasound
therapy provides low levels of focused thermal injury to the eccrine and apocrine glands.
Short term adverse effects of microwave thermolysis and ultrasound; pain, edema, blister, burn, ulceration, irritation
dermatitis and numbness. Long term adverse effect; altered sensation, skin sagging, hypotrichosis, hyperpigmentation,
bumps, nodules, neuropathy.. All side effects resolve over the course of months after treatment.
Fractional microneedle radiofrequency involves the insertion of microneedles into the skin of bipolar thermal energy
directly to the eccrine sweat glands with minimal epidermal trauma. Adverse effects include mild pain, swelling and
redness.
Non invasive laser treatments using 1064 nm Nd-yag laser, diode laser have shown mixed results. Some resulting in
reduced sweating and others exacerbating HH. Subdermal laser procedure treats HH by causing damage to eccrine
glands.
All these HH treatments with devices need tumescent anesthesia to diminish pain. Patient satisfaction differs after
treatments with the devices.
The evidence for the effectiveness and safety of device treatments for HH is limited..

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 INFLAMMATORY SKIN DISEASE & BOTULINUM TOXINS
Melike Kibar Ozturk
Novomed Centers, Abu Dhabi, United Arab Emirates

FDA approved cosmetic indications of botulinum toxin A (BoNT/A) are moderate to severe glabellar lines, and moderate
to severe lateral canthal lines for Botox Cosmetic® (onabotulinumtoxinA, ONA) and glabellar lines for Dysport®
(abobotulinumtoxinA, ABO).
In addition the above mentioned cosmetic benefits, according to a latest review, BoNT/A is used in different dermatological
conditions associated with hyperhidrosis, including dyshidrosis pompholyx, bromhidrosis, chromhidrosis, hidradenitis
suppurativa and Frey syndrome, in addition to skin diseases worsened by hyperhidrosis, such as Darier disease, Hailey–
Hailey disease, inverse psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita. Besides, BoNT/A
showed efficacy in various eccrine gland abnormalities in some case series, such as multiple eccrine hydrocystomas,
eccrine sweat gland naevi eccrine angiomatous hamartoma, and congenital eccrine naevus, and as a vasodilator in treating
Raynaud phenomenon. BoNT/A improved the quality of life and alleviated pain in patients with painful cutaneous
leiomyomas. It was proposed that other painful cutaneous conditions with and without neurological involvements, such
as leg ulcers, anal fissures, lichen simplex, postherpetic neuralgia and notalgia paraesthetica, might benefit from BoNT
therapy. BoNT/A has also shown therapeutic activity in patients with, lichen simplex, atopic dermatitis, plaque psoriasis,
linear IgA bullous dermatosis, alopecia areata, androgenetic alopecia, facial erythema, flushing and various forms of itch.
Regarding to oily skin, in a latest analysis the authors concluded that most of the studies have suggested that intradermal
injection of BoNT-A decreased sebum production and pore size. BoNT-A effectively decreased sebum production and
excretion, and based on prior studies, this decrease could be achieved via blockade of cholinergic signaling and the
neuromodulatory effect of BoNT-A on the arrector pili muscles.
For rosasea, inhibition of acetylcholine signaling has also been implicated in the prevention of erythema and flushing.
There are several case studies of patients with recalcitrant rosacea. Two Caucasian patients received microdroplet
intradermal injections of ONA into the glabella and/or cheeks at intervals of 0.5 cm. The total dose was 10 to 11 units.
Patients reported an improvement in symptoms within 2 weeks of treatment, and the effects lasted for up to 4 months.
In another study, two Korean patients underwent 2 treatment sessions with intradermal ONA at 1-week intervals. The
total dose of ONA was 50 units across the 2 sessions for the first patient and 40 units across 2 sessions for the second.
The cheeks, chin, and supra-eyebrow were injected at each session. Improvements in rosacea flushing were evident 1
week after the second treatment and lasted for 3 months. The only side-effect reported was mild pain during injection.
In another proof-of-concept study investigated ABO in 15 patients with facial erythema of erythematotelangiectatic
rosacea. Initially patients received intradermal injections to the nasal tip, nasal bridge, and nasal alae, but the protocol
was altered to also include the cheeks, forehead, and chin. The mean dose was 25 units (range 15-45 units). Compared
with baseline, erythema scores were significantly improved.
For atopic dermatitis, there is only one study with twenty-six patients. They found BTX-A as safe and effective therapy
for atopic dermatitis of all grades (mild, moderate, and severe). However, being more ideal for patients with severe atopic
dermatitis. Significant improvements were observed in the SCORAD score (mild, moderate, severe) were detected in
all subgroups after treatment. In the placebo group, the mean SCORAD score did not change before and after therapy.
There were no local or systemic serious side effects except for in six patients (29.2%) who reported injection site pain
and three patients who experienced injection site swelling in the BTX-A therapy group.
Regarding to inverse psoriasis Zanchi et al used ONA (50-100 units) to reduce sweating and inflammation in 15 patients
with inverse psoriasis. Treatment had been successful in 87% of cases. Ward et al demonstrated that ABO could induce
remission of psoriasis in the KC-Tie2 transgenic mouse model of psoriasis. There two studies on plaque psoriasis, it
was found effective in a study of 8 subjects, while a latest study with 20 patients did not see any statistical significant
difference between case and control groups.
As a conclusion BoNT/A may be helpful in dermatological conditions associated with: hyperhidrosis, hyperseborrhea,

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increased fibroblast and mast-cell activity, infiltration of cutaneous lymphocytes and acanthosis like hypertrophic scar,
acne, erythematotelangiectatic rosacea, atopic dermatitis and psoriasis but a few more extensive multi‐center RCT
using a large sample is still required to determine the specific treatment mechanisms of BoNT‐A, as well as the optimal
injection techniques and doses.

References
1. Khattab FM. Evaluation of Botulinum Toxin A as an Optional Treatment for Atopic Dermatitis. J Clin Aesthet
Dermatol. 2020 Jul;13(7):32-35. Epub 2020 Jul 1. PMID: 32983334; PMCID: PMC7492021.
2. Shuo L, Ting Y, KeLun W, Rui Z, Rui Z, Hang W. Efficacy and possible mechanisms of botulinum toxin treatment of
oily skin. J Cosmet Dermatol. 2019 Apr;18(2):451-457. doi: 10.1111/jocd.12866. Epub 2019 Jan 29. PMID: 30697928.
3. Grando SA, Zachary CB. The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly
molecule to treat disease in the skin and beyond. Br J Dermatol. 2018 May;178(5):1011-1019. doi: 10.1111/bjd.16080.
Epub 2018 Mar 25. PMID: 29086923.
4. Bagherani N, Smoller BR. The efficacy of botulinum neurotoxin A in the treatment of plaque psoriasis. Dermatol
Ther. 2018 Mar;31(2):e12587. doi: 10.1111/dth.12587. Epub 2018 Feb 20. PMID: 29464842.
5. Aschenbeck KA, Hordinsky MK, Kennedy WR, Wendelschafer-Crabb G, Ericson ME, Kavand S, Bertin A, Dykstra
DD, Panoutsopoulou IG. Neuromodulatory treatment of recalcitrant plaque psoriasis with onabotulinumtoxinA. J Am
Acad Dermatol. 2018 Dec;79(6):1156-1159. doi: 10.1016/j.jaad.2018.07.058. PMID: 30420008.
6. Odberg T, Zachariae C, Bregnhøj A, Hedelund L, Bonefeld KK, Nielsen K, Iversen L, Skov L. The effect of
botulinum neurotoxin A in patients with plaque psoriasis - an exploratory trial. J Eur Acad Dermatol Venereol. 2018
Feb;32(2):e81-e82. doi: 10.1111/jdv.14536. Epub 2017 Oct 5. PMID: 28833574.
7. Boozalis E, Sheu M, Selph J, Kwatra SG. Botulinum toxin type A for the treatment of localized recalcitrant chronic
pruritus. J Am Acad Dermatol. 2018;78(1): 192–194.
8. Schlessinger J, Gilbert E, Cohen JL, Kaufman J. New Uses of AbobotulinumtoxinA in Aesthetics. Aesthet Surg J.
2017 May 1;37(suppl_1):S45-S58. doi: 10.1093/asj/sjx005. PMID: 28388720; PMCID: PMC5434494.
9. Heckmann M, Heyer G, Brunner B, Plewig G. Botulinum toxin type A injection in the treatment of lichensimplex: an
open pilot study. J Am Acad Dermatol. 2002;46(4):617–619. JCAD
10. Wessler I, Reinheimer T, Kilbinger H, et al. Increased acetylcholine levels in skin biopsies of patients with atopic
dermatitis. Life Sci. 2003;72(18–19): 2169–2172.

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 UNDERSTANDING THE DIFFERENCE OF EMOLLIENT, MOISTURIZER AND HUMECTANT
Melike Kibar Ozturk
Novomed Centers, Abu Dhabi, United Arab Emirates

Abstract
The word “emollient” is derived from the Latin verb mollire, to soften. It helps overall improvement of skin texture,
eicosanoid production, membrane fluidity, cell signaling. Saturated and unsaturated hydrocarbons are examples of
emollients. On the other hand, humect means “to wet”, it consist of hygroscopic (hygro means moisture) low molecular
substances. They absorb water by attracting water from dermis and a humid environment into the epidermis. More
commonly they draw water from the dermis into the epidermis, making skin dryer. Combination with occlusives is highly
recommended. Urea, sorbitol, panthenol, glycerol, propylene glycol, butylene glycol, hyaluronic acid, honey, gelatin
and alpha hydroxy acids (glycolic acid, lactic acid, sodium pyrrolidine, carboxylic acid) are examples of humectants.
Moisturizer and emollient are synonymous, even when occlusives and humectants are also part of it. Most moisturizers
combine both emollients, and humectants.
Introduction
The first emollient recorded in human history is the cold cream invented by Galenus, Galen of Pergamon, a Greek
doctor who worked in the Roman Empire. This cold cream was made mostly of natural oils and wax, and was used as
surgical ointment rather than as a basic skin care product. From the 20th century people started to use soap to remove
makeup, and basic skin care products evolved in order to supply lost hygro and soften the skin. After the World War
II the industrialization of cosmetic ingredients and emollients spread, leading to the development of a wide variety of
synthetic oils and semisynthetic oils made from natural oils. Today progress in chemical technology such as asymmetric
synthesis has allowed the synthesis of a plethora of oils with different molecular weights using ceramides and other
natural oils. Additionally, the variety of natural oils like organic certified oils are more commonly used, and this has
become an alternative trend today.
Mechanism of moisturizers
There are four mechanisms: Occlusion, humectancy, hydrophilic matrices and photoprotection. The most occlusive
moisturizer is petrolatum. For humentancy, the dermis possesses glycosaminoglycans, including hyaluronic acid, to
function as humectants; however, other humectants include the following: glycerin, honey, sodium lactate, urea, propylene
glycol, sorbitol, pyrrolidone carboxylic acid, gelatin, vitamins, and some proteins. These topically applied ingredients
can draw water from the air; however, the moisturizer becomes sticky and unesthetic when this occurs. Glycerin is the
most effective humectant. Hydrophilic matrices are a less popular form of moisturization characterized by the colloidal
oatmeal bath where the oatmeal forms a physical protective coating over the skin preventing evaporation. Colloidal
oatmeal is also used in moisturizers for much the same reason. Other high molecular weight substances that can provide
a barrier to evaporation include proteins, such as growth factors and collagen fragments. Occlusion and humectancy are
much more effective methods of moisturization than hydrophilic matrices. The sunscreen, whether organic or inorganic,
is thought to prevent cellular damage and thus prevent dehydration.
Formulations of emollients and humectants
Creams and lotions are emulsions containing hydrophilic and hydrophobic ingredients. Creams generally have a higher
viscosity, but there is no viscosity that defines a cream or a lotion. In either viscosity, the emulsion can be oil-in-
water (O/W), where the oil is emulsified into the water, or water-in-oil (W/O), where the water is emulsified into the
oil. O/W emulsions are the most popular for moisturizer use; however, emulsifiers are responsible for many of the
problems associated with moisturizers as they can also solubilize intercellular lipids. Liquid crystal forming emulsifiers
that do not damage the intercellular lipids include lecithin or hydrogenated lecithin. Other skin friendly emulsifiers
include behentrimonium methosulfate and dicetyldimonium chloride. Ointments are anhydrous semisolid preparations
composed of fats, waxes, animal and plant oils, and hydrocarbons. Because they do not include water necessary for

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microbial growth, they can be formulated without preservatives or with a low preservative load. They are also waterproof;
however, they possess poor esthetics because they are sticky and stain clothing. This moisturizer formulation may be
preferred in patients with extremely dry skin or preservative allergies, but very few moisturizers and many therapeutic
moisturizers fall into this category. A new formulation in moisturizers is the serum, a thin water or oilbased product
applied to freshly washed skin. The serum provides minimal moisturization benefits but is used to apply an active agent
to the skin beneath a moisturizer. As the serum formulation is not necessarily an emulsion, it does not require emulsifiers
which could damage the active ingredient. Usually, the serum has few ingredients designed to optimize the availability
of the active agent, which may be a vitamin, growth factor, botanical extract, etc.
Ingredents humectants
Squalane is a component of the human sebum. Properties such as permeability, and diffusivity to the skin are superior
to other hydrocarbons and it is an ideal emollient. Most squalanes sold in the market today are obtained from deep-
sea shark liver oil. However, due to the decrease of catch in recent years botanical squalene is also used. Natural
moisturizing factor (NMF) is a commonly used scientific and cosmetic terms to delineate the combination of chemicals
the body uses to regulate the moisture content of the stratum corneum. NMF has been synthetically formulated as a
mixture of amino acids, derivatives of amino acids, and salts. Naturally occurring epidermal NMF contains amino acids,
pyrrolidone carboxylic acid, lactate, urea, ammonia, uric acid, glucosamine, creatinine, citrate, sodium, potassium,
calcium, magnesium, phosphate, chlorine, sugar, organic acids, and peptides. About 10% of the dry weight of the
stratum corneum cells is composed of NMF broken down from filaggrin; however, formulations attempt to remoisturize
the skin through synthetic NMF composed of ingredients and ratios mimicking the naturally occurring substance. One
ingredient of synthetic NMF is sodium PCA, which is a sodium salt of 2-pyrrolidone-5-carboxylic acid. Synthetic
sodium PCA has been shown to be a better moisturizer than glycerol and is found in several moisturizer products
functioning as a humectant when used in concentrations of 2% or higher. Urea and lactic acid are also components of
synthetic NMF and can diffuse into the outer stratum corneum disrupting hydrogen bonding exposing water binding
sites on the corneocytes and facilitating increased hydration. This is especially important in calluses, which can be
improved by foot products containing these ingredients to increase stratum corneum pliability in direct proportion to
the amount of lactic acid or urea absorbed. Panthenol (also called pantothenol) is the alcohol analog of pantothenic
acid (vit B5), In pharmaceuticals, cosmetics and personal-care products, panthenol is a moisturizer and humectant, used
in ointments, lotions, shampoos, nasal sprays, eye drops, lozenges, and cleaning solutions for contact lenses. Hyaluronic
acid is a glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. Hyaluronic acid
is a main component of the extracellular matrix, and has a key role in tissue regeneration, inflammation response,
and angiogenesis, which are phases of skin wound repair. Promotes wound healing, however, show only limited
evidence from clinical research to affect burns, diabetic foot ulcers, or surgical skin repairs. In gel form, hyaluronic acid
combines with water and swells, making it useful in skin treatments as a dermal filler for treating facial wrinkles lasting
about 6 to 12 months, a clinical treatment with regulatory approval by the FDA.
Ingredents of emollients
Saturated and unsaturated hydrocarbons are common examples of emollients. Common vegetable oils used in cosmetics
are olive oil, avocado oil, sesame oil, almond oil, rice bran oil, safflower oil, shea butter, camellia oil, castor oil,
macadamia nut oil. Common animal fats and oils used are beef tallow and egg yolk oil. Aliphatic higher alcohols and
fatty acids are not effective emollients when used alone, but they show emollient effects when used with hydrophilic
surfactants to form a self-organization called alpha gel. They have high occlusive and moisture-retaining properties.
Endogenous ceramide synthesis is the first step in barrier repair. Ceramides are one of the main components of stratum
corneum intercellular lipids, and are composed of 15% cholesterol ester, 5% cholesterol, 5% fatty acid, and 5% sugar
ceramide. Nine different ceramides have been identified and synthetically duplicated for inclusion in moisturizer
formulations distinguished by their polar head group architecture, as well as by their hydrocarbon chain proper.

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References
1. Cabout E, Eymere S, Launois R, Aslanian F, Taïeb C, Seité S. Cost Effectiveness of Emollients in the Prevention
of Relapses in Atopic Dermatitis. Clin Cosmet Investig Dermatol. 2020;13:987-996. Published 2020 Dec 21.
doi:10.2147/CCID.S279233
2. How KN, Yap WH, Lim CLH, Goh BH, Lai ZW. Hyaluronic Acid-Mediated Drug Delivery System Targeting for
Inflammatory Skin Diseases: A Mini Review. Front Pharmacol. 2020;11:1105. Published 2020 Jul 24. doi:10.3389/
fphar.2020.01105
3. Tadashi Sugahara et al. Formation of α-gel (α-form hydrated crystal) by oleic acid-based gemini surfactant. Colloids
and Surfaces A: Physicochemical and Engineering Aspects, 2019; 583: 123944
4. Purnamawati S, Indrastuti N, Danarti R, Saefudin T. The Role of Moisturizers in Addressing Various Kinds of
Dermatitis: A Review. Clin Med Res. 2017;15(3-4):75-87. doi:10.3121/cmr.2017.1363
5. van Zuuren EJ, Fedorowicz Z, Christensen R, Lavrijsen A, Arents BWM. Emollients and moisturisers for
eczema. Cochrane Database Syst Rev. 2017;2(2):CD012119. Published 2017 Feb 6. doi:10.1002/14651858.
CD012119.pub2
6. Xu S, Kwa M, Lohman ME, Evers-Meltzer R, Silverberg JI. Consumer Preferences, Product Characteristics,
and Potentially Allergenic Ingredients in Best-selling Moisturizers. JAMA Dermatol. 2017;153(11):1099-1105.
doi:10.1001/jamadermatol.2017.3046
7. Lodén M. Effect of moisturizers on epidermal barrier function. Clin Dermatol. 2012;30(3):286-296.
8. Diana Draelos Z. Therapeutic moisturizers. Dermatol Clin. 2000;18(4):597-607.

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 GUMMY SMILES AND TREATMENT
Hüray Hügül
Surgery, Turkey

A ‘’Gummy Smile’’ or “excessive gingival display,” is a smile in which the gums appear prominently and make the teeth
appear smaller. This can be due to the gums, teeth, or jaw being out of proportion with the other sections, or due to
the upper lip being hypermobile. The condition in which gingival tissue is located more on the cervical third of the
crowns; resulting in teeth that appear shorter describes ‘’Gummy Smile’’(1).
Also the condition chacterized by excessive exposure of maxilarry gingiva during smilling also called ‘’ high smile line’’
or ‘’ gingival smile line’’ (2). Oliveira, et al. defined ‘gummy smile’ as a continuous band of gingival display of more than
3 mm, during spontaneous smile (3). However, “Gummy Smile” is considered a descriptive term and not a diagnosis.
Usually, the main cause of increased interlabial space is dentoskeletal dishormany ( vertical maxillary excess and / or
protrusion of upper incisors), which may or not be associated with anatomical and/or functional changes in the upper
lip. A gummy smile is typically caused by genetics, though it can also be the result of certain medications. Diagnosing
of Gummy Smile’s muscular etiology is crucial for immediatelly recognizing the limitations of orthodontic threatment
and aeshetic solutions. It has four types to be evaluated. The fourth type of lip line which is widely known as ‘’Gummy
Smile’’ show more than 4. mm of maxilliary gingiva in full smilling. It’s biological mechanism appears to involve
the combined effects of anterior vertical excess, an anincreased muscular capasity to raise the upper lip in smilling,
short upper lip, and associated factors such as excessive inter-labial gap at rest and excessive overjet and overbite.
Hyperfunction of the lip elevator muscles often results in excessive gingival display (EGD) and is the primary factor
when lip lenght is normal and lower third of the face is proportional to the other thirds. Delayed eruption as a cause
of excessive gingival display and require orthognathic surgery. However in most cases,some or all of these factors
are correlated. Thus requiring complex treatment.
Gummy Smile can have a serious negative impact on overall self-confidence. People who are self-conscious about their
smiles will often try to cover their mouths when they laugh or smile without showing their teeth. This is particularly
true of people who worry about having gummy smiles — smiles that show too much of their gums, making their teeth
look small. Luckily, there are options available to help these people feel more comfortable and confident in their smiles.
There is no technical definition for when a person has a gummy smile, given that so much of the diagnosis relies on
perception. However, a smile is typically considered to be non-gummy if less than two millimeters of gum is visible
between the top of your teeth and the bottom of your upper lip when you smile. If more than that is visible (typically
more than three millimeters), then the smile is likely to be considered gummy. 14 percent of women and 7 percent
of men have gummy smiles. However, those statistics are based on the number of people who come in to have their
gummy smiles fixed — in reality, the numbers are probably higher. People often want to correct a gummy smile because
it is affecting their enjoyment of life. Often a gummy smile can affect a person’s overall confidence and well-being.
There are a number of options available for correcting a gummy smile, including a gingivectomy, crown lengthening,
orthognathic surgery, lip repositioning, and botox. Figuring out which option is right for you largely depends on the
root cause of your gummy smile. While there are many possible causes, the most common ones are gums that are long
or enlarged, a short or hyperactive upper lip, teeth that are comparatively small, or an upper jaw that is overgrown
and makes the gums bulge out. Different procedures tackle different root causes, so it’s important to speak to a doctor
before you begin correcting your smile.
Although correcting a gummy smile can be expensive and can involve some recovery time, the procedures are providing
more than just a more beautiful smile — they’re providing an improvement in your overall confidence and well-being.
There are different treatment options:
Gingivectomy: This procedure reshapes the excess gums to expose the natural shape of the teeth. It creates a nice
balance between the gums, which are shortened, and the teeth, which are lengthened. The procedure is relatively
painless and patients typically experience little post-operational discomfort.

171
Crown lengthening: In this procedure, the excess gum tissue and the underlying bone are cut and reshaped to expose
the full length of the teeth. The process takes around an hour and usually does not require additional post-operative
care.
Orthognathic surgery: This is a more intensive procedure that tackles a gummy smile that is caused by an excessively
long upper jaw (as compared to the bottom part of the skull). During the procedure, the upper jaw is recontoured to
the proper shape and then secured into a new position that reduces the amount of gumminess in the smile. Unlike the
other procedures, orthognathic surgery involves general anesthesia and a hospital stay.
Lip repositioning: This procedure addresses a gummy smile caused by either a short or hypermobile upper lip that
exposes too much gum when you smile. It is a simple and safe procedure that restricts the pull of the “elevator”
muscles in your upper lip. It doesn’t result in any external scarring given that all the work is done on the inner lip.
Botox: This is the least invasive and most short-term way of dealing with a gummy smile. Botox works by temporarily
paralyzing the elevator muscles so that they don’t drastically raise your upper lip. While this is a cheaper and faster fix
than surgery, the results typically only last around three to four months — Botox needs to be repeated frequently for
any long-term results. However, if you are considering eventual lip repositioning for a gummy smile, Botox can be a
great way to test out what you will look like before undergoing surgery.

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 VISUAL LOSS IN AESTHETIC DERMATOLOGY
Hüray Hügül
Surgery, Turkey

Any impairment or loss of vision (temporary or permanent) secondary to central retinal or retinal branch artery
occlusion occurring as a direct consequence of percutaneous injection for aesthetic treatment (4). Blindness after
facial injection is extremely rare and was first reported by von Bahr2 over 50 years ago after scalp injection of a
hydrocortisone suspension to treat alopecia (5). The first cases after aesthetic filler treatments were reported in the
1980s (four cases) and rose to at least 16 reported cases between 2000 and 2010, presumably related to the increase
in the number of treatments being performed (4).
Depending on which artery is occluded, vision loss can be classified into six subtypes: (6–8)
1. Ophthalmic artery occlusion (OAO)
2. Generalized posterior ciliary artery occlusion with relative central retinal artery sparing (PCAO)
3. Central retinal artery occlusion (CRAO)
4. Branch retinal artery occlusion (BRAO)
5. Anterior ischaemic optic neuropathy (AION)
6. Posterior ischaemic optic neuropathy (PION)
There are also four subtypes of periocular complications associated with blindness following cosmetic filler injection
(9):
Type I – Blindness without ophthalmoplegia (paralysis or weakness of ocular muscles) and ptosis
Type II – Blindness with ptosis but without ophthalmoplegia
Type III – Blindness with ophthalmoplegia but without ptosis
Type IV – Blindness with ophthalmoplegia and ptosis.
Based on previously reported case studies, improvement of visual acuity in patients with vascular occlusion after
filler injection is extremely rare. By contrast, periocular symptoms such as ptosis and ophthalmoplegia recovered
dramatically (9).

TREATMENT ALGORITHM FOR OCULAR PAIN AND BLINDNESS AFTER FACIAL FILLERS
Indications for treatment are sudden onset ocular pain and/or loss of vision. The goal is to quickly reduce the intraocular
pressure to allow for the emboli to dislodge downstream and improve retinal perfusion (4)
1. Treatment must start within 90 minutes.
2. Stop treatment immediately.
3. Place patient in supine position (10)
4. Call emergency medical service and prepare to transfer patient to hospital setting as soon as possible.

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 TEARS TROUGH PROBLEMS AND FILLERS
Hüray Hügül
Surgery, Turkey

Tear troughs are a complex area to treat and should only be attempted by experienced injectors. When performed
correctly, dermal filler in the tear trough can reduce the apperance of tiredness under the eyes and improve the sunken
effect that happens as we age. Tear troughs treatment should only be undertaken by experienced practitioners. As you
will see – problems can occur as a result of either poor filler choice, a lack of understanding of patients anatomy or
poor patient selection.
1. Overfilled tear troughs: Tear trough swelling complication
Problem: Even as infants we have a subtle tear trough and the aim of treating the under eye area should not be to
eliminate the trough entirely. Overfilling the tear trough can lead to lumps, often seen when smiling or when looking
at the tear trough from above. As injectors we often see patients who have had filler poorly placed in the tear trough,
often with a cannula, causing a sausage shaped lump under the eye.
Solution: Dissolve the filler and start again. As hard as this is to hear, overfilled tear troughs do not look good and it is
best to dissolve the filler and build up the area again using less product.
2. Blue/green discolouration under the eyes after filler. The ‘Tyndall effect’
Problem: The ‘Tyndall’ effect is a phenomenon seen when filler is injected too superficially under the skin. When we
treat the tear trough the filler should be placed deep under the skin. If placed too superficially the filler can give a blue
/ green discolouration which is seen easiest in daylight.
Solution: Filler placed too superficially should also be dissolved. We can use an enzyme to break down the filler. After
a week come back so we can place the filler in the correct area.
3. Swelling under the eyes after filler
Problem: Some patients can experience swelling in the mid cheek or under the eye after tear trough filler. The problem
here is that the filler has been placed above the orbicularis retaining ligament or too superficially under the skin.
Dermal filler attracts water and this can cause intermittent swelling under the eye if the filler is placed too closely under
the skin.
Solution: Again, the solution here is to dissolve the filler.
The dermal filler should be placed deep under the skin, under the retaining ligament to reduce the chance of swelling.
We have to be careful in our choice of dermal filler product as they vary in how much water they attract and how much
they have the potential to swell.

References
1. Mossby’s Dental Dictionary, 2nd edition. 2008 Elsevier.
2. Matthews TG. The anatomy of a smile. J Prosthet Dent 39:128-134 ,1978
3. Oliveira, et al. Gummy smile. A contemporary and multidisciplinary overview. Dental Hypothesis. 2013, 4:2. 55-60
4. Lazzeri D, Agonstini T, Figus M, et al. Blindness following cosmetic injections of the face. Plastic Reconstructive
Surgery. 2012;129(4):995–1012. April. [PubMed] [Google Scholar]
5. von Bahr G. Multiple embolisms in the fundus of an eye after an injection in the scalp. Acta Ophthalmol (Copenh.)
963(41):85–91. [PubMed] [Google Scholar]

174
6. Zhu GZ, Sun ZS, Liao WX, et al. Efficacy of retrobulbar hyaluronidase injection for vision loss resulting from hyaluronic
acid filler embolization. Aesthetic Surg J. 2017;38(1):12–22. [PubMed] [Google Scholar]
7. Szantyr A, Orski M, Marchewka I, et al. Ocular complications following autologous fat injections into facial area:
case report of a recovery from visual loss after ophthalmic artery ccclusion and a review of the literature. Aesthetic
Plast Surg. 2017;41(3):580–584. [PMC free article] [PubMed] [Google Scholar]
8. Park KH, Kim YK, Woo SJ. Iatrogenic occlusion of the ophthalmic artery after cosmetic facial filler injections. JAMA
Ophthalmol. 2014;132(6):714–723. [PubMed] [Google Scholar]
9. Yujin M, Sangjun Y, Jeong JH, et al. The classification and prognosis of periocular complications related to blindness
following cosmetic filler injection. Plastic and Recon Surg. 2017;140(1):61-64.
10. Lok KTD, Chua JJ. Prevention and management of vision loss relating to facial filler injections. Singapore Med J.
2016;57(8):438-443

175
 FAT PADS OF THE FACE AND AESTHETIC DERMATOLOGY
Zekayi Kutlubay
Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, Department of Dermatology, Istanbul, Turkey

Most of the facial fat compartments undergo atrophy with increasing ag however, the nasolabial fat compartment un-
dergoes hyperthrophy with aging. The lateral fat compartment has a tendency to deflate in the forth decade; it is thin,
fibrous and vascular. The middle fat compartment has a tendency to deflate in the forth decade as well; it is thick, rela-
tively avascular and easy to dissect. The malar fat pads (superficial and deep) undergo defletion in the fifth decase. The
superificial malar fat pad is vascular and fibrous along the transition between middle and malar compartments. The deep
malar fat pad’s halmark of deflation is the vertically long lower lid and the infraorbital V deformity. The jowl and the
nasolabial compartments rarely undergo deflation, instead they are accenuated with the deflation of the middle and the
malar compartments respectively.1
The face is arranged in five layers which are the skin; subcutaneous fat including the retinacula cutis (composed of
fibrous connective tissue); superficial musculo-aponeurotic system (SMAS); deep fat and the periosteum or deep fascia.
The thicknesses and number of layers depend on the region. Fatty tissue in the face is located in the superficial and deep
compartments, seperated by the SMAS.2
The superficial compartments of the face are superficial lateral forehead compartment, superficial central forehead com-
partment, superficial upper temporal compartment, superficial lower temporal compartment, superficial nasolabial fat
compartment, superficial medial cheek fat compartment, superficial middle cheek fat compartment, superficial lateral
cheek fat compartment and the jowl fat compartment. The deep compartments are (deep) upper temporal compartment,
(deep) lower temporal compartment, superior premasseter compartment, middle premasseter compartment, lower pre-
masseter compartment, deep lateral forehead compartments, deep central forehead compartment, retro-orbicularis oculi
fat compartment, medial suborbicularis oculi fat compartment, lateral suborbicularis oculi fat compartment, deep pyri-
form space, deep medial cheek fat compartment and deep lateral cheek fat compartment.2,3
One of the aesthetic procedures done using the fat compartments is the autologous fat injection. Here, fat compartments
provide topographic guidance to optimize injection outcome. Fat harvesting is done by manual lowpressure lipoaspi-
ration using a blunt 3-mm cannula. The inner thighs and abdomen are the ideal donor sites because they contain the
highest concentration of stromal vascular cells and the procedure is less painful when perforemed there. Approximately
1 to 3 cc is injected into each compartment, followed by gentle massage to the malar region. Approximately 1 to 2 cc is
injected into each side fort he chin. Approximately 1 to 3 cc is injected again in anterograde and retrograde fashion, with
improvement of aesthetic line as the endpoint to the mandibular border. One cc is injected to the temporal line. One cc
injection is then needed to correct the hollowing in a radial fashion lateral to the lateral eyebrow. Deep facial compart-
ments are always restored first because they are the foundation of facial volumization.4
One of the most important characteristics of facial aging is the deepening of the nasolabial fold with reduced malar hi-
ghlight caused by sagging of the midface. Midface lifting can be achieved by the use of polidioxanone threads. By way
of the PDO cog threads, deep medial fat pad and inner layer of the superficial muscular aponeurotic system are lifted.5

References
1- Cotofana S, Fratila AA, Schenck TL, Redka-Swoboda W, Zilinsky I, Pavicic T. The Anatomy of the Aging Face:
A Review. Facial Plast Surg. 2016 Jun;32(3):253-60. doi: 10.1055/s-0036-1582234. Epub 2016 Jun 1. PMID:
27248022.
2- Cotofana S, Lachman N. Anatomy of the Facial Fat Compartments and their Relevance in Aesthetic Surgery. J
Dtsch Dermatol Ges. 2019 Apr;17(4):399-413. doi: 10.1111/ddg.13737. Epub 2019 Jan 30. PMID: 30698919.
3- Stuzin JM, Rohrich RJ, Dayan E. The Facial Fat Compartments Revisited: Clinical Relevance to Subcutaneous
Dissection and Facial Deflation in Face Lifting. Plast Reconstr Surg. 2019 Nov;144(5):1070-1078. doi: 10.1097/
PRS.0000000000006181. PMID: 31688754.
4- Xue AS, Dayan E, Rohrich RJ. Facial Fat Augmentation Finesse. Plast Reconstr Surg. 2020 Oct;146(4):416e-
419e. doi: 10.1097/PRS.0000000000007205. PMID: 32970000.
5- Myung Y, Jung C. Mini-midface Lift Using Polydioxanone Cog Threads. Plast Reconstr Surg Glob Open. 2020
Jun 24;8(6):e2920. doi: 10.1097/GOX.0000000000002920. PMID: 32766067; PMCID: PMC7339253.

176
 BLEPHAROPLASTY FOR THE DERMATOLOGIST
Alp Kayıran, M.D.
Yeditepe University, Yeditepe School of Medicine, Ophthalmology Department

Upper eyelid blepharoplasty is one of the most common procedures in oculoplastic surgery practice which is also being
more commonly performed due to ageing population in recent years. In addition to being a major cosmetic procedure
for periocular rejuvenation, decreased peripheral vision and visual field loss, impaired visual acuity, compensatory
chin-up, backward head tilt, reading difficulties, eye strain and fatigue are functional indications for upper eyelid blep-
haroplasty. Upper eyelid blepharoplasty is also reported to provide significant relief for tension type headache and to
improve headache related quality of life. While upper lid blepharoplasty is considered to be quite straightforward and
safe, severe problems regarding not only the appearance but also the function of the eye and the quality of life may if it
is performed improperly.
Careful patient selection is the first crucial step as in every surgical procedure. Patients with psychological problems,
pre-existing dry eye conditions, active cicatrising skin conditions or history of keloids must be excluded at first. Detailed
patient history should be obtained including chronic systemic diseases, autoimmune conditions, anticoagulant medica-
tions and drug allergies.
Next comes thorough preoperative examination with photographic documentation in addition to full ophthalmic exa-
mination including best corrected visual acuity, anterior segment examination for the evaluation of lacrimal function
and possible dry eye disease, examination for pupillary reflexes, ocular alignment and extraocular motility tests. Stan-
dardized eyelid measurements are very useful for the evaluation of the case. These must include the measurement of
vertical palpebral fissure, levator excursion, lid crease height, margin reflex distances (MRD 1 and 2) in addition to the
evaluation of the strength of orbicularis oculi. Accompanying problems like eyelid ptosis, brow ptosis, lower lid laxity
and lacrimal gland ptosis which might affect the surgical outcome should be carefully evaluated for optimal planning.
Besides all these, understanding the expectations of the patient is one of the most important steps of the consultation
before the procedure.
One of the most significant steps of the preparation phase is appropriate marking of the eyelids before surgery. Marking
of the skin crease and skin for excision may be performed in sitting and/or supine position. Compass caliper is very
helpful in case of lid crease asymmetry. After marking the skin crease, forceps pinch technique is used to determine the
borders of the skin excision.
Local anesthesia with systemic intravenous sedation is the choice of anesthesia type but it depends on the preference of
the patient and other possible simultaneous procedures. Local anesthesia including dilute epinephrine is always utilized,
even in cases under general anesthesia.
For the surgical technique, skin incisions may be done with either scalpel blade, electrocautery, radiofrequency or la-
ser. Haemostasis should be carefully obtained to prevent complications. Small medial opening of the orbicularis oculi
should be adequate for fat removal which is typically medial. Gentle manipulation of the fat pads is crucial to prevent
bleeding. Care should be taken for appropriate amount of fat removal avoiding overexcision. If necessary, lid crease
fixation may be accomplished with separate absorbable sutures. Adjunctive procedures like levator surgery for ptosis,
brow elevation and/or fixation for brow ptosis and lacrimal gland repositioning are performed according to the presur-
gical planning. Although closure of the skin may be performed with different suture materials and suturing techniques,
running 6/0 prolene suture is of choice. Care must be taken to close the wound under minimal tension. Cold compresses
are applied for two days after the procedure with topical antibiotic ointments twice a day. Sutures are removed on the
7th postoperative day.
Although upper lid blepharoplasty is generally a straightforward procedure for an experienced and careful surgeon, it is
important to recognize potential complications and employ appropriate management. Most of these are not severe and
may be managed with conservative care including prolonged bruising and swelling of the eyelids, mild lagophthalmos
and exposure keratitis. Although vision threatening complications like retrobulbar haemorrhage causing orbital com-
partment syndrome and globe rupture are rare, they may end up with catastrophe. Infection, lagophthalmos, dry eye
syndrome, lacrimal gland injury, ptosis, diplopia, sulcus deformity, incision problems like canthal webbing, scarring,
asymmetry of the lid crease, skin, fat or brow position are other complications to be dealt with.

177
 SIMULATION MODELS IN DERMATOLOGY EDUCATION
Emin Özlü
Düzce University Faculty of Medicine, Turkey

Simulation-based training has gained favor as a means to teach technical skills without jeopardizing patient safety.
The use of simulation to teach basic dermatologic procedures in dermatology training is expanding rapidly. It has been
shown to directly improve
clinical knowledge, teamwork, communication, and procedural skills. In this talk, the scope and importance of simulation
models in dermatology education will be reviewed and discussed.

References
1- Hazan E, et al. Cadaveric simulation for improving surgical training in dermatology. Dermatol Online J 2018; 24 (6):
13030.
2- Adams CC, et al. Survey of medical student preference for simulation models for basic dermatologic surgery skills:
simulation platforms in medical education. Dermatol Surg 2014;40:427-35.

178
 EHEALTH TECHNOLOGIES IN DERMATOLOGY
Duygu Erdil
İstanbul Training and Research Hospital, Dermatology Clinic, Turkey

E-health (also written ehealth) is a relatively recent healthcare practice supported by electronic processes and
communication. The term can covers a range of medicine and healthcare services or systems including electronic health
records, computerized physician orders, e-prescribing, clinical decision support systems, telemedicine, telerehabilitation,
telesurgery, teledentistry, health informatics, virtual helathcare teams, m-health, medical research using grids, healthcare
information systems. M-health referred to health applications and links on mobile phones. Although it is a common
convention about the importance and potential benefits of e-health, the realisation of these benefits has generally been
slower than expected hitherto. However, with the start of the pandemic in the last year, e-health has become more
important than ever.
E-health can allow previously underserved populations to access services. Increasing population with more chronic
diseases is challenging health services in both developed and developing countries. Today, prevention of diseases and
encouragement of healthy lifestyles becomes even more important. E-health can be used to help positive behavioral
changes, assist to latch on to a healtier life style, more active patient engagement and patient involvement. Access to
e-health services may be easier than traditional services, and its usability has gained importance during the pandemic
period as it provides social distance. It also helps lighten the burden on healthcare. It provides the opportunity to provide
healthcare services to more people at a low cost.
In this lecture, a series of up-to-date dermatological studies from around the world that provide important information
on key issues related to e-health services will be presented.

References
1- Wynn R, Gabarron E, Johnsen JK, Traver V. Special Issue on E-Health Services. Int J Environ Res Public Health.
2020 Apr 22;17(8):2885. doi: 10.3390/ijerph17082885. PMID: 32331273; PMCID: PMC7215852.
2- Kampmeijer R, Pavlova M, Tambor M, Golinowska S, Groot W. The use of e-health and m-health tools in health
promotion and primary prevention among older adults: a systematic literature review. BMC Health Serv Res. 2016 Sep
5;16 Suppl 5(Suppl 5):290. doi: 10.1186/s12913-016-1522-3. PMID: 27608677; PMCID: PMC5016733.
3- Ross J, Stevenson F, Lau R, Murray E. Factors that influence the implementation of e-health: a systematic review
of systematic reviews (an update). Implement Sci. 2016 Oct 26;11(1):146. doi: 10.1186/s13012-016-0510-7. PMID:
27782832; PMCID: PMC5080780.
4- Scott RE, Mars M. Behaviour Change and e-Health - Looking Broadly: A Scoping Narrative Review. Stud Health
Technol Inform. 2020 Mar 2;268:123-138. doi: 10.3233/SHTI200011. PMID: 32141884.

179
 BEST DERMATOLOGY SOFTWARE
Ozan Erdem
Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey

Computers and smartphones have become an essential part of our everyday life as well as our daily clinical practice
during the last decade. These devices dramatically facilitate our complicated and challenging tasks by running various
third-party software and applications that are consistently increasing in number and variety over the years. As medical
care providers, we frequently use this software and applications on a daily basis during monitoring patients, diagnostic
processes, treatment decisions and algorithms, educational and academic activities, calculating complex scoring systems,
and storing and sharing clinical, dermoscopic, or pathologic images. On the other hand, patient-based applications may
provide consultation of skin lesions to an expert, early cancer self-detection, and patient education.
Software technology has been rapidly developing every year. In parallel with that, the number and variety of software
in the field of dermatology are increasing as well. Therefore, it is hard to make a decision which software is the best
in dermatology. However, we can try to define the properties of the best dermatologic software. The best dermatologic
software should completely fulfill its intended purpose, provide evidence-based information, be easy to use and access,
safe, well organized and designed, understandable by all users, open to development, affordable or free of charge, have
no conflict of or monetary interest. In this lecture, software and applications that could fulfill these criteria will be
discussed in detail.

References
1. Kaliyadan F, Ashique KT. Use of Mobile Applications in Dermatology. Indian J Dermatol. 2020;65(5):371-376.
doi:10.4103/ijd.IJD_422_20
2. Hu, Eileen & Chuchvara, Nadiya & Alamgir, Mahin & Rao, Babar. (2020). Mobile Apps for Professional Dermatology
Education: An Objective Review. Cutis. 106. 10.12788/cutis.0127.
3. Tongdee E, Markowitz O. Mobile app rankings in dermatology. Cutis. 2018 Oct;102(4):252-256. PMID: 30489561.
4. Brewer AC, Endly DC, Henley J, Amir M, Sampson BP, Moreau JF, Dellavalle RP. Mobile applications in dermatology.
JAMA Dermatol. 2013 Nov;149(11):1300-4. doi: 10.1001/jamadermatol.2013.5517. PMID: 24067948.

180
 INDUSTRY 4.0 / 5.0 AND DERMATOLOGY
Cahit Yavuz
Konya Training and Research Hospital, Turkey

The terms like Industry 4.0 and Industry 5.0 are the names corresponding to Industrial Revoution. It is proceed towards
more efficient life with the new technological developments in every field such as transportation, communication, daily
life and health.
1st Industrial Revolution has began offically with the production of first mechanical loom in 1764. Steam machine
invented by James Watt in 1776, caused big changes firstly in England and later all over the World. 2nd Industrial
Revolution has started with the coming up energy sources such as electric and petrol towards the end of 19th century. 3rd
Industrial Revolution called as digital revolution started in the middle of 20th century. The production and development
of semi-conductor electronic pieces have accelerated with the invention of first transistor in 1947 and integrated circuit
in 1959. 4th Industrial Revolution brought us newly terms like internet of things, industrial internet of things, cloud
storage, artificial intelligence (AI) etc. All the machines communicate with each other, effect of human minimized, datas
are handled in real time and digital twin can be formed. At the end industry 5.0 is the term for unmanned and public-
oriented technologies. Although superior technologies produced in this manner.
Artificial intelligence is a kind of machine software which can imitate cognitive personal behaviours such as learning
and problem solving. Learning of machines means completion and continuation of decision making process by learning
and making changes (1). Artificial intelligence terms was first used in Dartmouth College Conference in 1956. In
1970’s researchers reported that artificial intelligence can be used for health science (2). It has been seen that artificial
intelligence can be used for medical image scanning, diagnostic aid, biotechnology, medical research and development.
Artificial intelligence was not attracted attention in early periods and it could not find place itself for the applications.
This is because comparatively data is not collected enough and the lack of parameters (3). The dermatological usage of
artificial intelligence began later than the usage of radiological usage. Dermatology is a branch of science which is based
on morphological features and visual pattern evalution. From this point of view dermatology is very suitable for artificial
intelligence definition and diagnosis. In the study carried out in Stanford University 129,450 clinic images taken for
different diseases and loaded to artificial intelligence was taught to recognize the illness in the light of these images.
The results were compared with 21 board certified dermatologists, they were wanted to allocate keranitocyte carcinomas
from benign seborrheic keratoses and malignant melanomas from benign nevus. It was seen that artificial intelligence
evaluated the images as successful as the dermatologists in both groups (4). In another study carried out soon; artificial
intelligence educated with 12378 dermastoscopes images and 100 melanoma images, 145 dermatologists evaluated the
same images was compared and it was seen that the results of artificial intelligence was as true as dermatologists (5).
Artificial intelligence is not limited to the images sent to itself; it also speeds up the sharing in regional internet by the
way of data mining and the progress time which will be held with the way of adding database (6).
In recent years, many developed countries have developed new artificial intelligence strategies for the future. Among the
examples for these strategies are; National Al Researches and Development Strategic Plan developed by United States,
Growing the Al Industry in UK developed by United Kingdom, The State Council on Promoting Action Guidance for
Internet+, A new Generation of Al Development Plan developed by China and The Age of Al:Towards a European
Strategy for Human-Centric Machines developed by European Union.
There are some problems in clinical practice. Lack of image scale of skin disease, information sharing among centers
and not to prove image standardisation are the problems. Another problem is decreasing the reliability of research
results and the rate of artificial intelligence. The co-operation among computer science, biomedical and medical staff
is very important. Privacy of personal data and legal issues appeared with artificial intelligence are the other problems.
Should not be forgotten that images are not enough for diagnose. Additional information and anamnesis were needed to
diagnose, to plan treatment and to determine prognosis. These steps must be applied by artificial intelligence (7). At the
end artificial intelligence cannot replace the relationship between physcian and patient.
With the developments in mobile technology, smart phones are always there for end-users in every field of life. We can
load third party applications for adding unlimited process apart from their own functions. Mobile applications can be
used for diagnostic purpose by clinicians, educational purpose for the students and health status tracking purpose by
the patients. Health applications known as mHealth, they are incerasing day by day. Diabetes Mellitus is the leader for
mobile application count for a single disease (4). Teledermatology makes these applications popular and worthy for
dermatology. The most popular dermatological applications are teledermatology apps and dermatological informative

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applications (8). Mobile applications are also used for follow-up for diseases, treatment reminders, schedulers and co-
operation between patient and physcian (9).
Mobile dermatology applications are generally effective for determining risk of skin cancer. After the patient’s
informations are loaded, they can predict the risk by using related lesion’s image. It is not enough alone but it helps
people by giving an idea. Here it is important to be known that mobile applications decisions are not always true; false
positive decisons can be evaluated and corrected by clinicians but false negative decisions may cause delay for patients
to get effective treatment (10). Masud et al. evaluated dermatology applications under four criterions; convenience for
purpose, content, accuracy and design. 9 applications got high score and interestingly some of most downloaded apps
were not in this top 9 . Download count must not be enough for decision (11).
How to choose right application? criterias are; (12)
1- Application must be supported for different platforms especially for android and IOS,
2- Free applications should be preferred more than the paid applications in view of multiplicity use and sharing,
3- User friendly applications should be preferred for longer usage,
4- Large amount of data storage and high reliabilty for application should be preferred because these applications
include images and personal datas so; privacy rules must be read and approved carefully,
5- Comments about application should be read and the logical ones should be taken into account,
6- Regular update and easy feedback to developers should not be overlooked, both are necessary for app maintenance.
Conclusion
Artificial intelligence and computational neural networks are the new, exciting fields for diagnosis of skin diseases. It
is seen that artificial intelligence is very effective about melanom and non-melanom skin cancers and other diseses. It
was seen that the skin cancer evaluations made by neural networks as effective as the experts who have board certificate
(D34). It is seen that artificial intelligence will be more entegrated with mobile apps in the future. Co-operation with
dermatologists during development phases of application will increase reliability and accuracy.
Smartphones and applications are always with us. The new applications should be developed multidirectional and
effective. The biggest concern about the applications is their scientific validity and the way of increasing scientific
reliability is to study with expert dermatologists during the developing process of applications. Artificial intelligence
based and customizable applications are seen as the future of dermatological applications.
REFERENCES
1- Fujisawa Y, Inoue S, Nakamura Y et al. The possibility of deep learning-based, computer aided skin tumor classifiers. Front Med
(Lausanne). 2019;6:191
2- Patel VL, Shortliffe EH, Stefanelli M, Szolovits P, Berthold MR, Bellazzi R et al. The coming of age of artificial intelligence in
medicine. Artif Intell Med 2009;46:5-17.
3- Hou YQY, Quan JC, Wang HW. Review of deep learning development. Ship Electr Eng 2017;37:5-9.
4- Esteva A, Kuptel B, Novoa RA, Ko J, Swetter SM, Blau HM et al. Dermatologist-level classification of skin cancer with deep
neural networks. Nature 2017;542:115-118.
5- Brinker TJ, Hekler A, Enk AH, Klode J, Hauschild A, Berking C et al. A convolutional neural network trained with dermoscopic
images performed on par with 145 dermatologists in a clinical melanoma image classification task. Eur J Cancer 209;111:148-154.
6- Li CX, Shen CB, Xue K, Shen X, Jing Y, Wang ZY et al. Artificial intelligence in dermatology: past, present and future. Chinese
Med J 2019;132:2017-20.
7- Haenssle HA, Fink C, Schneiderbauer R, Toberer F, Buhl T, Blum A, et al. Man against machine: diagnostic performance of a
deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists. Ann Oncol
2018;29:1836-42.
8- Flaten HK, St Claire C, Schlager E, Dunnick CA, Dellavalle RP, et al. Growth of mobile applications in dermatology-2017
update. Dermatol Online J 2018;24:13030
9- Fruhauf J, Schwantzer G, Ambros-Rudolph CM et al. Pilot study on the acceptance of mobile teledermatology for the home
monitoring of high-need patients with psoriasis. Australas J Dermatol 2012;53:41-6.
10- Brewer AC, Endly DC, Henley J, Amir M et al. Mobile applications in dermatology. JAMA Dermatology 2013;149:1300-04.
11- Masud A, Shafi S, Rao BK, et al. Mobile medical apps for patient education: A graded review of available dermatology apps.
Cutis 2018;101:141-4.
12- Kaliyadan F, Ashique KT. Use of mobile applications in dermatology. Indian J Dermatol 2020;65:371-6.

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 FLOW CYTOMETRY IN DERMATOLOGY
Emine Müge Acar

Flow cytometry is the measurement of physical or chemical characteristics of cells or other biologic particles as they
flow through a fluid stream. Flow cytometry can be performed on a variety of tissues, including peripheral blood,
bone marrow aspirates, skin biopsies, and tissue culture cell lines. Flow cytometry is used in multiple disciplines such
as immunology, virology, molecular biology, cancer biology and infectious disease monitoring. In dermatology, flow
cytometry is also used in the diagnosis and follow up of various skin diseases.1
Mechanism
Flow cytometry systems have five components including a laser light source, fluidics that allow the cells to stream as a
single file through the laser, optics that collect the light generated by the cells in the beam, photomultipliers that convert
the light signals to electronic data, the computer system processing the data.
The angle of light emitted from the analyzed cell gives optical information known as forward scatter (FSC) and side
scatter (SSC). Forward scatter is light scattered at a small angle and detected by a sensor on the opposite side of the
laser source. This provides information on the relative size of the cells. Light that scatters off the cell at a 90° angle is
called “side-scatter,” and gives information about the granularity of the cells. Light scatter is not related to fluorescence.
A fluorophore, which is a fluorescent chemical bound to the antibody, is chosen according to the specific wavelength
of laser existing in each flow cytometer. If the selected markers are present on the cell surface the laser energy will
be absorbed by the bound antibody–fluorophore and subsequently a specific wavelength of light is emitted as the cells
passthrough the laser. The emitted light is detected by an optical system, allowing for multiple surface markers to be
read simultaneously and collected by a computer. 1
A major application of flow cytometry is sorting cells for further analysis which makes possible to capture and collect
cells of interest for further analysis. Therefore the cells can be analyzed microscopically, biochemically, or functionally.
“Gating” is the term used to describe the selection of a subpopulation of cells for analysis.
Flow cytometry is used in various areas including in particle analysis (size distribution, refractility, concentration), cell
sorting (cell enrichment, cell concentration, verification of analysis), oncology (cell classification, clone enumeration,
proliferation rate, DNA quantitation), cell biology (DNA content, RNA content, chromosome karyotyping, protein
content, enzyme activity, intracellular PH, membrane potential, viability, membrane fluidity), immunology (epitope
density, epitope type). 1,2,3
Cutaneous T-Cell Lymphoma
Cutaneous T cell lymphoma (CTCL) is a malignancy of phenotypic helper/inducer T cells which infiltrate the skin,
migrate into the epidermis and localize in T-cell zones of lymphoid structures. The pathologic evaluation of mycosis
fungoides (MF) is a challenging topic in dermatopathology. In addition to the histologic findings, immunohistochemistry
and molecular studies are frequently used to support the diagnosis of MF.1 Flow cytometry is an adjunctive method which
is efficient and sensitive in detecting and enumerating MF/SS cells in the peripheral blood. 4 Grossly abnormal cells are
often not present in MF and the lymphocyte compartment can be studied in greater detail with FCM. Lymphocyte typing
of peripheral blood is also a valuable staging and diagnostic tool in the evaluation of newly diagnosed cases. FCM can
also be used in the immunophenotyping of lymph node cells.
The first indication of hematogenous involvement in MF is an increasing CD4: CD8 ratio. This ratio will increase with
both the increase of malignant CD4+ cells in the circulation and with the decrease of CD8 +cells, which also occurs
in the progression of CTCL. In addition, patients with more normal CD4:CD8 ratios are more immunocompetent and
this finding shows a favorable response to immunotherapy with photopheresis. The CD4:CD8 ratio increases before the
white blood count is elevated. The best utilization of FCM in CTCL patients is to obtain baseline values at the time of
diagnosis and these values should be reassessed every 6 months, In case of new cutaneous eruptions it is valuable to
assess whether the peripheral subset status has changed.1 Flow cytometry can also be applied to routine skin biopsies
and contributes to the diagnosis and subclassification of cutaneous lymphoid lesions.5
HIV infection
HIV infects CD4 positive cells and leads to eventual cell death; this causes a marked decrease in circulating CD4+T cells.
FCM can be used to analyse the treatment response of antiretroviral treatment which can be evaluated by periodical
assesment of total CD4 and CD8 lymphocyte levels at the time of the diagnosis and in the follow up. 1
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Adult T-cell Lymphoma/Leukemia (ATL)
The characteristic finding of ATL is very high level expression of IL-2 receptor (Tat) by peripheral blood and skin-
infiltrating lymphocytes. ATL can often be detected by the presence of an increased amount of CD25 (Tat, the high
affinity IL-2 receptor) expression in the peripheral blood. With disease progression, the amount of CD25 expression
increases and this parameter can be used in the follow- up of patients on therapy. 1
Systemic Lupus Erythematosus
Two-color FCM analysis shows that the number of T4 + 2H4 + lymphocytes in SLE patients is reduced and this is
exaggerated in patients with active SLE.9 The T4 + 2H4 + subset is thought to be the subset of helper T-cells that play
a role in the activation of CD8 cells. These findings also support the CD8-mediated suppression of antibody-producing
B-cells which play a role in the pathogenesis SLE. 1
Progressive Systemic Sclerosis
Increased CD4: CD8 ratios in progressive systemic sclerosis (PSS) patients were seen in younger patients with shorter
disease duration and more extensive skin involvement than patients with a normal ratio. 1 In a study by Wohlfahrt, using
flow cytometry, type 2 innate lymphoid cell counts, which are similar to Th2 cells in cytokine production,were found to
be increased in patients with systemic sclerosis and was found to be correlated with the extent of skin fibrosis and the
presence of interstitial lung disease. 6
The circulating endothelial cells in patients detected by FCM, may point to endothelial disease and may be a promising
new clinical marker for active systemic sclerosis. 7 In literature there are studies about the use of flow cytometry in
several other cutaneous diseases. Sampaio et al. reported that detection of IgG anti leishmania antigen by FCM can be
used as a diagnostic test for cutaneus leishmaniasis. Scarsi et al reported the use of FCM to detect the HLA-B*58:01
positive individuals to analyse the risk of allopurinol induced severe cutaneous adverse reactions. 8 In a study by Fernandes,
flow cytometry based immunophenotypic analysis of bone marrow mast cells was found as the most adequate test for
systemic mastocytosis due to its high sensivity.9
Flow cytometry seems to be a promising adjunctive technique in the diagnosis and follow up in dermatological diseases.
As characteristics of circulating cells in these diseases are defined by further researches, FCM will have wider clinical
applications in dermatology.

References
1. Yan SL, Heald, PW. Flow cytometry in the evaluation of dermatology patients. Clin Dermatol 1991; 9(2): 149-156.
2. Jahan-Tigh, RR., Ryan C, Obermoser G, Schwarzenberger K. Flow cytometry. J Invest dermatol 2012 ;132(10), e1.
3. Hanson CA. Applications of flow cytometry in diagnostic pathology. Am J Clin Path 1989;91:(4 Suppl 1):27-31.
4. Lima M, Almeida J, dosAnjos Teixeira M, Queiros ML, Santos AH, Fonseca S, et al. Utility of flow cytometry
immunophenotyping and DNA ploidy studies for diagnosis and characterization of blood involvement in CD41 Sezary’s
syndrome. Haematologica 2003; 88: 874-7.
5. Wu, H, Smith M, Millenson, MM, Nicolaou,N., Van Deerlin, VM, Addya K et al. Contribution of flow cytometry in
the diagnosis of cutaneous lymphoid lesions. J Invest Dermatol, 2003; 121(6): 1522-30.
6. Wohlfahrt, T, Usherenko S, Englbrecht M, Dees C, Weber S, Beyer C et al. Type 2 innate lymphoid cell counts are
increased in patients with systemic sclerosis and correlate with the extent of fibrosis. Ann Rheum Dis 2016; 75(3): 623-6.
7. Del Papa N, Colombo G, Fracchiolla N, Moronetti LM, Ingegnoli F, Maglione W et al. Circulating endothelial cells
as a marker of ongoing vascular disease in systemic sclerosis. Arthritis&Rheum 2004; 50(4): 1296-1304.
8. Scarsi M, Bosio C, Coccoli S, Barucco A, Tavelli G, Airò P. Flow cytometry test to screen for HLA-B* 58: 01-associated
allopurinol hypersensitivity. Clinical Rheumatol 2014;33(6): 873-875.
9. Fernandes IC, Teixeira MDA, Freitas I, Selores M, Alves R, Lima, M. Adult mastocytosis: a review of the Santo
António Hospital’s experience and an evaluation of World Health Organization criteria for the diagnosis of systemic
disease. An Bras Dermatol, 2014;89(1):59-66.

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 BLUE LIGHT AND SKIN HEALTH
Cahit Yavuz
Konya Training and Research Hospital, Turkey

Nowadays, we are moving from the idea that light is only for enabling us to see to the idea that light is more than that,
since it is responsible for maintaining, and have a profound impact, on our circadian rhythm synchronisation. And this
simple fact alerts us for the quality and quantity of light that we need in order to accomplish a good vision and, also,
improve our health and wellbeing, not forgetting about our emotions.
Since becoming an industrialized society, we have introduced artificial lights in our life in order to extend “daylight”
time, this is called Light Pollution.
Blue light is emitted visible light between the wavelengths of 400 to 500 nm. The main source of blue light is sunlight,
but digital screens, light-emitting diodes (LEDs), and fluorescent lighting serve as additional sources. Concerns about
the negative effects of blue light on the skin have rapidly increased over the past 15 years, and consequently, the urge to
learn more about this topic is increasing as well (1). We spend most of our lifetime in indoor environments, thus we are
under longer and more intense exposures to artificial light, and nowadays it is almost the same that saying that we are
under blue light which has a significant impact in human wellbeing (2).
Exposure to blue light is unavoidable. Blue light sources are classified in two major group: Manmade blue-light and
natural blue-light. Man made blue-light sources are digital screens like laptops-cell-phones-tvs etc, fluorescent lights
and light emission diods (LEDs). The natural source is the sun, especially in cloudy weathers. Blue-light emitting
intensity decreases from sun to TVs, monitors, laptops and cell-phones.
Blue-light affects circadian rythm changes, eye health, skin health and mood changes (3). Blue light has been shown
to generate reactive oxygen species and induce oxidative damage in the skin similar to UV radiation. Blue light can
penetrate deeper into the skin layers, induce cellular dysfunction and DNA damage. Negatively impacts photoaging and
inflammatory skin conditions. Flavins are the main photosensitizers for blue light causing oxidative stress. These flavins
produce superoxide which is the main free radical caused by exposure to blue light. Blue light exposure stimulates flavins.
Flavins produce reactive oxygen species (ROS). ROS are significantly related with photo aging and carcinogenesis (4).
Blue light induces the enzymes matrix metalloproteinases (MMPs) in skin cells, contributing to photoaging. These
MMPs not only degrade the present collagen, but also block new collagen formation and in turn prevent repair. Blue
light also has a negative effect on collagen and elastin.
There are different suggestions for pigmentation mechanism caused by blue light. First theory is, exposure to blue-
light makes decrease in carotenoids, decreased carotenoids causes formation of free radicals, and so oxydative stress
on melanogenic precursors result in pigmentation changes. Pigmentation changes result in melasma and age spots.
Another theory of pigmentation is blue-light exposure promotes opsin-3 signaling and thus increases formation of
protein complexes result in hyperpigmentation. Darker skin types are more likely to generate hyperpigmentation from
blue light exposure (5).
It’s easy to use protector physical filters to avoid blue light exposure. Anti-glare screens and protectors, blue-light filters,
mobile 3rd party apps and the glasses with digital light protection may help to protect from blue-light harms. There are
numerous agents claim that they protect blue light’s hazardous affects. Exogenous antioxidants administered topically
and/or orally were shown to beneficial in the case of UV radiation; this effect has not been confirmed with blue light yet.
There are also beneficial effects of blue light in daily practice: Small doses of lower-energy blue light treatments are
effective for; actinic keratosis, psoriasis vulgaris, eczema, acne vulgaris and photorejuvenation (1).
As conclusion; it is known that the blue light from the sun can cause skin damage and oxidation, blue light from
devices may result in similar effects. The effects of blue light on the skin depend on the wavelength and the intensity
of the exposure. Low exposure to high energy blue light can be used for aiding skin problems and help minimize

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dermatological problems. Longer exposure to high energy blue light can increase the amount of DNA damage, cell and
tissue death, and injury, causing eye damage, skin barrier damage, hyperpigmentation, and photoaging
References
1- Blue Light Protection, Part I—Effects of blue light on the skin. Coats JG, Maktabi B, Abou-Dahech MS, Baki G. J
Cosmet Dermatol. 2020;00:1–4.
2- Blue light: A blessing or a curse? Gomes CC, Pretob S. Procedia Manufacturing 2015;3: 4472 – 4479.
3- Blue light disrupts the circadian rhythm and create damage in skin cells. Dong K, Goyarts EC, Pelle E, Pernodet N.
International Journal of Cosmetic Science, 2019;41:558–562.
4- Blue light-induced oxidative stress in live skin. Nakashima Y, Ohta S, Wolf AM. Free Radical Biology and Medicine
10.1016/j.freeradbiomed.2017.03.010.
5- Pigmentation effects of blue light irradiation on skin and how to protect against them. Campiche R, Curpen SJ,
Lutchmanen-Kolanthan V, Gougeon S, Cherel M, Laurent G, Gempeler M and Schuetz R. International Journal of
Cosmetic Science, 2020;42:399–406.

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 ELASTOGRAPHY IN DERMATOLOGY
İlkin Zindanci
University of Heath Science, Hamidiye School of Medicine , Department of Dermatology, Turkey

Palpation has played an important role in the general physical examination of patients because it provides information
about the physical characteristics of the tissues. A loss of elasticity or increase in rigidity of organs or tissues has
traditionally been associated with a poorer prognosis in inflammatory processes, which histologically tend to be
associated with fibrosis, and in tumor processes, in which the elastic properties of healthy tissues decrease . Estimation of
the elasticity or rigidity of tissues could therefore facilitate early, noninvasive monitoring and treatment of inflammatory
and tumor processes.
Elastography is a technique in which ultrasound is used to detect changes in tissues. It was first defined by Ophir et al.
as a method of determining the mechanical propperties of biological tisuues . Until today elastography has been used
in various diseases, including tumors of the breast, thyroid and liver, as well as in inflammatory processes in the same
organs.
In medical use, elastography is based on measuring the displacement that occurs before and immediately after mechanical
stress is applied to tissues . To understand elastography technique, it is necessary to learn some concepts. When a tissue
is subjected to pressure, it deforms and tends to recover its initial shape which is called elasticity. The resistance of
the tissue to deformation is called rigidity or stiffness. The term strain describes the change in the relative length of a
structure subjected to pressure with respect to the surrounding tissue. In addition to this physical phenomenon, a series
of waves perpendicular to the displacement of the pressure wave which is hnown known as shear waves -are also
generated in the tissue. Special equipment is required to detect small tissue displacements, as soft tissues in the body
have a high water content and are virtually incompressible
According to the clinical guidelines on elastography published by the European Federation of Societies for Ultrasound
in Medicine and Biology (EFSUMB), there are two basic types of elastography:
1. Strain elastography (SE), which assesses tissue deformation, a qualitative method
2. Shear wave elastography(SWE), which characterizes the shear waves, a quantitavi method
Today, elastography is used in the diagnosis and follow-up of various diseases in dermatology. The areas where
elastography is used most frequently in dermatology can be summarized as follows:
Skin Tumors : The most widely investigated application in elastography of skin tumors is the differentiation of benign
and malignant tumors. In tumors, the mechanical properties of the tissue are generally altered in a way that allows the
tumor to be differentiated from the adjacent healthy tissue. Although benign subcutaneous tumors have a recognizable
appearance in B-mode ultrasound, in doubtful cases elastography could play a useful role in the differential diagnosis.
Elastography shows that malignant skin tumors are stiffer than the surrounding tissue. Elastography has been used to
study melanoma. The melanomas were hypervascularized and had multiple vascular pedicles, it is shown that the lesions
were stiffer than the adjacent skin. The lesions with the highest degree of vascularization had the greatest stiffness.
The correlation between melanoma neovascularization and prognosis is well known in the literature. Therefore, lesion
stiffness could be a prognostic factor in melanoma.
Lymph Node Enlargement : The aim of ultrasound assessment of lymph nodes is to noninvasively diagnose malignant
lymph nodes in patients with clinically suspicious lesions. Lymph nodes have an elastic structure in which the cortex
tends to be less rigid than the capsule and the hilum.Benign enlarged nodes generally tend to be soft, whereas malignant
nodes tend to be stiffer. However, lymphomas are less stiff than metastatic nodes and similar in stiffness to inflamed
nodes. Therefore, benign and lymphomatous nodes cannot be distinguished with elastography alone.
Inflammatory Skin Diseases : Elastography has been more extensively developed in fibrotic and sclerotic processes
that are primarily cutaneous or systemic (morphea/systemic sclerosis), in which clinical measurement scales have very

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limited sensitivity and specificity. Initial studies carried out in systemic sclerosis, have indicated that dermal stiffness is
greater in patients with systemic sclerosis than in controls. However, the reproducibility of the technique at other sites,
such as the fingers, was variable, perhaps because of the proximity of the bony surface of the phalanges. The authors
concluded that elastography reduces inter- and intraobserver variability in the assessment of dermal thickness of the
fingers in patients with systemic sclerosis.
Elastography has also been used in other fibrotic processes, such as cutaneous processes secondary to irradiation.
Other Skin Conditions : It ıs suggested that lower strain values in patients with lipodermatosclerosis than in patients
with lymphedema, regardless of the degree of lymphedema, ın a study using elastography
Elastography has also been used to assess pressure ulcers. Experimental studies in phantoms and animals have found
that the stiffness of the surface skin increases quickly after sustained pressure and that this could be an early marker for
the detection of areas at risk of ulceration
As the conclusion, Elastography in dermatology is an emerging technique that has great potential in the physical
characterization of the tissues of the skin. Dermatologists also have new tasks in integrating the rapidly developing
technique into dermatology.

References
1. Ophir Alam SK, Garra BS, et al. Elastography: Imaging the elastic properties of soft tissues with ultrasound. J Med
Ultrason (2001) 2002;29:155
2. Roldan FA. Elastography in dermatology. Actas Dermosfiliograficas 2016:107(8): 652-660
3. Havre R, Waage J, Gilja O, Odegaard S, Nesje L. Realtime elastography: Strain ratio measurements are influenced by
the position of the reference area. Ultraschall in Med. 2012;33:559-68.
4.Nakajima M, Kiyohara Y, Shimizu M, et al. Clinical application of real time tissue elastography on skin lesions. Medix
Hitachi. 2007; Suppl.:36-39.
5.Hinz T, Wenzel J, Schmid-Wendtner M. Real-time tissue elastography: A helpful tool in the diagnosis of cutaneous
melanoma?J Am Acad Dermatol. 2011;65:424-6.
6. Choi Y, Lee J, Baek J. Ultrasound elastography for evaluation of cervical lymph nodes. Ultrasonography. 2015;34:157-64.
7. Iagnocco A, Kaloudi O, Perella C, et al. Ultrasound elastography assessment of skin involvement in systemic sclerosis:
Lights and shadows. J Rheumatol. 2010;37:1688-91
8.Suehiro K, Morikage N, Murakami M, et al. Skin and subcutaneous tissue strain in legs with lymphedema and
lipodermatosclerosis. Ultrasound Med Biol. 2015;41:1577-83

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 CONTINUOUS-WAVE LASER HYPERTHERMIA IN DERMATOLOGY (THERMOTHERAPY)
Abdullah Demirbaş
Department of Dermatology, Evliya Çelebi Training and Research Hospital, Kütahya Health Sciences
University, Kütahya, Turkey

Introduction
Heat has been used as a therapeutic and curing modality throughout human history. There are ancient Egyptian medical
papyri that describe the use of this method for treating strangulated hernias. Galen described the humors as warm, cold,
moist, and dry. Keeping them in balance was the key to good health. In several cultures, hot spas, steam baths, hot tea
and other hot drinks, heating pads and heat lamps have been used as local heat therapy. Heat treatment is useful for pain
relief and for treating deep cutaneous infections. The theory is, heat increases blood flow and therefore speeds healing.
The heat is used in many areas and the frequency of dermatological use has increased lately. Thermotherapy is successful
in the treatments of many skin diseases.

The use of thermotherapy in skin diseases

Bacterial infections Viral infections
Staphylococcal infections Human papillomaviruses
Streptococcal infections Herpes simplex viruses
Acne (P. acnes) Kaposi sarcoma
Mycobacterial infections Skin tumors
M. ulcerans Melanoma
M. chelonae Nonmelanoma skin cancers
M. marinum Bowen’s disease
M. avium complex
Fungal infections Primary cutaneous anaplastic large cell lymphoma
Mycetoma Sporotrichosis Postherpetic neuralgia
Chromomycosis Pernio
Parasites Cosmetology
Cutaneous larva migrans
Leishmaniasis
Thermotherapy has mostly been used in infectious skin diseases, skin tumors, and cosmetics. Although there is evidence
about thermotherapy has direct toxic effects on microorganisms and/or up-regulates the body’s immune response, its
anti-infective function is not completely clear. The most comprehensive experiences of thermotherapy has been in
the treatment of leishmaniasis, sporotrichosis, and chromomycosis. It has been shown that local heat application in
leishmaniasis lesions causes a systemic cytokine response that causes a decrease in interferon- α and tumor necrosis
factor-α. Thermotherapy can lead to a variety of changes that affect the antimicrobial activity, immune system responses,
and cytokine profiles. Thermotherapy has also been shown to have an antibacterial effect on Propionibacterium acnes,
which is involved in acne pathogenesis. When exposed to heat and other stresses, cells can respond by induction of
heat shock proteins that cause cell death. Therefore, thermotherapy plays a role in acne clearance through antibacterial
effects. The term ‘hyperthermia’ also refers to various techniques of heat application administered as an adjunct to
already established strategies in the treatment of cancer patients. In humans, a variety of superficial and deep tumors
have been treated by hyperthermia with different degrees of success.

189
• superficial cutaneous tumors,
• recurrent breast cancer,
• recurrent malignant melanoma,
• head and neck squamous cell carcinoma, lymph node metastases,
• glioblastoma,
• cervical carcinoma
More recent studies have focused on the hyperthermia’s effects on distinct cellular signaling pathways; particularly with
those involved in ‘heat shock response’, cell cycle regulation and apoptosis. Furthermore hyperthermia influences tumor
blood flow, oxygen and nutrient supply, as well as, the cellular immune response, by changing the microenvironment
under in vivo conditions. The morphological changes associated with hyperthermia include endothelial swelling, the
shift of plasma fluid into the interstitium, micro-thrombosis, and changes in the viscosity of blood cell membranes.
All of these factors also reduce the oxygen and nutrient supply, as well as, intratumoral acidosis. One of the many
studies investigating how hyperthermia acts on cell lines has revealed that heat reduces cell viability and proliferation
in a time and temperature-dependant manner. Cell sensitivity to hyperthermia treatment varied among different cell
lines, and a basal cell carcinoma (BCC) cell line turned out to be quite sensitive to heat. Several energy sources such
as electromagnetic energy, microwaves, sonic energy, and laser energy from Nd:Yag laser—referred to as laserthermia
have been used to produce local hyperthermia. The treatment rationale is based on the fact that diseased tissue is more
sensitive than normal tissue to the effects of elevated temperature; therefore, it is less able to recover after heat exposure.
No single mechanism of hyperthermia cytotoxicity has been generally accepted. One explanation is that cell death
occurs as a result of the heat-induced accumulation of nuclear proteins that restrict the rejoining of DNA strand breaks.
The use of physical methods in dermatoses and skin tumors is increasing in medical practice. In particular, laser-induced
thermotherapy is used frequently. The mechanisms of the effects of laser radiation on tissues and the final biological
effect of this interaction are determined primarily by the optical and energic properties of radiation, the ways of providing
energy to the tissue, and the properties of the biological tissue itself. However, the literature data regarding the use of
this method in the treatment of dermatological pathology are not systematic. Its advantages are low invasiveness, the
high selectivity of cancer tumor damage, no risk of severe local and systemic complications, early diagnosis and organ-
sparing treatment procedures, as well as simultaneous diagnosis and treatment. In the literature, there are case reports
about laser-induced thermotherapy treatments in basal cell carcinoma, Bowen’s disease, and resistant warts.
In a study, 37 BCC patients were treated with continuous-wave Nd: Yag laser hyperthermia at 6-week intervals. Following
the treatment, 36 patients were reported to have recovered completely. It was stated that only one recurrence (2.7%)
was encountered within the 3-5 year follow-up periods and that continuous-wave Nd: Yag laser hyperthermia could be
an alternative treatment for BCC.
In another study, 77 superficial and nodular BCC patients, 31 of them were multiple carcinomas, were treated with
laser-induced hyperthermia. The success rate in low stage cases was reported to be 97% and 78.3% in high stage cases.
In a case report, Nd: Yag laser hyperthermia treatment was applied twice with an interval of 6 weeks to a 54-year-old
female patient with resistant warts on her hands. Complete regression was reported after 2 sessions.
In conclusion, laser-induced hyperthermia can be regarded as an effective, easy, non-invasive alternative procedure to
treat dermatoses and skin tumors. Nd: Yag hyperthermia is particularly useful in areas that are more difficult to treat with
other methods, such as BCCs in the nose and areas around the eyes. It showed an excellent cure and cosmetic rate with
minimal complications.

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References
1. Badgwell Doherty C, Doherty SD, Rosen T. Thermotherapy in dermatologic infections. J Am Acad Dermatol. 2010
Jun;62(6):909-27; quiz 928. doi: 10.1016/j.jaad.2009.09.055.
2. Rodbard D, Wachslicht-Rodbard H, Rodbard S. Temperature: a critical factor determining localization and natural
history of infectious, metabolic, and immunological diseases. Perspect Biol Med. 1980 Spring;23(3):439-74. doi:
10.1353/pbm.1980.0062.
3. Hölze E. Physical therapy: Light, cold, heat. In: Burgdorf WHC, Plewig G, Wolff HH, Landthaler M, (eds). Braun
Falco’s Dermatology, 3rd Edition. Heidelberg: Springer Medizin Verlag. 2009, pp 1594–1602
4. Ellis SL, Finn P, Noone M, Leaper DJ. Eradication of methicillin-resistant Staphylococcus aureus from pressure
sores using warming therapy. Surg Infect (Larchmt). 2003 Spring;4(1):53-5. doi: 10.1089/109629603764655281.
5. Hiruma M, Kagawa S. The effects of heat on Sporothrix schenckii in vitro and in vivo. Mycopathologia. 1983 Dec
1;84(1):21-30. doi: 10.1007/BF00436993.
6. Hiruma M, Kagawa S. Effects of hyperthermia on phagocytosis and intracellular killing of Sporothrix schenckii by
polymorphonuclear leukocytes. Mycopathologia. 1986 Aug;95(2):93-100. doi: 10.1007/BF00437167.
7. Tagami H, Ginoza M, Imaizumi S, Urano-Suehisa S. Successful treatment of chromoblastomycosis with topical
heat therapy. J Am Acad Dermatol. 1984 Apr;10(4):615-9. doi: 10.1016/s0190-9622(84)80266-2.
8. Segal G, Ron EZ. Regulation of heat-shock response in bacteria. Ann N Y Acad Sci. 1998 Jun 30;851:147-51. doi:
10.1111/j.1749-6632.1998.tb08988.x.
9. El-Tonsy MH, El-Domyati MM, El-Sawy AE, El-Din WH, Anbar Tel-D, Raouf HA. Continuous-wave Nd:Yag laser
hyperthermia: a successful modality in treatment of basal cell carcinoma. Dermatol Online J. 2004 Oct 15;10(2):3.
PMID: 15530293.
10. Pfau A., Ahmed T., Baumler W., Hohenleutner U., and Landthaler M. Nd:Yag laser hyperthermia in the treatment of
recalcitrant verrucae vulgaris (Regensburg’s Technique). Acta Derm Venereol. 1994; 74: 212-4.

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 THERMOGRAPHY IN DERMATOLOGY
Ozan Erdem
Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey

Historically, body temperature has been described as an excellent indicator of health status since it was first noticed
by Hippocrates around the 4th century BC. The human body is homeothermic, which means it can maintain a constant
internal body temperature regardless of external influences. The human body keeps its temperature within a narrow limit
by various physiological processes, called thermoregulation. Any change in temperature by a few degrees can be a sign
of a possible illness.
Thermal imaging or thermography is a relatively new technology that allows observation of the thermal properties of
objects. This technique is mainly based on the fact that any object at a temperature above absolute zero (>-273 °C)
emits infrared (IR) radiation or thermal radiation, which can be detected by thermal cameras. Recent developments in
thermal camera technologies have provided access to these devices much easier than it was before. Therefore, it has
raised significant interest in the medical field. Undoubtedly, the greatest part of this interest has been experienced in the
field of dermatology.
The skin is the largest organ in the human body and lies superficially, so it is an ideal target for thermography. Several
diverse thermography applications have been performed in dermatology to monitor and assess different conditions
such as inflammatory lesions, malignant and vascular tumors, bacterial and viral infections, allergic diseases, ischemic
disorders, skin burns, and pressure ulcers.
In inflammatory skin lesions, an increase in temperature is usually observed due to an increase in vascularity.
Thermography has been used in scleroderma and morphea patients to detect and monitor disease activity. Likewise, a
decrease in IR radiation can be observed in psoriasis patients after treatment. Thermography has also been successfully
performed in hidradenitis suppurativa (HS) patients to identify the severity of disease activity. Further application of
thermography in HS is to help surgeons ensure disease borders during surgical excision.
Infectious conditions generally cause an increase in core and peripheral body temperature. Soft-tissue infections such
as cellulitis and erysipelas are usually diagnosed by clinical examination; nevertheless, various disorders may resemble
soft-tissue infections, called pseudo-cellulitis. Thermography has been performed to differentiate cellulitis from pseudo-
cellulitis successfully. Another interesting application of thermography in infectious diseases in dermatology is to predict
post-herpetic neuralgia in acute herpes zoster patients. It has been determined that as the temperature difference between
acute herpes zoster lesions and normal skin increases, the risk of developing post-herpetic neuralgia also increases. In
earlier studies, thermography has been used for the diagnosis of leprosy patients. It has been shown that cooler areas
such as the ear and nasal rim region were heavily affected.
Doppler US and MRI are standard imaging techniques in the diagnosis of vascular malformations and tumors. However,
these imaging modalities may not always be available and require trained personal. Thermography is more affordable,
portable, and easy-to-use. In addition to identifying the lesion borders, as the temperature difference correlates with
blood flow, it is possible to say the vascular lesion’s flow characteristics by thermography.
Maybe the most vital application of thermography is to use in the detection, treatment, and monitoring of malignant skin
tumors such as melanoma. There are several ongoing researches on this subject that will definitely help clinicians to be
more comfortable in taking care of skin cancer patients.
In conclusion, thermography is still an emerging technology in dermatology. It is easy to use, mobile, relatively
affordable, and open to improvement. Being aware of thermography’s clinical applications will provide dermatologists
more accurate precision of diagnosing, monitoring, and treating skin conditions in the future.

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References:
1. Ring F.J. (2017) Skin Thermal Imaging. In: Humbert P., Fanian F., Maibach H., Agache P. (eds) Agache’s Measuring
the Skin. Springer, Cham. https://doi.org/10.1007/978-3-319-32383-1_73
2. Gurjarpadhye AA, Parekh MB, Dubnika A, Rajadas J, Inayathullah M. Infrared Imaging Tools for Diagnostic
Applications in Dermatology. SM J Clin Med Imaging. 2015;1(1):1-5.
3. John HE, Niumsawatt V, Rozen WM, Whitaker IS. Clinical applications of dynamic infrared thermography in plastic
surgery: a systematic review. Gland Surg. 2016 Apr;5(2):122-32. doi: 10.3978/j.issn.2227-684X.2015.11.07. PMID:
27047781; PMCID: PMC4791361.
4. Jiang LJ, Ng EY, Yeo AC, Wu S, Pan F, Yau WY, Chen JH, Yang Y. A perspective on medical infrared imaging. J Med
Eng Technol. 2005 Nov-Dec;29(6):257-67. doi: 10.1080/03091900512331333158. PMID: 16287675.
5. Jiang LJ, Ng EY, Yeo AC, Wu S, Pan F, Yau WY, Chen JH, Yang Y. A perspective on medical infrared imaging. J Med
Eng Technol. 2005 Nov-Dec;29(6):257-67. doi: 10.1080/03091900512331333158. PMID: 16287675.
6. B.B. Lahiri, S. Bagavathiappan, T. Jayakumar, John Philip, Medical applications of infrared thermography: A review,
Infrared Physics & Technology, Volume 55, Issue 4, 2012, Pages 221-235, ISSN 1350-4495, https://doi.org/10.1016/j.
infrared.2012.03.007.
7. Ring EF, Ammer K. Infrared thermal imaging in medicine. Physiol Meas. 2012 Mar;33(3):R33-46. doi: 10.1088/0967-
3334/33/3/R33. Epub 2012 Feb 28. PMID: 22370242

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 CONFOCAL, USG, IMAGING METHODS IN DERMATOLOGY
Sümeyre Seda Ertekin
Aksaray Eğitim ve Araştırma Hastanesi, Aksaray, Türkiye

Although many dermatologic diseases can be diagnosed easily with “naked eye” examination,
there have been significant advances in ancillary non-invasive imaging technologies that aid in diagnosis, management
and follow-up of some dermatological conditions and tumors. Digital dermoscopy, confocal microscopy, optical
coherence tomography (OCT) and high-frequency ultrasound (HFUS) are the main examples of the technologies used
in dermatological practice (1, 2).
Confocal microscopy is an optical technique that provides cellular resolution of skin and cutaneous structures. It can be
performed in either reflectance or fluorescence mode. Reflectance confocal microscopy (RCM) highlights the refractive
index differences of some skin structures in vivo to provide contrast. Confocal microscopes have an 830-nm (near-
infra red laser). Melanin, keratin and collagen and inflammatory cells of the skin can provide contrast and have a strong
refractive index, with melanin having the strongest. These structures appear bright white, whereas nonreflective structure
appear dark when reflected light reaches the detector. Interplay between structures with different refractive indexes
generates a black white image representing the area at the cellular level. On contrast to the classical histopathological
sections, images created by CRM are parallel to the skin surface. The commercially available device is called VivaScope
(Caliber ID, Rochester) and has two different probs: Vivascope 1500 and Vivascope 3000. Vivascope 1500 is the large
prob of the device which is fixed to skin surface with a metal ring and automatic basic horizontal images of 0.5 x 0.5 mm
are taken and stitched together to create a 2D mosaic images of 8x8 mm (VivaBlock). A specific point can be marked on
a VivaBlock and series of consecutive single RCM images can be stacked vertically (Vivastack), from the skin surface
to superficial dermis, at the same point in the tissue. Vivascope 3000 is handheld device that enables imaging of curved
anatomic sites, such as face or flexures, and does not require fixation of the probe to the skin (3).
RCM has a wide range of use, specifically in the diagnosis of melanocytic and nonmelanocytic skin tumors, as the
cellular resolution of the images are quite high and that is why it has been called “virtual biopsy”. Its specificity is quite
high in melanocytic tumors and it is an important tool to avoid unnecessary excisions. It can be used to determine pre-
operative margins for skin tumors and in the follow-up of high-risk skin tumors to detect superficial recurrence early. Its
main limitation is its penetration depth of 200-300 um (level of the papillary dermis), so it can not provide information
for the deeper parts of the skin. It is also an expensive device and requires adequate training to analyze obtained images.
Ultrasound devices are used to create images using the reflection of ultrasound waves from the interfaces with different
acoustic impedances (4). Transducers contain piezoelectric crystals that produce sound waves once stimulated by an
electric voltage. The reflection/echoes generated by different skin structures are received back by the same transducer
and converted in electrical energy which is later transformed into points of greater or lesser luminous intensities on a
computer screen (B-mode image). Image brightness is determined by the amplitude of the echo reaching the transducer.
Keratin, collagen, fascia and connective tissue are hyperechoic and appear white on the B-mode image. Dermatologist
are interested in very superficial structures therefore the appropriate equipment is high frequency ultrasound (HFUS).
Exploration probe is usually linear, as we are interested in the skin structures parallel to the body surface. When combined
with Color Doppler, blod flow can be visualized by HFUS, so information about vascularization can be obtained.
HFUS might be used for several indications in dermatology. It can be used to determine disease activity in rheumatologic
skin conditions like scleroderma or lupus, to evaluate disease extension in hidradenitis suppurativa, to visualize depth
of affection in bacterial skin infections, to diagnose subcutaneous lesions, to characterize cutaneous vascular lesions, to
delimitate malignant skin neoplasms, and to evaluate filler complications like granulomas. Other than skin itself, nail
plate and nail matrix can also be evaluated by HFUS (4, 5).

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References:
1. Schneider SL, Kohli I, Hamzavi IH, Council ML, Rossi AM, Ozog DM. Emerging imaging technologies in
dermatology: Part I: Basic principles. Journal of the American Academy of Dermatology. 2019;80(4):1114-20.
2. Srivastava R, Manfredini M, Rao BK. Noninvasive imaging tools in dermatology. Cutis. 2019;104(2):108-13.
3. Acar A KI. İn vivo reflektans konfokal mikroskopi. Aydın F, editör. Dermatolojide
Görüntüleme Yöntemleri. 1. Baskı. Ankara: Türkiye Klinikleri; 2020. p.47-55.
4. FA. R. Clinical dermatologic ultrasound:Deepening non-invasive image diagnosis in dermatology. Aydın F, editör.
Dermatolojide Görüntüleme Yöntemleri. 1. Baskı. Ankara:Türkiye Klinikleri; 2020. p.42-6.
5. Schneider SL, Kohli I, Hamzavi IH, Council ML, Rossi AM, Ozog DM. Emerging imaging technologies in dermatology:
Part II: Applications and limitations. Journal of the American Academy of Dermatology. 2019;80(4):1121-31.

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 COLOURS IN DERMATOLOGY: WHITE, BLACK, BROWN, PURPLE, YELLOW,
GREEN AND REDNESS
Aylin Türel Ermertcan
Manisa Celal Bayar University, Faculty of Medicine, Department of Dermatology, Manisa, Turkey

Introduction
Dermatology is one of the most visual medical speciality, in addition diagnosis of most dermatological diseases
depended on dermatologist’s visual physical examination with or without equipments such as dermoscope and Wood’s
light. While performing dermatological examination, it is important to define skin lesions accurately. Lesion’s size,
distribution, arrangement and morphology should be determined correctly and particularly. Morphological features
should be detailed with definition of primary and if present secondary elementary lesions and colour. Abnormal colours
can be originated in consequence of different mechanisms such as alterations in pigment biosynthesis, altered blood
flow, depositions, cell proliferations and infections.
The term ‘chromophore’ describes all chemicals and structural items that change colour of skin. The term ‘pigment’ should
now be restricted to being used to describe melanotic chromophores, while ‘pigmentation’ is reserved for descriptions
of skin colour and its abnormalities related to melanocytes and melanin. The colour of the skin as determined by two
distinct groups of chromophores, those of the pigmentary system (i.e. melanin and melanocytes) and those composed of
other elements (chromatics) of the skin, such as collagen, blood, carotenes.
In this review, we discuss importance of common colours of skin lesions in a pathogenesis-oriented manner.
Common Dermatological Colours: Which pathogenetic mechanism-Which colour?
1. White Colour
a. Hypomelanosis, hypomelanocytosis and amelanosis:
Hypopigmentation is the term used to define decreased melanin and depigmentation is the term used to define absence of
melanin. Wood’s light examination is also beneficial to distinguish hypopigmentation from depigmentation. Depigmented
lesions seem chalky white under Wood’s light.
Hypomelanosis, hypomelanocytosis and amelanosis can be underlying pathogenetic mechanisms of white skin lesions.
Genetics, autoimmunity, chemical exposure, inflammation could be initial triggers. Hypomelanosis is the term used
to define decreased melanin with normal number of melanocytes; in addition hypomelanocytosis is decrease of both
melanin and melanocytes. In the absence of melanin using terms of amelanosis would be appropriate. All of these
situations can be distinguish from each other histopathologically.
Both hypopigmented and depigmented skin lesions could be congenital or acquired; localized or generalized which
could be easily detected with patient’s history and physical examination. Examples for hypomelanosis: Focal dermal
hypoplasia, hypomelanosis of Ito, naevus depigmentosus, tuberous sclerosis complex, oculocutaneous albinism, ataxia
telengiectasia, Hallerman Streiff syndrome, histidinemia, homocystinuria, hypomelanosis of immundeficiency, Menkes
kinky hair syndrome, oculocerebral syndrome with hypopigmentation, phenylketonuria, leprosy, sarcoidosis, drug-
induced hypopigmentation, Kwashiorkor, hypopituitarism, idiopathic guttate hypomelanosis, progressive macular
hypomelanosis, hypopigmented mycosis fungoides.
Examples for hypomelanocytosis: Waardenburg syndrome, Alezzandrini syndrome, piebaldism, vitiligo, lichen sclerosus
et atrophicus, depigmentation associated with melanoma.
b. Disarrangement in dermal connective tissue:
Scar tissue represent a tissue response to dermal injury characterized by local fibroblast proliferation and collagen
production. Keloids are fibrous growths that extend beyond the original area of injury to involve the adjacent normal
skin. Hypertrophic scars may have a similar clinical appearance, but in contrast with keloids, remain confined within the

196
boundaries of the wound area and tend to regress spontaneously over time. Although keloids and hypertrophic scars are
associated with increased fibroblast proliferation and excessive collagen overproduction; white colour is characteristic
feature of mature scar tissue.
Anetoderma, also known as macular atrophy, is an uncommon disorder of elastic tissue that is clinically characterized
by wrinkled and atrophic depressions or saccular outpouchings of the skin. Available evidence suggests increased
breakdown of elastic fibers may play a primary role. Examination of the skin demonstrates skin-colored or white,
wrinkled and atrophic depressions or saccular outpouchings that may herniate on digital pressure.
c. Decreased blood flow:
Insect bite reactions and urticaria can present with edematous, pale-white papule and plaques caused by excessive
dermal edema in the superficial dermis mediated by cutaneous mast cells. Basophils have also been spotted in lesional
biopsies. Mast cells and basophils release multiple mediators including histamine (which causes itching) and vasodilatory
mediators (which cause localized swelling in the uppermost layers of the skin) upon activation. Naevus anemicus and
Bier’s spots are another clinical antity characterized with white macules. Naevus anemicus is a congenital, localized,
cutaneous vascular anomaly presenting as a pale, irregularly shaped patch on otherwise normal skin, thought to be caused
by a localized increased vascular sensitivity to endogenous catecholamines resulting in persistent vasoconstriction. Bier
spots, also called physiologic anemic macules, is an uncommon benign vascular anomaly causes mottled skin which are
thought to be an exaggerated physiologic vasoconstrictive response of the small cutaneous vessels to hypoxia induced
by venous stasis or venous hypertension.
d. Epidermal proliferation:
Epidermal proliferation can be seen in malignant or begin processes and can be present with white plaques especially
in mucosal areas such as lichen sclerosus, lichen simplex chronicus, squamous intraepithelial lesions and squamous cell
carcinoma.
e. Microorganisms:
Candida infections are presented with white, easily removable white plaques. Pityriasis versicolor can be present with
white macules in dark-skinned patients. Molluscum contagiosum present with white, umblicated papules.
2. Black Colour and Brown Colour
a. Necrosis:
Acute cutaneous necrosis is represented by a wide range of aetiologies and is associated with significant morbidity
and mortality. Clinically, skin necrosis is characterized with black, well demarcated, dry, adherent ulcers. Warfarin and
heparin administration, calciphylaxis, chemical/thermal burns, pyoderma gangrenosum, peripheral gangrene, embolic
phenomena, purpura fulminans, brown recluse spider bite, necrotizing fasciitis, ecthyma gangrenosum, antiphospholipid
syndrome, cryoglobulinemia and hypergammaglobulinemia are situtations that result in skin necrosis.
b. Hypermelanosis and hypermelanocytosis:
Hyperpigmentation is the term used to define increased melanin. Hypermelanosis and hypermelanocytosis are
possible underlying pathogenetic mechanisms of brown to black skin lesions. According to Tyndall effect, superficial
hyperpigmentations tend to seem blacker. Genetics, chronic ultraviolet exposure, inflammation could be initial
triggers. Hypermelanosis is the term used to define increased melanin with normal number of melanocytes; in addition
hypermelanocytosis is increase of both melanin and melanocytes. All of these situations can be distinguish from each
other histopathologically.
Simple lentigo, solar lentigo, post-inflammatory hyperpigmentations, cafe au lait macules, melasma, acanthosis nigricans
are hypermelanotic; melanocytic nevi, dysplastic nevi and malignant melanomas are hypermelanocytic lesions.

197
c. Exogen pigmentation:
Tatoos, radiation induced pigmentation, traumatic tatooing can present with black-brown macule, papule or plaques.
d. Microorganisms:
Erythrasma is a superficial skin infection caused by Corynebacterium minutissimum, a gram-positive, non-spore-forming
bacillus which is a component of normal skin flora. Under conditions of moisture and occlusion, C. minutissimum
propagates in the upper levels of the stratum corneum and presents as well-defined scaly plaques between the toes or
erythematous to brown patches or thin plaques in intertriginous areas.
Pityriasis versicolor is a common superficial fungal infection caused by mycelial growth of fungi of the genus Malassezia.
Patients with this infection often present with hypopigmented, hyperpigmented (especially in light-skinned individuals),
or erythematous macules on the trunk and proximal upper extremities.
3. Purple Colour
a. Disruptions in vascular integrity:
Vascular integrity can be destroyed via trauma or inflammation (vasculitis). Petechias are milimetric red-purple macules.
Purpuras are purple macules smaller than 1 cm, palpable purpuras are significant for vasculitis. Ecchymoses are purple
patches or plaques bigger than 1 cm. Trauma, infections (i.e. Neisseria meningitidis), vasculitis, connective tissue
synthesis disorders, clotting disorders, anticoagulant-antiaggregant useage.
b. Inflammatory skin diseases:
Inflammatory diseases such as lichen planus, contact dermatitis, psoriasis, cutaneous lupus erythematosus present with
red-purple coloured lesions; purplish colour tend to be seem in dark-skinned patients.
c. Exogen pigmentation:
Tatoos can also be responsible for purple coloured lesions.
d. Malignity:
Kaposi sarcoma is an angioproliferative disease that is characterized by angiogenesis, inflammation and spindle cell
proliferation. Clinical features are purplish or reddish blue macules, plaques, and nodules on the skin.
4. Yellow Colour
a. Jaundice (Icterus):
Jaundice is a sign indicating the presence of variable underlying diseases, including bilirubin overproduction, impaired
bilirubin conjugation, biliary obstruction, and hepatic inflammation. Indirect bilirubinemia present with diffuse yellow
discoloration in scleras and skin.
b. Endogen deposition:
Xanthelesma palpebrarum is the term used to define cholesterol deposition on eyelids. It presents with yellow, soft
papule or plaques and often associated with hypercholesterolemia.
c. Dilated follicular infundibulum:
Dilated follicular infundibulum can easily filled with keratin and sebum; in addition it can be visualized with dermoscopy
easily as yellow dots. Yellow dots are the most common and most sensitive features of alopecia areata, but are also seen
in some cases of androgenetic alopecia and alopecia incognita.
d. Parakeratosis of nailbed:
One of the nail findings of psoriasis is “oil drop” sign that characterized as yellow dots on the nail occur as a result of
parakeratosis of nailbed.

198
e. Microorganisms:
Onychomycosis is a fungal infection that may caused by dermatophyte, yeast, or nondermatophyte molded nail.
Dermatophyte infections (also known as tinea unguium) are the most common and are estimated to account for 60-
70 % of infections. Mycologic infiltration of nail plate results yellow discoloration, subungual hyperkeratosis and
fragmentation of nailplate.
Impetigo is a common contagious superficial bacterial infection that may affects anyone but it is most frequently
observed in children, especially those ages 2-5. It may be classified as primary impetigo (direct bacterial invasion
of previously normal skin) or secondary impetigo (minor skin trauma such as abrasions, insect bites, or underlying
conditions such as eczema). Lesions begin as papules that progress to vesicles surrounded by erythema. Subsequently
they become pustules that enlarge and rapidly break down to form thick, adherent crusts with a characteristic golden
appearance.
5. Green Colour
a. Microorganisms:
Pseudomonas aeruginosa is one of the most commonly considered gram-negative aerobic bacilli in the differential
diagnosis of gram-negative infections. Patients with chronic onycholytic toenails who have prolonged immersion
exposure to fresh water may develop a characteristic green discoloration called the green nail syndrome. The green
color is due to the accumulation of debris below the nail and the pigment pyocyanin adhering to the undersurface of the
nail plate.
b. Exogen pigmentation:
Tatoos can also be responsible for green coloured lesions.
6. Red Colour
a. Inflammation:
Inflammation is an adaptive response that is triggered by endogenous or exogenous noxious stimuli and conditions such
as allergens, microorganisms, foreign bodies, malfunctioning cells and products of extracellular matrix breakdown.
Pain, redness, edema, heat and loss of function are five cardinal signs of inflammation. Inflammation can occur either
in acute or chronic process. Acute inflammation’s clinical manifestations are vivid erythema, edema, serosity and
sometimes blisters whereas chronic inflammation’s are faded erythema, dryness and lichenification. Atopic dermatitis,
contact dermatitis, psoriasis, erythema multiforme, cutaneous lupus erythematosus, erysipelas clinically present with
erythematous lesions in acute phase.
b. Vascular malformations and tumors:
Vascular malformations are histologically characterized by an increase of dysplastic and dilated vessels. They are present
at birth and grow proportionally as the child develops. Vascular tumors are composed of benign or malign proliferation
of endothelial cells. They both present with red macules, patches, plaques or nodules such as infantile hemangiomas,
congenital hemangiomas, pyogenic granuloma, hemangioendothelioma, capillary and venous malformations.
c. Microorganisms:
Erytrasma is an infectious disease caused by Corynebacterium minutissimum, present with well defined brown patches
particularly in inverse areas. Erythrasma has spesific coral red reflect under Wood’s light examination.
Conclusion
There are several elementary lesions and colours describing skin diseases in dermatology. This riot of colours are the
clues of the diagnosis of dermatological disorders and these colours make dermatology enjoyable.

199
References
1. Nordlund JJ, Cestari TF, Chan H, Westerhof W. Confusions about colour: a classification of discolorations of the skin.
Br J Dermatol 2006; Suppl 1:3-6.
2. Diagnosis and management of vulvar skin disorders: ACOG Practice Bulletin, Number 224. Obstet Gynecol 2020;
136(1): e1-e14.
3. Karimi K, Odhav A, Kollipara R, Fike J, Stanford C, Hall JC. Acute cutaneous necrosis: A guide to early diagnosis
and treatment. J Cutan Med Surg 2017; 21(5): 425-37.
4. Richey PM, Norton SA. John Tyndall’s effect on dermatology. JAMA Dermatol 2017; 153(3): 308.
5. Taylor SC. Skin of color: biology, structure, function, and implications for dermatologic disease. J Am Acad Dermatol
2002; 46 (2 Suppl Understanding): S41-62.
6. Fargo MV, Grogan SP, Saguil A. Evaluation of jaundice in adults. Am Fam Physician 2017; 95(3): 164-8.
7. Lipner SR, Scher RK. Onychomycosis: Clinical overview and diagnosis. J Am Acad Dermatol 2019; 80(4): 835-51.
8. Theiler M, Wälchli R, Weibel L. Vascular anomalies- a practical approach. J Dtsch Dermatol Ges 2013; 11(5): 397-405.
9. Klatte JL, van der Beek N, Kemperman PM. 100 years of Wood’s lamp revised. J Eur Acad Dermatol Venereol 2015;
29(5): 842-7.

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 DIAGNOSTIC CRITERIA IN DERMATOLOGY
Aysenur Botsali
Department of Dermatology, Faculty of Health Sciences, Gulhane Training and
Research Hospital, Ankara, Turkey

The art of medicine includes consecutive stages of assessment and judgement prior to providing recommendations.
Assessment is the central step and several attempts to codify assessment have been undergone. In addition to improved
patient care and research purposes, the accurate diagnosis of a particular disease is essential for billing and reimbursement.
In other words in addition to academic reasons, economic, political and social forces also empower the development of
diagnostic criteria (1).
The diagnosis process is more challenging in several disciplines including psychiatry, rheumatology and dermatology.
Thus, diagnostic criteria are more favored in these disciplines and the Diagnostic and Statistical Manual of Mental
Disorders (DSM) is likely the best-known example of diagnostic criteria.
During dermatological practice, rather than depending on a single ‘’gold standard’’ method of a clinical, laboratory,
pathological and/or radiological feature, patient reports and dermatological findings are admixed with advanced tests
to determine the diagnosis. Additionally, the presentation, course and outcome of dermatological diseases tend to be
heterogeneous.
Diagnostic criteria are fundamentally defined as a set of signs, symptoms and tests for use in routine clinical practice
to guide the care of individual patients. Diagnostic criteria are generally broad and must reflect the different features
of a disease in order to accurately identify as many people with the condition as possible including those with unusual
features and presentations. Thus, the development and validation of diagnostic criteria can be quite challenging (2).
Diagnostic criteria for any condition must be both valid and clinically sensible. Different methods can be used to
establish consensus among clinical experts for the content of a criteria set. Despite face-to-face communication may
provide certain advantages over remote voting, in dermatology, the most preferred method for establishing consensus is
Delphi method (3-6). Delphi is a completely anonymous process (7). The participants don’t meet and ideas are expressed
to the participants through a mailed questionnaire. Delphi method can be applied to high numbers of participants
who cannot meet simultaneously for economical or logistic reasons. The participants may be either leaders in their
clinical fields as evidenced by their roles as opinion makers within established organizations, authors who had papers
directly concerned with the topic of interest in peer-reviewed journals or local physicians for regional diseases. The
items of the questionnaire may be compiled from various resources including textbooks, published literature, personal
communications with faculty members who have experience in assessing and treating the topic of interest. After the
declaration of group responses to the first round, the second round is performed to drop or add items. Repeated iterations
of the process are performed until the achievement of consensus (7). This consensus establishes what the criteria set
should compromise and does not entirely ensure validity. Over the last decades, tremendous progress in focusing on
measurement has been undergone and the development of diagnostic criteria is also evolving. Along with the evolution
of clinical practice, the opinions of experts may also change. This is the rationale for the revision of existing diagnostic
criteria sets that is inevitable owing to the improved understanding on disease pathogenesis and the development of new
diagnostic tools.
The performance of diagnostic criteria is dependent on the prevalence of the disease in a given geographical area or
clinical setting. Despite the sensitivity and specifity of diagnostic criteria sets are not influenced by disease prevalence,
the predictive validity is altered. As an example, in Turkey where Behçet’s disease is endemic(high pre-test probability),
patients with recurrent apthous ulcers may be accurately diagnosed and treated even with few supporting criteria. Thus,
in Turkey, the diagnostic criteria of Behçet’s disease are implemented to patient identification during clinical research,
however they are not strictly applied during routine patient care. On the other hand, in the United States (low pre-test
probability) any set of diagnostic criteria will have a low positive predictive value. Diagnostic criteria will typically need

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to be based on local prevalence of the disease and of other diseases in the differential diagnosis that is not a practical
goal (2).
The feasibility, acceptability and available resources should be taken into account during the establishment of universally
accepted diagnostic criteria. Stringent criteria that require a particular laboratory, pathological or molecular test could
constitute a hurdle for patients and clinicians and has the potential to postpone the initiation of effective treatment.
Despite diagnostic criteria certainly provide improvement of patient care, the clinicians should be aware of the fact that
diagnosis is a complex multi-step process that is difficult to accomplish with a single set of criteria.

References
1. Chren M-M. Giving Scale New Meaning in Dermatology: Measurement Matters. Archives of dermatology.
2000;136(6):788-90.
2. Aggarwal R, Ringold S, Khanna D, Neogi T, Johnson SR, Miller A, et al. Distinctions between diagnostic and
classification criteria? Arthritis care & research. 2015;67(7):891.
3. Burden-Teh E, Thomas KS, Gran S, Murphy R. Development of clinical diagnostic criteria for plaque psoriasis
in children: an electronic Delphi consensus study with the International Psoriasis Council. The British journal of
dermatology. 2019;181(4):856.
4. Engelman D, Yoshizumi J, Hay RJ, Osti M, Micali G, Norton S, et al. The 2020 international alliance for the control
of scabies consensus criteria for the diagnosis of scabies. British Journal of Dermatology. 2020;183(5):808-20.
5. Maverakis E, Ma C, Shinkai K, Fiorentino D, Callen JP, Wollina U, et al. Diagnostic criteria of ulcerative pyoderma
gangrenosum: a Delphi consensus of international experts. JAMA dermatology. 2018;154(4):461-6.
6. Prost-Squarcioni C, Caux F, Schmidt E, Jonkman MF, Vassileva S, Kim SC, et al. International Bullous Diseases Group:
consensus on diagnostic criteria for epidermolysis bullosa acquisita. British Journal of Dermatology. 2018;179(1):30-41.
7. Nair R, Aggarwal R, Khanna D, editors. Methods of formal consensus in classification/diagnostic criteria and guideline
development. Seminars in arthritis and rheumatism; 2011: Elsevier.

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 HYPO / HYPER / ABSENCE (A)-CONDITIONS IN DERMATOLOGY
Banu Taşkın
Istanbul Bagcilar Training and Research Hospital, Turkey

In dermatology, there are many diseases and symptoms that are characterized by hypo or hyper-conditions. The most
common of these are hypopigmentations and hyperpigmentations. Some skin diseases and conditions may result in
generalized or localized hypopigmentation (decreased skin color), or hyperpigmentation (increased skin color), or
depigmentation (absent skin color). In this lecture, hypo-hyperpigmentations will be mentioned especially as they are
more common, as well as hypo-hypertrichosis, hyper-hypohydrosis, hyper-hypo keratosis and hypoplasic conditions.

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 RED SCROTUM SYNDROME AND MALE GENITAL DYSESTHESIA
Amr Abdelhamed
Department of Dermatology, Venereology & Andrology, Faculty of Medicine, Sohag University, Egypt

The Red Scrotum Syndrome (RSS) is a condition characterized by persistent scrotal erythema associated with a burning
sensation, hyperalgesia, and itching [1]. Its exact etiology is unknown, but suggested mechanisms may include rebound
vasodilation after prolonged topical corticosteroid use, localized erythromelalgia (a triad of erythema, warmth, and
burning pain), and neurogenic inflammation [1]. However, RSS was suggested to be a manifestation of corticosteroid
misuse rather than a primary disease [2].
Diagnosis of RSS is usually a diagnosis of exclusion. Histopathological features are non-specific. The epidermis might
show normal to spongiotic and atrophic changes. The dermis might show dilated blood capillaries with superficial
perivascular lymphocytic infiltrate [3].
RSS is a chronic condition with several treatment options that have been tried with variable responses. Stoppage of topical
steroid is necessary with therapeutic targeting of the proposed mechanisms including the rebound vasodilation, localized
erythromelalgia, and neurogenic inflammation might be helpful [1]. Doxycycline showed 50-80% improvement of RSS
within 2 weeks of therapy, with complete resolution of symptoms within 2-3 months [3]. Also, Doxycycline (100 mg
twice/day) was used for 2 months, followed by once daily until complete resolution [4]. Oral pregabalin (50 mg 3 times/
day) showed improvement in 2 cases [5]. It was suggested in a case report that doxycycline should be tried for 2 weeks
as a first-line, and the use of gabapentin is recommended as a second line in case of doxycycline failure [6].
Also, oral and topical β-blockers have been tried. Topical timolol maleate 0.5% eye gel showed dramatic improvement
after 2 weeks in a case report [7]. Oral carvedilol (6.25 mg/day) showed remission in 2 cases within 2-4 weeks of
treatment, without reported systemic side effects [8]. Recently, oral ivermectin (12 mg/week) showed near resolution
(>90%) of 3 cases of RSS after 1 month. Then, treatment was continued with topical ivermectin until the complete
resolution of symptoms [9].
Prevention of RSS might be done through reduction of topical corticosteroid misuse and increasing the patients’
awareness about the side effects associated with unmonitored use of these drugs [1]. It must be noted that data about
treatment options come from case reports/and or series. Therefore, randomized controlled clinical trials with a large
number of patients are needed.

References:
1. Khalil, S., M. Kurban, and O. Abbas, Red scrotum syndrome: An update on clinicopathologic features, pathogenesis,
diagnosis, and management. J Am Acad Dermatol, 2020.
2. Narang, T., et al., Red scrotum syndrome: idiopathic neurovascular phenomenon or steroid addiction? Sex Health, 2013.
10(5): p. 452-5.
3. Abbas, O., et al., Red scrotum syndrome: successful treatment with oral doxycycline. J Dermatolog Treat, 2008. 19(6): p. 1-2.
4. Byun, J.W., et al., Red scrotum syndrome: successful treatment with oral doxycycline. Int J Dermatol, 2012. 51(3): p. 362-3.
5. Miller, J. and S. Leicht, Pregabalin in the treatment of red scrotum syndrome: a report of two cases. Dermatol Ther, 2016.
29(4): p. 244-8.
6. Wollina, U., Red scrotum syndrome. J Dermatol Case Rep, 2011. 5(3): p. 38-41.
7. Pyle, T.M. and W.R. Heymann, Managing red scrotum syndrome (RSS) with topical timolol. Int J Dermatol, 2019. 58(8):
p. e162-e163.
8. Merhi, R., N. Ayoub, and M. Mrad, Carvedilol for the treatment of red scrotum syndrome. JAAD Case Rep, 2017. 3(5): p.
464-466.
9. Martinez, J.D., M. Soria Orozco, and J.A. Cardenas-de la Garza, Oral ivermectin for the treatment of red scrotum syndrome.
J Dermatolog Treat, 2020: p. 1-2.

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 JOLLY ROGER SIGN IN DERMATOLOGY
Bachar Memet
Şişli Florence Nightingale Hospital, Turkey

The “pirate brand” has long been tied to the skull and crossbones—the Jolly Roger—as a symbol of terror on the high
seas.
The Jolly Roger sign stands for drugs used in dermatological therapy but are actually toxic.
The skull-and-crossbones symbol, consisting of a human skull and two bones crossed together behind the skull, is today
generally used as a warning of danger of death, particularly in regard to poisonous substances.
The symbol, or some variation thereof, specifically with the bones (or swords) below the skull, was also featured on
the Jolly Roger, the traditional flag of European and American seagoing pirates. The Workplace Hazardous Materials
Information System (WHMIS) is Canada’s national workplace hazard communication standard. The Jolly Roger is also
part of the Canadian WHMIS home symbols placed on containers to warn that the contents are poisonous.
Potassium permanganate
Potassium permanganate is used as a medication for a number of skin conditions (1). This includes fungal infections
of the foot, impetigo, pemphigus, superficial wounds, dermatitis, and tropical ulcers (2). For tropical ulcers it is used
together with procaine benzylpenicillin. Typically it is used in skin conditions that produce a lot of liquid. It can be
applied as a soaked dressing or a bath (1).
Side effects may include irritation of the skin and discoloration of clothing (1). If it is taken by mouth, toxicity and death
may occur. Potassium permanganate is an oxidizing agent.The British National Formulary recommends that each 100
mg be dissolved in a liter of water before use (2).
Potassium permanganate was first made in the 1600s and came into common medical use at least as early as the 1800s.
It is on the World Health Organization’s List of Essential Medicines (3).
Uses include for fungal infections of the foot, impetigo, pemphigus, superficial wounds, dermatitis (eczema), and
tropical ulcers. Typically it is used in skin conditions that produce a lot of liquid.For tropical ulcers it is used together
with procaine benzylpenicillin for two to four weeks (1).
It can be used in children and adults. It can be applied as a soaked dressing or a bath. The U.S. Food and Drug
Administration does not recommend its use in either the crystal or tablet form (4).
Side effects
Topical
Side effects may include irritation of the skin and discoloration of clothing (1). A harsh burn on a child from an
undissolved tablet has been reported. For treating eczema, it is recommended using for a few days at a time due to the
possibility of it irritating the skin (5). Higher concentration solutions can result in chemical burns. Therefore, the British
National Formulary recommends 100 mg be dissolved in a liter of water before use to form a 1:10,000 (0.01%) solution
(5). Wrapping the dressings soaked with potassium permanganate is not recommended.
By mouth
If taken by mouth it is deemed to be very toxic.Side effects may include nausea, vomiting, and shortness of breath may
occur. If a sufficiently large amount (about 10 grams) is eaten death may occur (6).
Concentrated solutions when drunk have resulted in adult respiratory distress syndrome or swelling of the airway.
Recommended measures for those who have ingested potassium permanganate include gastroscopy.Activated charcoal
or medications to cause vomiting are not recommended.While medications like ranitidine and N-acetylcysteine may be

205
used in toxicity, evidence for this use is poor (7).
Arsenic
During the 18th, 19th, and 20th centuries, a number of arsenic compounds were used as medicines, including arsphenamine
(by Paul Ehrlich) and arsenic trioxide (by Thomas Fowler) (8). Arsphenamine, as well as neosalvarsan, was indicated for
syphilis, but has been superseded by modern antibiotics. However, arsenicals such as melarsoprol are still used for the
treatment of trypanosomiasis, since although these drugs have the disadvantage of severe toxicity, the disease is almost
uniformly fatal if untreated (9).
Arsenic trioxide has been used in a variety of ways over the past 500 years, most commonly in the treatment of cancer,
but also in medications as diverse as Fowler’s solution in psoriasis (10).

Referances
1. World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World
Health Organization. pp. 295, 300.
2. British Medical Association; Royal Pharmaceutical Society (2015). British national formulary (69 ed.). p. 840
3. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019.
Geneva: World Health Organization. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
4. “CFR - Code of Federal Regulations Title 21”. www.accessdata.fda.gov. Retrieved 11 October 2017.
5. “Should potassium permanganate be used in wound care?”. Nursing Times. 5 August 2003. Retrieved 12 October
2017.
6. Patnaik, Pradyot (2007). A Comprehensive Guide to the Hazardous Properties of Chemical Substances. John Wiley
& Sons. p. 710.
7. Dart, Richard C. (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 904–905. ISBN 9780781728454.
FR - Code of Federal Regulations Title 21”. www.accessdata.fda.gov. Retrieved 11 October 2017.
8. Gibaud, Stéphane; Jaouen, Gérard (2010). Arsenic – based drugs: from Fowler’s solution to modern anticancer
chemotherapy. Topics in Organometallic Chemistry. 32. pp. 1–20.
9. Büscher P, Cecchi G, Jamonneau V, Priotto G (2017). “Human African trypanosomiasis”. Lancet. 390 (10110): 2397–
2409.
10. Huet, P. M.; Guillaume, E.; Cote, J.; Légaré, A.; Lavoie, P.; Viallet, A. (1975). “Noncirrhotic presinusoidal portal
hypertension associated with chronic arsenical intoxication”. Gastroenterology. 68 (5 Pt 1): 1270–1277.

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 INTESTINAL BACTERIAL OVERGROWTH IN DERMATOLOGY
Amr Abdelhamed 1,Walaa Abdelhamed 2
1
Department of Dermatology, Venereology & Andrology, Faculty of Medicine, Sohag University, Egypt
2
Department of Tropical Medicine and Gastro-enterology, Faculty of Medicine, Sohag University, Egypt

Small intestinal bacterial overgrowth (SIBO) is a condition characterized by an increase in the number and/or abnormal
forms of bacteria in the small intestine. SIBO may occur due to disturbance of the gastric acid secretion and intestinal
motility which normally inhibit bacterial growth, leading to frequent gastrointestinal symptoms including diarrhea,
distension, malnutrition, and weight loss [1]. Diagnosis of SIBO can be made through intestinal aspirate which is the
gold standard. However, breath tests by measuring the exhaled gas after ingesting either glucose or lactulose are a more
commercially popular and non-invasive diagnostic tool. The breath test results depend on the bacterial metabolism of
the ingested material the bacteria [2].
In addition to gastrointestinal (GIT) symptoms, SIBO might affect the gut/skin axis, and a potential link has been found
between SIBO and numerous dermatological conditions including rosacea, psoriasis, and systemic sclerosis (SSc) [3].
Rosacea has been linked to SIBO and the treatment of SIBO with rifaximin which is a rifamycin derivative has shown
to have beneficial effects [4]. After treatment of SIBO in rosacea patients, remission has been maintained in 44% of
patients after 5 years of follow-up [5]. Treatment of the associated SIBO in patients with psoriasis showed improvement
in psoriasis area severity index (PASI) [6]. In patients with SSc, SIBO is more prevalent as compared to control, and
treatment of SIBO has been associated with GIT symptoms in those patients [7]. Therefore, special attention should be
on the possible gut/skin axis which may carry a potential therapeutic modality for several dermatological conditions

References:
1. Dukowicz, A.C., B.E. Lacy, and G.M. Levine, Small intestinal bacterial overgrowth: a comprehensive review.
Gastroenterol Hepatol (N Y), 2007. 3(2): p. 112-22.
2. Ghoshal, U.C., R. Shukla, and U. Ghoshal, Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A
Bridge between Functional Organic Dichotomy. Gut Liver, 2017. 11(2): p. 196-208.
3. Nickles, M.A., et al., Alternative Treatment Approaches to Small Intestinal Bacterial Overgrowth: A Systematic
Review. J Altern Complement Med, 2020.
4. Daou, H., et al., Rosacea and the Microbiome: A Systematic Review. Dermatol Ther (Heidelb), 2021. 11(1): p. 1-12.
5. Drago, F. and G. Ciccarese, Effects of the treatment for small intestine bacterial overgrowth on rosacea. 2017. 44(12):
p. e321.
6. Drago, F., et al., Psoriasis and small intestine bacterial overgrowth. Int J Dermatol, 2018. 57(1): p. 112-113.
7. Parodi, A., et al., Small intestinal bacterial overgrowth in patients suffering from scleroderma: clinical effectiveness
of its eradication. Am J Gastroenterol, 2008. 103(5): p. 1257-62.

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 CUTIBACTERIUM IN DERMATOLOGY
Elif Cömert-Özer
Marmara University Pendik Research Hospital, Istanbul, Turkey

Recent phenotypic and genomic (16S RNAr and CoreGenome) investigations led to some modifications in the
Propionibacterium genus taxonomy. Notably, specific genes were identified in these cutaneous species, and taxonomic
reclassification was therefore proposed in which Propionibacterium acnes was renamed Cutibacterium acnes. This new
name differentiates it from other environmental Propionibacteria species, including those present in dairy products and
cattle rumen. So, since 2016, Propionibacterium species living on skin changed their denomination to Cutibacterium.
The names in standard use are Cutibacterium acnes, Cutibacterium avidum, Cutibacterium granulosum, Cutibacterium
namnetense and Cutibacterium humerusii. C. acnes strains also have been classified into several subtypes, currently, it is
subdivided into six main phylotypes: IA1, IA2, IB, IC, II and III. Cutibacterium species are well known as a commensal
belonging to the healthy skin microbiota but also as an opportunistic pathogen mainly involved in skin inflammatory
diseases related to dysbiosis and implant associated infections. Other species from this genus such as Cutibacterium
avidum are mostly found in moist environment, Cutibacterium granulosum is generally found in dry area and the two
most recently described, Cutibacterium humerusii and Cutibacterium namnetense, exhibit dissimilar ecologies in terms
of topography (dry, moist or sebaceous environments) and pathogenic power.
C. acnes, a common skin organism, is most notably recognized for its role in acne vulgaris. C. acnes is also found in other
tissues such as intestine, stomach, lungs, mouth, conjunctiva, prostate and urinary tract. It also causes postoperative and
device-related infections and has been associated with a number of other conditions such as sarcoidosis and synovitis,
acne, pustulosis, hyperostosis and osteitis (SAPHO), progressive macular hypomelanosis (PMH), although its precise
role as a causative agent remains to be determined. C. acnes produces a number of virulence factors and is well known
for its inflammatory and immunomodulatory properties. On the skin surface, the microbial community is mostly
constituted by bacteria belonging to the three main genera of Corynebacteria, Propionibacteria and Staphylococci.
Interplay between members of this cutaneous microbiota is essential for the maintenance of a healthy skin. While the
commensal bacterium C. acnes, predominant in sebaceous sites, is critical in the regulation of skin homeostasis and
prevents colonization from other harmful pathogens, it can also act as an opportunistic pathogen in acne vulgaris. New
findings on C. acnes reveal that, contrary to what was previously thought, its proliferation is not the trigger of acne but
instead, a tight equilibrium between members of the skin flora and among C. acnes phylotypes might play a more critical
role in acne onset. Loss of the skin microbial diversity together with the activation of the innate immunity might lead
to this chronic inflammatory condition. Analyses showed that the load of C. acnes is similar among patients with acne
and healthy individuals (87%–89%). Two major studies previously decrypted skin microbiota in acne context. These
studies both showed that no clear difference was observed in C. acnes abundance between healthy and acne individuals,
whereas recent evidence highlighted a loss of C. acnes subgroups diversity in severe acne. Changes in physiological
conditions may lead to an imbalance between the different skin community members, called dysbiosis, and eventually
to the selection of more pathogenic C. acnes strains. Acne might be triggered by the selection of a subset of C. acnes
strains, including the acne-associated phylotype IA1. Biofilm formation and differences in virulence and inflammatory
potential of C. acnes strains might enhance their pathogenicity.
In conclusion, after being underestimated and almost in variably considered as a contaminant of samples, C. acnes
has been shown over the last decade to play a significant role, via its various subgroups, in several skin disorders. The
development of new methods has revealed C. acnes not just as a commensal bacterium but also as an organism involved
in various types of inflammatory dermatoses.

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References
1. Platsidaki, Eftychia, and Clio Dessinioti. “Recent advances in understanding Propionibacterium acnes (Cutibacterium
acnes) in acne.” F1000Research 7 (2018).
2. Perry, A. L., and P. A. Lambert. “Propionibacterium acnes.” Letters in Applied Microbiology 42.3 (2006): 185-188.
3. Scholz, Christian FP, and Mogens Kilian. “The natural history of cutaneous propionibacteria, and reclassification of
selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov.,
Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov.” International journal of systematic and evolutionary
microbiology 66.11 (2016): 4422-4432.
4. Corvec, Stéphane, et al. “Taxonomy and phylogeny of Cutibacterium (formerly Propionibacterium) acnes in
inflammatory skin diseases.” Annales de Dermatologie et de Vénéréologie. Vol. 146. No. 1. Elsevier Masson, 2019.
5. Dagnelie, M-A., et al. “Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process.”
Journal of the European Academy of Dermatology and Venereology 33.12 (2019): 2340-2348.
6. Dréno, Brigitte, et al. “Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest
updates.” Journal of the European Academy of Dermatology and Venereology 32 (2018): 5-14.
7. Tan, Jerry KL, et al. “Current concepts in acne pathogenesis: pathways to inflammation.” Seminars in cutaneous
medicine and surgery. Vol. 37. No. 3S. 2018.
8. Dagnelie, Marie-Ange, et al. “Inflammatory skin is associated with changes in the skin microbiota composition on the
back of severe acne patients.” Experimental dermatology 28.8 (2019): 961-967.
9. Inoue, Yumiko, and Yuichi Teraki. “Association of Propionibacterium acnes with the efficacy of minocycline therapy
for cutaneous sarcoidosis.” International journal of dermatology 59.6 (2020): 704-708.
10. McDowell, Andrew, Joseph McLaughlin, and Alison M. Layton. “Is Cutibacterium (previously Propionibacterium)
acnes a potential pathogenic factor in the aetiology of the skin disease progressive macular hypomelanosis?.” Journal of
the European Academy of Dermatology and Venereology (2020).

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 IGF IN DERMATOLOGY
Ufuk Kavuzlu

Insulin-like growth factor (IGF) is a hormon with an insulin-like structure. IGF-1 and IGF-2 are proteins that play
role in growth and also mediate some of effects of growth hormone. (1,2) There are various studies examining the
effects of insulin-like growth factor on some dermatological diseases such as acne, alopecia or acrochordon. (2,3,4) This
presentation summarizes role of IGF in dermatology

References:
1. Farag AGA, Abdu Allah AMK, El-Rebey HS, et al. Role of insulin-like growth factor-1 in skin tags: a clinical, genetic
and immunohistochemical study in a sample of Egyptian patients. Clin Cosmet Investig Dermatol. 2019;12:255-266.
2. Köseoğlu HG, Bozca BC, Başsorgun Cİ, Sarı R, Akbaş SH, Karakaş AA. The role of insulin-like growth factor in
Acrochordon Etiopathology. BMC Dermatol. 2020;20(1):14.
3. Trüeb RM. Further Clinical Evidence for the Effect of IGF-1 on Hair Growth and Alopecia. Skin Appendage Disord.
2018;4(2):90-95.
4. El-Tahlawi S, Ezzat Mohammad N, Mohamed El-Amir A, Sayed Mohamed H. Survivin and insulin-like growth
factor-I: potential role in the pathogenesis of acne and post-acne scar. Scars Burn Heal. 2019;5:2059513118818031.

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 GHRELIN IN DERMATOLOGY
Ufuk Kavuzlu

Ghrelin is a 28-aminoacid lipopeptide hormone secreted mainly from the stomach. (1,2). Ghrelin has antiinflammatory
activities due to its effect on T cells and monocytes. (2,3) It increases appetite and stimulates fat storage. Ghrelin levels
are low in obese patients. (3) There are some studies researching the relationship between serum ghrelin levels and some
skin diseases such as psoriasis and acne. (2,4) This presentation summarizes role of ghrelin in dermatology.

References:
1. Erden I, Ucak H, Demir B et al. Serum ghrelin levels in patients with Behcet’s disease. Postepy Dermatol Alergol.
2016 Dec; 33(6): 450-456.
2. Ucak H, Demir B, Cicek D et al. Metabolic Changes and Serum Ghrelin Level in Patients with Psoriasis. Dermatol
Res Pract. 2014;2014: 175693.
3. Pektas SD, Cinar N, Duman DD et al. The relationship among androgens, insulin resistance and ghrelin polymorphisms
in post-adolescent male patients with severe acne vulgaris. Postepy Dermatol Alergol. 2020 Oct; 37(5): 800-809.
4. Kanat Z, Kökçam İ, Yılmaz M, Aydın S, Özkan Z. Serum ghrelin and obestatin levels in patients with acne vulgaris:
are they important for the severity?. Postepy Dermatol Alergol. 2019;36(4):412-418.

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 ULTRASTRUCTURAL AND HISTOPATHOLOGICAL CHANGES AFTER COSMETIC
PROCEDURES IN HUMANS
Özge Aşkın
İstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, Türkiye

ABSTRACT
Cosmetic procedures such as fillers, botulinum toxin, lasers, microneedling, mesotherapy / PRP and radiofrequency
cause various structural and histopathological changes in the human body. The purpose of this presentation is to show
the effect of the mechanisms of cosmetic procedures and the changes they cause especially in the face.
Fillers show different effects according to their content and are metabolized in the body in different ways. For example;
hyaluronic acid modifies the organization of the actin cytoskeleton, influencing fibroblast shape and orientation, poli-
L-lactic acid increases fibroblast activity and stimulates collagen synthesis and calcium hydroxylapatite increases in
histiocytes and associated fibroblasts appears to anchor down the microspherules as well as to induce new collagen
formation as the aqueous gel is metabolized.1,2
Botulinum toxin causes distortion in muscle fibers, shortening of sarcomeres, disruption of the triad structure in tubules
and mitochondrial degeneration.3
CO2 laser therapy was confirmed by significant histological improvement in the form of significant decrease in number
of melanocytes, reduction in the degree of epidermal hyperpigmentation, decrease in number of melanophages and
decrease in dermal perivascular edema. Fractional laser therapy also causes a decrease in the number of melanocytes.4
According to the studies, although mesotherapy does not cause a significant histological and structural change in the
human body, PRP causes thickening in the reticular dermis and an increase in collagen and elastic fibers with an increase
in the number of active fibroblasts.5,6
Microneedling increases in the mean of collagen types I, III, and VII through secondary fibroblast proliferation.7
Radiofrequency causes instant collagen denaturation and subsequent new collagen formation with the effect of heat.8
Knowing how cosmetic procedures work and what kind of changes they cause allow us to have a better understanding
of the procedure.
References:
1. Cabral LRB, Teixeira LN, Gimenez RP, Demasi APD, de Brito Junior RB, de Araújo VC, Martinez EF. Effect of
Hyaluronic Acid and Poly-L-Lactic Acid Dermal Fillers on Collagen Synthesis: An in vitro and in vivo Study. Clin
Cosmet Investig Dermatol. 2020 Sep 29;13:701-710.
2. Marmur ES, Phelps R, Goldberg DJ. Clinical, histologic and electron microscopic findings after injection of a calcium
hydroxylapatite filler. J Cosmet Laser Ther. 2004 Dec;6(4):223-6.
3. Ma F, Zhai Z, Zhu S, Tang S. Ultrastructural changes in human masseter muscles after botulinum neurotoxin a
injection. Muscle Nerve. 2018 Jan;57(1):96-99.
4. El-Sinbawy ZG, Abdelnabi NM, Sarhan NE, Elgarhy LH. Clinical & ultrastructural evaluation of the effect of
fractional CO2 laser on facial melasma. Ultrastruct Pathol. 2019;43(4-5):135-144.
5. El-Domyati M, El-Ammawi TS, Moawad O, El-Fakahany H, Medhat W, Mahoney MG, Uitto J. Efficacy of mesotherapy
in facial rejuvenation: a histological and immunohistochemical evaluation. Int J Dermatol. 2012 Aug;51(8):913-9
6. Charles-de-Sá L, Gontijo-de-Amorim N, Sbarbati A, Benati D, Bernardi P, Borojevic R, Carias RBV, Rigotti G.
Photoaging Skin Therapy with PRP and ADSC: A Comparative Study. Stem Cells Int. 2020 Jul 16;2020:2032359.
7. El-Domyati M, Barakat M, Awad S, Medhat W, El-Fakahany H, Farag H. Microneedling Therapy for Atrophic Acne
Scars: An Objective Evaluation. J Clin Aesthet Dermatol. 2015 Jul;8(7):36-42.
8. Bonjorno AR, Gomes TB, Pereira MC, de Carvalho CM, Gabardo MCL, Kaizer MR, Zielak JC. Radiofrequency
therapy in esthetic dermatology: A review of clinical evidences. J Cosmet Dermatol. 2020 Feb;19(2):278-281.

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 MICROCHIMERISM AND SKIN DISEASES
Ahmet Metin
Ankara Yıldırım Beyazıt University Medical Faculty, Department of Dermatology and Venereology, Turkey

In Greek mythology, the chimera was a monstrous, fire breathing,

female creature with the body of a lioness, a tail that terminated in a
snake’s head and the head of a goat that protruded from the center of
its spine (Figure1).1
Today, the term is used to describe real-life entities that arise or are
created as amalgams of previously separate entities in fields such as
botany, genetics and molecular biology.2 The term chimerism was first
used by Liegeois et al. in the 1970s.3 In genetics, microchimerism (Mc)
is defined by the presence within an individual of a low level of cells or
DNA derived from a genetically different individual. Yani, Chimera is a
single organism that is made up of two or more different populations of
genetically distinct cells that originated from different zygotes involved
in sexual reproduction.4 Chimeras are formed from at least four parent
cells (two fertilized eggs or early embryos fused together). Each
population of cells retains its own character and the resulting organism
has a mixture of tissues.

There are two possible causes of microchimeric cells, natural and artificial.
Pregnancy, miscarriage, twinning and sexual intercourse are natural, organ-
tissue transplantation and blood transfusion are artificial causes. Among
various forms of chimerism and pregnancy is the most common and natural
cause (Figure 2). Fetal - maternal microchimerism occurs as a result of bi-
directional exchange of hematopoietic cells through the placenta during
pregnancy. It is now known that fetal-maternal microchimeric cells (F-MMcCs)
can pass through tissues and organs such as peripheral blood, bone marrow,
thymus, liver, lung, spleen, kidney, skin and brain. Therefore, we are all born as
microchimera and nobody is pure.5

It is assumed that fetal stem

cells that pass from the placenta
to the maternal circulation can
turn into various mature cells in the mother become active in time and
react to maternal antigens. Researchers have investigated the role of
microchimerism in some autoimmune diseases that primarily affect
women. Autoimmune diseases, which they find a relationship with
microchimerism, by detecting the fetal Y chromosomes that decades after
pregnancy, are shown in the picture.
Microchimerism has been investigated in different autoimmune disorders
such as GVHD, systemic sclerosis, systemic lupus erythematosus,
dermatomyositis, Sjogren’s yndrome autoimmune thyroid diseases,
primary biliary cirrhosis, and juvenile inflammatory myopathies.
While microchimeric cells sometimes help suppress tumor growth by assuming an immune surveillance role, sometimes,
they may act as cancer stem cells and contribute to the growth of tumors including squamous skin cell carcinoma.6

213
Identification of male fetal cells in maternal cesarean wounds that have healed after pregnancy suggests that fetal cells
migrate or proliferate locally to the site of damage, including maternal tissue repair, possibly in response to signals generated
by maternal skin injury during cesarean section.
Recent research data have demonstrated the promising role of microchimeric cells in maternal response to tissue
damage by differentiating many lineages. Therefore, a better understanding of fetal-maternal microchimerism can help
predict its effects on disease as well as more general women’s and children’s health problems.
Microchimerism has been investigated in lichen planus7,8, psoriasis9, alopecia areata10 and Behçet11 disease, apart from
autoimmune conditions; There was evidence that it may be associated with the last two diseases.
REFERENCES
1. Polejaeva I, Mitalipov S. Stem cell potency and the ability to contribute to chimeric organisms.
Reproduction 2013;145:R81-88.
2. Liegeois A, Escourrou J, Ouvre E, et al. Microchimerism: a stable state of low-ratio proliferation of
allogeneic bone marrow. Transplant Proc 1977;9:273-276.
3. Shrivastava S, Naik R, Suryawanshi H, et al. Microchimerism: A new concept. J Oral Maxillofac Pathol
2019;23:311.
4. Dierselhuis MP , Goulmy E. We are all born as microchimera. Chimerism 2014;4:18-19.
5. Sawicki JA. Fetal microchimerism and cancer. Cancer Res 2008;68:9567-9569.
6. Tanei R, Yokono H, Motoori T, et al. Microchimerism seems uninvolved in the pathogenesis of idiopathic
lichen planus. Dermatology 2000;201:373-374.
7. Weger W, Bauer M, Odell E, et al. Role of microchimerism in the pathogenesis of oral lichen planus. Exp
Dermatol 2006;15:125-129.
8. Niepieklo-Miniewska W, Baran W, Szepietowski JC, et al. Lack of detectable fetal microchimerism in
psoriasis vulgaris lesions and in non-affected skin in spite of its presence in peripheral blood CD34-
positive and CD34-negative cells. J EADV 2017;31:114-118.
9. Terzi E, Bulut B, Tursen U, et al. Microchimerism in alopecia areata. Int J Dermatol 2015;54:e448-452.
10. Alp R, Guney AU, Tursen U, et al. Microchimerism in Behcet’s disease. Int J Dermatol 2014;53:832-837.

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 MAS-RELATED G PROTEIN-COUPLED RECEPTOR X2 (MRGCRX2) AND ALLERGY
Kansu Büyükafşar
Department of Pharmacology, School of Medicine, Mersin University, Turkey

Allergy: Allergy is an abnormal reaction by the immune system in response to foreign substances called allergens. A
wide variety of substances can be allergic. Allergens cause the release of inflammatory substances via the high affinity
IgE receptors (FceRI) from mast cells upon activation.
Mast cells: Mast cells are long-lived mononuclear cells that reside in tissues near external surfaces, e.g., in skin or
mucosa, and thereby are among the first cells of the immune system (Galli et al., 2011; da Silva et al., 2014).). These cells
fulfill their tasks in innate and adaptive immune responses by secreting different kind of mediators including histamines
and various inflammatory and immunomodulatory substances (Galli et al., 2011). There are two populations of mast
cells are available. 1) Mucosal type, which is found predominantly at mucosal surfaces contain only tryptase (MCT). 2)
Connective tissue type, which contains tryptase, chymase, carboxypeptidase A and cathepsin G, (MCTC) located within
connective tissues including skin. Total tryptase level in blood is used as an indirect parameter of mast cell burden and
activation. Following activation, mast cell release both preformed mediators and newly synthesized compounds.
Mast Cell Activation and Degranulation: There are three activation mechanisms of mast cells:
1) IgE-dependent activation: Mast cells are activated through the crosslinking of antigen-specific IgE receptors
(FceRI), which causes the release of numerous mediators. In addition, these cells can also be activated by antibody-
independently in response to a range of cationic substances, which include peptides and amines such as substance P,
mast cell-degranulating peptide, neuropeptide Y, mastoparan, and compound 48/80, etc. (Bischoff, 2009).
2) Monomeric IgE-dependent activation: This has been taken place by binding of monomeric IgE to the high affinity
IgE receptor, even in the absence of cross-linking by allergens.
3) Non-immunological activation (e.g., through MRGPRX2): There are a huge number receptors on mast cell
membrane, which make these cells respond to a diverse range of stimuli, including via IgE-independent mechanisms.
Downstream pathways of each individual receptor are not fully understood but ultimately lead to MC degranulation
(Bischoff, 2009; Solinski et al., 2014).
MAS-Related G Protein–Coupled Receptors X (MRGPRX2): MRGPRX2 is a novel G protein-coupled receptor
activated by endogenous prodynorphin-derived peptides and opioid compounds (Lansu et al., 2017). MRGPRs are also
known as sensory neuron-specific receptors. MRGPR-encoding genes have been detected in mammals. The mammalian
family of MRGPR can be subdivided into nine separate subfamilies (A–H and X) being X is specific to primates
including humans, macaque, and rhesus monkey.

(Fredriksson et al., 2003;Katritch et al.,2013)

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Human Mas-related G protein-coupled receptor X2 binds promiscuously to structurally diverse peptides and small
molecules that tend to have basic properties (basic secretagogues), resulting in acute histamine-like adverse drug
reactions of injected therapeutic agents (Grimes et al., 2019). MRGPRX2 is the main receptor related to pseudo-allergic
reaction, which occurs quickly and can be life-threating. The MRGPRX2 subtype has several peptidergic ligands being
the most characterized ligand the cortistatin-14 peptide (Robas et al., 2003; Kamohara et al., 2005). This receptors
are widely expressed in the body, i.e., from primary sensory neurons to several brain areas, from mast cells to the
adrenal medulla (Kamohara et al., 2005). Apart from cortistatin-14, adrenomedullin has also been shown to activate
MRGPRX2 (Kamohara et al., 2005; Córdoba-Chacón et al., 2011). MRGPRX2 was also shown to be involved in mast
cell activation by a set of structurally similar, endogenous (Subramanian et al., 2016) or exogenous (Subramanian et
al., 2011). Substance P, somatostatin, mast cell degranulating peptide, neuropeptide Y, VIP, mastoparan and compound
48/80 etc have high affinity binding sites for MRGPRX2. This receptor is also activated by antimicrobial peptides such
as the cathelicidin, LL-37, human b-defensins, which can be released from epithelial cells in response to infectious
agents (Subramanian et al., 2011, 2016). Hence, MRGPRX2 can integrate paracrine input from various cell types by
detecting alterations of the local milieu and inducing mast cell degranulation. MRGPRX2-mediated responses seem to
be more rapid, but transient in comparison to IgE-triggered events.
MRGPRX2 is closely related to pseudo-allergic reactions, which are adverse, non-immunologic, anaphylaxis-like sudden
onset reactions that are mediated through an IgE-independent pathway. These reactions are hypersensitivity reactions
mediated via a non-IgE-dependent mechanism, thus, they do not require prior exposure to the sensitization process
of antigens, causing mast cell degranulation directly. G protein-coupled receptors (GPCRs) are seven transmembrane
domain receptors that convert extracellular signals into biological responses. MRGPRX2 is a newly discovered
MRGPRX family member that, can be activated by a diverse range of basic ligands, leading to non-immunologically
induced mast cell degranulation (Subramanian et al., 2011, 2016; Bischoff, 2009). At present, only few drugs are
available to treat allergy conditions and symptoms. The available clinical drugs mostly inhibit the downstream effectors
of anaphylaxis. Some medicines, such as immune suppressors, mast cell stabilizers, and antihistamine drugs, can only
alleviate suffering as a result of anaphylaxis and help relieve allergic symptoms. Furthermore, these medicines have
a number of adverse reactions. Among the antibody-independent substances that can uniquely activate mast cells are
a number of cationic amphiphilic substances. In addition to the prototypic compound 48/80, other cationic mast cell
activators include a variety of pharmacologic agents (tubocurarine, atracurium, icatibant, ciprofloxacin, and other
fluoroquinolone antibiotics), components of insect venom (e.g., mastoparan and kinins), antimicrobial peptides (eg, a-
and b-defensins and cathelicidins), secreted eosinophil products such as eosinophil peroxidase and major basic protein,
and neuropeptides (namely, substance P, vasoactive intestinal peptide, neuropeptide Y, somatostatin, and cortistatin)
(Olivera et al., 2018)
MRGPRX2-mediated mast cell degranulation depends on PTX-sensitive G proteins (Bischoff, 2009; Subramanian et
al., 2011). It has been demonstrated that MRGPRX2 activation by LL-37 or human b-defensin-3 involves two different
signaling cascades that act synergistically on degranulation. One is Gi/o-induced PKC activation, and the other is PTX-
insensitive pathway leading calcium influx and release from internal stores (Subramanian et al., 2011, 2016). Another
possible downstream signaling mechanism involves the activation of Rho-GTPases (Zang et al., 2020).
There is a cross-talk between sensory neurons and mast cells in that the neurons release a number of peptides such as
substance P, VIP, CGRP etc, which can lead to mast cell degranulation. So this neuron-to-mast cell signaling results
in neuroimmune interactions that eventually may contribute to chronic pain (Zuo et al., 2003). Since some basic
secretagogues e.g., substance P, vasoactive intestinal peptide (VIP) etc can be secreted by primary sensory neurons,
it is plausible to postulate that MRGPRX2 may also enhance neuron-to-mast cell signaling and hence resulting in
neuroimmune interactions. This has pharmacological relevance as mast cells contribute to chronic pain, so the inhibition
of such a paracrine signaling circuit would be an interesting approach for future analgesic therapy (Solinski et al., 2014).
The receptor that mediates above-mentioned interaction seems to be mostly MRGPRX2. Therefore, it can be postulated
that MRGPRX2 could be a target for pharmacological control of pain and itching (Solinski et al., 2014). Isoliquiritigenin
is a chalcone isolated from the roots and stems of Glycyrrhiza glabra, G. uralensis, and G. inflata. Liquiritigenin is used
in common foods as an alternative medicine, and its derivative-ISL is utilized as a food additive (Peng et al., 2015). This
compound inhibits IgE-independent allergy through the interaction with MRGPRX2 (Hou et al., 2018).

216
MRGPCRX2 Activators: There are a number of activators of MRGPRX2 with a diverse chemical structure. The
following are the agents demonstrated to cause pseudoallergic reactions so far through the activation of MRGPRX2.
However, number of this list is likely to be expanded over time due to its promiscuity.
Cortistatin-14
Somatostatin, substance P, VIP
PAMP(9-20), PAF, PACAP
Neuropeptide Y
Cathelicidin, b-defensin
Mast-cell degranulating peptide
Mastoparan (component of hymenoptera venom)
GnRH analogues (cetrorelix, leuprolide, sermorelin)
Angiotensin-converting enzyme inhibitors (ACEIs)
Certain antibiotics such as fluoroquinolons (e.g., ciprofloxacin)
Neuromuscular blocking agents (NMBAs)
Opioids, antipsychotics phenothiazines
Thimerosal
Icatibant
Octreotide
Inhibitors of MRGPRX2-mediated mast cell degranulation: Some compounds may inhibit mast cell degranulation
through the inhibition of MRGPRX2 either directly or the signal transduction mechanism downstream of the receptor
activation as follows:
Shikonin and paeoniflorin (Chinese herb-derived compounds), (Wang et al., 2020)
Piperine (a long pepper-derived alkaloid), quercetin (plant-derived flavonoid) and saikosaponin A (one of the major
active compounds inRadix bupleuri) (Ding et al., 2019; Wang et al., 2018)
Tripeptide, QWF (glutaminyl-D-tryptophylphenylalanine)
Roxithromycin (Zang et al., 2020)
Isoliquiritigenin (Hou et al., 2018)

References
1. Bischoff SC (2009). Physiological and pathophysiological functions of intestinal mast cells. Semin Immunopathol.
31(2):185-205.
2. Córdoba-Chacón J, Gahete MD, Pozo-Salas AI,Martínez-Fuentes AJ, de Lecea L, Gracia-Navarro F, Kineman RD,
Castaño JP, Luque RM (2011). Cortistatin is not a somatostatin analogue but stimulates prolactin release and Inhibits
GH and ACTH in a gender-dependent fashion: Potential role of ghrelin. Endocrinology. 152(12): 4800–4812.
3. da Silva EZM, Jamur MC, Oliver C (2014). Mast cell function, a new vision of an old cell. J Histochem Cytochem.
62(10): 698–738.
4. Ding Y, Che D, Li C, Cao J, Wang J, Ma P, Zhao T, An H, Zhang T (2019). Quercetin inhibits Mrgprx2-induced
pseudo-allergic reaction via PLCγ-IP3R related Ca2+ fluctuations. Int Immunopharmacol. 66:185-197.

217
5. Fredriksson R, Lagerström MC, Lundin LG, and Schiöth HB (2003) The G-protein-coupled receptors in the
human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol
63:1256–1272.
6. Galli SJ, Borregaard N, Wynn TA (2011). Phenotypic and functional plasticity of cells of innate immunity:
macrophages, mast cells and neutrophils. Nat Immunol 12(11):1035-1044.
7. Grimes J, Desai S, Charter NW, Lodge J, Santos RM, Isidro-Llobet A, Mason AM, Wu Z, Wolfe LA, Anantharaman
L, Green A, Bridges AM, Wilk DAD, Brown AJ. MrgX2 is a promiscuous receptor for basic peptides causing mast
cell pseudo-allergic and anaphylactoid reactions. Pharmacol Res Perspect. 2019;00:e00547.
8. Hou Y, Che D, Ma P, Zhao T, Zeng Y, Wang N. Anti-pseudo-allergy effect of isoliquiritigenin is MRGPRX2-
dependent. Immunol Lett. 2018;198:52-59.
9. Kamohara M, Matsuo A, Takasaki J,Kohda M. Matsumoto M, Matsumoto S, Soga T, Hiyama H, Kobori M, Katou M
(2005). Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides.
Biochem Biophys Res Commun;330(4):1146-1152.
10. Katritch V, Cherezov V, and Stevens RC (2013). Structure-function of the G protein coupled receptor superfamily.
Annu Rev Pharmacol Toxicol 53:531–556.
11. Lansu K, Karpiak J, Liu J, ,Huang XP, McCorvy JD, Kroeze WK, Che T, Nagase H, Carroll FI, Jian Jin J, Shoichet
BK, Roth BL (2017). In silico design of novel probes for the atypical opioid receptor MRGPRX2. Nat Chem Biol.
13(5):529-536.
12. Olivera A, Beaven MA, Metcalfe DD (2018). Mast cells signal their importance in health and disease. J Allergy Clin
Immunol 142:381-393.
13. Peng F, Du Q, Peng C, Wang N, Tang H, Xie X, Shen J, Chen (2015). A Review: The Pharmacology of Isoliquiritigenin.
J. Phytother Res. 29(7):969-977.
14. Robas N, Mead E, Fidock M (2003). MrgX2 Is a High Potency Cortistatin Receptor Expressed in Dorsal Root
Ganglion. J Biol Chem 278(45):44400-44404.
15. Solinski HS, Gudermann T, Breit A (2014). Pharmacology and signaling of MAS-related G protein–coupled
receptors, Pharmacol Rev 66:570–597.
16. Subramanian H, Gupta K, Ali, H (2016). Roles of MAS-related G protein coupled receptor-X2 (MRGPRX2) on
mast cell-mediated host defense, pseudoallergic drug reactions and chronic inflammatory diseases. J Allergy Clin
Immunol. 138(3): 700–710.
17. Subramanian H, Kashem SW, Collington SJ, Qu H, Lambris JD, Ali H (2011). PMX-53 as a dual CD88 antagonist
and an agonist for mas-related gene 2 (MrgX2) in human mast cells. Mol Pharmacol. 79(6): 1005–1013.
18. Wang J, Zhang Y, Li C, Ding Y, Hu S, An H (2020). Inhibitory function of Shikonin on MRGPRX2-mediated
pseudo-allergic reactions induced by the secretagogue. Phytomedicine, 68:153149.
19. Wang N, Che D, Zhang T, Liu R, Cao J, Wang J, Zhao T, Ma P, Dong X, He L (2018). Saikosaponin A inhibits
compound 48/80-induced pseudo-allergy via the Mrgprx2 pathway in vitro and in vivo. Biochem Pharmacol. 2018
148:147-154.
20. Voisin T, Bouvier A, Chiu IM (2017). Neuro-immune interactions in allergic diseases: novel targets for therapeutics
International Immunology, Vol. 29, No. 6, pp. 247–261
21. Zuo Y, Perkins NM, Tracey DJ, Geczy CL (2003). Inflammation and hyperalgesia induced by nerve injury in the rat:
a key role of mast cells. Pain. 105(3):467-479.

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 HEALING PLANTS FOR SKIN DISEASES
Erdem Yesilada
Yeditepe University, Faculty of Pharmacy, Ataşehir, Istanbul, Turkey

Scientific studies have shown that phytochemicals with antioxidant, anti-inflammatory and antimicrobial activities are
common in herbal medicinal products (HMP). Therefore, plant-based products, i.e., plant extracts or phytochemicals etc.
are used for thousands of years in dermatology, including wound healing, inflammatory skin problems, skin infections,
and beauty products, i.e., against hyperpigmentation or sunburns and antiageing, etc.
Among the HMP in dermatology flowering aerial parts St.John’s wort (Hypericum perforatum) has a unique place. Its
naphthodianthrone type components “hypericin, pseudohypericin” in oily extract have been shown to act as a potent
wound healing by increasing the collagen synthesis, fibroblast migration and infection resistance anti-inflammatory
activity. Therefore St.John’s wort oily extract is popularly used to reduce the healing period as well as scar in wounds
and even in decubitis ulcers.
Carotenoids and triterpene alcohols in dried flowers of Marigold (Calendula officinalis or C. arvensis), flavonoids and
volatile components in flowers of German chamomile (Matricaria recutita), sesquiterpene lactones in dried flowers
of Arnica (Arnica montana), triterpene saponins in the aerial parts of Centella (Centella asiatica) and seeds of Horse
chestnut (Aesculus hippocastanum) are the other popular wound healing HMPs.
Licorice roots (Glycyrrhiza glabra) also rich in triterpene saponins; glycyrrhizin, glycyrrhetinic acid. These components
are shown to be effective in atopic dermatitis, inflammatory dermatosis and recurrent aphthous stomatitis. Recent
investigations have shown that another group of components in the roots “prenylated isoflavonoids,” i.e. glabridin,
“chalcones,” i.e. isoliquiritigenin to possess tyrosinase inhibitory activity and these have been formulated against
hyperpigmentation.
Aloe gel is the jelly part in the middle part of Aloe vera leaves which is composed of polysaccharides. Aloe gel finds a
widespread application in various dermatological problems; burns, wounds, skin inflammations, skin ulcers, aphthous
wounds and also reported to increase the skin absorption rate of the chemical agents such as hydrocortisone.
Evening primrose oil, is obtained from the seeds of Oenothera biensis. Due to its rich Gamma-linolenic acid composition,
it has been prescribed against atopic dermatitis to reduce symptom scores (pruritus, cortication, size) and increase
recovery period.
Psoriasis is another severe dermatological problem with limited treatment options. Several HMP have been reported
to reduce the disease symptoms. Among these, liposomal Turmeric rhizome (Curcuma longa) extracts (Meriva) was
shown to increase filaggrin and involucrin levels and reduce phosphorylase kinase and proinflammatory cytokines
(IL-17, TNF-α). Another possible beneficial HMP is Olibanum (Boswellia serrata) resin. Its active triterpenic acid
component 3-acetyl-11-keto-beta-boswellic acid (AKBA) has shown to reduce the “psoriasis area severity index”
(PASI) significantly on 12-week external application by inhibition of PGE2, VEGF, TNF-α and LTN-B4. St.John’s wort
oil has also been shown to reduce the PASI by its anti-inflammatory activity as well as by reducing the cell proliferation,
TNFα expression and increasing the calcium influx, TRPC6 expression and cell differentiation.
For skin infections essential oils have been shown to possess a good antibacterial, antifungal and antiviral potentials.
Particularly 1,8-cineol (Eucalyptus, Sage, Teatree oils), eugenol (clove oil), thymol/carvacrol (thyme, oregano oils) and
bisabolol (German chamomile oil).
As conclusion, a wide range of plant metabolites, phenolics, flavonoids, procyanidins, triterpenes, volatile oils,
polysaccharides, as well as essential oils or fatty oils are used in dermatology for various skin problems. Their activity
profiles and mechanisms of actions are proven by detailed experimental and clinical investigations.

219
References
1. Antiga, E., et al., Oral Curcumin (Meriva) Is effective as an Adjuvant Treatment and Is able to Reduce IL-22 Serum
Levels in Patients with Psoriasis Vulgaris. BioMed Res. Int. 2015; 283634.
2. Jirawattanapong W, et al. Synthesis of glabridin derivatives as tyrosinase inhibitors. Arch Pharm Res. 2009; 32:647–
654.
3. Khorasani G. Aloe versus silver sulfadiazine creams for second-degree burns: a randomized controlled study. Surg
Today, 2009;39(7):587-91
4. Lavagna, S. M. et al. 2001. Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical
wounds in childbirth with caesarean section. Farmaco 56: 451–453.
5. Leuner, K., et al. Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired
differentiation and enhanced proliferation. PLoS ONE 2011; 6, e14716.
6. Mansouri, P., et al. The impact of topical Saint John’s Wort (Hypericum perforatum) treatment on tissue tumor
necrosis factor-alpha levels in plaque-type psoriasis: A pilot study. J. Postgrad. Med. 2017; 63, 215–220.
7. Morse, N.L.; Clough, P.M. A meta-analysis of randomized, placebo-controlled clinical trials of Efamol evening
primrose oil in atopic eczema. Where do we go from here in light of more recent discoveries? Curr. Pharm.
Biotechnol. 2006; 7, 503–524.
8. Muhammed, M. et al. Clinical evaluation of AKBBA in the management of psoriasis. Clin. Dermatol. 2014; 2,
17–24.
9. Najafizadeh, P., et al. The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in
plaque type psoriasis vulgaris: A pilot study. Australas. J. Dermatol. 2012; 53, 131–135.
10. Nardo, V.D., et al., Use of Curcumin in Psoriasis. Open Access Maced. J. Med. Sci. 2018; 6, 218–220.
11. Süntar IP, et al. Investigations on the in vivo wound healing potential of Hypericum perforatum L. J Ethnopharmacol.
2010;127:468-77.
12. Yokota T, et al. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment
Cell Res. 1998; 11:355–361.
13. Yücel A, et al. Effect of St.John’s wort (Hypericum perforatum) oily extract for the care and treatment of pressure
sores; a case report. J Ethnopharmacol. 2017;196:236-241.

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 KETOGENIC DIET IN DERMATOLOGY
Emine Ünal

Ketogenic diet is a kind of diet program which contains very low carbohydrate, moderate protein and high fat diet
designed to induce hepatic production of ketone bodies as an alternative fuel source. There are several participants in
the world and raising its popularity day to day . This diets users says that it’s very good for health and has no side effect
for their body. With the increase of holistic medicine applications in the recent years, many medical doctors have been
recommending this diet to the patients(1-6). Moreover, there are no large-scale studies of the ketogenic diet, there is no
verified standardization in iniating and monitoring it. There are anecdotal methods (1).
The historical evidence shows us that the diet was offered by Hipoccrates as well. In early ancient times, physicians
gave the diet to their patients for epilepsy and other neurological system (1,2). Today, it is widely used in childhood
and adult epilepsy, Alzhiemer’s Dementia, Parkinson’s disease, brain and other cancers, Autism Spectrum Disorder.
Ketogenic diet and its effects are also investigated in inflammatory disorders, cardiovascular disease, management of
diabetes mellitus, metabolic diseases, and malignacy (3-5).
Some adverse effect have been reported. The only known absolute contraindications to a ketogenic diet are porphyria and
pyruvate carboxylase deficiency secondary to underlying metobolic disregularity. Metabolic cytooathies and carnitine
deficiency are relative contraindications. Possible side effects are dehydration, acidosis, hypoglycemia, dyslipidemia,
and electrolyte imbalance. These side effects are temporary and can be easily managed (5).
Ketogenic diet reduces IL-1 beta levels by suppressing NLPR3 inflammasome. This provides clinical improvement in
inflammatory conditions such as Behçet’s disease, hidradenitis supurativa, gout, sunburn, contact hypersensitivity, and
metastatic melanoma (1). Very-low-calorie balanced ketogenic diet results in fewer produced reactive oxygen species
(ROS) and provides an increase in the nicotinamide adenine dinucleotide ratio produced by the mitochondria, and with
this mechanism, cellular energy can be provided through the mitochondrial system. Another hypothesis is that the levels
of glutathione, a powerful antioxidant, increases in the body as a result of the ketogenic diet (1).
Other therapeutical effects are antioxidation effects, possible effects on mammalian target of rapamycin (mTOR)
regulation, and exploitation of the Warburg effect. It suggested that ketogenic diet may play improvement on disease
states through hormonal normalization, and improvement of metabolic risk factors (1).
There are no clear proven clinical results from the ketojenic diet in the dermatology. Further, other diets have shown
benefit for many other disesase and health promotion purposes (1).
In recent years, it has been accepted that acne vulgaris is a metabolic disease of sebaceous glands (6). It is known
that insulin resistance, obesity, type 2 diabetes, cancer and Alzheimer’s disease develop through the pathway of a
kinase termed mammalian target of rapamycin complex 1 (mTORC1). Acne vulgaris is also suggested to occur through
the same pathway (6). It is claimed that by regulating the mTOR pathway, it can heal diabetes, obesity and related
cardiovascular problems. A ketogenic diet results in very little insulin secretion. Ketons also have anti-inflammatory
effects by itself. Therefore, many clinicians have adopted the opinion that ketogenic diet should be given in addition to
medical treatments in acne patients (6).
The relationship between acne vulgaris and high carbonhydrate diet has been researched for years, but there are conflicted
publications. Mediterranean type is adopted if the diet stoppes the inflammation on acne vulgaris. Karadag and collegues
studied acne and they found a positive correlation with chocolate, bread, green tea, milk, white sugar, ripe banana,
ice cream, apple, orange, and red meat consumption. The authors suggested that there was statistically significant
relationship between acne severity and dietary factors such as chocolate, dairy products such as milk, sunflower seed
consumption within the geographical regions (7) .
In a study Castaldo and their collegues investigated the effects of ketogenic diet with stable chronic plak psroriasis.
They follow the obesity-psoriasis patient with only very-low-calorie ketogenic diet within 10 weeks. The authors
reported a significant decrease in PASI scores, a decrease in itching score, and an improvement in the Dermatology Life
Quality Index score with significant weight loss. They suggested that a balanced, hypocaloric, Mediterranean-like diet,
may be an effective first-line strategy to reduce psoriasis severity (8). At the same time, ketogenic diet is recommended

221
to obese psoriasis patients by Barret et al (9).
Another common condition we as dermatologists see is skin disease due to diabetes mellitus. Ketogenic diet is
recommended in the control of conditions such as bullosis diabeticorum, diabetic dermopathy, varicose ulcers, acanthosis
nigricans, pruritus, necrobiosis lipoidica diabeticorum. Improvement has been shown to be due to reduced glycation end
products and free radicals, increased insulin sensitivity, and decreased inflammation, along with low sugar entry into
the body (1).
Prurigo pigmentosa may occur after severe ketogenic diet. There have been many notifications in recent years. In this
case, the patients improved by adding carbohydrates to their diet (10). It is thought that ketosis was caused by fasting,
and that diet may contribute to the pathogenesis of prurigo pigmentosa. Clinicians should keep this situation in mind
and question it in the anamnesis.
There have been no large scale, randomized, controlled studies on the relationship between dermatological cancers and
the ketogenic diet yet. There are hypotheses that cancer cells do not and may not metabolize ketone. It is suggested that
adding this diet to the treatments can slow down cancer growth (1).
It is thought that the ketogenic diet will be beneficial in inflammatory skin diseases such as acne, psoriasis, allergic skin
reactions and drug-related photosensitivity as it decreases tissue inflammation, increases glutathione and reduces free
oxygen radicals (1).
It is known that intermittent fasting, coffee consumption, low level aerobic activity also puts the individual in a ketogenic
state.
Conclusion :
Ketogenic diet may be used in dermatology practice, such as acne and similar eruptions, psoriasis, seborrheic dermatitis,
pruritus. It can be given in addition to medical treatments as adjunctive, (safety, tolerable, low-cost ) treatment. It is
important to select appropriate patient.
Key words: ketogenic, skin , inflammation, dermatology and diet.

References
1- Fomin DA, Handfield K. The ketogenic diet and dermatology: a primer on current literature. Cutis. 2020 Jan;105(1):40-43.
2-Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012 Apr
9;3:59. doi: 10.3389/fphar.2012.00059.
3- Storoni M, Plant GT. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Mult Scler Int.
2015;2015:681289. doi: 10.1155/2015/681289. Epub 2015 Dec 29.
4-Yancy WS Jr, Foy M, Chalecki AM, Vernon MC, Westman EC. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr
Metab (Lond). 2005 Dec 1;2:34. doi: 10.1186/1743-7075-2-34.
5-Castellana M, Conte E, Cignarelli A, Perrini S, Giustina A, Giovanella L, Giorgino F, Trimboli P. Efficacy and safety of very low
calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis. Rev Endocr Metab
Disord. 2020 Mar;21(1):5-16. doi: 10.1007/s11154-019-09514-y.
6- Melnik BC. Acne vulgaris: The metabolic syndrome of the pilosebaceous
follicle. Clin Dermatol 2018; 36: 29-40.
7-Karadağ AS, Balta İ, Saricaoğlu H, Kiliç S, Kelekçi KH, et al. The effect of personal, familial, and environmental characteristics on
acne vulgaris: a prospective, multicenter, case controlled study. G Ital Dermatol Venereol. 2019 Apr;154(2):177-185. doi: 10.23736/
S0392-0488.17.05532-8. Epub 2017 Jul 11.
8-Castaldo G, Rastrelli L, Galdo G, Molettieri P, Rotondi Aufiero F, Cereda E. Aggressive weight-loss program with a ketogenic
induction phase for the treatment of chronic plaque psoriasis: A proof-of-concept, single-arm, open-label clinical trial. Nutrition.
2020 Jun;74:110757. doi: 10.1016/j.nut.2020.110757. Epub 2020 Feb 5.
9-Barrea L, Megna M, Cacciapuoti S, Frias-Toral E, Fabbrocini G, Savastano S, Colao A, Muscogiuri G. Very low-calorie ketogenic
diet (VLCKD) in patients with psoriasis and obesity: an update for dermatologists and nutritionists. Crit Rev Food Sci Nutr. 2020
Sep 24:1-17. doi: 10.1080/10408398.2020.1818053. Epub ahead of print.
10-Maco MW, Lee E, Wu Y, Lee R. Treatment of Prurigo Pigmentosa with Diet Modification: A Medical Case Study. Hawaii J Med
Public Health. 2018 May;77(5):114-117.

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 DO VITAMINS WORK FOR SKIN DISEASES?
Hilal Kaya Erdoğan
Surgery, Turkey

Vitamins are important constituents of diet and they are classified as water-soluble (B group and C) and fat-soluble (A,
D, E, K). They are essen¬tial for the maintenance of body and as well as skin functions. They play roles in skin health
by exerting different actions such as antioxidant activity, synthesis of collagen, regulation of sebum and keratinisation,
collagen synthesis, photoprotection and extracellular matrix homeostasis (1,2).
Vitamins are used in prevention and treatment of numerous dermatological diseases including skin cancers, atopic
dermatitis, psoriasis, alopecia, vitiligo, acne and photoaging. They can be used both topically or systemically (1,3-5).
Biotin, nicotinamide, folic acid, vitamin A, C, D and E are used in dermatology practice (3, 6). Especially the role
of vitamin D in dermatological diseases has a growing interest. Vitamin D supplementation is recommended in
psoriasis, atopic dermatitis, ichthyosis congenita, acne, hidradenitis suppurativa, vitiligo, systemic lupus erythematosus,
polymorphic light eruption, alopecia areata, melanoma and nonmelanoma skin cancers (7).
Supplementation of vitamins may also have some risks such as teratogenicity, interactions with drugs, allergic reactions,
and others. Physicians should warn patients on these risks (8).

References:
1-Noguera-Morel L, McLeish Schaefer S, Chad Hivnor CM. Nutritional Diseases. In: Bolognia JL, Schaffer JV, Cerroni
L, editor. Dermatology. 4th ed. China: Elsevier; 2018.
2- Pérez-Sánchez A, Barrajón-Catalán E, Herranz-López M, Micol V. Nutraceuticals for Skin Care: A Comprehensive
Review of Human Clinical Studies. Nutrients 2018;10(4):403.
3- Keller KL, Fenske NA. Uses of vitamins A, C, and E and related compounds in dermatology: a review. J Am Acad
Dermatol 1998;39:611-25.
4-Almohanna HM, Ahmed AA, Tsatalis JP, Tosti A. The Role of Vitamins and Minerals in Hair Loss: A Review. Dermatol
Ther (Heidelb) 2019;9(1):51-70.
5-Grimes PE, Nashawati R. The Role of Diet and Supplements in Vitiligo Management. Dermatol Clin 2017;35(2):235-
243.
6-Thompson KG, Kim N. Dietary supplements in dermatology: A review of the evidence for zinc, biotin, vitamin D,
nicotinamide, and Polypodium. J Am Acad Dermatol 2020:S0190-9622(20)30744-1.
7-Navarro-Triviño FJ, Arias-Santiago S, Gilaberte-Calzada Y. Vitamin D and the Skin: A Review for Dermatologists.
Actas Dermosifiliogr 2019;110:262-272..
8-Burns EK, Perez-Sanchez A, Katta R. Risks of Skin, Hair, and Nail Supplements. Dermatol Pract Concept
2020;10(4):e2020089.

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 DOES PHYTOTHERAPY REAL OR NOT FOR SKIN THERAPY?
Hatice Kaya Özden
Derince Training and Research Hospital, Department of Dermatology, Kocaeli, Turkey

Phytotherapy is a herbal treatment approach in which standardized pharmaceutical formulations (tablet, capsule,
cream etc.) which consist of medicinal plants and their active compounds (drugs) are employed in order to prevent
diseases or to support conventional medical treatment (1). It has been applied in dermatology for a long period of time.
However, there are very few scientific research of which clinical effects are proved through evidence-based methods on
phytotherapeutic agents.
Dermatologists to be the authority being consulted and giving exact information in the field is inevitable with regard
to avoiding potential complications; considering negative experiences of patients on dermatological diseases with a
chronic course, the faith of patients on complementary therapies, and their increasing demands.
Although phytotherapeutic agents are applied in the treatment of many dermatological diseases; hyperpigmentation,
vitiligo, psoriasis, acne vulgaris, and anogenital warts can be counted among dermatological entities supported by
evidence-based studies.
Several botanicals such as, flavonoids in silymarin, pycnogenol, soy extract, licorice suppress melanogenesis by inhibiting
reactive oxygen species formation and tyrosinase enzyme Botanicals most effectively treat acute forms and superficial
(epidermal) forms of hyperpigmentation. They obtain a very low level of efficiency in cases of post inflammatory
hyperpigmentation, drug-induced and dermal pigmentation (2).
In vitiligo cases, Polypodium leucotomos extract, a species of shield fern, with a content of such bioactive components
as phenolic acid, benzoate, cinnamate, and ferulic acid, reduces UV radiation-mediated oxidative DNA damage,
demonstrating antioxidant and immunomodulatory effect. It has been shown that whereas PLE stimulates repigmentation
of NB-UVB / PUVA combination, it also lowers the risk of side effects via photoprotective effect (3).
It has been indicated that %52.3 of psoriasis patients are not satisfied with existing treatment, and %51 of them turn to
complementary methods despite the lack of studies on their efficiency and reliability (4). In plaque psoriasis and psoriatic
nails, Indigo naturalis with indirubin as its active component has an antipsoriatic effect with the regulator of keratinocyte
proliferation and differentiation, and IL-17 inhibitor (5). Hyperforin, the major lipophilic active ingredient of St. John’s
wort (Hypericum perforatum (L.)), shows anti-inflammatory effects, and stimulates calcium influx into psoriasis
keratinocytes. It also activates TRPC6 expression, reduces cell proliferation, and promotes proper cell differentiation.
With the usage of 5% St. John’s wort extract, it has been reported that a significant recovery was observed in patients
with psoriasis, erythema, extension and the psoriatic plaques thickness (6).
Epigallocatechin gallate (EGCG) (Polyphenon E ointment), which is obtained from dried leaves of green tea (Camellia
sinensis L.) is the first herbal medicine to get approval in the treatment of condyloma acuminata. Its mechanism of action
is to reveal antiangiogenic activity suppressing vascular endothelial growth factor (VEGF) stimulated by TNF-a, and IL-
8-mediated inflammation (7). It has been shown that EGCG provides regression in inflammatory and noninflammatory
lesions, inhibiting Propionibacterium acnes’ activity increase, hyperseborrhea, and follicular dyskeratinization steps
involved in the pathogenesis of acne vulgaris (8).
Ingenol mebutate has an active component of macrocyclic diterpene ester which is found in Euphorbia peplus (milkweed).
It received approval of FDA in the cases of actinic keratosis on the face, scalp, body, and extremities. Its efficiency has
been shown by many randomized controlled studies (9). Ingenol mebutate is found on the market as the trading name of
Picato gel at a concentration of 0.015% and 0.05%. Its mechanism of action is not completely known. However, it has
been estimated that it operates via a kind of chemo-ablation, triggering direct and rapid cell death over sharp cytotoxic
and neutrophil-mediated inflammatory effect (10).

224
As a result, the usage of phytotherapeutic agents in the field of dermatology has gathered speed nowadays. Nevertheless,
it is not likely to come to a clear conclusion on its efficiency since it has been employed in different methodological
approaches, and active ingredients are not in similar concentrations and standardized formulations. Thus, phytotherapy
taking its place in dermatology can only be possible with trainings included in positive sciences, and enhancing the
knowledge and experience of medical attendants in terms of effects, side effects and its interaction with conventional
treatments, being supported by evidence-based studies.

References:
1.Reuter J, Merfort I, Schempp CM. Botanicals in dermatology: an evidence-based review. Am J Clin Dermatol.
2010;11(4):247-67.
2.Fisk WA, Agbai O, Lev-Tov HA, Sivamani RK. The use of botanically derived agents for hyperpigmentation: a
systematic review. J Am Acad Dermatol. 2014 Feb;70(2):352-65.
3.Middelkamp-Hup MA, Bos JD, Rius-Diaz F, et al. Treatment of vitiligo vulgaris with narrow-band UVB and oral
Polypodium leucotomos extract: a randomized double-blind placebo-controlled study. J Eur Acad Dermatol Venereol.
2007; 21:942-950.
4.Gamret AC, Price A, Fertig RM, Lev-Tov H, Nichols AJ. Complementary and Alternative Medicine Therapies for
Psoriasis: A Systematic Review. JAMA Dermatol. 2018;154(11):1330-1337.
5.Lin Y-K, Leu Y-L, Yang S-H, et al. Anti-psoriatic effects of indigo naturalis on the proliferation and differentiation of
keratinocytes with indirubin as the active component. J Dermatol Sci. 2009;54(3):168-174.
6.Najafizadeh P, Hashemian F, Mansouri P, Farshi S, Surmaghi MS, Chalangari R.The evaluation of the clinical effect of
topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study. Australas J Dermatol.
2012; 53(2):131-5.
7.Tatti S, Stockfleth E, Beutner KR, Tawfik H, Elsasser U, Weyrauch P, Mescheder A. Polyphenon E: a new treatment
for external anogenital warts. Br J Dermatol. 2010;162(1):176-84.
8.Yoon JY, Kwon HH, Min SU, Thiboutot DM, Suh DH. Epigallocatechin-3-gallate improves acne in humans by
modulating intracellular molecular targets and inhibiting P. acnes. J Invest Dermatol. 2013;133(2):429-40.
9. Anderson L, Schmieder GJ, Werschler WP, Tschen EH, Ling MR, Stough DB, Katsamas J. Randomized, double-
blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025 % and 0.05 % for actinic keratosis. J Am
Acad Dermatol 2009; 60: 934–43.
10. Siller G, Gebauer K, Welburn P, Katsamas J, et al. PEP005 (ingenol mebutate) gel, a novel agent for the treatment
of actinic keratosis: results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study. Australas J
Dermatol. 2009; 50:16–22

225
 INTEGRATIVE APPROACHES OF PSORIASIS AND PSORIATIC ARTHRITIS
Şule Ketenci Ertaş
Kayseri City Education and Research Hospital, Kayseri, Turkey

Psoriasis and psoriatic arthritis are immune-mediated diseases with skin and joint involvement, but not limited to these
areas. These diseases have an increased risk of cardiovascular and metabolic diseases.
Psoriatic arthritis (PsA) is a heterogeneous, erosive and systemic inflamatory disease. Main clinical domains are
peripheral and axial joints, enthesitis, dactylitis, skin and nails. Psoriatic arthritis (PsA) affects up to 30% of patients
with psoriasis.
The first complaint of psoriatic arthritis patients is mostly skin lesions, and dermatologists are the first physicians
who see these patients. It is important for dermatologists to refer patients with critical symptoms to the rheumatology
department in order to avoid delay in diagnosis.
There are lots of new therapies available for PsA. Basic treatment of PsA is NSAIDS and traditional disease-modifying
anti-rheumatic drugs (DMARDs). However, these treatments have not been shown to prevent radiographic progression.
For this purpose, anti-TNF agents are good choices. Other alternetive medications are oral phosphodiesterase 4 inhibitor,
apremilast; a Janus kinase (JAK) inhibitor, tofacitinib; and several new biologics that target the IL-23/IL-17 pathway
including secukinumab, brodalumab, ixekizumab, and ustekinumab.

References
1. Menter A. Psoriasis and psoriatic arthritis overview. Am J Manag Care. 2016 Jun;22(8 Suppl):s216-24. PMID:
27356193.
2. Raychaudhuri SP, Wilken R, Sukhov AC, Raychaudhuri SK, Maverakis E. Management of psoriatic arthritis: Early
diagnosis, monitoring of disease severity and cutting edge therapies. J Autoimmun. 2017 Jan;76:21-37. doi: 10.1016/j.
jaut.2016.10.009. Epub 2016 Nov 9. PMID: 27836567.
3. Gottlieb A, Merola JF. Psoriatic arthritis for dermatologists. J Dermatolog Treat. 2020 Nov;31(7):662-679. doi:
10.1080/09546634.2019.1605142. Epub 2019 May 7. PMID: 31014154.
4. Raychaudhuri SP, Wilken R, Sukhov AC, Raychaudhuri SK, Maverakis E. Management of psoriatic arthritis: Early
diagnosis, monitoring of disease severity and cutting edge therapies. J Autoimmun. 2017 Jan;76:21-37. doi: 10.1016/j.
jaut.2016.10.009. Epub 2016 Nov 9. PMID: 27836567.

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 MANAGEMENT APPROACH TO PSYCHOCUTANEOUS DISORDERS
Mohammad Jafferany
Clinical Professor, Central Michigan University College of Medicine, Saginaw, Michigan USA

Psychodermatology is a growing specialty which is gaining momentum in different parts of the world. It focuses on the
connection between skin and psyche. Psychocutaneous conditions are characterized by those disorders where stress is
the key element in exacerbating skin conditions or flare ups of dermatoses like psoriasis and atopic dermatitis. There
is a direct relationship of stress with the course, and prognosis of the skin disease. In some situations, there is no skin
condition but the lesions are self-inflicted and such disorders are always associated with underlying psychopathology
or psychological conflicts. Sometimes emotional problems are more prominent as a result of having skin disease and
the psychological consequences may be more severe than the physical symptoms. Management of these conditions
require a combination of psychpharmacology, psychotherapy and liaison clinics of psychiatry and dermatology.
This presentation focuses on the common management approach which can be adopted by deramtologists in treating
patients with psychodermatological disorders, improving doctor-patient relationship and therapeutic bond. An optimal
jnowledge of psychotropic medications and basic psychotherapeutic techniques is vital in the long term mnagement of
these patients.

References:
1. Jafferany, M, Ferreira, BR, Patel, A. (2020) The Essentials of Psychodermatology. Switzerland AG: Springer
International Publishing. p. 29-34
2. Tohid H, Shenefelt PD, Burney WA, Aqeel N. Psychodermatology: An Association of Primary Psychiatric Disorders
With Skin. Rev Colomb Psiquiatr 2019;48(1):50-57.
3. Reichenberg JS, Kroumpouzos G, Magid M.Approach to a Psychodermatology Patient. G Ital Dermatol Venereol
2018;153(4):494-496.
4. Jafferany M, Franca K. Psychodermatology: Basics Concepts. Acta Derm Venereol 2016;96(217):35-7.
5. Korabel H, Dudek D, Jaworek A, Wojas-Pelc A. Psychodermatology: psychological and psychiatrical aspects of
dermatology. Przegl Lek 2008; 65(5):244-8.
6. Tran A, Desir AK, Okafor LC, Jafferany M, Copes LE. Psychodermatology in Clinical Practice: An Examination of
Physician Attitudes, Beliefs and Interventions Towards Psychocutaneous Disease. Dermatol Ther 2020;e13612.
7. Picari A, Abeni D. Stressful life events and skin diseases: disentangling evidence from myth. Psychother Psychosom
2001; 70: 118–136.
8. Dhabhar FS. Psychological stress and immunoprotection vs. immunopathology in the skin. Clin Dermatol 2013; 31:
18–30.
9. Jafferany M, Salimi S, Mkhoyan R, Kalashnikova N, Sadoughifar R, Jorgaqi E. Psychological Aspects of Aesthetic
and Cosmetic Surgery: Clinical and Therapeutic Implications. Dermatol Ther 2020;e13727.
10. Hafi B, Uvais NA, Jafferany M, Afra TP, Muhammed RT. Palliative Psychodermatology Care During COVID-19
Pandemic. Dermatol Ther 2020;e13732.

227
 TATTOO AND PSYCHOLOGY
Ezgi Özkur
Şişli Etfal Education Research Hospital, Turkey

Tattoos have become increasingly popular in recent years .The possession of the oldest known tattoo belongs to Iceman
Ötzi who lived 5300 years ago and is recognized as the oldest mummy of the world. Tattoos are not just an ink, figure or
drawing on the body, but a tool for individuals to express themselves and to construct self-identity. They have symbolic
meanings for emotions and they may be a clue for individuals behavior patterns. Consequently, tattooing is a complex
practice and a subject of psychodermatology.

228
 PERSONALITY DISORDERS IN DERMATOLOGY
Mohammad Jafferany
Clinical Professor, Central Michigan University College of Medicine, Saginaw, Michigan USA

There is a significant psychiatric comorbidity that exists in multiple dermatological conditions, stemming from the
patient’s own psychological make up. Patient’s childhood experiences, family structure and family dynamics during
developmental years play a significant role on patient’s personality. This presentation focusses on personality disorders
and their types, which influence the course and prognosis of several psychodermatological disorders. Self-inflicted
skin lesions, for example, are usually associated with obsessive-compulsive behavior, but they also share connections to
Narcissistic and Borderline personality disorders. Body dysmorphic disorder is another psychodermatological condition
seen in dermatology, aesthetic, and cosmetic surgery clinics, which is influenced by patient’s personality type. In general,
there is a significantly high proportion of personality disorders seen in aesthetic and cosmetic surgery. The management
of patients with personality disorders is challenging, but joint liaison between psychiatry and dermatology has proven
helpful and can provide patients with the best care for their psychological needs and dermatologic care.

References:
1. Judith A. Bahmer, Julius Kuhl, and Friedrich A. Bahmer. How Do Personality Systems Interact in Patients With
Psoriasis, Atopic Dermatitis and Urticaria? Acta Derm Venereol 2007; 87: 317–324
2. Ehlers A, Osen A, Wenninger K, Gieler U. Atopic dermatitis and stress: possible role of negative communications
with significant others. Int J Behav Med 1994; 1: 107–121
3. Burr S, Gradwell C. The psychosocial aspects of skin-diseases: need for support groups. Br J Nurs 1996; 5: 1172–1182
4. Raikhy, S., Gautam, S., & Kanodia, S. Pattern and prevalence of psychiatric disorders among patients attending
dermatology OPD. Asian Journal of Psychiatry, 2017;29, 85–88.
5. Paris, J. Understanding Self-mutilation in Borderline Personality Disorder: Harvard Review of Psychiatry. 2005;
13(3), 179–185.

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 BULLOUS DISEASES
Ayşe Akman Karakaş
Akdeniz University School of Medicine Department of Dermatology and Venereology, Antalya, Turkey

Bullous skin diseases are a group of potentially life-threatening dermatoses include the clinical features are blisters,
bullae and erosion in the skin and mucous membranes (1). Bullous skin diseases can be divided into autoimmune and
non-autoimmune bullous skin (ABD) diseases (2, 3). Pemphigus and bullous pemphigoid (BP) are the most prevalent
ABD. Pemphigus encompasses a group of autoimmune intraepidermal blistering diseases classically divided into two
major variants: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Pemphigus herpetiformis, IgA pemphigus,
paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms. The pemphigoid group represents a group of
autoimmune disorders characterized by subepidermal blistering. This group includes mainly BP, linear IgA disease,
dermatitis herpetiformis, and epidermolysis bullosa acquisita. ABD run a chronic course and are associated with
significant morbidity and even mortality (2-5). In this lecture, treatment of bullous diseases will discussed with four
challenging cases, we have seen in our clinical experience.

References
1. Yang M, Wu H, Zhao M, Chang C, Lu Q.J. The pathogenesis f bullous skin diseases. Transl Autoimmun. 2019 Aug
26;2:100014.
2. Alpsoy E, Akman-Karakas A, Uzun S. Geographic variations in epidemiology of two autoimmune bullous diseases:
pemphigus and bullous pemphigoid. Arch Dermatol Res. 2015 May;307(4):291-8.
3. Daltaban Ö, Özçentik A, Akman Karakaş A, Üstün K, Hatipoğlu M, Uzun S. Clinical presentation and diagnostic
delay in pemphigus vulgaris: A prospective study from Turkey. J Oral Pathol Med. 2020 Aug;49(7):681-686.
4. Patel PM, Jones VA, Murray TN, Amber KT. A Review Comparing International Guidelines for the Management of
Bullous Pemphigoid, Pemphigoid Gestationis, Mucous Membrane Pemphigoid, and Epidermolysis Bullosa Acquisita.
Am J Clin Dermatol. 2020 Aug;21(4):557-565.
5. Kasperkiewicz M, Schmidt E, Fairley JA, Joly P, Payne AS, Yale ML, Zillikens D, Woodley DT. Expert recommendations
for the management of autoimmune bullous diseases during the COVID-19 pandemic. J Eur Acad Dermatol Venereol.
2020 Jul;34(7):e302-e303.

230
 VASCULITIS
Sibel Doğan Günaydın
Hacettepe University Faculty of Medicine, Department of Dermatology and Venereology, Immunology

Vasculitis (also called angitis) is a general term for several conditions that cause inflammation in blood vessels (1-3).
The type and size of the vessels involved are taken into consideration in the classification of vasculitis, Skin involvement
rarely develops in large vessel vasculitis and is seen as diffuse necrosis of the skin. Livedo reticularis, retiform purpura,
nodules, ulcers, infarcts and necrosis are observed in medium sized vessel vasculitis.. Palpable purpura, macular purpura
and urticarial papules are most commonly observed in small vessel vasculitis. Small and medium sized vessels are
involved in ANCA-associated vasulitis (AAV) and also small and medium-sized arterioles in the upper layers of the
skin and in the deeper subcutaneous tissues are involved in AAVs Therefore the clinical examination spectrum includes
findings related to vasculitic involvement of these vessels. (4). Palpable purpura is the most common cause of clinical
signs of small and medium vessel involvement in AAV. When evaluating a case with a suspicion of vasculitis for the
presence of palpable purpura, the patient should be assessed systemically, laboratory tests and ANCA tests should be
performed, biopsy and histopathological examination is required and additional skin sample should also be taken for direct
immune fluorescence analysis method that determines the accumulation of immune reactant /deposits. Additional studies
should be conducted for classification. (5-6). AAVs are classified as granulomatous polyangitis (GPA), microscopic
polyangitis (MPA) ve and eosinophilic granulomotosis with polyangitis (EGPA). This group of vasculitits is quite rare,
they involve various organ systems and cause severe systemic vasculitis. Skin involvement is a common finding in AAV,
it is approximately found in %47 of GPA, %44 of MPA and %40 in EGPA (1-3). Unlike immune complex vasculitis,
vascular damage develops directly in AAVs. Vascular damage is mediated by neutrophils, therefore AAVs are also called
“pauci-immune” vasculitis. The formation of ANCAs in this group of vasculitis also causes impairment in neutrophil
apoptosis resulting in a long-term opportunity for autoantibody development. Cutaneous symptoms are common and
variable in GPA, EGPA and MPA and 50% of the cases with skin involvement have more than one cutaneous symptom.
The most important and common cutaneous finding is petechiae and purpura and should be considered a sign of systemic
vasculitis. Cutaneous involvement is observed more frequently in EGPA and GPA than MPA and there is a significant
relationship between skin involvement and systemic involvement severity in these diseases. Skin involvement increases
the risk of systemic involvement of the disease. In EGPA and ANCA (-) patients, non-vasculitic skin findings such as
itching, urticaria, maculopapular rash can be observed. In this talk, a case with marginal zone lymphoma later diagnosed
with eosinophilic granulomotosis with polyangitis (EGPA) will be discussed.

References
1. Francès C, Du LT, Piette JC et al. Wegener’s granulomatosis: dermatological manifestations in 75 cases with
clinicopathologic correlation. Arch Dermatol 1994; 130: 861–7.
2. Kluger N , Pagnoux C, Guillevin L, FrancèsC. French Vasculitis Study Group. Comparison of cutaneous manifestations
in systemic polyarteritis nodosa and microscopic polyangiitis. Br J Dermatol 2008; 159: 615–20.
3. Comarmond C, Pagnoux C, Khellaf M et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical
characteristics and long-term follow up of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis
Rheum 2013; 65: 270–81.
4. Kitching AR, Anders HJ, Basu N et al. ANCA-associated vasculitis Nat Rev Dis Primers. 2020 Aug 27;6(1):71.
5. Ball GV, Fessler BJ, Bridges SL. Oxford Textbook of Vasculitis. 3rd Ed. Oxford University Press 2014: 64-75.
6. Wetter DA, Dutz JP, Shinkai K, Fox PL. Cutaneous Vasculitis. In: Bolognia JL, Jorizzo JL, Rapini RP (eds). Bolognia
Textboook of Dermatology. 4th Ed. Elsevier, 2018: 409-439.

231
 HOW CAN WE TREAT CHALLENGE CASES? PRURITUS
Esra Pancar Yuksel
Associate Professor of Dermatology, Ondokuz Mayis University, Faculty of Medicine, Samsun, Turkey

Pruritus is a difficult condition to treat with a significant effect on quality of life.1 Several diseases could be the cause of
pruritus such as atopic dermatitis, mycosis fungoides, bullous pemphigoid, scabies.
Atopic dermatitis is a chronic disorder characterized by intense itching and recurrent eczematous lesions. Although
it usually starts in infancy, senile onset atopic dermatitis is seen in patients older than 60 years old. Pruritus is the
dominating symptom of atopic dermatitis.2
Cutaneous T Cell Lymphomas are the most common primary cutaneous lymphomas and pruritus is frequent in these
patients. It is unrelieved by emollients or oral antihistamines. It interferes with sleep. Water could worsen the situation.
In the advanced stages, patients generally define a severe and diffuse pruritus that may resemble “burning pain”.3
Bullous pemphigoid is an autoimmune subepidermal blistering disorder, characteristically presents with tense bullae.
Intense generalized pruritus is reported by the patients and in atypical cases, pruritus could be the only sign of the disease
without bullous lesions. These cases require a high degree of clinical suspicion.4
Scabies is a common parasitic skin infestation characterized by severe pruritus. Scratching and encrustation could be
recognized. Pruritus is the prominent symptom of scabies and it is generally difficult to manage.5
When the patients’ complaint is only pruritus, it is going to be difficult to make the diagnosis. Many dermatological
conditions are included in the differential diagnosis for the pruritus and atopic dermatitis, mycosis fungoides, bullous
pemphigoid, scabies are the diseases among them. We should consider these diseases in differential diagnosis in patients
with pruritus. If we make the correct diagnosis, we can treat challenge cases.

References
1.Song J, Xian D, Yang L, Xiong X, Lai R, Zhong J. Pruritus: Progress toward Pathogenesis and Treatment. Biomed
Res Int. 2018
2.Kahremany S, Hofmann L, Harari M, Gruzman A, Cohen G. Pruritus in psoriasis and atopic dermatitis: current
treatments and new perspectives. Pharmacol Rep. 2021
3.Misery L.Pruritus in Cutaneous T-Cell Lymphomas.In: Carstens E, Akiyama T, editors. Itch: Mechanisms and
Treatment. Boca Raton (FL): CRC Press/Taylor & Francis; 2014. Chapter 8.
4.Miyamoto D, Santi CG, Aoki V, Maruta CW. Bullous pemphigoid. An Bras Dermatol. 2019 Mar-Apr;94(2):133-146.
5.Jannic A, Bernigaud C, Brenaut E, Chosidow O.Scabies Itch. Dermatol Clin. 2018;36(3):301-308.

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 HIGHLIGHTS OF THE CURRENT TOPICAL ANTIBIOTIC GUIDE IN INFECTION DISEASES
Göknur Kalkan
Department of Dermatology, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara, Turkey

Topical antibiotics are widely used in skin diseases and they have many indications. However, bacterial resistance has
developed against many antibiotics due to unnecessary use or long-term use in some diseases. This situation leads to the
development of resistance in bacterial colonization in the host as well as resistance in the treatment of diseases. In this
presentation, principles regarding the use of topical antibiotics in superficial skin infections are presented along with the
literature. As a dermatologist, our primary goal is to prevent antibiotic resistance with rational approaches by preventing
unnecessary use of drugs as well as the correct and adequate use of drugs for appropriate indications. Correct and
rational use of antibiotics is very important, as well as starting the patient in need on time, stopping the drug on time, and
deciding on which indication to be given topical and which systemic treatment is very important. In this presentation,
respectively, under the guidance of the current topical antibiotic guide; the principles of topical antibiotic use and
indications for systemic treatment in impetigo, ecthyma, folliculitis, furuncle, carbuncle, abscess, erysipelas, cellulitis,
paronychia, ingrown toenails and corynebacterium-associated skin infections will be discussed. Topical antibiotics
commonly used in superficial skin infections are; mupirocin, retapamulin 1% ointment; a new class of topical antibiotic,
effective against bacteria with multiple antibiotic resistance, fusidic acid; which has increased resistance rates due to its
widespread empirical use recently, oxytetracycline and polymyxin B combination, bacitracin and neomycin combination
and ozenoxacin cream. In cases where Gram-negative infections are predominant, topical gentamicin and nadifloxacin
are preferred. In addition, the use of topical clindamycin, erythromycin, mupirocin, fusidic acid and benzoyl peroxide
comes into prominence in clinical pictures such as erythrasma, pitted keratolysis and trichobacteriosis, which develop
under appropriate conditions depending on the corinobacterium species.

References:
1. Lio PA, Kaye ET. Topical antibacterial agents. Infect Dis Clin North Am. 2009 Dec; 23(4):945-63.
2. LB Pereira. Impetigo – review. An Bras Dermatol. 2014 Mar-Apr; 89(2): 293–299.
3. Hartman-Adams H, Banvard C, Juckett G. Impetigo: Diagnosis and treatment. Am Fam Physician. 2014 Aug;90(4):229–35.
4. Tognetti L, Martinelli C, Berti S, Hercogova J, Lotti T, Leoncini F, et al. Bacterial skin and soft tissue infections:
review of the epidemiology, microbiology, aetiopathogenesis and treatment: a collaboration between dermatologists and
infectivologists. J Eur Acad Dermatol Venereol. 2012 Aug;26(8):931-41.
5. Luelmo-Aguilar J, Santandreu MS. Folliculitis recognition and management. Am J Clin Dermatol. 2004; 5(5):301-10.
6. Troxell T, Hall CA. Carbuncle. In: StatPearls. Treasure Island (FL): StatPearls Publishing;2020 Jan–.2020 Feb 28.
7. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the
diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.
Clin İnfect Dis. 2014 Jul;59(2):147-59.
8. Blaise G, Nikkels AF, Hermanns-Lê T, Nikkels-Tassoudji N, Piérard GE. Corynebacterium-associated skin infections.
Int J Dermatol. 2008 Sep;47(9):884-90.
9. Holdiness MR. Management of cutaneous erythrasma. Drugs. 2002 Oct;62(8):1131-41.
10. Bristow IR, Lee YL. Pitted keratolysis: a clinical review. J Am Podiatr Med Assoc.2014 Mar;104(2):177-82.

233
 ORAL
PRESENTATIONS

234
OP-01 [Urticaria, Angioedema] diseases with low systemic inflammation.We could not find a
correlation between CRP and UAS7 scores in our patients.We
The Relationship Between Uric Acid Level and Disease thought that the reason we could not find a correlation with CRP
might be that we looked at the standard CRP level in the study.
Duration and Disease Activation in Patients with Chronic
Uric acid value was found to be significantly higher in CSU
Urticaria cases than in the control group.Again, we found that uric acid
Selami Aykut Temiz1, Koray Durmaz2, Arzu Ataseven3 level not correlated with the UAS7 score,but correlated with
1
Clinic of Dermatology, Konya Ereğli State Hospital, Konya, the increase in the duration of the disease.Our findings can
Turkey show that the increase in disease duration rather than disease
2
Clinic of Dermatology, Bilecik Bozüyük State Hospital, severity(UAS7) increases metabolic complications in CSU.
Bilecik, Turkey
3
Department of Dermatology, Necmettin Erbakan University
Keywords: Urticaria, uric acid, metabolic comorbidity, urticaria
Meram Medical Faculty, Konya, Turkey
activity score 7 (UAS-7)

Table 1
INTRODUCTION & OBJECTIVES: Chronic urticaria is
characterized by spontaneously appearing itchy wheals anywhere
Control
on the body.If autoantibodies or unknown causes induce CSU group p value
group
the disease,it is called chronic spontaneous urticaria(CSU).
Uric acid is a metabolic marker whose importance has been 35.53 ±
Age 35.54 ± 11.57 >0.05
better understood in recent years.It has been reported that 12.15
high uric acid levels are associated with metabolic syndrome. Gender, woman
33 (53.2%) 36 (%52.2) >0.05
Because high uric acid levels are an indicator of oxidative n(%)
stress and inflammation.In the current literature, uric acid has CRP (mg/L) 4.46 ± 5.57 1.98 ± 1.54 ˂0.001
never been studied in patients with chronic urticaria.It was
Uric acid (mg/dL) 4.95 ± 1.37 4.35 ± 0.99 0.015
aimed to evaluate the relationship between the level of uric acid
The comparison of the CSU and control group
and disease duration and urticaria activation score in chronic
urticaria patients.
OP-02 [Autoimmune Connective Tissue Disorders]
MATERIAL & METHODS: We prospectively selected patients
who admitted to the Dermatology outpatient clinic between
Macrophage Activation Syndrome Due to Juvenile
March 2020-January 2021 and did not use any medication
diagnosed with CSU.The necessary approval was obtained from Amyopathic Dermatomyositis with Atypical Onset
the local ethics committee. Esma Inan Yuksel1, Betul Demir1, Metin Kaya Gurgoze2, Ilknur
Calik3
RESULTS:Atotal of 131 participants,62 CSU and 69 controls,were 1
Department of Dermatology, Firat University Faculty of
evaluated in the study.33 of 62 chronic urticaria patients included
Medicine, Elazig, Turkey
in the study were female(53.2%),and 36(52.2%) of 69 control 2
Department of Pediatric Rheumatology, Firat University
group patients were female.The mean age was 35.53±12.15 in the
Faculty of Medicine, Elazig, Turkey
urticaria group and 35.54±11.57 in the control group.There was 3
Department of Pathology, Firat University Faculty of
no difference between the two groups in terms of age and gender.
Medicine, Elazig, Turkey
CRP values were 4.46±5.57mg/L in the CSU group and
1.98±1.54mg/L in the control group.CRP was statistically INTRODUCTION: Macrophage activation syndrome (MAS) is
significantly higher in the CSU group(p˂0.001).The mean a life-threatening condition associated with rheumatic diseases.
UAS7 score in CSU patients was found to be 20±8.8.There It has been rarely reported in juvenile dermatomyositis.
was no correlation between the UAS7 score and CRP(p=0.98). Whereas classic dermatomyositis usually presents as
The uric acid value was 4.95±1.37mg/dl in the CSU group classical skin findings accompanying myopathy, atypical
and 4.35±0.99mg/dl in the control group.Uric acid levels were onset and misdiagnosis are common in juvenile amyopathic
found to be significantly higher in the CSU group(p=0.015).In dermatomyositis (JADM), since skin lesions are generally
correlation analysis, there was no correlation between UAS7 more atypical than in adults, and myopathy is not observed.
score and uric acid increase(p=0.25).Disease duration in CSU Because of the atypical onset, we reported a case of eight-year-
patients was found to be 21±15.9 months.Uric acid levels were old girl with JADM misdiagnosed as psoriasis, and rapidly
correlated with the increase in disease duration(p=0.001).The progressed to MAS.
data of the CSU and control group are summarized in Table1.
CASE: A eight-year-old girl admitted to the pediatric
CONCLUSIONS: Urticaria is divided into two classes as acute and rheumatology outpatient clinic with joint swelling and
chronic(lasting more than 6 weeks).It is known to be associated psoriasiform plaques on the dorsal surfaces of her elbows.
systemic inflammation with CSU.It has been reported that high She was diagnosed with psoriatic arthritis, and methotrexate
sensitive CRP(hs-CRP) is a better marker than standard CRP in therapy was started. Three months later, the patient

235
readmitted with intermittent fever, fatigue, weight loss, and erythematous-violaceous papulosquamous plaques on dorsal
arthralgias. On physical examination, body temperature surfaces of the elbows.
was 38.5°C. Hepatosplenomegaly was observed. Muscle
strengths were 5/5. On dermatological examination, facial Figure 2
edema, generalized maculoerythematous rash and xerosis
were present. Erythematous-violaceous papulosquamous
plaques were seen on dorsal surfaces of the elbows,
metacarpophalangeal and proximal interphalangeal joints.
Laboratory examination revealed cytopenia, hyperferritinemia,
and hypertriglyceridemia. Antinuclear antibody titers were
positive. On histopathological examination of the skin marked
vacuolar degeneration was observed in the basal layer.
Based on clinical and laboratory findings, according to the Figure 2: Histological images of the skin biopsy specimen from
diagnostic criteria of hemophagocytic lymphohistiocytosis a papulosquamous plaque on the elbow. Histopathological
(HLH)-2004 which include fever, splenomegaly, cytopenia, examination showing (A) mild spongiosis, necrotic
elevated triglycerides/decreased fibrinogen, increased ferritin, keratinocytes, vacuolar degeneration of basal layer, mild
histological demonstration of hemophagocytosis, decreased perivascular lymphohistiocytic infiltration (Hematoxylin-eosin
NK cell function, and increased soluble IL-2 receptor levels, stain; x 200), (B) increased dermal mucin highlighted by
the patient was considered MAS secondary to JADM. Alcian blue stain (x 200)
The cutaneous manifestations seen in MAS are not specific
but depend on the underlying rheumatic disease. In the Laboratory investigations
literature, the most common skin findings in patients with MAS
secondary to JDM are heliotrope erythema, Gottron’s papules, Normal
Gottron’s sign, and periungual changes. The cytokine storm Investigations Patient
range
seen in MAS may cause more atypical skin lesions, such as
facial or generalized edema, severe xerosis, and generalized 3.7 (58% neutrophils, 28%
WBC (103/dL) 3.8-8.6
maculoerythematous rash. heliotrope rash wasn’t present. lymphocytes)
Poddighe et al. reviewed the JDM cases developing MAS; two Hemoglobin (g/
10 11.1-17.1
out of 12 patients were diagnosed with amyopathic forms. The dL)
mortality rate in JDM might resemble quite similar to MAS Platelets (103/
89 140-360
in other rheumatic diseases. Unlike sJIA and SLE, MAS was dL)
usually the onset presentation of JDM. ESR mm/h 39 0-20
CONCLUSION: MAS may result in a progressive multi- ALT (IU/L) 133 <40
organ failure and, if not timely treated, it can be fatal, so early AST (IU/L) 618 <40
diagnosis is critical. In MAS with atypical skin findings, even if
myopathy is not accompanied, JADM should be considered in GGT (IU/L) 200 <55
the differential diagnosis. LDH(IU/L) 337 120-246
Total protein (g/
6.9 6.6-8.7
dL)
Keywords: Macrophage Activation Syndrome,
Dermatomyositis, Connective Tissue Diseases, Psoriasis Albumin (g/dL) 3.2 3.5-5.3
Ferritin (ng/mL) 968 2-276
Fibrinogen (mg/
Figure 1 202 170-420
dl)
CK (IU/L) 86 24-195
Triglyceride
205 40-180
(mg/dL)
CRP 3.2 <5
Positive
ANA
(1/100, granular pattern
Figure 1: On second hospital admission, the patient presented Abbrevations: WBC, White blood cell count; CRP, C-reactive
with (A) facial edema, maculoerythematous rash, and xerosis protein; ESR, Erythrocyte sedimentation rate; ALT, Alanine
on the face, (B) erythematous-violaceous papulosquamous transaminase; AST, Aspartate transaminase; GGT, Gama
plaques on dorsal surfaces of the metacarpophalangeal and glutamil transferase; LDH, Lactate dehydrogenase; CK,
interphalangeal joints, the cuticle was hypertrophic, (C) Creatine kinase; ANA, Antinuclear antibody.

236
OP-03 [Allergology and Immunology] GA(2)LEN task force report. Allergy 2011;66:317–30
2.Alessandra Vultaggio, Ioana Agache, Cezmi A Akdis,
COVID-19 infection in patients receiving omalizumab Mubeccel Akdis, Sevim Bavbek et al. Considerations on
biologicals for patients with allergic disease in times of the
treatment due to chronic urticaria COVID-19 pandemic: An EAACI statement. Allergy 2020
Güzin Özden Nov;75(11):2764-2774.
Department of Allergy Immunology Adana City Training and
Keywords: chronic urticaria, omalizumab, anti-viral efficacy
Research Hospital, Adana, Turkey

INTRODUCTION & OBJECTIVES: The prevalence of chronic OP-04 [Acne and Related Disorders, Hidradenitis
urticaria is reported as 0.5-5% in the literature. The second-
Suppurativa]
generation H-1 antihistamine drugs are the first step in the
standard treatment guidelines for chronic urticaria. Although
second-generation H 1 -antihistamines are the mainstay of Evaluation of the laboratory parameters in hidradenitis
symptomatic therapy in chronic spontaneous urticaria, up to suppurativa: Can we use new inflammatory biomarkers?
a quarter of patients remain symptomatic, even increasing the
dose up to four-fold above licensed doses. For these refractory Tubanur Çetinarslan1, Aylin Türel Ermertcan2, Beyhan Özyurt3,
patients, omalizumab is suggested in the guidelines. Omalizumab Kamer Gündüz2
may cause additive anti-inflammatory and immunomodulatory
1
Manisa City Hospital, Dermatology Clinic, Manisa
effects by restoring the capacity of human plasmacytoid
2
Manisa Celal Bayar University, Deparment of Dermatology,
dendritic cells and downregulation of high-affinity Ig E receptor Manisa
to produce IFN-α, lead to increasing antiviral activity.
3
Manisa Celal Bayar University, Deparment of Public Health,
Manisa
MATERIALS & METHODS: Thirty-two patients (22F, 9M)
between the ages of 21-59 were included in the study who BACKGROUND: HS is a chronic, recurrent, and debilitating
received regular omalizumab treatment for antihistamine skin disease. Increasing evidence suggests that HS involves
resistant chronic urticaria during the pandemic period in Adana dysfunctional immune responses in both adaptive and
City Hospital Allergy Clinic. They were asked whether they innate immune systems. This may affect the leukocyte types
have been infected by SARS- Cov-2 since the beginning of in circulation. Recent studies showed that inflammatory
the pandemic period. Patients with COVID-19 disease were biomarkers, such as neutrophil–lymphocyte ratio (NLR),
evaluated according to the disease severity (e.g., hospitalization, platelet–lymphocyte ratio (PLR) and Lymphocyte/HDL ratio
pneumonia severity, or other manifestations). The patients’ (LHR), Neutrophil/HDL ratio (NHR), Monocyte/HDL ratio
information about infection was obtained from records (MHR) are an indicator of inflammatory diseases and may be
retrospectively. In case of an active infection, the treatment of associated with disease severity and disease activity. There are
omalizumab was discontinued until recovery. few studies on this subject in HS.

RESULTS: Five (4F, 1M) of thirty-two patients between the AIM: To investigate NLR, PLR, LHR, NHR and MHR in HS
ages of 36-47 had a documented SARS-CoV-2 infection until patients. In addition, to compare erythrocyte sedimentation
now. Two of the female patients had pneumonia detected rate (ESR), C-reactive protein (CRP), complete blood count,
by thorax computerized tomography (CT). A diffuse ground leukocyte profile and biochemical parameters between the
glass appearance was detected in CT of the two patients, who control and the patient group.
presented with back pain first. One of those who had pneumonia MATERIALS-METHODS: Clinical and biochemical data
had hypertension and diabetes mellitus. They easily recovered of patients and healthy subjects were collected from medical
despite widespread lung lesions. The other three patients with records, retrospectively. In total, 166 patients with HS and 124
Covid-19 İnfection (1M, 2F) had myalgia and headache. None control subjects were included.
of them had an urticarial attack, and all of the patients recovered
in the outpatient clinics. Six patients (5F, 1M) had negative RESULTS: Average disease duration was 6.01 years. The
results even they had a close contact history with the positive most common affected area was axilla and groin in HS
family members. Other patients had no history of COVID-19 group. Triglyceride (p <0.001), total cholesterol (p <0.001),
disease. LDL (p <0.001) were significantly higher in patients, while
HDL (p <0.001) was significantly lower in the patient group.
CONCLUSIONS: Omalizumab therapy used in anti-histamine- We found no significant difference in NLR (p=0.207) and
resistant chronic urticaria may also have antiviral efficacy. PLR (p=0.257). LHR (p <0.001), NHR (p <0.001) and, MHR
(p <0.001) were significantly higher in the patient group. No
References: positive correlation was found between any of these markers and
disease severity according to Hurley staging system. However,
1.Maurer M, Weller K, Bindslev-Jensen C, Gimenez- MCV (Mean corpuscular volume), RDW (Red cell distribution
Arnau A, Bousquet PJ, Bousquet J, et al. Unmet width) and CRP showed a significant positive correlation
clinical needs in chronic spontaneous urticaria. A with disease severity. Among these markers, only MHR was

237
positively correlated with disease duration. old psoriasis patient stage 1 ingrown nail was observed in the
second month of cyclosporine treatment.Ingrown nail in four
CONCLUSION: Our study shows that CRP still maintains its patients was observed during isotretinoin treatment.Incorrect
value for HS patients compared to new inflammation markers. nail-cutting habits(71%),poorly fitting shoes(22.33%),excessive
Unlike the studies in other inflammatory diseases, no significant angulation of the nail plate(7.66%),obesity(12%),trauma
relationship was found with most of these inflammatory to the feet(10%),pregnancy(2.63% of women),bad foot
parameters. MHR may be more useful in patients with HS as an hygiene(20.66%) and hyperhidrosis(4%) were associated with
indicator of inflammation compared to other parameters. ingrown nails.The other studies have often focused on the
treatment of ingrown nails,therefore we think that these study
Keywords: C-reactive protein, hidradenitis suppurativa, data will be useful in the prevention of ingrown nail by revealing
inflammation, leukocyte profile, monocyte/high density and then eliminating conditions creating a predisposition to it.
lipoprotein ratio, neutrophil-to-lymphocyte ratio Keywords: Ingrown nails, Epidemiology, Infections
OP-05 [Nail Disorders/Diseases]
OP-06 [Psoriasis]

Clinical and demographic characteristics of patients with

Evaluation of systemic treatment approaches in Psoriasis
ingrown nails
Vulgaris: A single center retrospective study
Gözde Emel Gökçek, Emine Çölgeçen
Mustafa Tosun, Rukiye Yasak Güner, Melih Akyol
Department Of Dermatology, Yozgat Bozok University, Yozgat, Department of Dermatology, Sivas Cumhuriyet University,
Turkey Sivas, Turkey

İngrown nail describes the puncture of periungual skin by In this cross-sectional study, 3049 psoriasis patients who
its corresponding nail plate,resulting in a cascade of foreign applied to Sivas Cumhuriyet University Faculty of Medicine
body,inflammatory, infectious and reparative processes.The Department of Dermatology between 2006-2021 were
hallux nails are most often involved.It is highly uncomfortable retrospectively analyzed. It was observed that 606 (19.8%)
and painful for the patient and leads to workforce losses.The patients received systemic treatment. Of these patients, 1452
most predisposing factors for ingrown nails are factors such as (47.6%) were male and 1597 (52.4%) were female. Adalimumab
incorrect nail cutting habit,poorly fitting shoes,obesity,skeletal was started in 87 (14.3%) patients, acitretin in 96 (15.8%)
or nail deformities,pregnancy,medications,bad foot hygiene and patients, etanercept in 7 (1.1%) patients, infliximab in 26
hyperhidrosis.The soft tissue in the nail sulcus is not normally (4.2%) patients, ixekizumab in 2 (0.3%) patients, methotrexate
in contact with the nail edges.The balance between the lateral in 438 (72.2%) patients, secukinumab in 30 (4,9%) patients,
nail sulcus and nail body is impaired by the factors that cause certolizumab in 1 (0.1%) patient, cyclosporine in 10 (1,6%)
ingrown nails.There is not enough comprehensive study of patients, and ustekinumab in 85 (14%) patients. It was found
the clinical and demographic characteristics of ingrown nail. that the treatment of 9 patients from acitretin to adalimumab
Therefore,this study was planned in order to observe at which and 2 patients from adalimumab to acitretin were changed. It
stage our patients experienced the ingrown nails mostly, the was found that the treatment from etanercept to adalimumaba
factors causing the ingrown nails and our treatment approaches. was changed in 6 patients, and the treatment of none of the
This retrospective-study was approved by the Ethics Committee patients was changed from adalimumab to etanercep. It was
of Yozgat Bozok University.The study was performed with 300 found that the treatment of 10 patients was changed from
patients at 2-89 age with ingrown nails.The type of ingrown infliximab to adalimumab, and none of the patients’ treatment
nail was evaluated in 3 stages.The mean age was 32 years.152 was changed from adalimumab to infliximab. It was observed
women(50.66%) and 148 men(49.33%) were included in the that 5 patients switched from adalimumab to metotrexate, 24
study.The female to male ratio(FMR)was 1.02.Ingrown nail patients switched from metotrexate to adalimumab and 2 patients
was determined in 256 patients(85.33%) on single hallux,in used adalimumab and methotrexate together. It was observed
39 patients(13%) on both of hallux,in two patients(0.66%) on that 4 patients switched from adalimumab to secukinumab,
hallux and on the third finger of foot,in one patient(0.33%) 3 patients switch from secukinumab to adalimumab, and 1
on fingernail,in one patient (0.33%) on all fingernails and in patient switched from cyclosporine to adalimumab, 22 patients
one patient on both of hallux and on the first finger of hand. switched from adalimumab to ustekinumab, and no patient
Ingrown nail was in stage 1 in 117 patients(39%-45 female&72 switched from ustekinumab to adalimumab. As a result, when
male,FMR: 0.62),in stage 2 in 95(%31,66-54 female&41 systemic treatment approaches initiated in psoriasis vulgaris
male,FMR:1.31,in stage 3 in 88(%29,33-53 female&35 were evaluated, it was found that there was a transition from
male,FMR: 1.51).Sixteen patients(5.33%) had a previous history conventional agents to biological agents, and an increase in the
of nail extraction in the same or another nail.Four patients had transition from TNF alpha inhibitors to IL17 and IL12-IL23
ingrown nail during pregnancy.A total of 16 patients(5.33%) inhibitors among biological agents.
with ingrown toenail,ten of whom were at stage 1 and six of
whom were at stage 2,had onychomycosis also.In a 41-year- Keywords: psoriasis, systemic treatment, biological agents

238
OP-07 [Inflammatory Skin Diseases] Table 1. Inflammatory parameters of lichen planoplaris
patients and healty controls
Assessment of inflammatory parameters in patients with
Lichen pla-
lichen planoplaris Healty controls
Parameters noplaris P value
Atiye Akbayrak (n=49)
(n=49)
Department of Dermatology and Venereology, Gaziosmanpasa
WBC count (mean
University, Tokat, Turkey 7.30±1.62 6.60±1.51 0.030
± SD)x103
INTRODUCTION & OBJECTIVES: Lichen planopilaris (LPP) Neutrophil count
4.23±1.12 3.85±1.15 0.097
is a rare inflammatory condition causing progressive, permanent (mean ± SD)x103
hair loss with patches on the scalp. There is no exact data on Lymphocyte count
the presence of systemic inflammation in LPP, and little is 2.36±0.65 2.05±0.55 0.013
(mean ± SD)x103
known about its relationship to disease activity. In this study,
Platelet count
we evaluated the clinical role of inflammatory parameters in 256.53±49.49 250.78±51.66 0.575
(mean ± SD)x103
patients with LPP.
NLR (mean ± SD) 1.85±0.51 1.99±0.73 0.273
MATERIALS & METHODS: Data of individuals applying PLR(mean ± SD) 115.61±32.87 250.78±51.66 0.076
to Dermatology outpatient clinic between January 2001 and
January 2011 were retrospectively reviewed. Study participants MPV(mean ± SD) 9.55±1.44 8.93±1.11 0.020
were divided into two groups; the patient group consisted of 49 RDW (mean ± SD) 13.86±1.61 14.01±1.48 0.630
subjects who were clinically and histopathologically diagnosed WBC: White blood cell; NLR: Neutrophil / lymphocyte ratio;
with LPP, while 49 of similar age and gender, applying to PLR: Platelet / lymphocyte ratio; MPV: Mean platelet volume;
dermatology outpatient clinic with any complaint, formed the RDW: Red blood cell distribution width.
control group. Those with systemic / cutaneous inflammatory or
autoimmune disease and a history of infection in the last month
OP-08 [Dermatological Practice Management]
were not included. Demographic characteristics and white blood
cell (WBC), neutrophil, lymphocyte, platelet counts, neutrophil
/ lymphocyte ratio, platelet / lymphocyte ratio, mean platelet Epidemiological and Clinical Characteristics of Psoriasis
volume (MPV) and red blood cell distribution width of both Patients Admitted to Outpatient Clinic During Initial
groups were recorded and, after that, statistically analyzed.
Period of COVID-19 Pandemic (March-June 2020) and
Ethical permission was obtained from the Clinical Research
Ethics Committee (21-KAEK-038). The collected data were Effects of Pandemic on Treatment Preferences
analyzed using Statistical Package for the Social Sciences Incilay Kalay Yıldızhan, Nihal Kundakçı
(SPSS) version 19 (IBM SPSS 19.0, SPSS Inc). Department of Dermatology, Ankara University, Ankara,
Turkey
RESULTS: Both groups, composed of 98 participants, 49 (F /
M: 33 / 16) of the patient group and 49 (F / M: 34 / 15) of the OBJECTIVE: Psoriasis is a chronic inflammatory immune-
control group, were statistically similar in gender distribution mediated skin disease affecting around 2% of the worldwide
(p > 0.05). Mean age, where the patient group was 44.40 ± population. There is a concern that drugs used in the treatment of
14.71 years (19-65 years), and control group was 43.97 ± 13.39 some patients with psoriasis may increase the risk and severity
years (18-64 years), did not differ significantly between groups of infection with COVID-19. The decision on whether continue
(p > 0.05). Five patients, whose inflammatory parameters or withhold psoriasis treatment was uncertain for dermatologists
showed no statistically significant difference compared to at the beginning of the COVID-19. We aim to evaluate clinical
those without lichen planus (LP) skin lesions (p > 0.05), had characteristics of psoriasis patients that admitted to our outpatient
LP skin lesions; none had oral mucosa and nail involvement. clinic during COVID-19 and the effect of the pandemic on
WBC, lymphocyte counts, and MPV values appeared to be treatment preferences.
significantly higher in the patient group than in the control
group (p = 0.030; p = 0.013; p = 0.020, respectively) (Table 1). MATERIALS-METHODS: This is a retrospective descriptive
study. Psoriasis patients that had admitted to Ankara University,
CONCLUSIONS: Taking all these findings into consideration, Dermatology Department, Outpatient Clinic between March
we suggest that high WBC, lymphocyte counts, and MPV 2020 and June 2020 when the first restrictions had been imposed
values, parameters, in addition to clinical signs, also contributed by the government, were included in the study. Epidemiological
to assessing disease activity in LPP patients, predict the presence and clinical characteristics of patients, admission reasons,
of systemic inflammation. It is hoped that this study can provide subsequent admissions, treatments they received on admission
an essential insight into the relevant issue in the field. and treatment plans on admission were recorded from patients’
charts.
Keywords: Lichen planoplaris, inflammatory parameters,
neutrophil, mean platelet volume, white blood cell. RESULTS: Of the 71 psoriasis patients (41 males and 30 females),

239
the average age was 41.7±15.7 years. The majority of the patients the hair follicul and ectatic vascular structures. The diagnosis of
were between 18-64 years old (81.7%) and 71.8% of the patients Rosacea was confirmed by these histomorphological findings.
were follow-up patients. Forty patients (56.3%) had subsequent Rosacea is a common inflammatory skin disease. Rosacea
admission during the study period. Thirty-one patients(43.7%) presents with erythema, recurrent flushing, edema, telangiectasia,
had systemic treatment at admission and 83% (n:26) of those papules, pustules, rhinofima on facial convex region. Its etiology
were immunosuppressive or immunomodulatory drugs. is not clearly understood. Enviromental factors, genetic factors,
Eighteen patients (25.3%) had biological treatment including Demodex mites, H.pylori, neurovascular abnormalities,drugs
etanercept(n:3), adalimumab(n:4), ustekinumab(n:6), and have roles in development of Rosacea.
secukinumab(n:5), and eight patients(11.2%) had conventional
treatment including methotrexate(n:6) and cyclosporine(n:2).
Twenty of the patients who received immunosuppressive or Keywords: rosacea, facial erythema, recurrent flushing, anti-
immunomodulatory therapy continued their treatment according TNF agents
to physician’s decision, after excluding COVID-19 by PCR test Figure 1
and/or questioning of specific symptoms for COVID-19. For
two patients, cyclosporine treatment had switched to biological
treatment, ustekunimab for one patient and secucinumab for
one patient. For six patients, the dose of treatment was reduced
or discontinued due to the risk of COVID-19 or the patient’s
clinical well-being. While one patient was given biological
treatment again 3 months after.

CONCLUSION: Stopping immunosuppressive or

immunomodulating treatment in psoriatic patients unaffected
by COVID-19 could lead to exacerbation of the disease and
reduced response at re-treatment. Because of the lack of
evidence of adverse effect of biologics on severity and outcome
of COVID-19 in psoriatic patients, treatment of psoriatic
patients with biological agents has been suggested in literature.
Our daily practice was similar to literature, and according to our
Widespread sharply limited erythema, follicular prominence
knowledge, mortality due to COVID-19 has not occurred in our
patients that under immunosuppressive or biological treatment.
Figure 2
Keywords: Psoriasis, COVID-19, biologic,
immunosuppressive, treatment

OP-09 [Dermatopathology]

Red faced girl

Nur Gizem Aykıroğlu1, Yasemin Yuyucu Karabulut1, Ümit
Tursen2
A- Mild spongiosis, inflammatory cell infiltration around the
1
Department of Pathology, Mersin University, Mersin, Turkey
hair follicules and sebaceous glands (H&EX200). B- Demodex
2
Department of Dermatology, Mersin University, Mersin,
mites (H&EX400)
Turkey

A 26-year-old female patient presented with facial erythema and

mild itching past 2 weeks. She has get treatment with Humira
(Adalimumab), Methotrexate, Prednol, Folic acid due to clinical
diagnoses Rheumatoid Arthritis.

Widespread sharply limited erythema, scaling, follicular

prominence and Demodex mites were seen on dermatological
examination.

Microscopic examination revealed mild hyperkeratosis, irregular

acanthosis, spongiosis and follicular plugging. And also Demodex
follicularum took attention on microscopic examination. Heavy
mononuclear inflammatory cell infiltration was observed around

240
OP-11 [Dermatopathology] Figure 1

Fungal Infection Associated Erythroderma

Gözde Arslan1, Yasemin Yuyucu Karabulut1, Ümit Türsen2
1
Department of Pathology, Mersin University, Mersin, Turkey
2
Department of Dermatology, Mersin University, Mersin,
Turkey
A, B. Erythrodermic skin lesions. C. Targetoid lesions on the
An adult female patient applied to the dermatology clinic with leg. D. Erode areas with white plaques on the oral mucosa
complaints of wounds for 1 month. Her wounds started first in
the arms and then in the mouth spread to the whole body. She Figure 2
described widespread marginal edged rashes on the legs since
2014. Exacerbation of a chronic condition, which had persisted
for more than five years. Her peeling, red skin gets very itchy
and more extensive recently. She was concerned about recent
skin changes and decided to seek medical attention. She had no
personal or family history of either dermatitis or psoriasis.In
dermatologic examination the whole body is erythrodermic and
there are targetoid lesions on the legs. Erode areas with white
plaques on the oral mucosa were seen. An incisional biopsy was
performed by dermatology clinic with the preliminary diagnosis
of erythema multiforme and Steven Johnson syndrome. In
the histological serial sections hyperkeratosis, parakeratosis,
intracorneal neutrophile leukocyte infiltration was observed
in the epidermis. Subepidermal edema, congestion and mixed
inflammatory cell infiltration containing dense neutrophil
leukocytes were seen. At high power view fungal spore and
hyphaes was noticed in the intracorneal pustules. Periodic acid-
Intracorneal fungal spores and hyphaes are shown here (H&E,
Schiff (PAS) and Gomori mehtenamin Silver (GMS) stains
x400)
revealed positive hyphae in the stratum corneum, thereby
confirming a diagnosis of tinea infection. She experienced
Figure 3
complete resolution of her erythroderma after antifungal
therapy. Erythroderma or exfoliative generalized dermatitis is
a disease characterized by peeling and redness that involves
more than 90% of the body surface. Systemic diseases that
commonly cause erythrodermia; drug eruptions, dermatitis
(especially atopic dermatitis), psoriasis (in case of treatment
and discontinuation of systemic steroids), pityriasis rubra
pilaris. Diseases that cause this condition less frequently
include contact dermatitis, stasis dermatitis (venous eczema),
seborrheic dermatitis, staphylococcal scalded skin syndrome,
fungal infection, pemphigus, bullous pemphigoid, Sezary
syndrome). Erythrodermic patients with chronic dermatophyte
infection have been described in three clinical settings. One of
these scenarios is: erythroderma that is a direct consequence
of only the tinea corporis infection. The second situation
of erythroderma-related chronic tinea includes individuals
whose erythroderma is multifactorial; may be secondary to a
paraneoplastic phenomenon or an ‘id reaction’. The third setting
Intracorneal fungal spore and hyphaes with PAS histochemistry
of erythroderma-associated chronic tinea occurs in patients
stain, septas can be seen in the hyphaes (PAS,400)
with congenital disorders characterized by erythroderma who
subsequently acquire a persistent dermatophyte infection.

Keywords: Erythroderma, fungus, exfoliative, dermatitis

241
Figure 4 skin diseases such as psoriasis, contact dermatitis, mycosis
fungoides, malignancies, drug reactions and others. In our
case, recurrent erythroderma and pustulosis in the patient who
was followed up with the diagnosis of ichthyosis suggested a
second entity. The skin biopsy revealed pustular psoriasis and
ichthyosiform changes in the background. In the literature,
the physiopathological connections of these two entities were
investigated. In these articles, ichthyosiform erythroderma
accompanied by pustular psoriasis are presented. Although it is
known that they have the same genetic basis, it can not excluded
yet, if pustular psoriasis can be a result of ichthyosis. In the
presence of erythroderma in patients diagnosed with ichthyosis,
the possibility of a second entity should come to mind when
there is no response to treatment, even if the findings are non-
specific.

Keywords: Erythroderma, Pustular psoriasis, Ichtyosis

Intracorneal fungal spore and hyphaes with GMS vulgaris
histochemistry stain (GMS,400)
Figure 1
OP-12 [Dermatopathology]

A difficult case with recurrent erythroderma

Eda Gökalp Satıcı1, Yasemin Yuyucu Karabulut1, Melodi
Çekiç2
1
Department of Pathology, Mersin University, Mersin, Turkey
2
Department of Dermatology, Mersin University, Mersin,
Turkey

A 28-year-old female presented to the dermatology outpatient

clinic with skin lesions characterized by red-colored rashes on
the arm, leg and trunk. It is known that the case is followed up
with diagnosis of ichthyosis vulgaris and retinoid therapy was
given for several times.

Dermatologic examination revealed desquamed lesions on

erythematous background. Biopsy performed from the lesions
and non-spesific findings were observed in the histopathological
examination. The lesions decreased after the cyclosporine
treatment, then just in a few days the eruption had begun
with erythema of the trunk and legs and than extensive scaly
and pustular plaques appeared. A second biopsy was planned Figure 1: A: Lesions characterized by hyperkeratosis on
from the new lesions, for the presence of a second entity that extensive erythrodermic background. B:Erythematous
could cause erythroderma in the patient who did not benefit background C:Hyperkeratotic plaques on erythematous ground
from the treatment totally.Histopathological examination
revealed hyperkeratosis, thin granular cell layer, suprapapillary
thinning in the epidermis. Accompanied neutrophil leukocytes Figure 2
a mixed type inflammatory cell infiltration was observed in
the dermis. Neutrophilic pustules were seen in subcorneal and
intraepidermal location. Pustular psoriasis was considered
with these histomorphological findings. Ustekinumab
treatment was started after clinical evalution. She benefited
from the treatment and erythroderma regressed just in a week.
Erythroderma also known as exfoliative dermatitis is a clinical
presentation of many different diseases. In erythroderma,
eritema and scaly lesions must be present in more than %90
of the body surface. Common causes of erythroderma are Figure 2: A: Areas where granular layer is absent and
epidermal plates are thin. There are lymphohistiocytic

242
inflammatory cells around the vessels in the dermis (H&E in the dermal papillae with CD30 and CD20 positivity was not
x200). B: Compact hyperkeratosis and psoriasiform observed. The diagnosis of mycosis fungoides was confirmed
hyperplasia of the epidermis (H&E x40). by these histomorfologycal findings. Mycosis fungoides, which
is characterised by infiltration of the skin with malignant T cells
is the most common primary cutaneous lymphoma in adults
Figure 3 and children. It comprises approximately %65 of all primary
cutaneous lymphomas in pediatric patients.Similar to adults,
children may have an indolent clinical course that is difficult
to distinguish from inflammatory skin conditions. In adults,
classic MF presents initially with scaly erythematous patches
that may progress into infiltrated plaques and tumors in %35
and %20 of patients. The incidence of classic MF in children
is approximately %41. Unlike adults, the majority of children
with MF present with nonclassic variants of the disease, which
include hypopigmented, hyperpigmented, folliculocentric, and
poikilodermatous forms. Hypopigmented form is >%50 of
pediatric cases. According to the studies conducted for the last
10 years, the most common treatment method is phototherapy.
The patient was threated with phototherapy (narrow-band UVB
two times a week). Significant improvement was observed
clinically after the current treatment.

Keywords: Pediatric mycosis fungoides, erythema plaques,

Figure 3: İnflammatory infiltrate consisting of neutrophil primary cutaneous lymphoma, phototherapy
leukocytes in the intracorneal area.
1
OP-13 [Dermatopathology]

A Case of Pediatric Mycosis fungoides

Gizem Aydın1, Yasemin Yuyucu Karabulut1, Mustafa Anıl
Yılmaz2, Ümit Türsen2
1
Department of Pathology, Mersin University, Mersin, Turkey
2
Department of Dermatology, Mersin University, Mersin,
Turkey

A 9-year-old male patient presented with a non-itching red

swelling on lower abdomen for two months. There is no
medical illness in the medical history of his family and himself.
It was initially treated as tinea by family physician then he
was sent to our hospital for the persistence of the plaque. In 2
dermatological examination, there are two 4*2.5 and 4*1.5 cm
annular erythema plaques in the suprapubic area, 3*2 cm in
the right inguinal region and 4*2 cm in the left lumbar region.
Biopsy was performed and the histomorphological examination
of the biopsy specimen, orthokeratosis and follicular plugging
were observed in the epidermis. Lymphocytes that fill the
papillary dermis also lie transepidermally. These lymphocytes
have significant cytological atypia such as nuclear enlargement,
nuclear contour irregularity and perinuclear halo. In the
immunohistochemical study, strong cytoplasmic staining with
CD3, CD4 and CD5 in lymphocytes which filling the dermal
papillae, showing alignment at the dermoepidermal junction
and spreading transepidermal in patches was observed. Some
of these lymphocytes showed strong cytoplasmic staining with
CD8 and the ratio CD4/CD8 was 4. Most of the lymphocytes that
filling the dermal papillae showed loss of expression with CD7.
Moderate cytoplasmic staining was seen in very few lymphocytes

243
OP-14 [Corrective, Aesthetic and Cosmetic Dermatology] Immunology, Mersin City Training And Research Hospital,
Mersin,Turkey
Retrospective Analysis Of The Onabotulinum Toxin-A BACKGROUND: Idiopathic granulomatous mastitis is a
Patients Applying To The Cosmetology Unit Of A rare benign chronic inflammatory breast disease of women of
University Hospital reproductive age.There is not yet a complete consensus on IGM’s
treatment algorithm. its aetiology has not been fully elucidated.
Özge Aşkın, Defne Özkoca Although it is benign, abscess, fistula and sinus formation in the
İstanbul Üniversity-Cerrahpaşa, Cerrahpaşa Medical Faculty, course of granulomatous inflammation cause deformities in the
Department of Dermatology breast. Surgical procedures (such as mastectomy and excision)
INTRODUCTION AND OBJECTIVES: Onabotulinum cause tissue loss and cosmetic problems in the breast.These can
toxin-A is the combination of toxins produced by the bacterium lead to the deterioration of body image and mental disorders in
Clostridium Botulinum. It has been long used for cosmetic patients.The good response of IGM to steroids points to the role
purposes by paralysing facial expression muscles and thus of autoimmunity in the development of this disease. There are
reducing the fine wrinkles.1 In this study our aim is to anaylse limited data on the use of mtx in the treatment of IGM. In this
the demographic characteristics of the patients applying to the study, we evaluated the clinical effectiveness of mtx therapy for
cosmetology unit of İstanbul University-Cerrahpaşa, Cerrahpaşa IGM.
Medical Faculty, which is a public university hospital. PATIENTS and METHODS: Data from 15 patients who were
PATIENTS AND METHOD: The patients who have applied histopathologically diagnosed with IGM and referred to an
to the cosmetology unit of İstanbul University-Cerrahpaşa, immunology clinic between 2018-2021 were retrospectively
Cerrahpaşa Medical Faculty, Dermatology Department and who examined. The patients were divided into two groups as mtx
received Onabotulinum toxin-A injections from January 2020 and conservative.
to January 2021 were included in this study. The gender, age RESULTS: Fifteen patients who did not get a complete response
and session count of each patient were noted from the patient from surgery and antibiotic treatment were re-evaluated in
files retrospectively. The gender distribution, average ages and immunology. The patients were divided into two groups as
application frequency were analysed. mtx(methotrexate) and conservative. Data of six patients treated
RESULTS: A total of 153 patients applied to the cosmetology with MTX were compared with 9 patients on conservative
unit for Onabotulinum toxin-A treatment within the last year. Of follow-up. MTX monotherapy was started at 7.5-10 mg / week.
these patients, 142 (92.8%) were female and 11 (7.18%) were MTX treatment was applied for 6-12 months. No serious side
male; female patients were treated significantly more. The mean effects were observed during the treatment, and no recurrence
of the age of all patients was 43 years; the mean age of male was observed in any patient during the 12-month follow-up
patients was 40 years and the mean age of female patients was period. Three of the 9 patients followed-up conservatively had
43 years. Twenty-one of the patients received two applications a recurrence.
within the last year and 2 patients received three applications. CONCLUSIONS: Mtx monoterapy is a safe and effective
The average number of applications was 1.16. treatment in patients with igm.
CONCLUSIONS: This study showed that female patients
applied more for Onabotulinum toxin-A injections than the male Keywords: Idiopathic Granulomatous Mastitis, Methotrexate
patients and that the patients of both genders were of middle Therapy, Mastitis
age. Furthermore, an average of 1.16 injections per year was Clinical characteristcs of patients (Methotrexate 7.5-10 mg/
requested by patients. week oral route)
REFERENCES: 1- Satriyasa BK. Botulinum toxin (Botox)
Lesion Mtx Follow-
A for reducing the appearance of facial wrinkles: a literature Age Lactation Number O.C
ANA
Abscess
size AB treatment up period
review of clinical use and pharmacological aspect. Clin Cosmet (year) (mounth) of child use drainage
(mm) (month) (month)
Investig Dermatol. 2019 Apr 10;12:223-228. doi: 10.2147/
1 43 24 2 + - + 20 + 12 24
CCID.S202919. PMID: 31114283; PMCID: PMC6489637.
2 42 48 5 - - + 30 + 12 24
Keywords: botox, cosmetology, wrinkles, 3 30 12 3 + - + 70 + 6 20
4 30 12 3 + - + 25 + 6 22
OP-15 [Allergology and Immunology] 5 33 14 2 - - + 50 + 8 18
6 33 13 2 + - - 30 + 6 16
Methotrexate monotherapy for idiopathic granulomatous
Mastitis ANA, Anti-Nuclear Antibodies, Oc:Oral contraceptive, AB
Nurullah Yekta Akçam Antibiotic treatment
Nurullah Yekta AKÇAM Departman of Allergy and

244
OP-16 [Dermatopathology] Wood’s lamp examination results were compared.

RESULTS: Volunteers treated with favipiravir had a significantly

Alopecia neoplastica due to metastatic epithelioid sarcoma higher positivity of sparkling sign (p:0.0001), while it was
Mustafa Anıl Yılmaz1, Vali Nasirov2, Umit Tursen1 negative in those who did not receive favipiravir treatment. A
1
Department of Dermatology significant correlation was observed between the time passed
2
Department of Pathology over the infection and the distance of the sparkling sign from the
lunula (p:0.0001). The most common nail finding in volunteers
ABSTRACT: Alopecia neoplastica is defined as hair loss was splinter hemorrhage (13%), followed by leukonychia (12%),
secondary to a visceral malignancy that has spread to the scalp.. and longitudinal ridges (7.9%). One picture of the sparkling
We present a 22-year-old female patient reporting lesions at the sign has been illustrated in Figure 1 along with a normal nail
scalp, and who was asymptomatic with a six months evolution. appearance under Wood’s light in Figure 1.
The patient reported prior epithelioid sarcoma and was
undergoing chemotherapy at the time of consultation.We aimed CONCLUSIONS: The sparkling sign may be seen due to
to improve the knowledge on alopecia neoplastica, highlighting accumulation of favipiravir or its excipients on the nails.
that in case of alopecia neoplastica due to epithelioid sarcoma. Accordingly, this accumulation may be seen in the vital organs.
The most common finding was splinter hemorrhages in the
Keywords: Alopecia neoplastica, Epithelioid sarcoma,Scalp volunteers with Covid-19 infection history. We think that
Metastasis coagulopathy and microvascular vasculitis associated with
Covid-19 infection may have promoted the development of the
Figure 1 splinter hemorrhages.

Keywords: Covid-19 infection, nail findings, wood

findings, favipiravir, splinter hemorrhage, sparkling sign

Figure 1

Cicatricial alopecia area around the red crusted nodule on

postauricular scalp

OP-17 [Nail Disorders/Diseases]

Evaluation of Nail Findings in Patients with Covid-19

Infection History and Wood’s Lamp Examination
Irem Yanatma1, Hülya Cenk2 Sparkling sign on the proximal third of the nail (Picture on the
1
Seydisehir State Hospital, Department of Dermatology, left) along with a normal nail (Picture on the right) appearance
Konya, Turkey under Wood’s light
2
Pamukkale University, Department of Dermatology, Denizli,
Turkey

INTRODUCTION & OBJECTIVES: Various skin findings due

to coronavirus have been identified. Yet there is no literature
knowledge on nail findings of the disease excluding few case
reports. We aimed to document the nail findings of the Covid-19
survivors and shed light on the interesting sparkling seen under
the Wood’s light.

MATERIALS & METHODS: A total of 231 volunteers

diagnosed with Covid-19 infection in the last 100 days were
grouped in terms of the agents used in the treatment, as laid
down in the protocol released by the Turkey Ministry of Health.
Routine examination findings of the nails were recorded and

245
OP-18 [Lasers] OP-19 [Genetics]

Treatment of lip-localized venous lakes with long-pulsed A rare vascular and lymphatic syndrome- A late-diagnosed
Nd:YAG laser case of Hypotrichosis–lymphedema–telangiectasia
Sevil Savaş Erdoğan, Tuğba Falay Gür syndrome with new clinical findings
Department of Dermatology, University of Health Sciences, Tubanur Çetinarslan1, Aylin Türel Ermertcan2, Müge Gündüz2,
Sultan 2.Abdulhamid Han Training and Research Hospital, Mustafa Kürşat Evrenos3
Istanbul, Turkey 1
Manisa City Hospital, Dermatology Clinic, Manisa
BACKGROUND / OBJECTIVE: Venous lakes are papules or
2
Manisa Celal Bayar University, Department of Dermatology,
nodules, which are dome-shaped, ranging from dark blue to Manisa
purple, finger-compressible in middle-aged and elderly people,
3
Manisa Celal Bayar University, Department of Plastic and
often found in areas exposed to the sun such as the face, ear, Reconstructive Surgery, Manisa
and lips. In histopathology, the papillary dermis contains dilated INTRODUCTION: Hypotrichosis–lymphedema–telangiectasia
venules consisting of a thin layer of endothelial cells and syndrome (HLTS) is a rare vascular and lymphatic
thick fibrous walls. Since venous lake does not tend to regress malformation. Cardinal features include a generalized lack
spontaneously after it occurs, treatment is important both to of body hair, lymphedema of the extremities, and scattered
improve the cosmetic appearance and to prevent bleeding cutaneous telangiectasias. Less commonly observed
complications. Different treatment methods including surgical vascular defects include enlargement of the ascending
excision, sclerotherapy, cryosurgery, electrocoagulation, and aorta and renal failure from chronic microangiopathy
more recently, intense pulsed light and various lasers have of the glomerular and extraglomerular vasculature.
been described. In this study, we aimed to examine the effect of Here we described a patient with cutaneous telangiectasias,
Nd:YAG laser on venous lakes. congenital upper right extremity lymphedema, localized
MATERIALS AND METHODS: Ten patients with lip-localized hypotrichosis and lymphangioma. To the our knowledge, upper
venous lake were treated with Nd:YAG laser between 2019- limb localization and lymphangioma coexistence in HLTS has
2020 in our clinic. 1064 long-pulse Nd:YAG laser was applied not been reported.
to all patients with 3 mm spot size, 55 ms pulse width and 200- CASE REPORT: A 20-year-old female patient presented to
250 joules / cm² energy. Depending on the size of the lesion, the dermatology clinic with a history of multiple painless
1 to 3 shots were made without overlapping. Clinical response lesions on neck and chest since approximately four years. On
was determined by the lesion’s hardening, mild whitening, and dermatological examination, there were multiple translucent
an audible popping sound. According to the clinical response, papules on neck and chest (Figure 1). Dermoscopic examination
Nd:YAG laser was applied in a single session or two sessions revealed multiple white-yellowish well circumscrimbed roundish
with one month interval. lacunaes (Dermlite DL4, polarized, x10). She had congenital
RESULTS: Eight male and 2 female patients, aged between lymphedema on right arm and right hand (Figure 2). There were
35 and 71 years, were included in this study. All lesions were telangiectasias on right neck, right thoracic and lumbal region
located in the lip, nine of them were in the lower lip and one was and, right upper extremity (Figure 3). There was hypotricosis
in the upper lip. Lesions ranged in diameter from 4 mm to 10 in her right arm (Figure 4). Other physical examinations were
mm. Complete recovery was observed in 7 of 10 patients (70%) normal. She had no drug history or systemic disease. There
with a single session and 3 (30%) of them with two sessions of was no dysmorphic facial appearance. Hair growth was normal
Nd:YAG laser application. There were no complications other on the scalp. Neurologic exam was normal. Her parents were
than mild pain and edema. non-consanguineous and healthy. There was no known family
history or of any dermatological condition. There were no renal
CONCLUSION: Laser treatment has become a preferred or pulmonary abnormalities on laboratory examinations. Upper
method in the treatment of venous lakes due to its easier extremity MR showed lymphedema. No lymphatic flow was
application and less side effects compared to other treatment observed in the right upper extremity with lymphoscintigraphy.
options. The effectiveness of long-pulse Nd:YAG laser in the Transthoracic echocardiogram and abdominal ultrasound ruled
treatment of venous lakes is ensured by the absorption of 1064 out aortic dilation and kidney malformations. A punch biopsy
nm wavelength by methaemoglobin and its deep penetration and was performed from translucent lesions. Histopathological
thus, they show more effect than short wavelength lasers in deep examination demonstrated; enlarged lymphatic ducts and
and thick lesions. Consequently, the long-pulse Nd:YAG laser is vascular structures.
a simple, non-invasive, effective and safe treatment option that
can be preferred in lip-localized venous lakes. DISUSSION: HLTS combines features that represent failure
of proper vascularization, angiogenesis and hair formation.
Keywords: Laser, Lip, Nd:YAG laser, Venous lakes Dysfunctional development of blood vessels results in cutaneous
telangiectasias and dilations of superficial vasculature, while
disturbances in the maintenance of the lymphatic system are

246
manifested by lymphedemas. The third constituent of this Figure 2
syndrome involves defects in hair follicle development, leading
to progressive scalp hair loss and absence of eyebrows and
eyelashes (3). In our case, there was no involvement of scalp
and head and neck, and hypotricosis was only limited on the
right arm. Lymphedema was limited to the right upper extremity.
There were multiple lymphangiomas on trunk and neck. We
wanted to present our case because it is a rare syndrome and
shows different clinical features has not been reported yet.

Keywords: Hypotrichosis–lymphedema–telangiectasia
syndrome, vascular syndrome, lymphatic syndrome,
lymphangioma

Figure 1

Lymphedema on right arm and right hand.

Figure 3

Multiple translucent papules on neck and chest.

Telangiectasias on right upper extremity.

247
Figure 4 RESULTS: While donovan bodies were easily detected
in hematoxylin eosin in 18 of 84 cases, fewer donovan
bodies were seen by detailed search in 43 cases. Donovan
bodies were not observed in hematoxylin eosin in 23 cases.
In 60 (%71.4) of 84 cases, CD1a staining was detected.
Expression was observed in all 18 cases containing donovan
bodies that were easily detected in hematoxylin eosin. CD1a
positivity was detected in 32 of 43 cases. Positive staining with
CD1a was observed in 10 of 23 cases in which donovan bodies
could not be seen in hematoxylin eosin. In these cases, very few
donovan bodies became evident with CD1a.

CONCLUSION: In our study, high positivity was found with

CD1a. However, donovan bodies that could not be seen in
hematoxylin eosin were detected with CD1a. Therefore, we
think that the use of CD1a makes an important contribution in
the diagnosis of leishmaniasis.

Keywords: Leishmania, Cd1a, leishmania species

OP-21 [Autoimmune Bullous Diseases]

The management of bullous skin disorders in the era of

COVID-19 pandemic: A single center, retrospective, cross-
sectional study
Tuğba Kevser Uzunçakmak, Sera Nur Yücesoy
İstanbul Üniversitesi-Cerrahpaşa Cerrahpaşa Tıp Fakültesi Deri
Hypotricosis on her right arm. ve Zührevi Hastalıkları Anabilim Dalı

OP-20 [Dermatopathology] BACKGROUND: COVID-19, a serious pulmonary illness

caused by the highly contagious novel coronavirus, is a global
pandemic.
The Role of CD1a expression in the diagnosis of cutaneous
OBJECTIVE: In this retrospective study, we aimed to
leishmaniasis, its relationship with Leishmania species and
demonstrate the COVID-19 prevelance and treatment course of
clinicopathological features the patients with bullous skin disorders.
Yasemin Yuyucu Karabulut1, Funda Kuş Bozkurt1, Ümit
METHODS: A total of 151 patients with bullous skin disorders
Türsen2, Gülhan Temel4, Mehmet Emin Erdal3
who admitted to our department between the dates of October
1
Mersin University, Medical School, Department of Pathology
2019-October 2020 were enrolled in this study. The statistical
2
Mersin University, Medical School, Department of
analysis was performed with the SPSS-21.
Dermathology
3
Mersin University, Medical School, Department of Genetic RESULTS: One hundred twenty five patients were taking
4
Mersin University, Medical School, Department of statistics systemic steroid treatments and 113 patients were under
the treatment of adjuvant treatment including azathioprine,
BACKGROUND-OBJECTIVE: Leihmaniasis is a chronic
mycophenolate mofetil and dapsone. Eighty patients received
infectious disease caused by different protozoan species of
a minimum of a two-cure rituximab treatment during last year,
Leishmania. Although histopathological examination plays an
and 15 patients a minimum of a three-cure IVIG treatment in the
important role in diagnosis, donovan bodies may not always
last year. Only 4 of the 151 patients had a Covid-19 infection
be detected in biopsies. Few studies have shown that the
history where all of them experienced a mild disease without
CD1a marker is useful in detecting amastigotes. Our aim is to
hospitalization.
investigate the contribution of CD1a to diagnosis, especially in
cases where pronounced donovan bodies are not observed. CONCLUSION: There is no consensus as for the
immunosuppresive and biological treatments for autoimmune
METHODS: 84 cases suspected for cutaneous leishmaniasis
bullous diseases during the covid-19 pandemic.
were included in the study. Histopathologically, the presence
of granuloma and giant cell, the selectability of amastigotes in
hematoxylin eosin were investigated. Immunohistochemical Keywords: Azathioprin, bullous pemphigoid, bullous skin
study was performed with CD1a. disorders, corticosteroids, immunosuppression

248
OP-23 [Dermoscopy] the first study about nailfold capillary findings in aHUS patients.
Although our sample size is small, our patients were under
The Nailfold Dermoscopy Findings of Patients w,th remission and dermoscopy is not a gold standard technique to
Atypical Hemolytic Uremic Syndrome examine nailfold capillaries; nailfold capillary abnormalities
were significantly higher compared to the control group. Further
Esra Nagehan Akyol Önder1, Ece Gökyayla2, Aylin Türel extensive studies should be considered to confirm the findings
Ermertcan2, Pelin Ertan1 of the present study.
1
Manisa Celal Bayar University, Faculty of Medicine,
Department of Pediatrics, Pediatric Nephrology Keywords: atypical hemoliytic uremic syndrome,
2
Manisa Celal Bayar University, Faculty of Medicine, nailfold dermoscopy, capillaroscopy, microangiopathy
Department of Dermatology and Venereology
Figure 1
INTRODUCTION & OBJECTIVES: Atypical HUS (aHUS)
develops due to genetic disorders of the alternative complement
pathway and results in microangiopathy. Therefore, simple
and non-invasive tests are needed to evaluate the activity of
the disease by assessing the microvascular structure. Nailfold
Video Capillaroscopy (NVC) is a reliable method which the
microvascular structure can be examined non-invasively with
high-magnification (x200). However, this technique is not
easily accessible. The dermoscope (x10) is an easily portable
equipment used to visualise nailfold capillaries. In this study, we Normal nailfold capillary dermoscopic findings in control
aimed to evaluate the microvascular changings by comparing group, “Normal Pattern”
the findings of nailfold capillary dermoscopy in aHUS patients
with a healthy control group. Figure 2

MATERIALS & METHODS: 7 aHUS patients and 7 healthy

children were included in study. Patients’ demographic datas
were recorded andevery finger of both hands was examined
with paying a greater attention on fourth and fifth finger of non-
dominant hand. For both patient and control group; clarity of
image, capillary density, capillary enlargement, haemorrhages,
abnormal capillary shapes were examined and recorded for area
of focus (the most prominent dermoscopic areas) and widefield
view. To identify patients with abnormal capillary examination
findings, we adapted the definitions suggested by Radic et al.
and categorized as “Non-interpretable”, “Normal Pattern”,
“Scleroderma Pattern” or “Non-specific”.

RESULTS: The demographic data of the patients are shown in Decreased capillary density and disorganised capillaries in
Table 1. All children in control group classified as “Normal” in Patient 4, “Non-spesific”
AOF and WV. Dermoscopic findings of control group are shown
in Table 2. In patient group, 6 patients (85,7%) were classified Figure 3
as “Non-Specific” and one patient (14,2%) was classified as
“Scleroderma” pattern. Dermoscopic findings of patient group
are shown in Table 3.

CONCLUSION: In this study, we found abnormalities in nailfold

capillaries were higher in patients with aHUS. When we evaluate
4 CFH mutation positive patient, which triggers microvascular
damaging and associated with poor prognosis; one of them is
non-interpretable, all of them had decreased capillary density
(100%) and 2 of them had disorganised capillary architecture
(50%). 2 of 7 patients (28,6%) with the earliest age of onset
in our study (0,6 years both), which is also associated with
poor prognosis, had enlarged capillaries in AOF. All of our
patients were normotensive while their nailfold dermoscopy
was performed so we could not evaluate hypertension-capillary
abnormality correlation. To the best of our knowledge, this is Decreased capillary densitiy in Patient 1 “Non-spesific”

249
Figure 4 Table 2

Nailfold dermoscopy findings of control group

Table 3
Severe decrease in capillary density and capillary enlargement
in Patient 2, “Scleroderma Pattern”

Figure 5

Nailfold dermoscopy findings of patient group

OP-24 [Corrective, Aesthetic and Cosmetic Dermatology]

An Investigation Of The Effects Of Polydioxanone Thread,

Non-convex capillary detected (red circle) in area of field in Patient 6 Hyaluronic Acid Filler And Botulinum Toxin-A Materials
On The Rat Skin, Connective Tissue And Photoaging

Table 1 Koray Durmaz1, Recep Dursun2, Siddika Findik3, Ilknur Cinar4,

Hatice Gul Durakbasi Dursun4
1
Clinic of Dermatoloy, Bozuyuk State Hospital, Bilecik,
Turkey
2
Department of Dermatology, Necmettin Erbakan University
Meram Faculty of Medicine, Konya, Turkey
3
Department of Pathology, Necmettin Erbakan University
Meram Faculty of Medicine, Konya, Turkey
4
Department of Medical Biology, Necmettin Erbakan
University Meram Faculty of Medicine, Konya, Turkey

OBJECTIVE: In this in vivo study, we evaluated the single or

combined effects of polydioxanone (PDO) thread, hyaluronic
acid (HA) filler and botulinum toxin type-A (BTX-A) practices
on the rat skin and subcutaneous tissue. We also investigated
how the results of these three treatments were affected during
photodamage and photoaging caused by UV exposure.

MATERIALS-METHODS: The dorsal skin of 20 rats included

in the study was divided into 5 areas and marked. PDO thread,
HA filler and BTX-A were applied alone or in combination in
the other 4 areas outside the area reserved as the control area.
Demographical, clinical findings and treatment modalities of The rats were divided into 2 groups and the second group
seven patients with aHUS was exposed to UVA and UVB for 12 weeks, while the first
group was exempted from this exposure. Biopsy samples were
taken from the application areas of the rats in both groups at
the 4th and 12th weeks. Histopathologically tissue thickness,

250
qualitative levels and orientation of collagen fibers and elastin OP-25 [Dermatological Practice Management]
in dermis, neocollagenesis and neoelastogenesis, foreign body
granulomas, fibrosis, capsule-like structure formation, histiocyte Autologous Blood Injection for Treatment of Corticosteroid
and giant cell formation, fibroblast counts, inflammatory cells, Atrophy
vascularization, solar elastosis and tissue edema were evaluated
comparatively. In molecular analysis, type I collagen (Col1A1), Ömer Kutlu1, Pınar Özdemir Çetinkaya2
type III collagen (Col3A1), matrix metalloproteinase 2 (MMP- 1
Department of Dermatology and Venereology, Gaziosmanpaşa
2), matrix metalloproteinase 9 (MMP-9), NF-κB, and IL-6 gene Univesity Faculty of Medicine, Tokat, Turkey
expression levels were determined by the real-time polymerase 2
Department of Dermatology and Venereology, Nazilli State
chain reaction (RT-qPCR). Hospital, Aydın, Turkey

RESULTS: In histopathological examination, solar elastosis OBJECTIVES: Intramuscular corticosteroid injections are
was significantly higher in the UV group. The qualitative level frequently used for a variety of conditions in dermatology
and organization of collagen in all application areas were found practice. Unfortunately, many complications are associated with
to be higher than the control area. It was found that the amount systemic and local administration of corticosteroids. Cutaneous
of collagen decreased more irregularly in the UV group than adverse effects after intramuscular corticosteroid administration
in the non-UV group. Significant increases in inflammation and include dermal and/or subcutaneous atrophy, hyperpigmentation,
vascularity were observed in the application areas compared to hypopigmentation/depigmentation and alopecia. Localized
the control area. Capsule-like structure formation, giant cells and subcutaneous lipoatrophy is among the most common adverse
foreign body granuloma were also detected histopathologically effects that can lead to permanent disfigurement. There are
in the application areas. In molecular analysis changing the several treatment options for this condition such as intradermal
expressions of following genes: Col1A1, Col3A1, MMP2, saline injections, autologous fat grafting, poly-L-lactic acid
MMP9, NFkB and IL-6 at week 4 and 12 in all areas were injections and surgical excision with varying success rates.
summarized in tables. Autologous blood injection (ABI) is immediate injection of the
patients’ own blood into the affected tissue with the intention of
CONCLUSION: Single or combined applications of PDO stimulating the body’s own tissue-healing mechanisms through
thread and HA filler or combined with BTX have a protective cellular and humoral mediators. Herein, we would like to report
and healing effect on the skin and subcutaneous tissue against successful treatment of localized steroid atrophy in a 17-year-
chronological and photoaging. Especially until the first 4 weeks, old patient with ABI. To the best of our knowledge, this is the
PDO thread+HA filler combination is the application that first report evaluating the effectiveness of ABI in localized
increases type I collagen synthesis the most, followed by HA subcutaneous lipoatrophy.
filler, PDO thread+HA filler+BTX and PDO thread applications.
On the 12th week and after, the most effective application METHODS: This is a case report that presented a successful
was detected HA filler on collagen production. HA filler was treatment of localized steroid atrophy with ABI.
followed by the combination of PDO thread+HA filler+BTX.
Other applications do not seem to have a stimulating effect on RESULTS: A 17-year-old female patient presented with severe
type I collagen and type III collagen synthesis during this period. allergic contact dermatitis on her both hands. In addition to topical
steroid oinment and moisturizing agents, 40 mg intramuscular
Keywords: Polydioxanone thread: Botulinum Toxins, Type A: triamcinolone acetonide was prescribed to the patient for a rapid
Dermal Fillers: Rats, Wistar: Skin Aging: Photoaging recovery. Lesions due to allergic contact dermatitis improved
dramatically but within weeks, skin thinnig, depigmentation
and subcutaneous fat atrophy were observed in the left gluteal
region where is the site of corticosteroid injection (Figure 1).
With the patient’s history and clinical features, a diagnosis of
localized subcutaneous lipoatrophy was made and follow-up of
the lesion was planned considering that it would improve over
time. The changes subsided after 6 months and there were no
signs of spontaneous improvement, therefore ABI treatment was
initiated. 4 cc autologous blood was injected into the dermis
and subcutaneous fat tissue. One month later after ABI, there
was moderate improvement so ABI was performed for the
second time (Figure 2a-2b). At 2 months, there was significant
improvement (Figure 3). The size and depth of the atrophy was
markedly improved and depigmentation was resolved. The
patient was satisfied with the result of the ABI.

CONCLUSIONS: Various treatment options are already

available in the treatment of localized steroid atrophy with
varying success rates. This report shows that ABI is also a simple,

251
effective and safe procedure for correction of corticosteroid Figure 2b
induced cutaneous and subcutaneous atrophy with satisfying
results.

Keywords: autologous blood injection, corticosteroid atrophy,

steroid

Figure 1

Purple coloration of the lesion due to second autologous blood

injection

Figure 3

Skin thinnig, depigmentation and subcutaneous fat atrophy in

the left gluteal region

Figure 2a

Moderate improvement after first autologous blood injection

Significant improvement in the size and depth of the atrophy and

depigmentation

252
OP-26 [Psoriasis] Palmoplantar pustulosis

Palmoplantar Pustulosis - Clinical Characteristics and

Associated Diseases in a Single Tertiary Center
Sezgi Sarikaya Solak1, Hande Yelgen1, Yusuf Can Özdemir2
1
Department of Dermatology, School of Medicine, Trakya
University, Edirne, Turkey
2
School of Medicine, Trakya University, Edirne, Turkey

INTRODUCTION and OBJECTIVES: Palmoplantar pustulosis

(PPP) is a chronic inflammatory disease characterized by sterile,
macroscopically visible pustules affecting the palms and/or
soles. PPP has a significant negative impact on patients’ quality
of life as it occurs on functional areas of the body. The aim of this
study was to investigate the clinical characteristics, triggering
A clinical picture of severe palmoplantar pustulosis
factors and comorbidities of patients with PPP.

METHODS: We conducted a retrospective review of the patients

with PPP at Trakya University Department of Dermatology Characteristics of patients with palmoplantar pustulosis.
between January 1, 2018 and January 31, 2021.
All Patients Male Female p
RESULTS: A total of 22 patients with PPP consisting of 7 (n =22) (n =7) (n =15) value
(31.8%) male and 15 (68.2%) female were included in the Age ± SD, 45.36 ± 42.57 ±
study. The mean age at onset was 45.3 years. The vast majority 46.67 ± 11.66 0.437
mean years 11.18 10.35
of patients (95.5%) were current or ex-smokers. PPP usually Age at disease
started at only palmar (36.4%) or plantar area (40.9%) but then 43.36 ± 41.57 ±
onset ± SD, 44.20 ± 10.76 0.585
spread to the both localizations (90.9%). Most of the patients 10.16 9.27
mean, years
(63.7%) were overweight or obese and 40.9% had metabolic Disease onset,
syndrome. Almost two third of patients (63.7%) had at least n (%)
one comorbidity. Dyslipidemia and hypertension were the Early onset (≤
most frequent comorbidities. Half of the patients had psoriatic 8 (36.4) 3 (42.9) 5 (33.3) 1.000
40)
arthritis (PsA) (50.0%) whereas 68.2% had nail involvement. Late onset
Four patients (18.2%) had a paradoxical PPP associated with 14 (63.6) 4 (57.1) 10 (66.7)
(>40)
TNF-alfa inhibitors. Almost a quarter of patients (22.7%) Localization at
had co-existing psoriasis vulgaris (PsV). Smoking (95.5%) disease onset,
was found to be the most common triggering factor followed n (%)
by psychological stress (63.6%). There were no significant Palmar area 8 (36.4) 2 (28.6) 6 (40.0) 0.645
differences regarding clinical features between genders.
Plantar area 9 (40.9) 2 (28.6) 7 (46.7)
CONCLUSIONS: Many patients with PPP had co-existing Palmar and
5 (22.7) 3 (42.9) 2 (13.3)
psoriatic disease (nail psoriasis, PsV and PsA) and other plantar areas
comorbidities (obesity, metabolic syndrome, cardiovascular Current
disease) similar with patients with PsV. Smoking and stress localization,
were found to be considerable potential triggering factors. TNF- n (%)
alfa inhibitors was the causative agents for paradoxical PPP in No lesion 1 (4.5) 0 (0) 1 (6.7) 0.291
some patients. Determining the associated diseases and potential Palmar area 0 (0) 0 (0) 0 (0)
triggers is important for the appropriate management of patients Plantar area 1 (4.5) 0 (0) 1 (6.7)
with PPP. Palmar and
20 (90.9) 7 (100) 13 (86.7)
plantar areas
Keywords: palmoplantar pustulosis,characteristic,
Smoking
comorbidity, psoriasis vulgaris
status, n (%)
Never 1 (4.5) 0 (0) 1 (6.7) 0.710
Former 4 (18.2) 2 (28.6) 2 (13.3)
Current 17 (77.3) 5 (71.4) 12 (80.0)

253
Number of intervals for 5 sessions. Er-Yag laser was used in fractional
smoking pack 25 (15- mode with short pulse (SP: 250-350μs) 3joule/cm² energy, 10
20 (15-30) 19 (7-30) 0.514 Hz and 5mm spot size. In the combination group; Er-Yag laser
years, median 35)
(25th-75th) was followed by topical tazarotene application immediately
BMI ± SD, 27.07 ± 29.31 ± after the laser procedure and those patients were recommended
26.03 ± 3.79 0.063 to apply tazarotene topically at nights for 10 weeks. Patients in
mean 3.87 3.22
Nail the ‘only laser’ group received no additional topical treatment.
involvement, 15 (68.2) 6 (85.7) 9 (60.0) 0.350 One month after the final treatment 2 dermatologists who
n (%) were blinded from clinical data evaluated the pre-and post-
treatment photographs retrospectively according to Global
PsA, n (%) 11 (50.0) 3 (42.9) 8 (53.3) 1.000
Aesthetic Improvement Scale 4 (GAIS 4) point scoring system
Co-existing
5 (22.7) 2 (28.6) 3 (20.0) 1.000 as 0:worsen, 1: no difference, 2: mild, 3:moderate, 4:good.
PsV, n (%)
Family history RESULTS: The improvement scores of the patients in the
5 (22.7) 3 (42.9) 2 (13.3) 0.274
of PsV, n (%) combination group were listed as follows: 4 of 8 patients
Potential showed ‘good’ improvement, 3 patients ‘moderate’ and 1
triggering of them ‘mild’. While only 6 and 2 of 8 patients in the laser
factors group had ‘moderate’ and ‘mild’ scores respectively. No ‘good’
Smoking 21 (95.5) 7 (100) 14 (93.3) 1.000 response was detected in any patient in the laser group alone.
Psychological The difference in improvement scores between the 2 groups was
14 (63.6) 3 (42.9) 11 (73.3) .343
stress found statistically significant. (p= 0,041)
Seasonal
5 (22.7) 1 (14.3) 4 (26.7) 1.000 CONCLUSION: Results of this study suggest that both
changes
combination of Er: YAG laser and tazarotene and only Er: YAG
laser procedure with the regimen used in this study are found
OP-27 [Lasers] effective for the improvement of aging signs on hands. In line
with the results of our study, we recommend combining Er: YAG
The effectiveness of Combination of Er:YAG Laser and laser with tazarotene because it provides higher improvement
Tazorotene is Superior to Er:YAG Laser Alone for The scores in the treatment of hand aging.
Treatment of Photodamaged Hands Keywords: skin aging, Er-YAG Lasers, tazarotene
Özlem Dündar, Pelin Eşme, Ercan Çalışkan
Department of Dermatology and Venereology, University Figure 1
of Health Sciences Medical Faculty Gulhane Education and
Research Hospital

OBJECTIVE: Carbon dioxide (CO2) and erbium-doped yttrium

aluminum garnet (Er: YAG) lasers are the most commonly used
rejuvenation modalities in daily practice. The capability of
superficial skin ablation with the advantage of minimal thermal
damage of Er: YAG (2940 nm) laser makes it one of the most
preferred procedure for rejuvenation. Tazarotene is a third-
generation synthetic retinoid derivative that has been approved
by FDA for photoaging. Since the absorption of topical products
through the epidermis is limited physiologically, to overcome the
epidermal barrier, laser-assisted drug delivery has become more
popular with the advantages of accessibility and rapid onset of
topical products. This study aimed to evaluate the efficacy of
combining Er: YAG laser and tazarotene on hand rejuvenation
in comparison with Er: YAG laser alone.

PATIENTS AND METHOD: Data were retrospectively

collected from female patients’ medical records who were
treated in our clinic between January and March 2020 for the
signs of hand aging. Among 23 patients 7 were excluded for
various reasons including incompliance to the treatment and
personal reasons. A total of 16 patients’ medical records were
evaluated for the study. Patients’ mean age was 52,3±0.7. All Before and after photographs of a patient from laser and
patients had received Er: YAG laser on both hands with 2-week tazarotene combination group

254
OP-28 [Miscellaneous characteristics including previous treatment protocols were
recorded. Patients with a lack of sufficient data were excluded.
Human 3D Skin Models
Neslihan Fişek Izci RESULTS: A total of 43 patients (33 females and 10 males) were
included in the study. The mean age of initiation of systemic
isotretinoin was 25,3 years in female patients and 19,9 years in
Tissue engineering is used to fabricate 3-dimensional (3D) male patients (p=0.001). The combination of benzoyl peroxide
artificial scaffolds to create a microenvironment that mimics and erythromycin was the most commonly prescribed topical
human tissue. Bioprinting uses biomaterials, cells, and/or treatment, comprising 43,6% of the prescriptions. Doxycycline
bioink to fabricate prospective scaffolds to mirror the structural, was the most commonly prescribed systemic antibiotic with
compositional, and functional aspects of the skin (1). The a number of 13 patients. In this study, the average duration
relevance for in vitro three-dimensional (3D) tissue culture of topical and systemic treatment was 6,3 and 2,4 months
of skin has been present for almost a century. From using respectively. The duration of topical treatment was 0-3 months
skin biopsies in organ culture, to vascularized organotypic in 22 patients (53.7%), 6-9 months in 9 patients (22%), and more
full-thickness reconstructed human skin equivalents, in than 1 year in 10 patients (24,4%). The duration of systemic
vitro tissue regeneration of 3D skin has reached a golden treatment was 0-3 months in 13 patients (81,3%) and 6-9 months
era (2). The 3D Skin Model is a highly physiological, three- in 3 patients (%18,8).
dimensional cellular system of keratinocytes, fibroblasts,
and melanocytes for in vitro studies, suggesting an excellent CONCLUSIONS: To minimize antibiotic resistance, long-term
tool to examine aspects of epithelial function and disease, therapy with antibiotics is not recommended. Recent guidelines
particularly those related to skin biology and toxicology (3). suggest that it should be limited to 3 to 6 months. The mean
Threedimensional (3D) skin equivalents have been established duration of systemic antibiotic use in this study was found
as a valuable tool in dermatological research because they shorter than previous studies findings. In our study, systemic
contain a fully differentiated epidermal barrier that reflects the antibiotics was used for 6 months or less, in accordance with
morphological and molecular characteristics of normal human most consensus proposals. Expert guidelines recommend using
epidermis (4). Herein, we will summarize 3D skin bioprinting topical retinoids as effective maintenance therapy. In our study,
techniques, applications and approaches. the average duration of topical therapy before isotretinoin
treatment was 6.3 months. We observed that the combination
Keywords: bioprinting, 3D, human skin of benzoyl peroxide and antibiotics was used more frequently
than topical retinoid. Early recognition of patients who show no
OP-29 [Acne and Related Disorders, Hidradenitis improvement with appropriate topical therapies and long-term
oral antibiotics is necessary to prevent the potential long-term
Suppurativa] sequela.

A retrospective analysis of topical and systemic treatments Keywords: acne, systemic antibiotics, topical antibiotics,
topical retinoid, isotretinoin
before isotretinoin therapy in patients with acne
Bilgen Gencler OP-30 [Acne and Related Disorders, Hidradenitis
Department of Dermatology, Dıskapı Yıldırım Beyazıt Training
Suppurativa]
and Research Hospital, University of Health Sciences, Ankara,
Turkey
Dietary and Acne in Teenagers
INTRODUCTİON & OBJECTIVES: Acne vulgaris is a chronic
inflammatory disease of the pilosebaceous unit that can cause M Can Emeksiz
significant anxiety in affected patients. Standard acne treatments Department of Dermatology, Ufuk University, Ankara, Turkey
include both topical and systemic agents. Isotretinoin is widely BACKGROUND: The positive relationship between acne and
recognised as a very effective treatment for severe acne. Due fatty dairy products and high glycemic index food has been
to the development of resistance to antibiotic treatments, there implicated recently in the literature.
are growing concerns about reducing the duration of antibiotic
use. To the best of our knowledge there are not many studies OBJECTIVES: This study aimed to investigate the link
about treatment duration among patients with acne. In this study, between diet and acne in teenagers. We tested the hypothesis
our aim is to investigate the duration of topical and systemic that teenagers with acne consume more dairy than those without
treatments, that were previously used in patients, with acne who acne.
are currently receiving oral isotretinoin therapy.
METHODS: A case-control study was conducted among 246
MATERIALS & METHODS: Patients with moderate to participants (123 acne, 123 control), aging 13 to 21 years,
severe acne who received systemic isotretinoin treatment in with or without acne. The diagnosis of acne was determined
dermatology outpatient clinic, were retrospectively analyzed. by a dermatologist using the Global Acne Assessment Scale.
The demographic findings of the patients and their medical Participants then completed a dietary-acne questionnaire, and

255
food and nutrient intake were compared between groups with OP-32 [Dermatological Practice Management]
or without acne.

RESULTS: More dairy product intake was reported in the acne Comparison of dermatology consultations requested from
group (P =.01) than those with no acne. No significant difference pandemic wards and non-pandemıc wards
was found for glycemic diet intake or body mass index. No
Dilek Canat
difference was found between the patients with more facial and
Basaksehir Cam and Sakura City Hospital Dermatology
body lesions in the acne group.
INTRODUCTION: During the SARS-Cov-2 pandemic
Limitations: Limitations include self-report of diet by a
period, the number of patients admitted outpatient clinics and
questionnaire and the complex etiopathogenesis of acne
their profiles have changed. Also changes were observed in
CONCLUSIONS: Consumption of dairy products was positively dermatology consultations requested from inpatient clinics.
associated with acne In addition, it was noted that the diagnoses determined in the
requested Dermatology consultations differ between pandemic
Keywords: acne, diet, diary, glycemic, teenager wards and patients hospitalized in non-pandemic wards. The
aim of the study is to evaluate these observed changes and
OP-31 [Inflammatory Skin Diseases] differences between pandemic and non- pandemic wards.

MATERIALS-METHODS: This study was conducted in the

An Erythema Annular Centrifigum Case due to inactivated dermatology clinic of Istanbul Basaksehir Cam and Sakura City
SARS-CoV-2 vaccine (CoronaVac); a case report and Hospital between 1 October-31 December 2020, during the
literature review second wave of the pandemic. The pandemic and non-pandemic
inpatient dermatology consult database was reviewed and
Rabia Oztas Kara compared retrospectively.
Department of Dermatology, Sakarya University Training and
Research Hospital, Sakarya, Turkey RESULTS: A total of 414 patients were evaluated during
this period. The mean age of the patients was 44.3 (0-90
INTRODUCTION & OBJECTIVES: In this presentation, it is years). 90.5% (375) of the consultations were requested from
aimed to present an erythema annular centrifigum complication non-pandemic wards and 9.5% (39) from pandemic wards.
developed 3 days after coronavac vaccine and, review of the Among consultations requested from non-pandemic wards,
skin complications that may develop due to the vaccines. 286 (69%) from internal subspecialities, 68 (16,4%) from
MATERIALS & METHODS: A 24-year-old woman presented surgical subspecialities, 21 (5,1%) from intensive care unit.
with a history of erythematous annular plaques in the face and Diagnoses detected in all consultations were cutaneous infections
whole body that progress from the center to the periphery since 37,6%, followed by inflammatory skin disorders 17,3%,
7 days before admission. The medical history was positive wound and ulcers 14,7%, drug reactions 12.5%, pruritus 6.2%,
for covid 19 vaccination before the beginnig of symptoms. vasculitis/vasculopathy 4.8%, urticaria 3.4% and others 3.5%.
There was no history of any other disease or drug use in his Among the diagnoses of pandemic wards consultations, the
medical history. There were no features in his family history. most frequently detected ones were ulcers 34.7%, drug reactions
In the histopathological examination of the skin lesions with 32.6%, vasculitis / vasculopathy 18.7%. The order of frequency
hematoxylin and eosin staining, a mild inflammation consisting of consultations requested from non-pandemic services were
of polymorphonuclear leukocytes and sporadic eosinophils in the 39.3% for cutaneous infections, 18.9% for inflammatory skin
perivascular area was observed in the superficial dermis. Taking disorders, 12.2% for ulcers, and 10.6% for drug reactions.
into account clinical findings and the history of COVID-19 In this process, Dermatology consultations requested from
vaccination, the suspicion of COVID-19 was proposed. pandemic wards were found at a lower rate (9.5%) compared
to the literature. This situation has been associated with
RESULTS: The patient was treated with potent topical the fact that our hospital is a 3rd stage large metropolitan
corticosteroids. hospital with inpatient capacity of 2800 and has been
associated with the continuation of intensive patient
CONCLUSIONS: Skin complications due to coronavirus follow-up in non-pandemic wards during this period.
vaccines are very rare in the current published literature. This difference in diagnostic distribution of requested
Although these complications can often be treated with simple consultations from pandemic wards was thought to be related
interventions, It should be borne in mind that they may be an to the high selectivity, like for cases considered to be highly
alarm sign for vital complications complicated.
Keywords: Erythema Annular Centrifigum, CONCLUSION: The SARS-Cov2 pandemic has also caused
Type IV hypersensitivity reaction, inactivated SARS-CoV-2 changes in Dermatology consultations during this period. In the
vaccine (CoronaVac) SARS-Cov2 pandemic, differences were detected in the rate
and diagnosis of requested Dermatology consultations between
pandemic wards and non-pandemic wards. These differences

256
may vary according to the capacity of the hospital, the CONCLUSIONS: Annual testing for LTBI reactivation is
continuity of non-pandemic patient follow-up and the selectivity required for patients on biologics. Two tests commonly used
of consultations requested from pandemic services. The causes for this purpose, PPD and QFT have low concordance ratios,
of these differences needs to be supported by prospective multi- and QFT is generally accepted as more specific, therefore
center studies. more strongly recommended. Our cohort had a low rate of
seroconversion of QFT, although we live in a country with a
Keywords: Dermatology consultations, pandemic wards, non- relatively high TB disease burden. Interestingly, a higher ratio
pandemic wards, SARS-Cov-2 of patients exhibited seroreversion, which may have been
caused by isoniazide prophylaxis. Our cohort was too small to
OP-33 [Biologics, Immunotherapy, Molecularly Targeted compare seroconversion rates seen under different therapeutics.
Therapy] Notably, the two seroconversions in our cohort happened during
treatment with anti-IL17 agents, although these agents have
Quantiferon-TB Gold Test Conversion in Psoriasis Patients previously been favored in latent TB infection.
on Biologic Therapy: A Retrospective Study Keywords: biologics, quantiferon, tuberculosis, psoriasis
Burcu Beksaç, Sema Nur Çoban, Ercan Çalışkan, Gülşen
Akoğlu OP-34 [Biologics, Immunotherapy, Molecularly Targeted
University of Health Sciences Gulhane Research and Training Therapy]
Hospital, Dept. of Dermatology, Ankara, Turkey

INTRODUCTION & OBJECTIVES: Biologics are commonly The efficacy of ustekinumab treatment in patients with
used in dermatological practice, especially in psoriasis. Testing moderate-to-severe plaque psoriasis
for latent tuberculosis infection (LTBI) is mandatory at the
beginning and during biologic treatment, as they may lead to Fatma Tunçez Akyürek
reactivation. Department of Dermatology, Selcuk University, Konya, Turkey

MATERIALS & METHODS: This is a retrospective study with INTRODUCTION: Psoriasis is a chronic inflammatory skin
data obtained from our psoriasis patient database. Psoriasis disease and the TNFα–IL23–Th17 axis plays an important
patients on biologic drugs, having at least two consecutive role especially in plaque psoriasis. Ustekinumab is a human
Quantiferon-TB-Gold test (QFT) results one year apart were IgG1k monoclonal antibody and acts by binding to the p40, the
included in the study. Patients only evaluated through tuberculin common subunit of IL-12 and IL- 23. In this study, we aimed
skin test (PPD) were excluded. In patients with PPD also to evaluate the efficacy of ustekinumab in patients with plaque
available, cut-off value for PPD positivity was 10 mm. QFT psoriasis followed up in our clinic.
outcomes after one year treatment were defined according to MATERIALS & METHODS: Age, gender, previous systemic
baseline and follow-up QFT RESULTS: seroconversion if from and biological treatment, additional diseases, nail involvement,
negative to positive, seroreversion if from positive to negative, duration of treatment, Psoriasis Area and Severity Index (PASI)
persistently seronegative or persistently seropositive. values of patients who received ustekinumab treatment were
RESULTS: Thirty-nine patients, of whom 21 (53.85%) recorded.
were male were included in the study. Mean age was 45.67 RESULTS: Fourteen patients (10 males and 4 females) were
(24-85) and mean disease duration was 16.19 years (5-74). included in the study. A total of 5 patients had comorbidity
Mean follow-up duration was 39.1 months (14-108). Patient and one of them had psoriatic arthritis. One patient was using
distribution according to different biological medications ustekinumab at a dose of 90 mg and one patient was using the
were as follows: Adalimumab 6 (15.38%), Certolizumab 8 drug every 8 weeks. Of 14 patients,13 patients had PASI 50
(20.51%), Ixekizumab 8 (20.51%), Infliximab 1 (2.56%), response at the 16th week of the treatment, 9 patients had PASI
Secukinumab 8 (20.51%) and Ustekinumab 8 (20.51%). 90 response at the one year of the treatment.
The number of patients with a negative QFT at the beginning
of the treatment was 27 (69.23%) and the rest were positive. CONCLUSIONS: In our study, ustekinumab treatment well
21 patients also had PPD results, 14 (66.67%) of them were tolerated and no serious adverse effects were observed in any
10 mm or above. Only 8 (38.1%) of these patients also had of the patients. We think that ustekinumab is effective and safe
QFT positivity. QFT and PPD were concurrently negative in 6 in the treatment of moderate and severe plaque psoriasis. In
(28.58%) of patients. After one year of treatment, 31 (79.49%) patients who only partially respond to the initial regimen with
of patients had negative and 8 (20.51%) had positive QFT ustekinumab, the dose may be increased to 90mg or administered
results. Only 2 (5.13%) patients showed seroconversion. These every 8 weeks to achieve a complete response.
patients were on ixekizumab and secukinumab. Six (15.38)
exhibited seroreversion, three of which were on certolizumab, Keywords: biological agent, psoriasis, ustekinumab
one on adalimumab and two on ustekinumab. For persistent
seronegativity and seropositivity, the numbers were 25 (64.1)
and 6 (15.38) respectively. No cases of active TB were detected.

257
OP-35 [Dermatological Practice Management] in order to rapidly implement new measures in Turkish health
policies such as a referral system for dermatology outpatient
The role of dermatologists during early COVID-19 visits to equitably distribute dermatology services, widespread
use of telemedicine and virtual educations of residents.
pandemic in Turkey: Implications of the results of a nation-
wide online survey for Turkish health care system Keywords: clinical practice, coronavirus, dermatology, health
policy, pandemic, redeployment
Muazzez Cigdem Oba, Kursat Goker
Department of Dermatology, Health Sciences University, Figure 1
Sancaktepe Sehit Prof.Dr.Ilhan Varank Research and Training
Hospital, Istanbul, Turkey

INTRODUCTION & OBJECTIVES: The coronavirus disease

2019 (COVID-19) has led to a re-organization of health services
throughout many countries. In this study, we aimed to get an
overview of the role of the dermatologists during COVID-19
pandemic in Turkey. We aimed to interpret the results according
to current Turkish health care policies.

MATERIALS & METHODS: Dermatologists across Turkey

were asked to fill in an online 11-item questionnaire survey,
investigating their duty/duties (dermatology outpatient and
inpatient clinics, pandemic outpatient and inpatient clinics, Monthly distribution of participants working in dermatology
emergency etc.) month by month during March-June 2020. The outpatient clinics and number of daily visits performed
study was approved by both the local review board and Turkish
Ministry of Health. Figure 2

RESULTS: A total of 217 responses were obtained. Considering

there were 2351 actively working dermatologists in Turkey
during the study period, results of our survey with 217
participants has a 95% confidence interval and a margin error
of 6.3%. Dermatologists of all ages, from residents to senior
dermatologists, participated in the survey (age range: 27-70).
Vast majority of the participants were working in governmental
hospitals including research and training hospitals (28.1%)
and public hospitals (25.3%). Although respondents were
from nearly all cities of Turkey, dermatologists from three
biggest cities of Turkey dominated (34.6%, 10.1% and 6% for
Istanbul, Ankara and Izmir, respectively). Academic degrees Monthly distribution of participants involved in pandemic
of participants were specialist (66.4%), resident (18.9%), inpatient care and number of monthly shifts
associate professor (8.3%) and professor (6.5%). Vast majority
(91% to 98%) of the participants reported that they performed
dermatology outpatient visits. Each month, at least half of
dermatologists reported examining more than 30 patients per
day. While 41.5 to 56.2% of participants were redeployed
to pandemic inpatient clinics, 12.9 to 29% were mobilized to
pandemic outpatient clinics. Across four months, the percentage
of participants that were mobilized to COVID inpatient clinics
and outpatient clinics showed statistically significant changes.
These changes were in accordance with the rate of COVID
cases in Turkey. Each month, at least 90% of the residents that
participated in the questionnaire reported they were recruited to
pandemic inpatient clinics.

CONCLUSIONS: Our findings indicate that nearly all

participants continued the dermatology outpatient visits
during early pandemic. In addition, a significant percentage of
dermatologists were redeployed to COVID-19 wards in Turkey,
especially the residents. As the impact of COVID-19 pandemic
is ongoing in Turkey, this data should be taken into consideration

258
OP-36 [Infectious Diseases, Parasitic Diseases, Infestations] OP-37 [Epidemiology]

COVID-19 and Human Papillomavirus: Paradoxical Evaluation of dermatology consultations requested from
immunity the patients hospitalized in COVID-19 wards

Abdullah Demirbaş1, Hediye Eker2, Ömer Faruk Elmas3, Gözde Eda Ustaoglu
Ulutaş Demirbaş4, Mustafa Atasoy5, Ümit Türsen6, Torello Dermatology Department, Bursa City Hospital, Bursa, Turkey
Lotti7 INTRODUCTION & OBJECTIVES: Coronavirus 2019 disease
1
Department of Dermatology, Evliya Çelebi Training and (COVID-19) has affected the whole world since December
Research Hospital, Kütahya Health Sciences University, 2019, and the health system has been inevitably affected by
Kütahya, Turkey this pandemic. COVID-19 causes pneumonia that presents with
2
Department of Dermatology, Selçuk University, Konya, fever, cough, shortness of breath, and myalgia. However, skin
Turkey involvement has also been reported. The aim of this study is
3
Department of Dermatology, Kırıkkale University, Kırıkkale, to evaluate the dermatology consultation notes of patients with
Turkey Covid-19 pneumonia at covid wards.
4
Department of Dermatology, Akçaabat Haçkalı Baba State
Hospital, Trabzon, Turkey MATERIALS & METHODS: Patients hospitalized in covid
5
Department of Dermatology,Health Science University, wards at Bursa City Hospital between March 16, 2020, and
Kayseri City Hospital, Kayseri, Turkey February 15, 2021, were included in the study. Patients were
6
Department of Dermatology,Mersin University, Mersin, diagnosed with Covid pneumonia with either the positiveness
Turkey of polymerase chain reaction test or compatible computed
7
Department of Dermatology,Guglielmo Marconi University, tomography findings as described by the World Health
Rome, Italy Organization. Dermatology consultation notes of the patients
over 11 months were retrospectively analyzed.
Coronavirus disease 2019 (COVID-19) is a multisystemic
disease that can cause progressive lung failure, organ RESULTS: There were 94 patients; 53 (56.3%) of the those
dysfunction and coagulation disorder associated with high were male, and 41 (43.6%) were female. The average age of
mortality and morbidity. COVID-19 is known to either primarily male patients was 56.7, and female patients were 55.9 years old.
cause skin symptoms or increase existing skin diseases. Human The diagnoses made at consultations were drug eruption, 18%;
papillomavirus (HPV) is a DNA virus that can cause benign dermatitis, 17%; pruritus, 9%; urticaria, 7%; herpes zoster, 7%;
and malignant neoplasms. Mucocutaneous verruca vulgaris superficial fungal diseases, 6%; cellulite, 5%; decubitis ulcer,
are common benign lesions of HPV. Here, we report a case of 5%, and others, 26%.
verruca vulgaris regressed after COVID-19.
CONCLUSIONS: The covid-19 disease can be associated with
Keywords: COVID-19, Human Papillomavirus, Paradoxical various dermatological findings. The drugs used during the
immunity treatment of covid pneumonia and long-lasting hospital stays
may also cause rashes and a variety of dermatological disorders
Figure 1. by affecting the immunity and skin barrier. Understanding these
diseases and a multidisciplinary approach including dermatology
is very important in the management of Covid-19 disease.

Keywords: inpatient, dermatology, Covid-19

a. Periungual verruca vulgaris before COVID-19, b. Lesions

that spontaneously regress after COVID-19.

259
OP-38 [Infectious Diseases, Parasitic Diseases, Infestations] OP-39 [Systemic Treatment]

Evaluation of the frequency and economic impact of Retrospective Evaluation of Side Effects After Using
patients with scabies in a cross-sectional study Finasteride at a Hair Transplant Center
Şenay Ağırgöl Şule Güngör
Department of dermatology, Başakşehir Çam and Sakura City Department of Dermatology, Demiroğlu Bilim University,
Hospital İstanbul, Turkey

INTRODUCTION & OBJECTIVES: Scabies has been reported INTRODUCTION & OBJECTIVES: Finasteride is a 5-α
with increasing frequency in recent years. It has become a serious reductase inhibitor and it is widely used in the management of
health problem due to widespread nocturnal itching, sleep benign prostatic hyperplasia and androgenic alopecia (AGA).
disturbance, and a tendency to secondary skin infections. Also, Although these agents improve the quality of life in men
it can affect a large number of patients due to human-to-human suffering from these conditions, they are associated with some
transmission. With the scabies epidemic in our country, the data adverse effects. The aim of this study was to analyze the side
are gradually increasing. The aim of this study is to present the effects of finasteride treatment used in men with AGA.
economic and social dimension of the epidemic by giving the
number of individuals affected, the frequency of treatment, and MATERIALS & METHODS: We enrolled 59 male patients
the number of physician visits in infants, children, and adults. who administered to our hair transplantation center between
October 2019 and October 2020 and used finasteride for AGA.
MATERIALS & METHODS: Within the study, only one person We recorded their demographic data, duration and dosage
from the same family was evaluated among the patients diagnosed of finasteride usage, smoking status and side effects they
with scabies who applied to the dermatology outpatient clinic of experienced during usage or cessasion of the drug.
Başakşehir Çam and Sakura City Hospital. The patients were
questioned about the family member who started itching first RESULTS: The age of the patients were 39.06±6.79 years.
in the family, the duration of the disease onset, the number Patients started finasteride use in the age range of 24–52 years
of affected individuals in the family, the number of physician (34.23±6.67 years). Finasteride was used in a range of 6-240
visits of the patients, the number of treatments applied, and the months (38.5±47.5 months). 52 patients assumed finasteride at
treatments applied. dosage of 1 mg/day, 5 patients 1.25mg/day and 2 patients 2.5
mg/day. 14/59 (23.7%) patients reported side effects related with
RESULTS: Thirty adults, 30 children, 30 infant patients were finasteride and 9/14 (64.2%) pateints reported more than one
evaluated in the study. There were 32 female and 58 male side effects (Table1). Loss of libido was the most common side
patients (64.4%). The average age is 12.32 years; Male gender effect among our patients (9 patients), erectile dysfunction was
predominance was present in all infant, child, and adult groups. the second most common side effect (8 patients). Depression was
In the family, babies were the most common carriers of scabies, the least seen side effect (2 patients). Two patients taking 2,5mg/
and children took second place. The first person in the family day finasterid and five patients taking 1,25 mg/day finasterid had
where the symptom started was rarely seen as the father. side effects while seven of 52 patients taking 1mg/day finasterid
When the individuals with itching and rash in the family were had side effects. Side effects persisted for over 4.1±2.7 months
questioned, 384 patients were recorded. The disease’s duration after finasteride discontinuation.
was 315 months (average 4.5 months), the average number of
physician visits was 3.9, and the average number of repeated CONCLUSIONS:: Finasteride, decreases serum and scalp
treatments was 4.1. dihydrotestosterone by inhibiting conversion of testosterone
to DHT. Although finasterid has side effects, all is temporary
CONCLUSIONS: Scabies continues as an important health and disappear after cessation of the treatment. Our study shows
problem in our country. It is observed that infants and children that the side effects of finasterid is dose dependent and patients
are the most affected and carriers of the disease. We can say that should be warned to take low dosage of finasterid. New studies
there are four times more affected patients in the community that evaluates the effect and side effects of intermittent finasterid
than the number of patients identified in our study. Scabies treatment should be done.
patients create significant psychological and economic losses.
We think that cooperation with dermatology, family physicians, Keywords: finasteride, alopecia, side effect
pediatricians, and emergency physicians may be effective in the
control of the epidemic in terms of the epidemic outbreak.

Keywords: scabies, infants, outbreak

260
Demographic characteristics, Side effects of finasteride In her family history, her mother and two of her sisters were
sexual and non-sexual symptoms diagnosed with uveitis and granulomatous dermatitis. A
punch biopsy is performed. In histopathological examination,
Patients, N = 59 Mean severe neutrophilic inflammation is detected in dermis and
Characteristic or symptom subcutaneous tissue. She was diagnosed with Sweet’s syndrome
± SD or n (%)
and given 0,5 mg/kg oral methylprednisolone. Adalimumab can
Age, years 39.06±6.79
not be stopped because of recalcitrant uveitis even to other anti-
Age at starting finasteride assump- tumor necrosis factor (TNF) alpha agents.
34.2±6.6
tion, years
CONCLUSIONS: To the best of its knowledge, idiopathic
Duration of finasteride use, months 38.5±47.5
Sweet’s syndrome could be triggered by inflammatory
Dosage used, mg/day 1.13±0.58 disorders. Anti TNF alpha agents such as adalimumab have
Duration of side effects after cessa- been used successfully on many occasions to treat disorders
4.1±2.7 with neutrophilic dysfunction, including Sweet’s syndrome.
sion of drug, months
On the other side, four adalimumab-induced Sweet’s syndrome
Erectile dysfunction 8 cases were reported so far, suggesting that anti TNF-alpha
Decreased libido 9 agents may paradoxically potentiate neutrophilic dysfunction in
predisposed patients. The occurrence of Sweet syndrome can
Premature ejaculation 5
be integrated into the natural course of the Blau syndrome as an
Gynecomastia 4 autoinflammatory disease, but the imputability of adalimumab
Depression 2 is at issue. Follow-up is in progress.

Keywords: blau syndrome, Sweet’s syndrome, adalimumab

OP-40 [Inflammatory Skin Diseases]
Figure 1
Sweet Syndrome: The Natural Course of Blau Syndrome or
a Paradoxal Reaction to Adalimumab?
Ece Gökyayla1, Muhammed Altınışık2, Peyker Temiz3, Aylin
Türel Ermertcan1
1
Manisa Celal Bayar University, Faculty of Medicine,
Department of Dermatology and Venereology
2
Manisa Celal Bayar University, Faculty of Medicine,
Department of Ophtalmology
3
Manisa Celal Bayar University, Faculty of Medicine,
Department of Pathology

INTRODUCTION & OBJECTIVES: Blau syndrome is an

autosomal dominant inherited granulomatous autoinflammatory
disease which is caused by mutations in NOD2/CARD15
gene. Clinical presentation is characterized by skin eruption,
granulomatous arthritis/synovitis and uveitis triad which show Erythematous nodules in lower extremities
noncaseous granulomas under histopathological examination.
Sweet’s syndrome is an inflammatory and reactive dermatosis
which presents with pyrexia, neutrophilia, painful erytomatous
papules, nodules and plaques; in addition extensive infiltration
of neutrophils into dermis histologically. It can be idiopathic,
malignancy-associated or drug-induced. In this report, Sweet’s
syndrome is discussed etiologically in a patient with Blau
syndrome.

MATERIALS & METHODS: A Sweet’s syndrome

case with also had Blau syndrome was presented.
RESULTS: A 30-year old female patient had multiple tender
erythematous nodules on the lower extremities that developed
after second adalimumab injection (Day 0: 80 mg Adalimumab
sc, Day 7: 40 mg Adalimumab sc) was consulted. In her medical
history, she was followed by Blau syndrome with recurrent
uveitis, severe joint deformities and granulomatous dermatitis.

261
Figure 2 Figure 4

Neutrophil predominant mixed inflammatory infiltration in

dermis and subcutaneous fat tissue (HE, x20)

Figure 5

Camptodactily

Figure 3

Dermal perivascular dense neutrophilic infiltration (HE,x200)

Vitreal condensation and panuveitis

262
OP-41 [Inflammatory Skin Diseases] in psoriasis patients and correlated with disease severity. CAR
was not significant compared to the control group in our study.
C-reactive protein to albumin ratio: Is a prognostic factor The reason for this may be the small sample size of the patient
and control groups.
for the Behçet Diseases?
Keywords: CAR, CRP,Albumin, Behçet Diseases
Bülent Nuri Kalaycı, Rabia Aydogan
C-reactive protein to albumin ratio: Is a prognostic factor for
the Behçet Diseases?

INTRODUCTION: Behçet’s disease is recurrent oral and

genital ulcers, ocular and cutaneous lesions, and a multisystemic
inflammation involving various organs and systems. Although
some hypotheses have been created, including genetic, infection,
immune complexes, and environmental factors, the cause and
pathogenesis of Behçet’s disease have not yet been fully explained.
Diagnosis of Behçet’s disease is based on clinical parameters.
Laboratory tests can help to diagnose the disease and during the
follow-up period. In this study, it was aimed to evaluate whether
inflammatory markers such as CRP / Alb ratio, Neutrophil /
Lymphocyte ratio, MPV are significant for the disease in patients
diagnosed with Behçet’s disease in outpatient clinic conditions.

METHODS: We retrospectively examined the demographic and

clinical data of 28 patients with Behçet’s Disease, and similar
age 28 control groups. We calculated NLR, CAR, and MPV
values with the SPSS v25 program.

RESULTS: There were 28 patients, including 16 men (80%).

In the control group, there were 24 females (66.7%), 4 males
(20%). The mean age of the patient group was 38.8 (St: 12.2).
Mean Platelet Volume (MPV), p value:0.08 (mean: 0.54,
St:0.30), CRP/ALB rate (CAR) p:0.63(Mean: 0.008, St:0.17),
Neutrophil/Lymphocyte Ratio(NLR) p value:0.08(Mean:2.51,
St:1.19)

CONCLUSION: In Behçet’s disease, tests such as C reactive

protein (CRP), sedimentation (ESR), thrombocyte (Plt),
mean thrombocyte volume (MPV), neutrophil count, and
albumin are easily used routinely in the follow-up of the
disease and complications. The relationship between MPV and
complications such as recurrent aphthous stomatitis, thrombosis,
and ocular involvement in Behçet’s disease. High risk of MPV
and thrombosis is correlated with low-grade inflammatory
conditions, cardiovascular-cerebrovascular disorders. In
our study, the MPV ratio was not significant in the Behçet’s
disease group compared to the controls. Neutrophil (N) and
lymphocyte(L) count can be obtained from the complete white
blood count part. In Behçet’s disease, a higher N / L ratio was
found in the control and inactive Behçet groups. In our study, the
N / L ratio was not significantly higher than the control group.
CRP is an acute-phase reactant (AFR) synthesized mainly by
hepatocytes under the control of proinflammatory cytokines.
Albumin is a negative acute phase reactant.The CRP / Alb ratio
(CAR) is a new inflammatory marker. CAR has been shown
to have a prognostic value in lung cancer, with a significant
correlation with overall survival. In a retrospective study
involving patients with rheumatoid arthritis, CAR was found to
be higher than controls and positively correlated with DAS28-
ESH. Recently, CAR value was evaluated as a prognostic factor

263
 POSTER
PRESENTATIONS

264
PP-01 [Corrective, Aesthetic and Cosmetic Dermatology] PP-02 [Phototherapy, Photodynamic Therapy]

Treatment of Keratosis Pilaris Rubra with 577-nm Pro- Treatment Results of Mycosis Fungoides with continuously
yellow Laser 200 mJ / cm2 Narrow-band UVB: Case Series

Selami Aykut Temiz1, Arzu Ataseven2, Recep Dursun2 Selami Aykut Temiz1, Mavişe Yüksel2, Selim Gümüş3, Ali
1
Clinic of Dermatology, Konya Ereğli State Hospital, Konya, Balevi2, Şükrü Balevi3
Turkey
1
Clinic of Dermatology, Konya Ereğli State Hospital, Konya,
2
Department of Dermatology, Necmettin Erbakan University Turkey
Meram Medical Faculty, Konya, Turkey
2
Department of Dermatology, Istanbul Medipol University,
Istanbul, Turkey
Keratosis pilaris rubra (KPR) is a rare group of idiopathic hereditary 3
Department of Dermatology, Necmettin Erbakan University
disorders of keratinization, and it is considered as variants of Meram Medical Faculty, Konya, Turkey
keratosis pilaris. Keratosis pilaris rubra is an aesthetically
distressed situation, and especially vascular erythema is the Narrow-band UVB (NB-UVB) therapy remains the gold
most common complaint. In the literature, pro-yellow laser standard in early stage mycosis fungoides (MF) therapy. There
therapy has never been used before in keratosis pilaris rubra. is insufficient data in the literature about how to continue the
treatment in patients who cannot increase the dose due to erythema.
In our study, four patients with keratosis pilaris rubra treated with
pro-yellow laser in Necmettin Erbakan University Meram Faculty In this study, the files of seven patients who were clinically and
of Medicine Cosmetology Unit between December 2017 and histologically diagnosed as having MF between September 2010
March 2019 were evaluated. Objectifying a clearance of erythema and April 2020 and whose initial dose did not show erythema at
> 75% was clinically evident in three patients, in the fourth patient, 200 mJ/cm2 and could not tolerate the increase in dosage were
erythema regressed approximately 50 %. There has been no retrospectively evaluated. In our study, a complete response
recurrence of the lesions after a minimum six months follow-up. (CR) was seen in four patients (57.1%), and a partial response
(PR) was observed in three patients (42.9%). The mean number
As a result, the pro-yellow laser is a well option for the treatment of treatment sessions was 358.6 ± 222.6. The mean cumulative
of keratosis pilaris rubra. Additionally, we think that the well ultraviolet (UV) dose was 71.7 ± 44.9 J/cm2. The mean duration of
tolerance to treatment and a low incidence of serious side effects remission was 15.7 ± 10.5 months. The recurrence rate was 57.1%.
make it a very reliable therapy. Further clinical studies are
needed to improve our findings. As a result, although long treatment times are required in the
treatment of NB-UVB in such patients, treatment and recurrence
rates were not found to be very different from the literature.
Based on our findings, it may be recommended that NB-UVB
Keywords: Keratosis pilaris rubra, laser treatment, pro-yellow, treatment cannot tolerate the increase in dose, and that patients
577-nm laser, vascular laser who develop erythema continue with minimal doses. We think
that further prospective controlled studies are needed in this
regard.
Figure 1
Keywords: Mycosis fungoides, phototherapy, narrow-band
UVB, 200 mJ/cm2

Table 1
Patient Age, Skin TNM Clinical Number of Remissionduration
No gender phototype Stage response sessions (months)
1 45, F III IB PR 120 12
2 85, F III IA CR 310 8
3 36, F IV IA CR 160 24
4 64, M III IB CR 520 8
5 72, M IV IB CR 650 36
6 75, F III IA PR 590 10
The significant reduction in erythema of the lesion 7 55, F IV IB PR 160 12

The clinical features of patients (PR: Partial Response, CR:

Complete Response, M: Male, F: Female)

265
PP-03 [Dermatology and Internal Medicine, including Skin Figure 1
Manifestations of Systemic Diseases]

Superior vena cava syndrome: a case report

Mustafa Ürün, Yıldız Gürsel Ürün, Haydar Yöndem
Department of Dermatology, Faculty of Medicine, Trakya
University, Edirne, Turkey

INTRODUCTION: Superior vena cava syndrome (SVCS) is a

medical condition that consists of a collection of symptoms and
signs resulting from the obstruction of the superior vena cava
(SVC). The most common underlying cause is bronchogenic
carcinoma. Common presenting complaints of patients with
SVCS include dyspnea, cough, face or upper neck swelling,
The clinical pictures of the patient
upper extremity swelling, dilated chest veins, chest/shoulder
pain, hoarseness, flushing/plethora, syncope/presyncope and
headaches. Timely diagnosis of SVCS and treatment of the PP-04 [Acne and Related Disorders, Hidradenitis
underlying disease are critical. Here we report a case of SVCS Suppurativa]
caused by small cell lung cancer.

CASE: A 73-year-old male patient was admitted to our outpatient Nodular Cystic Acne Treated with Systemic Dapsone: Case
clinic with the complaint of swelling around his eyes for 3 series
weeks. He also complained of shortness of breath, difficulty
Munise Daye1, Selami Aykut Temiz2
in swallowing, cough, flushing, headache and hoarseness. In 1
Department of Dermatology, Necmettin Erbakan University
dermatological examination, in addition to bilateral infraorbital
Meram Medical Faculty, Konya, Turkey
edema, widespread edema in the neck region and on the back of 2
Clinic of Dermatology, Konya Ereğli State Hospital, Konya,
both hands, erythema on the face and neck region, and dilated
Turkey
vessels on the chest and back were present (Figure 1). There
was bilateral rhonchi in the lungs in other system examinations. Dapsone (4,4’-diamino diphenyl sulfone) is an aniline
Hemogram and biochemical tests were normal. He had a history derivative treatment agent derived from synthetic sulfones that
of chronic obstructive pulmonary disease, diabetes mellitus, have both anti-bacterial and anti-inflammatory effects. It was
benign prostatic hyperplasia and 30 pack-year smoking. In his first used in the treatment of leprosy in 1940. It was later used
family history, one of his uncles had died of lung cancer. Chest in the treatment of dermatitis herpetiformis and non-infectious
radiography showed a large mass in the right hilar region and inflammatory dermatoses.
bilateral perihilar lymphadenopathies. Thereupon, the patient
was consulted to the chest diseases department. Neck ultrasound Acne vulgaris (AV) is a chronic inflammatory disease of the
and computed thorax tomography were requested from the pilo-sebaceous unit. It is characterized by open and closed
patient. While edema was detected in the skin and subcutaneous comedones, inflammatory papules, pustules, nodules and cysts,
tissues in the neck ultrasound, computed thorax tomography which can cause scar formation and altered pigmentation.
revealed an 8 cm diameter mass compressing the SVC in the Abnormal follicular keratinization, increased sebum production,
upper right lobe of the lung. The patient subsequently underwent propionibacterium acnes colonization and inflammation are
a bronchoscopic biopsy and the biopsy was consistent with small blamed for AV pathogenesis.
cell lung cancer. With these findings, the patient was diagnosed
We planned dapsone treatment in four patients in whom
with SVCS and was referred to the thoracic surgery department.
systemic isotretionine was initiated due to severe nodular cystic
CONCLUSION: Here, we present a patient who applied to AV, but could not be continued due to elevated liver enzymes.
our outpatient clinic due to angioedema and was subsequently We present four AV cases who respond well to systemic dapsone
diagnosed with SVCS. Patients with SVCS may develop life- (Figure 1) to draw attention to dapsone as a treatment option in
threatening complications such as laryngeal or cerebral edema resistant AV.
and may sometimes be referred to the outpatient clinic with skin
Keywords: Dapsone, isotretinoin, nodulocytic acne
findings. We believe that early detection of the characteristic
skin manifestations by dermatologists is crucial for improving
the prognosis of patients with SVCS.

Keywords: Superior vena cava syndrome, angioedema, dilated

cutaneous vessels, lung cancer

266
Figure 1 and biological agents (including secukinumab and infliximab),
however successfully treated with adalimumab.

Keywords: Psoriasis, anti-tnf agents, biologics, adalimumab,

infliximab, secukinumab

PP-06 [Cutaneous Oncology]

Cutaneous Nodules as an Initial Manifestation of

Neuroendocrine Carcinoma with Unknown Primary Site: A
Case Report
Mahmut Esat Tanrıbilir1, Ceren Bilkan Öge2, Esra Adışen1
1
Department of Dermatology, Gazi University, Ankara, Turkey
2
Department of Pathology, Gazi University, Ankara, Turkey

Neuroendocrine tumors are heterogenous group of neoplasms

arising from cells of neuroendocrine origin. They have a wide
spectrum of clinical behavior and malignant potential. Cutaneous
metastases of these tumors have been reported very rarely. We
report a patient diagnosed with metastatic neuroendocrine
carcinoma after a biopsy was performed from his skin nodules.
Cutaneous nodules were one of the first manifestations of his
Clinical appearances before and after treatment internal malignancy and helped us to diagnose and manage the
patient.
PP-05 [Psoriasis] A 72-year old man visited our clinic with multiple nodules on
his trunk. He had a history of jaundice, malaise and weight
Successful treatment of severe pustular psoriasis with loss for 3 weeks. His cutaneous nodules first appeared on right
adalimumab after treatment failure of infliximab and subclavicular area, followed by 4 new nodules on trunk within
1 week. Nodules were rapidly enlarging, but he did not describe
secukinumab any symptoms. He was brought to emergency department with
Shohrat Arazov1, Arzu Ataseven1, Selami Aykut Temiz2, Koray intractable jaundice and constitutional symptoms a few days
Durmaz3 ago. Hepatobiliary ultrasonography was performed. In the head
1
Department of Dermatology, Necmettin Erbakan University of pancreas; 2.5-cm sized, hypoechoic mass containing cystic,
Meram Medical Faculty, Konya, Turkey necrotic areas was observed.
2
Clinic of Dermatology, Konya Ereğli State Hospital, Konya,
The patient was directed to oncology department and
Turkey
malignancy work-up has been started. He was consulted to our
3
Clinic of Dermatology, Bilecik Bozüyük State Hospital,
dermatology department for diagnosis of cutaneous nodules. In
Bilecik, Turkey
the dermatologic examination; painless, firm, dome-shaped, red-
Generalized pustular psoriasis (GPP) is a rare, severe and purplish five discrete nodules were present on right subclavicular
potentially life-threatening inflammatory skin disease that is area, abdomen and right lateral site of thorax. (Figure 1 and 2)
characterized by recurrent, acute onset, generalized pustular A biopsy was taken from the lesions, monomorphic, atypical
eruptions on inflamed or erythematous skin. small cells with round, hyperchromatic nuclei were seen in
subcutaneous tissue with hematoxylin&eosin staining. (Figure
Biological agents such as an interleukin (IL)-12 and IL-23 3) Tumor cells were stained positive with chromogranin,
blocker (ustekinumab), tumour necrosing factor (TNF)-α synaptophysin, CD56 and TTF-1 (Figure 4 and 5); but negative
blockers (infliximab, adalimumab, etanercept, e.g.) and IL-17 with CK7, CK20, CD45, CDX2. Immunohistochemical staining
inhibitors (e.g., ixekizumab, secukinumab) have revolutionized features of cells were compatible with metastatic neuroendocrine
the treatment of psoriasis and pustular psoriasis. However carcinoma. Ki-67 proliferation index was studied and more
concerns remain about drug options for the patients who have than %95 proliferative activity was reported. (Figure 6)
drug-resistant GPP. Again, there are deficiencies in the literature Further diagnostic tests were initiated to detect the primary
regarding which drug to choose after resistance development. tumor. In his thoracoabdominal computed tomography (CT);
In our case, the success of this treatment change, which was 12x10 cm sized, lobulated mass containing cystic and necrotic
not reported in the literature before, in pustular psoriasis, a rare areas was observed in the right lung parenchyma. The mass
disease, was remarkable. was obliterating right main bronchus and invading right
middle and inferior lobe arteries. Tumoral masses were also
Herein, we report a case of severe GPP resistant to conventional
observed in head and neck of pancreas and adrenal glands in

267
CT. Thoracentesis was performed, but atypical cells were not Figure 3
observed. Endoscopic retrograde cholangiopancreatography
(ERCP) procedure was performed by gastroenterologists.
During ERCP, a biopsy was taken from ampulla of Vater; but
neuroendocrine tumor or a tumor with epithelial origin could
not be detected histopathologically. The exact location of
primary tumor was still being investigated; etoposide/cisplatin
chemotherapy has been started for metastatic neuroendocrine
tumor.

Keywords: Neuroendocrine tumor, cutaneous metastasis,

cancer of unknown primary

Figure 1

Monomorphic, atypical small cells with round, hyperchromatic

nuclei in subcutaneous tissue are seen in hematoxylin&eosin
staining.

Figure 4

Immunohistochemical features of tumor cells. Tumor cells are

A firm, painless, 3x2-cm sized, purple nodule on the right immunoreactive with (A) chromogranin and (B) synaptophysin.
subclavicular area
Figure 5
Figure 2

Immunohistochemical features of tumor cells. Tumor cells are

immunoreactive with (A) TTF-1 (SP141 clone) and (B) CD56.

A painless, smooth-contoured, round-shaped, 2x2-cm sized red-

purple nodule on the right lateral site of thorax

268
Figure 6 CONCLUSIONS: Flagellate hyperpigmentation was previously
thought as a dose-dependent reaction with cumulative doses
greater than 100 U, however local and low dose administrations
may also lead the same reaction. Case 1 that we report here is
the second case in the literature that developed after one session
of intralesional bleomycin (30 U) administration for venous
malformation. Although harmless, pigmentation may be a
cosmetic concern for some patients. Clinicians should be aware
of this rare side effect of bleomycin that is independent of dose
and route of administration.

Keywords: flagellate hyperpigmentation, bleomycine,

acquired hyperigmentation, drup eruption

Figure 2

Tumor cells are stained diffusely positive with Ki-67.

PP-07 [Adverse Drug Reactions, TEN]

Flagellate hyperpigmentation as a unique complication

caused by either local or systemic bleomycin
administration: Two case reports
Ece Gökyayla1, Kamer Gündüz1, Beyza Türe1, Peyker Temiz2
1
Department of Dermatology and Venereology, Manisa Celal
Bayar University, Manisa, TURKEY
2
Department of Pathology, Manisa CelalBayar University, Ill-defined diffuse linear hyperpigmentation on dermoscopy
TURKEY (x10) of Case 1.

INTRODUCTION & OBJECTIVES: Bleomycin is used Figure 3

either systemically for the treatment of some malignancies
or intralesional for the treatment of warts and vascular
malformations. Flagellate hyperpigmentation is a rare and
unique side effect of bleomycin. The lesions are mostly found
on the back and flanks, preceding pruritic linear erythematous
lesions fade over time into hyperpigmentation.

MATERIALS & METHODS: Two flagellate hyperpigmentation

cases followed by either intralesional or systemic exposure to
bleomycin are presented.

RESULTS: Case 1. A 23-year old female patient had multiple

linear brown macules on the lomber region and on the lower
extremities that developed after one session of intralesional
bleomycin (30 mg) injection for the venous malformation on
her left palm. Dermoscopic examination revealed ill-defined
diffuse hyperpigmentation. Orthokeratosis, mild acanthosis
and dermal perivascular inflammatory cell infiltration were
seen in histopathological examination. Case 2. A 31-year
old male patient had multiple linear brown macules on his Brown, linear brown macules on the patient’s chest (a) and
chest and upper back. He was treated with one cycle of BEP back (b) of Case 2.
protocol (bleomycin, etoposid and cis-platin) for 21 days with
the diagnosis of testicular mixed germ cell tumor. Bleomycin
was given 30 mg per week with a total dose of 90 mg. Ill-
defined diffuse hyperpigmentation was seen on dermoscopic
examination.

269
Figure 4 PP-08 [Adverse Drug Reactions, TEN]

Neutrophil-to-lymphocyte Ratio Is A Prognostic Predictor

In Emergency Department Patients With Cutaneous
Adverse Drug Reaction
Zerrin Defne Dündar1, Munise Daye2
1
Department of Emergency Medicine,Necmettin Erbakan
University Meram Medical Faculty,Konya,Turkey
2
Department of Dermatology,Necmettin Erbakan University
Meram Medical Faculty,Konya,Turkey

INTRODUCTION & OBJECTIVES: The skin is the most

frequently affected organ by adverse drug reactions.While
the most common drug reactions with benign course are
maculopapular or urticarial rashes,severe cutaneous adverse
drug reactions are AGEP, DRESS, Stevens-Johnson syndrome
Superficial orthokeratosis, mild acanthosis and dermal (SJS), TEN aren’t good. Neutrophil-to-lymphocyte ratio (NLR)
perivascular inflammatory cell infiltration (H&E, x100) is a simple parameter that indicates the systemic inflammatory
state of patients, a good marker to predict prognosis and mortality
Figure1 in many diseases. There is limited data on the prognostic value
of NLR in patients with cutaneous adverse drug reactions. We
aimed to evaluate the prognostic value of NLR in emergency
department (ED) patients with cutaneous adverse drug reactions

MATERIAL & METHODS: In this retrospective study,patients

who admitted to the ED and requested consultation from the
Department of Dermatology with the diagnosis of cutaneous
adverse drug reaction between 2014 and2020 were included.The
ethical committee approved the study.Age(18>),gender,existing
comorbid diseases,drug history thought to trigger the rash,
dermatological examination findings,eruption distribution
areas,type of drug reaction, hospitalization information of the
patients were recorded.Patients with known hematological
diseases,received chemotherapy in the last week before ED
admission,patients who had missing complete blood count were
excluded from the study.The NLRs of patients were calculated
using the recorded neutrophil and lymphocyte counts.For
primary outcome(hospitalization), the patients were divided
into two groups: hospitalized and discharged from the ED. For
the secondary outcome(type of drug reactions), the patients
were grouped five groups.The hematological parameters were
compared between the patient groups.
Brown, linear brown macules on the patient’s back (a) and
femoral region (b) of Case 1. RESULTS: A total of 135 patients were included in the study.The
median age of patients was 50 (36-64),63(46.7%) of them were
male.79.3% of the patients had a history of taking a single drug,the
leading drugs that triggered the reaction in those patients taking
single drug were antibiotics(31.9%),analgesics(24.4%).The
most common comorbiditiy was hypertension (15.6%).71.9%
of the patients had acral,73.3% of the extremity,28.9% of
the oral mucosa involvement.The most common diagnoses
were maculopapular(32.6%), anaphylaxis/angioedema/
urticarial(31.1%),EM/SJS/TEN (13.3%). 79 (58.5%) of 135
patients were hospitalized.Hospitalized and discharged from
the ED patients compared, oral mucosal involvement was
significantly higher in hospitalized patients(39.2% vs.14.3%,
p=0.002).The median NLR of hospitalized patients was

270
significantly higher than discharged patients from the ED(6.13 with metil prednisolone 40 mg/day,antihistamines,emprically
vs.3.69,p=0.006).The median NLR of the patients with the EM/ ceftriaxone,topical moderate steroid,eau borique %2 cold dress
SJS/TEN was significantly higher than maculopapular and fixed and moisturizers.All of the eruption regressed in one week and
drug eruptions(p=0.022,p=0.015). labarotory tests were regressed.
CONCLUSION: NLR can be used prognostic parameter CONCLUSION: Hydroxychloroquine is a treatment choice
for the patients who admitted to th ED with severe cutanous for COVİD 19 an ıt has potential side effects, such as (AGEP).
adverse eruptions.It can be use to decide hospitalization of Tthere are few AGEP reports due to favipravir. SARSCoV2
patients with clinical symptoms might predispose at least some patients to develop severe
atypical AGEP like cutaneous pustular eruption as a late-
Keywords: Adverse Drug Eruption, Neutrophil-to-lymphocyte onset skin manifestation associated with COVID-19 due to its
ratio, Emergency, Dermatology possible effect on the immune system and may also prone the
patients to develop late-onset atypical and bizarre drug-induced
PP-09 [Inflammatory Skin Diseases] skin reactions.

An AGEP Case Due to COVİD-19 or Favipravir Keywords: COVİD-19,AGEP,Favipravir

Munise Daye1, Pembe Oltulu2 Figure 1

1
Department Of Dermatology,Necmettin Erbakan University
Meram Medical Faculty,Konya,Turkey
2
Department of Pathology,Necmettin Erbakan University
Meram Medical Faculty,Konya,Turkey

INTRODUCTION & OBJECTIVES: The new coronavirus

(SARS-CoV-2), the cause of the 2019 corona virus disease
(COVID-19),is very infectious and is the primary cause of
the current pandemic.Many systemic symptoms affecting
the upper airways, lungs, and gastrointestinal tract have been
associated with COVID-19.Urticarial, erythematous-papular/
vesicular lesions usually present on central body,and chilblains/
perniosis on acral sites are the reported COVID-19 associated
dermatological manifestations.These skin lesions have been
reported before or during the active COVID-19 infection.
Several drugs have been used empirically for the treatment
of COVID-19. Some of the described cutaneous eruptions in
COVID-19 could also be related to these drugs. There are few
reports about treatment-related mucocutaneous drug reactions
of COVID-19.AGEP is characterized by the acute onset of
generalized non-follicular sterile pustules. AGEP is mainly
caused by drugs in most cases, there have been few reports of
AGEP associated with viral infections.Here we present a patient
with AGEP triggered by COVİD19 or favipravir.

CASE: A 54-year-old man referred to our clinic with widespread

pustular lesions.1 month before He was COVİD19. At that
time, he was treated with oral favipravir,enoxoparin.He had Pustular lesions on an erythematous base and placed on his
no history of other diseases or using any other medications. trunk other parts of body
He abruptly developed extremely pruritic pustular lesions 2
weeks after recovering from COVID-19. The pustular lesions
first appeared on his face and neck and then spread to his trunk
and other parts of body(Figure 1).In labaratory test we observed
leucocytosis:13.940,SGOT:57,SGPT142.3,CRP:109 except this
he was in good general health.Blood,urinary cultures, chest
graphy,abdominal USG were normal. On histopathological
examination of skin lesions subcorneal pustul and papillary
edema, papillary edama and mild spongiosis in the epidermis,
eritrosit extravasaciation nearby subcorneal pustul,epitelyal
neutrophils,a few eosinophils were observed (Figure2).With
these findings we diagnosed the patient AGEP..We treated patient

271
Figure 2 with crusts and he had no other skin lesion on another part of
his body. He was administered oral tetracycline and niacin with
topical clobetasol propionate and called for examination two
months later. But, there was no improvement of the skin lesion
in the second examination. Furthermore, the lesion was enlarged
and there were thick, adherent crusts on it. Therefore, previous
treatments were discontinued and oral methylprednisolone
16 mg/day and topical mupirocin was administered by
reminding the measures to be taken for COVID-19. At the third
examination which was one month later, due to persistence of
the lesion, oral methylprednisolone dose was increased to 32
mg/day and azathioprine 100 mg/day was added with topical
clobetasol propionate and fusidic acid. Two weeks later,
the lesion showed a little improvement. Thus, azathioprine
100 mg/day and topical treatments were continued and oral
methylprednisolone dose was gradually reduced to 8 mg/day.
COVID-19 pandemic has affected individuals lives in many
ways not only with the disease itself but also with the necessities
that came with it such as continuous wearing of masks. Even
Resim: A) X40,H&E;Subcorneal pustul and papillary though Koebner phenomenon is rare in pemphigus, it was seen
edema B) X200,H&E; papillary edama and mild spongiosis in this patient in consequence of regular mask use.
in the epidermis C) X100,H&E;Subcorneal pustul D)
X400,H&E;Eritrosit extravasaciation nearby subcorneal Keywords: pemphigus, koebner, covid-19
pustul,epitelyal neutrophils,a few eosinophils
PP-11 [Inflammatory Skin Diseases]
PP-10 [Autoimmune Bullous Diseases]
A Rare Condition: Caucasian Patient with Pityriasis
Mask-İnduced Koebner Phenomenon: Persistent Rotunda
Pemphigus Vegetans On The Nose Ece Gökyayla1, Beyza Türe1, Cemal Bilaç1, Peyker Temiz2
Ilknur Kıvanç Altunay, Ilayda Esna Gülsunay, Yasemin Erdem,
1
Manisa Celal Bayar University, Faculty of Medicine,
Ezgi Özkur Department of Dermatology and Venereology
University of Health Sciences, Sisli Hamidiye Etfal Training
2
Manisa Celal Bayar University, Faculty of Medicine,
and Research Hospital Department of Pathology

Pemphigus vegetans is a variant of pemphigus vulgaris; a INTRODUCTION & OBJECTIVES: Pityriasis rotunda is
group of autoimmune blistering disordes characterized by a rare acquired condition and a keratinization disorder which
acantholysis. Pemphigus vegetans is typically characterized by presents with perfectly sharped, scaly, brownish, round patches
vegetating plaques mostly affecting intertriginous areas, scalp usually occur on the buttocks, thighs, trunk, upper and lower
and face. Koebner phenomenon, namely isomorphic response, extremities. The etiology of pityriasis rotunda is not certain but
which is defined as the development of new skin lesions of a it thought to be a variant of ichthyosis vulgaris and diagnosis
pre-existing skin disease following trauma is infrequently is usually based on clinical examination. Pityriasis rotunda is
described in pemphigus. commonly seen in black race with no sex predilection. There are
two types of pityriasis rotunda has defined. Type 1 is the most
Herein, we present a case of 56 year old man with pemphigus common type, seen mostly in black race, patients older than age
vegetans who developed new lesions on his nose following 60, less than 30 lesions and mostly associated with malignancies
the continuous mask wearing due to coronavirus disease-2019 (especially with solid organ malignancies), systemic diseases
(COVID-19) pandemic. The patient had a history of 3 years (most commonly liver disease, female genital tract diseases
pemfigus vegetans. The disease activity had been under control by and malnutrition), and chronic infections (most commonly
different choices of therapies that included methylprednisolone tuberculosis). Type 2 is rare in addition commonly seen in ages
60 mg/day and rituximab. Last infusion of rituximab was younger than 40. It usually presents with more than 30 lesions
administered on 17 February 2020 and methylprednisolone and can be familial in some cases. Type 2 is not associated with
dose was gradually reduced and cessated, The patient had no internal diseases or malignancies. In this report, we represent a
lesions afterwards. However, a short while after the COVID-19 rare case of pityriasis rotunda in a Caucasian patient.
pandemic and the necessity to wear a mask, the patient referred to
our dermatology outpatient clinic with new lesions on his nasal MATERIALS & METHODS: Nineteen year-old male patient
dorsum where the mask irritated the most. At first examination, had non other systemic disorders with pityriasis rotunda is
he had vegetating erythematous plaque on his nasal dorsum presented.

272
RESULTS: Nineteen year-old male patient presented with two Figure 2
weeks history of brownish, scaly round patches on his thigh. He
had no history of any medical conditions or drug use. He did not
have relevant family medical history or any previous skin disease.
Dermatological examination revealed 36 hyperpigmented well-
defined perfectly circular patches 5 to 20 mm in diameter on
left thigh. Dermoscopic examination showed an erythematous
hyperpigmented macules surrounded with peripheral scaling.
Mycological examination was negative for fungal infections.
Skin biopsy was performed. Histopathology of lesion had
superficial hyperkeratosis, perifollicular parakeratosis,
diminished granular cell layer, epidermal acanthosis and
perivascular inflammatory cell infiltration in dermis. The patient
is diagnosed with pityriasis rotunda and topical oinment with
10% urea is given.

CONCLUSIONS: Pityriasis rotunda is a rare skin disorder

may be difficult to diagnose. It seems further rare in white race
and could be a diagnostic dilemma. In differential diagnosis
hereditary or acquired ichthyosis, nummular dermatitis,
mycosis fungoides, tinea corporis, erythrasma, leprosy and
pityriasis alba can be assumed. For work-up, examining scales
with using potassium hydroxide,Wood’s lamp examination and
performing a skin biopsy is required for definitive diagnosis and
exclude other diseases mentioned in differentials. If history and
physical examination is suggestive for any systemic disease or
malignancy, laboratory test should be extended. The prognosis Dermoscopic examination shows central hyperpigmentation
for pityriasis rotunda is good and lesions are not associated with with pinpoint vessels surrounded by scales and crusts
morbidity and mortality by oneself.

Keywords: pityriasis rotunda, caucasion, dermatopathology Figure 3

Figure 1

Superficial hyperkeratosis, parakeratosis located in periphery

of a hair follicle, mild acanthosis, loss of granular layer in
some areas. Some hair follicles are dilated and plugged.
Dermal perivascular chronic inflammatory cell infiltration is
Hyperpgimented, peripherally scaled macules on lower noted.
extremity

273
PP-12 [Dermatology and Internal Medicine, including Skin hydroxychloroquine and anti-RA drugs has been demonstrated.
Manifestations of Systemic Diseases] Excision is considered if joint movement is restricted. In our
study, we wanted to emphasize that rheumatoid nodules should
be considered in the differential diagnosis of diseases with
Rheumatoid Nodule: Is It Due To Medication Or Disease
cutaneous nodules.
Munise Daye1, Begüm Işık1, Sıddıka Fındık2
1
Department of Dermatology, Necmettin Erbakan University Keywords: Rheumatoid Arthritis, Rheumatoid Nodule,
Meram Faculty of Medicine, Konya,Turkey. Cutaneous nodules
2
Department of Pathology, Necmettin Erbakan University
Figure 1
Meram Faculty of Medicine, Konya, Turkey

INTRODUCTION: Rheumatoid nodules(RNs) are the

most common extra-articular manifestation of rheumatoid
arthritis. Rheumatoid factor(RF) is positive in most patients
with rheumatoid nodules. Nodules are nontender and seen on
extensor surfaces such as the olecranon and dorsal part of the
hand, and areas of pressure or repetitive trauma. Nodules can
be seen in lungs, pleura, pericardium, tendons, synovial, bones.
The differential diagnosis of rheumatoid nodules contains
chronic gouty tophi, rheumatic fever nodules, the subcutaneous
nodules found in SLE, nodular or keloidal scleroderma, and the
nodules seen in necrobiosis lipoidica and granuloma annulare. A
63 year-old femalepatient was admitted to our polyclinic having
had the nodules 2 cm and they are firm, nontender, moveable
in subcutaneous space. It was learned that the patient had been
treated for rheumatoid arthritis. To the best of our knowledge,
RNs is important as a clue to dermatologists in the early
diagnosis of Rheumatoid Arthritis(RA).

METHODS AND RESULTS: A 63-year-old female patient

was admitted to our polyclinic having presented with a firm,
non-tender, inflamed, red swelling.1 month of redness in both
elbows and İnflammatory dİscharge ın the left elbow. She had
RA and hypertensıon use methotrexate, methylprednisolone,
hydroxychloroquine. In the dermatological examination, a
firm, nontender, moveable nodules on the olecranon(Figure
1).Histopathologically; Fibrin deposition and necrobiosis is
often seen in center of nodule surrounded by well developed
palisading of CD68(+) histiocytes, vascular granulation firm, nontender, moveable nodules on the olecranons
tissue, lymphocytes were observed (Figure 2a,b,c).Differential
diagnosis were panniculitis,pilomatriccoma,sarcoidosis,lupus Figure 2
tumidus,mycosis fungoides-like panniculitis.The patient was
diagnosed RNs with clinical and histopathological findings.
Topical clobetasol is planned until the biopsy is completed.We
recommended RA treatment and nodule excision to the patient.

DISCUSSION: Classical RNs occur in about 20- 25% of

seropositive RA patients and are the most common extra- a) x20 H&E Rheumatoid nodules in deep reticular dermis.
articular manifestation of RA. Rheumatoid nodules are painful b) x 40 H&E. Rheumatoid nodules in deep reticular dermis
and can cause infection.Rheumatoid nodules are an indication c) X40 CD-68. Histiocytic marker. Positive in palisading of
that extra-articular symptoms will be more severe. Most RNs histiocytes.
are localized for the elbows and fingers. It has been observed
that drugs such as methotrexate, azathioprine, cyclosporine
A increase the risk of developing rheumatoid nodules. In our
case, rheumatoid nodule occurred five years after the disease.
It is not possible to reveal whether the rheumatoid nodule is
due to extraarticular activation of the disease or to DMARDs.
The rheumatoid nodule is self-limited and controlled with
nonsteroidal anti-inflammatory drugs.The effectiveness of

274
PP-14 [Autoimmune Connective Tissue Disorders] Figure 1

A case of dermatomyositis associated with breast cancer

Mustafa Ürün, Yıldız Gürsel Ürün, Nazan Akdağ
Department of Dermatology, Faculty of Medicine, Trakya
University, Edirne, Turkey

INTRODUCTION: Dermatomyositis (DM) is an idiopathic

inflammatory myopathy characterized by proximal muscle
weakness, rash, and other systemic manifestations. It is
associated with malignancy in 3% to 60% of cases. Cancers
that are more strongly associated with DM are lung, ovarian,
pancreatic, gastric, colorectal cancers and non-Hodgkin’s
lymphoma. Breast cancer, the most frequent malignancy
diagnosed in women, may rarely be associated with DM. Here
we report a cases of DM associated with breast cancer.

CASE: A 50-year-old woman was admitted to our clinic with

complaints of swelling around the eyes and gradually increasing
weakness in her arms. Her complaints had been present for
The clinical pictures of the patient
a month and she had applied to the emergency room several
times. In dermatological examination, bilateral periorbital Figure 2
edema, erythema on the face, upper back, and the chest “V”
region, violaceous plaques on the dorsal metacarpophalangeal
and proximal interphalangeal joints, periungual erythema and
cuticular overgrowth were present (Figure 1). Other system
examination revealed mild weakness in the proximal upper
extremities and a 2x2 cm palpable firm mass over the right
breast. Laboratory investigations showed sedimentation rate:
60 mm/hr, C-reactive protein:48 mg/L, creatin kinase: 1980,
ANA 1:160 (+). Skin biopsy taken from the chest was consistent
with interface dermatitis. Elongated capillaries and hemorrhagic
spots were observed on the dermoscopic examination of
the periungual tissue (Figure 2). Electromyography showed
myopathic changes in both proximal superior limbs. Breast
ultrasonography revealed a 2x2,5-cm, irregularly-shaped
nodule in the right breast. A needle biopsy was performed
and pathological diagnosis was ductal carcinoma. With these
findings, the patient was diagnosed with DM associated with
breast cancer and was referred to medical oncology and general Dermoscopy of the periungual tissue showed elongated
surgery department for treatment. capillaries and hemorrhagic spots

CONCLUSION: DM is an idiopathic inflammatory myopathy

that is characterized by distinct skin lesions. Patients with
DM have a high incidence of malignancy. All patients newly
diagnosed with DM should be evaluated for the possibility of an
underlying malignancy. A comprehensive history and physical
examination along with the appropriate investigations should be
done.

Keywords: dermatomyositis, breast cancer, paraneoplastic

syndrome

275
PP-15 [Cutaneous Oncology] Figure 2

Sister mary joseph nodule: a case report

Mustafa Ürün, Yıldız Gürsel Ürün, Çağdaş Yılmaz
Department of Dermatology, Faculty of Medicine, Trakya
University, Edirne, Turkey

INTRODUCTION: Sister Mary Joseph Nodule (SMJN) is a

metastatic umbilical lesion secondary to a primary malignancy
of any viscera, stomach and colon. In approximately 50% of
cases, the SMJN is associated with gastrointestinal malignancies.
It is not only shows the presence of visceral malignancy but
also reveals the poor prognosis of these malignancies. Here,
we present a 53-year-old male patient who presented with an
umbilical nodule and was subsequently diagnosed with SMJN
(umbilical metastasis) associated with gastric signet ring cell-
type adenocarcinoma.
Histopathology revealed signet ring and plasmacytoid cells.
CASE: A 53-year-old male patient was referred to dermatology
outpatient clinic for evaluation of an umbilical lesion. It
was learned that he had a total gastrectomy 5 years ago due PP-16 [Nail Disorders/Diseases]
to stomach cancer and then had received chemotherapy.
Dermatology examination revealed a painless, firm nodule with Periungual basal cell carcinoma: a case report
a diameter of 1.5 cm in the umbilicus (Figure 1). The lesion
had first appeared a month ago and had enlarged gradually. Fatih Göktay, Güldehan Atış, Simge Süel Eroğlu, Pembegül
Laboratory examination showed a normocytic anemia (Hb: 10 Güneş
g/dl, Htc: 28.7%). All other blood chemistry tests were within University of Health Sciences, Hamidiye Medicine
in the normal range. His mother’s father had died of gastric Faculty, Haydarpaşa Numune Training and Research
cancer. A skin biopsy was performed from the umbilical nodule Hospital,Istanbul,Turkey
and histopathology was compatible with signet ring cell-type INTRODUCTION: Basal cell carcinoma (BCC) is the most
adenocarcinoma (Figure 2). The patient was referred to the common skin cancer and is commonly localized on sun-exposed
oncology department for further management. areas such as head, neck and hands. Here we report a case of
CONCLUSION: We find it appropriate to present a case of SMJN BCC occuring in the periungual region which has been described
associated with gastric signet ring cell-type adenocarcinoma rarely in the literature.
because of its rarity. MATERIAL AND METHODS: A 90-year-old man presented
Keywords: sister mary joseph nodule, gastric cancer, signet with a nonhealing wound on the thumb for 6 years. The patient
ring cell carcinoma, cutaneous metastasis had worked as a construction worker in the past and he had
a history of hitting his hand with a hammer several times.
Figure 1 Dermatological examination revealed a 10 x 10 mm in size
erythematous hemorrhagic ulcerated asymptomatic nodule
on the periungual region of left thumb. His medical history
included prostatectomy, bladder stone and an eye region tumor
of which the name is unknown by the patient, excised 30 years
ago. He had no known history of arsenic and X-rays exposure,
and his family history was unremarkable for BCC. Our
preliminary diagnosis was squamous cell carcinoma. A punch
biopsy was performed and resulted as BCC. Standard excision
was performed. Surgical wound was left secondary healing.
Cosmetic and functional result was excellent.

DISCUSSION / CONCLUSION: BCC occurs on the hand only

0.37-2% of all cases. Nail unit BCC has only been reported in
approximately 30 cases in the literature. The average age of the
cases is about 65 year. The fact that BCC is extremely rare in
The umbilical nodule the nail unit although it is an area exposed to sunlight, has been
explained as that other etiological factors such as trauma, arsenic
and radiation exposure may have a role in the development of

276
the disease. The lesions can be seen as onycholysis, longitudinal mm3 confirming the diagnosis of AIDS. Biopsies taken from
melanonychia and periungual ulcerations. Periungual BCC may the tumors showed an increase of spindle cells accompanied
be often confused with other diseases such as chronic paronychia, by cells with mild to complete nuclear atypia, classic sieve-
herpes simplex, pyogenic granuloma, eczema, dermatophyte like pattern and HHV-8 positivity. Meanwhile the PET-CT
or bacterial infections, squamous cell carcinoma, amelanotic scan revealed disseminated pulmonary and gastrointestinal
melanoma. In the treatment of the lesions, the most widely used involvement. The patient was followed up in the intensive care
method with low relapse rate is Mohs micrographic surgery and unit and immediately treated with HAART and single agent
the next one is standard excision. Other treatments are the use chemotherapy (liposomal doxorubicin).
of topical imiquimod, radiation therapy, topical 5-fluorouracil,
intralesional interferon, electrodesiccation, curettage and The presentation of KS ranges from minimal mucocutaneous
cyrosurgery. Our patient had a history of trauma which can be the disease to extensive organ involvement. A surge in KS cases
etiological factor of his lesion. Our case presented clinically with was noted just prior to the identification of the AIDS epidemic
ulceration like other periungual BBCs reported in the literature. in the early 1980s. AIDS-related KS is the most common KS
BCC was not among our prediagnoses due to its atypical presentation in the United States. Estimates indicate that the risk
localization and clinical characteristics. After histopathological of KS in people living with HIV from 2009-2012 was 500-fold
diagnosis, standard excision was performed with clear surgical higher than for the US general population. KS accounts for 12%
margins. An excellent result was obtained with secondary healing. of cancers in people living with HIV, with 765 to 910 new cases
BCC should be kept in mind in the differential diagnosis of per year in the US. The AIDS related Kaposi sarcoma is known
ulcerated lesions located around the nail. Such lesions should to have a more aggressive course and patients diagnosed in late
not be treated empirically without a histopathological diagnosis. stages are related to high mortality and morbidity. We want to
Early diagnosis and appropriate treatment of lesions are present this case to remind the importance of the early diagnosis
important in preserving the function of the fingers of patients. and treatment of HIV related Kaposi sarcoma with its aggressive
and poor course.In these patients all mucosal surfaces should be
Keywords: basal cell carcinoma, nail unit, unusual site examined.

PP-17 [Cutaneous Oncology] Keywords: dermatology, dermato-oncology, HHV-8, HIV,

Kaposi sarcoma
Generalized Mucocutaneous Involvement of Kaposi
Sarcoma in a HIV-Positive Patient Figure 1

Tugba Kevser Uzunçakmak, Dursun Dorukhan Altınışık, Özge

Aşkın, Zekayi Kutlubay, Server Serdaroglu
Istanbul Univrsity-Cerrahpasa, Cerrahpasa Medical Faculty,
Department of Dermatology

Kaposi sarcoma(KS) is usually a slow growing angioproliferative

spindle cell tumor derived from enndothelial and immune cells
infected by Human herpes virus (HHV)-8.Kaposi sarcoma was
classified into 4 different types according to etiology including
the AIDS-related (epidemic), iatrogenic (immunosuppressant
therapy related). Although all types of KS have in common
infection with HHV-8, each has a distinct clinical course.

Herein we want to present a 57-year old patient presented to our

out-patient clinic with the chief complaint of dysphagia and weight
loss due to large tumours covering the gingiva, buccal mucosa and
the hard palate, physical examination revealed multiple violaceous
tumours on his face and neck, he had remarkably large tumours
located on his upper and lower eyelids, large plaques covering
his body and upper extremities, his trunk and large nodular
lesions on the face, upper and lower eyelids and the neck. In the
buccal mucosa he had multiple large tumours biggest measuring
up to 3*1,5cm in size. The patient’s history previously revealed
the tumours appearing 2 years before the patients presentation,
but the patient didn’t seek any medical care. Viral serology,
biopsy and PET-CT scan was performed for diagnosis and
staging. The viral serology resulted in positive anti-HIV and
HIV RNA confirming. CBCs revealed a CD4+ count of 232/

277
PP-18 [Inherited Skin Diseases] Figure 2

A Rare Case of Pachyonychia Congenita in a 19-month-old boy

Hatice Pelin Demirel Bulut1, Düriye Deniz Demirseren2, Emine
Tamer1
1
Department of Dermatology, University of Health Sciences,
Ankara, Turkey
2
Department of Dermatology, University of Ankara Yildirim
Beyazit, Ankara, Turkey
bilateral hyperkeratotic follicular papules on knees
I. INTRODUCTION
Pachyonychia congenita (PC) is one of the rare autosomal Figure 3
dominant disorders of keratinisation caused by a mutation in
the genes encoding keratin. Mutant keratin gene is also defining
phenotypic features of the disease. Affected areas included nail
bed, oral mucosa, teeth pilosebaceus unit and palmoplantar
skin. The main presentation of the disease is including toenail
dystrophy, focal keratoderma and plantar pain but also
presents with hyperhidrosis, oral leukokeratosis, follicular
hyperkeratosis, hoarseness, and palmoplantar keratoderma.
Here, we present a case of Pachyonychia congenita who
applied mainly with nail findings and diagnosed both physical Nevus flammeus (a) and anguler cheilits (b)
examination and genetic testing.
2. CASE REPORT PP-19 [Dermatopathology]
A 19 month--old boy was referred to our department because
of the onset and progression of nail deformity and difficult to A case of discoid lupus erythematosus: Widespread
trim. (Figure 1) Nail deformity had been since birth. He had no erythematous involvement of the face
family history. In pyhsical examination, he had hyperkeratotic
and discolorated nails all of the digits. He had also follicular Derya Erdoğan1, Yasemi̇ n Yuyucu Karabulut1, Ümi̇ t Türsen2
hyperkeratotic papules both on his knees, anguler cheilitis and
1
department of pathology,mersin university,mersin,turkey
pink-to-red, patch with irregular borders located on the occipital
2
department of dermatology,mersin university,mersin,turkey
area thought as nevus flammeus. (Figure 2-3) With these A 57-year-old female patient was admitted to the dermatology
findings we thought it was the one of the keratinisation disorders outpatient department with the complaint of crusting and redness
with sporadic mutation. The diagnosis of Pachyonychia on her nose, cheeks and forehead that started 3 months ago. In
congenita was made in consideration of the clinical examination her medical history she had NSAID medication for joint pain.
and genetic tests. He consultated to otorhinolaryngology for Dermatological examination revealed the erythematous, scaly
laryngeal involvement and genetic department about to type the plaques over the face, nose and accompanied by scarring and
mutation. Application of emollient with urea was recommended hypopigmentation.
considering the age of the patient.
The aim of this case report to underline the importance of Histopathologic findings show mild hyperkeratosis with
the dermatological examination. Patient presenting with nail follicular plugging, atrophic epidermis, thickening and tortuosity
findings should have a detailed physical examination and of the basement membrane, hydropic degeneration of basal
pachyonychia congenita should be kept in mind in differantial cells, dermal perifollicular and periappendicular lymphocytic
diagnosis. inflammatory infiltrate, intersititial mucin deposition, edema,
extravasation of erythrocytes and lymphoplasmacytic infiltrates
Keywords: pachyonychia congenita, nail dystrophy,
surround ecrine coils in the deep dermis. İnterstitial mucin deposits
genodermatoses, keratinisation disorders.
are present in the adjacent stroma among collogen bundles.
Figure 1 Diagnosis: Discoid lupus erythematosus(DLE)

DISCUSSION: DLE is a dermatosis that is localized in 80% of

patients and occurs mainly on sun-exposed areas of the skin,
such as the scalp, face, and ears. In 20% of cases it occurs on
the extremities and upper trunk (1) The lesions are typically
scaly, erythematous macules or papules and are found on
sun-exposed skin areas, including the face, scalp and neck. A
Hypertrophic nail distrophy on both hands (a) and foot (b) digits. case report eyelid lesions occur in only 6% of cutaneous LE
cases,and isolated eyelid involvement is an extremely unusual

278
presentation; case typifies the frequent delay in diagnosing DLE fibrin deposits within multiple capillaries, and no remarkable
due to its nonspecific clinical presentation in unusual anatomical inflammation (Figure 2). Clinical and histopathological
sites.(2) Due to its autoimmune etiology, women are affected findings were consistent with Nicalou syndrome (embolia
more than men, and it can affect any age group, although it is cutis medicamentosa). After 15 days of treatment, the lesion
more common in individuals between the ages of 20 and 40 (3). completely regressed with only minimal hypopigmented
DLE is a common type of cutaneous lupus that is chronic and is irregular scarring (Figure 3). Besides, serum creatine kinase
typically associated with atrophy and scarring of the skin. The level reduced to normal limits (76 U/L).
primary discoid lesion is a discrete erythematous papule or plaque
with adherent scaling, follicular plugging, atrophic scarring, CONCLUSION: Nicolau syndrome is a rare drug adverse
central hypopigmentation, and hyperpigmented borders. reaction that may emerge out following subcutaneous glatiramer
Direct immunofluorescence (DIF) of lesions shows granular acetate injection although the patient is on a long-lasting
deposits of immunoglobulin G at the dermal-epidermal junction. treatment.
DIF should be used as a confirmative, not as a necessary criterion Keywords: Nicalou syndrome, embolia cutis medicamentosa,
for DLE diagnosis (4,5). glatiramer acetate, intramuscular injection
Keywords: Discoid lupus
erythematosus,mucin,immunoglobulin G PP-21 [Angiology, Haemangiomas, Vascular Malformations,
Vasculitis]
PP-20 [Adverse Drug Reactions, TEN]
Cavernous hemangioma of the foot: A case report
Nicolau Syndrome Following Subcutaneous Glatiramer Gül Şekerlisoy1, Ceylan Başkan1, Ilknur Altunay1, Yasemin
Acetate Injection Erdem1, Deniz Tunçel2
1
Department of Dermatology, Şişli Hamidiye Etfal Research
Pelin Eşme1, Irfan Gahramanov1, Egemen Akıncıoğlu2, Gulşen and Training Hospital, İstanbul, Turkey
Akoğlu1 2
Department of Pathology, Şişli Hamidiye Etfal Research and
1
University of Health Sciences, Gulhane Training and Research Training Hospital, İstanbul, Turkey
Hospital, Department of Dermatology and Venereology,
Ankara, Turkey INTRODUCTION: Cavernous hemangiomas are benign
2
University of Health Sciences, Gulhane Training and Research vascular tumors. Cavernous hemangioma. It is most often
Hospital, Department of Pathology, Ankara, Turkey seen at birth or infancy. The incidence of these tumors in the
extremities varies from 4.9% to 28.5%. The pathogenesis of
INTRODUCTION: Nicolau syndrome (embolia cutis cavernous hemangiomas is not certain yet. Pregnancy, infection,
medicamentosa) is a rare iatrogenic complication of injectable and trauma are associated with their formation and development.
medications usually after intramuscular injection that can lead to Microscopically, cavernous hemangiomas are masses of dilated,
skin necrosis. Herein we report a case of a 34-year-old woman thin-walled vessels or sinuses, lined with endothelium and
with a history of tenderness, local heat sensation, and redness surrounded by a fibrous connective tissue stroma. We present
on umbilical region who was diagnosed with Nicolau syndrome a 17-years old male with cavernous hemangioma of the foot
following subcutaneous glatiramer acetate injection.

CASE PRESENTATION: A 34-year-old woman presented with CASE: 17- years old male patient referred to our clinic for
painful discoloration over her abdominal skin. She had been on multiple painless nodule his foot present for 4 years and no
treatment with subcutaneous glatiramer acetate injections thrice other pathological symptoms. He had no previous history
weekly for multiple sclerosis for 18 months. Shortly after the of any medical illness. In his dermatological examination,
last injection, she described tenderness, local heat sensation, and there are multiple viyolese conglemerated nodules. There
redness around the injection site. On the second day, the lesion is no anomaly on the blood sample. An incisional biopsy
had expanded with some purple blotches. When the patient was from lesions were performed. The histopathological
admitted to our centre on the third day, we observed a large, examination was reported as cavernous hemangioma.
tender, and erythematous patch with bizarre livedoid purpuric
areas on the left side of the umbilical region (Figure 1). Laboratory DISCUSSION: Several classification systems have been
analyses revealed complete blood count, liver and renal function described for hemangiomas ranging from four to nine categories,
tests, inflammatory markers, and coagulation parameters were which are based on depth, clinical appearance, histology, and
within normal limits except elevated serum creatine kinase level location. In general, there are capillary hemangiomas, cavernous
(714 U/L; normal range: 24-170). Superficial ultrasonography hemangiomas, combined or mixed types, and diffuse or systemic
showed dermal oedema without any collection of fluid. After hemangiomas. The occurrence of cavernous hemangiomas
performing a skin biopsy, topical betamethasone valerate cream involving the foot is rare.
and mucopolysaccharide polysulfate cream twice daily were Keywords: Cavernous hemangioma, Foot, Vascular Tumor
recommended. Histopathological examination of the lesion
showed marked epidermal ischemia, necrotic keratinocytes,

279
PP-22 [Adverse Drug Reactions, TEN] Figure 2.

A case of erythema multiforme major in a patient with

COVID 19: The role of corticosteroid treatment
Abdullah Demirbaş1, Ömer Faruk Elmas2, Mustafa Atasoy3,
Ümit Türsen4, Torello Lotti5
1
Department of Dermatology, Evliya Çelebi Training and
Research Hospital, Kütahya Health Sciences University,
Kütahya, Turkey
2
Department of Dermatology, Kırıkkale University, Kırıkkale,
Turkey
3
Department of Dermatology, Health Science University,
Kayseri City Hospital,, Kayseri, Turkey
4
Department of Dermatology, Mersin University, Mersin,
Turkey
5
Department of Dermatology, Guglielmo Marconi University,
Rome, Italy

In December 2019, the cases of pneumonia of unknown etiology Erythematous targetoid lesions distributed over the palmar
were reported in Wuhan city Hubei province of China. Severe surfaces.
acute respiratory syndrome coronavirus 2 (SARS - CoV - 2)
pathogen, a novel coronavirus, was detected from the lower Figure 3.
respiratory tract samples of infected patients, and this virus-caused
respiratory tract infection was termed Coronavirus Disease 2019
(COVID - 19). The disease has been reported to show different
types of cutaneous findings including urticarial, maculopapular,
erythema multiforme-like, varicella-like, purpuric, livedoid, and
thrombotic-ischemic lesions. Given the high mortality rate of the
disease, prompt and accurate identification of the relevant skin
manifestations may play a significant role in the early diagnosis
and appropriate management of the entity.Here, we will present
an erythema multiforme major developing in a 37-year-old
female patient with COVID-19.

Keywords: COVID-19, Erythema multiforme major,

Corticosteroid
Ulcerated lesions involved the lower lip and tongue
Figure 1.

Erythematous targetoid lesions distributed over the dorsal sides

of the hands.

280
PP-23 [Dermatology and Internal Medicine, including Skin caused by HAART-related immune restoration are called
Manifestations of Systemic Diseases] Immune Reconstitution Inflammatory Syndrome (IRIS), and
the relationship between IRIS and Jessner’s lymphocytic
infiltration has not been reported previously.
Superficial thrombophlebitis in a patient with COVID 19:
Heparin treatment after evaluation of D – Dimer Keywords: Jessner’s Lymphocytic Infiltration, Hiv, Immune
Reconstitution Inflammatory Syndrome
Abdullah Demirbaş1, Ömer Faruk Elmas2, Ümit Türsen3,
Mustafa Atasoy4, Torello Lotti5 Figure 1.
1
Department of Dermatology, Evliya Çelebi Training and
Research Hospital, Kütahya Health Sciences University,
Kütahya, Turkey
2
Department of Dermatology, Kırıkkale University, Kırıkkale,
Turkey
3
Department of Dermatology, Mersin University, Mersin,
Turkey
4
Department of Dermatology, Health Science University,
Kayseri City Hospital,, Kayseri, Turkey
5
Department of Dermatology, Guglielmo Marconi University,
Rome, Italy Erythematous infiltrated multiple plaques on the forehead
Coronavirus Disease 2019 (COVID-19) is a respiratory tract
disease caused by severe acute respiratory syndrome coronavirus Figure 2.
2 (SARS-CoV-2), which first appeared on December 1, 2019
in Wuhan, China. The pandemic was declared by World Health
Organization on March 11, 2020. The role of obstructive
vasculopathy has been an essential topic of discussion in
the pathogenesis of COVID-19. Endothelial damage and
autoimmune mechanisms have been reported to contribute to
the development of microvascular thrombosis and occlusion.
Furthermore, severe COVID-19 cases have been shown to be
complicated by disseminated intravascular coagulation. Here,
we present a case of superficial thrombophlebitis that developed
in a patient with COVID-19
Keywords: COVID-19, Superficial thrombophlebitis, Heparin,
D-Dimer

PP-24 [Inflammatory Skin Diseases]

Jessner’s lymphocytic infiltration as a symptom of Immune Erythematous infiltrated multiple plaques on the neck.
Reconstitution Inflammatory Syndrome in an HIV-infected
patient: A case report Figure 3.
Abdullah Demirbaş1, Zeliha Esin Çelik2
1
Department of Dermatology, Evliya Çelebi Training and
Research Hospital, Kütahya Health Sciences University,
Kütahya, Turkey
2
Department of Dermatology, Selçuk University, Konya,
Turkey

Jessner’s lymphocytic infiltration is a benign, chronic, T cell

infiltrative skin disease that often appears as erythematous
papules or plaques on the face, neck and back. We are
presenting a case which is 36-year-old male patient with HIV
infection, presenting with a large number of erythematous
infiltrated plaques on forehead and neck depending on
immune restoration following highly active antiretroviral In the dermis, perivascular and periadnexal intensive
therapy (HAART). Inflammatory or autoimmune disease cases lymphocyte infiltration (HE X 100).

281
PP-25 [Dermatopathology] with brown pigments (Papanicolaou, x100; Papanicolaou,
x200) (a,b), loosely cohesive, atypical epithelioid cells with
Refining diagnosis is the prerequisite for the correct multinucleation, prominent nucleoli and intranuclear inclusion
(cell block; H&E stain, x200) (c), cytoplasmic HMB-45 staining
treatment: the cytodiagnostic utility of SOX10 in the in cell block (x200) (d), focal weak positivity with Melan-A
diagnosis of metastatic melanoma (x200) (e), diffuse nuclear positivity for SOX10 (x200) (f).
Asuman Kilitçi1, Ömer Faruk Elmas2, Abdullah Demirbaş3,
Mehmet Gamsızkan4, Mustafa Atasoy5, Ümit Türsen6, Torello PP-26 [Infectious Diseases, Parasitic Diseases, Infestations]
Lotti7
1
Department of Pathology, Kırşehir Ahi Evran University, Eccrine chromhidrosis due to SARS-CoV-2 virus infection
Kırşehir, Turkey
2
Department of Dermatology, Kırıkkale University, Kırıkkale, treated with favipiravir
Turkey Muge Gore Karaali
3
Department of Dermatology, Evliya Çelebi Training and Department of Dermatology, Erzincan Binali Yıldırım
Research Hospital, Kütahya Health Sciences University, University, Mengücek Gazi Training and Research Hospital,
Kütahya, Turkey Erzincan, Turkey
4
Department of Pathology, Düzce University, Düzce, Turkey
5
Department of Dermatology, Health Science University, A 31-year-old otherwise healthy male was examined in
Kayseri City Hospital, Kayseri, Turkey dermatology outpatient clinic for abnormal palmar pigmentation
6
Department of Dermatology,Mersin University, Mersin, for 2 days. On dermatologic examination, well-demarcated,
Turkey irregularly-edged brown, hyperpigmented patches on his left
7
Department of Dermatology,Guglielmo Marconi University, palm were noted and, there was brown hyperpigmentation
Rome, Italy on the tip of the 5th finger of his right hand and on that nail
bed. He had applied to the emergency department 2 weeks
Melanoma is known to have a strong tendency to metastasize to ago with the complaint of muscle pain and sore throat. A
any part of the body. It is usually not easy to made a diagnosis nasopharyngeal swab was taken for PCR (polymerase chain
based only on cytological characteristics in metastatic melanoma, reaction) for SARS-CoV-2, which was positive. He had been
since melanoma can exhibit a wide variety of cytological diagnosed as COVID-19 infection without pneumonia or any
features, imitating different types of epithelial, mesenchymal, other complications. He received 5 days of oral favipiravir and
lymphoid malignancies. Metastatic tumors may have different 10 days of subcutaneous enoxaparin treatment. Laboratory tests
cytological characteristics than primary ones. Therefore, were normal. Wood examination was unremarkable. Exogenous
an accurate diagnosis of metastatic melanoma can be a real pigmentation was ruled out because the patient denied the
challenge. HMB-45, Melan-A, S-100, cytoplasmic markers history of with any substance, dye, henna, antiseptics, etc. A
for melanocytes, are frequently used immunocytochemical 4-mm punch biopsy was taken and the patient was diagnosed
markers in cytology practice. However, their sensitivity has as eccrine chromhidrosis and treated with topical emollient
been demonstrated to be suboptimal, and their expression rates only. Five days later the lesions were markedly disappeared.
may be lower in metastatic lesions. SOX10, a nuclear marker, A 28-year-old male admitted to the emergency department
is considered more reliable than cytoplasmic and membranous for abnormal hand pigmentation for 1 day. Due to COVID-19
markers. Here, we present the utility of cytodiagnostic markers infection he received the same regimen, that ended 5 days
such as SOX 10 in a 60-year-old male patient with metastatic ago. Due to clinical diagnosis of eccrine chromhidrosis he
melanoma. was treated with topical emollient without histopathological
examination. His complaints regressed completely within 3 days.
Keywords: Metastatic melanoma, SOX10,Treatment Coronavirus disease is a pandemic disease caused by the
SARS-CoV-2 virus, that primarily affects the respiratory
Figure 1. tract epithelium. It has been reported that the disease
is frequently seen with acral chilblain and pernio-like
lesions,erythematous maculopapular rashes, viral exanthem,
vesicular eruptions, urticarial eruptions and livedoid lesions.
Eccrine chromhidrosis is a rare disorder characterised by the
excreation of coloured sweat via the eccrine sweat glands.
Although it is known that exogenous excretions of the drugs
can also cause eccrine chromhidrosis, it has been shown in
publications that SARS-CoV-2 spike proteins are found in
eccrine cells in chilblain-like skin lesions. To the best of our
knowledge there has been no previous reported cases in the
Cytomorphological examination of the metastatic melanoma literature with eccrine chromhidrosis in COVID-19 patients.
demonstrated large, pleomorphic, atypical tumor cells
Keywords: chromhidrosis, ecrine, COVID-19, palmoplantar

282
PP-27 [Cutaneous Oncology] early diagnosis of PCMZL, early detection of relapses, and
Trichoscopic Features of Primary Cutaneous B-Cell rapid tumor intervention.
Lymphoma
Keywords: Cutaneous, dermoscopy, lymphoma, scalp,
Dilara Güler, Işın Öncü, Gülhan Gürel trichoscopy
Department of Dermatology, Afyonkarahisar Health Science
University, Afyonkarahisar, Turkey Figure 1

Primary Cutaneous Marginal Zone B-Cell Lymphoma (PCMZL)

is very rare, malignant lymphoproliferative B-cell disorder.
PCMZL mainly involves the skin and extracutaneous spread
is rare. PCMZL is characterized by slowly growing infiltrated
red to violaceous multifocal papules, plaques, or nodules with
a predilection for trunk, arm or head. Lesions sometimes may
resolve spontaneously but patients may have recurrence.

The prevalence of scalp involvement in PCMZL is unknown. To

our knowledge, trichoscopic features of scalp PCMZL have not
been previously reported.

A 43-year-old woman presented with a nodule on scalp for

several months. Hodgkin lymphoma in the patient’s sibling
of family history. An incisional biopsy was performed in
another center about 1 month ago, histopathological diagnosis
was unknown.On physical examination, there was a endure,
erythematous and painless nodule on the scalp (Fig. 1). The
dermoscopic examination an organized lesion with multiple Asymptomatic erythematous nodule on the scalp
follicular plugs, that were surrounded by shiny white lines and
thin, subtle arborizing and serpentine vessels on the periphery Figure 2
over an salmon colored background (Fig. 2). Excisional
biopsy of the nodule was performed and histopathological
examination showed a distinct diffuse small lymphocytic cell
infiltration was detected around the perivascular and skin
appendages accompanied by histiocytes, eosinophils, and a
small number of multinucleer giant cells, starting from the
superficial dermis to the subcutaneous adipose tissue, leaving
a thin grain zone in the epidermis forehead. Neoplastic small
lymphoid cells were CD19, CD20, CD23, Bcl-2-124 positive,
CD10, CD30, Cyclin D1, Bcl-6, EBV negative. The patient
was evaluated by the hematology department for systemic
involvement. Considering the clinical and histopathological
findings, the patient was diagnosed with PCMZL.
In the literatures, the studies reports PCMZL cases within the
head/neck area, but no clinical photographs and dermoscopy
concerning specifically the scalp area were included in the
manuscript. The most commonly reported dermoscopic features
in other areas were branching/arborizing or serpentine vessels,
scale, white lines/circles, follicular plugging, ulceration and
a orange-salmon-colored background. Trichoscopic features
similars to the dermoscopy of common areas of PCMZL.
PCMZL presenting as solitary tumors can be confused with
pseudolymphomas, amelanotic melanoma, BCC, SCC, and
adnexal tumors, keloid among others. Although dermoscopic
findings may improve the clinical recognition of PCMZL useful Dermoscopy of the nodule revealed an organized lesion with multiple
in clinical practice, these features are not sufficient for the follicular plugs (black arrow) that were surrounded by shiny white lines
(yellow arrow) and thin, subtle arborizing and serpentine vessels on the
diagnosis of PCMZL and histopathology remains mandatory.
periphery (red arrow) over an orange background and pink periphery
In conclusion, this report shows for the first time trichoscopic (polarized light dermoscopy, original magnification ×10). The asterisk
features of scalp PCMZL. The dermoscopic findings of scalp represents a previous biopsy site.
PCMZL are not specific, but these findings are important for

283
PP-28 [Dermatological Surgery] Figure 1.

Axillary giant lipoma opening to the skin surface: A unique

presentation mimicking accessory breast
Asuman Kilitçi1, Ömer Faruk Elmas2, Abdullah Demirbaş3,
Osman Memiş4, Mustafa Atasoy5, Ümit Türsen6, Torello Lotti7
1
Department of Pathology, Kırşehir Ahi Evran University,
Kırşehir, Turkey
2
Department of Dermatology, Kırıkkale University, Kırıkkale,
Turkey
3
Department of Dermatology, Evliya Çelebi Training and
Research Hospital, Kütahya Health Sciences University,
Kütahya, Turkey
4
Department of General Surgery, Manavgat State Hospital,
Antalya, Turkey
5
Department of Dermatology,Health Science University,
Kayseri City Hospital, Kayseri, Turkey
6
Department of Dermatology,Mersin University, Mersin,
Turkey
7
Department of Dermatology,Guglielmo Marconi University,
Rome, Italy
Lipomas are benign tumors of mature adipose tissue originating A giant axillary mass with spontaneous rupture 11x8,5 cm in
from subcutaneous tissue or internal organs. A total of ten diameter, protruding from the left axillary region (a). Gross
patients with axillary giant lipoma has been reported in the examination of the excision specimen showed an encapsulated
relevant literature (Table 1). However, none of them showed yellow fatty tissue partially opened to the skin surface (b).
spontaneous perforation. The pathogenesis of the uncontrolled H&E sections of the overlying skin showed epidermal atrophy,
growth of giant lipomas is clearly unknown. It has been suggested degenerated collagen fibers, numerous dermal dilated vascular
that rupture of the fibrous septa following trauma may cause structures and mixed inflammatory infiltration (c). H&E sections
proliferation of adipose tissue. According to another hypothesis, of the mass revealed mature benign adipose tissue (d).
local inflammation related to trauma may induce differentiation Figure 2.
of pre-adipocytes and disrupt the normal regulation of adipose
tissue. We though that, in the current patient, the growth of
the lesion may have been triggered by repetitive microtrauma
caused by each movement of the upper limb. Prolonged pressure
on the lesional area due to the patient being bedridden may have
caused the overlying skin to break down and eventually rupture.
Here, we present a 78-year-old female patient with a large
lipoma in the left axillary region.

Keywords: Giant lipoma, accessory breast, histopathological

examination

Perforated part of the lipoma with surrounding skin (H&E).

284
Table 1

Pathologic speci- Pathologic specimen

Case Gender Age Duration Site Treatment
men size size
Left Total excision with
1 Male 15 9 years 19x16x14 cm None
axilla primary closure

Right Total excision with

2 Female 50 18 months 20x18x9 cm None
axilla primary closure

Right Total excision with Unremarkable except for

3 Male 32 4 years 24x10x6 cm
axilla primary closure dilated veins

Left Total excision with

4 Female 62 5 years 16x15x5 cm None
axilla primary closure

Right Total excision with

5 Male 70 6 years Unavailable None
axilla primary closure

Right Total excision with

6 Male 47 4 months 28x24x4 cm None
axilla primary closure

Left Total excision with

7 Female 42 2 months 10.5x8x3 cm None
axilla primary closure

Right Total excision with

8 Male 60 5 years 15x10 cm None
axilla primary closure

Left Total excision with

9 Male 38 9 years 32x15x6 cm None
axilla primary closure

Left Total excision with

10 Male 18 unavailable 23x10x5 cm None
axilla primary closure
The main features of the patients with axillary giant lipoma
reported in the relevant literature

PP-29 [Autoimmune Bullous Diseases]

A case of COVID-19 in a patient with pemphigus COVID-19 is an infection caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) that first identified
on azathioprine: successful management with
December 2019. It is not considered just a respiratory disease
methylprednisolone but a multisystem disorder. Well-known risk factors for mortality
Abdullah Demirbaş1, Ömer Faruk Elmas2, Mustafa Atasoy3, and morbidity include advanced age, male gender, hypertension
Ümit Türsen4, Asuman Kilitçi5, Torello Lotti6 and immunosuppressive conditions. We present a case of
1
Department of Dermatology, Evliya Çelebi Training and COVID-19 that developed in a 36-year-old female patient who
Research Hospital, Kütahya Health Sciences University, received azathioprine therapy with a diagnosis of pemphigus.
Kütahya, Turkey
2
Department of Dermatology, Kırıkkale University, Kırıkkale,
Turkey Keywords: Pemphigus, COVID-19, azathioprine,
3
Department of Dermatology, Health Science University, methylprednisolone
Kayseri City Hospital,, Kayseri, Turkey
4
Department of Dermatology, Mersin University, Mersin,
Turkey
5
Department of Pathology, Kırşehir Ahi Evran University,
Kırşehir, Turkey
6
Department of Dermatology, Guglielmo Marconi University,
Rome, Italy

285
PP-30 [Autoimmune Bullous Diseases] and sulci is especially more visible in dark-skinned patients
due to the contrast with unaffected dark skin. Here, we would
Case of COVID-19 in a patient with Pemphigus successfully like to briefly discuss the role of dermatoscopy as an adjunctive
managed with favipiravir diagnostic tool that will facilitate the diagnosis of AN.
Abdullah Demirbaş1, Ömer Faruk Elmas2, Mustafa Atasoy3, Keywords: Dermatoscopy, Acanthosis nigricans, Diagnosis
Gözde Ulutaş Demirbaş4, Ümit Türsen5, Torello Lotti6
1
Department of Dermatology, Evliya Çelebi Training and Figure 1.
Research Hospital, Kütahya Health Sciences University,
Kütahya, Turkey
2
Department of Dermatology, Kırıkkale University, Kırıkkale,
Turkey
3
Department of Dermatology, Health Science University,
Kayseri City Hospital,, Kayseri, Turkey
4
Department of Dermatology, Akçaabat Haçkalı Baba State
Hospital, Trabzon, Turkey
5
Department of Dermatology, Mersin University, Mersin,
Turkey
6
Department of Dermatology, Guglielmo Marconi University,
Rome, Italy

Coronavirus disease 2019 (COVID-19) is a multisystemic

infectious disease caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2). COVID-19 has caused many
social, cultural, and economic problems since declared as
a pandemic by the World Health Organization and caused
disruptions in health activities. The management of cutaneous
diseases, including pemphigus, has also been affected from Dark, velvety papules and plaques distributed over the axillary
the difficulties and disruptions caused by the pandemic.Here, region
we present a case of COVID-19 in a patient with Pemphigus
successfully managed with favipiravir. Figure 2.

Keywords: COVID-19, Pemphigus, Favipiravir

PP-31 [Dermoscopy]

The utility of dermatoscopy in the diagnosis of acanthosis

nigricans
Ömer Faruk Elmas1, Abdullah Demirbaş2, Ömer Kutlu3,
Asuman Kilitçi4, Mustafa Atasoy5
1
Department of Dermatology,Kırıkkale University,
Kırıkkale,Turkey
2
Department of Dermatology, Evliya Çelebi Training and
Research Hospital, Kütahya Health Sciences University,
Kütahya, Turkey
3
Department of Dermatology, Uşak University, Uşak, Turkey
4
Department of Pathology, Kırşehir Ahi Evran University,
Kırşehir, Turkey
5
Department of Dermatology,Health Science University,
Kayseri City Hospital, Kayseri, Turkey

Recently, dermatoscopy has become an indispensable diagnostic

tool in dermatology practice. Dermatoscopic features of many
neoplastic and non-neoplastic cutaneous conditions have been well Dermatoscopic examination showed multiple cristae (blue
described. However, only a few studies have aimed to identify the arrows) and sulci (red arrows), multiple white to brown
dermatoscopic features ofAN.The reported dermatoscopic features exopyhtic papillary structures (black arrows) and black
for mild to moderate AN include diffuse dark brown background, blotches (white arrows).
cerebriform appearance, multiple cristae, sulci, milia-like cysts
hyperpigmented dots, and streaks.The pattern of multiple cristae

286
Figure 3. Figure 1.

Confluent, scaly, and annular plaques with central clearance

on the back (a). Complete clearance of the lesions following
Histopathological examination showed epidermal hydroxychloroquine treatment (b). Dermatoscopic examination
papillomatosis, hyperkeratosis, hyperpigmentation of the basal revealed a peripheral distribution of dotted and irregular
layer, and upward finger-like projection of dermal papillae linear vessels on a reddish background (c). Histopathological
(H&E, x100) examination showed basal vacuolar degeneration, and
subepidermal perivascular and periadnexal lymphocytic
infiltration (d).
PP-32 [Autoimmune Connective Tissue Disorders]

PP-33 [Atopic Dermatitis/Eczema]

Dermatoscopy of subacute cutaneous lupus erythematosus
Ömer Faruk Elmas1, Abdullah Demirbaş2, Asuman Kilitçi3, Unilateral and Flexural Pityriasis Rosea: An Atypical
Mustafa Atasoy4
1
Department of Dermatology,Kırıkkale University, Presentation
Kırıkkale,Turkey Orhan Şen1, Seray Külcü Çakmak1, Emine Tamer1, Devrim
2
Department of Dermatology, Evliya Çelebi Training and Tuba Öcalan2
Research Hospital, Kütahya Health Sciences University, 1
Departmant of Dermatology, Ankara City Hospital, Ankara,
Kütahya, Turkey Turkey
3
Department of Pathology Ahi Evran University, 2
Departmant of Pathology, Ankara City Hospital, Ankara,
Kırşehir,Turkey Turkey
4
Department of Dermatology, Health Science University,
Kayseri City Hospital,, Kayseri, Turkey Pityriasis rosea (PR) is an acute, self-healing, papulosquamous
eruption of unknown etiology. It usually presents as symmetrical,
Dermatoscopic examination may provide helpful clues in multiple, oval, scaly papules and plaques on the trunk.
differentiating SCLE from other differential diagnoses including
pityriasis rosea, psoriasis, granuloma annulare, and mycosis A 45-years-old man was admitted to our outpatient clinic with a
fungoides. Pityriasis rosea generally shows peculiar peripheral mild pruritic eruption which started on his left axilla 2 weeks ago.
collarette scales and patchy distribution of dotted vessels. On dermatological examination there were multiple macules and
Psoriasis is usually characterized by regularly distributed dotted patches with peripheral collarette scaling on the left axillar and
vessels on a dull red background. Granuloma annulare displays popliteal fossa. The physical examination and routine laboratory
red to yellow background with or without dotted and short linear tests were normal. Histopathological examination revealed
vessels. Mycosis fungoides is characterized by spermatozoon- parakeratosis, mild spongiosis, erythrocyte extravasation in
shaped vascular structures, short linear vessels, and orange to superficial dermis and perivascular dematitis with lymphocytic
yellow patchy areas. Here, we present a case of subacute lupus infiltration. The patient was diagnosed as unilateral pityriasis
erythematosus in a 43-year-old male patient. rosea with flexual distribution and topical corticosteroid therapy
was prescribed.
Keywords: Dermatoscopy, subacute cutaneous lupus
erythematosus, histopathology We wanted to share our patient as unilateral pityriasis rosea
which also has a flexural distribution is a very rare condition.

Keywords: pityriasis rosea, unilateral, atypical, flexural

287
Figure 1 Figure 1

PP-34 [Inflammatory Skin Diseases]

Early prurigo pigmentosa: A diagnostic challenge

Muazzez Cigdem Oba
Department of Dermatology, Health Sciences University,
Sancaktepe Sehit Prof.Dr.Ilhan Varank Research and Training
Hospital, Istanbul, Turkey

INTRODUCTION: Prurigo pigmentosa is a recurrent

inflammatory skin disease with unknown etiology. Typical
clinical features are reticularly arranged pruritic urticarial
Clinical features at initial presentation with erythematous
papules and reticular hyperpigmentation. However, early
papulovesicles
presentations may lack specific features of the disease. Here,
we report a case of early prurigo pigmentosa misdiagnosed as
Figure 2
insect bite reaction.

CASE: A 24-year-old lady presented to our outpatient clinic

with a four-day history of intensely itchy eruption. She did
not have any medical antecedents and denied any medication
use. Dermatologic examination revealed erythematous
papulovesicular lesions on the lateral neck, nape of the neck,
at supraclavicular and intermammary regions (Figure 1). An
insect bite reaction was suspected. The patient was prescribed
topical steroid and systemic antihistamine. One week later, she
presented with exacerbation of her symptoms. Papulovesicular
lesions were replaced by reticularly arranged urticarial papules
(Figure 2). Upon questioning, the patient reported cutting down
on carbohydrates. She refused biopsy. With clinical diagnosis
of prurigo pigmentosa doxycycline 100 mg BID was started.
Lesions completely resolved at one week, leaving only subtle
hyperpigmentation (Figure 3). At three month follow up there
was no recurrence.

CONCLUSION: It is difficult to diagnose early stages of

prurigo pigmentosa, especially in the lack of reticular pattern
and hyperpigmentation. A change in diet should be questioned
in young patients with a recent onset of pruritic eruption. As
patients may refuse biopsy due to cosmetic concerns, clinicians
should be familiar with typical dermatologic findings of the
disease.
Clinical features at 1 week with typical reticularly arranged
Keywords: diagnosis, diet, prurigo pigmentosa urticarial papules

288
Figure 3 Dermatological examination revealed multiple vesicles, 2 mm
in size, on the patient’s both soles with ant-bite sign (Figure 1).
Hyperpigmented macules and desquamation were also seen.
Based on the patient’s history and physical examination infantile
acropustulosis was diagnosed. The lesions resolved with use
of topical mometasone furoate. Milder attacks were observed
in the six-month follow-up period, all of which responded to
topical steroids.

CONCLUSION: Infantile acropustulosis is very frequently

misdiagnosed as scabies, leading to repetitive and unnecessary
use of anti-scabietic treatment. Distinguishing clinical features
of the two conditions is important. An acral rather than a truncal
eruption with typical ant-bite sign, lack of burrows and absence
of shared pruritus are typical for infantile acropustulosis.

Keywords: acral, acropustulosis of infancy, infant, pustules,

pustulosis, scabies

Figure 1

Complete resolution of the lesions following doxycycline

therapy

PP-35 [Inflammatory Skin Diseases]

A case of infantile acropustulosis with ant-bite sign

Muazzez Cigdem Oba
Department of Dermatology, Health Sciences University,
Sancaktepe Sehit Prof.Dr.Ilhan Varank Research and Training
Hospital, Istanbul, Turkey

INTRODUCTION: Infantile acropustulosis is a benign,

recurrent neutrophilic dermatosis of unknown etiology,
predominantly affecting children aged between 1 to 3 years.
The disease typically presents with episodic attacks of itchy 1 to
4mm vesicles or pustules on the soles and palms. “Ant-bite sign”
without known exposure to ants has been reported as a clue to
the diagnosis of infantile acropustulosis. The major differential
diagnosis is active scabies infestation. Here, we report a case of
infantile acropustulosis with ant-bite sign responsive to topical
steroid treatment.

CASE: A 4-month-old female infant was referred to dermatology

clinic for evaluation of a pruritic pustular rash on both soles. Multiple vesicles with linear arrangement along with
She had a history of scabies that was treated successfully when hyperpigmented macules and desquamation
she was one-month-old. The patient was otherwise healthy. The
lesions had first appeared one month earlier, lasted for two weeks
and subsided spontaneously. New lesions had appeared a week
ago. Topical permethrin was prescribed by the family physician
due to presumed scabies infestation, without improvement.

289
PP-36 [Inherited Skin Diseases] of both forms are similar, showing acantholytic dyskeratosis.
By reporting this case, we would like to point out a different
Segmental Darier Disease: An Unusual Presentation manifestation of DD. DD can present with various clinical
subtypes and physicians should be aware of them to avoid
Ahmet Kağan Özdemir1, Emine Tamer1, Esranur Ünal1, Esra diagnosis delay.
Uçaryılmaz Özhamam2
1
Department of Dermatology, Ankara City Hospital, Ankara, Keywords: Darier disease, segmental, unilateral
Turkey
Figure 1
2
Department of Pathology, Ankara City Hospital, Ankara,
Turkey

INTRODUCTION AND OBJECTIVES: Darier disease (DD) is

a rare autosomal dominant disorder with variable expressivity.
The clinical characteristics of the disease include multiple, red
to brown, crusted, follicular and nonfollicular hyperkeratotic
papules most commonly affecting the seborrheic areas of the
trunk, scalp, face, and neck symmetrically. In approximately
10% of cases, DD may present with localized pattern such as
unilateral, linear, segmental, and zosteriform arrangements.
In this case report, we present a rare case of clinically and
histopathologically confirmed segmental Darier disease.

CASE: A 41-year-old woman who attended to our dermatology

outpatient clinic with a six-year history of itchy skin lesions
on the right side of her neck, which were reportedly worsen
in the hot climates. Physical examination showed numerous
hyperkeratotic, some excoriated, erythematous papules in a
blaschkoid distribution (Figure 1). Lesions were localized
unilaterally, extending from neck to substernal area. Full body
examination did not reveal similar lesions elsewhere; moreover,
mucosal and nail examinations were normal. She did not recall Erythematous keratotic papules in a unilateral blaschkoid
any relatives with a similar condition. A punch biopsy was distribution.
performed on the neck. Histology revealed focal acantholytic
Figure 2
dyskeratosis (Figure 2). The diagnosis of segmental type 1 DD
was rendered, and treatment with tazarotene gel 0.1% instituted
with moderate improvement.

DISCUSSION: DD is caused by mutations in the ATP2A2

gene found on chromosome 12q23-24.1, which encodes the
calcium pump Ca2+ ATPase type 2 (SERCA2), an integral
part of intracellular calcium signal transduction mechanism.
Impaired activity of endoplasmic reticulum disrupts junctional
protein production and causes stress induced apoptosis,
which latter leads to acantholysis and dyskeratosis in DD.
Segmental DD is subclassified into two groups, both with
a distribution of lesions along the lines of Blaschko. Type
1 segmental DD is caused by postzygotic somatic mutation
in the ATP2A2 gene during embryogenesis. In type 1
DD, only affected skin harbors heterozygous ATP2A2
mutation, not the background skin. Type 2 segmental
DD is characterized with generalized DD, with more Biopsy demonstrating suprabasillar acantholytic dyskeratosis
prominent lesions or erosions along the lines of Blaschko. (hematoxylin and eosin stain x100).
Phenotypically, type 1 segmental DD may differ from classic
DD. Nail and oral mucosa lesions are usually absent in this form
and, lesions do not typically involve seborrheic areas. Another
proposed difference of type 1 DD is the age that lesions first
present. The first manifestations of DD usually appear between
ages 6 and 20; but our case and previous case reports demonstrate
a late-onset disease in type 1 segmental DD. Histopathology

290
PP-37 [Allergology and Immunology] PP-38 [Angiology, Haemangiomas, Vascular
Malformations, Vasculitis]
Real-Life Experience of Omalizumab Treatment in 134 Eczematous reaction within a port-wine stain
Patients with Chronic Spontaneous Urticaria
Armağan Kutlay
Elcin Akdas, Esra Adısen, Murat Orhan Oztas, Ahmet Burhan Başakşehir Çam ve Sakura City Hospital
Aksakal, Nilsel Ilter, Ayla Gulekon
A 23-year-old female patient presented with a large port-wine
Department of Dermatology, Gazi University, Ankara, Turkey
stain (PWS) located on the anteromedial surface of her right
BACKGROUND: Omalizumab (anti-Ig E monoclonal thigh that stretched to her right inguinal and pubic regions. The
antibody) is known to be an effective and safe treatment agent patient complained of an itchy and scaly reaction confined to the
in the treatment of chronic urticaria. However, real-life data on borders of the PWS that began 6 years ago and had a waxing
omalizumab therapy in patients with chronic urticaria are still and waning course. The surface of the PWS was uneven, while
limited. the periphery of the lesion was bright red with a slight elevation,
there were blotchy pale and atrophic areas in the center. There
OBJECTIVE: In this study, we aimed to present the survival in were areas of crusting and scaling interspersed on the surface of
the initial dose regimen as well as the responses to the drug dose the PWS. A punch biopsy revealed orthokeratotic hyperkeratosis,
and interval changes in patients who started 300 mg omalizumab focal parakeratosis and crusting, lymphocyte exocytosis in the
every 4 weeks in the treatment of chronic spontaneous urticaria. epidermis, spongiosis, and irregular acanthosis. There was a
mild perivascular lymphocytic infiltration in the dermis with
MATERIALS-METHODS: In this single-center retrospective
sparse eosinophils overlying capillary ectasia. Pathological
analysis, 134 patients who started omalizumab with a diagnosis
findings were consistent with an eczematous reaction.
of chronic spontaneous urticaria between June 2019 and
The patient had no history of atopy or eczema, nor had received
January 2021 and received at least three doses of treatment
laser treatment for her PWS. She could not remember an eliciting
were examined. During the observation period, disease activity,
factor for the eczematous reaction. Color duplex ultrasonography
duration of drug response, clinical response to dose and
did not reveal any venous insufficiency, and there was no
interval changes, duration of treatment, survival of urticaria-
accompanying soft tissue overgrowth. Eczema subsided within
related concomitant medications, and time to relapse after
days following topical corticosteroid therapy but frequent
discontinuation of treatment were analyzed.
relapses were observed, necessitating intermittent use. The
RESULTS: Patients were grouped according to the number of patient was advised to receive pulsed dye laser (PDL) treatment.
doses they stayed on 300 mg omalizumab every 4 weeks. The PWS is a congenital vascular malformation (CVM) characterized
proportions of patients receiving ≤6, 7-15 and ≥16 doses of by well-demarcated, bright or deep red macules and patches
continuous fix 300 mg/4 weeks were 41.8% (n=56), 41% (n=55) clinically, and by ectatic dermal capillaries pathologically. There
and 17.1% (n=23), respectively. 61.9% of the patients were able have been some reports of eczematous reactions seen in CVMs,
to discontinue concomitant antihistamines within the first 6 children with lesions located in the head and neck area comprise
months of the omalizumab treatment. During the observation the majority. There are much fewer reports of adults with lesions
period, 84.3% (n=113) of patients with chronic spontaneous in other locations, which led us to present and discuss our case.
urticaria achieved complete remission or well-controlled The pathomechanism of the eczematous reaction observed in
disease symptoms, 12.7% (n=17) moderately controlled disease CVMs is unclear. It is possible that the somatic mutations harbored
symptoms. by CVMs lead to a pro-inflammatory microenvironment. It
has also been postulated that in grossly visible malformations
CONCLUSION: Omalizumab is an effective and safe treatment with large vascular dilations, such as in the context of Klippel-
to control symptoms in the long term. We recommend adding Treanaunay syndrome, a pathogenesis similar to stasis dermatitis
omalizumab treatment without delay to CSU patients resistant may be the case. In most cases reported in the literature, the
to non-sedative antihistamines. When disease symptoms eczematous reaction is confined to the borders of the vascular
are controlled with 300 mg omalizumab every 4 weeks, we malformation. However, there are a few cases of children with
recommend dose reduction or extending intervals for a cost- a history of atopic dermatitis. Considering the predilection
effective approach. of atopic dermatitis to the head and neck area in children,
eczematous changes observed in the CVMs in these cases may
possibly be a collision dermatosis. There have also been some
Keywords: omalizumab, chronic spontaneous urticaria, real
cases triggered by the inflammation following PDL treatment.
life experience
Although the precise cause is not known, it is a benign and self-
limiting condition. Most patients are responsive to a short course
of topical steroids. In cases with frequent relapses, treatment
with PDL often leads to permanent resolution of eczema.
Keywords: port wine stain, vascular malformation, eczema,
nevus flammeus, Meyerson phenomenon

291
PP-39 [Cutaneous Oncology] Fig 1.

Association of carcinoma en cuirasse and carcinoma

erysipeloides ın a patient with breast carcinoma
Seçil Soylu1, Irem Nur Durusu1, Gülhan Gürel1, Hacer Demir2
1
Department of Dermatology and Venerology, Afyonkarahisar
Health Sciences University, Afyonkarahisar, Turkey
2
Department of Medical Oncology, Afyonkarahisar Health
Sciences University, Afyonkarahisar, Turkey
INTRODUCTION & OBJECTIVES: Of all the carcinomas that
metastasize to the skin, breast cancer is the one with the widest
range of clinical lesions, ranging from carcinoma erysipeloides
The skin on the lesions was stone-hard sclerotic with palpation and
to carcinoma en cuirasse. A woman with primary right ductal
sclerotic tissue with edema and crepitation at the rigth arm
breast cancer complicated with multiple organ metastases and
peritoneal acid, diagnosed with carcinoma erysipeloides and Fig 2.
carcinoma en cuirasse is presented here.
MATERIALS & METHODS: A 60-year-old female patient
with primary right ductal breast carcinoma, was consulted with
seriously hard, red and edematous skin lesions at the right upper
torso, while she was hospitalised at the oncology clinic due to the
multiple organ metastases, pleurisy and acid in the peritoneum.
Dermatological examination revealed a diffuse, darkly colored,
sharply limited erythema with stone-hard sclerotic with palpation
covered the right side of the trunk including the mammarian
tissue and extanding to the right side of the upper abdomen and
back. There were sclerotic tissue with edema and crepitation at
the rigth arm. A skin biopsy was planned with the preliminary
diagnosis of carcinoma erysipeloides, carsinoma en cuirasse,
but the patient was died immediately after her consultation.
RESULTS: From 5%–10% of the patients with breast cancer
develop skin metastases. Of all the carcinomas that metastasize
to the skin, breast cancer may be the one with the widest range
of clinical lesions varying from papulonodules to patches with
erythema mimicking erysipelas (inflammatory carcinoma) Closer view of carcinoma erysipeloides and carcinoma en cuirasse
to woody induration with a peau d’orange appearance. The
latter is often referred to as “en cuirasse ” due to its clinical Fig 3.
resemblance to the leather armor of a soldier ( cuirassier ).
Inflammatory carcinoma (carcinoma erysipeloides) is
characterized by lesions similar to erysipelas. While the histologic
presence of invasive carcinoma invading dermal lymphatics is
supportive of the diagnosis, it is not required, nor is dermal
lymphatic invasion without typical clinical findings sufficient
for a diagnosis of inflammatory breast cancer, as in our patient.
Carcinoma en cuirasse is a diffuse infiltration of the skin that
imparts an indurated and hidebound leathery quality to skin.
This type mainly seen with the breast as within our patient.
CONCLUSIONS: Carcinoma erysipeloides, an inflammatory
carcinoma, has many characteristic features that could be
diagnosed easily by a dermatologist but its association with
carcinoma en cuirasse, a sclerotic form is reported very rarely in
the literature. This case here presented had a distinctive features
that consistent with carcinoma en cuirasse and association with
carsinoma erysipeloides. We wanted to remind as such very rare
disease and emphasize the need for more studies.
Keywords: Carcinoma erysipeloides, inflammatory carcinoma, There were sclerotic tissue with edema and crepitation at the rigth
breast cancer, skin metastase upper right back

292
PP-40 [Pharmacology and Skin-related Toxicology,
Phlebology]

Subcutaneous fat necrosis following transcatheter arterial

chemoembolization with drug-eluting beads
Armağan Kutlay, Harbiye Dilek Canat
Başakşehir Çam ve Sakura City Hospital

A 65-year-old female patient presented to our clinic with the

complaint of numerous painful subcutaneous lumps on her torso.
Her complaints had begun a year ago. On physical examination,
there were subcutaneous lobulated nodules that were hard and
painful upon palpation, dispersed on the abdominal region.
The biggest lump was roughly 10x10 cm wide, located in the
right lower quadrant. On the skin overlying the lesion, there
were patches of brownish discoloration with slight depression.
The patient had a history of chronic hepatitis C virus infection and
hepatocellular carcinoma diagnosed in 2018. Partial hepatectomy
was performed shortly after diagnosis, and transcatheter arterial
chemoembolization with drug-eluting beads (DEB-TACE)
loaded with doxorubicin was performed in 2019. At the time
of presentation, the disease had metastasized to vertebrae.
Two punch biopsies were obtained from the biggest lesion, with
suspicion of panniculitis and cutaneous metastasis. Pathological
examination revealed foreign bodies in the deep dermis that were
consistent with the microparticles used in chemoembolization,
lipid necrosis, foreign-body type multinucleated giant cells,
histiocytes, and chronic active inflammation.

The patient complained of pain despite nonsteroidal anti-

inflammatory drug usage. Intralesional steroid injection was
performed in two sessions, one month apart wih moderate
reduction of pain and some softening of the nodules.

TACE is widely used in the treatment of liver tumors. By

occluding the hepatic artery, it allows selective treatment
of the liver, occluding blood flow to the tumor and
delivering a sustained dose of chemotherapy. However,
some particles used in embolization may reach the skin
through extrahepatic collateral vessels, or through the hepatic
falciform artery, which originates from the hepatic artery.
There have been several reports of transient periumbilical skin
rash following hepatic intraarterial chemotherapy infusion.
However, fat necrosis and foreign body reaction following
DEB-TACE is a very rare complication. Unlike conventional
chemotherapy, DEBs are designed to release drugs slowly, which
leads to a prolonged inflammatory reaction. It is important to
keep it in mind as a delayed complication.

Keywords: TACE, DEB, embolization, fat necrosis

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