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The Diagnosis and Treatment of Nail Disorders

Article  in  Deutsches Ärzteblatt International · August 2016

DOI: 10.3238/arztebl.2016.0509

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CONTINUING MEDICAL EDUCATION

The Diagnosis and Treatment of

Nail Disorders
Uwe Wollina, Pietro Nenoff, Gunter Haroske, Holger A. Haenssle

SUMMARY
Background: Nail disorders can arise at any age. About
T he nail primordia at the ends of the fingers and
toes come into being from the 8th and 9th weeks
of gestation onward; in the 13th week, the nail field
half of all nail disorders are of infectious origin, 15% are and the nail matrix are formed. The latter gives rise to
due to inflammatory or metabolic conditions, and 5% are
the nail plate from the 14th week onward. By the 20th
due to malignancies and pigment disturbances. The differ-
week, the nail plate already covers the entire nail bed.
ential diagnosis of nail disorders is often an area of uncer-
At birth, the nail plate extends beyond the tips of
tainty.
the fingers and toes (eTable) Bezug zur Tabelle
Methods: This review is based on publications and guide- unklar.
lines retrieved by a selective search in PubMed, including The mature nail organ comprises the nail matrix,
Cochrane reviews, meta-analyses, and AWMF guidelines. the nail bed, the nail plate, and the nail fold. The
Results: Nail disorders are a common reason for dermato- proximal portion of the nail matrix is immediately
logic consultation. They are assessed by clinical inspec- adjacent to the distal interphalangeal joint and the in-
tion, dermatoscopy, diagnostic imaging, microbiological sertion of the extensor tendon. The latter gives rise to
(including mycological) testing, and histopathological a dense superficial connective-tissue lamina en-
examination. Some 10% of the overall population suffers veloping the nail matrix (e1). The distal portion of
from onychomycosis, with a point prevalence of around the nail matrix is attached to the nail bed. The nail
15%. Bacterial infections of the nails are rarer than fungal plate covers the distal matrix and nail bed and ends
colonization. High-risk groups for nail disorders include in the free edge of the nail [distal edge of the nail
diabetics, dialysis patients, transplant recipients, and plate?]. The nail plate is covered proximally by the
cancer patients. Malignant tumors of the nails are often cuticle; it is held within the nail fold both proximally
not correctly diagnosed at first. For subungual melanoma, and laterally. The epithelium that directly covers the
the mean time from the initial symptom to the correct di- nail plate proximal to the cuticle is the eponychium.
agnosis is approximately 2 years; this delay is partly re- The horns of the nail plate, which lie under the lat-
sponsible for the low 10-year survival rate of only 43%. eral proximal nail fold, are connected to the bony
Conclusion: Evaluation of the nail organ is an important distal phalanx. The nail bed is distally delimited by
diagnostic instrument. Aside from onychomycosis, which the nail isthmus, which is continuous with the hy-
is a common condition [a common nail disorder?], import- ponychium lying under the free edge of the nail [s.o].
ant differential diagnoses such as malignant diseases, The most distally located structure is the distal
drug side effects, and bacterial infections must be con- groove (1). The isthmus of the nail is [may be? is
sidered. often?] completely covered in congenital pterygium
inversum unguis (2).
►Cite this as:
The nail plate consists mainly of parallel keratin
Wollina U, Nenoff P, Haroske G, Haenssle HA: The diag-
filaments, which give it mechanical stability. Aside
nosis and treatment of nail disorders. Dtsch Arztebl Int
from minerals and cholesterol, about 7% of the con-
2016; 113: 509–18. DOI: 10.3238/arztebl.2016.0509
tent of the nail is water. The nail bed is essential for
horizontal nail growth. The nail plate is 1000 times

Department of Dermatology and Allergology, Dresden-Friedrichstadt Hospital,

Academic Teaching Hospital of the Technical University of Dresden [OK?
Deutsch: “Städtisches Klinikum”?]: Prof. Dr. med. Wollina Components of the nail
Laboratory for Medical Microbiology, Mölbis: Prof. Dr. med. Nenoff The mature nail organ comprises the nail
Georg Schmorl Institute of Pathology, Dresden-Friedrichstadt Hospital, Aca- matrix, the nail bed, the nail plate, and the
demic Teaching Hospital of the Technical University of Dresden [OK?]: Prof. Dr.
med. Haroske nail folds.
Department of Dermatology, Heidelberg University Hospital: PD Dr. med.
Haenssle
 Figure 1: ● be aware of the main types of infectious disease
anatomy of the nail affecting the nail organ and their treatment.
organ Nail plate
(modified from
Nail involvement in inflammatory skin diseases
Blausen.com staff.
Nail involvement in psoriasis often points to the diag-
“Blausen gallery Cuticle
2014”. nosis. It is independent of the severity of skin involve-
Wikiversity Journal ment and can cause functional and cosmetic disturb-
of Medicine. ances and pain (5, e3, e4). Nail symptoms are seen in
DOI:10.15347/wjm two-thirds of all patients with psoriatic arthritis and in
“2014.010. ISSN about 40% of psoriasis patients without arthritis (6,
20018762) Nail fold
e5) (Table 1).
Nail matrix Psoriatic arthritis can be distinguished from rheu-
matoid arthritis by the combination of distal arthritis
with nail changes.

Case presentation
A 46-year-old man presented with pain in one big toe
with isolated yellowish thickening of the nail plate. His
family physician had diagnosed gout, but medication to
lower the uric acid level had not led to any sustained
Nail bed improvement.
Inwiefern gehören die folgenden beiden Absätze noch
zur Fallbeschreibung?
The three-P syndrome (onycho-pachydermo-perios-
titis) [I count only 2 P’s here!] is a special type of psor-
iatic arthritis and an important element in the differen-
more permeable to water than the intact skin and can tial diagnosis of acute gout. An elevated uric acid level
also be a site where exogenous substances are de- is often seen in psoriasis vulgaris because of acceler-
posited, such as medications, drugs of abuse, and ar- ated cutaneous metabolism.
senic (3). The horizontal growth of the nail depends Nail symptoms are present [in Abhängigkeit von der
on an intact connection of the nail plate to the nail Schubschwere] in up to 66% of cases of alopecia area-
bed (e2). Fingernails generally grow faster than toe- ta, with speckling as the main type (e6, e7). Working
nails (3.5 vs. 1.7 mm/month) (4). with wet hands can cause irritative hand eczema, result-
ing in distal onycholysis and brittle nails (8). Allergic
Methods contact eczema with inflammation of the nail folds can
This review is based on pertinent articles retrieved by a be seen in acrylate sensitization due to the use of artifi-
selective search in PubMed and the Cochrane Library, cial nail extensions. Severe cases can be associated
along with the pertinent guidelines of the Association with destruction of the nail plate and acquired ptery-
of Scientific Medical Societies in Germany (Arbeitsge- gium inversum unguis. Ordinary disinfection of the
meinschaft der Wissenschaftlichen Medizinischen hands is ineffective in persons who have artificial nail
Fachgesellschaften, AWMF). extensions (9).

Learning objectives Nail symptoms in general medical disease

This article aims to enable the reader to Inspection of the nail organs is part of the routine
● understand the anatomy of the nail organ, physical examination in internal medicine (Table 2). It
● recognize nail involvement in skin diseases and can reveal a number of conditions:
other medical conditions, ● In the differential diagnosis of rheumatoid vs.
● diagnose the clinical features of the main types of psoriatic arthritis, the nails should be inspected
tumor affecting the nail organ, and for typical psoriatic changes (speckled nails, psor-

Nail involvement in inflammatory dermatoses Nail manifestations of internal diseases

Nail involvement in psoriasis often points to the Inspection of the nail organs is part of the routine
diagnosis. It is independent of the severity of physical examination in internal medicine.
skin involvement and can cause functional and
cosmetic disturbances and pain.
 iatic oil spot, psoriatic onychomadesis) (5, e4). TABLE 1
● As many as 60% of persons with chronic renal disease
have nail manifestations. The double transverse white Nail involvement in selected inflammatory dermatoses
lines known as Muehrcke lines are a sign of hypoalbu- Dermatosis Frequency of nail Manifestations
minemia (< 2.2 g/dL) hin (10). involvement
● Distal ischemia of the acral skin in scleroderma is (%)
a cause of [?] acquired irreversible pterygium in- Alopecia areata 7–66 speckling, trachyonychia, longi-
versum unguis (1, e8). tudinal grooves, leukonychia
● Hourglass nails are a secondary phenomenon aris- Atopic eczena 25 shiny nails, transverse grooves,
ing from clubbing of the fingers. Clubbing is due speckling, paronychia
either to thickening of the soft-tissue covering of Dyskeratosis follicularis 90 onychodystrophy,
the distal phalanx, as in cor pulmonale, or to distal pachyonychia, anonychia
hypertrophic osteoarthropathy, as in chronic dis- Contact eczema 80 (hands) transverse grooves, parony-
eases of the lung or intestines, cancer (as a para- chia, hyperkeratosis or loss of
cuticle and eponychium, brittle
neoplastic phenomenon or as a manifestation of nails
metastases), cardiac valvular anomalies, or
Lichen ruber 10 Onychoschisis, anonychia, dys-
Graves’ disease (1). trophy
Pityriasis rubra pilaris 80 pachyonychia, trachyonychia
Drug-induced nail diseases
Nail symptoms arise in 10–60% of patients undergoing Psoriasis 50 speckling, psoriatic oil spot,
crumbling nails, pachyonychia
anticancer treatment (11) (Table 3). Chronic paronychia
causes pain which restricts fine motor activity (12). Im- Scleroderma 80 trachyonychia, paronychia, pte-
rygium inversum, splinter he-
munosuppressants and chemotherapeutic agents can morrhages
damage the nail plate, leading to Beau-Reil transverse
Systemic lupus 20 red lunule, splinter hemorrha-
grooves and onychomadesis (reversible, painless, non- erythematosus ges
inflammatory proximal detachment of the nail plate)
(e8).

Subungual and periungual tumors

Warts due to HPV are the most common type of be-
nign growth affecting the nails. About 10% of all
children and adolescents have ungual [HPV-in-
duced?] warts; precise data on the [their?] epidemi- Subungual exostoses and mucoid pseudocysts can
ology [of ungual warts] are unavailable. Combi- cause nail deformities. Painful types of nail tumor
nation therapy is more successful than monother- include glomus tumor, osteoid osteoma, and ac-
apy; for example, cryotherapy plus topical salicylic quired digital arteriovenous malformation
acid is more effective than salicylic acid alone (risk (ADAVM) (15–18).
ratio 1.24) (13). Warts should be treated cautiously The most common malignancies affecting the
in order to avoid permanent iatrogenic nail dys- nails are squamous cell carcinoma and Bowen’s dis-
trophy (14). ease (Figure 2e, f). The clinical manifestations of
Granuloma teleangiectaticum arises as a sequela of Bowen’s disease with periungual involvement are
trauma or infection. These lesions tend to bleed (15). erythema, hyperkeratosis, fissures, and scaling; sub-
Fibrokeratoma is an asymptomatic tumor of adulthood ungual involvement leads to onycholysis. Human pa-
that usually arises as a solitary lesion measuring only a millomavirus of types 16, 31, 33, 56, and 71 has been
few millimeters (16). Koenen tumors are usually demonstrated (19). Nodules, hemorrhages, and ulcer-
multiple, are of variable size, and appear periungually ation are signs of invasive squamous cell carcinoma
and subungually; half of all cases arise in persons (e10). These tumors can arise spontaneously, after
under age 18. Koenen tumors are a major diagnostic chronic arsenic exposure, or after organ transplan-
criterion for the tuberous sclerosis complex (e9). tation (19, 20).

Sub- and periungual tumors Common malignancies of the nails

Subungual exostoses and mucoid pseudocysts The most common malignancies affecting the
can cause nail deformities. Painful types of nail nails are squamous cell carcinoma and Bowen’s
tumor include glomus tumor, osteoid osteoma, disease.
and acquired digital arteriovenous malformati-
on.
 TABLE 2

Nail involvement in general medical diseases

Manifestations Diseases
Beau-Reil lines (transverse grooves) Raynaud syndrome, pemphigus, infectious diseases, intoxications
Dolichonychia (long, narrow nails) Marfan syndrome
Yellow nails lymphedema, chronic lung disease, chronic cough, pleural effusion
Mees lines (transverse leukonychia) chronic renal disease, chronic ischemic heart disease, severe infectious diseases,
intoxications (arsenic, thallium, carbon monoxide, other)
Muehrcke lines (transverse double bands) chronic renal disease, cirrhosis, malnutrition
Koilonychia (spoon nails) iron-deficiency anemia, hemochromatosis
Lindsay nails (white proximally, pink-reddish- chronic renal disease with azotemia
brown distally, no blanching)
Quincke’s pulse (alternating flushing and pal- severe, chronic aortic insufficiency
lor of the nail beds)
Acquired tennis-racket nails hyperparathyroidism
Splinter hemorrhages subacute bacterial endocarditis, rheumatoid arthritis, Terry nails (whitish, opaque nail
bed without lunule),cirrhosis, chronic ischemic heart disease, diabetes mellitus,
hyperthyroidism
Triangular lunule and nail dystrophy nephrotic syndrome due to LMX1B mutation
Clubbing of the fingers chronic obstructive pulmonary disease, lung cancer, asbestosis, chronic bronchitis,
congenital heart disease, endocarditis, chronic inflammatory bowel disease
Hourglass nails hypertrophic pulmonary osteoarthropathy (lung cancer, bronchiectasis) –
associated with clubbing

inspection alone.
Case illustration Pigmentation of the cuticle and proximal nail fold (the
A 45-year-old woman presented to a dermatologist with Hutchinson sign) is typical of melanoma, though it is not
progressive onychomadesis of the left thumbnail. Myco- seen in all cases (Figure 2a, c) (22, 23). Dermatoscopy, an
logical cultures were negative. A nail bed biopsy revealed optical technique, is useful for the differential diagnosis
nonspecific inflammatory changes. of nail pigmentation. It reveals individual pigment lines
Onychodystrophy with destruction of the nail plate in of varying color and intensity (Figure 2b, c–f). The ad-
the absence of fungal infection aroused the suspicion ditional information provided by dermatoscopy enables
[”muss an ... denken lassen”] of a malignant tumor of the early detection of disease (23) [Referenz korrekt plat-
nail organ. A second biopsy performed some time later ziert?].
yielded the diagnosis of an acrolentiginous melanoma. The The Hutchinson sign is often absent in in situ or early
definitive treatment was a 3D-guided partial amputation of invasive melanoma (Figure 2a) (24). Advanced melanoma
the distal phalanx of the thumb. is associated with ulcerations, hemorrhages, loss of paral-
Subungual melanoma accounts for 2% of all melanom- lelism of the bands, multiple colors, blurry borders, and
as in persons of European ancestry and up to 20% in per- marked invasion into the neighboring skin. Thicker tumors
sons of Asian ancestry (21). Timely nail biopsy enables the are more likely to infiltrate the bone as well (21). Subun-
definitive diagnosis. Subungual melanoma cannot be re- gual melanomas can also be amelanotic, in which case
liably distinguished from longitudinal melanonychia by they are harder to recognize clinically. A biopsy to rule out

Nail dystrophy of uncertain type Onychomycosis

A biopsy to rule out melanoma is necessary for any Onychomycosis is an infection of the nail apparatus
patient with nail dystrophy, subungual hyperpigmen- by dermatophytes, yeasts, or molds.
tation, or persistent “hematomas” of unknown cau-
se.
 TABLE 3

Drug-induced nail abnormalities

Drug Nail abnormality

Vitamin A dystrophy
Anthracyclines and taxanes painful (photo-)onycholysis, subungual abscesses, melanonychia
EGFR inhibitors paronychia, unguis incarnatus, granuloma telangiectaticum
D-penicillamine, bucillamine yellow nail syndrome
Hydroxyurea melanonychia (brownish-black discoloration)
Indinavir, retinoids, chemotherapeutic drugs onychomadesis, Beau-Reil lines
mTOR inhibitors dystrophy, yellow nail syndrome, distal onycholysis, paronychia
Rituximab multiple granulomata telangiectatica
Tetracyclines, retinoids, clofazimine, zidovudine, quinolo- photo-onycholysis, discoloration
nes

EGFR, epidermal growth factor receptor; mTOR, mammalian target of rapamycin

melanoma is necessary for any patient with nail dystrophy, 29%, molds in 3%, and mixed flora in 5–15% (30).
subungual hyperpigmentation, or persistent “hematomas” Of all the dermatophytes isolated from patients with
of unknown cause. Unfortunately, the mean delay from the onychomycosis, T. rubrum is the most common species
onset of symptoms to surgery is 2.2 years. The prognosis (ca. 91%), followed by T. interdigitale (earlier name:
of subungual melanoma is, therefore, much worse than T. mentagrophytes var. interdigitale) (ca. 7.7%) (30).
that of cutaneous melanoma, with a disease-specific Rarely isolated organisms include Epidermophyton flocco-
10-year survival rate of only 43% (25, 26). It is treated sum and T. tonsurans. These are anthropophilic dermato-
with micrographically guided surgery (21, 22). phytes, i.e., they cause disease only in humans.
Yeasts are so-called emerging pathogens [klingt global -
Infectious diseases of the nails bezieht sich dies hier nicht ausschließlich auf die Ony-
Onychomycosis is an infection of the nail apparatus by chomykosen?] that are now being more commonly diag-
dermatophytes, yeasts, or molds. Tinea unguium (this is nosed as the causative organisms of onychomycosis. Can-
the plural form; if only one nail is affected, tinea unguis) is dida parapsilosis is the most common one, followed by C.
caused exclusively by dermatophytes. Fungal infections of guilliermondii. C. albicans causes chronic mucocutaneous
the nails are stigmatizing for the patient, causing difficul- candidiasis, which involves the entire nail apparatus (e11).
ties in both personal and professional life (27). Molds, also called non-dermatophyte molds (NDM),
Onychomycoses are found all over the world (28). In are also being increasingly diagnosed as the causative or-
Europe and the USA, their population-based prevalence is ganisms of onychomycosis (31). Scopulariopsis brevicau-
4.3%; hospital-based studies reveal a prevalence of 8.9% lis causes onychomycosis of the big toenails. Fusarium
(29). The prevalence increases with age and is highest in spp. is considered an emerging pathogen (28). Further
persons over age 65. Men are more commonly affected mold pathogens include Onychocola canadensis (e12),
than women, children markedly less so. Aspergillus fumigatus, Acremonium spp., Chrysosporium
The pathogen most commonly causing onychomycosis pannorum, Neoscytalidium dimidiatum (earlier name:
is Trichophyton rubrum, accounting for about 65% of Hendersonula toruloidea), Arthrographis kalrae, Chaeto-
cases. Molds are found in 13.3% of cases, yeasts in 21.1% mium globosum together with [along with? as well as? Was
(29). In the authors’ own retrospective study, the pa- ist genau gemeint? Mehrfachinfektion?] T. interdigitale,
thogens were dermatophytes in 68% of cases, yeasts in and Chaetomium globosum alone (31, 32, e13).

Common dermatophytes Sources of infection

Of all the dermatophytes isolated from patients with These infections can be transmitted within the family,
onychomycosis, T. rubrum is the most common spe- e.g., in the home bathtub, either horizontally (from
cies (ca. 91%), followed by T. interdigitale (earlier na- one spouse to the other) or vertically (across genera-
me: T. mentagrophytes var. interdigitale) (ca. 7.7%). tions).
 pedis, psoriasis vulgaris, psoriasis unguium, and hyperhi-
drosis. Older persons often have multiple risk factors. Can-
dida onychomycoses often affect immunosuppressed per-
sons (33).
There is an autosomal dominant genetic predisposition
to distal subungual onychomycosis due to T. rubrum (e14).
Onychomycosis is present in only about half of all path-
a b ological changes of the nails that visually suggest a fungal
infection (e14). The differential diagnosis includes non-in-
fectious nail diseases such as psoriasis unguium, lichen
ruber, yellow nail syndrome, and tumors.
Toenails are affected much more often by onychomyco-
sis than fingernails because of trauma (shoes) and underly-
ing vascular diseases. Onychomycosis most commonly
appears in the form of distal and/or lateral subungual ony-
c d chomycosis. The pathogens invade the distal/lateral por-
tion of the nail bed, leading to subungual hyperkeratosis,
discoloration (dyschromia), and onycholysis (Figure 3).
In white superficial onychomycosis (leukonychia tri-
chophytica), a rarer condition, the fungal pathogens invade
from the surface of the nail plate. This condition exclus-
ively affects toenails. The most common pathogen is T. ru-
brum; T. interdigitale is rare. The mold Fusarium spp. is a
further cause.
e f In proximal subungual onychomycosis, the infection
Figure 2: the clinical and dermatoscopic features of common nail disorders proceeds from the cuticle (particularly in immunosup-
a) and b): early subungual acrolentiginous melanoma. pressed patients). The maximal variant of fungal disease of
a) Clinical image of subungual blue discoloration in the area of the lunula. the nail is total dystrophic onychomycosis. In endonyx ony-
b) Dermatoscopy showing remodeled blueish-gray lunular pigmentation with incipient longi- chomycosis—caused in the tropics by T. soudanense—the
tudinal pigment striae in the nail plate.
nail plate is thickened. Candida onychomycosis is generally
c) and d): subungual invasive melanoma.
c) Black pigmentation under then nail and also within the partially destroyed nail plate. In-
associated with paronychia (inflammation of the nail fold)
cipient Hutchinson phenomenon on the proximal nail fold and cuticle. (34).
d) Dermatoscopy showing longitudinal bands of varying widths and colors.
e) and (f): Bowen’s disease of the nail bed. Diagnostic evaluation
e) Clinical appearance resembling that of a chronic paronychia. Onychomycosis has broad differential diagnosis and can-
f) Dermatoscopy showing partial destruction of the distal nail groove and hyponychium, to- not be diagnosed on clinical grounds alone (Figure 3).
gether with the characteristic “dots along lines” pattern (red dots along dilated vessels). Mere inspection has the highest false-positive rate of any
diagnostic method. Rather, the diagnosis should be based
on mycological laboratory tests—either a potassium hy-
droxide [Kalilauge?] preparation or an optical fluor-
escence preparation, along with growth of the pathogenic
These infections can be transmitted within the family, fungus in culture [im unbehandelten Patienten] (the diag-
e.g., in the home bathtub, either horizontally (from one nostic gold standard). The histologic demonstration of
spouse to the other) or vertically (across generations). fungi causing nail infections by means of the periodic acid
Further sources of infection include swimming pools, bath- Schiff (PAS) reaction after a punch biopsy of the nails, or
houses, saunas, sporting facilities, etc. Predisposing factors nail clippings, is likewise highly sensitive. Neither the
include prior nail trauma, advanced age (slower nail native preparation nor the histologically examined speci-
growth, poorer limb circulation), vascular diseases, lymph men enables determination of the genus or species of the
edema, diabetes mellitus, immune compromise, tinea responsible fungus; culture alone enables identification

Non-infectious causes of nail disease The diagnosis of onychomycosis

Onychomycosis is present in only about half of all Onychomycosis should not be diagnosed on clinical
pathological changes of the nails that visually sug- grounds alone. The diagnosis should be based on
gest a fungal infection. The differential diagnosis in- mycological laboratory tests, including the de-
cludes a variety of non-infectious nail diseases. monstration of the fungal pathogen by culture of
a specimen taken from the untreated patient.
down to the species level (e15, e16). There are also newer
molecular-biological methods such as the polymerase
chain reaction (PCR) for the direct demonstration of der-
matophyte DNA in nail specimens. A PCR enzyme immu-
noassay (EIA) with primers specifically directed against
the topoisomerase II gene can directly detect the dermato-
phytes T. rubrum, T. interdigitale, and Epidermophyton
floccosum in clinical material (35). Used as a complement
to conventional fungal culture, the direct demonstration of
pathogenic fungi in nail tissue by PCR, multiple-fungus
PCR for the simultaneous identification of (for example)
20 relevant types of fungus, or real-time PCR for the de- a b
tection of dermatophyte DNA enable much faster, highly
sensitive, and very specific diagnosis (33). In vitro sensi-
tivity testing, although a routine part of the work-up of
bacterial infections, is not commonly done for fungi.
A limited onychomycosis that does not involve the ma-
trix often responds to topical treatment alone. On the other
hand, matrix involvement—often recognizable from the
so-called yellow streaks—should be treated with a sys-
temic antimycotic drug, generally in combination with a
topical one. The decision on the optimal type of treatment
is also based on the number of affected fingernails or toe-
nails, the extent of nail involvement, multimorbidity, drug
interactions, and the identified pathogen (Table 4). For c d
topical use, water-soluble ciclopiroxolamine nail varnish is Figure 3: Onychomycoses
more effective than amorolfin (36). a) Distal-lateral subungual onychomycosis due to T. rubrum in a
Confirmed dermatophyte infections should be treated 79-year-old man.
with terbinafin, fluconazole, or itraconazole, while con- b) Onychomycosis of the big toenail in the same patient, with lateral
firmed Candida spp. infections are preferably treated with white streaks. There is visible subungual hyperkeratosis of the
fluconazole. Either continuous or intermittent therapy is markedly thickened nail plate, which is no longer transparent and
possible, depending on the preparation; terbinafin yields manifests a yellowish-brown discoloration.
c) White superficial onychomycosis (leuconychia trichophytica) in a
the highest response rate (37). Persons with liver disease
41-year-old man.
should only be given systemic antimycotic drugs for strict d) Total dystrophic onychomycosis of the fingernails due to C. albicans
indications. The recurrence rate of fungal nail infections and Aspergillus niger in an 88-year-old man.
within 36 months of the end of treatment ranges from 20%
to 50% (e17).
Onychomycosis due to molds generally does not re-
spond to systemic antimycotic treatment. In infections the nail. Subungual bacterial infection can also be
with Aspergillus species and Scopulariopsis brevicaulis, a [das Original lautet anders] caused by Pseudomonas
trial of oral terbinafin may be successful. There remains aeruginosa. Risk factors include repetitive minor trau-
the option of atraumatic nail removal with 40% urea (34). ma, working in damp conditions, onychotillomania
The utility of laser treatment for onychomycosis is de- (compulsive nail-picking or nail-tearing), psoriasis,
bated (38–40). thumb-sucking, diabetes mellitus, and immunosup-
pression. The greenish nail discoloration character-
Bacterial infections of the nails istic of Pseudomonas infection is probably caused by
Bacterial infections of the nails often arise out of the diffusion of pyocyanin into the nail tissue, or else
acute or chronic paronychia, from which Staphylococ- by bacterial invasion of the nail plate (e18).
cus aureus bacteria or streptococci can spread under Artificial fingernails are more heavily colonized

Onychomycosis and molds The state of the evidence

Onychomycosis due to molds generally does not There have not been any controlled clinical trials
respond to systemic antimycotic treatment. In in- on the treatment of bacterial nail infections.
fections with Aspergillus species and Scopulariopsis
brevicaulis, a trial of oral terbinafin may be success-
ful.
 TABLE 4

The treatment of onychomycosis (usual duration: 6 weeks for fingernail involvement, 12 weeks for toenail involvement)*

Treatment Indication Active agent Dosing schedule and cure rate Level of
(culture) evidence
Atraumatic nail extraction prior to specific treatment 20–40% urea with occlusion daily III
cure rate unknown
Antifungal nail varnish monotherapy only if <50% of the ciclopiroxolamine daily for 48 weeks, 58.3% Ia
nail surface is affected and no
more than 3 nails are affected, amorolfin 1 × / week for 48 weeks, 26.7% Ia
without matrix involvement
Systemic antifungal treatment involvement of > 50% of the terbinafin 250 mg qd for 6-12 weeks, 76% Ia
nail surface or of > 3 nails, or
if there is proximal subungual itraconazole 200 mg bid for 1 week, then Ia
onychomycosis pause for 3 weeks and repeat
6–12 weeks (pulse therapy), Ia
63%
200 mg qd for 6–12 weeks
(continuous treatment), 69%
fluconazole 150–300 mg 1 ×/ week for Ia
3–12 months, 48%
Laser therapy currently debated various kinds of laser – IV

*modified from (40)

than natural ones by both bacteria (mainly Gram- Manuscript dates

Submitted on 8 January 2016, accepted after revision on 25 March 2016.
negative bacilli) and fungi (mainly Candida spp.) (e19,
e20). Translated from the original German by Ethan Taub, M.D.
There have not been any controlled clinical trials
on the treatment of bacterial nail infections. There REFERENCES
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Klinik für Dermatologie und Allergologie
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Friedrichstr. 41, D-01309 Dresden, Germany
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23. Chokoeva AA, Tchernev G, Patterson JW, Lotti T, Wollina U: Life-
threatening onychomycosis imitator. J Biol Regul Homeost Agents
2015; 29: 31–2.
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nail pigmentation. Arch Dermatol 2002; 138: 1327–33.
25. Nguyen JT, Bakri K, Nguyen EC, Johnson CH, Moran SL: Surgical
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27. Szepietowski J C, Reich A; National Quality of Life in Dermatology
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update. Part 1: Dermatomycoses: causative agents, epidemiology
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global population—a literature study. J Eur Acad Dermatol Vene- This article has been certified by the North Rhine Academy for Postgraduate and
reol 2014; 28: 1480–91. Continuing Medical Education. Deutsches Ärzteblatt provides certified continuing
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2006; 4: 218–28. sociations of the German federal states (Länder). CME points of the Medical As-
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chomycosis: diagnosis, clinical types, epidemiology, and treat- cme.aerzteblatt.de.
ment. J Am Acad Dermatol 2012; 66: 494–502.
32. Vennewald I, Wollina U: Cutaneous infections due to opportunistic Participants in the CME program can manage their CME points with their 15-digit
molds: uncommon presentations. Clin Dermatol 2005; 23: “uniform CME number” (einheitliche Fortbildungsnummer, EFN). The EFN must
565–71. be entered in the appropriate field in the cme.aerzteblatt.de website under “meine
33. Nenoff P, Krüger C, Schaller J, Ginter-Hanselmayer G, Schulte- Daten” (“my data”), or upon registration. The EFN appears on each participant’s
Beerbühl R, Tietz HJ: Mycology—an update part 2: dermatomy- CME certificate. This CME unit can be accessed until 16 October 2016, and ear-
coses: clinical picture and diagnostics. J Dtsch Dermatol Ges
2014; 12: 749–77. lier CME units until the dates indicated:
34. Seebacher C, Brasch J, Abeck D, et al.: Onychomycosis. Mycoses – “Breastfeeding and Complementary Feeding” (Issue 25/2016) until 18 Septem-
2007; 50: 321–7. ber 2016,
35. Winter I, Uhrlaß S, Krüger C, et al.: Molekularbiologischer Di-
rektnachweis von Dermatophyten im klinischen Material bei Ver- – “The Diagnosis and Treatment of Hair and Scalp Diseases“ (Issue 21/2016) un-
dacht auf Onychomykose und Tinea pedis – eine prospektive Studie til 21 August 2016.
zum Vergleich konventioneller dermatomykologischer Diagnostik
Please answer the following questions to participate in our certified Continuing Medical Education
program. Only one answer is possible per question. Please select the most appropriate answer.

Question 1 Question 6
The end product of the nail organ is the nail plate. What structure is Dermatoscopy, an optical technique, is particularly useful in
essential for horizontal nail growth? the differential diagnosis of what type of nail abnormality?
a) the nail root a) nail pigmentation
b) the lateral nail fold b) onychorrhexis
c) the nail bed c) speckling
d) the hyponychium d) trachyonychia
e) the horns of the nail plate e) tender nail plate

Question 2 Question 7
What manifestation is of greatest help in the differential diagnosis What type of fungus is the most common casuse of ony-
of rheumatoid arthritis from psoriatic arthritis? chomycosis in Germany and elsewhere in Europe?
a) the combination of distal arthritis with nail changes a) Trichophyton rubrum
b) the combination of nail plate discoloration with nail fragility b) Trichophyton interdigitale
c) the combination of scalp dandruff with onycholysis c) Epidermophyton floccosum
d) the combination of melanonychia with pterygium inversum d) Candida albicans
unguis e) Trichophyton tonsurans
e) the combination of work with damp hands and brittle nails

Question 8
Question 3 What diagnostic method is most likely to yield a false positive
Hypoalbuminemia should be ruled out if which of the following diagnosis of onychomycosis?
manifestations is present? a) a potassium hydroxide preparation
a) splinter hemorrhages of the nail plate b) fungal culture
b) Muehrcke lines c) nail histology
c) Beau-Reil lines d) visual inspection
d) brittle nails e) dermatoscopy
e) hourglass nails

Question 9
What nail change is a sign of chronic renal disease with
Question 4 azotemia?
What kind of cancer is common among persons with nail dis- a) Lindsay’s nails
orders? b) Beau-Reil lines
a) fibrokeratoma c) Muehrcke lines
b) Koenen tumor d) yellow nails
c) squamous cell carcinoma e) hourglass nails
d) granuloma teleangiectaticum
e) hyperkeratosis

Question 10
What nail change is due to excessive vitamin A intake?
Question 5 a) distal onycholysis
What change causes hourglass nails? b) dystrophy
a) shortening of the distal phalanx c) subungual abscesses
b) a disturbance of the nail matrix d) melanonychia
c) hypertrophy of the distal phalanx or of the subcutaneous soft tissue e) paronychia
d) thinning of the nail plate Answers: 1c, 2a, 3b, 4c, 5c, 6a, 7a, 8d, 9a, 10b
e) onychomycosis
 MEDICINE

Supplementary material to:

The Diagnosis and Treatment of Nail Disorders
by Uwe Wollina, Pietro Nenoff, Gunter Haroske, and Holger A. Haenssle
Dtsch Arztebl Int 2016; 113:

–

. DOI: 10.3238/arztebl.2016.0

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mann H: Mucocutaneous candidiasis. Dtsch Med Wochenschr
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Deutschland erstmals isoliert aus Nagelmaterial von fünf Pa-
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Deutsches Ärzteblatt International | Dtsch Arztebl Int 2016; 113: XXX–XX | Supplementary material 11
MEDICINE

eTABLE

A selection of identified mutations that affect the nail organ

Mutation Consequence
Frizzled6 nail dystrophy
Frizzled agonist anonychia
R-spondin 4 (RSPO4)
FZD6 severe isolated autosomal recessive nail dysplasia
Keratin 16 and keratin 6a pachyonychia congenita type 1
Keratin 17 and keratin 6b pachyonychia congenita type 2
KRT74, KRT85, or pure ectodermal hair and nail dysplasia (PHNED)
HOXC13 (nails: koilonychia, micronychia, distal onycholysis)
LMX1B nail-patella syndrome
MSX1 Witkop syndrome (hypodontia-nail dysplasia syndrome
with koilonychia or anonychia)
MSX2-noggin polydactyly
TP63 acrodermato-ungual-lacrimal-tooth (ADULT) syndrome
ankyloblepharon-ectodermal dysplasia-clefting syndrome
(AEC or Hay-Wells syndrome)
WNT10A odonto-onychodermal dysplasia (OODD)

12 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2016; 113: XXX–XX | Supplementary material

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