5  Oral Mucosal Patches Striae Diseases 95

5.4 Oral Lichen Planus

Case 50 Oral Lichen Planus

(Non-erosive Type)

a b

Fig. 5.14 (a) Pearl white streaks on the lower lip. (b) Pearl white streaks on the right buccal mucosa. (c) Pearl white
patches on the dorsum of the tongue

Age: 23 years Diagnosis:

Sex: Female Oral lichen planus (non-erosive type)
Chief Complaints: Diagnosis Basis:
A 23-year-old woman with pain while eating
spicy food for more than 1 year 1 . Pearl white lacy streaks and patches.
History of Present Illness: 2. No obvious inducing factors.
A 23-year-old woman came with a complaint of Management:
pain on the tongue when she was eating hot or
spicy food for more than 1  year. There was no 1. Medication
spontaneous pain. Rp.: Thymosin enteric-coated tablets 20 mg ×
Past Medical History: None. 30 tablets
Allergy: None. Sig.: 20 mg q.d. p.o.
Physical Examination: Beta-carotene 6 mg × 60 tablets
Pearl white lacy streaks and patches were seen on Sig.: 6 mg q.d. p.o.
the lower lip, left and right buccal mucosa, and Dexamethasone paste 15 g × 1
dorsum of the tongue (Fig. 5.14). There was no Sig.: topical use t.i.d.
erythematous or erosive lesion. No abnormality 2. Regular follow-up visits were suggested.
was found on the fingernails and skin.
96 H. Dan et al.

Case 51 Oral Lichen Planus (Erosive Type) Sig.: rinse t.i.d.

Dexamethasone paste 15 g × 1
Sig.: topical use t.i.d.
2. Aerosol therapy
Rp.: Dexamethasone sodium phosphate injec-
tion 1 ml × 1
Gentamycin sulfate injection 2 ml × 1
Vitamin B12 injection 1 ml × 1
Vitamin C injection 2.5 ml × 1
Sig.: aerosol therapy b.i.d.
3. A follow-up visit after 1 week was scheduled.

Follow-Up Treatment:
Fig. 5.15  Pearl white lacy streaks and patches with inter- In the follow-up visit, the erosions got localized,
spersed erythematous and erosive lesions on the buccal
mucosa intra-lesional injection of triamcinolone ace-
tonide was given, and the oral medication was
Age: 58 years switched to tripterygium hypoglaucum tablets
Sex: Female (two tablets t.i.d. p.o.).
Chief Complaints:
A 58-year-old woman with erosion and pain on [Review] Oral Lichen Planus
the buccal mucosa for 2 months Oral lichen planus (OLP) is a chronic inflamma-
History of Present Illness: tory disorder of the oral mucosa. It affects about
A 58-year-old woman complained of erosion 0.5–3% of the population, especially women aged
and pain on the buccal mucosa for 2  months. from 30 to 60 years. Compared with the normal
The pain got worse when she was eating hot or oral mucosa, OLP has a higher risk of cancer
spicy food. development and is thus classified by the World
Past Medical History: None. Health Organization as one of the oral potentially
Allergy: None. malignant disorders [22].
Physical Examination: Although the etiology of OLP is still unclear,
Pearl white lacy streaks and patches with inter- the association of immune dysregulation with the
spersed erythematous and erosive lesions were pathogenesis of this disease is widely accepted.
seen on the buccal mucosa. No abnormality was The primary event of this process is the interac-
found on the fingernails and skin (Fig. 5.15). tion between endogenous and exogenous fac-
Diagnosis: tors (antigens, drugs, viruses, psychological
Oral lichen planus (erosive type). stress [23], and so on) with keratinocytes (KCs),
Diagnosis Basis: which then leads to degranulation of mast cells,
activation of macrophages, and release of pro-­
1. Pearl white lacy streaks and patches with ery- inflammatory cytokines such as tumor necro-
thematous and erosive lesions. sis factor-α (TNF-α). TNF-α not only affects
2. No obvious inducing factors. T-lymphocyte homing but also induces the
expression of adhesion molecules by endothelial
Management: cells and KCs. The expression of adhesion mol-
ecules promotes the infiltration of lymphocytes,
1. Medication which further promote degranulation of mast
Rp.: Prednisone acetate tablets 5  mg  ×  35 cells and produce interferon-γ (IFN-γ), leading
tablets to extension of the lesion. IFN-γ not only upregu-
Sig.: 25 mg q.m. p.o. lates expression of major histocompatibility com-
Compound chlorhexidine solution 300 ml × 1 plex (MHC) class I but also induces expression of
5  Oral Mucosal Patches Striae Diseases 97

MHC class II by KCs. Modified surface antigens is still controversial [32].Some researchers sug-
of KCs can be recognized by Langerhans cells gested that patients with or without HCV had
(LC) and presented to T lymphocytes. KCs then different hereditary basis, which might be related
become the target of cytotoxic T cells. Damaged with the allele of HLA-DR6 gene [32].
keratinocytes release cytokines which could fur- There are six types of OLP lesions: papular,
ther stimulate the differentiation and chemotaxis reticular, plaque-like, atrophic, erosive/ulcer-
of Langerhans cells, as well as the growth of T ative, and bullous. Reticular OLP usually presents
lymphocytes. as asymptomatic pearl white lacy streaks distrib-
Although the relationship between genetic uted in a reticular or circular pattern (Fig. 5.16).
factors and OLP is still controversial, studies This type of lesion is most commonly seen on
have shown that gene polymorphisms of several the buccal mucosa but can also be observed on
cytokines, such as TNF-α and interleukin (IL)- the lips, gingiva, and tongue. Papular OLP is
10, may be associated with individual’s suscepti- clinically characterized by small white dots on
bility to OLP [24–27]. the mucosa (Fig. 5.17), which usually intermin-
Studies on the association between OLP and gles with other forms of OLP.  Plaque-­like OLP
infective factors mainly focus on hepatitis C often locates on the buccal mucosa and dorsal
virus (HCV) infection. Researches carried out surface of the tongue. This type of lesion is usu-
in different regions provide us with different ally smooth, flat, or slightly elevated, similar to
results, some of them are contradictory [28–31]. homogeneous oral leukoplakia (Figs.  5.18 and
The association of OLP and HCV infection HCV 5.19). Atrophic OLP is most frequently observed

Fig. 5.16  Reticular form: pearl white lacy streaks on left Fig. 5.18  Plaque-like form: single pearl white patch on
buccal mucosa dorsum of the tongue

Fig. 5.17  Papular form: lots of white dots densely dis- Fig. 5.19  Plaque-like form: multiple pearl white patches
tributed on the left buccal mucosa on dorsum of the tongue, flat or slightly elevated
98 H. Dan et al.

on dorsum of the tongue, presenting as atrophy a waxy luster and white streaks (Wickham’s
of lingual papilla surrounded by white streaks striae) (Figs. 5.22 and 5.23). Skin lesions can be
(Fig. 5.20). Patients with atrophic OLP may have itchy. If the scalp is involved, hair follicles can
burning sensation and pain while eating. Erosive/ be destroyed, leading to alopecia. Affected nails/
ulcerative OLP are characterized by erosive/ toenails are usually thin, wrinkled, and reluster,
ulcerative lesions surrounded by white streaks with tiny scales, longitudinal grooves, pits, and
[33].The bullous lesions in OLP are usually quite ridges (Fig.  5.22). Skin of the scrotum is occa-
small, with a diameter of about 2 mm; sometimes sionally involved [33].
larger bulla can also be seen (Fig.  5.21). The OLP is considered as an oral potentially malig-
forms mentioned above can be divided into two nant disorder (Fig.  5.24); however, due to the
major types: erosive type and non-erosive type. heterogenicity of different studies, the reported
Some OLP patients have skin lesions, with frequency of malignant transformation varies a
predilection for the flexor aspects of the extremi- lot. A recent study carried out by a Chinese group
ties. Cutaneous lesions are mostly symmetrical, showed that the malignant transformation rate
presenting as flat violaceous papules. The papules of OLP was less than 1% [34]. Since malignant
can get confluent and form patches or plaques transformation was frequently found at locations
that are slightly elevated, well-­demarcated, with distant to OLP lesions, some researchers thought

Fig. 5.22  Skin and nail/toenail lesions: violaceous pap-

ules forming patches or flat-topped plaques with a waxy
Fig. 5.20  Atrophic form: atrophy of lingual papilla sur- luster and white streaks; atrophic nails with longitudinal
rounded by pearl white streaks grooves

Fig. 5.21  Bullous form: bullous lesions of various sizes

surrounded by pearl white streaks on the inner surface of Fig. 5.23  Skin lesions: violaceous flat papules on the
the left lower lip skin of the leg
5  Oral Mucosal Patches Striae Diseases 99

thymosin enteric-coated tablets (20  mg q.d./

b.i.d./t.i.d. p.o.), pidotimod (400  mg q.d./b.i.d.
p.o.), or bacillus Calmette-Guerin polysaccharide
nucleic acid injection (1 ml q.o.d. i.m.), used for
a month. Topical treatment agents such as 0.01%
chlorhexidine mouth wash and compound borax
solution (diluted fivefold with water before use)
can be used three times a day. Glucocorticoids
like dexamethasone paste, prednisolone acetate
solution, triamcinolone acetonide (diluted five-
fold with water before use), triamcinolone ace-
Fig. 5.24  Malignant transformation of OLP on the lat- tonide dental paste, and dexamethasone ointment
eral and ventral surface of the tongue can be applied topically three times a day.
For patients with a limited number of small
erosive lesions, triamcinolone acetonide injection
that malignant transformation might be a result or compound betamethasone injection ­combined
of external factors rather than the natural termi- with sterile water or 2% lidocaine (at a ratio of
nate of OLP. They also believed that those cases 1:1) can be used for intra-lesional injection. Oral
with malignant transformation might not be OLP medications and topical agents are similar to
but lichenoid reactions [35]. In short, the risk of those used for patients with non-­erosive OLP and
malignant transformation is low in OLP. Besides pain while eating.
elimination of irritation factors, regular follow- For patients with larger or multiple small ero-
up visits at the frequency of at least twice a year sive lesions, triamcinolone acetonide injection
are recommended. or compound betamethasone injection combined
The treatment goal of OLP is to facilitate with sterile water or 2% lidocaine (at a ratio
healing of erosion and ulceration, alleviate pain of 1:1) can be used for intra-lesional injection.
and discomfort, and reduce the risk of malignant Tripterygium hypoglaucum tablets (two tablets
transformation. t.i.d. for 2 weeks or longer) can be used. Topical
For patients with asymptomatic non-erosive agents are similar to those used for patients with
OLP, no treatment but regular follow-up visits non-erosive OLP and pain while eating.
are recommended. For patients with widespread erosive lesions,
For patients with non-erosive OLP and no systemic prednisone acetate (15–30  mg daily,
discomfort other than roughness, the follow- in a single morning dose, for 1–2 weeks) can be
ing medication regimens may be used: com- used in combination with aerosol therapy (dexa-
pound danshen dripping pill (10 pills t.i.d. p.o.), methasone sodium phosphate injection, genta-
β-carotene capsules (6  mg q.d./b.i.d. p.o.), or mycin sulfate injection, vitamin C injection, and
vitamin E capsules (100 mg q.d. p.o.), used con- vitamin B12 injection, once or twice a day for
tinuously for 1  month. Cod liver oil, vitamin A 3–5 days). Once the erosive lesions are controlled,
and D drops, and vitamin E can be applied topi- the medication regimen can be switched to tripte-
cally 3–4 times a day. If the lesions are extremely rygium hypoglaucum tablets (two tablets t.i.d.
keratotic and thick, 0.1–0.3% acitretin oral paste for 2 weeks or longer) or tripterygium glycosides
or 1% viaminate oral paste can be applied topi- tablets (1–1.5 mg/kg/day, divided to three doses,
cally once or twice a day. for 2 weeks or longer). Topical agents are similar
For patients with non-erosive OLP and pain to those used for patients with non-­erosive OLP
while eating, if immunodeficiency is indicated, and pain while eating. Moreover, 2–4% sodium
medications containing immunopotentiators may bicarbonate mouthwash and nystatin liniment
be used: transfer factor capsules (6 mg t.i.d. p.o.), can also be used topically.
100 H. Dan et al.

5.5 Lichenoid Reactions

Case 52 Lichenoid Reaction Caused by

Dental Amalgam

a b

Fig. 5.25 (a) White striae and ulcerative lesion on the mucosa next to the amalgam restoration. (b) White striae on the
mucosa next to the amalgam restoration

Age: 41 years Diagnosis:

Sex: Male Lichenoid reaction.
Chief Complaints: Diagnosis Basis:
A 41-year-old man with white striae on the oral
mucosa for more than 3 months 1 . White striae and ulcer in the center.
History of Present Illness: 2. Amalgam restorations right next to the lesion.
A 41-year-old man complained of white striae on 3. Lesions disappeared after the amalgam resto-
the oral mucosa for more than 3 months. There rations were replaced with resin.
was no discomfort until 1  week ago, when an
ulcer appeared in the center of the lesion. Management:
Past Medical History:
The patient had his teeth filled 6 months ago. He 1. Medication
denied any history of systemic diseases. Rp.: Dexamethasone paste 15 g × 1
Allergy: None. Sig.: topical use t.i.d.
Physical Examination: 2. Amalgam restorations were replaced with resin.
White striae were observed on the mucosa close
to the amalgam restorations on the buccal side of Follow-Up Treatment:
mandibular first premolar teeth (Fig. 5.25a-b); an One month after amalgam restorations were
ulcer with a diameter of 4  mm was seen in the replaced with resin, the lesion regression was
center of the white lesion on the right side. observed.
5  Oral Mucosal Patches Striae Diseases 101

Case 53 Lichenoid Reaction (Chronic

Graft-­Versus-­Host Disease)

a b

Fig. 5.26 (a) White striae with interspersed erythema on the right buccal mucosa. (b) White striae on the left buccal
mucosa, with erythematous and erosive lesions on the mucosa lining the vestibular groove of the left mandibular molars

Age: 43 years Diagnosis:

Sex: Male Lichenoid reaction (chronic graft-versus-host
Chief Complaints: disease)
A 43-year-old man with recurrent erosions and Diagnosis Basis:
pain of the oral mucosa for 6 months
History of Present Illness: 1. White striae with interspersed erythematous
A 43-year-old man complained that he had been lesions and erosion on the buccal mucosa.
suffering from recurrent erosions and pain of the 2.
Lesions appeared after bone marrow
oral mucosa since he had bone marrow trans- transplantation.
plantation 6  months ago. The symptoms could
be partially relieved when he used mouth rinses Management:
prescribed by local doctors.
Past Medical History: 1. Medication
Bone marrow transplantation 6 months ago due Rp.: Compound chlorhexidine solution 300 ml × 1
to leukemia. Sig.: rinse t.i.d.
Allergy: None. Dexamethasone paste 15 g × 1
Physical Examination: Sig.: topical use t.i.d.
White striae with interspersed erythematous Triamcinolone acetonide (TA) injection
lesions were observed on the buccal mucosa; ero- 40 mg × 1
sion with a size of 12 mm × 4 mm was seen on Sig.: Intra-lesional injection at the dose of
the mucosa lining the vestibular groove of the left 8 mg/site s.t.
mandibular molars (Fig. 5.26a-b).
102 H. Dan et al.

[Review] Lichenoid Reactions The primary treatment of oral lichenoid con-

Lichenoid reactions may involve the skin and tact lesions and oral lichenoid drug reactions is to
oral mucosa. Oral lichenoid reactions (OLR) eliminate the irritation factors, such as replacing
present as lesions similar to OLP, such as white the dental restoration material and changing the
streaks, white patches, and erythematous/ulcer- medication regimen. The treatment goal of oral
ative lesions. According to the etiological fac- GVHD is to relieve pain and eating difficulty and to
tors, OLR can be classified into three types: oral improve the life quality of patients. To control the
lichenoid contact lesions, oral lichenoid drug existing lichenoid reactions, topical therapy similar
reactions, and oral lichenoid reactions of graft-­ to that used for erosive OLP is recommended.
versus-­host disease (GVHD) [36].
Oral lichenoid contact lesion is a special type
of allergic contact stomatitis. It belongs to the 5.6 Oral Erythroplakia
group of delayed hypersensitivity reactions. The
lesions are usually right next to dental restoration Case 54 Oral Erythroplakia
materials, such as dental amalgam. Partial or total
remission can be achieved shortly after elimina-
tion of the irritation [37].
Oral lichenoid drug reactions are often
induced by medications such as β-blockers,
angiotensin-converting enzyme inhibitors, non-
steroidal anti-inflammatory agents, and methyl-
dopa and hypoglycemic agents [38].
GVHD is quite common in patients receiv-
ing either peripheral blood stem cell or bone
marrow stem cell transplantation [39]. Patients
receiving organ transplantation can also develop
GVHD.  The risk of GVHD is higher when the Fig. 5.27  A soft, well-defined erythematous lesion with a
host is unrelated with the donor or when the slightly rough surface on the lingual mucosa
donor or host is old. Acute GVHD typically pres-
ents as erythematous eruptions, diarrhea, and/or Age: 63 years
hepatitis, which most commonly occur within Sex: Female
the first 3–4 months. Chronic GVHD (cGVHD) Chief Complaints:
can affect almost all the major organ systems. A 63-year-old woman with pain on the tongue for
The skin, conjunctiva, oral and vaginal mucosa, 1 year
liver, and salivary and lacrimal glands are most History of Present Illness:
commonly involved [40].The number of patients A 63-year-old woman complained of pain on the
receiving allogenic hematopoietic cell transplan- tongue for 1 year. The patient was diagnosed with
tation each year is around 15,000 worldwide. The oral lichen planus at a local hospital and had been
estimated incidence of cGVHD is about 40–70% taking traditional Chinese medicine since then.
in patients who survived the initial transplanta- However, no improvement had been achieved
tion [40]. and the pain was getting worse.
Oral lesions occur in 45–83% of cGVHD Past Medical History: None.
cases. Lichenoid lesions and dryness of the oral Allergy: None.
mucosa are two of the most common oral mani- Physical Examination:
festations. The former can last for a long time A soft, well-defined erythematous lesion with a
and can be difficult to be differentiated from OLP slightly rough surface was observed on the left
clinically and histologically [22, 41]. ventral and lateral surface of the tongue (Fig. 5.27).
5  Oral Mucosal Patches Striae Diseases 103

Laboratory Investigations: Allergy: None.

A lesional biopsy was made on left margin of the Physical Examination:
tongue, and histopathological findings were in A well-defined erythematous lesion with inter-
accord with erythroplakia with mild-to-­moderate spersed erosions was observed on the right cheek.
epithelial dysplasia. The anterior part of the lesion was accompanied
Diagnosis: with some irregular white dots (Fig. 5.28).
Oral erythroplakia Laboratory Investigations:
Diagnosis Basis: A lesional biopsy was made on the right buc-
cal mucosa, and histopathological findings sug-
1. Well-defined erythematous lesion on the oral gested carcinoma in situ with focal infiltration
mucosa. into the lamina propria.
2. Findings of histopathological examination. Diagnosis:
Carcinoma in situ (malignant transformation of
Management: oral erythroleukoplakia)
The patient was referred to the Department of Diagnosis Basis:
Oral and Maxillofacial Surgery for further exam-
inations and treatment. 1. Well-defined erythematous lesion with irregu-
lar white dots.
Case 55 Malignant Transformation of Oral 2. Findings of histopathological examination.
Erythroleukoplakia
Management:
The patient was referred to the Department of
Oral and Maxillofacial Surgery for further exam-
inations and treatments.

[Review] Oral Erythroplakia

According to Kramer et al., the definition of oral
erythroplakia is “any lesion of the oral mucosa that
presents as bright red velvety plaques which can-
not be characterized clinically or pathologically as
any other recognizable condition” [42]. In an arti-
cle by Villa et al., several studies on the prevalence
Fig. 5.28  A well-defined erythematous lesion with inter- of oral erythroplakia carried out between 1971
spersed white dots and erosions was observed on the right and 2007 were analyzed; the reported prevalence
buccal mucosa ranges from 0.02% to 0.2% (mean prevalence,
0.11%), and the estimated malignant transforma-
Age: 45 years tion rate was 44.9% [43, 44]. Oral erythroplakia
Sex: Male usually affects middle-­aged and senior citizens.
Chief Complaints: No gender preference has been observed.
A 45-year-old man with pain on the right cheek The etiology and pathogenesis of oral erythro-
for 6 months plakia is still unclear. Most patients have history
History of Present Illness: of smoking and excessive drinking. Besides, aber-
A 45-year-old man complained of pain on the rant DNA content (DNA aneuploidy), mutation
right cheek for 6  months. The patient also had of p53 gene, human papillomavirus, and candida
pain when he was eating. He had been using some infection may also contribute to the development
over-the-counter oral paste, but no improvement of this disorder. There is no consensus whether
had been achieved. oral erythroplakia is a primary disease or a dis-
Past Medical History: None. ease that evolves from oral leukoplakia [45].
104 H. Dan et al.

Oral erythroplakia most commonly locates

on the ventral surface of the tongue, the floor of
the mouth, the palate, and the tonsillar fossa. The
patients usually complain of pain or a burning
sensation on the mucosa. A typical lesion of oral
erythroplakia is a bright red velvety plaque with a
smooth, speckled, or nodular surface. The lesion
is usually well-defined, and the red color doesn’t
fade under pressure. The lesions won’t disappear
after anti-infective therapy. Sometimes, the red
lesion is interspersed with yellow-white spots.
The lesion is usually single and soft. However, Fig. 5.29  Homogeneous erythroplakia: well-defined red
it may become indurated during the process of lesion with a smooth surface and with normal mucosa
malignant transformation [46]. Oral erythropla- scattered in the lesion
kia is divided into three subtypes according to the
clinical manifestation:
mucosal diseases, such as stomatitis associated
1. Homogeneous erythroplakia: well-defined
with local irritation, erythematous candidiasis,
red lesion with a smooth surface, either flat oral lichen planus, chronic discoid lupus erythe-
or slightly raised, with a diameter of less than matosus, medicamentous reaction, and syphilitic
2 cm; usually locates on the buccal or palatal mucous patches. The first thing is to remove the
mucosa; normal mucosa may be seen in the irritating factor. Anti-infective therapy may be
lesion (Fig. 5.29). followed. Two percent sodium bicarbonate solu-
2. Interspersed erythroplakia: white spots inter- tion and nystatin suspension can be used if fungal
spersed among an erythematous lesion, simi- infection is suspected. If non-fungal infection or
lar to lichen planus. traumatic stomatitis is considered, mouthwash
3. Granular or speckled erythroplakia: granules such as compound chlorhexidine solution, com-
can be observed on the erythematous lesion. pound borax solution (using 1:5 dilution), or 1%
This is the most common type of oral eryth- povidone iodine solution can be used; topical
roplakia which can affect almost any part of corticosteroids such as dexamethasone ointment,
the oral mucosa. The histological examina- prednisolone suspension, and triamcinolone ace-
tion often shows carcinoma in situ or invasive tonide oral paste can also be applied. Moreover,
cancer. intra-lesional injection of triamcinolone aceton-
ide can be performed. If the lesion doesn’t heal
Under histological examination, oral eryth- or improve in 10–14  days, a lesional biopsy is
roplakia often present as epithelial atrophy, lack strongly recommended [48].
of cuticle, and epithelium dysplasia. Cancer in Once the diagnosis of oral erythroplakia is
situ or squamous cell carcinoma can be observed confirmed, the recommended treatment is sur-
in some advanced cases [43]. Some research- gical excision. Nevertheless, there is no widely
ers proposed that atrophy of the epithelium and accepted guideline regarding the range of exci-
the exposed microvasculature might account for sion. Few data on the recurrence of this disease
the red appearance of the lesion. However, this are available [49]. Comprehensive evaluation of
hypothesis could not explain the thickening of the related symptoms and clinical signs, early
the epithelium in some parts of the lesion [47]. detection of the disease, long-term follow-up,
Oral erythroplakia is a diagnosis of exclu- and reasonable biopsy should be applied to pre-
sion. It should be differentiated from several oral vent malignant transformation [50].
5  Oral Mucosal Patches Striae Diseases 105

5.7 Oral Submucous Fibrosis

Case 56 Oral Submucous Fibrosis

a b

Fig. 5.30 (a) Blanching of right buccal mucosa. (b) Blanching of left buccal mucosa. (c) Blanching of the palatal mucosa

Age: 25 years Laboratories and Imaging Studies:

Sex: Male A lesional biopsy was made on the right buccal
Chief Complaints: mucosa. Histological findings indicated the diag-
A 25-year-old man with pain eating hot or spicy nosis oral submucous fibrosis.
food for 2 years and restriction of mouth opening Diagnosis:
for 2 months Oral submucous fibrosis (OSF)
History of Present Illness: Diagnosis Basis:
A 25-year-old man complained of a burning sen-
sation on the oral mucosa when he was eating hot 1 . History of betel quid chewing.
or spicy food and brushing his teeth over the past 2. Restriction of mouth opening.
2  years. He also had progressive restriction of 3. Blanched fibrotic oral mucosa with palpable
mouth opening for 2 months. He had been smok- fibrotic bands.
ing for 7 years and had a long-standing habit of 4. Findings of histopathological examination.
chewing betel quid for around 6 years.
Past Medical History: Superficial gastritis. Management:
Allergy: None.
Physical Examination: 1. Medication
Buccal mucosa and the posterior portion of the Rp.: Triamcinolone acetonide (TA) injection
soft palate were extensively blanched and rigid 40 mg × 1
with palpable fibrous bands underneath (Fig. Sig.: Intra-lesional injection at the dose of
5.30a-c). Mouth opening was restricted to about 6 mg/site s.t.
the width of two fingers.
106 H. Dan et al.

Tripterygium hypoglaucum tablet 1  g  × mucous fibrosis and hyalinization, most studies

200 tablets on the pathogenesis of this disease are focused on
Sig.: 2 g t.i.d. p.o. metabolism and pathological change of the extra-
Compound danshen dripping pill 600 cellular matrix. In essence, the disease is a colla-
tablets gen metabolic disorder due to interruption of the
Sig.: 10 tablets t.i.d. p.o. collagen synthesis and degradation equilibrium.
Compound chlorhexidine solution 300 ml × 1 Areca nut contains various chemical compo-
Sig.: rinse t.i.d. nents. Among all these components, arecoline
Dexamethasone paste15g × 1 makes the most important contribution to the devel-
Sig.: topical use t.i.d. opment of OSF, while flavonoid components like
2. The patient was instructed to discontinue the tannins have a synergistic role. Extracts of areca nut
habit of chewing betel quid, and a follow-up or chemically purified arecoline could stimulate the
visit was scheduled. proliferation and collagen production of fibroblasts
in vitro. When stimulated by arecoline, fibroblasts
Follow-Up Treatment: from OSF patients produce more collagen fibers
Once the remission of the burning sensation and compared with normal fibroblasts, which is prob-
restriction of mouth opening was achieved, regu- ably associated with mutation of the fibroblast in
lar follow-up visits were suggested. OSF [53, 54].
Apart from increase of collagen formation,
[Review] Oral Submucous Fibrosis reduction of collagen degradation also contributes
Oral submucous fibrosis (OSF) is a chronic, pro- to the development OSF. Tannin and crude extract
gressive disease characterized by collagen accu- of areca nut hampers the collagenase activity.
mulation in lamina propria and submucosal tissue. Another study revealed that type III collagen was
Oral cavity, oropharynx, and the upper section of almost entirely replaced by type I collagen as the
the esophagus can be involved. Blanching of the disease progressed. Due to alteration of molecular
oral mucosa and stiffness of the submucosal con- structures, collagen fibers from OSF could be more
nective tissue is commonly detected. Formation of difficult to degrade than normal ones [55, 56].
thick bands of collagen can be seen in advanced Collagen degradation by fibroblast phago-
stage of this disease, leading to restriction of cytosis is important in physiological renewal of
mouth opening. OSF predominantly affects the extracellular matrix. In OSF, this process was dis-
Asian population, especially people from India, turbed. The capability of collagen phagocytosis by
Sri Lanka, Taiwan, and Hunan Province of China. fibroblasts is hampered by arecoline and nicotine
No gender preference is observed. In 1996, it in a dose-dependent manner [57]. Interruption of
was reported that about 2.5 million people were the balance between matrix metalloproteinases
suffering from this disease worldwide; the prev- (MMPs) and tissue inhibitors of matrix metallo-
alence was still increasing, probably due to grow- proteinases (TIMPs) may also lead to cumulative
ing consumption of areca nut [51]. deposition of extracellular matrix [58, 59].
Evidences from epidemiologic studies con- Altered cytokine secretions have also been
firmed betel quid chewing as the major risk of noticed in OSF.  Decrease or absence of IFN-γ
OSF.  The development of OSF is related to the production and increase of interleukin-1 and
frequency and duration of betel quid chewing. interleukin-6 production might be related with
Case-control studies suggested that the incidence the development of OSF.  Increased expression
rate of OSF in the subjects below the age of 21 was of platelet-derived growth factor, transforming
almost twice as that in the subjects between 21 and growth factor-β, and basic fibroblast growth fac-
40. In the younger group, it took around 3.5 years tor could also be observed in OSF tissue [60].
to develop the disease from the start of the habit, Circulating immunocomplex, immunoglobu-
while in the older group, it took about 6.5  years lin, and various autoantibodies could be detected
[52]. Since OSF is mainly characterized by sub- in the sera of OSF patients. It was revealed that
5  Oral Mucosal Patches Striae Diseases 107

the serum levels of antinuclear antibody, anti-­

smooth muscle antibody, and anti-gastric parietal
cell antibody were significantly higher in OSF
patients than in healthy controls. Increased levels
of immunocomplex and serum immunoglobins
have also been reported. These all support the
role of immunological factor in the development
of OSF [61].
The studies of the role of genetic factors in
OSF have been focused on gene polymorphisms
and their association with the susceptibility of
OSF.  Gene polymorphisms of TNF-α has been Fig. 5.31  Marble-like appearance of the buccal mucosa
associated with risk of OSF. Major histocompati-
bility complex class I chain-related gene A (MICA)
has also been related with this disease [62]. facilitated, while the absorption will be hindered.
Areca nut contains a large amount of copper. These combined effects will result in extended
Compared with healthy subjects, patients with exposure of the oral mucosa to carcinogens [65].
OSF have higher concentration of soluble cop- The clinical manifestations of OSF depend on
per in the saliva and the oral mucosa. The effect the development of the disease. Burning sensation
of copper on collagen formation is dependent on and intolerance to irritative food and beverages
lysyl oxidase, which is upregulated in OSF tis- are commonly reported at the early stage. Vesicles
sue. In vitro studies have shown that the increase and erosion may be present, followed by indura-
of copper concentration could promote the pro- tion of the oral mucosa involving the lip, tongue,
liferation of fibroblasts. However, since no fibro- buccal mucosa, and palate. Restriction of mouth
sis of the visceral organs has been found using opening to various degrees can be observed. The
ultrasonic examination and copper level in the characteristic clinical manifestations include
excrement of OSF patients is within the normal blanching and opacity of the oral mucosa with a
range, the effect of copper on fibroblasts is prob- marble-like appearance (Fig. 5.31). Fibrous bands
ably localized to the oral mucosa [63, 64]. could be found by palpation. Epithelial dysplasia
OSF is considered as one of the oral poten- can be found in OSF lesions, which may later
tially malignant disorders. The reported malig- result in malignant transformation. Due to restric-
nant transformation rate ranges from 7% to 13%. tion of mouth opening caused by the disease,
In a follow-up duration of 17 years, the malignant early diagnosis of cancer can be difficult [65].
transformation rate of OSF was about 7.6%. The diagnosis of OSF is based on history of
Areca nut has been considered as a chemical betel quid chewing and typical clinical manifes-
carcinogen. The genotoxic and mutagenic effects tations, which can further be confirmed by histo-
of areca nut are closely related with polyphenols, pathological findings.
alkaloids, and areca nut-specific nitrosamines. Quitting betel quid chewing is necessary for
Moreover, slaked lime in the quid could enhance the treatment of OSF. An optional treatment regi-
the level of reactive oxygen species and then lead men commonly used by the authors is as follows:
to oxidative DNA damage. The risk of malignant tripterygium hypoglaucum tablet (2 g t.i.d. p.o.)
transformation could be further enhanced by and compound danshen dripping pill (10 pills
factors such as older age, nutritional deficiency, t.i.d. p.o.) consecutively for 1 month, local corti-
trauma, tobacco smoking, and genetic suscep- costeroids such as dexamethasone paste or triam-
tibility. Furthermore, due to epithelial atrophy cinolone acetonide oral paste, and intra-lesional
and reduced vascularity underneath the epithe- injection of triamcinolone acetonide at the dose
lium, the permeability of the carcinogen will be of 6 mg/site if necessary.
108 H. Dan et al.

5.8 Discoid Lupus Erythematosus Management:

Case 57 Discoid Lupus Erythematosus 1. Medication

Rp.: Triamcinolone acetonide (TA) injection
40 mg × 1
Sig.: Intra-lesional injection at the dose of
6 mg/site s.t.
Hydroxychloroquine 0.1 g × 28 tablets
Sig.: 0.1 g b.i.d. p.o.
Vitamin B6 10 mg × 100 tablets
Sig.: 5 mg b.i.d. p.o.
Compound chlorhexidine solution 300 ml × 1
Sig.: labial hydropathic compress t.i.d.
Dexamethasone paste 15 g × 1
Sig.: topical use t.i.d.
Fig. 5.32  Erythematous lesion on the lower lip, with 2. A follow-up visit after 2  weeks was sched-
radiating keratotic striae along the mucosal side and pig- uled. The patient was advised to avoid expo-
mentation along the cutaneous side of the lesion
sure to sunlight or eating spicy food.
Age: 58 years
Sex: Male Follow-Up Treatment:
Chief Complaints: If complete or partial remission was achieved
A 58-year-old man with recurrent ulceration, in the follow-up visit, the treatment plan can be
bleeding, and pain in the lower lip for 6 months switched to the following regimen: total gluco-
History of Present Illness: sides of paeony capsules (0.6  g b.i.d./t.i.d. p.o.
A 58-year-old man complained of recurrent for about 3–4  weeks). If no improvement was
ulceration, bleeding, and pain in the lower lip for achieved, the treatment plan can be switched to
6 months. The lesion took about 14 days to heal a regimen with tripterygium hypoglaucum tablet
but usually recurred after 1 month. (2 g t.i.d. p.o.) or thalidomide (75 mg q.d. p.o.)
Past Medical History: None. for about 2 weeks.
Allergy: None.
Physical Examination: [Review] Discoid Lupus Erythematosus
An 8 mm × 3 mm erosive and erythematous lesion (DLE)
coved with blood crust was found on the lower lip. Discoid lupus erythematosus (DLE) is a chronic
The erythematous lesion is surrounded with short cutaneous lupus erythematosus featured by dis-
white streaks in a radial pattern. Pigmentation could coid erythematous-to-violaceous plaques involv-
be observed on the skin side of the lesion (Fig. 5.32). ing the skin and mucosa. It usually affects the
Laboratory Investigations: sun-exposed skin, primarily the facial region
Routine laboratory tests, including whole blood [66]. DLE is more likely to affect women than
cell count, blood glucose examination, as well as men. There is a slight racial predilection for peo-
liver and kidney function panels, were normal. ple of African descents. The common age of dis-
Diagnosis: ease onset is around 20–40 years.
Chronic discoid lupus erythematosus (CDLE). The etiology of DLE remains obscure,
Diagnosis Basis: although a number of factors have been sug-
gested. Among them, sunlight has been con-
1. Erosive and erythematous lesion on the lower firmed to be associated with the development and
lip. exacerbation of DLE.  Photosensitivity to ultra-
2. White striae radiating from the border of the violet is quite common in patients with DLE,
lesion. which may be associated with the interactions
3. Pigmentation. between T cells and heat shock proteins (HSPs).
5  Oral Mucosal Patches Striae Diseases 109

One hypothesis is that HSPs are unveiled by UV is still debatable whether these deposits directly
radiation; this process is followed by interac- participate in the pathogenesis of DLE or are just
tion of HSPs with accumulated T cells, leading secondary to the development of DLE lesions. It
to liquefactive degeneration of basal epithelial is noticeable that increased immunoglobulin pro-
cells [67]. duction has been reported in DLE, most of which
Genetic background also played an important are induced by activation of B cells, indicating
part in the pathogenesis of DLE. Several haplo- that humoral and cellular immune responses are
types, such as human histocompatibility (HLA) both involved in DLE [67] .
-B7, B8, and Cw7, have been related with indi- The skin lesion of DLE usually emerged in
vidual’s susceptibility to DLE. HLA-DQA-0102 the form of an erythematous papule and then fol-
and HLA-DRB-1601 alleles have also been con- lowed by hyperkeratosis with follicular plugging.
sidered as potential genetic marker for DLE [68, Pigmentary changes may happen. The center of
69]. Recently, genome-wide association studies the lesion is usually atrophic and hypopigmented,
(GWAS) have shed a new light on the genetic while the periphery is often hyperpigmented.
background of systemic lupus erythematosus The face, scalp, ears, and chest are frequently
(SLE). Nevertheless, it is still uncertain whether affected. The lesions are persistent and may pro-
those genes recognized by GWAS have exactly duce scarring [71] (Fig. 5.33).
the same role in the development of DLE. Approximately 20% of the patients with DLE
Several observations suggest that DLE may be have oral lesions, with or without skin involve-
affected by hormones. For instance, the incidence ment [67, 72]. The vermilion, buccal mucosa,
of DLE is higher in women and the severity of and tongue are commonly affected. Although
DLE in women’s menstrual cycle, pregnancy, the lesions most often locate on the lower lip,
and menopause [70]. both the upper and lower lip can be involved at
Even though defined autoantibodies of SLE the same time (Figs.  5.34, 5.35, and 5.36). The
are not often detected in DLE, tissue binding typical lesion is a well-demarcated plaque with
of immunoglobulins and complements are usu- central erythema surrounded with short white
ally found at the dermo-epidermal junction. streaks in a radial pattern. The cutaneous side of
Therefore, DLE is considered as a chronic auto- the lesion could be pigmented, with or without
immune mucocutaneous disorder. However, it white striae. The borderline of mucosa and skin
can be blurry, and the lesion has a tendency to
invade into the skin.
The diagnosis of DLE may be made accord-
ing to the clinical appearance and be further con-
firmed by histopathological findings.

Fig. 5.33  DLE lesions involving the lower lip and the
skin of the right cheek. Erosive lesion with radiating white
striae and blood crust was observed on the lower lip, while
atrophic lesion with central hypopigmentation and periph-
eral hyperpigmentation was observed on the skin of the
right cheek Fig. 5.34  DLE lesions involving the upper and lower lips
110 H. Dan et al.

Fig. 5.35  DLE lesion on the left buccal mucosa Fig. 5.36  DLE lesion on the ventrum of the tongue

Typical histopathological changes include of patients at high risk. The patient may also
vacuolar degeneration of basal cells, lympho- be referred to rheumatologists or nephrologists
cyte infiltration surrounding the blood vessels, when necessary. It has been reported that treat-
and appendages in the dermis. Epidermal atro- ment with hydroxychloroquine or chloroquine
phy, hyperkeratosis with follicular plugging, at an early stage could delay the occurrence of
and vascular dilation with colloid bodies may be SLE in DLE patients and may prevent or alleviate
observed [67]. damage to peripheral organs [76] .
Direct immunofluorescence (DIF) can be used The recommended first-line systemic therapy
for the differential diagnosis of DLE and other for DLE is hydroxychloroquine (0.1  g b.i.d. for
diseases. Linear or granular deposits of immuno- 2 weeks or longer). Vitamin B6 (5 mg b.i.d.) is sup-
globulins and complement components along the posed to be taken at the same time to ameliorate
dermo-epidermal junction may be detected. gastrointestinal reaction. Besides, thalidomide
DLE is classified as one of the oral poten- (50–100  mg q.d.) or tripterygium hypoglaucum
tially malignant disorders by World Health tablets (2 g t.i.d. for 2 weeks or longer) can also
Organization. Although the incidence of DLE is be used. Systemic prednisone acetate (15–25 mg
higher in women and people of African descents, daily, in a single morning dose, for 5–7  days)
the malignant transformation is more likely to is often given in short courses to patients with
happen in European males. It has been reported widespread lesions or acute exacerbation, before
that in a follow-up period of 26–41 years, 3.3% switching the treatment plan to the reagents men-
of the patients developed squamous cell carci- tioned above. Total glucosides of paeony capsules
noma [73]. In another retrospective study, 6 out (0.6  g b.i.d./t.i.d. for 3  weeks or longer) can be
of 87 patients with diagnosis of oral DLE devel- used by patients with mild symptoms. Topical
oped oral cancer [74]. agents that had been reported effective for DLE
Around 5% of DLE cases may develop to SLE, include mouth rinse and liniments. Mouth rinses,
especially patients with HLA-B8 [75]. Identified including compound chlorhexidine solution, com-
clinical risk factors include widespread DLE pound borax solution (diluted fivefold with water
lesions, telangiectasias, arthritis, arthralgias, and before use), and 1% povidone iodine solution, can
Raynaud’s phenomenon. Laboratory risk factors be used for hydropathic compress, three times a
include anemia, leucopenia, thrombocytopenia, day. Liniments are mainly topical corticosteroids,
high erythrocyte sedimentation rates (ESRs), such as dexamethasone paste, prednisolone ace-
high levels of anticardiolipin antibodies, high tate suspension, triamcinolone acetonide, triam-
titres of antinuclear antibodies (ANAs), and cinolone acetonide oral paste, and dexamethasone
positive DIF findings in skin with normal appear- ointment. Additionally, triamcinolone acetonide
ance. More aggressive treatments and frequent injection or compound betamethasone injection
follow-up may be necessary for the management combined with sterile water or 2% lidocaine
5  Oral Mucosal Patches Striae Diseases 111

(at a ratio of 1:1) can be used for intra-lesional must be minimized by avoiding the peak hours for
injection. Aerosol therapy with dexamethasone sun exposure and by wearing protective clothing
sodium phosphate injection, gentamycin sulfate and high efficiency sunscreens. Diet containing
injection, vitamin C injection, and Vitamin B12 large amount of spicy food and seafood should be
injection, once or twice a day for 3–5 days, is an avoided. A regular follow-up is necessary to pre-
optional topical therapy. Moreover, sun exposure vent potentially malignant transformation.

5.9 Oral Fordyce Spots

Case 58 Oral Fordyce Spots

a b

Fig. 5.37 (a) Yellowish-white spots were observed on the vermillion. (b) Yellowish-white spots on the right buccal
mucosa. (c) Yellowish-white spots on the left buccal mucosa

Age: 50 years Physical Examination:

Sex: Male Multiple yellowish-white granules were found on the
Chief Complaints: vermillion and the buccal mucosa (Fig. 5.37a-c). No
A 50-year-old man with “white spots” on the lip erythematous or ulcerative lesions were observed.
and buccal mucosa for 2 days Diagnosis:
History of Present Illness: Oral Fordyce spots.
A 50-year-old man came to the clinic after he Diagnosis Basis:
found painless “white spots” on the lip and buc-
cal mucosa 2 days ago. 1 . Involvement of buccal mucosa and the lips.
Past Medical History: None. 2. Asymptomatic yellowish-white granules on

Allergy: None. the oral mucosa.
112 H. Dan et al.

Management: but usually don’t have hair follicles or ducts that

Explain the cause and prognosis of the disease to connect to the surface of the oral mucosa.
the patient. Oral FSs usually appear after puberty, prob-
ably due to the changes of hormone levels.
[Review] Oral Fordyce Spots However, some investigations have indicated that
Oral Fordyce spots (FSs) are ectopic sebaceous the formation of ectopic sebaceous glands might
glands. They appear as yellow or yellowish-white be related with the nervous system. Factors like
painless granules with a smooth and soft surface, insulin-like growth factor and corticotrophin-­
about 1–3  mm in dimension. They can be scat- releasing hormone may induce the formation
tered on the mucosa or distributed in aggregates of ectopic sebaceous glands by facilitating the
and are most commonly seen on the vermilion growth of nervous fibers. Valid research data
of upper lip, buccal mucosa, and the retromolar on the etiology of this disorder is still lacking
area, often bilaterally [77]. [77–80].
Oral FSs are usually not biopsied as they can be It is not necessary to treat oral FSs. If the gran-
readily diagnosed based on the clinical features. ules must be removed due to cosmetic reasons,
When examined under a microscope, they have carbon dioxide super-pulsed laser can be a safe
appearance similar to normal sebaceous glands, and effective treatment option [81].

5.10 M
 orsicatio Buccarum et
Labiorum

Case 59 Morsicatio Buccarum et Labiorum

a b

Fig. 5.38 (a) The inner surface of the lower lip was cov- the underneath mucosa was intact and didn’t have any sig-
ered by squama that was partially attached to the epithe- nificant color change or ulceration. (c) The right buccal
lium. In the area where the squama was peeled off, the mucosa was covered by squama that was partially attached
underneath mucosa was intact and didn’t have any signifi- to the epithelium. In the area where the squama was peeled
cant color change or ulceration. (b) The left buccal mucosa off, the underneath mucosa was intact and didn’t have any
was covered by squama that was partially attached to the significant color change or ulceration
epithelium. In the area where the squama was peeled off,
5  Oral Mucosal Patches Striae Diseases 113

Age: 24 years planus, oral candidiasis, and white sponge nevus.

Sex: Male Some studies suggest that it is most common in
Chief Complaints: adolescents aged 15–19  years. The lesions are
A 24-year-old man with rough feeling on the inner more often bilateral [82].
surface of lips and the buccal mucosa for 1 year Morsicatio buccarum et labiorum often affects
History of Present Illness: parts of the oral mucosa that are in direct contact
A 24-year-old man came to our clinic, complain- with the teeth, such as the lower lip and the buc-
ing of 1-year history of chronic desquamation cal mucosa. The mucosa is covered with loose
and rough feeling on the inner surface of lips and squama that can be peeled off without causing
the buccal mucosa. History of habitual cheek and any significant color change, bleeding, or ulcer-
lip biting was reported. Treatment with vitamin ation of the underneath mucosa. The patients
B2, folic acid, acetylspiramycin tablets, cydio- usually don’t have any discomfort other than a
dine buccal tablets, and bezoar antidotal pills did rough feeling on the mucosa involved [83].
not show any significant effect. Morsicatio buccarum et labiorum is a form of
Past Medical History: None. self-induced injury. It is closely related with psy-
Allergy: None. chological factors. Some researchers think that
Physical Examination: the compulsion represents aggressive feelings
The inner surface of the lips and the buccal or a form of self-punishment. The habit is often
mucosa were covered with squama that was par- combined with teeth grinding. Some investigators
tially attached to the epithelium (Fig. 5.38a-c). think that some form of surface irregularity, such
The squama could be wiped off without any pain as oral white sponge nevus or linea alba, precedes
using a cotton stick and didn’t cause any signifi- the onset of the cheek biting.. The patients may
cant color change, bleeding, or ulceration on the feel compelled to remove these lesions, which is
underneath mucosa. how the habit begins. Some patients with this dis-
Diagnosis: order are unaware of the habits. Questioning the
Morsicatio buccarum et labiorum. patient’s family members or close friends who
Diagnosis Basis: have witnessed the habits can help the clinicians
to obtain necessary information [84].
1. Buccal mucosa and inner surface of lips covered The diagnosis of morsicatio buccarum et
with squama that could be wiped off without labiorum is often based on clinical manifesta-
any pain or subsequent bleeding or ulceration. tions and the history of habitual cheek and/or lip
2. History of habitual cheek and lip biting. biting. Pathological characteristics of this disor-
der are acanthosis of the epithelium with super-
Management: ficial erosion lined by an irregular, frayed layer of
parakeratosis. The surface is basophilic because
1. Medication of accumulated cellular debris and bacteria on
Rp.: Vitamin E 0.1 g × 60 the intact epithelium and among torn fragments.
Sig.: topical use t.i.d. Beneath the erosion there is a necrotic layer of
2. Stop habitual cheek and lip biting. cells with characteristic eosinophilic staining [85].
The lesions of morsicatio buccarum et labio-
[Review] Morsicatio Buccarum et Labiorum rum can heal spontaneously without any sequela
Morsicatio buccarum et labiorum is caused if the patient can quit the habit. Topical agents,
by self-injury, and the target of injury is oral such as vitamin E, can be used to reduce the
mucosa. It appears as whitish squama on the oral roughness of the mucosa affected. The patient
mucosa and can be difficult to be distinguished should be referred to a psychologist or psychia-
from other mucosal disorders, such as oral lichen trist if needed.