APPROACH TO ORAL LESIONS DR.

Pelin Kuteyla CAN

Learning goal: Atst
Atst: Ayırıcı tanı yapar, semptomatik tedavi yapar. Makes the differential diagnoses,
treats symptomatically.
COMMON ORAL MUCOSAL
FINDINGS
FORDYCE GRANULES
•are ‘Free’ sebaceous glands (i.e. not
associated with hair follicles) evident in
as many as 75% of adults.
•Multiple 1- to 2-mm yellowish papules
on the vermilion lips (upper > lower) and
oral mucosa (especially buccal).
GEOGRAPHIC TONGUE
(MIGRATORY GLOSSITIS)
•Incidental finding on the dorsum of the
tongue in ~2–3% of the population; may
occasionally be associated with psoriasis,
especially pustular variants.
•Well-demarcated areas of erythema and
atrophy of the filiform papillae, surrounded
by a whitish, hyperkeratotic serpiginous
border are the features
•Lesions tend to migrate over time, may
affect other oral sites
•Occasionally associated with a burning
sensation. 
•No treatment is generally necessary
SCROTAL (FISSURED) TONGUE
•Asymptomatic finding that is
occasionally associated with conditions
such as granulomatous cheilitis and Down
syndrome.
•Multiple grooves or furrows are present
on the dorsal tongue, especially
centrally.
HAIRY TONGUE
(BLACK HAIRY TONGUE)
Reflects accumulation of keratin on the dorsum
of the tongue; contributing factors may include
poor oral hygiene, smoking, and a soft diet.
Confluence of hairlike projections, which
represent elongated papillae, with yellowish to
brown-black discoloration
May have exogenous staining from food,
tobacco, or chromogenic bacteria (especially
following antibiotic therapy)
Some patients report an unpleasant odor or
taste. 
DDx: pigmented papillae of the tongue (in
individuals with darkly pigmented skin).
Rx: scraping or brushing the tongue.
LEUKOEDEMA
•Normal variant that is more often
evident in smokers and individuals with
darkly pigmented skin.
•Grayish-white, opalescent, sometimes
‘moth-eaten’ appearance of the buccal
> labial mucosa; typically becomes less
evident upon stretching.
MEDIAN RHOMBOID GLOSSITIS
•Found in ~1% of adults, often
associated with local overgrowth
of Candida .
•Well-demarcated diamond- or
oval-shaped area of erythema and
atrophy on the dorsum of the tongue
•Rx: clotrimazole troches or oral
fluconazole
OROPHARYNGEAL CANDIDIASIS
•Often asymptomatic. • Erythematous or Atrophic
•Burning or pain on eating spices/acidic foods,
Candidiasis.
diminished taste sensation. Dorsum of tongue is smooth, red, atrophic (Areas
•Cosmetic concern about white curds on tongue. of thrush may also be present.
•Odynophagia. • Candidal Leukoplakia.
•In HIV disease, may be the initial presentation. Presents as white plaques that cannot be wiped
off but regress with anticandidal therapy.
• Pseudomembranous Candidiasis.
Distribution: buccal mucosa, tongue, hard palate.
Presents as white cottage cheeselike flecks (colonies of
Candida) on any mucosal surface • Angular Cheilitis.
Vary in size from 1–2 mm to extensive and Intertrigo at the angles of lips.
widespread.
Removal with a dry gauze pad leaves an erythematous Erythema; slight erosion.
mucosal surface.
White colonies of Candida in some cases.
Distribution: It locates Dorsum of tongue, buccal mucosa,
hard/soft palate, pharynx extending down into Usually associated with oropharyngeal
esophagus and tracheobronchial tree. colonization with Candida.
 Oral candidiasis: atrophic and
Oral candidiasis: thrush White curd-like material on the mucosal surface of the pseudomembranous A 48-yearold male with
lower lip of a child; the material can be abraded with gauze HIV disease. The surface of the tongue is shiny Angular cheilitis
(pseudomembranous), revealing underlying erythema. and red; posterior tongue has a white coating
(thrush).

Oral candidiasis: thrush Extensive cottage cheese-like

plaques, gauze (pseudomembranous),
on the palate and uvula of an individual with advanced
HIV/AIDS. Patches of erythema
between the white plaques represent erythematous
(atrophic) candidiasis. Involvement
may extend into the esophagus and become associated
with dysphagia.
PERIODONTAL AND DENTAL
CONDITIONS WITH DERMATOLOGIC
RELEVANCE
Desquamative Gingivitis
Is a clinical finding that can occur in several
immune-mediated vesicular and erosive disorders; it
favors women over 40 years of age.  
Diffuse gingival erythema with varying degrees of
sloughing and erosion; frequently painful.
Because desquamative gingivitis is often a
manifestation of mucous membrane (cicatricial)
pemphigoid and other autoimmune bullous disorders,
evaluation should include routine histology plus direct
and indirect immunofluorescence studies.
Rx: treatment of underlying condition plus meticulous
oral hygiene.
GINGIVAL ENLARGEMENT
(HYPERPLASIA, OVERGROWTH)
Drug-related gingival enlargement
typically develops during the first year
of administration and is first evident in
the interdental papillae.
SEQUELAE OF TRAUMA OR TOXIC
INSULTS
FIBROMA (BITE FIBROMA)
•Results from reactive connective tissue
hyperplasia in response to local trauma.
•Smooth pink papulonodule; most often
located on the labial mucosa, especially
of the lateral lower lip, or along the ‘bite
line’ of the buccal mucosa.
•Rx: if bothersome, excision with
histologic evaluation to exclude a
neoplastic condition.
MORSICATIO BUCCARUM (CHRONIC
CHEEK CHEWING)
•Characteristic mucosal changes related
to habitual chewing or biting.
•Shaggy white mucosa, usually bilaterally
in the buccal region along the ‘bite line’
MUCOCELE
•Translucent to bluish papule due to
disruption of a minor salivary gland duct,
most often located on the lower mucosal
lip
CHEMOTHERAPY- AND RADIATION
THERAPY-INDUCED MUCOSITIS
•Results from cytotoxic effects on the oral epithelium,
especially in the setting of neutropenia; typically
develops 4–7 days after administration of
chemotherapy and ≥2 weeks after beginning
radiation therapy.
•Multiple erosions and/or ulcerations favor the
gingivae, lateral tongue, and buccal mucosa;
self-limited.
•DDx: herpetic or candidal infections (may be
concomitant).
•Rx: topical anesthetics, analgesics, maintenance of oral
hygiene; palifermin (recombinant human keratinocyte
growth factor) can reduce severity but produces whitish
discoloration of the dorsum of the tongue due to
hyperkeratosis.
CHEILITIS
Cheilitis glandularis , seen primarily in
men with a history of chronic sun
exposure and/or lip irritation, is
characterized by inflammatory
hyperplasia of the lower labial salivary
glands; this results in tiny erythematous
macules (at sites of salivary ducts) and
variable hypertrophy of the lower lip
OTHER INFLAMMATORY CONDITIONS
APHTHAE (APHTHOUS STOMATITIS; CANKER
SORES)
Common condition characterized by recurrent oral ulcers, with a peak
prevalence during the second and third decades of life; outbreaks may
be triggered by trauma, psychological stress, or hormonal fluctuations.

Minor aphthae (most frequent form): painful, round to ovoid,

shallow ulcers that are usually <5 mm in diameter; feature (it has) a
yellowish-white to gray pseudomembranous base, well-defined border,
and prominent erythematous rim; favor the buccal or labial mucosa
and typically heal in 1–2 weeks without scarring. 

Major aphthae: larger (>1 cm), deeper ulcers that persist for up

to 6 weeks; occasionally affect keratinized mucosa (e.g. dorsum of
tongue, hard palate, attached gingiva) as well as nonkeratinized
mucosa, may heal with scarring, and are more common in HIV-infected
individuals. 
Herpetiform aphthae: simultaneous development of
numerous small lesions that tend to coalesce; tends to
favor nonkeratinized mucosa, unlike recurrent oral HSV,
which favors keratinized mucosa.
Complex aphthosis: frequent outbreaks of multiple (≥3)
oral aphthae, or recurrent genital as well as oral
aphthae, in the absence of Behçet's disease
Recurrent aphthae can occur in the setting of systemic
disorders such as inflammatory bowel disease, SLE, and
Behçet's disease
DDx: Mouth ulcers can arise from local causes, malignancy, drug adverse effects, and systemic
conditions (particularly infections, blood disorders, gastrointestinal disorders, and skin
diseases).
Recurrent multiple ulcers are most typical of the following conditions (before making a
diagnosis of recurrent aphthous stomatitis [RAS], potentially overlooked causes of oral ulcers
must be considered):
Hematinic deficiency (eg, iron, folate, vitamin B-12)
Celiac disease
Crohn disease
Behçet syndrome
Sweet syndrome
HIV infection, neutropenia, and other immunodeficiencies
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) in
children
Laboratory studies: Diagnosis of recurrent aphthous stomatitis (RAS) is based on history and
clinical features. No specific tests are available; however, to exclude systemic disorders
discussed above, the following tests may be helpful:

?Complete blood cell count

?Hemoglobin test
?White blood cell count with differential
?Red blood cell indices
?Iron studies (usually an assay of serum ferritin levels)
?Red blood cell folate assay
?Serum vitamin B-12 measurements
?Serum antiendomysium antibody and transglutaminase assay (positive in celiac disease)
Rarely, biopsy may be indicated in cases in which a different diagnosis is suspected.
Occasionally, for example, pemphigus may mimic RAS. Occasional RAS can mimic a
neoplasm, necrotizing sialometaplasia, or TUGSE (traumatic ulcerative granuloma with
stromal eosinophilia).
 
Rx: superpotent topical CS gel, topical analgesics; if severe or frequent recurrences: vitamin
B 12, colchicine, dapsone, thalidomide (the latter is especially helpful for major aphthae).
GRANULOMATOUS CHEILITIS AND OTHER FORMS OF OROFACIAL
GRANULOMATOSIS

The term orofacial granulomatosis refers to non-infectious,

non-necrotizing granulomatous inflammation of the lips, face,
and/or oral cavity; this term includes isolated granulomatous
cheilitis as well as manifestations of Crohn's disease and
sarcoidosis; usually develops during the second or third decade of
life.
Granulomatous cheilitis presents as diffuse swelling of the lip(s)
(lower> upper or both) that can initially be intermittent (raising the
possibility of angioedema) but is eventually persistent; patients
may have oral cobblestoning, recurrent aphthae, and gingival
enlargement, and the less frequent association with a scrotal
tongue and/or facial nerve palsy is referred to
as Melkersson–Rosenthal syndrome.  
Rx: intralesional CS, topical calcineurin inhibitors, dapsone,
tetracyclines (given for several months), thalidomide or TNF
inhibitors (for severe disease); patients should be evaluated for
signs of Crohn's disease and sarcoidosis.
CONTACT STOMATITIS
Irritant or allergic contact stomatitis can
result from a variety of foods, food
additives, and materials used in dentistry; in
particular, cinnamon flavoring and dental
amalgam (‘silver’ fillings) can lead to a
lichenoid mucositis histologically.
Shaggy white or erythematous areas, most
often on the buccal mucosa or lateral
tongue; lacy white streaks (resembling lichen
planus) or erosions may be seen. 
Rx: evaluation with patch testing and
avoidance of offending agents, sometimes
requiring replacement of amalgam with
other materials.
NICOTINE STOMATITIS
Presents as gray-white discoloration of
the palate, often with umbilicated
papules that represent inflamed salivary
ducts
 
ATROPHIC GLOSSITIS
•Manifestation of several nutritional
deficiencies (e.g. vitamin B 12 [pernicious
anemia], folate, iron, niacin [pellagra],
riboflavin) and candidiasis. 
•Presents with a smooth, ‘beefy red’ tongue;
•Involvement may initially be patchy but is
eventually diffuse
•May be associated with a burning sensation
or sore mouth.
PREMALIGNANT AND MALIGNANT
CONDITIONS
LEUKOPLAKIA AND ERYTHROPLAKIA
Leukoplakia refers to a white patch or plaque on the oral mucosa that cannot be
clinicopathologically characterized as a specific disease process; typically occurs in middle-aged
and older adults (men > women), especially those who use tobacco ± alcohol, and is regarded as
a premalignant condition for SCC.
– Often a homogeneous white patch or plaque, but may be nonhomogeneous and ‘speckled’ (e.g.
white flecks on a red base); usually has sharply demarcated borders.  
Similarly, erythroplakia is defined as a red intraoral patch or slightly elevated, velvety plaque
that cannot be diagnosed as a particular disease; biopsies usually show more severe epithelial
dysplasia than leukoplakia.
- Often affects the buccal mucosa, lower inner lip, floor of the mouth, and lateral or ventral
tongue.
The degree of histologic epithelial dysplasia influences the risk of transformation to SCC;
nonhomogeneous leukoplakia, erythroplakia, and lesions located on the floor of the mouth or
lateral/ventral tongue also have higher malignant potential.
DDx of leukoplakia: may include SCC, lichen
planus, candidiasis, morsicatio buccarum (see
above), and nicotine or contact stomatitis. 
After elimination of possible causative factors
(e.g. tobacco use, candidiasis, irritation/trauma)
for 2–6 weeks, persistent lesions should be
biopsied.
Rx: for leukoplakia with moderate to severe
dysplasia or in high-risk sites and for
erythroplakia – excision, cryosurgery, or laser
ablation; all patients need longitudinal
evaluation and should avoid carcinogenic habits.
Proliferative verrucous leukoplakia , which tends
to occur in women without traditional risk factors,
is characterized by multifocal red and white
patches that eventually develop a verrucous
surface; difficult to treat and associated with
high risk of transformation to SCC.
SQUAMOUS CELL CARCINOMA
Most common malignancy of the oral cavity, favoring
middle-aged and older men; risk factors include tobacco
and alcohol use, HPV infection, and betel nut chewing.
May present as an ulcer, exophytic mass, or area of
induration; it is most often on the lateral or ventral tongue
and floor of the mouth.
DDx: leukoplakia, traumatic ulcer, salivary gland tumor,
amelanotic melanoma.  
Rx: combinations of surgery, radiation therapy (especially if
HPV-associated), and chemotherapy.
Verrucous carcinoma ( oral florid papillomatosis ) is a
low-grade variant of SCC that presents as slowly growing,
exophytic papillomatous masses that favor the buccal
mucosa and gingiva.
Rx: excision, traditionally avoiding radiation therapy due to
a possible association with anaplastic transformation.
MELANOMA
•Uncommon oral malignancy that favors
middle-aged and older men; often
diagnosed at a locally advanced stage.
•Pigmented (with findings similar to
cutaneous melanoma) > amelanotic, with
a predilection for the hard palate and
maxillary gingivae.
•DDx: for pigmented lesions – foreign
body tattoo, blue nevus, oral melanotic
macule, physiologic pigmentation. 
ORAL SIGNS OF SYSTEMIC DISEASE
In addition to common benign lesions such as bite fibromas and mucoceles, oral
findings often represent clues to the diagnosis of skin disorders (e.g. lichen planus,
early pemphigus vulgaris) or cutaneous signs of systemic disease.
Disorder Oral Findings
Primary systemic Macroglossia, often with scalloped edges (due to dental impressions) or hemorrhagic papulonodules; xerostomia
amyloidosis
Nutritional o Atrophic glossitis, stomatitis
deficiencies
Scurvy: gingival enlargement, hemorrhage and erosions
Inflammatory bowel o Crohn's disease : oral cobblestoning and ulcers, angular cheilitis, orofacial granulomatosis
disease
Pyostomatitis vegetans (ulcerative colitis > Crohn's): oral pustules and erosions in a ‘snail track-like’ arrangement
Behçet's disease o Aphthae
Sarcoidosis Orofacial granulomatosis, xerostomia, salivary gland enlargement
Sjögren's syndrome Xerostomia
Wegener's o Gingival hemorrhage with a friable micropapular surface
granulomatosis
Leukemia o Hemorrhage due to thrombocytopenia, infections (viral, fungal, bacterial), gingival enlargement due to leukemic infiltration (especially
in [myelo]monocytic forms)
Genodermatoses o Tuberous sclerosis: oral fibromas, dental enamel pits

o Cowden disease: oral papillomas favoring lips and tongue

o Multiple endocrine neoplasia type 2B: mucosal neuromas – papulonodules favoring lips and anterior tongue

o Darier disease: whitish papules and rugose plaques favoring palate and gingivae

o Lipoid proteinosis: diffuse infiltration or cobblestoned papules favoring lips and tongue/frenulum, xerostomia

o Chronic mucocutaneous candidiasis

o Classic hyper-IgE syndrome: retention of primary teeth, candidiasis

o Ectodermal dysplasias hypodontia, cone-shaped teeth

o Nevoid BCC syndrome: odontogenic keratocysts of mandible> maxilla

o Gardner syndrome: osteomas of maxilla and mandible

ORAL HAIRY LEUKOPLAKIA
EBV emerges from latency in advanced HIV disease and causes benign
mucosal hyperplasia. Occurs with CD4+ cell count <300/μL
Asymptomatic, but stigmatization of HIV disease.
White or grayish-white, well-demarcated plaques with corrugated
texture. Most commonly on the lateral and inferior surfaces of the
tongue.
Often present bilaterally.
Oropharyngeal candidiasis often present as well.
DDx: Pseudomembranous candidiasis (thrush), geographic or migratory glossitis,
tobacco-associated leukoplakia, mucous patch of secondary syphilis.
Dx: Clinical diagnosis. Lesions do not rub off; does not clear with adequate
anticandidal therapy.
Course. Usually resolves with cART and immune restoration. Recurs when cART
failing.
Rx: Podophyllin 25% in tincture of benzoin applied to the lesion with a
cotton-tipped applicator for 5 minutes. Effective cART results in regression and
clearing of OHL.
BEHÇET’S DISEASE
A multisystem disease whose mucocutaneous features include aphthous orogenital ulcers,
sterile pustules (occasionally follicular), and palpable purpura due to small vessel vasculitis,
as well as superficial thrombophlebitis and erythema nodosum-like lesions.
Because the diagnosis is made clinically, there are several sets of criteria, including the
ones outlined in Table
There are countries in which the disease is more commonly seen, e.g. Turkey, Japan, and
those along the ancient Silk Road; the peak incidence is ages 20–35 years.
DDx: recurrent genital and oral HSV, complex aphthosis, inflammatory bowel disease, SLE,
pemphigus vulgaris, Marshall's syndrome (periodic fever, aphthous stomatitis, pharyngitis,
cervical adenitis).
 Systemic manifestations of Behçet's disease.

∙ Ocular (leading cause of morbidity) ∙ Neurologic

o • Occurs in 90% of patients; favors men, in whom it is more o • Usually appears later during the evolution of the disease
severe
o • Associated with a poor prognosis
o • Can be painful and may lead to blindness
o • Acute meningoencephalitis that may resolve spontaneously
o • Retinal vasculitis (more frequently associated with
blindness) o • Cranial nerve palsies
o • Posterior uveitis (most characteristic ocular finding) o • Brain stem lesions that can induce swallowing difficulties,
laughter, and crying
o • Anterior uveitis, hypopyon
o • Pyramidal or extrapyramidal signs
o • Secondary glaucoma, cataracts
o • Conjunctivitis, scleritis, keratitis, vitreous hemorrhage, optic
neuritis
∙ Joints Gastrointestinal
o • Approximately 50% of patients develop arthritis • Abdominal pain and/or hemorrhage may be difficult to distinguish
from IBD
o • In majority (~80% of patients), duration of attacks is <2
months • Ulcerations develop within the small bowel (particularly the
ileocecal region) as well as the transverse and ascending colon and
o • Mono- or polyarthritic and non-erosive esophagus; perforation can occur
o • Most commonly knees, wrists, and ankles
∙ Cardiopulmonary ∙ Vascular
o • Coronary arteritis, valvular disease, myocarditis o • Aneurysmal or occlusive arterial disease
o • Recurrent ventricular arrhythmias o • Superficial or deep venous thrombosis
• Pulmonary artery aneurysms
∙ Renal
The ISG criteria defined Behçet's disease as recurrent oral ulceration plus two of the following: recurrent genital
ulcerations, eye lesions, skin lesions, or a positive pathergy test.
International study group criteria for the diagnosis of Behçet's disease.
Criteria Required Features
Major Criterion:
Recurrent oral ulceration Aphthous (idiopathic) oral ulceration observed by physician or patient,
recurring at least three times in a 12-month period
Plus any two of the following minor criteria:
Recurrent genital ulceration Aphthous genital ulceration or scarring, observed by physician or patient

Eye lesions Anterior or posterior uveitis; cells in the vitreous by slit lamp
examination; or retinal vasculitis observed by ophthalmologist
Cutaneous lesions Erythema nodosum-like lesions observed by physician or patient;
papulopustular lesions or pseudofolliculitis; or characteristic acneiform
nodules observed by physician in postadolescent patient not on
corticosteroids
Pathergy test * Interpreted at 24–48 hours by physician
* Pathergy test is performed on the flexor forearm by obliquely inserting a 20- to 22-gauge sterile hypodermic
needle to a depth of 5 mm ± an intradermal injection of 0.1 ml of normal saline. A positive reaction is defined
as the development of a papule or pustule.
CUTANEOUS DISORDERS INVOLVING
THE ORAL MUCOSA
Cutaneous disorders may present in oral mucosa; may be confined to this site for months
before cutaneous involvement occurs.
 
PEMPHIGUS VULGARIS (PV)
Often presents in oral mucosa; may be confined to this site for
months before cutaneous bullae occur.
Blisters are very fragile, rupture easily, rarely seen.
Sharply marginated erosions of the mouth (buccal mucosa, hard
and soft palate, and gingiva) are presenting symptoms.
Gingivitis can be a presenting sign. Erosions are extremely
painful, interfering with nutrition.
Clinically, almost all patients with pemphigus vulgaris have
painful erosions of the oral mucosa and at least half will have
flaccid bullae of the skin plus erosions due to their rupture;
lesions can be localized or widespread
There may be involvement of other mucosal surfaces, e.g.
conjunctival, nasal, vaginal.
Additional clinical clues include the development of hemorrhagic crusts of the
vermilion lips and a positive Nikolsky sign in areas of active disease – the
epidermis can be easily moved laterally with rubbing (due to reduction in
intercellular adhesion)
Biopsy, immunofluorescence, or antibody titers against desmogleins 1 or 3 confirm the
diagnosis.
 DIF of perilesional skin demonstrates
immunostaining of the cell surface of keratinocytes
within the epidermis or mucosa in almost all
patients, and the staining may be more
predominant in the lower portion of the epithelium;
IIF and ELISA of sera is positive in more than 90%
of patients
DDx: other forms of pemphigus, bullous
pemphigoid, linear IgA bullous
Rx: oral CS, steroid-sparing agents (e.g.
mycophenolate mofetil, azathioprine,
cyclophosphamide), IVIg, plasmapheresis (plus
immunosuppression), and rituximab
BULLOUS
PEMPHIGOID
In contrast to pemphigus vulgaris, bullous pemphigoid
uncommonly affects the oropharynx.
Findings: Blisters, which initially are tense, erupt on the
buccal mucosa and the palate, rupture, and leave
sharply defined erosions that are practically
indistinguishable from those of PV or cicatricial
pemphigoid.
However, erosions less painful and less extensive than
in PV.
Immunobullous disease due to circulating
autoantibodies that bind two components of
hemidesmosomes, i.e. structures that provide adhesion
between the epidermis and the dermis; the two
antigens are collagen XVII (also referred to BP
antigen 2 [BPA2] or BP180) and BPA1/BP230.
Occurs more commonly in the elderly
Can be drug-induced (e.g. furosemide);
rarely, lesions are induced by ultraviolet
light or radiation therapy.
Both pruritic fixed urticarial plaques and
tense bullae are seen, the latter can
develop within normal skin or areas of
erythematous skin and produce erosions
when they rupture; oral lesions are much less
common than in pemphigus vulgaris
(10–30% of patients).
Pruritus and nonspecific eczematous or
papular lesions can precede the more
characteristic cutaneous lesions and may be
the predominant finding; unusual variants
include dyshidrosiform (palms and soles),
vegetans (major body folds), and localized
(e.g. pretibial in adults; vulvar in children,
acral in infants), as well as those that mimic
prurigo nodularis and toxic epidermal
necrolysis.
Histologically, a subepidermal bulla plus an
infiltrate of eosinophils is seen when the lesions
are bullous; DIF demonstrates immunodeposits of
IgG and/or C3 in a linear array along the
basement membrane zone in general, by
salt-split skin immunofluorescence studies, the
immunodeposits are in the roof (epidermal side)
of the blister
At least 50% of patients have a peripheral
eosinophilia.
DDx: linear IgA bullous dermatosis (LABD),
epidermolysis bullosa acquisita (EBA), mucous
membrane pemphigoid, various forms of
pemphigus, hypersensitivity reactions (including to
drugs), primary pruritus, allergic contact
dermatitis, scabies, urticaria (but individual
lesions transient
Therapeutic ladder for bullous pemphigoid.
Key to evidence-based support: (1) prospective controlled trial;
(2) retrospective study or large case series; (3) small case series or individual case reports .

Note : Superpotent topical corticosteroids

Mild and/or localized disease Extensive/persistent cutaneous disease should be considered in any patient and
• Superpotent topical • Superpotent topical corticosteroids (1 * ) may be combined with a systemic
therapy.
corticosteroids (1 * ) * Validated.
• Oral corticosteroids † (1 ‡ )
† Prednisone doses of at least
• Nicotinamide in association 0.5–0.75 mg/kg/day seem to be
• Azathioprine (2) necessary to control extensive
with minocycline, disease but increase serious side
doxycycline, or tetracycline • Mycophenolate mofetil (2) effects, including mortality.
‡ Validated for prednisone.
(3)
• Methotrexate § (2) § In elderly patients, low-dose
regimen (2.5–10 mg/week) can be
• Erythromycin, penicillins effective.
• Chlorambucil (3)
(3)
• Cyclophosphamide (3)
• Dapsone, sulfonamides (3)
• IVIg (3)
• Topical immunomodulators
(e.g. tacrolimus) (3) • Plasma exchange (2)
• Rituximab (3)
Characteristics of major autoimmune bullous diseases.
PV BP DH LABD
Cutaneous Flaccid vesicles and erosions Large tense bullae Grouped papules and Small vesicles and/or large
lesion small vesicles, often bullae
excoriated
Distribution Mucosae; can be widespread Trunk, extremities, Extensor surfaces, Similar to DH or BP
occasionally mucosal symmetrical
surfaces
Histology Intraepidermal vesicle with Subepidermal bullae withSubepidermal bullae with Subepidermal bullae with
acantholysis eosinophilic infiltrate neutrophilic infiltrate neutrophilic infiltrate
Direct IF Intercellular C3, IgG; occasionally Linear IgG and C3 at Granular IgA in dermal Linear IgA at BMZ,
IgA *(‘chickenwire’ pattern) BMZ papillae possibly also IgG
Site to biopsy Perilesional Perilesional Adjacent Perilesional
for direct IF normal-appearing skin
Indirect IF Intercellular IgG (90%) Linear IgG at BMZ (70%) Negative Linear IgA at BMZ (70%)
ELISA Distinguishes anti-Dsg1 vs. anti-Dsg3 Detects anti-BP180 and Anti-tissue n/a
Ab -BP230 IgG antibodies transglutaminase (TG2) &
anti-epidermal
transglutaminase (TG3)
antibodies
Enteropathy None None >90% Rare
Dapsone Mild ** Minimal to moderate Excellent Good, may also require
responsivenes systemic corticosteroids
s
CICATRICIAL PEMPHIGOID
Autoimmune mucosal blistering disease that heals with
scarring.
Clinical manifestations dependent on sites involved.
Persistent painful erosions on mucous membranes.
Desquamative gingivitis with painful erosions on tongue,
buccal, and palatal mucosa.
Ocular symblepharon and corneal scarring are feared
complications.
May be associated with malignancy, particularly if
antibodies against epiligrin are noted.
Sequelae: decreased vision/blindness; hoarseness, upper
airway compromise, esophageal stenosis.
Chronic immunobullous disease due to
autoantibodies that bind several components of the
BMZ of the skin and mucosae, most often BP180
and laminin 332 (laminin 5); although
heterogenous in its presentation, a tendency to
scarring is typically seen.
The mucous membranes represent the major site of
involvement, in particular conjunctival (erosions,
scarring with symblepharon formation, blindness)
and oral mucosae (persistent erosions of the buccal
and palatal mucosae, desquamative gingivitis)
DDx: pemphigus vulgaris, occasionally BP, EBA,
and LABD; if limited to oral mucosa, lichen planus
or pemphigus vulgaris; if limited to scalp, consider
other causes of scarring alopecia.
Rx: potent topical or intralesional CS, dapsone,
cyclophosphamide (severe or progressive ocular
disease), alone or in combination with systemic CS,
and rituximab.
 
LUPUS ERYTHEMATOSUS
Mucosal involvement occurs in approximately 25% of those
with chronic cutaneous lupus erythematosus.
Findings: Lesions: painless erythematous patches to chronic
plaques, sharply marginated, irregularly scalloped white
borders, radiating white striae, and telangiectasia. In older
lesions: central depression, painful ulceration.
Distribution: buccal mucosa; palate, alveolar process,
tongue. Chronic plaques may also appear on the vermilion
border of the lips.
In acute systemic lupus erythematosus, ulcers arise in
purpuric necrotic lesions of the palate (80%), buccal
mucosa, or gums.
 
 
STEVENS-JOHNSON SYNDROME/
TOXIC EPIDERMAL NECROLYSIS
Idiopathic reaction to medications and occasionally
viral agents that lead to epidermal necrosis and
desquamation. It is essential to discontinue possible
culprits as soon as possible. There is a better
prognosis with culprit drugs of shorter halflife.
Classification schemes depend on extent of body
surface area involved, but greater than 30%
involvement generally agreed to be TEN with
mucosal involvement.
Most common mucosal location affected is the
oropharynx.
Mucosal lesions can precede cutaneous involvement
by 1–3 days. In the mouth, presenting symptoms are
burning sensation of the mouth and decreased oral
intake.
Erosions are seen in up to 90% of cases.
Desquamation can follow soon thereafter.
 
FIXED DRUG ERUPTION
A fixed drug eruption (FDE) is an adverse cutaneous reaction to an
ingested drug, characterized by the formation of a solitary (but at times
multiple) erythematous patch or plaque.
Occur from 30 min to 8 h after ingestion of drug in previously sensitized
individual.
A sharply demarcated macule, round or oval in shape, occurring within
hours after ingestion of the offending drug.
Initially erythema, then dusky red to violaceous.
Commonly, lesions are solitary and can spread to become quite large, but
they may be multiple with random distribution.
Lesions may evolve to become a bulla and then an erosion.
Eroded lesions, especially on genitals or oral mucosa, are quite painful.
After healing, dark Brown with violet hue postinflammatory
hyperpigmentation.
References: Bolognia Essentials of Dermatology, 2014, page 563-570, 220-223, 230-240. Fitzpatrick’s Color Atlas
and Synopsis of Clinical Dermatology, 7th Edition, Mc Graw and Hill Education, 2013, introduction, Dermatology,
p:817-841.