Vesiculobullous Lesions
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Direct answer
Fluid-filled lesions of the oral mucosa rarely survive intact to be seen — vesicles under 5 mm and bullae above rupture within hours on wet epithelium — so the clinician reconstructs the blister from its footprint, its distribution and its histology. The autoimmune pair anchors the topic: pemphigus vulgaris splits suprabasally through acantholysis, stains as intercellular fishnet immunofluorescence, begins in the mouth in over half of patients and threatens life; mucous membrane pemphigoid splits subepithelially, stains as a linear band along the basement membrane zone, presents as desquamative gingivitis and scars the eyes. Around them sit the viral vesicles — herpes simplex, varicella-zoster in a dermatome, coxsackieviruses — and the drug-reactive spectrum of erythema multiforme and Stevens-Johnson syndrome.
What you must remember
- Size first: a vesicle is under about 5 mm, a bulla larger; oral bullae rupture early, so chronic erosions with a history of blistering are the presenting reality.
- Pemphigus vulgaris: flaccid bullae and broad erosions, oral lesions frequently the first sign; histology shows suprabasal clefting with a residual row of basal cells (the "tombstone" row) and acantholysis; direct immunofluorescence shows IgG and C3 in an intercellular fishnet pattern; target antigen desmoglein 3 (with desmoglein 1 as skin disease advances).
- Mucous membrane pemphigoid: subepithelial split on histology, linear IgG-C3 at the basement membrane zone on immunofluorescence, desquamative gingivitis as the oral signature, tense skin bullae in some, and scarring — ocular synechiae demand ophthalmology referral from diagnosis.
- Nikolsky's sign — superficial epithelium shearing under lateral pressure — is classically positive in pemphigus; the Tzanck smear shows acantholytic cells but is not specific (herpes does the same).
- Viral cluster: primary herpes simplex gingivostomatitis (fever, widespread ulcers, both mucosal types); recurrent HSV on keratinised mucosa; herpes zoster strictly unilateral in a dermatome, not crossing the midline, with post-herpetic neuralgia and Ramsay Hunt syndrome as complications; coxsackieviruses causing hand-foot-mouth disease and herpangina of the posterior pharynx.
- Erythema multiforme: target or iris lesions, recurrent attacks, triggered characteristically by herpes simplex or drugs; Stevens-Johnson syndrome and toxic epidermal necrolysis are the severe drug-mediated end of the continuum — sulphonamides, anticonvulsants and allopurinol among the culprits.
- Diagnosis is two-biopsy work: perilesional mucosa for direct immunofluorescence plus routine histology; desmoglein serology supports monitoring.
- Therapy: pemphigus demands systemic corticosteroids with steroid-sparing agents (azathioprine, mycophenolate, rituximab); pemphigoid may run on topical and moderate systemic therapy with dapsone in selected patients — both are physician partnerships, not dental solo flights.
Diagnosing a woman with a sore mouth
A 45-year-old presents with four months of soreness: broad erosions on the buccal mucosa and palate, gingivae that peel and bleed (desquamative gingivitis), and a history of blisters that broke within a day. Skin examination reveals a few flaccid, fragile bullae on the trunk. Two candidates float — pemphigus vulgaris and mucous membrane pemphigoid — and the workup separates them. Two biopsies are taken from a fresh erosion's periphery: one in formalin for histology, one perilesional in Michel's medium for direct immunofluorescence. Histology reports a suprabasal cleft with acantholytic cells; immunofluorescence reports intercellular IgG-C3 in a fishnet pattern — pemphigus vulgaris confirmed. She is referred jointly to dermatology for systemic therapy (high-dose prednisolone with a steroid-sparing agent), with ocular assessment arranged and dental care kept gentle — hygiene, candidosis control, no abrasive manipulation. A subepithelial split with linear fluorescence would instead label it mucous membrane pemphigoid — and the first referral becomes ophthalmology, because conjunctival scarring blinds quietly.
Where students slip
The histology slide decides this topic and candidates lose it at the split line: suprabasal with tombstones is pemphigus; subepithelial with an intact epithelial roof is pemphigoid — reversing them reverses the prognosis and the urgency. The second slip is distribution reasoning: desquamative gingivitis invites three names — pemphigoid, lichen planus, pemphigus — and quoting the trio is expected before any single diagnosis. The third is the zoster rule "unilateral, dermatomal, crossing nothing" and its corollary that oral zoster blisters stop at the midline — a favourite image-based question. Finally, do not present the Tzanck test as diagnostic; it is a bedside aid, nonspecific, and modern practice rests on biopsy with immunofluorescence.
Frequently asked questions
How do pemphigus vulgaris and pemphigoid differ histologically?
Pemphigus splits suprabasally through acantholysis, leaving tombstone basal cells; pemphigoid splits below the whole epithelium at the basement membrane zone.
What immunofluorescence patterns distinguish the two?
Pemphigus: intercellular IgG-C3 fishnet; pemphigoid: linear IgG-C3 along the basement membrane zone.
Why do oral vesicles rarely present intact?
Mastication and moisture rupture the thin roof within hours, leaving erosions — the blister is inferred from history and shape.
What are the three classical causes of desquamative gingivitis?
Mucous membrane pemphigoid, erosive lichen planus and pemphigus vulgaris — roughly in that order.
How are erythema multiforme and Stevens-Johnson syndrome related?
One continuum of acute mucocutaneous reaction — target lesions typically herpes- or drug-triggered, with Stevens-Johnson its severe drug-driven extension.
Why does zoster stop at the midline?
Reactivation is confined to the unilateral sensory dermatome; blisters crossing the midline are not zoster.