10.2 Vesiculobullous & Ulcerative Disorders
Key Takeaways
- Pemphigus vulgaris is mediated by autoantibodies to desmoglein 3, produces flaccid intra-epithelial blisters and erosions with a positive Nikolsky sign, and can be fatal — it needs urgent systemic immunosuppression
- Mucous membrane pemphigoid is a subepithelial split (anti-BP180/desmoglein 1), affects older patients, heals with scarring and is generally less severe than pemphigus
- Erythema multiforme presents with target skin lesions and oral erosions; major form (Stevens-Johnson syndrome) is usually triggered by HSV or drugs
- Desquamative gingivitis is a clinical pattern, not a diagnosis — it most commonly reflects pemphigoid, pemphigus, or lichen planus and needs biopsy with immunofluorescence
- Primary herpetic gingivostomatitis (HSV-1) in children causes fever, painful gingivitis, and vesicles; management is supportive with hydration and, if severe, oral aciclovir
Pemphigus Vulgaris (PV)
Pemphigus vulgaris is a potentially fatal autoimmune blistering disease. Autoantibodies target desmoglein 3 (a desmosomal cadherin in mucosal epithelium), causing loss of keratinocyte adhesion (acantholysis) and a suprabasal intra-epithelial split.
Clinical features
- Painful flaccid blisters that rupture quickly, leaving irregular erosions on the buccal mucosa, palate, and gingiva
- Nikolsky sign positive — gentle lateral pressure shears off the superficial epithelium
- Skin involvement common; may precede oral lesions by months
- Untreated, can be fatal from fluid loss and sepsis
Diagnosis
- Incisional biopsy of perilesional tissue for H&E (shows suprabasal split and acantholytic Tzanck cells)
- Direct immunofluorescence — intercellular fishnet IgG/C3 deposition between keratinocytes
- Serum anti-desmoglein 3 ELISA for monitoring
Management
Urgent referral to dermatology/oral medicine. Systemic corticosteroids (high-dose prednisolone) are first-line; steroid-sparing agents such as azathioprine, mycophenolate, or rituximab reduce cumulative steroid burden. Oral hygiene and topical anaesthetics help with painful erosions.
Mucous Membrane Pemphigoid (MMP)
Mucous membrane pemphigoid (previously cicatricial pemphigoid) is a subepithelial autoimmune blistering disease of older patients (typically >60). Autoantibodies target BP180 and desmoglein 1, producing a sub-epithelial split — the epithelium shears off in one sheet.
| Feature | Pemphigus vulgaris | Mucous membrane pemphigoid |
|---|---|---|
| Split level | Intra-epithelial (suprabasal) | Sub-epithelial |
| Target antigen | Desmoglein 3 | BP180, desmoglein 1 |
| Blister | Flaccid, fragile | Tense, more intact |
| Nikolsky | Positive | Often negative |
| Healing | No scarring | Scarring (ocular risk) |
| Severity | Potentially fatal | Generally less severe |
MMP most often affects oral mucosa and the conjunctiva. Ocular scarring (symblepharon) threatens vision, making urgent ophthalmology referral essential. Diagnosis is biopsy with direct immunofluorescence showing linear IgG/C3 along the basement membrane zone. Treatment is topical and systemic steroids, with dapsone or cyclophosphamide in resistant disease.
Erythema Multiforme (EM) & Stevens-Johnson Syndrome
Erythema multiforme is an acute mucocutaneous reaction pattern. Oral lesions are widespread erosions with crusted bloody lips; skin lesions are classic target lesions (concentric rings of erythema).
- EM minor — skin target lesions, little/no mucosa
- EM major — skin and mucosa involved; recurrent cases often triggered by HSV
- Stevens-Johnson syndrome (SJS) — severe drug reaction (sulphonamides, anticonvulsants, NSAIDs) with >10% epidermal detachment; high mortality
Oral EM frequently follows a HSV prodrome and recurs with viral reactivation, so suppressive aciclovir may prevent recurrences. SJS is a medical emergency needing inpatient care.
Desquamative Gingivitis
Desquamative gingivitis is a clinical sign — diffuse erythema and sloughing of the attached gingiva, made worse by brushing — not a diagnosis. The three underlying causes to differentiate are:
- Mucous membrane pemphigoid — most common cause
- Pemphigus vulgaris
- Erosive oral lichen planus
Biopsy with direct immunofluorescence is essential to separate them, as treatment and prognosis differ. Misdiagnosis as simple plaque-induced gingivitis is a classic exam trap.
Primary Herpetic Gingivostomatitis
Primary HSV-1 infection in young children (age 1-5) presents with:
- Fever, malaise, cervical lymphadenopathy
- Painful, diffuse gingivitis (erythematous, swollen, bleeding gingivae)
- Vesicles on oral mucosa that rupture to form shallow ulcers
- Usually self-limiting in 10-14 days
Management is supportive: hydration, soft diet, analgesia, and oral hygiene. Oral aciclovir is recommended in severe presentations or immunocompromised children. Aspirin is contraindicated in children (Reye syndrome).
Oral Inflammatory Bowel Disease
- Crohn disease — oral manifestations include lip swelling, cobblestone buccal mucosa, mucosal tags, linear ulcers, and aphthous ulcers; may precede gut disease
- Orofacial granulomatosis — non-caseating granulomas in oral tissues without gut involvement; can progress to Crohn; associated with dietary antigens (cinnamon, benzoates)
- Pyostomatitis vegetans — rare but specific marker of inflammatory bowel disease: snail-track pustules and vegetating plaques
Biopsy and referral to gastroenterology confirm the diagnosis.
Diagnostic Workflow for Oral Blistering
A structured approach to a patient with oral blistering or desquamation prevents a missed immunobullous diagnosis:
- Biopsy perilesional tissue for routine H and E to define the split level (intra-epithelial versus sub-epithelial).
- Biopsy adjacent normal-appearing mucosa for direct immunofluorescence - sampling intact mucosa is preferred because the blister itself disrupts immune deposits and can give a false negative.
- Serum indirect immunofluorescence or ELISA (anti-desmoglein 3 and 1, anti-BP180 and BP230) to confirm and monitor disease activity.
- Refer urgently - pemphigus vulgaris can be life-threatening and ocular MMP threatens vision; both need specialist-led systemic immunosuppression.
Other Immunobullous and Related Entities
| Disease | Split and target | Note |
|---|---|---|
| Linear IgA disease | Sub-epithelial, linear IgA | Children and adults; responds to dapsone; rare |
| Epidermolysis bullosa acquisita | Sub-epithelial, type VII collagen | Fragile skin; oral involvement; treatment-resistant |
| Paraneoplastic pemphigus | Intra-epithelial, multiple antigens | Associated with lymphoma or leukaemia; severe; investigate for occult malignancy |
| Chronic ulcerative stomatitis | Resembles erosive OLP | Anti-nuclear antibodies to delta-Np63alpha; often refractory; hydroxychloroquine helps |
A vesiculobullous presentation resistant to topical steroids, or with skin or ocular involvement, mandates biopsy with immunofluorescence before empirical treatment, because misdiagnosed pemphigus can progress to life-threatening disease.
A 45-year-old woman presents with painful oral erosions and a positive Nikolsky sign. Direct immunofluorescence shows intercellular fishnet IgG deposition between keratinocytes. Which antigen is the autoantibody directed against?
A 68-year-old man has tense oral blisters and conjunctival involvement. Biopsy shows a sub-epithelial split with linear IgG along the basement membrane zone. What is the most serious long-term risk requiring urgent referral?
A 16-year-old presents with diffuse erythema and sloughing of the attached gingiva that bleeds on brushing. A colleague diagnoses plaque-induced gingivitis, but scaling has not helped over three months. What is the most appropriate next step?
A 3-year-old has fever, swollen bleeding gingivae, and multiple shallow oral ulcers following a viral prodrome. What is the most likely diagnosis and first-line management?