Mucous membrane pemphigoid (MMP), also called cicatricial pemphigoid, is a chronic autoimmune subepidermal blistering disorder primarily affecting mucous membranes with a tendency toward scarring. Common sites include oral, ocular, nasal, pharyngeal/laryngeal, esophageal, and anogenital mucosa; skin involvement occurs in a subset. Autoantibodies target components of the basement membrane zone (e.g., BP180 C-terminal, BP230, laminin-332, type VII collagen, integrin α6β4). Early recognition and risk stratification (particularly for ocular, laryngeal, and esophageal disease) are critical to prevent irreversible fibrosis and vision loss. Treatment ranges from topical therapies for low-risk oral disease to systemic immunosuppression and biologics for high-risk scarring sites.
Epidemiology
- Onset typically 60–80 years; female predominance.
- Rare disease; underdiagnosed due to oral-only presentations.
Pathophysiology
- Autoantibodies to hemidesmosomal and basement membrane proteins lead to complement activation, inflammatory cell recruitment, and subepithelial blistering with subsequent fibrosis.
- Laminin-332 autoantibodies associated with increased malignancy risk in some studies.
Clinical Features
- Oral mucosa: desquamative gingivitis, erosions, blisters; painful eating.
- Ocular: chronic conjunctivitis, symblepharon, entropion, trichiasis, corneal scarring; risk of blindness.
- Laryngeal/pharyngeal: hoarseness, dysphagia; airway stenosis risk.
- Nasal: epistaxis, crusting; esophageal: dysphagia/strictures; anogenital erosions.
- Skin: tense blisters/erosions that may scar.
Differential Diagnosis
- Bullous pemphigoid (usually non-scarring mucosal disease), erosive lichen planus (reticular striae), pemphigus vulgaris (flaccid intraepithelial blisters), epidermolysis bullosa acquisita, linear IgA disease, drug-induced pemphigoid.
Diagnostic Workup
- Biopsy: lesional for H&E shows subepidermal split with mixed infiltrate; perilesional for DIF shows linear IgG/C3 at basement membrane.
- Indirect IF on salt-split skin to determine binding side; ELISAs for BP180 (including C-terminal), BP230, laminin-332, type VII collagen; immunoblotting for laminin-332 where available.
- Ophthalmology/ENT evaluation at baseline in any ocular/airway symptoms.
- Consider malignancy screening if laminin-332 positive and per regional protocols.
Risk Stratification
- Low-risk: isolated oral mucosa without scarring.
- High-risk: ocular, laryngeal, esophageal, widespread mucosal, or rapidly progressive disease.
Management
- Local therapy (low-risk, localized)
- High-potency topical steroids (clobetasol gel in custom dental trays).
- Topical calcineurin inhibitors for maintenance; meticulous oral hygiene; antifungal prophylaxis if prolonged steroids.
- Systemic therapy (high-risk or refractory)
- First-line systemic corticosteroids often combined with steroid-sparing agents.
- Steroid-sparing: dapsone (after G6PD testing) effective for mucosal disease; methotrexate, mycophenolate mofetil, azathioprine, cyclophosphamide (particularly for severe ocular disease).
- Biologics/advanced therapies: rituximab effective for refractory or ocular MMP; IVIG for severe disease; dupilumab emerging data in mucosal pemphigoid with prominent inflammation.
- Ocular: early ophthalmology interventions, lubricants, topical corticosteroids/calcineurin inhibitors; manage symblepharon; surgical corrections after disease control.
- Monitoring
- Regular multidisciplinary follow-up (dermatology, ophthalmology, ENT).
- Monitor therapy labs per agent; infection prophylaxis as appropriate.
Prognosis
- Chronic relapsing course; scarring complications can be vision- or life-threatening.
- Early aggressive control in high-risk sites improves outcomes.
References (recent guidelines and reviews)
- International consensus guidelines for MMP diagnosis and management, 2022–2024.
- Ophthalmology–dermatology joint statements on ocular MMP, 2022–2024.
- Studies of rituximab and IVIG in refractory MMP, 2021–2024.
- Laminin-332 autoantibody and malignancy association reviews, 2021–2024.