Bullous pemphigoid is the most common autoimmune subepidermal blistering disorder of older adults, characterized by tense bullae on erythematous or urticarial bases and severe pruritus. Autoantibodies target hemidesmosomal antigens BP180 (type XVII collagen, NC16A domain) and BP230 at the dermal–epidermal junction. Diagnosis combines clinical features with histopathology and immunopathology. High-potency topical or systemic corticosteroids with steroid-sparing agents are standard; newer evidence supports doxycycline as a safer initial option in some. Biologic therapies (omalizumab, dupilumab) show promise, especially in refractory pruritic disease.
Epidemiology
- Incidence increases with age (peak >70 years); slight male predominance in some series.
- Associations: neurologic disease (Parkinson, dementia, stroke), possibly due to shared antigens; medications (DPP-4 inhibitors like vildagliptin, loop diuretics), and immune checkpoint inhibitors.
Pathophysiology
- IgG (and IgE) autoantibodies to BP180/BP230 trigger complement activation, eosinophil recruitment, and subepidermal blistering.
- IgE-mediated pruritus component may explain omalizumab responsiveness.
Clinical Features
- Prodrome: weeks to months of severe pruritus with urticarial/eczematous plaques.
- Bullous phase: tense bullae on normal or erythematous skin; negative Nikolsky sign; mucosal involvement in ~10–20% (usually mild).
- Distribution: trunk, flexural areas; elderly patients often frail with secondary infection risk.
Differential Diagnosis
- Other subepidermal AIBDs: mucous membrane pemphigoid (predominant mucosal scarring), epidermolysis bullosa acquisita (trauma-prone sites, anti–type VII collagen), bullous drug eruptions, arthropod reactions, bullous scabies.
Diagnostic Workup
- Biopsy: lesional skin for H&E shows subepidermal blister with eosinophils.
- DIF on perilesional skin: linear IgG and C3 along basement membrane zone.
- Serology: ELISA for BP180 NC16A and BP230; salt-split skin IIF helps differentiate antigen side (epidermal side in BP).
- Baseline labs to guide therapy; review medications (notably DPP-4 inhibitors).
Management
- Core treatments
- High-potency topical corticosteroids (e.g., clobetasol 0.05% whole-body regimens) effective even in extensive BP; reduce systemic steroid adverse effects in elderly.
- Systemic corticosteroids when topical not feasible or severe disease: prednisone ~0.5 mg/kg/day then taper.
- Tetracycline-class plus nicotinamide (e.g., doxycycline 100 mg bid + nicotinamide 500 mg tid) as steroid-sparing; RCTs support doxycycline 200 mg/day as noninferior for short-term control with fewer adverse events compared with prednisolone.
- Immunosuppressants for steroid-sparing: methotrexate (low-dose weekly), azathioprine, mycophenolate mofetil.
- Biologic/targeted therapies (refractory or contraindications to standard therapy)
- Omalizumab (anti-IgE): reduces pruritus and blisters; useful with high IgE or eosinophilia.
- Dupilumab (IL-4Rα blocker): increasing evidence for efficacy and safety in BP, including steroid-sparing outcomes.
- Rituximab in refractory cases.
- Emerging: IL-5 blockade for eosinophilic BP, complement inhibitors in trials.
- Adjunctive care
- Pruritus control: antihistamines, gabapentinoids for neuropathic component.
- Wound care: nonadherent dressings, infection prevention; treat secondary impetiginization.
- Review and discontinue potential culprit drugs (e.g., DPP-4 inhibitors).
- Special situations
- ICI-induced BP: coordinate with oncology; may require holding ICI and initiating steroids/dupilumab/rituximab.
- Frail elderly: prefer topical regimens and doxycycline-based strategies to minimize systemic steroid harms.
Prognosis and Monitoring
- Mortality elevated in first year due to age/comorbidities and treatment side effects; control often achieved within months, but relapses occur.
- Monitor for steroid complications, infection, and treatment toxicity; track BP180 ELISA for disease activity adjunctively.
References (recent guidelines and key reviews)
- European/International S3 guidelines on BP, 2022–2024.
- RCTs comparing doxycycline vs prednisolone; cohort data on omalizumab and dupilumab, 2021–2024.
- Reviews on ICI-induced BP and neurologic associations, 2022–2024.