Bullous Pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, with IgG and IgE autoantibodies against hemidesmosomal proteins BP180 (collagen XVII, NC16A domain) and BP230.

• Incidence is 10 to 40 per million per year and rising, with a median onset age of 75 to 80 years. One year mortality is 20 to 40% from comorbidity and treatment.
• Associations: neurological disease (dementia, stroke, Parkinson disease, multiple sclerosis), psoriasis.
• Drug triggers: DPP-4 inhibitors (gliptins), furosemide, spironolactone, antibiotics, PD-1 and PD-L1 inhibitors, and NSAIDs.

• Intensely itchy tense blisters on erythematous or urticated plaques, flexures, limbs and trunk. Prodromal non-bullous phase of itch, eczema or urticaria lasting weeks to months.
• Mucosal involvement in 10 to 20%. Nikolsky negative. Blisters heal without scarring.
• Variants: non-bullous, dyshidrosiform, localised pretibial.

• Skin biopsy at the edge of a blister: subepidermal blister with eosinophils.
• DIF perilesional: linear IgG and C3 along the basement membrane zone; salt split skin shows deposition on the epidermal roof (blister roof).
• Serum anti-BP180 NC16A ELISA (sensitivity about 85 to 90%; titres track disease activity), anti-BP230.
• Eosinophilia and raised IgE are supportive.
• Exclude epidermolysis bullosa acquisita, mucous membrane pemphigoid, pemphigus, dermatitis herpetiformis, bullous drug eruption, and scabies.

• Topical clobetasol propionate 0.05% (cream or ointment): 10 to 30 g/day to the whole body in moderate to extensive disease, tapering over 4 to 12 months. First line for extensive disease, with superior survival compared with oral steroids in elderly patients.
• Oral prednisolone: 0.3 to 0.5 mg/kg/day when topical therapy is impractical or ineffective; avoid high doses (1 mg/kg adds mortality).
• Steroid sparing agents:
  • Doxycycline 200 mg daily (effective, with safer profile in the elderly).
  • Methotrexate 5 to 15 mg weekly with folic acid.
  • Azathioprine 1 to 2.5 mg/kg or mycophenolate 1 g twice daily.
  • Dapsone 25 to 100 mg daily.
• Biologics: dupilumab 600 mg then 300 mg every 2 weeks (approved), rituximab 1000 mg on days 1 and 15, omalizumab, IVIG for refractory disease.
• Stop triggering drugs, treat wounds, prevent infection, and supplement calcium and vitamin D.
• Relapse is common on withdrawal; monitor anti-BP180.