What is the best management approach for bullous pemphigoid?

Management of Bullous Pemphigoid

For extensive bullous pemphigoid, initiate treatment with clobetasol propionate 0.05% cream 30-40 g daily applied to the entire body (sparing the face), which provides superior disease control and significantly lower mortality compared to oral corticosteroids. 1, 2

Disease Severity Classification and Initial Treatment Selection

Localized/Limited Disease

• Apply clobetasol propionate 0.05% cream 10-20 g daily directly to lesional skin only 2, 3
• This achieves complete healing in all patients within 4-17 days 3

Mild/Moderate Disease

• Apply clobetasol propionate 0.05% cream 20 g daily over the entire body except the face (reduce to 10 g daily if weight <45 kg) 2, 4
• A mild regimen (10-30 g/day) is non-inferior to standard dosing (40 g/day) for disease control, with 98% achieving control versus 100% with standard dosing 5, 6

Extensive/Severe Disease

• Apply clobetasol propionate 0.05% cream 30-40 g daily in two applications over the entire body including normal skin, blisters, and erosions, but sparing the face 1, 2
• If disease control is not achieved within 1-3 weeks, increase to the maximum dose of 40 g daily 1, 2
• This regimen achieves disease control in 73.5% of severe cases and complete remission in 41.2% 7

Disease control is defined as the time point when new lesions or pruritic symptoms cease to form and established lesions begin to heal. 1

Tapering Schedule (Critical for Minimizing Adverse Effects)

Begin dose reduction exactly 15 days after achieving disease control—earlier reduction has not been validated in controlled studies. 1, 2

Structured 4-Month Tapering Protocol

• Month 1: Daily application 1
• Month 2: Application every 2 days 1
• Month 3: Application twice weekly 1
• Month 4: Application once weekly 1

Maintenance Phase (After 4 Months)

• Reduce to 10 g clobetasol propionate once weekly, applied preferentially to previously affected areas 2, 4
• Continue maintenance for 8 additional months (total treatment duration of 12 months) 2, 4
• Aim to stop treatment completely 4-12 months after initiation 2

Second-Line Systemic Therapies

When Topical Therapy Fails or Is Impractical

Oral prednisone 0.5 mg/kg daily is effective for mild disease—doses below 0.5 mg/kg are ineffective, and doses above 0.75 mg/kg provide no additional benefit but significantly increase mortality. 2, 8

• Implement osteoporosis prevention measures immediately when starting systemic corticosteroids 2, 4
• Oral prednisone achieves 91.1% complete healing at 6 weeks but carries 9.7% one-year mortality 6

Alternative for Patients with Comorbidities or Steroid Contraindications

Doxycycline 200 mg daily (or tetracycline 500-2000 mg daily, or minocycline 100-200 mg daily), often combined with nicotinamide 500-2500 mg daily 2, 4

• Doxycycline achieves 73.8% complete healing at 6 weeks (less than prednisolone's 91.1%) but reduces one-year mortality to 2.4% compared to 9.7% with prednisolone (NNTB = 14) 6
• Doxycycline improves quality of life by 1.8 points on the Dermatology Life Quality Index compared to prednisolone 6
• Avoid tetracycline in renal impairment and doxycycline/minocycline in hepatic impairment 4
• Discontinue minocycline if hyperpigmentation, pneumonia, or eosinophilia develop 4

Adjunctive Immunosuppressants

Azathioprine added to prednisone allows reduction of steroid dose by approximately 45%, though evidence for improved disease control or mortality is limited 4, 8

• Mycophenolate mofetil 0.5-1 g twice daily is an alternative, though no superiority over azathioprine has been demonstrated 2, 8

Refractory Disease Management

Rituximab (anti-CD20 antibody) 375 mg/m² weekly for 4 weeks is the most studied biologic for refractory bullous pemphigoid, achieving satisfactory response in 78% and complete clearance in 55% of recalcitrant cases. 2

• Consider intravenous immunoglobulin (IVIg) for cases unresponsive to all standard therapies 2
• Exclude serum IgA deficiency before administering IVIg 1

Monitoring Protocol

Follow-Up Schedule

• Every 2 weeks for the first 3 months 2, 4
• Monthly for months 4-6 2, 4
• Every 2 months thereafter 2, 4

Laboratory Monitoring

Baseline and regular monitoring should include: 1, 2, 4

• Complete blood count, erythrocyte sedimentation rate, C-reactive protein
• Creatinine, blood electrolytes, fasting glucose
• Liver function tests (transaminases, γ-glutamyltransferase, alkaline phosphatase, bilirubin)
• Albumin
• Blood pressure

Disease Activity Monitoring

• Anti-BP180 IgG by ELISA at days 0,60, and 150—values >27 U/mL indicate increased relapse risk 2, 4
• Relapse is defined as ≥3 new lesions per month or extension of established lesions 4

Pre-Treatment Screening (When Immunosuppression Planned)

• Serology for hepatitis B, hepatitis C, and HIV 1
• Screen for underlying neoplasm and infection (particularly Mycobacterium tuberculosis) 1
• Test thiopurine methyltransferase if considering azathioprine 1
• Test glucose-6-phosphate dehydrogenase if considering dapsone 1

Critical Pitfalls to Avoid

Local Adverse Effects of Topical Steroids

Monitor for skin atrophy (14.9% incidence) and purpura (5.4% incidence) with prolonged high-dose topical corticosteroid use. 7

Systemic Adverse Effects

• Systemic effects from topical clobetasol are rare (3/74 patients in one series) but include deep vein thrombosis, hypertrichosis, and adrenocortical insufficiency 7
• Severe or life-threatening adverse events occur in 35% of patients on oral prednisolone versus 59% with doxycycline (doxycycline is safer) 6

Blister Management

• Leave small blisters intact 4
• Puncture and drain larger blisters, leaving the blister roof in place 4

Special Considerations

• Bullous pemphigoid is a self-limiting disease that usually remits within 5 years 4
• Extensive disease in polymorbid elderly patients usually requires hospitalization in a dermatology department for initial management 1
• Advanced age and comorbidities (neurological, cardiovascular, neoplastic, metabolic, respiratory) make management more challenging 1
• Consider discontinuing treatment after 12 months if symptom-free for at least 1-6 months on minimal therapy 4
• Positive direct immunofluorescence or BP180 ELISA >27 U/mL indicates increased risk of relapse 4