What is the primary treatment for a patient with bullous pemphigoid?

Bullous Pemphigoid Treatment

Primary Treatment Recommendation

For extensive bullous pemphigoid, initiate 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 systemic corticosteroids. 1, 2

Treatment Algorithm by Disease Extent

Localized/Limited Disease

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

Mild Disease (More Widespread Distribution)

• Apply clobetasol propionate 0.05% cream 20 g daily over the entire body except the face 2, 3
• Reduce to 10 g daily if patient weight is <45 kg 1

Extensive/Moderate-to-Severe Disease

• Apply clobetasol propionate 0.05% cream 30-40 g daily to the entire body surface in two applications, including both normal skin and blisters/erosions, but sparing the face 1, 2
• Use 20 g daily if weight <45 kg 1
• If disease control is not achieved within 1-3 weeks, increase to the maximum dose of 40 g daily 1, 2

The evidence strongly supports topical corticosteroids over systemic therapy: a 2024 retrospective cohort study of 5,849 patients demonstrated that systemic corticosteroids increased all-time mortality risk (HR 1.43), MACE risk (HR 1.33), and infection risk (HR 1.33) compared to topical clobetasol propionate 4. This mortality benefit persists even with low-dose systemic steroids (1-10 mg prednisone equivalent) 4.

Tapering Schedule

Begin dose reduction exactly 15 days after achieving disease control (defined as cessation of new lesions/pruritic symptoms and healing of established lesions) 1, 2, 3:

• Month 1: Daily treatment 1
• Month 2: Treatment every 2 days 1
• Month 3: Treatment twice weekly 1
• Month 4 onward: Treatment once weekly 1

Maintenance Phase (After 4 Months)

• Reduce to 10 g clobetasol propionate once weekly, applied preferentially to previously affected areas 2, 3
• Continue maintenance for 8 additional months (total treatment duration 12 months) 2, 3
• Aim to stop treatment completely 4-12 months after initiation 2

Second-Line Systemic Options

When Topical Therapy Fails or Is Impractical

Oral prednisone 0.5 mg/kg daily is the systemic option for mild disease 2, 3:

• Doses <0.5 mg/kg are ineffective 2
• Critical caveat: Doses >0.75 mg/kg provide no additional benefit and significantly increase mortality 3
• Implement osteoporosis prevention measures immediately when starting systemic corticosteroids 2, 3

Alternative for Patients with Comorbidities

Tetracyclines combined with nicotinamide 2, 3:

• Doxycycline 200 mg daily 2
• Tetracycline 500-2000 mg daily 2, 3
• Minocycline 100-200 mg daily 2
• Combined with nicotinamide 500-2500 mg daily 2

Important contraindications:

• Avoid tetracycline in renal impairment 3
• Avoid doxycycline/minocycline in hepatic impairment 3
• Discontinue minocycline if hyperpigmentation, pneumonia, or eosinophilia develop 3

Adjunctive Immunosuppression

Azathioprine allows reduction of steroid dose by approximately 45% when added to systemic corticosteroids 3, though one randomized trial showed no significant difference in disease control or recurrence rates 5.

Refractory Disease Management

Third-Line Biologics

Rituximab (anti-CD20 antibody) 375 mg/m² weekly for 4 weeks is the most studied biologic for refractory cases 2:

• Achieves satisfactory response in 78% of patients 2
• Complete clearance in 55% of recalcitrant cases 2

Other Options for Treatment-Resistant Disease

• Mycophenolate mofetil 0.5-1 g twice daily 2
• Intravenous immunoglobulin (IVIg) for cases unresponsive to all standard therapies 2

Monitoring Protocol

Follow-Up Schedule

• Every 2 weeks for the first 3 months 2, 3
• Monthly for the next 3 months 2, 3
• Every 2 months thereafter 2, 3

Laboratory Monitoring

• Baseline and regular monitoring: complete blood count, liver function tests, glucose, renal function, blood pressure 2
• Anti-BP180 IgG by ELISA at days 0,60, and 150 2, 3
• Values >27 U/mL indicate increased relapse risk 2, 3

Common Pitfalls and Adverse Effects

Topical Corticosteroid Side Effects

• Monitor for skin atrophy (occurs in 14.9% of patients) 3, 6
• Monitor for purpura (occurs in 5.4% of patients) 3, 6
• Systemic adverse effects are rare but include deep vein thrombosis, hypertrichosis, and adrenocortical insufficiency 6

Relapse Definition and Management

• Relapse is defined as ≥3 new lesions per month or extension of established lesions 3
• Despite higher relapse risk with topical therapy (HR 0.85 for continued disease with systemic vs. topical), the mortality benefit of topical treatment outweighs this concern 4

Blister Management

• Leave small blisters intact 3
• Puncture and drain larger blisters while leaving the blister roof in place 3

Treatment Discontinuation

Consider discontinuing treatment after 12 months if the patient has been symptom-free for at least 1-6 months on minimal therapy 3. Bullous pemphigoid is self-limiting and usually remits within 5 years 3.