What is the treatment for bullous pemphigus?

Treatment of Bullous Pemphigoid

First-Line Treatment Selection

For extensive bullous pemphigoid (>10% body surface area or >10 new blisters daily), topical clobetasol propionate 0.05% cream at 30-40 g per day is the preferred first-line treatment, as it achieves superior disease control with significantly lower mortality compared to systemic corticosteroids. 1

Topical Corticosteroid Regimen (Extensive Disease)

• Apply clobetasol propionate 0.05% cream 30-40 g daily (20 g daily if weight <45 kg) in two applications over the entire body, including normal skin, blisters, and erosions, but sparing the face 1
• Continue daily application until disease control is achieved (defined as cessation of new lesions and pruritic symptoms, with established lesions beginning to heal) 1
• Begin tapering 15 days after disease control using this validated schedule: daily treatment for month 1, every 2 days in month 2, twice weekly in month 3, once weekly starting month 4 1
• If disease control is not achieved within 1-3 weeks on doses <40 g daily, increase to 40 g daily 1

This approach is supported by Level 1 evidence showing complete healing in all patients within 17 days and highlights the mortality risk associated with high-dose oral corticosteroids. 1

Localized or Mild-to-Moderate Disease

• Topical clobetasol propionate 0.05% remains first-line for localized disease 1
• Alternative first-line option: tetracyclines (500-2000 mg daily) or doxycycline (200-300 mg daily) combined with nicotinamide, with or without topical corticosteroids 1
• Erythromycin (1000-3000 mg daily) is preferred in children and can be combined with topical corticosteroids 1
• Beneficial effects typically seen within 1-3 weeks of starting antibiotic therapy 1

Important contraindications: avoid tetracycline in renal impairment; avoid doxycycline and minocycline in hepatic impairment; discontinue minocycline immediately if hyperpigmentation or pneumonia with eosinophilia develops. 1

Systemic Corticosteroids (When Topical Therapy Insufficient)

Critical dosing principle: prednisolone doses should NOT exceed 0.75 mg/kg/day (approximately 52.5 mg daily for a 70-kg patient), as higher doses provide no additional benefit but significantly increase mortality risk in elderly patients. 1

• Starting dose: 0.5-0.75 mg/kg/day prednisolone or prednisone 1, 2
• Continue until cessation of new blister formation, then gradually taper according to clinical response 1
• Lower starting doses of 20-40 mg daily have been recommended more recently for less severe presentations 1
• Implement osteoporosis prevention measures at treatment initiation in all patients 1

The mortality rate with systemic corticosteroids ranges from 6-41%, compared to 24% in the pre-corticosteroid era, emphasizing the need for careful patient selection and monitoring. 1

Adjuvant Immunosuppressive Therapy

Azathioprine

• Dose: up to 2.5 mg/kg daily as adjunct to systemic corticosteroids for steroid-sparing effect 1
• Evidence is conflicting: one RCT showed 45% reduction in cumulative prednisolone over 3 years, while another larger RCT found no difference in remission rates at 6 months 1
• Optimize dosing by measuring thiopurine methyltransferase (TPMT) activity prior to initiation to minimize myelosuppression risk 1
• Consider only as second-line due to side-effect profile 1

Mycophenolate Mofetil

• Equally effective as azathioprine when combined with oral corticosteroids 3
• Less myelosuppressive and hepatotoxic than azathioprine, with better safety profile 3
• May gradually replace azathioprine as first-line adjuvant for moderate-to-severe disease 3

Rituximab

• Emerging as effective option, particularly when administered early in disease course 4
• Should be considered to reduce cumulative corticosteroid doses and their side effects 4
• Associated with relatively high mortality rate (29%) in patients >80 years, requiring meticulous patient selection 5

Monitoring Protocol

Follow-up every 2 weeks during the first 3 months (initial phase) to assess treatment response, adjust therapy, and monitor for steroid side effects. 2

• Use serial photography to track disease progression 2
• After 3 months (maintenance phase), reduce to monthly follow-up visits 2
• Gradually reduce and taper steroids whenever disease has been well controlled for ≥1 month 2
• Monitor complete blood count, erythrocyte sedimentation rate, C-reactive protein, creatinine, electrolytes, fasting glucose, liver function tests, and albumin regularly 1

Critical Pitfalls to Avoid

• Never use prednisolone doses >0.75 mg/kg/day - no additional benefit and significantly increased mortality in elderly patients 1, 2
• Recognize that BP predominantly affects patients >70 years who are at highest risk for medication-related toxicity 1, 6
• Do not delay treatment initiation for diagnostic confirmation - all investigations (histology, immunofluorescence) can be performed after treatment has started, though prolonged treatment reduces positive IF results 1
• Topical corticosteroid application requires high-functioning patient or third-party assistance for extensive disease 5
• The disease is self-limiting and usually remits within 5 years, so treatment goals focus on tolerability rather than complete suppression 1

Treatment Algorithm Summary

1. Extensive disease (>10% BSA): Topical clobetasol propionate 30-40 g daily as first-line 1
2. Localized/mild disease: Topical clobetasol propionate OR tetracyclines + nicotinamide 1
3. Inadequate response to topical therapy: Add systemic corticosteroids (0.5-0.75 mg/kg/day prednisolone, NEVER >0.75 mg/kg/day) 1, 2
4. Steroid-sparing needed: Consider mycophenolate mofetil over azathioprine due to better safety profile 3
5. Refractory disease: Consider rituximab with careful patient selection, especially in elderly 4, 5