What is the treatment for bullous pemphigoid?

Treatment of Bullous Pemphigoid

For all patients with bullous pemphigoid, superpotent topical corticosteroids (clobetasol propionate 0.05%) should be the first-line treatment, as this approach provides superior disease control with significantly lower mortality compared to systemic corticosteroids. 1, 2

Initial Treatment Selection Based on Disease Severity

Localized or Limited Disease

• Apply clobetasol propionate 10-20 g daily to lesional skin only (not the entire body surface), which achieves complete healing in all patients within 4-17 days 1, 3
• If disease control is not achieved within 1-3 weeks, increase the dose to 40 g daily 1
• Alternative option: oral prednisone 0.3 mg/kg daily (weaning dose once control achieved) combined with topical steroids applied to lesional skin 1

Mild Disease (fewer than 10 new blisters per day with disseminated distribution)

• Apply clobetasol propionate 20 g daily over the entire body except the face (10 g daily if weight <45 kg) 1, 2
• This whole-body application works both locally and systemically, causing immediate drop in eosinophil count 4
• If no disease control within 1-3 weeks, escalate to 40 g daily 1

Extensive or Moderate-to-Severe Disease

• First-line: Clobetasol propionate 30-40 g daily applied to the entire body surface (if patient or carer is capable of application) 1
• This approach achieved disease control in 73.5% of severe cases with significantly reduced mortality compared to oral steroids 4, 5
• Alternative if topical therapy is impractical: Oral prednisone 0.5-0.75 mg/kg daily (NOT 1.0 mg/kg, as higher doses provide no additional benefit but increase mortality) 1, 5

Critical caveat: Doses of prednisone >0.75 mg/kg daily are associated with higher mortality and should never be used 1, 5

Tapering and Maintenance Protocol

Initial Tapering (First 4 Months)

• Begin dose reduction 15 days after achieving disease control (defined as no new lesions and healing of established lesions) 1, 2
• Gradually taper topical steroids over 4 months 1

Maintenance Phase (Months 4-12)

• After 4 months, reduce to 10 g clobetasol propionate once weekly, applied preferentially to previously affected areas 1, 2
• Continue maintenance for 8 additional months (total treatment duration: 12 months) 1, 2
• Aim to stop treatment completely 4-12 months after initiation 1

Monitoring for Relapse

• Relapse is defined as ≥3 new lesions per month, extension of established lesions, or daily pruritus after achieving disease control 1, 2
• For localized relapse: restart clobetasol propionate 10 g daily 1
• For extensive relapse: restart 30 g daily 1

Second-Line and Adjunctive Therapies

When Topical Steroids Fail or Are Impractical

• Oral prednisone 0.5 mg/kg daily is effective for mild disease (validated evidence) 1
• Prednisone doses <0.5 mg/kg are ineffective and cannot be recommended 1
• Mandatory: Implement osteoporosis prevention measures at the outset of systemic corticosteroid treatment 1, 2

Anti-inflammatory Antibiotics (Safer Alternative for Patients with Comorbidities)

• Doxycycline 200 mg daily, tetracycline 500-2000 mg daily, or minocycline 100-200 mg daily, often combined with nicotinamide 500-2500 mg daily 1, 2
• Particularly useful for patients with diabetes or hypertension where systemic steroids pose higher risk 1
• Beneficial effect typically seen within 1-3 weeks 1
• Contraindications: Avoid tetracycline in renal impairment; avoid doxycycline/minocycline in hepatic impairment 1, 2
• Stop minocycline immediately if hyperpigmentation, pneumonia, or eosinophilia develops 1, 2

Steroid-Sparing Immunosuppressants

• Azathioprine 1-2.5 mg/kg daily can reduce cumulative prednisone dosage by 45% over 3 years 1
• Optimize dosing by measuring thiopurine methyltransferase (TPMT) activity before starting 1
• Methotrexate 5-15 mg weekly or dapsone 50-200 mg daily are alternative options 1
• These agents are used when disease is refractory to first-line treatments or relapses occur on unacceptably high steroid doses 1

Refractory Disease (Third-Line Options)

Biologic Therapies

• Rituximab (anti-CD20 antibody): 375 mg/m² weekly for 4 weeks is the most studied biologic for refractory BP 1, 6
• Achieved satisfactory response in 78% and complete clearance in 55% of recalcitrant cases 6
• Most effective when used after average of 2.11 prior treatment failures 6
• Serious adverse events: Two deaths reported (nosocomial pneumonia, bacterial sepsis) and persistent hypogammaglobulinemia in one pediatric case 1
• Consider only in exceptional circumstances when conventional immunosuppressants have failed 1

Other Refractory Options

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

Monitoring Schedule and Laboratory Tests

Follow-up Visits

• Every 2 weeks for the first 3 months, then monthly for the next 3 months, then every 2 months 2

Laboratory Monitoring

• Baseline and regular monitoring: complete blood count, liver function tests, glucose, renal function, blood pressure 1, 2
• Anti-BP180 IgG by ELISA at days 0,60, and 150 (values >27 U/mL indicate increased relapse risk) 2, 7

Common Pitfalls and Important Caveats

Local Side Effects of Topical Steroids

• Skin atrophy (14.9% of cases) and purpura (5.4%) are the most common local adverse effects 4
• Monitor for infections as potential complication 2

Systemic Effects Despite Topical Application

• Whole-body clobetasol application causes systemic absorption with immediate eosinophil count drop and decreased morning urine cortisol 4
• Rare systemic adverse effects include deep vein thrombosis, hypertrichosis, and adrenocortical insufficiency 4

Blister Management

• Leave small blisters intact; puncture and drain larger blisters while leaving the blister roof in place 2

Treatment Discontinuation

• Consider stopping treatment after 12 months if symptom-free for at least 1-6 months on minimal therapy 2
• Positive direct immunofluorescence or BP180 ELISA >27 U/mL indicates increased relapse risk 2
• Bullous pemphigoid typically remits within 5 years (self-limiting disease) 2