Management of Bullous Pemphigoid
First-Line Treatment: Superpotent Topical Corticosteroids
Superpotent topical corticosteroids, specifically clobetasol propionate 0.05%, are the first-line treatment for bullous pemphigoid, providing superior disease control with significantly lower mortality compared to systemic corticosteroids, particularly in extensive disease. 1, 2, 3
Dosing Based on Disease Severity
For localized or limited disease:
- Apply clobetasol propionate 10-20 g daily directly to lesional skin only 1, 2
- Complete healing typically occurs within 4-17 days 1, 4
For mild disease with widespread distribution:
For extensive or moderate-to-severe disease:
- Apply clobetasol propionate 30-40 g daily to the entire body surface 1, 2
- If disease control is not achieved within 1-3 weeks, increase to 40 g daily 1, 2
- In extensive disease, topical corticosteroids achieved 99% disease control at 3 weeks with 76% one-year survival versus 58% with oral prednisone 3
Tapering and Maintenance Protocol
Once disease control is achieved (absence of new lesions or established lesions healing):
- Begin dose reduction 15 days after achieving disease control 1, 2
- Gradually taper topical steroids over 4 months 1
- After 4 months, reduce to maintenance therapy of 10 g clobetasol propionate once weekly, applied preferentially to previously affected areas 1, 2
- Continue maintenance for 8 additional months (total treatment duration of 12 months) 1, 2
Monitoring for Side Effects
Monitor for skin atrophy, purpura, and infections as potential side effects of topical steroids 2, 5. Local adverse effects occur in approximately 15% of patients (primarily skin atrophy) with rare systemic effects 5.
Second-Line Treatment: Systemic Corticosteroids
If topical corticosteroids fail or are impractical, oral prednisone is the second-line option, but doses must be carefully selected to balance efficacy and toxicity.
Systemic Corticosteroid Dosing
For mild or localized disease:
For moderate disease:
- Prednisolone 0.3 mg/kg daily 6
For severe or widespread disease:
- Prednisolone 0.75-1.0 mg/kg daily 6
- Doses of 0.75-1.0 mg/kg achieve disease control in 60-90% of cases within 1-4 weeks 6
Critical caveat: Higher doses of oral prednisone (>0.75 mg/kg/day) do not confer additional benefit and are associated with significant mortality 2, 7. Starting doses greater than 0.75 mg/kg/day should be avoided 6, 7.
Systemic Corticosteroid Tapering
Once new inflammatory or blistered lesions are few or absent within 4 weeks:
- Reduce daily dose by one-third or one-quarter at fortnightly intervals down to 15 mg daily 6
- Then reduce by 2.5 mg decrements down to 10 mg daily 6
- Then reduce by 1 mg each month 6
- Approximately 50% of patients will relapse during dose reduction, indicating the previous dose is the minimal effective dose 6
Essential Adjunctive Measures
Implement osteoporosis prevention measures at the outset of systemic corticosteroid treatment 1, 2. This is critical given the elderly population typically affected by bullous pemphigoid.
Steroid-Sparing Agents
Azathioprine as adjunctive therapy:
- Allows reduction of steroid dose by approximately 45% 2
- Does not improve disease control rates but reduces cumulative steroid exposure 6, 7
Tetracyclines with nicotinamide (alternative for patients with comorbidities):
- Doxycycline 200 mg daily, tetracycline 500-2000 mg daily, or minocycline 100-200 mg daily 1, 2
- Often combined with nicotinamide 500-2500 mg daily 1
- Avoid tetracycline in renal impairment and doxycycline/minocycline in hepatic impairment 2
- Discontinue minocycline if hyperpigmentation, pneumonia, or eosinophilia develop 2
Biologic Therapy: Dupilumab
Dupilumab is FDA-approved for bullous pemphigoid in adult patients. 8
Dosing regimen:
- Initial dose: 600 mg (two 300 mg injections) 8
- Maintenance: 300 mg every 2 weeks 8
- Use in combination with a tapering course of oral corticosteroids 8
- Once disease control occurs, gradually taper corticosteroids and continue dupilumab as monotherapy 8
- In case of relapse, corticosteroids may be added if medically advisable 8
This represents a significant advancement for patients who cannot tolerate or fail conventional therapies.
Refractory Disease Management
For patients unresponsive to topical and systemic corticosteroids:
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 1
Mycophenolate mofetil: 0.5-1 g twice daily for cases unresponsive to standard therapies 1
Intravenous immunoglobulin (IVIg): Consider for cases unresponsive to all standard therapies 1
Plasma exchange: Historical data showed mixed results, with one study demonstrating better disease control when combined with prednisone, but another study showing no significant difference and nearly significant increase in adverse events 6, 7.
Monitoring Schedule
Follow-up visits:
- Every 2 weeks for the first 3 months 1, 2
- Monthly for the next 3 months 1, 2
- Every 2 months thereafter 1, 2
Laboratory monitoring:
- Baseline and regular monitoring: complete blood count, liver function tests, glucose, renal function, blood pressure 1
- Anti-BP180 IgG by ELISA at days 0,60, and 150 1, 2
- Values >27 U/mL indicate increased relapse risk 1, 2
Relapse definition: ≥3 new lesions per month or extension of established lesions 2
Treatment Discontinuation
Consider discontinuing treatment after 12 months if the patient has been symptom-free for at least 1-6 months on minimal therapy 2. Bullous pemphigoid is a self-limiting disease that usually remits within 5 years 2.
Predictors of relapse: