Initial Treatment for Bullous Pemphigoid
For extensive/generalized bullous pemphigoid, start with superpotent topical corticosteroids (clobetasol propionate 0.05% cream) 30-40 g daily applied over the entire body except the face, as this provides superior disease control with significantly lower mortality compared to systemic corticosteroids. 1, 2
Treatment Selection Based on Disease Extent
Localized or Mild Disease
- Apply clobetasol propionate 0.05% cream 10-20 g daily directly to lesional skin only 1
- For mild disease with disseminated lesions, apply 20 g daily over the entire body except the face (reduce to 10 g daily if weight <45 kg) 1
- Alternative first-line option: tetracycline (500-2000 mg daily) or doxycycline (200-300 mg daily) combined with nicotinamide, particularly when topical steroids are impractical 1, 2
Extensive/Generalized Disease
- Apply clobetasol propionate 0.05% cream 30-40 g daily in two applications over the entire body including normal skin, blisters, and erosions, sparing the face (20 g daily if weight <45 kg) 1
- This topical approach is superior to oral prednisone 1 mg/kg/day, showing better survival rates and fewer severe complications in extensive disease 1, 2
- If disease control is not achieved within 1-3 weeks, increase to 40 g daily 1
When to Use Systemic Corticosteroids
Systemic corticosteroids should be reserved for patients who fail topical therapy or when topical application is impractical 1:
- For extensive disease: Start prednisone 0.5-0.75 mg/kg/day, NOT 1 mg/kg/day 1
- For mild disease: Prednisone 0.5 mg/kg/day 1
- Doses below 0.5 mg/kg/day are ineffective and not recommended 1
- Doses above 0.75 mg/kg/day provide no additional benefit and are associated with significantly higher mortality 1, 3
The evidence strongly contradicts older practices: a landmark study showed that prednisone 1 mg/kg/day caused higher mortality and more severe complications compared to topical clobetasol in extensive disease 1. Another trial found no significant difference between 0.75 mg/kg/day and 1.25 mg/kg/day, but the higher dose caused more adverse effects 1, 4.
Tapering Schedule
For Topical Corticosteroids
Begin tapering 15 days after achieving disease control (defined as cessation of new lesions and healing of established lesions) 1, 2:
- Month 1: Daily application
- Month 2: Every 2 days
- Month 3: Twice weekly
- Month 4 onward: Once weekly 1
- Continue maintenance for 8 months (total 12 months treatment duration) 2
For Systemic Corticosteroids
Start tapering 15 days after disease control 1:
- Reduce by one-third to one-quarter every 2 weeks down to 15 mg daily
- Then reduce by 2.5 mg decrements down to 10 mg daily
- Then reduce by 1 mg monthly 1
Adjunctive Therapy
Add azathioprine 1.7-2.4 mg/kg/day if systemic steroids cannot be tapered to acceptable maintenance levels, as this reduces cumulative prednisone dose by approximately 45% over 3 years 1, 2. However, one large trial showed no difference in remission rates at 6 months, and azathioprine was associated with more severe complications 1.
Critical Pitfalls to Avoid
- Do not start with high-dose oral prednisone (1 mg/kg/day) in extensive disease—this is associated with significantly higher mortality compared to topical therapy 1
- Implement osteoporosis prevention measures immediately when starting systemic corticosteroids 1
- Avoid tetracycline in renal impairment; avoid doxycycline and minocycline in hepatic impairment 1, 2
- Do not increase steroid doses for occasional blisters during maintenance—this represents overtreatment 1
- Relapse occurs in approximately 50% of patients during dose reduction; this indicates the previous dose was the minimal effective dose for that patient 1