What is the best treatment approach for bulbous pemphigoid?

Treatment of Bullous Pemphigoid

The best treatment approach for bullous pemphigoid is clobetasol propionate 0.05% cream applied to lesions twice daily as first-line therapy, due to its superior efficacy and safety profile compared to oral corticosteroids. 1

First-Line Treatment Options

Topical Corticosteroids

• Clobetasol propionate 0.05% cream is recommended as the first-line treatment for all severities of bullous pemphigoid 1
• Application regimens:
  • For mild to moderate disease: Apply to lesions only, twice daily
  • For extensive disease: Whole body application (20-40g/day) may be effective, achieving disease control in 73.5-90% of patients 2
• Advantages: Fewer systemic side effects compared to oral corticosteroids, with improved survival rates in extensive disease 3
• A mild regimen using lower doses (10-30g/day) with shorter duration (4 months) has shown similar efficacy to standard regimens while reducing cumulative steroid exposure by 70% 4

Oral Corticosteroids

• Reserved for cases where topical therapy is impractical or ineffective
• Dosing based on disease severity:
  • Mild/localized disease: 0.5 mg/kg/day prednisolone
  • Moderate disease: 0.3 mg/kg/day prednisolone
  • Severe disease: 0.75-1.0 mg/kg/day prednisolone 1
• Higher doses (>0.75 mg/kg/day) do not provide additional benefit but increase adverse effects 3, 5

Disease Control and Monitoring

• Disease control should be achieved within 1-4 weeks, defined as absence of new inflammatory or blistered lesions 1
• Assessment for treatment response should be performed after 2-3 weeks of therapy
• BPDAI score threshold of 49 points can help predict disease control at day 21 1
• Anti-BP180 IgG ELISA at days 0,60, and 150 may help predict outcomes 1

Tapering Protocol

1. Begin tapering 15 days after disease control is achieved
2. Initial reduction: Reduce dose by one-third or one-quarter down to 15 mg daily at fortnightly intervals
3. Then reduce by 2.5 mg decrements down to 10 mg daily
4. Finally reduce by 1 mg each month
5. Aim for minimal therapy dose of 0.1 mg/kg/day (approximately 7 mg daily) within 4-6 months 1

Second-Line and Adjunctive Treatments

When first-line treatments are ineffective, contraindicated, or causing significant side effects:

1. Dapsone:

   • Starting dose: 50 mg/day
   • Therapeutic range: 50-200 mg/day (typically 1.0-1.5 mg/kg/day) 1
   • Requires weekly blood counts initially, then monthly once stable

2. Steroid-sparing agents:

   • Azathioprine (1-2.5 mg/kg/day): Can reduce prednisolone requirements by almost half 3
   • Tetracycline (e.g., doxycycline 200-300mg daily) with nicotinamide: May be as effective as prednisolone 3
   • Mycophenolate mofetil (0.5-1g twice daily)
   • Methotrexate (5-15 mg weekly)
   • Chlorambucil (0.05-0.1 mg/kg/day) 1

3. Plasma exchange: May achieve better disease control when combined with prednisone, though evidence is mixed 3

Managing Relapse

• If relapse occurs during tapering: Return to the previous effective dose
• If relapse occurs after treatment discontinuation: Restart at appropriate dose based on severity
• Relapse definition: New blisters, eczematous lesions, or urticarial plaques that don't heal within 1 week 1

Wound Care and Prevention

• Leave small to medium-sized blisters intact; drain larger blisters
• Apply non-adherent dressings to erosive lesions
• Consider antisepsis baths
• For leg lesions: Elevate legs, use compression stockings (if no open lesions), gentle exercise, avoid prolonged standing/sitting 1

Preventing Complications

• Implement osteoporosis prevention from the start of therapy:
  • Vitamin D and calcium supplements
  • Consider bisphosphonates for treatment >3 months
• Use proton pump inhibitors for gastric protection
• Vaccinate against influenza and pneumococci (avoid live vaccines)
• Avoid furosemide due to its association with bullous pemphigoid 1

Treatment Discontinuation

Treatment can be discontinued in patients who are symptom-free for at least 1-6 months on minimal therapy, though ongoing monitoring is necessary to detect potential relapse 1

Common Pitfalls and Caveats

• Overtreatment with systemic steroids: Higher doses of oral prednisolone (>0.75 mg/kg/day) do not provide additional benefit but increase mortality risk 3, 5
• Underutilization of topical therapy: Many practitioners default to oral steroids despite evidence that topical clobetasol propionate is equally effective and safer, even in extensive disease 3, 6
• Inadequate monitoring: Weekly blood counts are essential initially when using dapsone or other immunosuppressants, then monthly once stable 1
• Neglecting adjunctive care: Osteoporosis prevention and gastric protection are essential components of management 1
• Abrupt discontinuation: Treatment should be tapered gradually over months to prevent relapse 1