What is the best management approach for bullous pemphigoid?

Management of Bullous Pemphigoid

Topical clobetasol propionate 0.05% cream applied twice daily should be the first-line treatment for bullous pemphigoid due to its effectiveness and significantly lower risk of mortality compared to systemic corticosteroids. 1, 2

Treatment Algorithm

First-Line Treatment

• Topical therapy:
  • Clobetasol propionate 0.05% cream applied to lesions only, twice daily 1
  • Continue until all lesions are healed and for 2 weeks thereafter 3
  • After healing, gradually taper to less potent topical corticosteroids for maintenance 3

Second-Line/Alternative Treatments

• Systemic corticosteroids (when topical therapy is impractical or ineffective):

  • Dosing based on disease severity 1:
    • Mild/localized disease: 0.5 mg/kg/day
    • Moderate disease: 0.3 mg/kg/day
    • Severe widespread disease: 0.75-1 mg/kg/day
  • Note: Higher doses (>0.75 mg/kg/day) have not shown additional benefit but increase adverse effects 4

• Steroid-sparing agents (for refractory cases or to reduce steroid burden):

  • Dapsone: 50-200 mg/day (typically 1.0-1.5 mg/kg/day) 1
  • Azathioprine: 1-2.5 mg/kg/day 1
  • Tetracycline (e.g., doxycycline 200-300mg daily) with nicotinamide 1, 4
  • Other options: mycophenolate mofetil (0.5-1g twice daily), methotrexate (5-15 mg weekly) 1

Treatment Duration and Tapering

1. Initial treatment phase:

   • Maintain treatment until disease control is achieved (typically 1-4 weeks) 1
   • Disease control defined as absence of new inflammatory or blistered lesions 1

2. Tapering regimen for systemic corticosteroids:

   • Reduce dose by one-third or one-quarter down to 15 mg daily at fortnightly intervals
   • Then by 2.5 mg decrements down to 10 mg daily
   • Finally by 1 mg each month
   • Aim for minimal therapy dose of 0.1 mg/kg/day within 4-6 months 1

3. Total treatment duration:

   • Typically ranges from 4-12 months 1
   • Treatment can be discontinued in patients symptom-free for at least 1-6 months on minimal therapy 1

Supportive Care

• Wound care:

  • Leave small to medium-sized blisters intact
  • Drain larger blisters
  • Apply non-adherent dressings to erosive lesions
  • Consider antisepsis baths 1

• Preventive measures:

  • Proton pump inhibitors for gastric protection
  • Calcium and vitamin D supplements
  • Consider bisphosphonates to prevent osteoporosis
  • Vaccinate against influenza and pneumococci (avoid live vaccines) 1
  • Avoid furosemide (associated with bullous pemphigoid) 1

Monitoring

• Laboratory monitoring:

  • Weekly blood counts initially, then monthly once stable
  • Monitor for hemolysis, methemoglobinemia, and agranulocytosis if using dapsone
  • Liver function tests every 3 months
  • Consider anti-BP180 IgG ELISA at days 0,60, and 150 to predict outcome 1

• Clinical monitoring:

  • Assess clinical response after 2-3 weeks of treatment
  • More vigilant monitoring in elderly patients due to increased risk of adverse effects 1

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

Important Considerations and Caveats

• Evidence strongly favors topical treatment: Recent research shows significantly lower mortality risk with topical clobetasol propionate compared to systemic corticosteroids (HR 1.43,95% CI 1.28-1.58) 2

• Balancing efficacy and safety: While systemic corticosteroids may have a lower risk of relapse (HR 0.85,95% CI 0.77-0.94), this benefit is outweighed by increased risks of death, major adverse cardiac events (HR 1.33), and infections (HR 1.33) 2

• Practical limitations: Extensive disease may present challenges for topical therapy due to application difficulties, especially in elderly patients with limited mobility 4

• Adjunctive therapies: Consider azathioprine early as it can reduce the required prednisone dose by almost half, potentially reducing steroid-related complications 4

• Common pitfall: Overtreatment with high-dose systemic steroids; most deaths in studies were associated with high-dose oral corticosteroids 4