What is the role of dapsone in the treatment of bullous pemphigoid?

Role of Dapsone in Bullous Pemphigoid Treatment

Dapsone should be considered as a second-line or adjunctive treatment for bullous pemphigoid when first-line treatments are ineffective, contraindicated, or causing significant side effects. 1

Treatment Algorithm for Bullous Pemphigoid

First-Line Treatments

1. Topical corticosteroids

   • Clobetasol propionate 0.05% cream applied twice daily to lesions is recommended as first-line treatment due to fewer systemic side effects 2

2. Systemic corticosteroids

   • For mild-moderate disease: Prednisolone 0.5 mg/kg/day
   • For severe disease: Prednisolone 0.75-1.0 mg/kg/day
   • Higher doses (>1.0 mg/kg/day) provide no additional benefit but increase side effects 2

When to Consider Dapsone

Dapsone should be considered in the following scenarios:

• When first-line treatments fail to control disease
• When corticosteroid-related side effects are problematic
• As a steroid-sparing agent to reduce cumulative steroid dose
• In patients with contraindications to systemic corticosteroids 1

Dapsone Treatment Protocol

Dosing

• Starting dose: 50 mg/day
• Therapeutic range: 50-200 mg/day (typically 1.0-1.5 mg/kg/day) 1, 3
• Titrate gradually based on clinical response and tolerance

Pre-Treatment Evaluation

• Screen for glucose-6-phosphate dehydrogenase (G6PD) deficiency (mandatory)
• Baseline complete blood count, liver function tests, and renal function
• Particular caution in elderly patients due to higher risk of adverse effects 1

Efficacy

• Response rate: Approximately 45% in most studies 1
• Onset of action: Slower than systemic corticosteroids (2-3 weeks) 1
• May be used as:
  • Monotherapy (44% control rate reported in some studies) 4
  • Combined with topical corticosteroids 1
  • Combined with systemic corticosteroids as a steroid-sparing agent 3, 5

Monitoring

• Weekly blood counts initially, then monthly once stable
• Monitor for hemolysis, methemoglobinemia, and agranulocytosis
• Liver function tests every 3 months
• Assess clinical response after 2-3 weeks 1, 3

Evidence for Dapsone Use

Comparative Efficacy

• A randomized study comparing methylprednisolone with either dapsone or azathioprine found that dapsone appeared to have a moderately higher corticosteroid-sparing effect than azathioprine 5
• Dapsone combined with methylprednisolone and topical clobetasol propionate allowed reduction of methylprednisolone to <10 mg/day in 71% of patients after 3 months and 91% after 6 months 3

Safety Profile

• Most common adverse effect: Hemolysis (dose-dependent, expected in most patients) 6
• Serious adverse events (rare): Severe anemia, agranulocytosis 3
• Side effects are usually reversible upon dose reduction or discontinuation 6
• In elderly patients, close monitoring is essential due to increased risk of adverse effects 1

Clinical Pearls and Pitfalls

Pearls

• Dapsone may be particularly effective in neutrophil-rich variants of bullous pemphigoid 6
• Response to dapsone is often rapid (within 2 weeks) when effective 4
• Maximum doses typically do not need to exceed 100 mg/day 4

Pitfalls

• Failure to screen for G6PD deficiency before initiating therapy
• Inadequate monitoring of blood counts, especially in the initial weeks
• Overlooking drug interactions (e.g., with trimethoprim)
• Using dapsone as first-line therapy when more established options are appropriate
• Continuing dapsone despite lack of response after 4 weeks 1, 4

Conclusion from Evidence

The evidence suggests that dapsone is an underutilized but potentially effective agent in bullous pemphigoid treatment 6, 7. While not recommended as first-line therapy, it has demonstrated efficacy as both monotherapy and as a steroid-sparing agent. Its use should be considered particularly when trying to minimize corticosteroid exposure in elderly or fragile patients, though close monitoring for adverse effects is essential.