What is the treatment for pemphigus foliaceus?

Treatment of Pemphigus Foliaceus

Rituximab combined with short-term corticosteroids is the most effective first-line treatment for pemphigus foliaceus, achieving high complete remission rates of 89% at 2 years compared to 34% with corticosteroids alone. 1, 2

First-Line Treatment Options

Preferred First-Line Approach

1. Rituximab + Short-term Prednisone
   • Rituximab dosing: 1000 mg IV on days 0 and 15, followed by 500 mg at months 12 and 18 1, 2
   • Prednisone: 0.5 mg/kg/day for moderate disease or 1 mg/kg/day for severe disease, tapered over 3-6 months 3, 1
   • This combination has shown superior efficacy with 90% of pemphigus foliaceus patients achieving complete remission off corticosteroids for ≥2 months at 24 months 2

Alternative First-Line Approach (if rituximab unavailable)

1. Systemic Corticosteroids

   • Prednisone 0.5-1 mg/kg/day, tapered gradually based on clinical response 3, 1
   • Before corticosteroids were introduced, pemphigus mortality was approximately 75% 3

2. Corticosteroids + Adjuvant Immunosuppressant

   • Add one of the following to reduce steroid requirements:
     • Azathioprine (1-3 mg/kg/day) 3, 1
     • Mycophenolate mofetil (1 g twice daily) 1, 4
     • These adjuvants have steroid-sparing effects, with azathioprine showing a mean reduction of 3919 mg in cumulative prednisolone dose 5

Treatment for Mild Disease

For localized or mild pemphigus foliaceus:

• Topical corticosteroids: Clobetasol propionate 0.05% cream applied twice daily 1, 6
• In mild cases, topical therapy alone may achieve control in approximately 57% of patients, with healing of cutaneous lesions within 15 days 6
• Consider systemic therapy if inadequate response after 2 weeks or if disease extends beyond limited areas 6

Treatment for Refractory Disease

For patients who fail first-line therapy:

1. Intravenous Immunoglobulin (IVIg)

   • Dosing: 2 g/kg every 4 weeks 1
   • Can be combined with low-dose rituximab (0.5 g) for refractory cases 7

2. Cyclophosphamide

   • Consider if other options have failed
   • Has demonstrated steroid-sparing effects (mean reduction of 3355 mg in cumulative prednisolone dose) 5
   • Caution: potential risk of secondary infertility 3

3. Plasma Exchange/Plasmapheresis

   • Reserved for difficult cases unresponsive to other therapies
   • Should be combined with steroids and immunosuppressants 3

Monitoring and Follow-up

1. Clinical Assessment

   • Weekly to biweekly during induction phase
   • Monthly during maintenance phase
   • Assess for new blister formation and healing of existing lesions 1

2. Laboratory Monitoring

   • Complete blood count
   • Liver and kidney function tests
   • Blood glucose and lipid profile 1

3. Medication Adjustments

   • Adjust doses according to clinical response and organ function
   • Occasional blisters are acceptable during maintenance and indicate the patient is not being overtreated 3

Prophylaxis Considerations

1. Infection Prophylaxis

   • Pneumocystis jirovecii pneumonia prophylaxis during treatment and for at least 6 months following 1
   • Herpes virus prophylaxis during treatment 1

2. Bone Health

   • Calcium and vitamin D supplementation
   • Consider bisphosphonates if systemic corticosteroid duration exceeds 3 months 1

Special Populations

Pregnancy

• Prednisolone is the first-line systemic agent during pregnancy 1
• Avoid mycophenolate mofetil, methotrexate, and cyclophosphamide due to teratogenicity 1
• Azathioprine may be used if necessary (low teratogenic risk) 3, 1
• IVIg is safe in pregnancy 3

Children

• The course of pemphigus in children is generally more favorable than in adults 3
• Treatment approach is similar to adults after initial systemic corticosteroids 3

Common Pitfalls and Caveats

1. Steroid-Related Complications

   • Current morbidity of pemphigus is largely iatrogenic, caused by side effects of long-term, high-dose corticosteroid therapy 4
   • Use steroid-sparing agents early to minimize complications

2. Infection Risk

   • Serious infections are a major concern, especially with rituximab
   • In clinical trials, 8% of patients treated with rituximab experienced serious infections 2
   • Monitor closely for signs of infection, particularly respiratory infections

3. Hypogammaglobulinemia

   • Can occur with rituximab treatment (72% of patients in pediatric studies had prolonged low IgG levels) 2
   • Monitor immunoglobulin levels periodically

4. Relapse Management

   • For relapse after rituximab, administer rituximab 1000 mg IV and consider resuming or increasing glucocorticoid dose 1
   • Approximately 25% of patients may experience relapse and require additional treatment 2

The ultimate aim of management should be treatment withdrawal, with complete remission rates of 38%, 50%, and 75% achieved at 3,5, and 10 years from diagnosis, respectively 3.