What are the guidelines for steroid treatment in pemphigus vulgaris?

Guidelines for Steroid Treatment in Pemphigus Vulgaris

Oral prednisolone at 1 mg/kg/day (or 0.5-1 mg/kg/day in milder cases) combined with an adjuvant immunosuppressant is the recommended first-line treatment for pemphigus vulgaris. 1

Initial Corticosteroid Dosing

• Standard dosing: Prednisolone 1-2 mg/kg/day is the common practice worldwide for moderate to severe disease 1
• Mild disease: More conservative dosing of 0.5-1 mg/kg/day may be appropriate 1
• Dose adjustment: If no response within 5-7 days, increase dose in 50-100% increments until disease control is achieved 1
• Treatment failure definition: Failure to achieve disease control despite 3 weeks of prednisolone 1.5 mg/kg/day 1

Pulsed Intravenous Corticosteroids

• Consider when:
  • Oral prednisolone doses above 1 mg/kg/day are required
  • Initial treatment for severe disease 1
• Dosing: Intravenous methylprednisolone 10-20 mg/kg or 250-1000 mg daily for 2-5 consecutive days 1
• Evidence: Benefits not conclusively demonstrated; one small retrospective study showed increased complete remission rates (44% vs 0%) and lower maintenance oral corticosteroid doses 1

Adjuvant Immunosuppressive Therapy

Adding an adjuvant immunosuppressant is crucial for:

1. Reducing cumulative corticosteroid dose
2. Maintaining remission
3. Minimizing steroid-related adverse effects

First-line Adjuvant Options:

1. Azathioprine:

   • Dosing: 2-3 mg/kg/day (if TPMT normal) 1, 2
   • Evidence: Well-established corticosteroid-sparing effect with complete remission rates of 28-45% 1
   • Latent period: At least 6 weeks before effects are seen 1

2. Mycophenolate mofetil:

   • Dosing: 2-3 g/day in divided doses 1, 2
   • Alternative: Mycophenolic acid 720-1080 mg twice daily if GI side effects occur 2

3. Rituximab (emerging first-line therapy):

   • Dosing: Two 1000 mg IV infusions separated by 2 weeks 3
   • Maintenance: 500 mg at month 12 and every 6 months thereafter 3
   • Evidence: Superior efficacy with complete remission rates of 89% vs 28% with prednisolone alone at 2 years 1, 2

Monitoring and Tapering

• Clinical improvement: Usually seen within days of starting corticosteroids
• Complete healing: Takes approximately 3-8 weeks 1
• Tapering: Begin once remission is induced with absence of new blisters and healing of most lesions
• Goal: Reduce to 10 mg daily or less 2

Long-term Management

• Treatment withdrawal: A realistic goal with complete remission rates of 38%, 50%, and 75% at 3,5, and 10 years from diagnosis, respectively 1
• Caution: Withdrawal should be gradual as relapse rates are high (47% when treatment stopped after 1 year) 1

Treatment of Relapse

• Rituximab: 1000 mg IV infusion on relapse 2, 3
• Corticosteroids: Consider resuming or increasing glucocorticoid dose 2
• Timing: Subsequent rituximab infusions should not be administered sooner than 16 weeks following the previous infusion 3

Prophylaxis and Supportive Care

• Osteoporosis prevention: Assess risk immediately upon starting steroids 1
• PCP prophylaxis: Recommended during treatment and for at least 6 months following the last rituximab infusion 3
• Herpes virus prophylaxis: Recommended during treatment 3

Common Pitfalls and Caveats

1. Avoid excessive corticosteroid doses: Historical high-dose regimens (prednisolone 120-400 mg/day) led to significant corticosteroid-related mortality (up to 77% of deaths) 1

2. Don't undertreat: Inadequate initial dosing may lead to poor disease control and prolonged disease activity

3. Don't use adjuvants as monotherapy for severe disease: Azathioprine monotherapy should be reserved only for mild cases due to its delayed onset of action 1

4. Recognize the value of adjuvant therapy: One RCT showed that prednisolone plus azathioprine resulted in lower cumulative corticosteroid doses at 1 year compared to prednisolone alone 1

5. Consider rituximab early: The first conclusive RCT demonstrating benefit of an adjuvant showed rituximab with short-term prednisolone was superior to prednisolone alone 1