What is the initial treatment for Pemphigus?

Initial Treatment for Pemphigus Vulgaris

The initial treatment for pemphigus vulgaris should be oral prednisolone (1 mg/kg/day or equivalent) combined with an adjuvant immunosuppressant (azathioprine, mycophenolate mofetil, or rituximab). 1

First-Line Therapy

Corticosteroids

• Starting dose:

  • Prednisolone 1 mg/kg/day in most cases
  • Lower doses (0.5-1 mg/kg/day) may be appropriate for milder cases
  • Tailored dosing according to disease severity is appropriate

• Dose adjustment:

  • If no response within 5-7 days, increase dose in 50-100% increments until disease control is achieved
  • Consider pulsed intravenous corticosteroids if oral prednisolone >1 mg/kg/day is required
  • Disease control is defined as no new lesions and onset of healing in existing ones

• Important considerations:

  • Assess risk of osteoporosis immediately
  • Provide appropriate prophylaxis (calcium, vitamin D, bisphosphonates)
  • Taper dose once remission is induced and maintained
  • Aim to reduce to 10 mg daily or less

Adjuvant Immunosuppressants (to be combined with corticosteroids)

One of the following should be added from the start:

1. Azathioprine: 2-3 mg/kg/day (if TPMT normal)

   • Well-established choice with demonstrated corticosteroid-sparing effect
   • Takes at least 6 weeks before effects are seen
   • Treatment failure should only be determined after at least 3 months at appropriate dose

2. Mycophenolate mofetil: 2-3 g/day

   • Often used as first-line adjuvant
   • Given in divided doses (typically 1-1.5 g twice daily)
   • Alternative: mycophenolic acid (720-1080 mg twice daily) if GI side effects occur

3. Rituximab: Rheumatoid arthritis protocol (2 × 1 g infusions, 2 weeks apart)

   • Most recent evidence shows superior efficacy when combined with short-term prednisolone
   • In a landmark 2017 RCT, rituximab plus prednisolone achieved complete remission in 89% of patients vs. 28% with prednisolone alone at 2 years 1
   • FDA-approved dosing: two 1,000 mg intravenous infusions separated by 2 weeks in combination with tapering course of glucocorticoids 2

Treatment Monitoring and Adjustment

• Clinical improvement may be seen within days of starting corticosteroids
• Cessation of blistering typically takes 2-3 weeks
• Full healing may take 3-8 weeks
• Indirect immunofluorescence titers fall with treatment but lag behind clinical improvement

Second-Line Therapy

If treatment failure with first-line adjuvant drug:

• Switch to an alternate corticosteroid-sparing agent
• Consider mycophenolic acid (720-1080 mg twice daily) if GI symptoms from mycophenolate mofetil

Common Pitfalls and Caveats

1. Delayed recognition of treatment failure: Treatment failure is defined as continued disease activity or failure to heal despite 3 weeks of prednisolone (1.5 mg/kg/day) or equivalent.

2. Premature discontinuation of adjuvant therapy: Adjuvants have a delayed onset of action (6-8 weeks) but are critical for remission maintenance.

3. Overly aggressive corticosteroid tapering: Taper should be gradual after disease control is achieved to prevent relapse.

4. Inadequate monitoring for corticosteroid side effects: Immediate assessment and prophylaxis for osteoporosis is essential.

5. Failure to recognize that adjuvant drugs have different onset times: Rituximab may show faster response than azathioprine or mycophenolate mofetil.

6. Withdrawal of treatment too early: Relapse rates are high if treatment is stopped prematurely; complete remission off therapy may take years to achieve.

The management of pemphigus vulgaris requires careful balancing of disease control and medication side effects. While high-dose corticosteroids were historically used, the modern approach favors moderate corticosteroid doses combined with adjuvant immunosuppressants to minimize corticosteroid-related morbidity and mortality.