What is the treatment for Pemphigus vulgaris?

Treatment of Pemphigus Vulgaris

First-line treatment for pemphigus vulgaris should combine systemic corticosteroids with an adjuvant immunosuppressant, with rituximab emerging as the most effective adjuvant therapy based on recent evidence. 1

First-Line Therapy

Corticosteroids

• Initial dosing: Prednisolone 1 mg/kg/day (0.5-1 mg/kg/day in milder cases) 1
• If no response within 5-7 days, increase dose in 50-100% increments until disease control is achieved 1
• Consider pulsed intravenous corticosteroids if oral prednisolone >1 mg/kg/day is required, or as initial treatment in severe disease 1
• Taper dose once remission is induced (no new blisters and healing of most lesions)
• Aim to reduce to ≤10 mg daily 1
• Assess risk of osteoporosis immediately and implement preventive measures 1

Adjuvant Immunosuppressants (to be combined with corticosteroids)

1. Rituximab (2 × 1 g infusions, 2 weeks apart - rheumatoid arthritis protocol) 1, 2

   • FDA-approved for moderate to severe pemphigus vulgaris 2
   • Most effective adjuvant with 89% complete remission rate at 2 years compared to 28% with prednisolone alone 1
   • Monitor for infusion reactions, which occur in up to 58% of patients but are typically mild to moderate 2

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

   • Well-established adjuvant with corticosteroid-sparing effect 1
   • Allow at least 3 months at therapeutic dose before determining treatment failure 1

3. Mycophenolate mofetil (2-3 g/day) 1

   • Alternative first-line adjuvant
   • If gastrointestinal side effects occur, consider switching to mycophenolic acid 720-1080 mg twice daily 1, 3

Treatment Algorithm

1. Assess disease severity:

   • Mild: Limited oral/cutaneous involvement
   • Moderate to severe: Extensive oral/cutaneous involvement

2. Initiate therapy:

   • Start prednisolone 1 mg/kg/day (0.5-1 mg/kg in mild cases)
   • Simultaneously start adjuvant therapy (preferably rituximab if available)
   • For severe disease resistant to oral therapy, consider pulsed IV corticosteroids

3. Monitor response:

   • Clinical improvement typically begins within days
   • Cessation of blistering takes 2-3 weeks
   • Complete healing may take 3-8 weeks 1

4. Taper corticosteroids:

   • Begin tapering once 80% of lesions have healed and no new lesions for at least 2 weeks
   • Initial reduction by 5-10 mg weekly until 20 mg/day, then more slowly 1
   • Aim for maintenance dose ≤10 mg/day 1

5. Maintenance phase:

   • Continue adjuvant therapy for remission maintenance
   • Treatment withdrawal should be cautious as relapse rates are high initially (47% when stopped after 1 year) 1
   • Complete remission off therapy increases over time (38% at 3 years, 50% at 5 years, 75% at 10 years) 1

Second-Line Therapy

If treatment failure with first-line adjuvant therapy:

• Switch to an alternate corticosteroid-sparing agent 1
• For mycophenolate mofetil intolerance, switch to mycophenolic acid 720-1080 mg twice daily 1, 3

Third-Line Therapy

Consider these options based on individual patient assessment:

• Cyclophosphamide 1
• Immunoadsorption 1
• Intravenous immunoglobulin 1
• Methotrexate (use with caution as some studies suggest it should be avoided) 1, 4
• Plasmapheresis or plasma exchange 1

Special Considerations

Pregnancy

• Prednisolone is the first-line systemic agent in pregnancy 1
• Prednisolone is 90% inactivated by placenta (preferred over betamethasone/dexamethasone) 1
• Avoid mycophenolate mofetil, methotrexate, and cyclophosphamide due to teratogenicity 1
• Azathioprine may be used if necessary (low teratogenic risk) 1
• IVIg is safe in pregnancy 1
• Rituximab manufacturers advise against pregnancy for 1 year following therapy 1

Wound Care

• Infection and sepsis are significant risks and major causes of mortality 1
• Daily washing with antibacterial products to decrease colonization
• Monitor closely for signs of infection and treat promptly with appropriate antibiotics
• Provide adequate pain control, especially during dressing changes 1

Common Pitfalls to Avoid

1. Premature tapering of corticosteroids before disease control is established and consolidated 1
2. Failure to add adjuvant therapy early in the disease course
3. Inadequate monitoring for corticosteroid side effects, particularly osteoporosis
4. Delayed recognition of treatment failure (defined as continued disease activity despite 3 weeks of prednisolone 1.5 mg/kg/day) 1
5. Underestimating infection risk in patients with extensive erosions
6. Abrupt discontinuation of therapy, which can lead to high relapse rates

The treatment of pemphigus vulgaris has evolved significantly, with combination therapy showing superior outcomes to corticosteroid monotherapy. While corticosteroids remain the cornerstone of initial treatment, early introduction of adjuvant therapy, particularly rituximab, has dramatically improved remission rates and reduced corticosteroid-related morbidity.