What is the recommended treatment protocol for pemphigus vulgaris?

Treatment Protocol for Pemphigus Vulgaris

The recommended first-line treatment for pemphigus vulgaris consists of oral corticosteroids (prednisolone 1 mg/kg/day) combined with an adjuvant immunosuppressant, with rituximab now considered the preferred adjuvant agent due to superior efficacy and steroid-sparing effects. 1

First-Line Therapy

Corticosteroids

• Start with oral prednisolone at 1 mg/kg/day in most cases; use 0.5-1 mg/kg/day for milder disease 1
• If no response within 5-7 days, increase dose in 50-100% increments until disease control is achieved 1
• For severe disease or if doses above 1 mg/kg/day are required, consider pulsed intravenous corticosteroids (methylprednisolone 250-1000 mg or equivalent) 1
• Once remission is achieved (no new lesions and healing of existing ones), taper dose gradually with the aim to reduce to 10 mg daily or less 1
• Assess risk of osteoporosis immediately and implement preventive measures 1

Adjuvant Therapy (to be combined with corticosteroids)

• Rituximab: Preferred first-line adjuvant due to superior efficacy 1, 2

  • Administer as two 1,000 mg intravenous infusions separated by 2 weeks 2
  • For maintenance, administer 500 mg at month 12 and every 6 months thereafter 2
  • For relapse, administer 1,000 mg and consider resuming or increasing glucocorticoid dose 2

• Alternative adjuvants if rituximab is contraindicated:

  • Azathioprine: 2-3 mg/kg/day (if TPMT normal) 1
  • Mycophenolate mofetil: 2-3 g/day in divided doses 1

Second-Line Therapy

• Consider switching to an alternate corticosteroid-sparing agent if treatment failure with first-line adjuvant drug 1
• For patients with gastrointestinal symptoms from mycophenolate mofetil, switch to mycophenolic acid 720-1080 mg twice daily 1
• Treatment failure is defined as continued disease activity or failure to heal despite:
  • 3 weeks of prednisolone 1.5 mg/kg/day, or
  • 12 weeks of azathioprine (2.5 mg/kg/day), mycophenolate mofetil (1.5 g twice daily), cyclophosphamide (2 mg/kg/day), or methotrexate (20 mg/week) 1

Third-Line Therapy

For refractory cases, consider the following options based on individual patient needs and multidisciplinary team consensus 1:

• Cyclophosphamide (oral or intravenous pulse therapy) 1
• Immunoadsorption 1
• Intravenous immunoglobulin 1
• Methotrexate 1
• Plasmapheresis or plasma exchange 1

Important Clinical Considerations

Monitoring and Disease Control

• Disease control is defined as no new lesions and the onset of healing in pre-existing ones 1
• Monitor for clinical improvement (usually seen within days) and complete healing (typically 3-8 weeks) 1
• Immunofluorescence titers fall with treatment but lag behind clinical improvement 1

Steroid-Sparing Benefits of Rituximab

• Recent evidence strongly supports rituximab as a first-line agent with corticosteroids 3
• Patients treated with rituximab plus short-term prednisone showed 90% complete remission at 24 months versus 28% with prednisone alone 3
• Median cumulative prednisone dose was significantly lower with rituximab (5,800 mg vs. 20,520 mg) 3
• Fewer severe corticosteroid-related adverse events occur with rituximab (34% vs. 67%) 3

Common Pitfalls and Caveats

• Avoid premature treatment withdrawal; relapse rates are high initially with 47% of successfully treated patients relapsing when treatment is stopped after 1 year 1
• Be aware of the latent period (6-8 weeks) before effects of azathioprine and mycophenolate mofetil are seen 1
• Corticosteroid side effects are common and dose-related, with one study estimating that up to 77% of deaths were corticosteroid-related 1, 4
• For pregnant patients, prednisolone is preferred as it is 90% inactivated by the placenta, unlike betamethasone and dexamethasone 1
• Infection and sepsis are significant risks and major causes of mortality; maintain vigilance for signs of infection 1

Special Situations

• For mild cases with oral lesions only, consider lower dose prednisolone (0.5 mg/kg/day) combined with adjuvant therapy 1, 5
• For patients with contraindications to systemic corticosteroids, rituximab combined with high-potency topical corticosteroids has shown effectiveness 6
• For pregnant patients, close cooperation between dermatologist, obstetrician, and neonatologist is required 1

The treatment approach should be tailored according to disease severity, with early initiation of rituximab now recommended to improve efficacy and reduce cumulative doses of corticosteroids and their side effects 7, 3.