What is the treatment protocol for pemphigus vulgaris?

Treatment Protocol for Pemphigus Vulgaris

Start with oral prednisolone 1 mg/kg/day (40-100 mg/day depending on severity) combined immediately with a steroid-sparing agent such as azathioprine 2-3 mg/kg/day or mycophenolate mofetil 2-3 g/day to minimize corticosteroid-related mortality. 1, 2

Initial Treatment Strategy

Corticosteroid Dosing

• Begin with prednisolone 0.5-1 mg/kg/day for mild disease or 1 mg/kg/day (60-100 mg/day) for moderate-to-severe disease 1, 2, 3
• If no response within 5-7 days, increase the dose in 50-100% increments until disease control is achieved (defined as no new lesions and healing of existing ones) 1, 2, 3
• For doses exceeding 100 mg/day or rapidly progressive disease, switch to pulsed intravenous methylprednisolone 250-1000 mg daily for 2-5 consecutive days 1, 2, 3
• In pregnant patients, prednisolone is preferred over betamethasone or dexamethasone because it is 90% inactivated by the placenta 1, 2

Mandatory Adjuvant Immunosuppression

Add a steroid-sparing agent immediately at treatment initiation—do not wait for corticosteroid response. 1, 2, 3

• Azathioprine 2-3 mg/kg/day (requires normal TPMT testing first) 1, 2, 3
• Mycophenolate mofetil 2-3 g/day in divided doses, or mycophenolic acid 720-1080 mg twice daily if gastrointestinal intolerance occurs 1, 2
• Expect a 6-8 week latent period before these agents demonstrate clinical effect; maintain adequate corticosteroid coverage during this time 1, 2, 3

The rationale for immediate adjuvant therapy is critical: up to 77% of deaths in pemphigus vulgaris are corticosteroid-related, and early introduction of steroid-sparing agents reduces cumulative corticosteroid exposure and associated mortality 1, 2, 4

Essential Supportive Measures

• Implement osteoporosis prophylaxis immediately upon starting corticosteroids 1, 2, 3
• Maintain high vigilance for infection and sepsis, which are major causes of mortality 1, 2

Tapering Protocol

Once remission is achieved:

• Reduce prednisolone by 5-10 mg weekly initially, tapering more slowly below 20 mg daily 1
• Alternative approach: reduce by one-third to one-quarter every 2 weeks down to 15 mg daily, then by 2.5 mg decrements down to 10 mg daily, and finally by 1 mg monthly 3
• Aim for ≤10 mg daily or complete discontinuation 1, 2, 3
• Continue adjuvant immunosuppression throughout the taper and beyond 1, 2, 3

Second-Line Therapy for Treatment Failure

Treatment failure is defined as:

• Continued disease activity despite 3 weeks of prednisolone 1.5 mg/kg/day, OR
• Failure to respond after 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, 2

Switch to an alternate steroid-sparing agent if the first-line adjuvant fails. 1, 2

Third-Line Therapy: Rituximab for Refractory Disease

Rituximab is the preferred third-line agent, demonstrating superior efficacy with 89% complete remission rates at 2 years when combined with short-term corticosteroids. 1

Rituximab Dosing Protocol

• Administer two 1,000 mg intravenous infusions separated by 2 weeks in combination with a tapering course of glucocorticoids 5
• Premedicate with methylprednisolone 100 mg intravenously (or equivalent) 30 minutes prior to each infusion 5
• Clinical response typically begins within 6 weeks 1
• Maintenance treatment: 500 mg intravenous infusion at Month 12 and every 6 months thereafter 5
• Treatment of relapse: 1,000 mg intravenous infusion on relapse; subsequent infusions may be administered no sooner than 16 weeks following the previous infusion 5

Important Rituximab Considerations

• Continue adjuvant immunosuppressants but reduce doses to decrease infection risk 1
• Relapse after rituximab occurs in up to 65% of patients, typically 13-17 months post-treatment; close monitoring is necessary 1
• Consider Pneumocystis jirovecii prophylaxis during and following rituximab treatment 5
• For rituximab-resistant cases, consider immunoadsorption combined with rituximab, which can reduce desmoglein antibodies by up to 95% 1

Alternative Third-Line Options

• Cyclophosphamide protocols (such as Dexamethasone-Cyclophosphamide Pulse Therapy) with reported 86% remission off therapy for ≥2 years and 2% mortality 1
  • Requires Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole 800/160 mg on alternate days or 400/80 mg daily 1
  • Monitor for toxicity including amenorrhea, azoospermia, and pituitary-adrenal suppression 1
• Intravenous immunoglobulin 1, 2
• Immunoadsorption 1, 2
• Methotrexate 1, 2
• Plasmapheresis (note: one RCT showed no benefit over steroids alone) 1

Critical Monitoring and Common Pitfalls

Avoid Premature Treatment Withdrawal

Do not withdraw treatment prematurely: 47% of successfully treated patients relapse when treatment is stopped after only 1 year. 1, 2, 3

Infection Surveillance

• Infection and sepsis are major causes of mortality 1, 2
• Patients requiring ≥5 g total prednisone to induce remission during the acute stage have a high mortality rate 4
• Most deaths occur during the first 2-3 months of therapy 4

Delayed Response from Adjuvants

• Immunofluorescence titers fall with treatment but lag behind clinical improvement 2
• Maintain adequate corticosteroid coverage during the 6-8 week latent period before steroid-sparing agents take effect 1, 2, 3

Disease Control Monitoring

• Disease control is defined as no new lesions and onset of healing in pre-existing ones 1, 2
• Clinical improvement is usually seen within days, but complete healing typically takes 3-8 weeks 2