What are the S2K (Strength of Recommendation Taxonomy) guidelines for managing Pemphigus?

S2K Guidelines for Management of Pemphigus

The current S2K guidelines recommend a combination of systemic corticosteroids with rituximab as first-line therapy for moderate-to-severe pemphigus vulgaris, as this approach has demonstrated superior efficacy and a significant steroid-sparing effect compared to corticosteroids alone. 1, 2

First-Line Treatment Options

Corticosteroids

• Initial prednisolone dosing should be 0.5-1 mg/kg/day for mild disease and 1 mg/kg/day for moderate-to-severe 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) 3
• 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
• Implement osteoporosis prevention measures immediately, including calcium and vitamin D supplementation and bisphosphonates 3

Rituximab

• For moderate-to-severe pemphigus, administer rituximab as two 1,000 mg intravenous infusions separated by 2 weeks in combination with a tapering course of glucocorticoids 4
• For maintenance, administer rituximab as a 500 mg intravenous infusion at Month 12 and every 6 months thereafter 4
• For treatment of relapse, administer rituximab as a 1,000 mg intravenous infusion, with subsequent infusions no sooner than 16 weeks following the previous infusion 4
• The 2 g rheumatoid arthritis dosing protocol is preferred due to cost considerations, with similar efficacy to the lymphoma protocol 3

Adjuvant Immunosuppressive Agents

First-line adjuvants

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

Second-line adjuvants

• 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 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), or cyclophosphamide (2 mg/kg/day) 1

Third-line options

• Cyclophosphamide: can be administered orally (1-2 mg/kg/day) or as intravenous pulse therapy 3
• Dexamethasone-cyclophosphamide pulse therapy: three daily doses of dexamethasone (100 mg) with a single dose of cyclophosphamide (500 mg) given monthly 3
• Immunoadsorption for refractory cases 3
• Intravenous immunoglobulin (IVIG) 3
• Plasma exchange (not recommended as routine; may be considered for difficult cases if combined with steroids and immunosuppressants) 3

Monitoring and Disease Assessment

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

Important Clinical Considerations

Treatment Duration

• Avoid premature treatment withdrawal as relapse rates are high (47% of successfully treated patients relapse 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

Potential Complications

• Corticosteroid side effects are common and dose-related, with one study estimating that up to 77% of deaths were corticosteroid-related 3
• Infection and sepsis are significant risks and major causes of mortality; maintain vigilance for signs of infection 1
• When using rituximab, provide prophylaxis for Pneumocystis jirovecii pneumonia (PCP) during and following treatment 4

Comparative Efficacy

• A randomized controlled trial demonstrated that rituximab plus short-term prednisone was more effective than prednisone alone, with 90% of patients achieving complete remission off corticosteroids at 24 months versus only 28% with prednisone alone 2
• The median cumulative prednisone dose was significantly lower with rituximab plus prednisone (5800 mg) compared to prednisone alone (20,520 mg) 2
• Fewer patients experienced grade 3 or 4 corticosteroid-related adverse events with rituximab plus prednisone (34%) compared to prednisone alone (67%) 2

Topical Therapy

• For localized and mild forms of pemphigoid, superpotent topical corticosteroids can be effective 5
• In bullous pemphigoid, topical clobetasol propionate 0.05% cream (20g) applied all over twice daily has shown significant benefit compared to oral prednisone for disease control, adverse events, and mortality 3