A 40-year-old man presents with saddle nose deformity, sinusitis, haemoptysis, haematuria, and serum creatinine 2.8 mg/dL rising over 3 weeks. c-ANCA (PR3-ANCA) is strongly positive. What is the most appropriate induction therapy?

• A Cyclophosphamide + high-dose methylprednisolone
• B Rituximab + high-dose methylprednisolone ✓
• C Plasma exchange + steroids alone
• D Mycophenolate mofetil + steroids

Explanation

Granulomatosis with polyangiitis (GPA) with severe organ involvement (rising creatinine indicating rapidly progressive GN) requires induction immunosuppression. The RAVE trial demonstrated rituximab non-inferior to cyclophosphamide for induction in ANCA vasculitis, with rituximab now preferred per ACR/EULAR 2022 guidelines (particularly in younger patients or those wishing to preserve fertility). Both are combined with high-dose glucocorticoids. The PEXIVAS trial showed plasma exchange does not reduce the primary endpoint in severe ANCA vasculitis, so it is no longer routinely recommended.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.