Management of CAPS Overlapping with ANCA‑Associated Vasculitis

Glucocorticoid Regimen (initial high‑dose therapy)

Administer intravenous methylprednisolone 500–1000 mg daily for three consecutive days, then continue with oral prednisolone 1 mg/kg/day (maximum 60–80 mg/day) in patients with suspected CAPS ± vasculitis. [International CAPS Consensus] 1

Initiate plasma exchange when the patient has a serum creatinine > 3.4 mg/dL (≈300 µmol/L), requires dialysis, or shows a rapidly rising creatinine, indicating severe renal involvement. [American College of Rheumatology (ACR) guideline] 2

Add cyclophosphamide (2 mg/kg/day oral, maximum 200 mg/day, or pulsed intravenous 0.6 g/m²) to the glucocorticoid regimen for life‑threatening vasculitic disease. [ACR guideline] 2
Add rituximab (375 mg/m² intravenously weekly for four weeks) as an alternative to cyclophosphamide, especially in relapsing disease or when fertility preservation is a concern. [ACR guideline] 3
Level 1A evidence supports rituximab as the preferred agent for granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in relapsing cases or when fertility is a priority. [ACR guideline] 3

In patients with rapidly progressive renal failure (creatinine > 3.4 mg/dL) or those requiring dialysis, plasma exchange should be strongly considered as part of the initial management. [ACR guideline] 2

The presence of granulomatous inflammation, necrotizing vasculitis on biopsy, or a positive ANCA test indicates primary ANCA‑associated vasculitis and warrants immunosuppression beyond the CAPS triple‑therapy regimen. [ACR guideline] 2

Provide Pneumocystis jirovecii prophylaxis with trimethoprim‑sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) to all patients receiving cyclophosphamide or high‑dose steroids. [ACR guideline] 2
Administer MESNA concomitantly with cyclophosphamide to prevent hemorrhagic cystitis. [ACR guideline] 2
Ensure aggressive hydration (oral fluids or intravenous fluids on cyclophosphamide infusion days) to reduce nephrotoxicity. [ACR guideline] 2

Do not use serial ANCA titers to guide changes in therapy; instead, rely on structured clinical assessment of organ involvement and disease activity. [International CAPS Consensus] 1

Do not withhold therapeutic‑dose heparin for procedures such as renal biopsy solely because of bleeding risk; the diagnostic yield is unlikely to change management when CAPS is strongly suspected. [ACR guideline] 2

When refractory CAPS persists despite triple therapy (including rituximab), eculizumab may be employed; it requires immediate meningococcal vaccination and concurrent antibiotic prophylaxis before initiation. [International CAPS Consensus] 5

If no clinical response is observed after four weeks of cyclophosphamide, switch to rituximab (or vice‑versa) to achieve disease control. [International CAPS Consensus] 1