Churg-Strauss syndrome

EGPA is an ANCA-associated vasculitis affecting small and medium-sized vessels, distinguished from other ANCA vasculitides by its strong association with asthma and marked peripheral eosinophilia (often >10%). The disease classically progresses through three phases: (1) a prodromal allergic phase with asthma, allergic rhinitis, and sinusitis; (2) an eosinophilic phase with peripheral eosinophilia and eosinophilic tissue infiltration (lungs, GI tract); and (3) a vasculitic phase with necrotizing vasculitis of small/medium vessels, extravascular granulomas, and eosinophilic infiltration causing systemic symptoms. Common vasculitic manifestations include mononeuritis multiplex (classic finding, due to vasa nervorum involvement), palpable purpura, migratory pulmonary infiltrates, cardiac involvement (myocarditis, pericarditis - major cause of death), and renal involvement (though less severe than in GPA or MPA, typically pauci-immune glomerulonephritis). Biopsy shows necrotizing vasculitis with eosinophilic infiltration and extravascular granulomas. p-ANCA/anti-MPO is positive in 40-60% of patients, more often in those with renal/vasculitic-predominant disease; ANCA-negative patients tend to have more cardiac and pulmonary involvement. Treatment involves systemic corticosteroids as first-line therapy, with cyclophosphamide added for severe/organ-threatening disease; mepolizumab (anti-IL-5) is now approved for refractory cases given the eosinophil-driven pathology. Important to distinguish from GPA (c-ANCA/PR3, no asthma, more upper respiratory/renal destruction) and MPA (p-ANCA, no asthma, no granulomas, more renal-predominant).