EGPA (Eosinophilic Granulomatosis with Polyangiitis) Classification

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a rare necrotizing vasculitis of small and medium vessels characterized by asthma, blood and tissue eosinophilia, and granulomatous inflammation. It classically evolves through three phases: a prodromal allergic phase (asthma and rhinitis, lasting years), an eosinophilic phase (peripheral eosinophilia and eosinophilic organ infiltration), and a vasculitic phase (neuropathy, purpura, glomerulonephritis). Cardiac involvement - including eosinophilic myocarditis and pericarditis - is a major cause of morbidity and mortality, occurring in approximately 25-50% of patients.

Marked eosinophilia (≥1x10&sup9;/L) is the single most discriminating feature of EGPA from other vasculitides. GPA and MPA essentially never cause eosinophilia at this level - in fact, eosinophilia at this threshold subtracts 4 points from both the GPA and MPA scores. The +5 weight in EGPA reflects this near-complete specificity: a patient with vasculitis and this degree of eosinophilia is overwhelmingly more likely to have EGPA than GPA, MPA, PAN, or other vasculitides. Eosinophilia combined with obstructive airflow (+3) nearly reaches the classification threshold of 5 on its own.

EGPA has two distinct clinical phenotypes based on ANCA status. ANCA-positive EGPA (approximately 30-40% of cases, usually MPO-ANCA) is associated with a vasculitic phenotype: glomerulonephritis, peripheral neuropathy (mononeuritis multiplex), and purpura. The ANCA-negative group (approximately 60-70%) has more prominent eosinophilic features: cardiac involvement, pulmonary infiltrates, and higher eosinophil counts. ANCA-negative EGPA may have a different pathogenesis, driven more by eosinophil-mediated tissue damage than by ANCA-mediated neutrophil activation. This distinction has therapeutic implications - ANCA-positive EGPA may benefit more from rituximab.

PR3-ANCA (c-ANCA) is the serologic hallmark of GPA and is extremely rare in EGPA. When a patient presents with apparent EGPA features but has PR3-ANCA, the diagnosis should be reconsidered - they likely have GPA with incidental asthma or eosinophilia, or a GPA-EGPA overlap. The -3 weight is the largest negative item in the EGPA criteria and is designed to prevent GPA patients from being misclassified as EGPA on the basis of respiratory features. A patient with eosinophilia (+5) and PR3-ANCA (-3) would have a net of only +2 from these two items, appropriately raising doubt about the EGPA classification.

Cardiac involvement in EGPA occurs in approximately 25-50% of patients and is the leading cause of EGPA-related death, accounting for approximately 50% of mortality. It can manifest as eosinophilic myocarditis (causing cardiomyopathy, heart failure, arrhythmias), pericarditis, endomyocardial fibrosis, and coronary arteritis. Cardiac MRI with gadolinium is the most sensitive imaging modality, showing late gadolinium enhancement in characteristic patterns. Troponin and BNP are useful biomarkers. Notably, cardiac involvement is more common in ANCA-negative EGPA and may not correlate with peripheral eosinophil count. Cardiac EGPA requires aggressive immunosuppression and close cardiologic follow-up.

Both EGPA and GPA involve the upper airways but through different mechanisms. In EGPA, nasal polyps result from eosinophilic inflammation of the sinonasal mucosa - similar to severe eosinophilic chronic rhinosinusitis (ECRS). The polyps are soft, pale, and often recurrent after surgery. In GPA, sinonasal involvement is granulomatous and destructive: nasal cartilage erosion, septal perforation, saddle nose deformity, and subglottic stenosis. GPA does not typically cause polypoid lesions. The 2022 criteria reflect this: nasal polyps score +3 in EGPA, while nasal cartilage destruction and subglottic stenosis score +2 and +3 in GPA respectively, with no overlap.

EGPA classically progresses through three overlapping phases, though not all patients follow this sequence. The prodromal (allergic) phase features adult-onset asthma - often severe and difficult to control - along with allergic rhinitis and sinusitis. This phase can last for years, often a decade or more, before vasculitis develops. The eosinophilic phase is characterized by marked blood eosinophilia and eosinophilic organ infiltration: Loffler-like pulmonary infiltrates, eosinophilic gastroenteritis, and endomyocardial infiltration. The vasculitic phase brings systemic small-vessel vasculitis: purpura, mononeuritis multiplex, glomerulonephritis, and potentially life-threatening cardiac involvement. Recognition of the prodromal phase in an asthmatic patient with unexplained eosinophilia is critical for early diagnosis.

In the 2022 ACR/EULAR validation study, the EGPA criteria (score ≥5) demonstrated sensitivity of 85.0% and specificity of 99.0% against other vasculitides and comparators. The specificity of 99% is the highest among the 2022 AAV criteria, reflecting how distinctive EGPA is from other vasculitides when the full clinical and laboratory picture is considered. The lower sensitivity (85%) compared to GPA (93%) and MPA (91%) reflects the clinical heterogeneity of EGPA and the fact that some EGPA patients - particularly ANCA-negative patients with predominantly cardiac or pulmonary manifestations - may not accumulate 5 points using these criteria.