Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

Abstract

Objective

To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA.

Methods

Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease.

Results

The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p = 0.005) and with the presence of ANCA (p < 0.001). Overall, 59% of patients had polyangiitis as defined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifestations including arthralgias (p = 0.02) and renal disease (p = 0.024), had higher peripheral eosinophilia (p = 0.027), and a trend towards less myocarditis (p = 0.057). Using predefined criteria of vasculitis and surrogates of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features.

Conclusion

We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as hypereosinophilic asthma with systemic (non vasculitic) manifestations.

Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss syndrome) is defined as an eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, with necrotizing vasculitis predominantly affecting small to medium-sized vessels, occurring in patients with asthma and eosinophilia [1]. Although early studies [2] reported on cases of late stage disease with florid systemic manifestations, the diagnosis is now more frequently made before multiple severe organ involvement [3].

Although the terminology of Churg-Strauss syndrome was replaced by EGPA, ANCA are present in only about 40% of patients in recent series [4], [5], [6], [7], [8]. Although nonspecific and not validated as diagnostic biomarkers, ANCA when present are usually considered contributive to EGPA diagnosis. Since many patients lack confident criteria of documented systemic vasculitis and/or are ANCA negative [9], the current terminology and classification require further refinement.

Recently, several studies have described phenotypes of clinical manifestations of EGPA patients according to their ANCA status [4], [5], [6], [8], [10], [11]. Patients with ANCA more frequently have a “vasculitic” phenotype (i.e. more frequent glomerulonephritis, alveolar hemorrhage, and/or biopsy-proven vasculitis), whereas those without ANCA more frequently have an eosinophilic “tissue” phenotype, with more frequent cardiomyopathy. The phenotype of EGPA is influenced by genetic predisposition [12], suggesting that different manifestations are not only explained by the disease stage. However, whether phenotype distinction should be based on ANCA status and/or on organ manifestations, is unknown. In a recent workshop [13], it was emphasized that future efforts should aim at determining whether EGPA represents a single or multiple nosologic entities, and at validating the diagnostic utility of ANCA in eosinophilic lung diseases.

Although EGPA clinical manifestations are highly heterogeneous, no study has yet described EGPA patients' manifestations according to the presence or not of genuine vasculitis features. Here, we aimed to describe organ manifestations and ANCA status in a large series of EGPA patients based on the presence or not of vasculitis features, with the additional aim of guiding future recommendations for nosology and classification.