Two subtypes of Churg–Strauss syndrome with neuropathy: the roles of eosinophils and ANCA

Abstract

The aim of this study was to clarify the differences in the pathogenesis of neuropathy between myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive and -negative patients with Churg-Strauss syndrome (CSS). Eight MPO-ANCA-positive and 14 MPO-ANCA-negative patients were included. In addition to the standard histology, nerve biopsies were examined, employing immunohistochemistry for eosinophil major basic protein and electron microscopy. The groups did not differ significantly in clinical profiles, including the peak disability score and number of blood eosinophils. In nerve biopsies, necrotizing vasculitis was found in 63% (5/8) of the ANCA-positive and 21% (3/14) of the ANCA-negative patients. Fibrinoid necrosis of vessel walls was noted in 4 ANCA-positive patients (50%), and in one ANCA-negative patient (p = 0039). In contrast, a large number of eosinophilic infiltrations in the epineurium was shown in 36% (5/14) of the ANCA-negative patients, with no eosinophilic infiltrations shown in ANCA-positive patients. In 3 ANCA-negative patients, endoneurial eosinophils were seen where focal axonal loss and capillary dilatation were occasionally noted. There may be 2 pathogenetic mechanisms of neuropathy with CSS: ANCA-related vascular fibrinoid necrosis, and a toxic eosinophilic effect on nerve fibers which is independent of ANCA. Therapy targeting activated eosinophils may be a possible treatment for intractable neuropathy of CSS.

Antineutrophil cytoplasmic autoantibodies and clinical phenotype in patients with Churg-Strauss syndrome

“…3 In the article by Sabl e-Fourtassou et al, 3 ''ELISA assay showed that serum specimens of 34 of 39 patients with perinuclear ANCA (5 patients' specimens were not tested) had anti-MPO specificity.'' 2 More recently, similar results were obtained by Baldini et al 6 and Oka et al, 7 who found anti-MPO antibodies in 15 (39%) of 38 and 8 (36.4%) of 22 patients, respectively.…”

“…7 In conclusion, Healy et al 1 confirm that ANCAs (mainly with specificity for MPO) are present in approximately 40% of patients with CSS and that ANCA status correlates with organ involvement, even though some associations should be verified in more numerous case series. …”

ANCA negative eosinophilic granulomatosis with polyangiitis: sometimes it really IS vasculitis

“…Neuropathy is frequently described in the literature as occurring in around 70% of cases 12 26. Owing to the eosinophilic infiltration and the release of toxic mediators, this leads to small vessel arteritis of peripheral nerves.…”

Transient Cerebral Ischemic Attack and Delirium Heralding the Vasculitic Phase of Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome)

“…However, the presence of high titer of ANCA hallmarks the vasculitic disease complications, as some large studies demonstrated that ANCA were positive in among 30-40% of EGPA patients and that ANCA-positive patients more frequently had peripheral neuropathy, glomerulonephritis, purpura and CNS involvement (which are due to small-vessel vasculitis) [1,9,10]. Thus ANCA should be tested in patients with cerebrovascular disease associated with systemic inflammation or eosinophilia and anamnestic asthma.…”