Differential clinicopathologic features of EGPA-associated neuropathy with and without ANCA
Ryoji Nishi, Haruki Koike, Ken Ohyama, Yuki Fukami, Shohei Ikeda, Yuichi Kawagashira, Masahiro Iijima, Masahisa Katsuno, Gen Sobue
Abstract
<h3>Objective</h3> To investigate the clinicopathologic features of eosinophilic granulomatosis with polyangiitis (EGPA)–associated neuropathy with a focus on the presence or absence of anti-neutrophil cytoplasmic antibodies (ANCAs). <h3>Methods</h3> We examined the clinical features and pathologic findings of sural nerve biopsy specimens from 82 patients with EGPA-associated neuropathy. Of these patients, 32.9% were myeloperoxidase (MPO)-ANCA positive, and 67.1% were MPO-ANCA negative. PR3-ANCA was negative in all of 78 examined patients. <h3>Results</h3> Upper limb symptoms were more frequently reported as initial neuropathic manifestations in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (44.4% vs 14.6%, <i>p</i> < 0.01). The serum levels of C-reactive protein were significantly higher in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (<i>p</i> < 0.05). Sural nerve biopsy specimens showed findings suggestive of vasculitis (i.e., destruction of vascular structures) in epineurial vessels; these results were seen more frequently in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (<i>p</i> < 0.0001). Conversely, the numbers of eosinophils in the lumen of the epineurial vessels (<i>p</i> < 0.01) and epineurial vessels occluded by intraluminal eosinophils (<i>p</i> < 0.05) were higher in the MPO-ANCA–negative group than in the MPO-ANCA–positive group. Furthermore, the incidence of eosinophil infiltration in the endoneurium was higher in the MPO-ANCA–negative group than in the MPO-ANCA–positive group (<i>p</i> < 0.01). <h3>Conclusions</h3> This study suggests that the pathogenesis of EGPA comprises at least 2 distinct mechanisms: ANCA-associated vasculitis resulting in ischemic effects and inflammation, which is prominent in MPO-ANCA–positive patients, and eosinophil-associated vascular occlusion leading to ischemia and eosinophil-associated tissue damage, which is conspicuous in MPO-ANCA–negative patients.