Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis characterized by asthma, eosinophilia, and frequent peripheral nerve involvement. However, the precise mechanisms of nerve injury remain incompletely understood.
A 46-year-old woman with a 10-year history of asthma presented with lower-limb edema and progressive numbness distal to the ankles. Neurological examination revealed decreased tendon reflexes. Laboratory testing showed marked peripheral eosinophilia (10,330/μL), and myeloperoxidase antineutrophil cytoplasmic antibodies were negative. Sural nerve biopsy demonstrated axonal degeneration of myelinated fibers with perivascular eosinophilic infiltration and necrotizing vasculitis, leading to a diagnosis of EGPA.
To evaluate eosinophil-associated nerve injury, double immunofluorescence staining was performed for major basic protein (MBP) and galectin-10 (Charcot-Leyden crystal protein). Intact eosinophils were positive for both markers, whereas extracellular deposition of eosinophil granule proteins released through cytolytic degranulation was detected by MBP staining alone.1 As shown in the Figure, marked accumulation of eosinophils was observed in and around blood vessels and within the epineurium. Further, extracellular MBP deposition lacking galectin-10 was observed, consistent with eosinophil cytolysis and degranulation. Notably, eosinophils and extracellular MBP deposition were also present within nerve fascicles surrounded by the perineurium, corresponding to the endoneurium. These findings suggest that direct axonal injury mediated by cytotoxic eosinophil granule proteins at the endoneurial level may contribute to EGPA-associated peripheral neuropathy.
(Left) H&E-stained section of the sural nerve. Blood vessels are indicated by V, and nerve fascicles by N. (Right) Immunofluorescence staining of consecutive sections showing eosinophil granule protein MBP (red), eosinophil cytoplasmic protein galectin-10 (green), and DNA (blue). Scale bar indicates 500 μm. MBP: major basic protein.
Under physiological conditions, the endoneurium is protected by the blood-nerve barrier. The findings in the Figure are consistent with reports indicating direct eosinophil entry into nerve fascicles.2,3 Activated eosinophils undergo cytolytic cell death, releasing cytotoxic granule proteins and extracellular traps.1 Our case supports eosinophil-mediated endoneurial injury and highlights the importance of controlling eosinophilic inflammation in EGPA-associated neuropathy.
Footnotes
CONTRIBUTIONS
KT: investigation, visualization, writing – original draft, writing – review & editing; HT, NO: resources, writing – review & editing; SU: conceptualization, investigation, supervision, funding acquisition, visualization, writing – original draft, writing – review & editing.
FUNDING
SU is supported by grants from a Grant-in-Aid for Scientific Research (KAKENHI 24K11593), the Japan Agency for Medical Research and Development (JP25ek0410138), the Akita University Key Research Fund, the Environmental Restoration and Conservation Agency, and the Ministry of Health, Labour and Welfare (MHLW 202213003A).
COMPETING INTERESTS
SU received grants and honoraria for lectures from AstraZeneca; honoraria for lectures from GSK and Sanofi; and grants from VIB, Cytrill, and Maruho. All funding was unrelated to the current work. The remaining authors declare no conflicts of interest relevant to this article.
ETHICS AND PATIENT CONSENT
Institutional review board approval was not required according to the authors’ institutions. Informed consent was obtained from the patient.
- Copyright © 2026 by the Journal of Rheumatology
