Eosinophilic granulomatosis with polyangiitis, abbreviated EGPA and formerly called Churg-Strauss syndrome, is a rare form of vasculitis, meaning it involves inflammation of blood vessels. It belongs to a family of conditions known as antineutrophil cytoplasmic antibody, or ANCA, associated vasculitides, although not every patient produces these antibodies. The disease is characterised by an overabundance of eosinophils, a type of white blood cell normally deployed against parasites and involved in allergic reactions. When these cells accumulate and activate inappropriately, they can wreak havoc on organs throughout the body, including the lungs, skin, heart, and, critically, the peripheral nerves, the delicate wiring that carries signals between the spinal cord and the rest of the body.

Peripheral neuropathy, the medical term for damage to these nerves, is among the most feared manifestations of EGPA. Patients may experience numbness, tingling, weakness, or excruciating pain, typically beginning in the feet and hands. In the most severe cases, the damage follows a pattern known as mononeuritis multiplex, in which multiple individual nerves fail in unpredictable succession, leaving patches of the body paralysed or insensate. Despite decades of clinical observation, the underlying mechanisms that drive nerve injury in EGPA remain poorly understood, and clinicians have lacked dependable laboratory markers to identify which patients are developing or will develop this complication.

The new study, published in the Journal of Neurology, set out to address this gap. Researchers led by Yuichi Masuda and Shogo Matsuda of Osaka Medical and Pharmaceutical University, together with collaborators at Kyoto University, Osaka Metropolitan University, Yodogawa Christian Hospital, Tenri Hospital, and Kurashiki Sweet Hospital, assembled data from the REVEAL cohort, a multicentre database covering patients diagnosed across Japan. They enrolled individuals newly diagnosed with EGPA between 2006 and 2024, applying the 2022 classification criteria jointly developed by the American College of Rheumatology and the European Alliance of Associations for Rheumatology, the current international standard for identifying the disease.

From an initial pool of 159 patients in the REVEAL cohort, the investigators focused on 107 patients who were newly diagnosed and had not yet received any treatment, a design choice that eliminates the confounding effects of prior immunosuppressive therapy on laboratory values and clinical findings. The results were striking. Peripheral neuropathy was present in 93 of the 107 patients, an extraordinary 86.9 percent, underscoring just how central nerve involvement is to the clinical picture of EGPA in this Japanese population. Meanwhile, 45 patients, or 42.1 percent, tested positive for myeloperoxidase ANCA, one of the two major antibody types associated with this disease family.

When the researchers compared patients with neuropathy against those without, several laboratory parameters stood out. Patients with peripheral nerve involvement had significantly higher levels of white blood cells, eosinophils, serum immunoglobulin G, and serum immunoglobulin G4 at the time of diagnosis. Among these candidates, IgG4 emerged as the most useful clinical indicator for detecting neuropathy in EGPA patients. This finding carries particular biological interest. IgG4 is an unusual antibody subclass, associated with immune tolerance rather than aggressive inflammation, and it has previously been implicated in IgG4-related disease, a distinct fibroinflammatory condition. Earlier work had already documented IgG4 immune responses in Churg-Strauss syndrome, and pathological studies have found IgG4-related features in inflammatory neuropathies, making the new cohort data a compelling piece of a growing puzzle.

The study also examined what happens to patients over time, and here the news was mixed. Using Kaplan-Meier survival analysis, a standard statistical technique for tracking events over follow-up periods, the team calculated that the five-year relapse rate of peripheral neuropathy among EGPA patients who had experienced it was 18.6 percent. In other words, nearly one in five patients whose nerve disease had initially been brought under control saw it return within five years. Relapse in vasculitis is a persistent clinical challenge, and identifying which patients are at risk has been an ongoing goal of international research efforts, including the European Vasculitis Study Group trials, which previously documented the burden of peripheral neuropathy in ANCA-associated vasculitis more broadly.

Perhaps the most actionable finding concerned treatment. The researchers found that the administration rate of intravenous cyclophosphamide, a potent immunosuppressive drug long used in severe forms of vasculitis, was significantly lower among patients whose neuropathy relapsed than among those who remained in remission. While the observational design of the study means it cannot definitively prove that cyclophosphamide prevents relapse, the association suggests that more aggressive induction therapy at the outset may protect the nerves over the long term. This aligns with contemporary European guidelines for managing ANCA-associated vasculitis, which recommend cyclophosphamide or rituximab for organ-threatening disease, and with recent trials exploring glucocorticoids combined with cyclophosphamide in EGPA patients with poor-prognosis factors.

The implications for clinical practice are potentially significant. A readily available serum marker like IgG4 could help clinicians stratify newly diagnosed EGPA patients, flagging those who need close neurological monitoring, nerve conduction studies, or early escalation of immunosuppression. It could also complement existing prognostic tools, such as the revised five-factor score used to assess mortality risk in systemic necrotizing vasculitides, and disease activity measures like the Birmingham Vasculitis Activity Score version 3.0, which the current study used to characterise patients at baseline. For a disease in which diagnosis is often delayed for years while patients are treated for asthma alone, any additional diagnostic lever is welcome.

Caution is nonetheless warranted. The study involved 107 patients from a single country, and the authors themselves note that the aetiology of peripheral neuropathy in EGPA remains unclear. Whether IgG4 is merely a correlate of the eosinophilic, ANCA-negative disease subset that tends toward neuropathy, or plays a direct role in nerve injury, awaits further mechanistic work. The finding that lower cyclophosphamide use was associated with relapse could reflect confounding by disease severity, since physicians may reserve the drug for the sickest patients. Still, with newer targeted therapies such as the anti-interleukin-5 agent mepolizumab showing promise for EGPA-related neuropathy in recent reports, the landscape of treatment options is expanding. The REVEAL cohort study adds an important piece of evidence to this evolving picture, offering clinicians a potential biomarker and a hint that early, intensive immunosuppression may keep patients’ nerves, and their independence, intact for longer.

Subject of Research: Peripheral neuropathy in eosinophilic granulomatosis with polyangiitis

Article Title: Clinical features and prognosis of EGPA-associated peripheral neuropathy: a multicentre REVEAL cohort study

Article References: Masuda, Y., Matsuda, S., Okazaki, A., Tsuge, R., Manabe, A., Taniguchi, T., Hiwa, R., Hatta, M., Shiomi, M., Watanabe, R., Suwa, N., Fujiki, Y., Miyake, H., Yamamoto, W., Hashimoto, M., Takeuchi, T., & Kotani, T. (2026). Clinical features and prognosis of EGPA-associated peripheral neuropathy: a multicentre REVEAL cohort study. Journal of Neurology, 273(10), Article 641. https://doi.org/10.1007/s00415-026-14196-z

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14196-z

Keywords: EGPA, peripheral neuropathy, vasculitis, IgG4, ANCA, cyclophosphamide, eosinophils, autoimmune disease, REVEAL cohort, biomarker, relapse, Journal of Neurology