E164 Eosinophilic granulomatosis with polyangiitis with life-threatening cardiac and neurological involvement despite IL-5 therapy

Background/Aims A 66-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA) developed life-threatening neurological and cardiac involvement despite benralizumab therapy. Methods Initially diagnosed 2.5 years earlier after recurrent chest infections, asthma and pericardial effusion, he responded to mepolizumab but was switched to benralizumab for persistent eosinophilia, maintaining control for 10 months. He presented unable to walk, with rapidly progressive weakness and numbness following antibiotic-related diarrhoea. Further history revealed 2.5 kg weight loss, mild epistaxis and sinus symptoms over the last few months. Examination showed lower limb and hand sensory loss, power 2-3/5 and absent ankle jerks. Though initially thought to have Guillain-Barré syndrome (GBS), findings suggested an EGPA flare. Eosinophils were 3.04 × 109/L, CRP 167 mg/L, CK 2000 U/L. Rheumatoid factor became positive at 50 IU/ml. CXR showed a right-lower-zone cavitating lesion. Nerve conduction confirmed confluent mononeuritis multiplex. He was treated with cyclophosphamide (12.5 mg/kg) and prednisolone 60 mg; rising eosinophils (9.77 × 109/L), troponin (5652 ng/L) and BNP (2802 pg/mL) prompted 500 mg methylprednisolone, resulting in rapid recovery. He was discharged ambulant with mild residual sensory symptoms. Maintenance therapy is planned with either methotrexate or azathioprine in addition to benralizumab. Results EGPA can cause a range of cardiac and neurological symptoms. Cardiac involvement may be coronary, myocardial, pericardial or intramural. Neurological involvement may be central or peripheral. Aetiology involves eosinophil-mediated vascular inflammation causing thrombosis or ischaemia. In peripheral neuropathy, eosinophil migration can directly damage nervous tissue. High eosinophil counts correlate with disease severity. Benralizumab is an IL-5 receptor inhibitor with real-world data showing 86% patients respond to treatment. Pulmonary relapses tend to occur from week 24, though can appear as early as week 16 and may be related to drug-antibody development. However, extra-pulmonary relapses while on benralizumab are rare. Our patient developed mild nasal symptoms around week 24 but attributed them to hayfever and weight loss to increased activity. Eosinophils stayed normal until acute neurological deterioration. This case highlights that clinical relapse may occur independently of circulating eosinophil levels, suggesting tissue-level eosinophil activation or IL-5-independent pathways. Rheumatoid factor positivity in ANCA-associated vasculitis may predict worse prognosis and warrants close monitoring. Conclusion Benralizumab is an effective treatment in EGPA but secondary failure can emerge around weeks 16-24, possibly related to waning receptor occupancy or anti-drug antibody formation. Clinicians should maintain vigilance for subtle early signs such as sinus symptoms, fatigue, or weight loss — even when blood eosinophils appear suppressed. Extra-pulmonary relapses are rare but can present with both cardiac and neurological involvement, which can mimic GBS or spinal pathology. Rapid deterioration may necessitate escalation to cytotoxic induction such as cyclophosphamide. Disclosure M. Iftikhar: None. U. Ahmed: None. K. Sharma: None. A. Ahmed: None.