D3.148 - ANCA-Negative Systemic Vasculitis Developing Despite Anti-IL-5R Therapy and High Dose of Glucocorticosteroids: A Diagnostic and Therapeutic Challenge

Background

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides are heterogeneous small‑vessel inflammatory disorders (1). Although ANCA serology is a key diagnostic marker, up to one‑third of patients with a clinical phenotype suggestive of eosinophilic or microscopic vasculitis remain ANCA‑negative (2,3). These variants often present with prominent respiratory involvement and reduced responsiveness to glucocorticoids or anti‑eosinophilic biologics (3). Early recognition is essential to prevent irreversible organ damage. We present a case of ANCA‑negative vasculitis developing despite high‑dose glucocorticosteroids and anti‑IL‑5 receptor therapy.

Case Presentation

A 52‑year‑old woman with long‑standing severe asthma treated with methylprednisolone (32 mg/day) and benralizumab presented with progressive polyarthralgia, joint swelling and paresthesias of all extremities. Her history included multiple tracheotomies, tracheal stenosis, Graves’ disease after radioiodine therapy, osteoporosis and an L4 compression fracture. She reported multiple drug hypersensitivities. Immunologic testing showed ANA 1:320 (granular) and 1:160 (cytoplasmic), with positive ThT0 and PMScl autoantibodies; ANCA were repeatedly negative.

Diagnostic Assessment

High‑resolution chest CT showed new bilateral ground‑glass opacities and upper‑lobe and perihilar consolidations that were absent six months earlier. Bronchoscopy grew Streptococcus viridans; both QuantiFERON and MTB PCR were negative. Dermatologic evaluation confirmed vasculitic skin lesions. The combination of severe steroid‑dependent asthma, interstitial lung abnormalities, neuropathic symptoms, vasculitic skin changes and negative ANCA supported the diagnosis of ANCA‑negative systemic vasculitis.

Therapeutic Intervention

Induction therapy with rituximab was initiated (375 mg/m² weekly × 4), consistent with established treatment strategies for ANCA‑associated vasculitis (4,5). Follow‑up chest CT demonstrated regression of ground‑glass opacities and consolidations. Despite these benefits, the patient continued to experience dyspnea and severe asthma, and BVAS remained >2. Given persistent respiratory symptoms and ongoing inflammatory activity, the multidisciplinary team considered escalation to mepolizumab as an additional biologic option targeting eosinophilic inflammation (6).

Conclusion

This case highlights the diagnostic and therapeutic challenges of ANCA‑negative systemic vasculitis in patients with severe asthma and overlapping eosinophilic or autoimmune features. Importantly, it demonstrates that systemic vasculitis may develop despite high‑dose glucocorticoids and anti‑IL‑5 receptor therapy. Rituximab remains an effective induction strategy, although selected patients may require additional biologic modulation targeting eosinophilic pathways.