EGPA: Early Recognition & Targeted Intervention Improve Outcomes

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that can affect multiple organ systems, including the lungs, skin, heart, gastrointestinal tract, and peripheral nervous system. The disease course is heterogeneous, ranging from mild, asthma-predominant phenotypes to severe, life-threatening vasculitic manifestations. Diagnostic delays are common due to the non-specific nature of early symptoms and the rarity of the condition, often leading to irreversible organ damage and increased morbidity.¹

The clinical presentation of EGPA typically evolves through three phases: a prodromal phase characterised by allergic rhinitis, asthma, and sinusitis; an eosinophilic phase with peripheral and tissue eosinophilia; and a vasculitic phase involving systemic symptoms and organ-specific damage.² The presence of ANCA, particularly anti-myeloperoxidase (MPO) ANCA, is observed in approximately 30-40% of EGPA patients and is often associated with a more severe vasculitic phenotype.³ However, ANCA negativity does not exclude the diagnosis, underscoring the importance of clinical and histopathological criteria.⁴ The estimated annual incidence of EGPA ranges from 0.5 to 6.8 cases per million adults, with a prevalence of 11 to 50 cases per million adults. The disease affects individuals of all ages, though it typically manifests in adulthood, with a mean age of onset around 40-50 years. There is no significant gender predominance. Understanding these epidemiological patterns is crucial for raising awareness among clinicians and facilitating earlier diagnosis.

Advancing EGPA Management

Discussions at EULAR 2026 underscored the critical need for a multidisciplinary approach to EGPA, involving pulmonologists, rheumatologists, neurologists, and dermatologists, to ensure comprehensive patient evaluation and management. The diagnostic criteria, including the American College of Rheumatology (ACR) 1990 criteria and the Chapel Hill Consensus Conference (CHCC) definitions, provide a framework, but clinical acumen remains paramount for timely identification.^5,6 Early recognition is particularly challenging given the overlap with other hypereosinophilic syndromes and severe asthma. Biomarkers such as eosinophil count, IgE levels, and specific ANCA patterns can aid in diagnosis and prognostication.⁷ Histopathological confirmation, often through biopsy of affected tissues (e.g., skin, nerve, lung), revealing eosinophilic infiltration, granulomas, and vasculitis, provides definitive evidence, though it is not always feasible or necessary in all cases for diagnosis.

Treatment strategies for EGPA traditionally involve corticosteroids, often in combination with immunosuppressants such as cyclophosphamide for severe, organ-threatening disease, or methotrexate/azathioprine for maintenance.⁸ However, these broad immunosuppressive regimens are associated with significant side effects and do not always achieve sustained remission. The advent of targeted biological therapies has transformed the treatment landscape. Mepolizumab, an anti-IL-5 monoclonal antibody, has demonstrated efficacy in reducing relapse rates and allowing for corticosteroid dose reduction in patients with refractory or relapsing EGPA.⁹ In the pivotal MENSA trial, mepolizumab reduced the annualised relapse rate by 50% (rate ratio 0.50; 95% CI 0.35-0.72; p<0.001) compared to placebo, and increased the proportion of patients achieving remission at weeks 36 and 48.⁹ Mepolizumab specifically targets interleukin-5 (IL-5), a cytokine central to the growth, differentiation, recruitment, activation, and survival of eosinophils, thereby reducing eosinophil counts and subsequent tissue damage.

Other biologics, such as benralizumab (anti-IL-5Rα) and dupilumab (anti-IL-4Rα), are also being investigated for their potential role in EGPA, particularly in patients with prominent allergic or asthmatic features.¹⁰ These therapies offer a more precise approach by targeting specific pathways involved in eosinophilic inflammation, thereby potentially improving efficacy and reducing systemic toxicity. The choice of therapy is increasingly guided by disease phenotype, ANCA status, and the presence of specific organ involvement. For instance, ANCA-positive patients with severe vasculitis may still require initial aggressive immunosuppression, while ANCA-negative patients with predominant eosinophilic features might benefit more from IL-5 pathway inhibitors.¹¹

Despite advances, challenges remain. Long-term management requires careful monitoring for disease flares and treatment-related adverse events. The optimal duration of biological therapy and the role of combination therapies are areas of ongoing research. Furthermore, access to these newer, often expensive, treatments remains a barrier in some healthcare systems. Future research will likely focus on identifying additional biomarkers to predict treatment response and developing personalised medicine approaches to tailor therapy to individual patient profiles, ultimately aiming to achieve sustained remission with minimal side effects.¹² A deeper understanding of the genetic and environmental factors contributing to EGPA pathogenesis is also needed to develop preventative strategies and more effective early interventions.