Overlapping forms of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis: Insights from a European multicenter study

Abstract

Abstract Background Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) are distinct forms of antineutrophil cytoplasm antibody (ANCA)‐associated vasculitis (AAV). Increasing evidence suggests overlapping features, particularly in proteinase 3 (PR3)‐ANCA‐positive EGPA and GPA with eosinophilia. This study aimed to characterize overlapping EGPA/GPA forms and assess their clinical and therapeutic implications. Methods We conducted a European, multicenter, observational study, including 135 patients with overlapping EGPA/GPA features. Definitions were based on ACR/EULAR classification criteria and other clinical and biological findings. Clinical, biological, and histological characteristics were analyzed using unsupervised hierarchical clustering approach. Comparisons were made with established EGPA and GPA control cohorts. Results Three clusters emerged: Cluster 1, a hybrid phenotype (pulmonary nodules, PR3‐ANCA positivity, high relapse rate); Cluster 2, a systemic inflammatory phenotype (constitutional symptoms, PR3‐ANCA positivity, moderate renal involvement); and Cluster 3, a severe vasculitis form (severe renal disease, alveolar hemorrhage). Including typical EGPA and GPA control cohorts revealed two main clusters a posteriori: an EGPA cluster and a GPA cluster. Cluster 1 overlapped with both EGPA and GPA clusters, whereas Clusters 2 and 3 predominantly aligned with GPA. Kaplan–Meier analysis revealed that Cluster 1 and the typical EGPA cohort had the best overall survival, whereas Cluster 3 had the poorest survival. Relapse‐free survival was highest in typical EGPA and poorest in Cluster 3 and typical GPA. Conclusion This study delineates the heterogeneity of EGPA/GPA overlap and underscores the need for personalized treatment approaches. Future prospective studies should explore targeted therapies, including rituximab and IL‐5 blockade, in these overlapping AAV subtypes.

Affiliated Institutions

• Azienda Ospedaliera San Gerardo IT
• University of Milan IT
• University of Udine IT
• Hôpital Louis Pradel FR
• Marche Polytechnic University IT
• University of Milano-Bicocca IT
• Maastricht University NL
• University of Algarve PT
• University of Cambridge GB
• University of Padua IT
• University Medical Center Freiburg DE
• Université de Caen Normandie FR
• Istituti di Ricovero e Cura a Carattere Scientifico IT
• Fatebenefratelli Hospital IT
• Centre Hospitalier Compiègne-Noyon FR
• Hospices Civils de Lyon FR
• University of Verona IT
• Centre Hospitalier du Mans FR
• A. O. Ordine Mauriziano di Torino IT
• Tallaght University Hospital IE
• University of Palermo IT
• Sechenov University RU
• Centre Hospitalier Intercommunal Toulon-La Seyne-sur-Mer FR
• Istituto Ortopedico Gaetano Pini IT
• Manchester University NHS Foundation Trust GB
• Centre Hospitalier Universitaire de Clermont-Ferrand FR
• University Hospital of Geneva CH
• Hôpital Bichat-Claude-Bernard FR
• University of Freiburg DE
• Centre Hospitalier Territorial de Nouvelle-Calédonie NC
• ASST Fatebenefratelli Sacco IT
• University of Brescia IT
• Mount Sinai Hospital CA
• Hôpital Manchester FR
• University of Florence IT
• Hôpital Edouard Herriot FR
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia IT
• Centre Hospitalier Universitaire de Reims FR
• University of Alberta CA

Related Publications