Does PR3-ANCA+ Eosinophilic Granulomatosis with Polyangiitis (Churg–Strauss)Really Exist?

Matthias Papo¹, Renato A. Sinico ², Vítor Teixeira ³, Maria-Letizia Urban ⁴, Juliane Mahrhold ⁵, Francesco Locatelli ⁶, Giulia Cassone ⁷, Franco Schiavon ⁸, Benjamin Seeliger ⁹, Thomas Neumann ¹⁰, Claus Kroegel ¹¹, Matthieu Groh ¹², Chiara Marvisi ¹³, Maxime Samson ¹⁴, Thomas Barba ¹⁵, David Jayne ¹⁶, Bernhard Hellmich ⁵, Sara Monti ¹⁷, Carlomaurizio Montecucco ⁶, Carlo Salvarani ¹⁸, Jean-Emmanuel Kahn ¹², Cécile-Audrey Durel ¹⁵, Loic Guillevin ¹⁹, Giacomo Emmi ⁴, Augusto Vaglio ²⁰ and Benjamin Terrier ¹⁹, ¹Department of Internal Medicine, Hôpital Cochin, Université Paris Descartes, Sorbonne Paris Cité, INSERM Unité 1016, Centre de Référence pour les Maladies Auto-immunes Rares, Paris, France, Paris, France, ²Department of Medicine and Surgery, Università degli Studi di Milano - Bicocca , Italy, Milan, Italy, ³Rheumatology and Bone Diseases Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte; Lisbon, Portugal., Lisbon, Portugal, ⁴Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy, Florence, Italy, ⁵Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Kirchheim-Teck, Germany, Kirchheim, Germany, ⁶Department of Rheumatology, IRCCS Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy, Pavia, Italy, ⁷Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy. Rheumatology Unit, IRCCS Arcispedale Santa Maria Nuova, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy, Modena and Reggio Emilia, Italy, ⁸Operative Unit of Rheumatology, Department of Medicine DIMED, University of Padova, Padova, Italy, Padova, Italy, ⁹Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany, Hannover, Germany, ¹⁰Division of Rheumatology and Immunolog, Kantonsspital St. Gallen, St. Gallen, Sankt Gallen, Switzerland, ¹¹Department of Pneumology and Allergology, Clinic of Internal Medicine I, Jena University Hospital, Jena, Germany, Jena, Germany, ¹²Service de Médecine Interne, Centre de Référence des Syndromes Hyperéosinophiliques-CEREO, Hôpital Foch, Université Versailles–Saint-Quentin-en-Yvelines, Suresnes, France, Suresnes, France, ¹³Nephrology Unit, Parma University Hospital, Parma, Italy, Parma, Italy, ¹⁴CHU Dijon, Dijon, France, ¹⁵Department of Internal Medicine, Hôpital Edouard Herriot, Lyon, France, Lyon, France, ¹⁶Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, University of Cambridge, UK, Cambridge, United Kingdom, ¹⁷University of Pavia, Pavia, Italy, ¹⁸Division of Rheumatology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, ¹⁹National Referral Center for Rare Systemic Autoimmune Diseases Paris Cochin, Paris, France, ²⁰Nephrology Unit, Parma University Hospital, Parma, Italy, Nephrology Unit, Parma University Hospital, Parma, Italy, Italy

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ANCA, vasculitis and Churg-Strauss syndrome

Session Information

Date: Monday, November 11, 2019

Title: Vasculitis – ANCA-Associated Poster II

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss) is a small-vessel necrotizing vasculitis characterized by blood and tissue eosinophilia and asthma. Only a third of EGPA patients are ANCA+, mainly directed against myeloperoxidase (MPO). ANCA+ patients have more neurological and renal involvements, while ANCA– patients have more cardiac manifestations. ANCA directed against proteinase (PR3) are rarely found in EGPA, and their interpretation remains unclear. We aimed to examine the significance of PR3-ANCA in EGPA.

Methods: We set up a multicenter, European, EGPA cohort including 845 patients who satisfied the American College of Rheumatology criteria, 2012 Chapel Hill Consensus Conference definitions and/or MIRRA trial criteria. Baseline characteristics and outcomes were analyzed and compared according to ANCA status.

Results: ANCA status and specificity were available for 734 patients: 508 (69.2%) ANCA–, 209 (28.5%) MPO-ANCA+ and 17 (2.3%) PR3-ANCA+. At diagnosis, PR3-ANCA+ patients, compared to those MPO-ANCA+ or ANCA–, respectively, had: less frequent asthma (71% vs 91% or 93%, P=0.004), especially steroid-dependent asthma (21% vs. 34% or 46%, P=007); more skin manifestations (65% vs. 38% or 34%, P=0.03); less frequent pulmonary infiltrates (41% vs. 40% or 58%, P=0.03) but more frequent nodules (25% vs. 10% or 8%, P=0.046); less frequent peripheral neuropathy (29% vs. 72% and 47%, P< 0.0001); and lower median [IQR] eosinophil count/mm3(2015 [IQR 802–5826] vs. 5718 [2330–10444] or 3224 [1332–7570], P< 0.0001). Renal involvement did not differ between PR3-ANCA+ and MPO-ANCA+ patients.
Median follow-up was74 [37–116] months for the whole cohort. PR3-ANCA+ vs. MPO-ANCA+ or ANCA– patients, respectively, experienced vasculitis relapses more frequently (47% vs. 34% or 24%; P=0.004). Moreover, vasculitis relapse-free survival was much shorter for PR3-ANCA+ [hazard ratio (HR) 7.32, 95% CI 2.02–26.5; P=0.002] and MPO-ANCA+ patients (HR 1.71, 95% CI 1.23–2.37; P=0.002) compared to those ANCA–. Also, median prednisone doses at 24 and 60 months, respectively, were significantly higher for PR3-ANCA+ than MPO-ANCA+ or ANCA– patients (P=0.02 and P=0.007). Finally, at 24 months of follow-up, PR3-ANCA+ vs. MPO-ANCA+ or ANCA– patients, respectively, had less frequent chronic asthma (38% vs. 51% or 60%, P=0.04) but more frequent renal damage (20% vs. 10% or 1%, P< 0.0001).

Conclusion: PR3-ANCA+ EGPA patients’ characteristics differ from those MPO-ANCA+ or ANCA–, especially asthma and eosinophil counts, which are the cardinal features of EGPA. Since eosinophilia can be mild-to-moderate in granulomatosis with polyangiitis (GPA, Wegener’s), we wonder if PR3-ANCA+ EGPA is not a third phenotype of EGPA but rather a particular form of GPA.

Disclosure: M. Papo, None; R. Sinico, None; V. Teixeira, None; M. Urban, None; J. Mahrhold, None; F. Locatelli, None; G. Cassone, None; F. Schiavon, None; B. Seeliger, None; T. Neumann, None; C. Kroegel, None; M. Groh, None; C. Marvisi, None; M. Samson, None; T. Barba, None; D. Jayne, Astra Zeneca, 5, Boehringer-Ingelheim, 5, Celgene, 5, ChemoCentryx, 2, 5, GSK, 2, 5, Infla-Rx, 5, InflaRx GmbH, 5, Insmed, 5, Roche Genetech, 2, Sanofi Genzyme, 2, Takeda, 5; B. Hellmich, InflaRx GmbH, 5, Roche, 2, 8; S. Monti, None; C. Montecucco, None; C. Salvarani, None; J. Kahn, None; C. Durel, None; L. Guillevin, None; G. Emmi, None; A. Vaglio, None; B. Terrier, Grifols, 8, GSK, 8, LFB, 8, Roche, 8.

To cite this abstract in AMA style:

Papo M, Sinico R, Teixeira V, Urban M, Mahrhold J, Locatelli F, Cassone G, Schiavon F, Seeliger B, Neumann T, Kroegel C, Groh M, Marvisi C, Samson M, Barba T, Jayne D, Hellmich B, Monti S, Montecucco C, Salvarani C, Kahn J, Durel C, Guillevin L, Emmi G, Vaglio A, Terrier B. Does PR3-ANCA+ Eosinophilic Granulomatosis with Polyangiitis (Churg–Strauss)Really Exist? [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/does-pr3-anca-eosinophilic-granulomatosis-with-polyangiitis-churg-straussreally-exist/. Accessed .

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