Cutaneous Vasculitis in Primary Sjögren Disease

Breillat, Paul MD
Le Guern, Véronique MD
d’Humières, Thomas MD; PhD
Battistella, Maxime MD; PhD
Legendre, Paul MD
Lenormand, Cédric MD; PhD
Kottler, Diane MD
Mathian, Alexis MD; PhD
Jachiet, Marie MD
El Khalifa, Jihane MD
Mahévas, Thibault MD
Comarmond, Chloé MD; PhD
Sene, Damien MD; PhD
Amoura, Zahir MD; PhD
Gottenberg, Jacques-Eric MD; PhD
Mouthon, Luc MD; PhD
Bouaziz, Jean-David MD; PhD
Mariette, Xavier MD; PhD
Chasset, François MD; PhD

¹Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d’Ile de France, de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP)-CUP, Université de Paris Cité, Paris, France
²INSERM, U970, Paris Centre de Recherche Cardiovasculaire (PARCC), Paris, France
³Department of Physiology, FHU SENEC, Henri Mondor Hospital, Assistance Publique Hôpitaux de Paris, INSERM IMRB U955, Université Paris Est, Créteil, France
⁴Department of Pathology, AP-HP, Saint-Louis Hospital, Université Paris Cité, Paris France
⁵Clinical Immunology Department, Centre Hospitalier du Mans, Le Mans, France
⁶Department of Dermatology, Hôpital Civil-Hôpitaux Universitaires de Strasbourg, Strasbourg, France
⁷Department of Dermatology, Caen University Hospital, Caen, France
⁸Médecine Interne 2, AP-HP, Hôpital Pitié Salpetrière, Sorbonne Université, Faculté de Médecine, Paris, France
⁹Department of Dermatology, AP-HP, Saint-Louis Hospital, Université Paris Cité, Paris France
¹⁰Dermatology Department, Bichat, AP-HP, Paris, France
¹¹Internal Medicine Department, Département Médico-Universitaire INVICTUS, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Nord–Université Paris Cité, Paris, France
¹²Department of Rheumatology, CHU Hautepierre, Strasbourg, France
¹³Service de Rhumatologie, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, INSERM UMR1184, Le Kremlin-Bicêtre, France
¹⁴Dermatology and Allergology, AP-HP, Hôpital Tenon Sorbonne Université, Faculté de Médecine, Paris, France
¹⁵INSERM U1135, CIMI, Paris, France

Article Information

Accepted for Publication: June 11, 2025.

Published Online: August 6, 2025. doi:10.1001/jamadermatol.2025.2665

Corresponding Author: Paul Breillat, MD, INSERM, U970, Paris Centre de Recherche Cardiovasculaire (PARCC), 56 rue Leblanc, 75015 Paris, France ([email protected]).

Author Contributions: Drs Breillat and Chasset had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Breillat, Le Guern, Bouaziz, Mariette, Chasset.

Acquisition, analysis, or interpretation of data: Breillat, Le Guern, d’Humières, Battistella, Legendre, Lenormand, Kottler, Mathian, Jachiet, El Khalifa, Mahévas, Comarmond, Sene, Amoura, Gottenberg, Mouthon, Mariette, Chasset.

Drafting of the manuscript: Breillat, Le Guern, d’Humières, Chasset.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Breillat, d’Humières.

Administrative, technical, or material support: Kottler, Mathian, Sene, Gottenberg, Mouthon, Mariette.

Supervision: Le Guern, Amoura, Bouaziz, Chasset.

Conflict of Interest Disclosures: Prof Mariette reported personal fees from Bristol Myers Squibb, GSK, Novartis, and Otsuka outside the submitted work. Dr Chasset reported grants from AstraZeneca, Bristol Myers Squibb, and GSK outside the submitted work. No other disclosures were reported.

Funding/Support: The ASSESS cohort was set up in 2006 with a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2005 P060228).

Role of the Funder/Sponsor: The French Ministry of Health had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The ASSESS Study Investigators: Joelle Benessiano, Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Jacques Morel, Claire Larroche, Corinne Miceli-Richard, Gaétane Nocturne, Aleth Perdriger, Xavier Puéchal, Philippe Ravaud, Stephanie Rist, Carinne Salliot, Alain Saraux, Raphaèle Seror, Jean Sibilia, and Olivier Vittecoq.

Group Information: The EMSED (Etude des maladies systémiques en dermatologie) study group and the French ASSESS cohort members appear listed in Supplement 2.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We thank the patients, nurses, and medical staff who participated in this study. We also thank all of the other members of the EMSED study group, the investigators of the ASSESS cohort for providing the data collection, and all of the patients for their contributions.

Received February 28, 2025

Accepted June 11, 2025

JAMA Dermatology 161(10):p 1057-1062, October 2025. | DOI: 10.1001/jamadermatol.2025.2665

Importance

Cutaneous vasculitis (CV) is a heterogenous and severe complication of primary Sjögren disease, often indicating systemic involvement and poor prognosis. Understanding its characteristics and outcomes is essential for patient management.

Objective

To describe the clinical features, management, and prognosis of different CV types in patients with Sjögren disease.

Design, Setting, and Participants

This retrospective multicenter cohort study included patients with Sjögren disease and CV from pathology departments of 3 university hospitals in Paris, France (2011-2021), and a national case call. Patients met American College of Rheumatology/European League Against Rheumatism criteria and were matched 1:2 to controls patients with Sjögren disease but without CV. Data were collected and analyzed between March 2023 and March 2025.

Exposure

Presence of CV classified using the Chapel Hill classification dermatological addendum.

Main Outcomes and Measures

Demographics, clinical characteristics, immunological parameters, and received treatments were recorded. Primary outcomes were lymphoma occurrence and mortality risk, as well therapeutic response.

Results

Among 54 patients with CV and Sjögren disease (median [IQR] age at diagnosis of CV, 42 [27.7-56.0] years; 49 [91%] female), CV was more frequently classified as cryoglobulinemic vasculitis (29 patients [57%]) or hypergammaglobulinemic vasculitis (15 patients [28%]). Compared to controls, patients with Sjögren disease and CV had a higher lymphoma incidence (12 of 54 [13%] vs 4 of 108 [4%]; P = .04). Compared to other types of CV, type II cryoglobulinemic vasculitis was associated with increased mortality or lymphoma risk (hazard ratio, 6.8; 95% CI, 1.8-25.5; P = .005), higher ESSDAI (EULAR Sjögren Syndrome Disease Activity Index) scores (median [IQR], 15 [12-23]; P = .005), and more frequent kidney involvement (7 of 24 patients [29%] vs 1 of 25 patients [4%]; P = .02) and peripheral nervous system involvement (15 of 24 patients [63%] vs 3 of 25 patients [12%]; P < .001). Rituximab-based therapy showed no survival benefit for patients with type II cryoglobulinemic vasculitis compared to other treatments.

Conclusions and Relevance

In this cohort study, among CV subtypes in patients with Sjögren disease, only type II cryoglobulinemic vasculitis was associated with poor prognosis. Early recognition and monitoring for systemic complications, particularly lymphoma, are essential in these patients. Further research is needed to evaluate optimal treatment strategies for improving outcomes.