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Autoinflammatory disorders
Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry
  1. Benjamin de Valence1,
  2. Marion Delaune2,
  3. Yann Nguyen3,
  4. Vincent Jachiet1,
  5. Mael Heiblig4,
  6. Alexis Jean5,
  7. Stanislas Riescher Tuczkiewicz6,
  8. Pierrick Henneton7,
  9. Philippe Guilpain7,
  10. Nicolas Schleinitz8,
  11. Guillaume Le Guenno9,
  12. Hervé Lobbes9,
  13. Valentin Lacombe10,
  14. Samuel Ardois11,
  15. Estibaliz Lazaro5,
  16. Vincent Langlois12,
  17. Roderau Outh13,
  18. Julien Vinit14,
  19. Jean-Philippe Martellosio15,
  20. Paul Decker16,
  21. Thomas Moulinet16,
  22. Yannick Dieudonné17,
  23. Adrien Bigot18,
  24. Louis Terriou19,
  25. Alexandre Vlakos20,
  26. Baptiste de Maleprade21,
  27. Guillaume Denis22,
  28. Jonathan Broner23,
  29. Marie Kostine24,
  30. Sebastien Humbert25,
  31. Francois Lifermann26,
  32. Maxime Samson27,
  33. Susann Pechuzal28,
  34. Achille Aouba29,
  35. Olivier Kosmider30,
  36. Jeremie Dion2,
  37. Sylvie Grosleron31,
  38. Rim Bourguiba32,
  39. Benjamin Terrier33,
  40. Sophie Georgin-Lavialle32,
  41. Olivier Fain1,
  42. Arsène Mekinian1,
  43. Marjolaine Morgand1,
  44. Thibault Comont2,
  45. Jerome Hadjadj1
  46. French VEXAS Group
    1. 1 Médecine Interne, Sorbonne université, Hopital Saint-Antoine, Paris, France
    2. 2 Médecine interne, Université Toulouse III-Paul Sabatier Faculté de santé, Centre Hospitalier Universitaire de Toulouse Pole IUC de Toulouse Oncopole CHU, Toulouse, France
    3. 3 Médecine interne, Université Paris Cité, Hôpital Beaujon, Clichy, France
    4. 4 Hématologie clinique, Université Claude Bernard Lyon 1, Centre Hospitalier Lyon-Sud, Pierre-Benite, France
    5. 5 Médecine interne, CHU de Bordeaux, Bordeaux, France
    6. 6 Médecine interne, CHU Nantes, Nantes, France
    7. 7 Service de Médecine Interne A, Hôpital Saint Eloi, CHRU de Montpellier, Montpellier, France
    8. 8 Médecine interne, Aix-Marseille Universite, Hôpital de la Timone, Marseille, France
    9. 9 Médecine interne, CHU Estaing, Clermont-Ferrand, France
    10. 10 Médecine interne et immunologique clinique, CHU Angers, Angers, France
    11. 11 Médecine interne, CHU Rennes, Rennes, France
    12. 12 Médecine interne et infectieuse, Hospital Group Le Havre, Le Havre, France
    13. 13 Service de médecine interne et générale, CH Perpignan, Perpignan, France
    14. 14 Médecine interne, Hospital Centre Chalon-sur-Saon, Chalon-sur-Saone, France
    15. 15 Médecine interne, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
    16. 16 Médecine interne et immunologie clinique, CHU de Nancy, Nancy, France
    17. 17 Immunologie Clinique et Médecine Interne, CHU de Strasbourg, Strasbourg, France
    18. 18 Médecine interne, CHU de Tours, Tours, France
    19. 19 Médecine interne – hématologie, CHU Lille, Lille, France
    20. 20 Médecine interne, Haute-Saône Hospital Group Vesoul Site, Vesoul, France
    21. 21 Rhumatologie, CHU de Rouen, Rouen, France
    22. 22 Médecine interne et hématologie, Centre Hospitalier de Rochefort, Rochefort, France
    23. 23 Médecine interne, CHU Nimes, Nimes, France
    24. 24 Rhumatologie, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux, France
    25. 25 Hématologie, Centre Hospitalier Universitaire de Besancon, Besancon, France
    26. 26 Service de médecine interne, CH Dax, Dax, France
    27. 27 Médecine interne, CHU Dijon, Dijon, France
    28. 28 Médecine interne-polyvalente, Hôpitaux Drôme Nord, Romans, France
    29. 29 Médecine interne, CHU Caen, Caen, France
    30. 30 Service d’Hématologie Biologique, DMU BioPhyGen, APHP, Paris, France
    31. 31 Médecine interne, Centre Hospitalier Agen-Nérac, Agen, France
    32. 32 Médecine interne, CEREMAIA, Sorbonne Université, Hospital Tenon, Paris, France
    33. 33 Médecine interne, Université Paris Cité, Hospital Cochin, Paris, France
    1. Correspondence to Dr Jerome Hadjadj, Médecine interne, Sorbonne université, Hopital Saint-Antoine, Paris, Île-de-France, France; jerome.hadjadj{at}aphp.fr

    Abstract

    Introduction Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors.

    Methods Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models.

    Results Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV-2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5–7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections.

    Conclusion VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.

    • Immune System Diseases
    • Therapeutics
    • Glucocorticoids
    • Tumor Necrosis Factor Inhibitors
    • Inflammation

    Data availability statement

    Data are available on reasonable request.

    https://doi.org/10.1136/ard-2023-224819

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      Data availability statement

      Data are available on reasonable request.

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      Footnotes

      • Handling editor Josef S Smolen

      • Twitter @MarieKostine, @Maxime_Samson21, @SophieGeorgin

      • BdV, MD, TC and JH contributed equally.

      • Collaborators French VEXAS group: Isabelle Melki, Pierre Fenaux, Lionel Ades, Alexandra Audemard, Mikael Ebbo, Yvan Jamilloux, Odile Rauzy, Alexandre Belot, Raphaël Borie, Alexis Mathian, Laurent Arnaud, Francois Chasset, Jean-David Bouaziz, Pierre Sujobert, Ygal Benhamou, Gaetan Sauvetre, Khalil El-Karoui, Laurent Sailler, Guillaume Moulis, Sébastien De Almeida Chaves, François Rodrigues.

      • Contributors BdV and MD performed research, analysed results and wrote the paper. YN performed statistical analysis. All other authors provided clinical or biological care and reviewed the paper. TC and JH analysed results and reviewed the paper. JH is the guarantor for this work and had access to the data.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests None declared.

      • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.