Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry.
Benjamin de Valence
(1)
,
Marion Delaune
(2)
,
Yann Nguyen
(3)
,
Vincent Jachiet
(1)
,
Mael Heiblig
(4)
,
Alexis Jean
(5)
,
Stanislas Riescher Tuczkiewicz
(6)
,
Pierrick Henneton
(7)
,
Philippe Guilpain
(7)
,
Nicolas Schleinitz
(8)
,
Guillaume Le Guenno
(9)
,
Hervé Lobbes
(9)
,
Valentin Lacombe
(10)
,
Samuel Ardois
(11)
,
Estibaliz Lazaro
(5)
,
Vincent Langlois
,
Rodreau Outh
(12)
,
Julien Vinit
(13)
,
Jean-Philippe Martellosio
(14)
,
Paul Decker
(15)
,
Thomas Moulinet
(15)
,
Yannick Dieudonne
(16)
,
Adrien Bigot
(17)
,
Louis Terriou
(18, 19)
,
Alexandre Vlakos
(20)
,
Baptiste de Maleprade
(21)
,
Guillaume Denis
(22)
,
Jonathan Broner
(23)
,
Marie Kostine
(24)
,
Sebastien Humbert
(25)
,
François Lifermann
(26)
,
Maxime Samson
(27)
,
Susann Pechuzal
,
Achille Aouba
(28)
,
Olivier Kosmider
,
Jeremie Dion
(2)
,
Sylvie Grosleron
(29)
,
Rim Bourguiba
(30)
,
Benjamin Terrier
(31)
,
Sophie Georgin-Lavialle
(30)
,
Olivier Fain
(1)
,
Arsène Mekinian
(1)
,
Marjolaine Morgand
(1)
,
Thibault Comont
(2)
,
Jérôme Hadjadj
(1)
1
CHU Saint-Antoine [AP-HP]
2 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
3 Hôpital Beaujon [AP-HP]
4 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
5 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
6 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
7 Hôpital Saint Eloi [CHU Montpellier]
8 TIMONE - Hôpital de la Timone [CHU - APHM]
9 CHU Estaing [Clermont-Ferrand]
10 CHU Angers - Centre Hospitalier Universitaire d'Angers
11 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
12 Centre Hospitalier Saint Jean de Perpignan
13 Centre Hospitalier Chalon-sur-Saône William Morey
14 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
15 CHU Nancy - Centre Hospitalier Universitaire de Nancy
16 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
17 CHU Trousseau [Tours]
18 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
19 LIRIC - Lille Inflammation Research International Center - U 995
20 GH70 - Groupe Hospitalier de La Haute-Saône
21 CHU Rouen
22 CH Rochefort - Centre Hospitalier de Rochefort
23 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
24 Groupe hospitalier Pellegrin
25 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
26 Centre Hospitalier de Dax
27 Service d'hématologie biologique [CHU de Dijon]
28 CHU Caen
29 Centre Hospitalier Agen-Nérac
30 CHU Tenon [AP-HP]
31 Hôpital Cochin [AP-HP]
2 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
3 Hôpital Beaujon [AP-HP]
4 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
5 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
6 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
7 Hôpital Saint Eloi [CHU Montpellier]
8 TIMONE - Hôpital de la Timone [CHU - APHM]
9 CHU Estaing [Clermont-Ferrand]
10 CHU Angers - Centre Hospitalier Universitaire d'Angers
11 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
12 Centre Hospitalier Saint Jean de Perpignan
13 Centre Hospitalier Chalon-sur-Saône William Morey
14 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
15 CHU Nancy - Centre Hospitalier Universitaire de Nancy
16 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
17 CHU Trousseau [Tours]
18 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
19 LIRIC - Lille Inflammation Research International Center - U 995
20 GH70 - Groupe Hospitalier de La Haute-Saône
21 CHU Rouen
22 CH Rochefort - Centre Hospitalier de Rochefort
23 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
24 Groupe hospitalier Pellegrin
25 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
26 Centre Hospitalier de Dax
27 Service d'hématologie biologique [CHU de Dijon]
28 CHU Caen
29 Centre Hospitalier Agen-Nérac
30 CHU Tenon [AP-HP]
31 Hôpital Cochin [AP-HP]
Vincent Jachiet
- Fonction : Auteur
- PersonId : 1210142
- ORCID : 0000-0002-1163-9796
- IdRef : 273433431
Vincent Langlois
- Fonction : Auteur
Susann Pechuzal
- Fonction : Auteur
Olivier Kosmider
- Fonction : Auteur
Olivier Fain
- Fonction : Auteur
- PersonId : 1166060
- ORCID : 0000-0002-1974-3870
- IdRef : 069538476
Arsène Mekinian
- Fonction : Auteur
- PersonId : 818189
- ORCID : 0000-0003-2849-3049
- IdRef : 131898493
Résumé
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.