Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients

doi:10.1111/bjd.20805

Multicenter Study

. 2022 Mar;186(3):564-574.

doi: 10.1111/bjd.20805. Epub 2021 Nov 28.

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients

S Georgin-Lavialle¹, B Terrier², A F Guedon³, M Heiblig⁴, T Comont⁵, E Lazaro⁶, V Lacombe⁷, L Terriou⁸, S Ardois⁹, J-D Bouaziz¹⁰, A Mathian¹¹, G Le Guenno^{12

13}, A Aouba¹⁴, R Outh¹⁵, A Meyer¹⁶, M Roux-Sauvat¹⁷, M Ebbo¹⁸, L P Zhao¹⁹, A Bigot²⁰, Y Jamilloux²¹, V Guillotin^{12

13}, E Flamarion²², P Henneton²³, G Vial^{12

13}, V Jachiet²⁴, J Rossignol²⁵, S Vinzio²⁶, T Weitten²⁷, J Vinit²⁸, C Deligny²⁹, S Humbert³⁰, M Samson³¹, N Magy-Bertrand³⁰, T Moulinet³², R Bourguiba¹, T Hanslik³³, C Bachmeyer¹, M Sebert¹⁹, M Kostine³⁴, B Bienvenu³⁵, P Biscay³⁶, E Liozon³⁷, L Sailler³⁸, F Chasset³⁹, A Audemard-Verger²⁰, E Duroyon⁴⁰, G Sarrabay⁴¹, F Borlot⁴², C Dieval⁴³, T Cluzeau⁴⁴, P Marianetti⁴⁵, H Lobbes^{12

13}, G Boursier⁴¹, M Gerfaud-Valentin⁴, J Jeannel²², A Servettaz⁴⁵, S Audia³¹, M Larue⁴⁶, B Henriot⁴⁷, B Faucher¹⁸, J Graveleau⁴⁸, B de Sainte Marie^{12

13}, J Galland⁴⁹, L Bouillet²⁶, C Arnaud³⁸, L Ades¹⁹, F Carrat³, P Hirsch⁵⁰, P Fenaux¹⁹, O Fain²⁴, P Sujobert³⁰, O Kosmider⁴⁰, A Mekinian²⁴; French VEXAS group; GFEV, GFM, CEREMAIA, MINHEMON

Affiliations

¹ Sorbonne Université, AP-HP, Hôpital Tenon, Service de Médecine Interne, CeRéMAIA, Paris, France.
² Department of Internal Medicine, University of Paris, AP-HP, Cochin Hospital, Paris, France.
³ Sorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Département de Santé Publique, Hôpital Saint-Antoine, AP-HP, Paris, France.
⁴ Department of Haematology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France.
⁵ Department of Internal Medicine and Clinical Immunology, University Hospital of Toulouse, Toulouse, France.
⁶ Department of Internal Medicine and Infectious Diseases, Hôpital Haut-Lévêque, Bordeaux, France.
⁷ Department of Internal Medicine, Angers University Hospital, Angers, France.
⁸ Department of Internal Medicine, Lille University Hospital, Lille, France.
⁹ Service de Médecine Interne, CHU de Rennes, Rennes, France.
¹⁰ Université de Paris, Service de Dermatologie, Hôpital Saint Louis, AP-HP, INSERM U944, Paris, France.
¹¹ Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Paris, France.
¹² Department of Internal Medicine and Clinical Immunology, University Hospital Centre of Bordeaux, Saint Andre Hospital, Bordeaux, France.
¹³ CHU de Clermont-Ferrand, Hôpital Estaing, Service de Médecine Interne, Clermont-Ferrand, France.
¹⁴ Department of Internal Medicine, Caen Université, Hôpital de Caen, Caen, France.
¹⁵ Service de Médecine Interne et Générale, Centre Hospitalier de Perpignan, Perpignan, France.
¹⁶ Service d'Immunologie Clinique et Médecine Interne, Nouvel Hôpital Civil, CHU Strasbourg, Strasbourg, France.
¹⁷ GHND, Centre Hospitalier Pierre Oudot, BP 40348, Bourgoin-Jallieu Cedex, France.
¹⁸ Department of Internal Medicine, Aix Marseille Université, AP-HM, Hôpital de la Timone, Marseille, France.
¹⁹ Hematology Department, AP-HP, CHU of Saint Louis, Paris, France.
²⁰ Department of Internal and Clinical Medicine, University of Tours, Tours, France.
²¹ Department of Internal Medicine and Clinical Immunology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France.
²² Université de Paris, Service de Médecine Interne, Paris, France.
²³ Service de Médecine Vasculaire, CHU Montpellier, Montpellier, France.
²⁴ Sorbonne Université, AP-HP, Hôpital Saint Antoine, Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DMU i3), Paris, France.
²⁵ Université de Paris, Service d'Hématologie, Necker Enfants Malades, Paris, France.
²⁶ Service de Médecine Interne, Groupe Hospitalier Mutualiste, Grenoble, France.
²⁷ Service de Médecine Interne, Centre Hospitalier (CHICAS), Gap, France.
²⁸ Service de Médecine Interne, Centre Hospitalier, Chalons, France.
²⁹ Service de Rhumatologie - Médecine Interne 5D, CHU de Martinique, Hôpital P. Zobda-Quitman, France.
³⁰ CHU de Besançon, Service de Médecine Interne, Besançon, France.
³¹ Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France.
³² Department of Internal Medicine and Clinical Immunology, Regional Competence Center for Systemic and Autoimmune Rare Diseases, Nancy University Hospital, UMR 7365, IMoPA, Lorraine University, CNRS, Vandoeuvre-lès-Nancy, France.
³³ AP-HP, Hôpital Ambroise Paris, Service de Médecine Interne, Paris, France.
³⁴ Department of Rheumatology, Hôpital Haut-Lévesque, Bordeaux, France.
³⁵ Hôpital Saint Joseph, Service de Médecine Interne, Marseille, France.
³⁶ Clinique Mutualiste Pessac Médecine Interne, Pessac, France.
³⁷ Service de Médecine Interne, CHU Dupuytren, Limoges, France.
³⁸ Department of Internal Medicine, University Hospital of Toulouse, Toulouse, France.
³⁹ Sorbonne Université, Hôpital Tenon, Service de Dermatologie et Allergologie et Inflammation-Immunopathology-Biotherapy Department (DMU i3), Paris, France.
⁴⁰ Service d'Hématologie Biologique, DMU BioPhyGen GH AP-HP, Centre-University de Paris, Paris, France.
⁴¹ Laboratory of Rare and Autoinflammatory Genetic Diseases and Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), CHU Montpellier, University of Montpellier, Montpellier, France.
⁴² Service de Médecine Interne, CH Béziers, Béziers, France.
⁴³ Service de Médecine Interne et Hématologie, CH Régional, Rochefort, France.
⁴⁴ Hematology Department, CHU of Nice, Cote d'Azur University, Nice, France.
⁴⁵ CHU de REIMS, Service de Médecine Interne, Maladies Infectieuses, Immunologie Clinique, Reims, France.
⁴⁶ AP-HP, Service de Rhumatologie, Hôpital Henri Mondor, Créteil, France.
⁴⁷ Service de Médecine Interne, Centre Hospitalier René Pleven, Dinan, France.
⁴⁸ CHU de Nantes Hôtel Dieu, Service de Médecine Interne, Nantes, France.
⁴⁹ Service de Médecine Interne, Hôpital Fleyriat, Centre Hospitalier Bourg-en-Bresse, France.
⁵⁰ Sorbonne Université, AP-HP, Hôpital Saint Antoine, Service d'Hématologie Biologique, Paris, France.

PMID: 34632574
DOI: 10.1111/bjd.20805

Free article

Multicenter Study

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients

S Georgin-Lavialle et al. Br J Dermatol. 2022 Mar.

Free article

. 2022 Mar;186(3):564-574.

doi: 10.1111/bjd.20805. Epub 2021 Nov 28.

Authors

Affiliations

¹ Sorbonne Université, AP-HP, Hôpital Tenon, Service de Médecine Interne, CeRéMAIA, Paris, France.
² Department of Internal Medicine, University of Paris, AP-HP, Cochin Hospital, Paris, France.
³ Sorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Département de Santé Publique, Hôpital Saint-Antoine, AP-HP, Paris, France.
⁴ Department of Haematology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France.
⁵ Department of Internal Medicine and Clinical Immunology, University Hospital of Toulouse, Toulouse, France.
⁶ Department of Internal Medicine and Infectious Diseases, Hôpital Haut-Lévêque, Bordeaux, France.
⁷ Department of Internal Medicine, Angers University Hospital, Angers, France.
⁸ Department of Internal Medicine, Lille University Hospital, Lille, France.
⁹ Service de Médecine Interne, CHU de Rennes, Rennes, France.
¹⁰ Université de Paris, Service de Dermatologie, Hôpital Saint Louis, AP-HP, INSERM U944, Paris, France.
¹¹ Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Paris, France.
¹² Department of Internal Medicine and Clinical Immunology, University Hospital Centre of Bordeaux, Saint Andre Hospital, Bordeaux, France.
¹³ CHU de Clermont-Ferrand, Hôpital Estaing, Service de Médecine Interne, Clermont-Ferrand, France.
¹⁴ Department of Internal Medicine, Caen Université, Hôpital de Caen, Caen, France.
¹⁵ Service de Médecine Interne et Générale, Centre Hospitalier de Perpignan, Perpignan, France.
¹⁶ Service d'Immunologie Clinique et Médecine Interne, Nouvel Hôpital Civil, CHU Strasbourg, Strasbourg, France.
¹⁷ GHND, Centre Hospitalier Pierre Oudot, BP 40348, Bourgoin-Jallieu Cedex, France.
¹⁸ Department of Internal Medicine, Aix Marseille Université, AP-HM, Hôpital de la Timone, Marseille, France.
¹⁹ Hematology Department, AP-HP, CHU of Saint Louis, Paris, France.
²⁰ Department of Internal and Clinical Medicine, University of Tours, Tours, France.
²¹ Department of Internal Medicine and Clinical Immunology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France.
²² Université de Paris, Service de Médecine Interne, Paris, France.
²³ Service de Médecine Vasculaire, CHU Montpellier, Montpellier, France.
²⁴ Sorbonne Université, AP-HP, Hôpital Saint Antoine, Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DMU i3), Paris, France.
²⁵ Université de Paris, Service d'Hématologie, Necker Enfants Malades, Paris, France.
²⁶ Service de Médecine Interne, Groupe Hospitalier Mutualiste, Grenoble, France.
²⁷ Service de Médecine Interne, Centre Hospitalier (CHICAS), Gap, France.
²⁸ Service de Médecine Interne, Centre Hospitalier, Chalons, France.
²⁹ Service de Rhumatologie - Médecine Interne 5D, CHU de Martinique, Hôpital P. Zobda-Quitman, France.
³⁰ CHU de Besançon, Service de Médecine Interne, Besançon, France.
³¹ Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France.
³² Department of Internal Medicine and Clinical Immunology, Regional Competence Center for Systemic and Autoimmune Rare Diseases, Nancy University Hospital, UMR 7365, IMoPA, Lorraine University, CNRS, Vandoeuvre-lès-Nancy, France.
³³ AP-HP, Hôpital Ambroise Paris, Service de Médecine Interne, Paris, France.
³⁴ Department of Rheumatology, Hôpital Haut-Lévesque, Bordeaux, France.
³⁵ Hôpital Saint Joseph, Service de Médecine Interne, Marseille, France.
³⁶ Clinique Mutualiste Pessac Médecine Interne, Pessac, France.
³⁷ Service de Médecine Interne, CHU Dupuytren, Limoges, France.
³⁸ Department of Internal Medicine, University Hospital of Toulouse, Toulouse, France.
³⁹ Sorbonne Université, Hôpital Tenon, Service de Dermatologie et Allergologie et Inflammation-Immunopathology-Biotherapy Department (DMU i3), Paris, France.
⁴⁰ Service d'Hématologie Biologique, DMU BioPhyGen GH AP-HP, Centre-University de Paris, Paris, France.
⁴¹ Laboratory of Rare and Autoinflammatory Genetic Diseases and Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), CHU Montpellier, University of Montpellier, Montpellier, France.
⁴² Service de Médecine Interne, CH Béziers, Béziers, France.
⁴³ Service de Médecine Interne et Hématologie, CH Régional, Rochefort, France.
⁴⁴ Hematology Department, CHU of Nice, Cote d'Azur University, Nice, France.
⁴⁵ CHU de REIMS, Service de Médecine Interne, Maladies Infectieuses, Immunologie Clinique, Reims, France.
⁴⁶ AP-HP, Service de Rhumatologie, Hôpital Henri Mondor, Créteil, France.
⁴⁷ Service de Médecine Interne, Centre Hospitalier René Pleven, Dinan, France.
⁴⁸ CHU de Nantes Hôtel Dieu, Service de Médecine Interne, Nantes, France.
⁴⁹ Service de Médecine Interne, Hôpital Fleyriat, Centre Hospitalier Bourg-en-Bresse, France.
⁵⁰ Sorbonne Université, AP-HP, Hôpital Saint Antoine, Service d'Hématologie Biologique, Paris, France.

PMID: 34632574
DOI: 10.1111/bjd.20805

Abstract

Background: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome').

Objectives: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.

Methods: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded.

Results: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis.

Conclusions: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

PubMed Disclaimer

Comment in

Working towards a better understanding of VEXAS syndrome.
Nicholson LT, Madigan LM. Nicholson LT, et al. Br J Dermatol. 2022 Mar;186(3):392-393. doi: 10.1111/bjd.20949. Epub 2022 Mar 1. Br J Dermatol. 2022. PMID: 35230698 No abstract available.

Cited by

The First Korean Case of VEXAS Syndrome Caused by a UBA1 Somatic Variant.
Yoon JG, Lee S, Kim S, Kim MJ, Chang YH, Park JK, Shin DY, Moon J. Yoon JG, et al. Ann Lab Med. 2023 Mar 1;43(2):217-220. doi: 10.3343/alm.2023.43.2.217. Epub 2022 Oct 25. Ann Lab Med. 2023. PMID: 36281520 Free PMC article. No abstract available.
Sensitivity to targeted UBA1 inhibition in a myeloid cell line model of VEXAS syndrome.
Chiaramida A, Obwar SG, Nordstrom AEH, Ericsson M, Saldanha A, Ivanova EV, Griffin GK, Khan DH, Belizaire R. Chiaramida A, et al. Blood Adv. 2023 Dec 26;7(24):7445-7456. doi: 10.1182/bloodadvances.2023010531. Blood Adv. 2023. PMID: 38091008 Free PMC article.
Comparison between idiopathic and VEXAS-relapsing polychondritis: analysis of a French case series of 95 patients.
Khitri MY, Guedon AF, Georgin-Lavialle S, Terrier B, Saadoun D, Seguier J, le Besnerais M, De Moreuil C, Denis G, Gerfaud-Valentin M, Allain JS, Maria A, Bouillet L, Grobost V, Galland J, Kosmider O, Dumont A, Devaux M, Subran B, Schmidt J, Marianetti-Guingel P, Audia S, Palat S, Roux-Sauvat M, Jachiet V, Hirsch P, Fain O, Mekinian A; French VEXAS group and MINHEMON. Khitri MY, et al. RMD Open. 2022 Jul;8(2):e002255. doi: 10.1136/rmdopen-2022-002255. RMD Open. 2022. PMID: 35868738 Free PMC article.
Spectrum of clonal hematopoiesis in VEXAS syndrome.
Gutierrez-Rodrigues F, Kusne Y, Fernandez J, Lasho T, Shalhoub R, Ma X, Alessi H, Finke C, Koster MJ, Mangaonkar A, Warrington KJ, Begna K, Xie Z, Ombrello AK, Viswanatha D, Ferrada M, Wilson L, Go R, Kourelis T, Reichard K, Olteanu H, Darden I, Hironaka D, Alemu L, Kajigaya S, Rosenzweig S, Calado RT, Groarke EM, Kastner DL, Calvo KR, Wu CO, Grayson PC, Young NS, Beck DB, Patel BA, Patnaik MM. Gutierrez-Rodrigues F, et al. Blood. 2023 Jul 20;142(3):244-259. doi: 10.1182/blood.2022018774. Blood. 2023. PMID: 37084382 Free PMC article.
Kidney involvement in VEXAS syndrome: insights from a rare case of secondary amyloidosis and systematic review of renal biopsy-confirmed reports.
Ştefan G, Niculescu A, Cinca S, Chiriac C, Zugravu A, Cristina P, Ionescu RA, Pompilian VM, Petre N, Căpusa C, Stancu S. Ştefan G, et al. Clin Rheumatol. 2025 Jul;44(7):3101-3108. doi: 10.1007/s10067-025-07506-9. Epub 2025 May 30. Clin Rheumatol. 2025. PMID: 40445522 Free PMC article. Review.

See all "Cited by" articles

References

1. Beck DB, Ferrada MA, Sikora KA et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 2020; 383:2628-38.
1. van der Made CI, Potjewijd J, Hoogstins A et al. Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of VEXAS patients. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2021.05.014.
1. Ferrada MA, Sikora KA, Luo Y et al. Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS syndrome. Arthritis Rheumatol 2021; 73:1886-95.
1. Tsuchida N, Kunishita Y, Uchiyama Y et al. Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2021-220090.
1. Bourbon E, Heiblig M, Gerfaud-Valentin M et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 2021; 137:3682-4.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

[1] Beck DB, Ferrada MA, Sikora KA et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 2020; 383:2628-38.

[2] Beck DB, Ferrada MA, Sikora KA et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 2020; 383:2628-38.

[3] van der Made CI, Potjewijd J, Hoogstins A et al. Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of VEXAS patients. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2021.05.014.

[4] van der Made CI, Potjewijd J, Hoogstins A et al. Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of VEXAS patients. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2021.05.014.

[5] Ferrada MA, Sikora KA, Luo Y et al. Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS syndrome. Arthritis Rheumatol 2021; 73:1886-95.

[6] Ferrada MA, Sikora KA, Luo Y et al. Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS syndrome. Arthritis Rheumatol 2021; 73:1886-95.

[7] Tsuchida N, Kunishita Y, Uchiyama Y et al. Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2021-220090.

[8] Tsuchida N, Kunishita Y, Uchiyama Y et al. Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2021-220090.

[9] Bourbon E, Heiblig M, Gerfaud-Valentin M et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 2021; 137:3682-4.

[10] Bourbon E, Heiblig M, Gerfaud-Valentin M et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 2021; 137:3682-4.

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients

Affiliations

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients

Authors

Affiliations

Abstract

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous

Abstract

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous