USAID Associated with Myeloid Neoplasm and VEXAS Syndrome: Two Differential Diagnoses of Suspected Adult Onset Still’s Disease in Elderly Patients

Marion Delplanque (1, 2) , Achille Aouba (3) , Pierre Hirsch (4, 5) , Pierre Fenaux (6) , Julie Graveleau (7) , Florent Malard (4, 5) , Damien Roos-Weil (8) , Nabil Belfeki (9) , Louis Drevon (4, 5) , Artem Oganesyan (10) , Matthieu Groh (11) , Matthieu Mahévas (12) , Jerome Razanamahery (13) , Gwenola Maigne (3) , Matthieu Décamp (14) , Sébastien Miranda (15) , Thomas Quemeneur (16) , Julien Rossignol (17) , Laurent Sailler (18) , Marie Sébert (6) , Louis Terriou (19) , Anna Sevoyan (10) , Yervand Hakobyan (10) , Sophie Georgin-Lavialle (1, 2) , Arsène Mekinian (4, 5)

1 GRC 28 - GRAASU - Groupe de recherche clinique Amylose AA Sorbonne Université
2 CHU Tenon [AP-HP]
3 Service de médecine interne [CHU Caen]
4 CHU Saint-Antoine [AP-HP]
5 CRSA - Centre de Recherche Saint-Antoine
6 AP-HP - Hopital Saint-Louis [AP-HP]
7 Centre hospitalier de Saint-Nazaire
8 CHU Pitié-Salpêtrière [AP-HP]
9 Centre hospitalier Marc Jacquet (Melun)
10 NAS RA - National Academy of Sciences of the Republic of Armenia [Yerevan]
11 Hôpital Foch [Suresnes]
12 Hôpital Henri Mondor
13 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
14 Service de Génétique [CHU Caen]
15 Service de Médecine Interne [CHU Rouen]
16 Centre hospitalier [Valenciennes, Nord]
17 Hôpital Necker - Enfants Malades [AP-HP]
18 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
19 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]

Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusions: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.

Mots clés: adult-onset Still's disease; myelodysplastic syndrome; SAID; USAID; VEXAS; azacytidine

Domaines: Médecine humaine et pathologie

Marion Delplanque, Achille Aouba, Pierre Hirsch, Pierre Fenaux, Julie Graveleau, et al.. USAID Associated with Myeloid Neoplasm and VEXAS Syndrome: Two Differential Diagnoses of Suspected Adult Onset Still’s Disease in Elderly Patients. Journal of Clinical Medicine, 2021, 10 (23), pp.5586. ⟨10.3390/jcm10235586⟩. ⟨hal-03511806⟩