Ab0020 Susceptibility to Mycobacterial Infection in Vexas Syndrome

Background: Disseminated Non-Tuberculous Mycobacterial infections (dNTMi) have mainly been described in patients living with HIV at the AIDS stage with a CD4 count < 50/mm³. Data regarding the etiological spectrum of HIV-negative dNTMi in Europe are limited. In the recent years, we were puzzled to diagnose dNTMi in several patients treated for an auto-immune/inflammatory disease including 2 VEXAS patients. Objectives: The aim of this study was to describe clinical features and immunological conditions associated with dNTMi at our center. Methods: We retrospectively reviewed the medical charts of all adult patients diagnosed with dNTMi at Nantes University Hospital between January 2008 and December 2020. The criteria for dNTMi were either a positive blood or bone marrow culture, 2 positive cultures from 2 distinct sites (stool, biopsy...) or a positive culture from a deep site (bone, soft tissue…) with at least 2 distinct involved sites. Patients were divided into 2 groups according to HIV serologic status. Results: Among 20 cases, 11 were HIV-negatives. Diagnostic delay was highly variable (up to 1 year) in both groups, without significant difference. Clinical manifestations included fever (15/20, 75%), pulmonary infiltrates (8/20, 40%), lymphadenopathy (8/20, 40%) and cytopenia (13/20, 65%). In HIV-negative group, 6 out of 11 (54%) were treated with corticosteroids (Cs) and/or immunosuppressants. In this group, only 1 patient lived with an organ transplant, and 1 had GATA-2 deficiency. By contrast, 3 had a myeloid neoplasm, 3 had a chronic immune-mediated disease, and 2 had a VEXAS syndrome. One had no identified etiology (Figure 1). Among 3 patients with myeloid neoplasm, none had received prior immunosuppressive/cytotoxic treatment. Two had dNTMi and myeloid neoplasm diagnosed simultaneously (1 Phi+ CML and 1 acute promyeloblastic leukemia) and one had transfusion-dependent 5q- myelodysplastic syndrome, diagnosed one year prior to infection. Among 3 patients with an immune-mediated disease, 1 had refractory antisynthetase syndrome treated with rituximab, mycophenolate mofetil and low-dose Cs, and 1 had multi-organ sarcoidosis. The last was an asplenic patient with immunological thrombocytopenic purpura refractory to rTPO agonists who had received azathioprine, vinblastine infusion and multiple courses of Cs. Among 2 VEXAS, one had a Sweet syndrome with orbital cellulitis and lung micronodules under anakinra and Cs for less than 1 year. He died soon after anti-mycobacterial regimen was started. The second one received hydroxychloroquine and Cs for a steroid-dependant polychondritis-like multi-systemic disease. Past therapies only included colchicine and Methotrexate. Systemic symptoms improved after anti-mycobacterial regimen. He died 2 years later (cardiac failure). Biologically, CD4 count was significantly higher in HIV-negative cases (median CD4: 515/mm3 vs. 38/mm3, p<0.001). Monocyte count was similar in both groups (median: 420/mm3) (Figure 2). Monocytopenia (≤ 200/mm3) was present in 2/9 (22%) of seropositive cases and 5/11 (45%) of seronegative patients. Conclusion: Our findings highlight that VEXAS may be an emergent cause of dNTMi. Two other underappreciated predisposing conditions were myeloid neoplasm and immune-mediated disease. dNTMi is a difficult to diagnose opportunistic infection. Thus, rheumatologists should have a high degree of suspicion in refractory VEXAS patients. Along with Cs exposure, disease-specific monocyte dysfunction may contribute to NTMi susceptibility. Recent data suggest that the burden, etiological spectrum, and prognostic impact of infections seen in VEXAS patient remain to be fully appreciated [1]. REFERENCES: [1] De Valence B, et al. Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry. Ann Rheum Dis. 2023:ard-2023-224819. Acknowledgements: NIL. Disclosure of Interests: None declared.