Infections in VEXAS syndrome: a systematic review of the literature.

Vacuolation, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a multisystem disease for which chronic immunosuppression is needed. Opportunistic infections are common; however, a clear prophylaxis regimen is not defined. A systematic review of the literature was undertaken. Six publications with 123 patients were evaluated. Of 86 patients with demographic data; most were males (n = 85, 98.8 %) and median age was 73 years. UBA1 mutational status was reported in 80 patients: p.Met41Thr (n = 43, 53.8 %), p.Met41Val (n = 17, 21.3 %) and p.Met41Leu (n = 12, 15.0 %) were most common. In these patients, 48 (60 %) had underlying myelodysplastic syndrome. Many of the patients had multiple hospitalizations. Infections were reported as follows: COVID19 (n = 20), Pneumocystis jiroveci pneumonia (PJP) (n = 16), nontuberculous mycobacterium (NTM) species (n = 16), Enterobacteriaceae species (n = 14), Legionella species (n = 13), Varicella Zoster virus (n = 11) and Herpes Simplex Virus (n = 8) infections, respectively. Daily prednisolone dose was at, or greater than 10 mg and overall median long term steroid treatment duration was 3.1 years. Notably, for NTM the median daily prednisolone dose was 12.5 mg. Median prednisolone dosing for PJP was only reported in one of the publications, comprising six patients, at 17 mg per day. Where data was available, 45 of the 95 patients (47.3 %) were deceased at last follow-up. Of the 45 deaths, 32 (71.1 %) were attributed to the intercurrent infection. In summary, opportunistic infections are commonly reported in VEXAS syndrome. Prophylaxis for such infections remains paramount but no clear consensus on recommendations exists, highlighting the need for prospective studies. Moreover, furthering our understanding of pathophysiology of VEXAS syndrome and impairment in both innate and humoral immunity may clarify its contribution to infections in addition to high background immunosuppressive therapies.