Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) took the centre stage when it was first introduced at ACR20 last year. It got everyone’s thinking that they might have encountered one or two patients in their rheumatology lifetime who might have this condition. One year on, more cases have been reported and this article summarises some breakthroughs pertaining to research in VEXAS.
At ACR21, Koster et al (Abstract#1457) described a case series of 9 patients with VEXAS. The most frequent variant (i.e. 7/9) was the p.Met41Thr. The top 3 common features were refractory constitutional symptoms (88%), ear/nose chondritis (55%) and inflammatory arthritis (55%). All patients had significantly elevated inflammatory markers and macrocytic anaemia while two-thirds had thrombocytopenia. 8/9 patients had bone marrow biopsies which showed hypercellular and vacuolization of the erythroid (100%) and/or myeloid precursors (75%). In terms of therapy, no other effective immunosuppressant apart from prednisolone ≥20 mg/day was observed. Interestingly, 1/9 patient with co-existing plasma cell myeloma received plasma cell directed therapy followed by autologous stem cell transplant resulted in improvement of the inflammatory response.
Since VEXAS was associated with high rate of deaths, can we predict poor prognostic factors? Ferrada et al. (Abstract#1426) presented data from a multicentre observational study of 83 patients with VEXAS. Comparing clinical features between the three most common variants, patients with the p.Met41Val variant were least likely to have relapsing polychondritis (22%) but most likely to feature an undifferentiated fever (55%). Sweet’s syndrome occurred the most (60%) in patients the p.Met41Leu variant. In multivariable analysis, transfusion dependence (HR 4.47 (95% CI 1.8-11.1) and the p.Met41Val variant (2.56 (1-6.4) were associated with increased risk of time-to-death while ear chondritis conferred a protective role (0.32 (0.1-0.9).
The results above highlighted the heterogeneity of VEXAS and the importance of careful characterisation of our patients as some features appeared to be independently predictive of mortality. The success of plasma cell therapy and autologous stem cell transplantation in one patient is intriguing and could catalyse future prospective definitive study in the hunt of effective therapies for this rare but potentially deadly condition.