Real‐world outcomes of vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome at a tertiary referral centre

Real-world outcomes of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome at a tertiary referral centreTo the Editor, Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently described clonal myeloid disorder that presents with autoinflammatory manifestations.It arises from the acquisition of somatic mutations in UBA1, a gene that encodes the ubiquitin-like modifier activating enzyme E1 and lies on the X chromosome. 1 This most commonly manifests as a treatment-refractory and often fatal autoinflammatory disease in older men, but women can rarely be affected.2,3 Other systemic manifestations include dermatological involvement, colitis, pneumonitis and thrombosis.4 The haematological features of VEXAS include prominent vacuolation in the erythroid and myeloid precursors in the bone marrow, as well as a macrocytic anaemia and predisposition towards myelodysplastic syndromes (MDS) and monoclonal gammopathies.5 Identification of somatic, inactivating mutations in UBA1 is mandatory to establish the diagnosis of VEXAS.These most commonly occur at the p.Met41 codon, but novel mutations are now being described.6 Corticosteroids are effective in reducing autoinflammatory manifestations of VEXAS but result in substantial toxicity, particularly with long-term exposure.6,7 First-line steroid-sparing treatments include anti-interleukin (IL)-1 agents, anti-IL6 agents (e.g.tocilizumab) and Janus kinase inhibitors for patients with primarily inflammatory manifestations.8,9 For patients with concomitant MDS and primarily haematological manifestations, chemotherapy agents such as azacitidine are often used.10 Allogeneic haematopoietic cell transplantation (allo-HCT) is a potentially curative option but can be associated with significant treatmentrelated morbidity and mortality.11,12 The optimal approach for allo-HCT in VEXAS is not yet known.13 The majority of data on outcomes in VEXAS syndrome come from large cohorts ascertained at the National Institutes of Health and by other large collaborative groups, and there remains a need to understand clinical presentations and treatment patterns in real-world settings.To address this, we retrospectively analysed a cohort of consecutive patients treated at a Canadian tertiary referral centre.Medical records were examined by two independent reviewers using a standardized form designed to capture demographic features, clinical characteristics, peripheral

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.