Abstract: AB1456
Authors: Melkonian A et al.

zum Abstract

Key content:
VEXAS syndrome is an adult-onset autoinflammatory disease primarily affecting males, caused by a somatic mutation of the UBA1 gene in hematopoietic progenitor cells. It was first reported in The New England Journal of Medicine in October 2020 by the principal author David B. Beck.
The name VEXAS is an acronym deriving from the core features of the disease: V: Vacuoles, identified in the bone marrow stem cells E: E1 ubiquitin conjugating enzyme encoded by the UBA1 gene is mutated in patients X: The mutated UBA1 gene is recessive and located on the X-chromosome A: Patients with VEXAS present with a wide array of Autoinflammatory conditions S: The mutations which cause VEXAS are Somatic: they are acquired throughout life, not inherited, and are not passed on to offspring.
In this case series from a French multicenter registry between November 2020 and January 2022 the clinical characteristics, laboratory findings and outcomes of VEXAS syndrome were described.
Among 256 patients, 207/221 (94%) were males with median age at diagnosis of 65 years [49-86]. Main clinical features were skin lesions (n=215; 84%), non-infectious fever (n=121; 47%), lung involvement (n=146; 57%), relapsing chondritis (n=69; 27%), venous thrombosis (n=128; 50%), lymph nodes (n=55; 21%), and arthralgia (n=65; 25%) with arthritis (n=26). Ocular inflammatory involvement was present in 119 cases (46%), mainly uveitis (n=21) and scleritis/ episcleritis (n=43). Peripheral nervous system was noted in 18 patients (7%) with peripheral neuropathy (n=11), polyneuritis (n=3) and chronic inflammatory demyelinating polyneuropathy (n=5). The skin lesions were mainly neutrophilic dermatosis (n=74) and vasculitis (n=45). Hematological diseases were myelodysplastic syndrome (n= 81; 32%), monoclonal gammopathy of unknown significance (n=18),
chronic myelomonocytic leukemia (n=7). AA amyloidosis was present in 2 cases. Median CRP levels were at 56 [1-423] mg/l.
Previous immunosuppressive therapies were methotrexate (n=15; 6%), cyclophosphamide (n=6; 3%), MMF (n=5; 4%). JAK inhibitors were used in 24 cases and were stopped in 5 cases (3 for inefficacy and 2 for adverse events). IL1R inhibitors were used in 12 cases with discontinuation for inefficacy (n=7) and adverse events (n=1), and IL6R inhibitors in 12 cases with discontinuation for inefficacy in 4 cases and adverse events in 1 case.

In this study from a French patient registry, 256 patients with VEXAS syndrome were described. This number of patients is astounding, since this adult-onset autoinflammatory disease was first described in October 2020. There was a wide range of autoinflammatory and hematological manifestations. JAK and Il-6 inhibitors seem to have a particularly good therapeutic effect.

Dr. Thomas Langenegger