The rare disease was only discovered in 2020 and originates from a mutation of the UBA1 gene. Symptoms are similar to those of hematologic and rheumatologic disorders
Is called VEXAS syndromea new autoinflammatory disease rare and serious that, if left untreated, it can be lethal. The disease, induced by innate immunity, in particular by the cytokine interleukin -1, has clinical features that place it between rheumatological and hematological diseases. Those who have it often wander from one specialist to another (pulmonologist, rheumatologist, urologist, dermatologist) in an attempt to give a name to a pathology that has a great impact on the quality of life. Although the syndrome is rare, it has one high mortality: About half of people over 50 die within 5 years of diagnosis. THE symptoms of the syndrome are several: unexplained fever, low blood oxygen levelssigns of chronic inflammation, anemia, reduced white blood cellssymptoms common to myelodysplastic syndromes, namely, bone marrow diseases leading to reduced cell production he explains Charles Selmihead of rheumatology and immunology at the Humanitas hospital in Milan and professor at Humanitas University.
The UBA1 mutation
VEXAS stands for vascuoles, E1 enzyme, X-linked, autoinflammatory, somatic and is based on the most prominent features of the syndrome. The fact that arriving at a diagnosis is difficult has a good reason: until recently, its existence was not known. The syndrome was only discovered in 2020 by the National Institutes of Health scientists who described it on the New England Journal of Medicine. The disease was identified through genomics “in reverse” – says Selmi -. There were a number of case samples of unnamed diseases in the NIH biobank, and the scientists sequenced the genome of these cases, finding two patients with the UBA1 mutationwhich is created in the course of life, linked to the X chromosome. From the moment in which the disease was discovered and then searched for, it was found all over the world in people who until then had had unclear diagnoses, above all vasculitis, or inflammation of veins or arteries.
How widespread is the syndrome?
The inflammatory syndrome seems to be more widespread than previously thought according to the results of a survey that studied its prevalence just published in JAMA. Research estimates that approx 1 in 13,500 people in the United States have mutations in the UBA1 genewhich lead to develop VEXAS syndrome with age. In the observational study, researchers analyzed the medical records of 163,096 men and women enrolled in the Pennsylvania health system from January 1996 to January 2022 who agreed to undergo a blood DNA screen to identify genetic disorders. Eleven of them had the UBA1 mutation, all with VEXAS symptoms (only two women in the group). Only three of them are still alive. Seven had arteritis, which is a vasculitis that affects the arteries, four had psoriasis or sarcoidosis which causes small, swollen lumps to form on the body. All suffered from anemia. From a statistical point of view it means that 1 man out of 4,269 over 50 and 1 woman out of 26,238 has or is at risk of developing the syndrome. For researchers the significant prevalence compared to other inflammatory conditions such as vasculitis and myelodysplasia. This study showed that there are probably thousands of patients in the United States who have this disease, and in the vast majority of cases this it is not recognized why doctors don’t consider broadening the spectrum for diagnosis, he says David Beckgeneticist and principal investigator of the study.
Non-hereditary disease, diagnosis with a genetic test
VEXAS syndrome is not hereditary, so those affected do not pass it on to their children. The UBA1 gene is located on the X chromosome. For this reason it predominantly affects men, carriers of only one X chromosome. Women have two X chromosomes so if one is affected by the mutation, the other intervenes by silencing the defective one. The good news that there is a genetic testing to diagnose the disease to which all those elderly patients, with systemic inflammation and low red blood cells who do not respond to other treatments, if not to cortisone or other immunosuppressants which however have well-known side effects, may undergo.
There is no standardized cure or treatment but the symptoms can be managed with steroid or immunosuppressant drugs. Today it is treated with the same drugs that we use in autoinflammatory diseases, namely glucocorticoids and interlukina 1 inhibitors such as the biological drugs anakinra and canakinumab concludes Selmi. An effective treatment may be bone marrow transplantation which certainly carries risks but this underlines how serious the disease is, comments Becks. In Italia VEXAS syndrome was first diagnosed in December 2022 in Reggio Emilia and since then the Rheumatology and Hematology departments of many Italian hospitals have equipped themselves to carry out genetic tests on patients whose diagnosis is uncertain.
A curiosity. In an episode of the popular TV series Chicago Med, one of the doctors dealing with a patient with an unknown disease exclaims in front of his colleagues: I just read about the new VEXAS syndrome in New England, this one!. happened just two three months after the real publication in the scientific journal. The (real) doctors at the National Institute of Health are said to be proud of the pop breakthrough of their discovery.
February 7, 2023 (change February 7, 2023 | 09:09)
© breaking latest news