VEXAS syndrome and its cutaneous manifestations

VEXAS syndrome is a relatively newly discovered autoinflammatory syndrome. Since skin manifestations are an early indicator of this disease, dermatologists play an important role in identifying patients with suspected VEXAS syndrome.

Dr Joost Meijer (University Medical Center Groningen, the Netherlands) shared key diagnostic insights and clues with the audience [1].

“VEXAS syndrome has been recognised as an autoinflammatory disorder for about 5 years now,” noted Dr Meijer. It remains unrecognised by many dermatologists, who should start incorporating VEXAS syndrome into diagnostic algorithms. VEXAS is an acronym for vacuoles, E1-enzyme, X-linked, auto-inflammatory, and somatic. Typical cutaneous manifestations of VEXAS syndrome are ear or nose chondritis, unilateral periorbital oedema, urticaria-like lesions, neutrophilic dermatosis, medium-vessel vasculitis, and leukocytoclastic vasculitis (see Figure). It predominantly affects men above 50 years of age.

Figure: Typical manifestations of VEXAS syndrome [1]



Reprinted from https://www.niams.nih.gov/labs/grayson-lab/vexas. Permission from Dr Peter Grayson.

VEXAS syndrome is an acquired disease caused by a somatic mutation in the UBA1 gene, which occurs in the myeloid progenitor cells. This mutation hampers the intracellular degradation of proteins and leads to an uncontrolled proinflammatory cascade. “As dermatologists, we mainly observe the skin manifestations, but it is, in fact, a multisystemic condition, affecting the lungs, bone marrow, joints, and other organ systems,” explained Dr Meijer.

The diagnosis is made through the identification of a UBA1 mutation, in combination with symptoms in at least 2 organ systems and laboratory abnormalities such as anaemia or thrombocytopenia. While the exact epidemiology of this syndrome is currently not well established, the estimated incidence in the USA is 1 in 4,269 white men over the age of 50. “We have no idea about the incidence of VEXAS syndrome in the Netherlands because we normally do not test for this,” added Dr Meijer. It is, however, important to get this disease on the radar because the later the diagnosis is made, the worse the prognosis. In advanced stages, patients may be too frail to tolerate certain therapies. “There are not many effective treatment options for this syndrome, and the ones available carry an increased risk of infection,” said Dr Meijer.

Over 80% of the patients with VEXAS syndrome have skin manifestations, and in 60% of the patients, these are the first symptoms. The dermatologist is, therefore, potentially the first specialist who may suspect the presence of VEXAS syndrome. The cutaneous manifestations are typically distributed across the upper body, including the upper extremities, torso, and face. Common lesions are nodules, maculae, and erythema, while petechia and purpura are less frequently observed. “The skin manifestations are often annular or circinate in shape,” added Dr Meijer. In addition, the skin lesions may mimic erythema nodosum, panniculitis, vasculitis, livedo reticularis, and ulcers [2]. Dr Meijer emphasised the importance of looking for systemic signs, including fever, elevated ESR and CRP, periorbital oedema, and chondritis of the ears or nose, which are typical features in patients with VEXAS syndrome. Neutrophilic dermatosis and possible leucocytoclasia, with or without vasculitis, are characteristic histopathological findings. Moreover, 2 known clinical phenotypes of VEXAS syndrome have been described: the leucine variant, characterised by neutrophilic dermatosis, and the valine variant, characterised by cutaneous vasculitis. Finally, Dr Meijer highlighted that men above 50 years of age who are diagnosed with Sweet syndrome may, in fact, have VEXAS syndrome. A small study in review for publication, including 10 of those men, showed that 30% had VEXAS syndrome.

“Although we have learned a lot about VEXAS syndrome in recent years, much is still unknown,” concluded Dr Meijer. “For now, it is important to identify typical skin manifestations of VEXAS syndrome early. If a patient is diagnosed with Sweet syndrome but something does not quite add up, assessing for VEXAS syndrome should be considered,” Dr Meijer advised.

1. Meijer J. VEXAS syndrome: cutaneous manifestations with a new auto-inflammatory syndrome. Dermatologendagen 2025, 10–11 April, Apeldoorn, the Netherlands.
2. Tan IJ, et al. JAMA Dermatol. 2024;160(8):822-829.

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Posted on 5 June 20255 June 2025