VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist

D, Sterling; Duncan, M; Philippidou, M.; Salisbury, Jon; Kulasekararaj, Austin; Basu, Tanya

doi:10.1016/j.jaad.2022.01.042

Cited by 38 publications

(67 citation statements)

References 32 publications

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“…Skin manifestations are also common in VEXAS syndrome, including Sweet's syndrome, erythema, nodules, papules, erythema nodosum, and panniculitis (14,29,(32)(33)(34)(35)(36). The histological hallmark of skin lesions is neutrophilic dermatosis, which is often accompanied by LCV.…”

Section: Skin Manifestationsmentioning

confidence: 99%

“…The most commonly affected sites are the neck and trunk, but they also appear in the extremities ( 37 ). According to a literature review, approximately 90% (126/141) of published cases of VEXAS syndrome had cutaneous signs ( 14 ).…”

Section: Clinical Phenotypes Of Vexas Syndromementioning

confidence: 99%

“…The most common vasculitis is small-vessel vasculitis, particularly LCV. The reason stems from the fact that skin manifestations, which are observed in 80–90% of patients, often reveal the histopathology of LCV ( 14 , 37 , 60 ). LCV is histologically characterized by angiocentric segmental inflammation, fibrinoid necrosis, and neutrophilic infiltration around the blood vessel walls ( 14 , 61 ).…”

Section: Vasculitis Associated With Vexas Syndromementioning

confidence: 99%

“…The reason stems from the fact that skin manifestations, which are observed in 80–90% of patients, often reveal the histopathology of LCV ( 14 , 37 , 60 ). LCV is histologically characterized by angiocentric segmental inflammation, fibrinoid necrosis, and neutrophilic infiltration around the blood vessel walls ( 14 , 61 ). In the initial report, LCV was histologically confirmed in seven of 25 patients (28%) with VEXAS syndrome and in seven of 22 patients (31.8%) with dermatologic manifestations.…”

Section: Vasculitis Associated With Vexas Syndromementioning

confidence: 99%

“…In addition, patients with VEXAS syndrome sometimes develop vasculitis such as giant cell arteritis (GCA) and polyarteritis nodosa (PAN) ( 11 ). However, as case reports and series of VEXAS syndrome have been accumulated, various types of coexisting vasculitis have been reported, including leukocytoclastic vasculitis (LCV), immunoglobulin A (IgA) vasculitis, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) ( 12 – 14 ). Moreover, this disease was considered to be found only in males, since UBA1 lies on the X chromosome.…”

Section: Introductionmentioning

confidence: 99%

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Vasculitis associated with VEXAS syndrome: A literature review

Watanabe¹,

Kiji²,

Hashimoto³

2022

Front. Med.

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Vasculitis is an inflammatory disorder of the blood vessels that causes damage to a wide variety of organs through tissue ischemia. Vasculitis is classified according to the size (large, medium, or small) of the blood vessels. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. Somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation, are attributed to this disorder. This new disease entity connects seemingly unrelated conditions: inflammatory syndromes (relapsing chondritis, Sweet's syndrome, or neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Notably, such patients sometimes develop vasculitis, such as giant cell arteritis and polyarteritis nodosa, and fulfill the corresponding classification criteria for vasculitis. Thus, vasculitis can be an initial manifestation of VEXAS syndrome. In this research topic exploring the link between autoinflammatory diseases and vasculitis, we first provide an overview of the disease mechanisms and clinical phenotypes of VEXAS syndrome. Then, a literature review using the PubMed database was performed to delineate the clinical characteristics of vasculitis associated with VEXAS syndrome. Finally, the therapeutic options and unmet needs of VEXAS syndrome are discussed.

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Section: Skin Manifestationsmentioning

confidence: 99%

Section: Clinical Phenotypes Of Vexas Syndromementioning

confidence: 99%

Section: Vasculitis Associated With Vexas Syndromementioning

confidence: 99%

Section: Vasculitis Associated With Vexas Syndromementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vasculitis associated with VEXAS syndrome: A literature review

Watanabe¹,

Kiji²,

Hashimoto³

2022

Front. Med.

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Skin Manifestations of VEXAS Syndrome and Associated Genotypes

Tan,

Ferrada,

Ahmad

et al. 2024

JAMA Dermatol

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ImportanceVEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations.ObjectiveTo define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features.Design, Setting, and ParticipantsThis observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland.Main Outcomes and MeasuresTo define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS.ResultsAmong the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]).Conclusions and RelevanceResults of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.

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VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management

Koster,

Lasho,

Olteanu

et al. 2023

American J Hematol

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VEXAS (Vacuoles, E1 enzyme, X‐linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic alterations in UBA1 which produce a recalcitrant inflammatory state along with hematologic disturbances. Patients with VEXAS can have a wide spectrum of clinical symptoms and providers should be familiar with the heterogeneity of associated clinical features. While hematologic parameters may be generally non‐specific, peripheral blood features of macrocytosis, monocytopenia, and/or thrombocytopenia coupled with bone marrow vacuolization of erythroid or myeloid precursors should raise suspicion for this condition. Due to an increased mortality, prompt recognition and accurate diagnosis is paramount. Access to testing for confirmation of UBA1 variants is not yet universally available but clinicians should understand the current available options for genetic confirmation of this disease. Treatment options are limited due to lack of prospective clinical trials but cytokine directed therapies such as interleukin‐6 inhibitors and JAK–STAT inhibitors as well as hypomethylating agents such as azacitidine have shown evidence of partial effect. Though cases are limited, allogeneic stem cell transplantation holds promise for durable response and potential cure. The intent of this review is to outline the pathophysiology of VEXAS syndrome and to provide a practical approach to diagnosis and treatment.

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VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist

Cited by 38 publications

References 32 publications

Vasculitis associated with VEXAS syndrome: A literature review

Vasculitis associated with VEXAS syndrome: A literature review

Skin Manifestations of VEXAS Syndrome and Associated Genotypes

VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management

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