Vasculitis associated with VEXAS syndrome: A literature review

Abstract

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.

VEXAS Syndrome and Thrombosis: Findings of Inflammation, Hypercoagulability, and Endothelial Dysfunction

“…Both patients had raised endothelial markers ICAM-1, VCAM-1, VWF:Ag, and glycoprotein 1B binding activity, with the presence of vasculitis in VEXAS syndrome in patient 2, suggesting evidence for ongoing endothelial dysfunction. In a recent literature review vascular inflammation with involvement of small, medium, and large vessels was identified 9 and in a report by Karadeniz et al of two patients with VEXAS syndrome there was severe thickening of the walls of large veins detected on Doppler ultrasound, suggestive of venulitis. 10…”

“…8 Both patients had raised endothelial markers ICAM-1, VCAM-1, VWF:Ag, and glycoprotein 1B binding activity, with the presence of vasculitis in VEXAS syndrome in patient 2, suggesting evidence for ongoing endothelial dysfunction. In a recent literature review vascular inflammation with involvement of small, medium, and large vessels was identified 9 and in a report by Karadeniz et al of two patients with VEXAS syndrome there was severe thickening of the walls of large veins detected on Doppler ultrasound, suggestive of venulitis. 10 In summary, given the findings of inflammation, hypercoagulability and endothelial dysfunction, long-term anticoagulation treatment in VEXAS patients with known thrombosis, together with anti-inflammatory and immunosuppressive therapies, may provide an appropriate therapeutic approach to VEXAS syndrome.…”

Vaskulitis mimics

“…B. rezidivierende Polychondritis, Riesenzellarteriitis oder Sweet-Syndrom) erfüllten, durch die gleiche Mutation erklärt werden konnten. Das VEXAS-Syndrom kann neben einer Chondritis auch mit einer Vaskulitis von Gefäßen unterschiedlicher Größe einhergehen und zum Beispiel RZA, PAN oder Kleingefäßvaskulitiden (insbesondere leukozytoklastische Hautvaskulitis, in Einzelfällen auch GPA oder MPA) imitieren 75 76 .…”

VEXAS Syndrome—Review

“…Ubiquitylation is essential for a variety of cellular processes, such as cell-cycle progression, deoxyribonucleic acid damage response, and immune signaling pathways. 10 Mutations in UBA1 lead to reduced ubiquitination and activation of autoimmune pathways, resulting in inflammatory manifestations. 1,2,13,15 X-Linked UBA1 is located on the X chromosome (Xp11.3) and can escape X chromosome inactivation.…”

“…Chest computed tomography demonstrated diffuse bilateral ground-glass opacities and pleural effusions. 1,10,22 Hematologic Aspects…”