The dermatologic gateway to early diagnosis of VEXAS syndrome: a comprehensive review of cutaneous manifestations and their pathognomonic significance

Paola Denisse Osorio Casimiro; María Fernanda Leyva Mondragón; Paola Pérez Lee; Juan Enrique Aguiñaga Morales; Luis David Díaz Hill

doi:10.18203/issn.2455-4529.IntJResDermatol20263751

Authors

Paola Denisse Osorio Casimiro Hospital General Regional No. 2 El Marqués, Instituto Mexicano del Seguro Social, Querétaro, México
María Fernanda Leyva Mondragón Hospital General Regional No. 2 El Marqués, Instituto Mexicano del Seguro Social, Querétaro, México
Paola Pérez Lee Hospital General Regional No. 2 El Marqués, Instituto Mexicano del Seguro Social, Querétaro, México
Juan Enrique Aguiñaga Morales Hospital General Regional No. 2 El Marqués, Instituto Mexicano del Seguro Social, Querétaro, México
Luis David Díaz Hill Hospital General Regional No. 2 El Marqués, Instituto Mexicano del Seguro Social, Querétaro, México

DOI:

https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20263751

Keywords:

VEXAS syndrome, UBA1 gene, Autoinflammatory diseases, Dermatology, Neutrophilic dermatoses, Leukocytoclastic vasculitis, Relapsing polychondritis, Sweet syndrome, Clonal hematopoiesis, Myelodysplastic syndrome, Early diagnosis

Abstract

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently recognized adult-onset autoinflammatory disorder caused by somatic mutations in the ubiquitin-activating enzyme UBA1. Since its initial description in 2020, its clinical spectrum has expanded considerably, yet diagnosis remains challenging because of its heterogeneous multisystem manifestations. Cutaneous involvement occurs in up to 90% of patients and is frequently an early or presenting feature, making dermatological findings particularly valuable for clinical suspicion and diagnosis. This narrative review summarizes current evidence on the dermatological manifestations of VEXAS syndrome, emphasizing their role as accessible markers of systemic inflammation. The cutaneous phenotype is highly heterogeneous, encompassing neutrophilic dermatoses, including sweet syndrome-like lesions, leukocytoclastic vasculitis, periorbital edema, and other inflammatory dermatoses. Histopathological findings range from dense neutrophilic infiltrates with leukocytoclasia to nonspecific perivascular inflammation. Emerging genotype-phenotype associations suggest that the p.Met41Leu variant is more frequently associated with neutrophilic dermatoses, whereas p.Met41Val may be linked to vasculitic manifestations. We also examine the evolving understanding of the genetic and clonal basis of cutaneous inflammation in VEXAS. Recognition of characteristic skin findings, particularly in older men with treatment-refractory inflammatory dermatoses, cytopenias, and systemic inflammation, should prompt consideration of VEXAS and targeted UBA1 testing. Greater dermatological awareness may facilitate earlier diagnosis, reduce diagnostic delay, and enable timely initiation of potentially life-changing therapy.

Author Biographies

Paola Denisse Osorio Casimiro, Hospital General Regional No. 2 El Marqués, Instituto Mexicano del Seguro Social, Querétaro, México

.

Luis David Díaz Hill, Hospital General Regional No. 2 El Marqués, Instituto Mexicano del Seguro Social, Querétaro, México

.

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