Expanding the Clinical Spectrum of VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome: The First Report of Histologically Confirmed Neutrophilic Colitis With Rare Muscular and Pancreatic Involvement

TL;DR

This paper reports a rare case of VEXAS syndrome with unusual symptoms like facial muscle inflammation, pancreatic issues, and colitis, highlighting the need for broader awareness of the condition.

Contribution

The first histologically confirmed case of neutrophilic colitis in VEXAS syndrome with rare muscular and pancreatic involvement is reported.

Findings

A 77-year-old male with VEXAS syndrome exhibited facial myositis, pancreatic hypermetabolism, and neutrophilic colitis.

Histopathology confirmed neutrophilic infiltration and vascular injury in the colon, a first in VEXAS syndrome.

Positron emission tomography showed pancreatic head hypermetabolism, suggesting broader organ involvement in VEXAS.

Abstract

VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a rare, adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene, most commonly affecting older men and associated with systemic inflammation and hematologic abnormalities. Although hematologic, cutaneous, and cartilaginous manifestations are well recognized, involvement of other organs, including muscle, pancreas, and colon, has been infrequently reported. We report a case of a 77-year-old male who initially presented with orbital inflammation, facial myositis, and laryngeal edema, followed by extensive superficial and deep venous thromboses. His clinical course subsequently included recurrent fevers and gastrointestinal bleeding. Laboratory evaluation revealed macrocytic anemia and elevated inflammatory markers. Colonoscopy demonstrated findings consistent with ulcerative colitis, and histopathology showed dense neutrophilic infiltration with microthrombi and fibrinoid necrosis. Positron emission tomography scanning revealed hypermetabolic uptake in the pancreatic head, lymph nodes, and bone marrow. Genetic testing confirmed a somatic UBA1 mutation, thereby establishing the diagnosis of VEXAS syndrome.

This case report broadens the recognized clinical spectrum of VEXAS syndrome by combining three rarely described manifestations - facial (orbital/masseter) myositis, pancreatic hypermetabolism, and neutrophilic colitis with vascular injury. To our knowledge, this is the first report to present detailed colonic histopathologic findings in VEXAS syndrome. VEXAS syndrome remains underrecognized, particularly in the presence of atypical organ involvement. Awareness of uncommon features- such as colonic neutrophilic vasculitis or facial myositis - may prompt earlier clinical suspicion, facilitate targeted genetic testing, and support timely, appropriate management. Further systematic studies are needed to delineate the full clinical spectrum, histopathologic features, and optimal therapeutic strategies for VEXAS.

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