VEXAS syndrome: a comprehensive clinicopathologic and genetic analysis of a predominantly Indian cohort
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: VEXAS syndrome is a recently recognized, acquired monogenic adult onset hemato-inflammatory syndrome characterized by somatic mutations within the UBA1 gene. The acronym VEXAS stands for vacuoles, E1 enzyme, X-linked inheritance, autoinflammatory tendencies, and somatic mutations. It presents as a severe progressive disease displaying varied characteristics that bridge hematologic and rheumatologic domains. Herein, we describe a series with a detailed evaluation of 11 cases of VEXAS syndrome. MATERIALS AND METHODS: A comprehensive retrospective analysis of patients diagnosed with VEXAS syndrome over the last 5 years (2020-2025) was conducted. Data on clinical presentation, histopathological findings, genetic characteristics, and outcomes were recorded for systematic characterization. RESULTS: A total of 11 cases of VEXAS syndrome were identified. All the patients were males with an age range from 42 to 77 years. Prominent clinical characteristics included history of fever (11), arthritis/arthralgia (10), inflammatory skin lesions (7), vasculitis (6), ocular inflammatory conditions (6), relapsing polychondritis (6), unprovoked venous thrombosis (5), and auricular chondritis (4). Persistent unexplained cytopenia was present in all the patients, manifesting as anemia (10, 8 of which were macrocytic), thrombocytopenia (4), and neutropenia (2). Bone marrow examination was performed in nine cases, five showed morphologic dysplasia. Furthermore, all nine cases characteristically showed cytoplasmic vacuolations in hematopoietic precursors. UBA1 somatic mutations included p.Met41Thr (c.122 T>C Exon 3) (55%), p.Met41Val (c.121 A>G Exon 3) (27%), p.Met41Leu (c.121 A>C Exon 3) (9%), and a variant in the acceptor splice site of Exon 3 (c.118 G>C) (9%). p.Met41Val is associated with inferior overall survival (OS). CONCLUSION: This study characterizes the clinical, morphologic, and laboratory features of VEXAS syndrome and presents the first comprehensive patient cohort from India. With a complex and heterogeneous clinical profile, awareness of the disease is particularly essential among hematologists, rheumatologists, and dermatologists for accurate diagnosis and management.
Source: Journal of Hematopathology
Authors: Dheeraj Chinnam, Aadya Kerkar, Rohit Gulati, Prateek Bhatia, Sreejesh Sreedharanunni, Praveen Sharma, Minu Singh, Shikha Shah, Narayanan Baskaran, Ramya Puligari, Neha Avtarkrishan Ganju, Prakashini Mruthyunjaya, Lekshmon K.S., Anuradha Bishnoi, Dipanker De, Sarath Chandra Mouli Veeravalli, Vishvdeep Khushoo, Avtar Krishan Ganju, Prasanta Padhan, Paul Antony, Vikas Gupta, Anand Balakrishnan, Arushi Sharma, Dikshat Gopal Gupta, Aman Sharma, Pankaj Malhotra
Institutions: Indiana University School of Medicine, Post Graduate Institute of Medical Education and Research, Krishna Institute of Medical Sciences, KIIT University, Amala Institute of Medical Sciences, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,890
OpenAlex ID: W7161413769