TY - JOUR
T1 - VEXAS syndrome
T2 - Clinical, hematologic features and a practical approach to diagnosis and management
AU - Koster, Matthew J.
AU - Lasho, Terra L.
AU - Olteanu, Horatiu
AU - Reichard, Kaaren K.
AU - Mangaonkar, Abhishek
AU - Warrington, Kenneth J.
AU - Patnaik, Mrinal M.
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2024/2
Y1 - 2024/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85176733661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85176733661&partnerID=8YFLogxK
U2 - 10.1002/ajh.27156
DO - 10.1002/ajh.27156
M3 - Review article
C2 - 37950858
AN - SCOPUS:85176733661
SN - 0361-8609
VL - 99
SP - 284
EP - 299
JO - American journal of hematology
JF - American journal of hematology
IS - 2
ER -