Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic Abnormality

VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome is a rare disorder caused by somatic UBA1 gene mutations, characterized by autoinflammation and hematologic abnormalities, particularly affecting myeloid‐lineage progenitors. Sensitive markers include macrocytic anemia, vacuol...

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Main Authors: Laura Di Centa, Simone Longhino, Valeria Manfrè, Stefania Sacco, Luca Quartuccio
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:ACR Open Rheumatology
Online Access:https://doi.org/10.1002/acr2.70064
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author Laura Di Centa
Simone Longhino
Valeria Manfrè
Stefania Sacco
Luca Quartuccio
author_facet Laura Di Centa
Simone Longhino
Valeria Manfrè
Stefania Sacco
Luca Quartuccio
author_sort Laura Di Centa
collection DOAJ
description VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome is a rare disorder caused by somatic UBA1 gene mutations, characterized by autoinflammation and hematologic abnormalities, particularly affecting myeloid‐lineage progenitors. Sensitive markers include macrocytic anemia, vacuolization of bone marrow precursors, and myelodysplasia. Here, we report the first case of VEXAS syndrome presenting with neutrophilic dermatosis and a serum monoclonal component, without myeloid‐lineage hematologic abnormalities atonset. This case underscores the importance of including VEXAS syndrome in the differential diagnosis when monoclonal gammopathy is associated with rheuamtologic features, particularly in older patients presenting with unexplained cutaneous inflammatory manifestations and a serum clonal component, as such presentations may precede the development of classical hematologic abnormalities.
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spelling doaj-art-e8d47940b9fb40fa9ad8c8698462271d2025-08-20T03:35:25ZengWileyACR Open Rheumatology2578-57452025-06-0176n/an/a10.1002/acr2.70064Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic AbnormalityLaura Di Centa0Simone Longhino1Valeria Manfrè2Stefania Sacco3Luca Quartuccio4Division of Rheumatology, Department of Medicine University of Udine, Academic Hospital “Santa Maria della Misericordia,” Udine ItalyDivision of Rheumatology, Department of Medicine University of Udine, Academic Hospital “Santa Maria della Misericordia,” Udine ItalyDivision of Rheumatology, Department of Medicine University of Udine, Academic Hospital “Santa Maria della Misericordia,” Udine ItalyDivision of Rheumatology, Department of Medicine University of Udine, Academic Hospital “Santa Maria della Misericordia,” Udine ItalyDivision of Rheumatology, Department of Medicine University of Udine, Academic Hospital “Santa Maria della Misericordia,” Udine ItalyVEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome is a rare disorder caused by somatic UBA1 gene mutations, characterized by autoinflammation and hematologic abnormalities, particularly affecting myeloid‐lineage progenitors. Sensitive markers include macrocytic anemia, vacuolization of bone marrow precursors, and myelodysplasia. Here, we report the first case of VEXAS syndrome presenting with neutrophilic dermatosis and a serum monoclonal component, without myeloid‐lineage hematologic abnormalities atonset. This case underscores the importance of including VEXAS syndrome in the differential diagnosis when monoclonal gammopathy is associated with rheuamtologic features, particularly in older patients presenting with unexplained cutaneous inflammatory manifestations and a serum clonal component, as such presentations may precede the development of classical hematologic abnormalities.https://doi.org/10.1002/acr2.70064
spellingShingle Laura Di Centa
Simone Longhino
Valeria Manfrè
Stefania Sacco
Luca Quartuccio
Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic Abnormality
ACR Open Rheumatology
title Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic Abnormality
title_full Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic Abnormality
title_fullStr Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic Abnormality
title_full_unstemmed Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic Abnormality
title_short Unveiling VEXAS Syndrome: When Skin Manifestations and Monoclonal Gammopathy Precede Myeloid‐Lineage Hematologic Abnormality
title_sort unveiling vexas syndrome when skin manifestations and monoclonal gammopathy precede myeloid lineage hematologic abnormality
url https://doi.org/10.1002/acr2.70064
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