A case of VEXAS syndrome associated with EBV-associated hemophagocytic lymphohistiocytosis

Roy L. Kao; Audrey A. Jacobsen; Charles J. Billington; Sophia L. Yohe; Amy K. Beckman; Gregory M. Vercellotti; David R. Pearson

doi:10.1016/j.bcmd.2021.102636

A case of VEXAS syndrome associated with EBV-associated hemophagocytic lymphohistiocytosis

Roy L. Kao, Audrey A. Jacobsen, Charles J. Billington, Sophia L. Yohe, Amy K. Beckman, Gregory M. Vercellotti, David R. Pearson

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Vacuoles, E1, X-linked, autoimmunity, somatic (VEXAS) syndrome is characterized by a pathogenic mutation in UBA1, which leads to protean complications including autoimmunity and myelodysplasia. A 56-year-old man with steroid-dependent, later steroid-refractory cutaneous polyarteritis nodosa and Sweet syndrome developed recurrent daily fever, macrocytic anemia, thrombocytopenia, acute hypoxic respiratory failure, and anasarca. He was eventually diagnosed with Epstein-Barr virus (EBV) viremia and hemophagocytic lymphohistiocytosis (HLH). He improved clinically with rituximab, ruxolitinib, and increased glucocorticoids before expiring from Pseudomonas sepsis. UBA1 exon 3 mutational analysis in myeloid enriched peripheral blood revealed a c.122T>C (p.Met41Thr) pathogenic variant, consistent with VEXAS syndrome. We describe the first case of EBV-associated HLH in a patient diagnosed with VEXAS syndrome. Early identification of this syndrome will be important in order to offer potential therapies before life-threatening complications arise.

Original language	English (US)
Article number	102636
Journal	Blood Cells, Molecules, and Diseases
Volume	93
DOIs	https://doi.org/10.1016/j.bcmd.2021.102636
State	Published - Mar 2022

Bibliographical note

Funding Information:
G.M.V. receives research funding from Astellus/Mitobridge and is a consultant. He also receives research funding from CSL Behring. D.R.P. is a consultant for Biogen Inc. Clinical trials principal/sub investigator for Corbus Pharmaceuticals, Elorac, Inc., Eli Lilly and Company, Emerald Health Pharmaceuticals, Kadmon, Inc., Pfizer, Inc., and Soligenix, Inc. None of these are directly relevant to this manuscript or the disease reported therein (VEXAS).

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

Epstein-Barr virus
Hemophagocytic lymphohistiocytosis
Polyarteritis nodosa
Sweet syndrome
UBA1
Ubiquitin-proteasome system
VEXAS syndrome

PubMed: MeSH publication types

Case Reports
Journal Article

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10.1016/j.bcmd.2021.102636

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title = "A case of VEXAS syndrome associated with EBV-associated hemophagocytic lymphohistiocytosis",

abstract = "Vacuoles, E1, X-linked, autoimmunity, somatic (VEXAS) syndrome is characterized by a pathogenic mutation in UBA1, which leads to protean complications including autoimmunity and myelodysplasia. A 56-year-old man with steroid-dependent, later steroid-refractory cutaneous polyarteritis nodosa and Sweet syndrome developed recurrent daily fever, macrocytic anemia, thrombocytopenia, acute hypoxic respiratory failure, and anasarca. He was eventually diagnosed with Epstein-Barr virus (EBV) viremia and hemophagocytic lymphohistiocytosis (HLH). He improved clinically with rituximab, ruxolitinib, and increased glucocorticoids before expiring from Pseudomonas sepsis. UBA1 exon 3 mutational analysis in myeloid enriched peripheral blood revealed a c.122T>C (p.Met41Thr) pathogenic variant, consistent with VEXAS syndrome. We describe the first case of EBV-associated HLH in a patient diagnosed with VEXAS syndrome. Early identification of this syndrome will be important in order to offer potential therapies before life-threatening complications arise.",

keywords = "Epstein-Barr virus, Hemophagocytic lymphohistiocytosis, Polyarteritis nodosa, Sweet syndrome, UBA1, Ubiquitin-proteasome system, VEXAS syndrome",

author = "Kao, {Roy L.} and Jacobsen, {Audrey A.} and Billington, {Charles J.} and Yohe, {Sophia L.} and Beckman, {Amy K.} and Vercellotti, {Gregory M.} and Pearson, {David R.}",

note = "Funding Information: G.M.V. receives research funding from Astellus/Mitobridge and is a consultant. He also receives research funding from CSL Behring. D.R.P. is a consultant for Biogen Inc. Clinical trials principal/sub investigator for Corbus Pharmaceuticals, Elorac, Inc., Eli Lilly and Company, Emerald Health Pharmaceuticals, Kadmon, Inc., Pfizer, Inc., and Soligenix, Inc. None of these are directly relevant to this manuscript or the disease reported therein (VEXAS). Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2022",

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AU - Kao, Roy L.

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AU - Yohe, Sophia L.

AU - Beckman, Amy K.

AU - Vercellotti, Gregory M.

AU - Pearson, David R.

N1 - Funding Information: G.M.V. receives research funding from Astellus/Mitobridge and is a consultant. He also receives research funding from CSL Behring. D.R.P. is a consultant for Biogen Inc. Clinical trials principal/sub investigator for Corbus Pharmaceuticals, Elorac, Inc., Eli Lilly and Company, Emerald Health Pharmaceuticals, Kadmon, Inc., Pfizer, Inc., and Soligenix, Inc. None of these are directly relevant to this manuscript or the disease reported therein (VEXAS). Publisher Copyright: © 2021 Elsevier Inc.

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N2 - Vacuoles, E1, X-linked, autoimmunity, somatic (VEXAS) syndrome is characterized by a pathogenic mutation in UBA1, which leads to protean complications including autoimmunity and myelodysplasia. A 56-year-old man with steroid-dependent, later steroid-refractory cutaneous polyarteritis nodosa and Sweet syndrome developed recurrent daily fever, macrocytic anemia, thrombocytopenia, acute hypoxic respiratory failure, and anasarca. He was eventually diagnosed with Epstein-Barr virus (EBV) viremia and hemophagocytic lymphohistiocytosis (HLH). He improved clinically with rituximab, ruxolitinib, and increased glucocorticoids before expiring from Pseudomonas sepsis. UBA1 exon 3 mutational analysis in myeloid enriched peripheral blood revealed a c.122T>C (p.Met41Thr) pathogenic variant, consistent with VEXAS syndrome. We describe the first case of EBV-associated HLH in a patient diagnosed with VEXAS syndrome. Early identification of this syndrome will be important in order to offer potential therapies before life-threatening complications arise.

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A case of VEXAS syndrome associated with EBV-associated hemophagocytic lymphohistiocytosis

Abstract

Bibliographical note

Keywords

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