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A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has recently been described as an autoinflammatory disease associated with severe adult-onset inflammatory manifestations. The various clinical manifestations include recurrent high-grade fever, neutrophilic dermatoses, cutane...

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Autores principales: Tozaki, Nagie, Tawada, Chisato, Niwa, Hirofumi, Mizutani, Yoko, Shu, En, Kawase, Aki, Miwa, Yuki, Ohnishi, Hidenori, Sasai, Hideo, Miyako, Keisuke, Hosokawa, Junichi, Kato, Ayaka, Kobayashi, Kazuhiro, Miyazaki, Tatsuhiko, Shirakami, Yohei, Shimizu, Masahito, Iwata, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760706/
https://www.ncbi.nlm.nih.gov/pubmed/36544501
http://dx.doi.org/10.3389/fmed.2022.1046820
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author Tozaki, Nagie
Tawada, Chisato
Niwa, Hirofumi
Mizutani, Yoko
Shu, En
Kawase, Aki
Miwa, Yuki
Ohnishi, Hidenori
Sasai, Hideo
Miyako, Keisuke
Hosokawa, Junichi
Kato, Ayaka
Kobayashi, Kazuhiro
Miyazaki, Tatsuhiko
Shirakami, Yohei
Shimizu, Masahito
Iwata, Hiroaki
author_facet Tozaki, Nagie
Tawada, Chisato
Niwa, Hirofumi
Mizutani, Yoko
Shu, En
Kawase, Aki
Miwa, Yuki
Ohnishi, Hidenori
Sasai, Hideo
Miyako, Keisuke
Hosokawa, Junichi
Kato, Ayaka
Kobayashi, Kazuhiro
Miyazaki, Tatsuhiko
Shirakami, Yohei
Shimizu, Masahito
Iwata, Hiroaki
author_sort Tozaki, Nagie
collection PubMed
description VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has recently been described as an autoinflammatory disease associated with severe adult-onset inflammatory manifestations. The various clinical manifestations include recurrent high-grade fever, neutrophilic dermatoses, cutaneous vasculitis, chondritis of the ear and nose, pulmonary infiltrates, cytopenia, uveitis, gastrointestinal pain or inflammation, aortitis, hepatosplenomegaly, and hematological disorders. VEXAS syndrome is caused by somatic mutations of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene in myeloid-lineage cells. It is characterized by vacuolated myeloid and erythroid progenitor cells seen by bone marrow biopsy. We report the case of a 64-year-old Japanese man with VEXAS syndrome. At age 63, he was referred to us with a recurrent erythema on the hands associated with a general fever of 38–40°C that had persisted for 4 or 5 days and had recurred about once a month for a year. The skin rash appeared 2 or 3 days after the onset of each fever episode. Computed tomography (CT) of the chest revealed bilateral hilar lymphadenopathy (BHL), and the mediastinal lymph nodes were swollen. Sarcoidosis was suspected but was ruled out by several tests. Laboratory examinations showed elevated inflammatory markers. Bone marrow examination showed the vacuolization of myeloid precursor cells. A skin biopsy revealed dense dermal, predominantly perivascular, infiltrates. These consisted of mature neutrophils admixed with myeloperoxidase-positive CD163-positive myeloid cells, lymphoid cells and eosinophils. Sequencing analysis identified the somatic UBA1 variant c.122T > C, which results in p.Met41Thr. Treatment with oral prednisone (15 mg/day) and monthly intravenous tocilizumab injections (400 mg) completely resolved the symptoms. Neutrophils are a major source of reactive oxygen species, and the present case demonstrated numerous neutrophilic infiltrates. We hypothesize that the patient might have had elevated derivatives of reactive oxygen metabolites (d-ROMs). d-ROM quantification is a simple method for detecting hydroperoxide levels, and clinical trials have proven it useful for evaluating oxidative stress. In this study, we measured serum d-ROM before and after oral prednisone and tocilizumab treatment. The levels decreased significantly during treatment.
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spelling pubmed-97607062022-12-20 A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment Tozaki, Nagie Tawada, Chisato Niwa, Hirofumi Mizutani, Yoko Shu, En Kawase, Aki Miwa, Yuki Ohnishi, Hidenori Sasai, Hideo Miyako, Keisuke Hosokawa, Junichi Kato, Ayaka Kobayashi, Kazuhiro Miyazaki, Tatsuhiko Shirakami, Yohei Shimizu, Masahito Iwata, Hiroaki Front Med (Lausanne) Medicine VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has recently been described as an autoinflammatory disease associated with severe adult-onset inflammatory manifestations. The various clinical manifestations include recurrent high-grade fever, neutrophilic dermatoses, cutaneous vasculitis, chondritis of the ear and nose, pulmonary infiltrates, cytopenia, uveitis, gastrointestinal pain or inflammation, aortitis, hepatosplenomegaly, and hematological disorders. VEXAS syndrome is caused by somatic mutations of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene in myeloid-lineage cells. It is characterized by vacuolated myeloid and erythroid progenitor cells seen by bone marrow biopsy. We report the case of a 64-year-old Japanese man with VEXAS syndrome. At age 63, he was referred to us with a recurrent erythema on the hands associated with a general fever of 38–40°C that had persisted for 4 or 5 days and had recurred about once a month for a year. The skin rash appeared 2 or 3 days after the onset of each fever episode. Computed tomography (CT) of the chest revealed bilateral hilar lymphadenopathy (BHL), and the mediastinal lymph nodes were swollen. Sarcoidosis was suspected but was ruled out by several tests. Laboratory examinations showed elevated inflammatory markers. Bone marrow examination showed the vacuolization of myeloid precursor cells. A skin biopsy revealed dense dermal, predominantly perivascular, infiltrates. These consisted of mature neutrophils admixed with myeloperoxidase-positive CD163-positive myeloid cells, lymphoid cells and eosinophils. Sequencing analysis identified the somatic UBA1 variant c.122T > C, which results in p.Met41Thr. Treatment with oral prednisone (15 mg/day) and monthly intravenous tocilizumab injections (400 mg) completely resolved the symptoms. Neutrophils are a major source of reactive oxygen species, and the present case demonstrated numerous neutrophilic infiltrates. We hypothesize that the patient might have had elevated derivatives of reactive oxygen metabolites (d-ROMs). d-ROM quantification is a simple method for detecting hydroperoxide levels, and clinical trials have proven it useful for evaluating oxidative stress. In this study, we measured serum d-ROM before and after oral prednisone and tocilizumab treatment. The levels decreased significantly during treatment. Frontiers Media S.A. 2022-12-05 /pmc/articles/PMC9760706/ /pubmed/36544501 http://dx.doi.org/10.3389/fmed.2022.1046820 Text en Copyright © 2022 Tozaki, Tawada, Niwa, Mizutani, Shu, Kawase, Miwa, Ohnishi, Sasai, Miyako, Hosokawa, Kato, Kobayashi, Miyazaki, Shirakami, Shimizu and Iwata. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Tozaki, Nagie
Tawada, Chisato
Niwa, Hirofumi
Mizutani, Yoko
Shu, En
Kawase, Aki
Miwa, Yuki
Ohnishi, Hidenori
Sasai, Hideo
Miyako, Keisuke
Hosokawa, Junichi
Kato, Ayaka
Kobayashi, Kazuhiro
Miyazaki, Tatsuhiko
Shirakami, Yohei
Shimizu, Masahito
Iwata, Hiroaki
A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment
title A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment
title_full A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment
title_fullStr A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment
title_full_unstemmed A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment
title_short A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment
title_sort case of vexas syndrome (vacuoles, e1 enzyme, x-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760706/
https://www.ncbi.nlm.nih.gov/pubmed/36544501
http://dx.doi.org/10.3389/fmed.2022.1046820
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