Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784852537091817472 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9760706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tozakinagie acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT tawadachisato acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT niwahirofumi acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT mizutaniyoko acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT shuen acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT kawaseaki acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT miwayuki acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT ohnishihidenori acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT sasaihideo acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT miyakokeisuke acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT hosokawajunichi acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT katoayaka acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT kobayashikazuhiro acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT miyazakitatsuhiko acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT shirakamiyohei acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT shimizumasahito acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT iwatahiroaki acaseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT tozakinagie caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT tawadachisato caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT niwahirofumi caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT mizutaniyoko caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT shuen caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT kawaseaki caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT miwayuki caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT ohnishihidenori caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT sasaihideo caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT miyakokeisuke caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT hosokawajunichi caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT katoayaka caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT kobayashikazuhiro caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT miyazakitatsuhiko caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT shirakamiyohei caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT shimizumasahito caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment AT iwatahiroaki caseofvexassyndromevacuolese1enzymexlinkedautoinflammatorysomaticwithdecreasedoxidativestresslevelsafteroralprednisoneandtocilizumabtreatment |