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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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1046820/full |
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| author | Nagie Tozaki Chisato Tawada Hirofumi Niwa Yoko Mizutani En Shu Aki Kawase Yuki Miwa Hidenori Ohnishi Hideo Sasai Hideo Sasai Keisuke Miyako Junichi Hosokawa Ayaka Kato Kazuhiro Kobayashi Tatsuhiko Miyazaki Yohei Shirakami Masahito Shimizu Hiroaki Iwata |
| author_facet | Nagie Tozaki Chisato Tawada Hirofumi Niwa Yoko Mizutani En Shu Aki Kawase Yuki Miwa Hidenori Ohnishi Hideo Sasai Hideo Sasai Keisuke Miyako Junichi Hosokawa Ayaka Kato Kazuhiro Kobayashi Tatsuhiko Miyazaki Yohei Shirakami Masahito Shimizu Hiroaki Iwata |
| author_sort | Nagie Tozaki |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T07:14:56Z |
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| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-11T07:14:56Z |
| publishDate | 2022-12-01 |
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| spelling | doaj.art-d45633eee96a4d5d81924831c388d6942022-12-22T04:38:02ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-12-01910.3389/fmed.2022.10468201046820A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatmentNagie Tozaki0Chisato Tawada1Hirofumi Niwa2Yoko Mizutani3En Shu4Aki Kawase5Yuki Miwa6Hidenori Ohnishi7Hideo Sasai8Hideo Sasai9Keisuke Miyako10Junichi Hosokawa11Ayaka Kato12Kazuhiro Kobayashi13Tatsuhiko Miyazaki14Yohei Shirakami15Masahito Shimizu16Hiroaki Iwata17Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Pediatrics, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Pediatrics, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Pediatrics, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Pediatrics, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Applied Genomics, Kazusa DNA Research Institute, Chiba, JapanDepartment of Applied Genomics, Kazusa DNA Research Institute, Chiba, JapanDepartment of Applied Genomics, Kazusa DNA Research Institute, Chiba, JapanDepartment of General Medicine, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Pathology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of General Medicine, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, JapanVEXAS (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.https://www.frontiersin.org/articles/10.3389/fmed.2022.1046820/fullVEXASvacuolesE1 enzymeX-linkedautoinflammatory diseasessomatic |
| spellingShingle | Nagie Tozaki Chisato Tawada Hirofumi Niwa Yoko Mizutani En Shu Aki Kawase Yuki Miwa Hidenori Ohnishi Hideo Sasai Hideo Sasai Keisuke Miyako Junichi Hosokawa Ayaka Kato Kazuhiro Kobayashi Tatsuhiko Miyazaki Yohei Shirakami Masahito Shimizu Hiroaki Iwata A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment Frontiers in Medicine VEXAS vacuoles E1 enzyme X-linked autoinflammatory diseases somatic |
| 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 | VEXAS vacuoles E1 enzyme X-linked autoinflammatory diseases somatic |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1046820/full |
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