Myelodysplastic Syndrome Associated With Auto-Immune Inflammatory Disease in VEXAS Syndrome

Thomas, Vibha Taneja; Penmetcha, Mohan

doi:10.14740/jh940

Cited by 5 publications

(5 citation statements)

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“…It is well known that significant side effects of tocilizumab may include the reactivation of tuberculosis; infection by opportunistic bacteria, fungi, and viruses; and intestinal perforation. Of note, there have been two reports of intestinal perforation in patients with VEXAS syndrome receiving tocilizumab ( 5 , 6 ). Certainly, additional data and long-term follow-ups are needed to further validate these findings.…”

Section: Discussionmentioning

confidence: 99%

“…VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is the first example of an autoinflammatory disease arising exclusively from somatic mutations and is one of an emerging class of acquired errors of immunity. Although this disorder was only first reported in 2020, hundreds of patients have been identified (1)(2)(3)(4)(5). VEXAS syndrome is caused by pathogenic variants in ubiquitin-like modifier activating enzyme 1 (UBA1), a gene on the X chromosome that encodes UBA1, and these mutations are restricted to myeloid-lineage cells (1).…”

Section: Introductionmentioning

confidence: 99%

“…VEXAS syndrome is caused by pathogenic variants in ubiquitin-like modifier activating enzyme 1 (UBA1), a gene on the X chromosome that encodes UBA1, and these mutations are restricted to myeloid-lineage cells (1). Patients with this syndrome are characterized by adult-onset recurrent fever, neutrophilic dermatoses, leukocytoclastic vasculitis, polyarteritis nodosa, ear and nose chondritis, venous thromboembolism, pulmonary infiltrates, gastrointestinal pain or inflammation, aortitis, hepatosplenomegaly, macrocytic anemia, elevated acutephase reactants, myelodysplastic syndrome (MDS), multiple myeloma, and bone marrow vacuolization restricted to myeloid and erythroid precursor cells (1)(2)(3)(4)(5). The majority of the patients have myeloid lineage-restricted somatic mutations in UBA1, affecting the Met41 residue of the protein.…”

Section: Introductionmentioning

confidence: 99%

“…The majority of the patients have myeloid lineage-restricted somatic mutations in UBA1 , affecting the Met41 residue of the protein. These mutations promote the production of an inactive isoform (UBA1c) from a downstream translation site (Met67), resulting in hyperinflammation and decreased ubiquitylation ( 1 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2022

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2022

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“…While several DMARDs have been trialled in VEXAS patients, including azathioprine, hydroxychloroquine, leflunomide and sulfasalazine, DMARDs have shown limited effectiveness 11,43,51–53 …”

Section: Vexas Syndrome Treatmentsmentioning

confidence: 99%

VEXAS syndrome: A review of cutaneous findings and treatments in an emerging autoinflammatory disease

Saad,

Patil,

Cruz

et al. 2024

Experimental Dermatology

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VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory and somatic mutation) syndrome is a novel autoinflammatory, late‐onset, disorder first identified in 2020. It is caused by mutations in the UBA1 gene. The most prominent clinical features reported by VEXAS patients are cutaneous and haematological, having characteristic skin features reported as the initial presenting findings of the disease. VEXAS is a severe and treatment‐resistant condition with high morbidity and mortality rates. Here, we examine all case reports and case series of VEXAS syndrome through March 2023 focusing on those presenting cutaneous manifestations. We discuss these manifestations and their reported treatment strategies. In many cases, it might be first suspected and diagnosed by dermatologists, highlighting their vital role in initiating timely multidisciplinary care.

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Pulmonary manifestations in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome: a systematic review

et al. 2023

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Background VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly described auto-inflammatory disease. Many cases feature pulmonary infiltrates or respiratory failure. This systematic review aimed to summarize respiratory manifestations in VEXAS syndrome described to date. Methods Databases were searched for articles discussing VEXAS syndrome until May 2022. The research question was: What are the pulmonary manifestations in patients with VEXAS syndrome? The search was restricted to English language and those discussing clinical presentation of disease. Information on basic demographics, type and prevalence of pulmonary manifestations, co-existing disease associations and author conclusions on pulmonary involvement were extracted. The protocol was registered on the PROSPERO register of systematic reviews. Results Initially, 219 articles were retrieved with 36 ultimately included (all case reports or series). A total of 269 patients with VEXAS were included, 98.6% male, mean age 66.8 years at disease onset. The most frequently described pulmonary manifestation was infiltrates (43.1%; n = 116), followed by pleural effusion (7.4%; n = 20) and idiopathic interstitial pneumonia (3.3%; n = 9). Other pulmonary manifestations were: nonspecific interstitial pneumonia (n = 1), bronchiolitis obliterans (n = 3), pulmonary vasculitis (n = 6), bronchiectasis (n = 1), alveolar haemorrhage (n = 1), pulmonary embolism (n = 4), bronchial stenosis (n = 1), and alveolitis (n = 1). Several patients had one or more co-existing autoimmune/inflammatory condition. It was not reported which patients had particular pulmonary manifestations. Conclusion This is the first systematic review undertaken in VEXAS patients. Our results demonstrate that pulmonary involvement is common in this patient group. It is unclear if respiratory manifestations are part of the primary disease or a co-existing condition. Larger epidemiological analyses will aid further characterisation of pulmonary involvement and disease management.

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Myelodysplastic Syndrome Associated With Auto-Immune Inflammatory Disease in VEXAS Syndrome

Cited by 5 publications

References 1 publication

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

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

VEXAS syndrome: A review of cutaneous findings and treatments in an emerging autoinflammatory disease

Pulmonary manifestations in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome: a systematic review

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