How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies

Lara D. Veeken, Journal Year: 2023, Volume and Issue: 62(11), P. 3518 - 3525

Published: May 26, 2023

Abstract Objectives To evaluate the effectiveness and safety of current treatment strategies for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Methods A protocolized systematic review according to Preferred Reporting Items Systematic Reviews Meta-Analyses (PRISMA) guidelines was performed. Three databases were searched reports on VEXAS. Data from included publications extracted a narrative synthesis Treatment response recorded as complete (CR), partial (PR) or none (NR) depending changes in clinical symptoms laboratory parameters. Patient characteristics, data previous treatments analysed. Results We identified 36 with total 116 patients; 113 (98.3%) male. The azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) 11/33, 33%; 9/33, 27.3%), tocilizumab 3/15, 20%; 6/15, 40%), allogeneic stem cell transplantation 6/7, 85.7%; one patient died), anakinra 4/5, 80%; NR 1/5, 20%), canakinumab 1/2, 50%; 50%) glucocorticoid monotherapy 1/6, 16.7%; 4/6, 66.7%). Individual available TNF inhibitors, rituximab MTX. adverse events 67 patients (67/116, 57.8%) included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (6/67, 8.9%), cytopenias (4/67, 5.9%), acute 5.9%) chronic graft-vs-host-disease (2/67, 2.9%). Conclusion Current VEXAS are limited inhomogeneous. decisions should be individualized. For devolvement algorithms trials needed. Adverse remain challenge, especially an elevated risk thromboembolism associated JAKi carefully considered.

Language: Английский

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Vasculitis associated with VEXAS syndrome: A literature review

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Aug. 15, 2022

Vasculitis is an inflammatory disorder of the blood vessels that causes damage to a wide variety organs through tissue ischemia. classified according size (large, medium, or small) vessels. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, novel autoinflammatory was described. Somatic mutations in methionine-41 UBA1, major enzyme initiates ubiquitylation, are attributed this disorder. This new disease entity connects seemingly unrelated conditions: syndromes (relapsing chondritis, Sweet's neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome multiple myeloma). Notably, such patients sometimes develop vasculitis, as giant cell arteritis polyarteritis nodosa, fulfill corresponding classification criteria for vasculitis. Thus, vasculitis can be initial manifestation syndrome. research topic exploring link between diseases we first provide overview mechanisms clinical phenotypes Then, literature review using PubMed database performed delineate characteristics associated with Finally, therapeutic options unmet needs discussed.

Language: Английский

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Autoimmune manifestations in VEXAS: Opportunities for integration and pitfalls to interpretation

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 151(5), P. 1204 - 1214

Published: March 21, 2023

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a novel entity manifesting with multiplicity of clinical features. Somatic mutations the UBA1 gene in hematopoietic stem cells constitute genetic basis VEXAS. As an X-linked disorder, most cases occur men, classically developing symptoms during fifth to sixth decade life. Considering its multidisciplinary nature involving numerous branches internal medicine, has elicited wide medical interest and several conditions have been associated this disease. Even so, recognition everyday practice not necessarily straightforward. Close collaboration between different specialists mandatory. Patients may manifest range features from manageable cytopenias disabling life-threatening autoimmune phenomena limited responses therapy, potential for progression hematological malignancies. Diagnostic treatment guidelines are exploratory include rheumatological supportive care treatments. Allogeneic cell transplantation potentially curative, but risks significant position algorithm yet be defined. Herein, we present variegated manifestations VEXAS, provide criteria diagnostic testing UBA1, discuss options, including allogeneic transplantation, current evidence, future directions.

Language: Английский

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

Rheumatology International, Journal Year: 2023, Volume and Issue: 43(6), P. 1023 - 1032

Published: Jan. 8, 2023

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

Language: Английский

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Case Report: Tocilizumab Treatment for VEXAS Syndrome With Relapsing Polychondritis: A Single-Center, 1-Year Longitudinal Observational Study In Japan

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 13, 2022

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an autoinflammatory disease caused by variants in the UBA1 gene that lead to severe systemic inflammation and myelodysplastic syndrome. Although no standard therapy has been established yet, azacitidine bone marrow transplantation have reported be promising possibilities; however, indications for these treatments are problematic not necessarily applicable all patients. We previously results of short-term treatment with tocilizumab (TCZ) glucocorticoids three patients VEXAS In this paper, we report combination TCZ allowed continue at least one year without significant progression. Glucocorticoids were able reduced from start TCZ. Adverse events herpes zoster, skin ulceration after cellulitis, decreased blood counts. The suggest significance as a bridge development future therapies.

Language: Английский

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

Experimental Dermatology, Journal Year: 2024, Volume and Issue: 33(3)

Published: March 1, 2024

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

Language: Английский

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Myelodysplastic syndrome and autoimmune disorders: two sides of the same coin?

The Lancet Haematology, Journal Year: 2022, Volume and Issue: 9(7), P. e523 - e534

Published: June 27, 2022

Language: Английский

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JAK inhibitors for the treatment of VEXAS syndrome

Experimental Biology and Medicine, Journal Year: 2023, Volume and Issue: 248(5), P. 394 - 398

Published: March 1, 2023

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a novel described autoinflammatory entity for which the diagnosis defined by mutations of UBA1 X-linked gene in hematopoietic progenitor cells. The clinical manifestations are heterogeneous since they range from symptoms to presence underlying hematologic disorders such as myelodysplastic syndromes. Response treatment VEXAS very poor and date, therapeutic strategies adopted only partially effective. However, recently cohorts subjects with treated Janus kinase inhibitors (JAK-I) proved that these drugs can be effective several related disease. Herein, we carried out brief literature review includes single cases JAK-I were promising strategy manage patients. Subsequently, our experience VEXAS, illustrating first case, knowledge, 65-year-old man who was successfully selective JAK-1 inhibitor filgotinib.

Language: Английский

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VEXAS Syndrome—Review

Global Medical Genetics, Journal Year: 2023, Volume and Issue: 10(03), P. 133 - 143

Published: July 10, 2023

Abstract VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined refractory adult-onset autoinflammatory caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene hematopoietic stem and progenitor cells, resulting shift UBA1 isoform expression. Thus, patients develop spectrum of systemic inflammatory manifestations hematologic symptoms. To date, respond poorly to immune suppressive drugs, except high-dose glucocorticoids, no treatment guidelines have been established. Given high mortality rate, needs be taken seriously physicians all specialties. This article aims describe key features, pathogenesis, clinical better understand targeted improve prognosis syndrome.

Language: Английский

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VEXAS syndrome: A newly identified X-Linked hematoinflammatory disorder – A comprehensive overview of its genetic, molecular, inflammatory, and clinical landscape

Journal of Autoimmunity, Journal Year: 2025, Volume and Issue: 154, P. 103425 - 103425

Published: April 29, 2025

Language: Английский

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