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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An update on VEXAS syndrome

Expert Review of Clinical Immunology, Journal Year: 2022, Volume and Issue: 19(2), P. 203 - 215

Published: Dec. 20, 2022

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described, late-onset, acquired autoinflammatory disorder caused by mutations in the UBA1 gene. The various clinical manifestations of broadly divided into inflammatory or haematological. defines new disease category - hematoinflammatory disorders triggered somatic restricted to blood but causing systemic inflammation with multi-organ involvement and associated aberrant bone marrow status. causes significant morbidity reduced life expectancy, optimum standard care remains undefined.This review describes discovery VEXAS, relevant genetic immunopathology disease. A detailed account its mimics provided. Current treatment management options are discussed.New rare variants VEXAS-like negative cases reported. Consensus diagnostic criteria might be required define related disorders. Investigation sporadic, will require application deep sequencing using DNA obtained from cellular tissue locations. Prospective studies needed optimal supportive for patients varying severity prognosis. VEXAS-specific hematopoietic stem cell transplant selection also development.

Language: Английский

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Tocilizumab for treatment of cutaneous and systemic manifestations of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome without myelodysplastic syndrome

JAAD Case Reports, Journal Year: 2022, Volume and Issue: 23, P. 15 - 19

Published: March 2, 2022

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a newly described, adult-onset, autoinflammatory disorder caused by mutations in the X-linked UBA1 gene. This characterized fevers, cytopenias, peripherally circulating myeloid and erythroid precursors with cytoplasmic vacuoles dysplastic changes, pulmonary inflammation, chondritis, vasculitis, joint pain swelling.1,2 Nearly all patients VEXAS present cutaneous manifestations of disease, most commonly robust neutrophilic dermatosis.

Language: Английский

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Novel causative variants of VEXAS in UBA1 detected through whole genome transcriptome sequencing in a large cohort of hematological malignancies

Leukemia, Journal Year: 2023, Volume and Issue: 37(5), P. 1080 - 1091

Published: Feb. 23, 2023

UBA1 is an X-linked gene and encodes ubiquitin-activating enzyme. Three somatic mutations altering the alternative start codon (M41) in hematopoietic precursor cells have recently been described, resulting a syndrome of severe inflammation, cytopenias, presence intracellular vacuoles precursors - termed VEXAS syndrome, predominantly male disease. Here we present patient with clinical features who harbored two novel variants (I894S N606I). To better understand relevance biological consequences non-M41 (UBA1non-M41) variants, analyzed whole genome transcriptome data 4168 patients hematological malignancies detected additional 16 UBA1non-M41 putative clear sex-bias myeloid malignancies. Patients diagnosed carrying either had or immunodysregulatory symptoms. Analysis confirmed neutrophil activation compared to healthy controls but did not result specific transcriptomic signature UBA1M41 comparison MDS patients. In summary, described multiple various expanding genomic spectrum syndrome.

Language: Английский

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Novel Somatic UBA1 Variant in a Patient With VEXAS Syndrome

Arthritis & Rheumatology, Journal Year: 2023, Volume and Issue: 75(7), P. 1285 - 1290

Published: Feb. 10, 2023

Somatic mutations in UBA1 have recently been causally linked to a severe adult-onset inflammatory condition referred as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Ubiquitin-activating enzyme (UBA-1) is of fundamental importance the modulation ubiquitin homeostasis and majority downstream ubiquitylation-dependent cellular processes. Direct sequencing analysis exon 3 containing prevalent variants p.Met41Leu, p.Met41Val, and/or p.Met41Thr usually used confirm disease-associated mutations.

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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Cutaneous involvement in VEXAS syndrome: clinical and histopathologic findings

International Journal of Dermatology, Journal Year: 2023, Volume and Issue: 62(7), P. 938 - 945

Published: March 8, 2023

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory disease with frequent cutaneous manifestations.We conducted a retrospective study of all patients genetically confirmed seen at our institution. Available clinical photographs and skin biopsy slides were reviewed.Cutaneous manifestations developed in 22/25 (88%) syndrome. From this group, 10/22 (45%) involvement before or the time other features VEXAS. Twenty distinct dermatologic presentations from 14 reviewed, histopathologic patterns classified as follows: neutrophilic urticarial dermatosis (n = 5, 25%), leukocytoclastic/urticarial vasculitis 4, 20%), tissue reaction 3, 15%), panniculitis 2, 10%), nonspecific chronic septal 10%). Common systemic findings included macrocytic anemia (96%), fever (88%), thrombocytopenia (76%), weight loss ocular inflammation (64%), pulmonary infiltrates (56%), deep venous thrombosis embolism (52%), inflammatory arthritis (52%).Cutaneous common feature syndrome, exist on spectrum dermatoses.

Language: Английский

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VEXAS syndrome: complete molecular remission after hypomethylating therapy

Annals of Hematology, Journal Year: 2024, Volume and Issue: 103(3), P. 993 - 997

Published: Jan. 12, 2024

Abstract The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While therapeutic strategies have explored case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation considered only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of underlying UBA1 mutant clone outside context HCT. Both received hypomethylating agent azacitidine, deep triggered de-escalation even cessation sustained one them. Prospective studies are necessary to clarify which will benefit most from therapy understand variability response different strategies.

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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Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 20, 2022

Somatic genetic mutations involving the innate and inflammasome signaling are key drivers of pathogenesis myelodysplastic syndromes (MDS). Herein, we present a patient, who suffered from long-standing refractory adult-onset autoinflammatory syndrome (AIS), previously interpreted as various distinct rheumatic disorders. Developing pancytopenia particularly macrocytic anemia prompted screening for hematological malignancy, which led to diagnosis TET-2-positive MDS. The impressive continuously changing range organ involvement, with remarkable refractoriness anti-inflammatory treatment, exceeded common phenotype MDS patients. This us suspect recently discovered disease, characterized by somatic UBA1 gene: VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, was ultimately confirmed testing. Reevaluation previous bone marrow biopsies showed presence characteristic vacuoles in myeloid- erythroid progenitor cells. Our case illustrates that triad an unresponsive multisystemic abnormalities progenitors biopsy should prompt syndrome.

Language: Английский

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