Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, and Somatic (VEXAS) Syndrome: A Diagnostic and Therapeutic Conundrum

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome is an adult-onset systemic autoinflammatory condition notable for being simultaneously a hematologic disease. Here, we present clinical case of 67-year-old man referred to the Autoimmune Diseases Outpatient Clinic two-year history maculopapular rash involving face, trunk, back, upper limbs. At time, patient had already undergone three skin biopsies, with conflicting results. His physical exam was only remarkable multiple roundly shaped maculopapules extremities. Laboratory evaluation revealed elevated erythrocyte sedimentation rate C-reactive protein, increased alpha-2 zone in serum protein electrophoresis, positive IgM antibodies against Borrelia burgdorferi. A diagnosis Lyme disease assumed, trial doxycycline two weeks introduced, as well hydroxychloroquine at maximum dosage 5 mg/kg, without noticeable improvement. new biopsy performed, suggestive amyopathic dermatomyositis. Prednisolone 0.5 mg/kg/day then started, some Two years later, developed episodes deep vein thrombosis along de novo macrocytic anemia neutropenia. positron emission computed tomography showed nonspecific medullar activation, whereas bone marrow aspirate suggested myelodysplastic syndrome. The became progressively more reliant on regular blood product transfusions, and, recrudescence his lesions also noted under prednisolone mg/day. Although increase association methotrexate dapsone were tried, no improvement noted. Bone repeated, aberrant vacuolized cells observed. genetic analysis Met41Leu mutation ubiquitin-activating enzyme 1 (UBA1) gene, confirming VEXAS started tocilizumab 6 but profound neutropenia required therapeutical switch ruxolitinib.

Language: Английский

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Clinical features and treatments of VEXAS syndrome in critical care: a scoping review

Critical Care, Journal Year: 2025, Volume and Issue: 29(1)

Published: April 17, 2025

Abstract Background Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently discovered severe disorder that predominantly affects adult males, characterized by systemic inflammation and hematologic abnormalities. Despite its profound impact on patient outcomes, awareness of VEXAS among critical care providers remains severely limited, often leading to delayed recognition, diagnosis, initiation appropriate treatment. This study aims address this knowledge gap conducting scoping review in the setting. Methods followed PRISMA-ScR guidelines Joanna Briggs Institute methodology, analyzing data from Cochrane CENTRAL, MEDLINE via PubMed, EMBASE, Web Science May 19, 2024. We included studies reported clinical features treatments patients with requiring care. Results Of 1262 reports identified, 78 met inclusion criteria, including 45 case reports/series, 17 observational studies, 15 reviews, one systematic review. Analysis 55 cases revealed median age 69 strong male predominance (54/55). ICU admission rates ranged 28 33%, mortality between 18 40%. Critical manifestations shock, hemophagocytic lymphohistiocytosis, acute respiratory distress syndrome, thrombosis, airway edema. Sepsis was cause death, other causes related organ failure, cardiovascular events, intestinal perforation. Treatment approaches combined conventional measures immunosuppressive immunomodulatory therapies, although infectious complications were frequently reported. Conclusion lack systematically analyzed focusing setting, suggesting significant understanding characteristics optimal for syndrome. Further research focused setting essential improve early develop standardized treatment protocols, ultimately outcomes complex population.

Language: Английский

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Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review

Rheumatology International, Journal Year: 2023, Volume and Issue: 44(7), P. 1219 - 1232

Published: Dec. 21, 2023

Language: Английский

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VEXAS and Myelodysplastic Syndrome: An Interdisciplinary Challenge

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(4), P. 1049 - 1049

Published: Feb. 12, 2024

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in hematopoietic progenitor cells. This case series of four patients with and comorbid myelodysplastic (MDS) aims to describe clinical, imaging, hematologic presentations as well response therapy. Four MDS are described. A detailed analysis imaging features, hemato-oncological presentation including bone marrow microscopy clinical–rheumatological features treatment outcomes given. All were male; ages ranged between 64 81 years; all diagnosed MDS. CT was available for three patients, whom exhibited pulmonary infiltrates varying severity, resembling COVID-19 or hypersensitivity pneumonitis without traces scarring. Bone showed maturation-disordered erythropoiesis pathognomonic vacuolation. Somatic mutation the UBA1 codon 41 found next-generation sequencing. Therapy regimes included glucocorticoids, JAK1/2-inhibitors, nucleoside analogues, IL-1 IL-6 receptor antagonists. No fatalities occurred (observation period from symptom onset: 18–68 months). Given potential underreporting syndrome, we highly recommend contemporary screening presenting ambiguous signs symptoms which persist over 18 months despite treatment. The emergence cytopenia, especially macrocytic hyperchromic anemia, should prompt early testing mutations. Notably conspicuous, alterations therapy-resistant be discussed interdisciplinary medical teams (Rheumatology, Hematology, Radiology further specialist departments) facilitate timely diagnosis during clinical course disease.

Language: Английский

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Relapsing Polychondritis in a Patient With Rheumatoid Arthritis: Improved With Pentoxifylline

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 15, 2023

Relapsing polychondritis (RP) is a rare autoimmune condition that involves the recurrent inflammation of cartilage throughout body, with predilection for auricular and nasal cartilage. Given its rarity diverse clinical presentations, RP frequently misdiagnosed or left untreated, which can lead to significant morbidity mortality. When it correctly diagnosed, there are no standardized guidelines on treatment date. Management this disease requires multidisciplinary approach, about 30% patients have other disorders, further complicating approach targeted treatment. Biologic agents (including TNF inhibitors) commonly used. We present compelling case 46-year-old female rheumatoid arthritis (well-controlled adalimumab) hypothyroidism who presented dermatology clinic episodes painful, swollen, erythematous ears, leading diagnosis relapsing polychondritis. Off-label use oral pentoxifylline, along topical corticosteroids, led improvement in her symptoms. Dermatologists play an important role disorder, as skin manifestations may be initial presenting sign RP. Further research into potentially effective treatments needed. Timely identification management prevent progression destruction, thus improving patients' long-term prognosis overall quality life.

Language: Английский

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Refining Vascular Care Through Science Without Losing the Art

Annals of Vascular Surgery, Journal Year: 2023, Volume and Issue: 101, P. 11 - 14

Published: Dec. 16, 2023

Language: Английский

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VEXAS Syndrome—Successful Diagnosis with Multidisciplinary Cooperation

rheuma plus, Journal Year: 2024, Volume and Issue: 23(5), P. 271 - 277

Published: May 15, 2024

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Die häufigsten Fiebersyndrome und autoinflammatorischen Erkrankungen im Erwachsenenalter

Zeitschrift für Rheumatologie, Journal Year: 2024, Volume and Issue: 83(5), P. 363 - 375

Published: May 27, 2024

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Krankheitsbilder im Alter: Polymyalgia rheumatica, Riesenzellarteriitis, Schnitzler-Syndrom und VEXAS-Syndrom

Aktuelle Rheumatologie, Journal Year: 2024, Volume and Issue: 49(05), P. 310 - 316

Published: Sept. 26, 2024

Zusammenfassung Die Behandlung von älteren Patient:innen bedarf besonderer Aufmerksamkeit und spezieller Fachkenntnisse. Altersbedingte Veränderungen des Immunsystems, multiple Komorbiditäten eine altersabhängige Pharmakokinetik -dynamik erfordern individuelle sorgfältige Herangehensweise. Ziel dieses Artikels ist es, aktuelle Erkenntnisse praxisrelevante Ansätze zur Diagnostik Therapie ausgewählter rheumatologischer Erkrankungen im höheren Lebensalter, wie Polymyalgia rheumatica (PMR), Riesenzellarteriitis (RZA), Schnitzler-Syndrom VEXAS-Syndrom zu präsentieren.

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How Protein Ubiquitination Can Influence Cytokine Expression—Updated Review on Autoinflammatory VEXAS Syndrome

Immuno, Journal Year: 2024, Volume and Issue: 4(3), P. 286 - 300

Published: Sept. 23, 2024

VEXAS syndrome is a new disease entity with symptoms that can mimic hematological, rheumatic and dermatological diseases. It important to take multidisciplinary approach patient care, taking into account genetic testing, in which the presence of mutations UBA1 gene confirm diagnosis. mutation has been shown be involved induction inflammatory response through many different mechanisms. NF-κB TNF-α pathways appear most syndrome. There are result outcomes, suggesting it possible prognostic factor. Furthermore, differ how they impair function. Cytokines have significantly altered patients; however, their exact expression importance were not clearly defined. Interleukins, such as interleukin (IL)-6, IL-1, IL-2R others, reported expressed at an level, similarly other cytokines, IFN-γ or TNF-α. worth noting certain cytokines vary between patients, poses therapeutic difficulties selecting right drug. Therefore, aim this review was describe associate mutation.

Language: Английский

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