VEXAS-Syndrom – Ein Kurzreview

Zusammenfassung

VEXAS (Vakuolen, E1-Enzyme, X-chromosomal, Autoinflammation, Somatisch)-Syndrom, 2020 erstmals beschrieben, ist verursacht durch Mutationen des UBA1-Gens im X-Chromosom, was zu Dysregulation des angeborenen Immunsystems infolge von fehlerhafter Ubiquitinierung führt. Die Störungen des Proteinstoffwechsels führen zu multiplen Autoinflammationen verschiedener Organe. Zugleich induziert diese Mutation hämatologische Autoinflammationen mit insbesondere Panzytopenien. Allgemeinsymptome sind Fieber und Anämie. An der Haut kommt es zu einer Reihe von Manifestationen wie Sweet-Syndrom, Urtikaria, Livedo-Syndrome, periokuläre Ödeme, verschiedene Formen von Vaskulitis sowie auch vergrößerte Lymphknoten. Histologisch sind neutrophile Infiltrate in der Dermis und eine leukozytoklastische Vaskulitis typisch. Sehr charakteristisch sind rezidivierende Chondritiden der Nase und Ohren, daneben multiple Organinflammationen der Lunge, Augen, Gelenke und gastrointestinal. Therapeutisch am effektivsten sind derzeit hochdosierte Glukokortikoide und die allogene Stammzelltransplantation.
Deshalb: Bei Männern über 40 Jahre mit Sweet-Syndrom-ähnlichen Plaques, Fieber und Chondritis an Ohr oder Nase und/oder anderen Inflammationen an das VEXAS-Syndrom denken und eine Hautbiopsie veranlassen!

Abstract

VEXAS (vacuoles, E1 enzymes, X-linked, autoinflammation, somatic) syndrome, first described in 2020, is caused by mutations in the UBA1 gene on the X chromosome, leading to dysregulation of the innate immune system as a result of defective ubiquitination. The disturbances in protein metabolism lead to multiple autoinflammation of various organs. At the same time, this mutation induces hematological autoinflammation, primarily pancytopenia. General symptoms include fever and anemia. A number of skin manifestations occur, such as Sweet syndrome, urticaria, livedo syndrome, periocular edema, various forms of vasculitis, and enlarged lymph nodes. Histologically, neutrophilic infiltrates in the dermis and leukocytoclastic vasculitis are typical. Recurrent chondritis of the nose and ears are very characteristic, along with multiple organ inflammation of the lungs, eyes, joints, and gastrointestinal tract. Currently, high-dose glucocorticoids and allogeneic stem cell transplantation are the most effective treatments.
Therefore: In men over 40 years of age with Sweet syndrome-like plaques, fever, and chondritis of the ear or nose and/or other inflammation, consider VEXAS syndrome and arrange for a skin biopsy!

Schlüsselwörter

Neutrophile Dermatose - Chondritis - Vaskulitis - Panzytopenie

Keywords

neutrophilic dermatosis - chondritis - vasculitis - pancytopenia

Publikationsverlauf

Eingereicht: 03. August 2025

Angenommen: 04. August 2025

Artikel online veröffentlicht:
15. Oktober 2025

• Literatur

• 1 Beck DB, Ferrada MA, Sikora KA. et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 2020; 383: 2628-2638
• 2 Bourbon E, Heiblig M, Valentin M G. et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 2021; 137: 3682-3684
• 3 Koster M J, Lasho T L, Olteanu H. et al. VEXAS syndrome: clinical, hematological features and a practical approach to diagnosis and management. Am J Hematol 2024; 99: 284-299
• 4 Georgin-Lavialle S, Terrier B, Guedon AF. et al. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients. Brit J Dermatol 2022; 186: 564-574
• 5 Dehghan N, Marcon KM, Sedlic T. et al. Vacuoles, E 1 enzyme linked, autoinflammatory, somatic (VEXAS) syndrome: fevers, myalgia, arthralgia, auricular chondritis, and erythema nodosum. Lancet 2021; 398: 621
• 6 Zakine E, Schell B, Battistella M. et al. UBA 1 variants in neutrophilic dermatosis skin lesions of patients with VEXAS syndrome. JAMA Dermatol 2021; 157: 1349-1354
• 7 Huang H, Zhang W, Cai W. et al. VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder. Exp Haematol Oncol 2021; 10: 23-27
• 8 Sterling D, Duncan ME, Philippidou M. et al. Vexas syndrome (vakuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist. J Am Acad Dermatol 2023; 89: 1209-1214
• 9 Beck DB, Bodian DL, Shah V. et al. Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population. JAMA 2013; 32: 318-324
• 10 Van der Made CI, Potjewijd J, Hoogstins A. et al. Adult-onset autoinflammation caused by somatic mutations in UBA 1: A Dutch case series of patients with VEXAS. J Allerg Cilin Immunol 2022; 149: 432-439.e4
• 11 Muratore F, Marvisi C, Castrignano P. et al. VEXAS syndrome: a case series from a single-center cohort of Italian patients with vasculitis. Arthritis Rheumatol 2022; 74: 665-670
• 12 Zhau LP, Schell B, Sebert M. et al. Prevalence of UBA1 mutations in MDS/CMML patients with systemic inflammatory and auto-immune disease. Leukemia 2021; 35: 2731-2733
• 13 Boyadzhieva Z, Ruffer N, Kotter L. et al. How to treat VEXAS syndrome: a systemic review on effectiveness and safety of current treatment strategies. Rheumatology 2023; 62: 3518-3525
• 14 Magnol M, Couvaras I, Deghoe Y. et al. Vexas syndrome in a patient with previous spondylarthritis with favorable response to intravenous immunoglobulin anti il-17 therapy. Rheumatology 2021; 60: e314-e315
• 15 Heiblig M, Ferrafa MA, Koster MJ. et al. Ruxolithinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study. Blood 2022; 140: 927-930
• 16 Comont T, Heiblig M, Riviere E. et al. Azacitidine for patients with vakuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) and myelodysplastic syndrome: data from the French VEXAS registry. Br J Haematol 2022; 196: 969-974
• 17 Diarra A, Duployez N, Fournier E. et al. Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience. Blood Adv 2022; 6: 998-1003