VEXAS syndrome
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Introduction
Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic
Etiology
Epidemiology
- not rare, ~ 1 in 13,500 people in U.S. may have VEXAS syndrome[2]
- predominantly men aged 55-65 years
- women with monosomy X hve been reported
- UBA1 variants found in 1 of 4,269 men > 50 years & in 1 of 26,238 women > 50 years[3]
Pathology
- systemic autoinflammatory disease
- involvement of the lungs, skin, blood vessels, & joints
- aberrant activation of innate immune-signaling pathways
- skin biopsy
- subepidermal clefting; lymphocytic infiltrate
- myeloperoxidase- & CD68-positive immature myeloid* & histiocytic cells
* not myleoblasts (image[5])
- bone marrow biopsy:
- normocellular marrow with cytoplasmic vacuoles in myeloid & erythroid precursors (image[5])
Genetics
- X-linked disease
- somatic mutation in UBA1 gene
Clinical manifestations
- recurrent fevers
- skin lesions (usually neutrophilic dermatosis)
- erythematous, edematous annular (oval) plaques (image[5])
- systemic inflammation
- pulmonary infiltrates, venous thrombosis, periorbital edema, hearing loss[5]
- clinical heterogeneity
Laboratory
- complete blood count (CBC)
- sequencing of UBA1 gene
- serum inflammatory markers are increased.
- serum tumor necrosis factor
- serum interleukin-8
- serum interleukin-6
- serum interferon-inducible protein-10
- serum interferon-gamma,
- serum C-reactive protein
- erythrocyte sedimentation rate
Complications
- high risk of hematologic disease.
- macrocytic anemia (96%)
- venous thromboembolism (44%)
- myelodysplastic syndrome (24%)
- multiple myeloma or MUGUS (20%)
Differential diagnosis
- patients often meet criteria for other autoimmune diseases[5]
- response to treatment less successful with Vexas syndrome[5]
Management
- generally resistant to treatment
- high-dose glucocorticoids
- tocilizumab may have steroid-sparing effects[5]
- Janus kinase inhibitors are investigational[1]
- ruxolitinib may be useful in patients with myelodysplastic syndrome[5]
- azacitidine & stem cell transplantation have been used to treat myelodysplastic syndrome[5]
- mortality is 50% at 5 years
More general terms
References
- ↑ 1.0 1.1 Guidnot C Have you heard of VEXAS syndrome? MDEdge. Internal Medicine. Dec 12, 2022 https://www.mdedge.com/internalmedicine/article/260055/mens-health/have-you-heard-vexas-syndrome
Medscape. Dec 12, 2022 https://www.medscape.com/viewarticle/985324 - ↑ 2.0 2.1 Dotinga R VEXAS Syndrome: More Common, Variable, and Severe Than Expected. Medscape. January 25, 2023 https://www.medscape.com/viewarticle/987466
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. 2023;329(4):318-324 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36692560 https://jamanetwork.com/journals/jama/article-abstract/2800661 - ↑ 3.0 3.1 AMA Morning Rounds. Jan 25, 2023 American Medical Association
- ↑ Fiore K Inflammatory VEXAS Syndrome May Not Be So Uncommon. Is new disease being missed by physicians? MedPage Today January 24, 2023 https://www.medpagetoday.com/rheumatology/generalrheumatology/102772
Beck DB et al Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease N Engl J Med 2020; 383:2628-2638 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33108101 PMCID: PMC7847551 Free PMC article https://www.nejm.org/doi/full/10.1056/NEJMoa2026834 - ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 Raess PW, Sendowski M, Fett N Treatment-Resistant Edematous Annular Plaques and Mild Leukopenia in a Man in His 60s. JAMA Dermatol. 2023;159(8):878-879 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37378991 https://jamanetwork.com/journals/jamadermatology/fullarticle/2806311 https://edhub.ama-assn.org/jn-learning/module/2806311