Table of ContentsView AllTable of ContentsKnowns and UnknownsSymptomsDiagnosisPrognosisTreatmentFinding Care
Table of ContentsView All
View All
Table of Contents
Knowns and Unknowns
Symptoms
Diagnosis
Prognosis
Treatment
Finding Care
The prevalence of VEXAS syndrome is not yet known, but it is believed to be underestimated.Some research estimates that it affects 1 in 13,000 people, but more research is needed.
VEXAS syndrome affects mostly males and has an age at diagnosis of about 43 to 87 years.Characteristics of VEXAS syndrome includeinflammationof the skin, joints, vessels, and cartilage, visual and hearing impairment, and hematological disorders.
There is currently no standard protocol for treating VEXAS syndrome because the condition is novel and still being researched. Some treatments that may be offered includeglucocorticoids, conventional disease-modifyingantirheumaticdrugs (DMARDs), biologically targeted drugs, andallogeneic hematopoieticstem cell transplantation(blood cell-producing stem cells from a donor are given to the recipient).
This article will discuss the knowns and unknowns of VEXAS syndrome, the symptoms and affected organs with VEXAS syndrome, the diagnosis and prognosis of VEXAS syndrome, and treatments to manage VEXAS syndrome.
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VEXAS Syndrome: Knowns and Unknowns
The acronym “VEXAS” stands for:
A Note on Gendered Language
VEXAS syndrome is considered an autoinflammatory disease, involving inflammation-related damage to organs and tissues.
Without the E1 enzyme, damaged proteins and waste build up within the cells. This triggers the immune system to attack healthy tissue because it sees the excess waste as a threat, leading to inflammation, impaired blood cell development, and other characteristics of VEXAS syndrome.
The UBA1 gene variants that cause VEXAS syndrome are found only in certain immune system cells and blood-forming cells in thebone marrow.
Because the UBA1 gene is on the X chromosome, VEXAS syndrome is more common in people with only one X chromosome, such as those with the XY chromosome combination (typical for males) and people withcertain genetic conditions.
People with two X chromosomes would need to have a mutation in both copies of the UBA1 gene or a defect in the X chromosome without the mutated gene to develop VEXAS syndrome.
Some estimates suggest about 13,200 men and 2,300 women in the United States have VEXAS syndrome.Prevalence in men over 50 years of age has been estimated to be 1 in 4,269.
Risk factors for VEXAS syndrome include:
VEXAS Syndrome and Affected Organs
The main symptoms of VEXAS syndrome include:
Other symptoms of VEXAS syndrome are:
Blau Syndrome: Autoimmune Symptoms in Children and Adults
VEXAS Syndrome Phenotypes
Three basic phenotypes (patterns of observable characteristics) for VEXAS syndrome have been suggested.
Phenotype 1 includes mild to moderately severe symptoms, including:
Phenotype 2 characteristics related to MDS include:
Phenotype 3’s inflammatory characteristics occur in older adults and include:
VEXAS Syndrome RashVEXAS syndrome often (more than 85% of the time) causes skin symptoms, such as:Neutrophilic dermatoses (resemblingSweet syndrome): Tender, firm, pigmented or purpuric (red or purple spots on lighter skin tones, brown to black on darker skin tones, that don’t change color when pressed) nodules, and plaques that may have a small depression in the middle (resembling a navel)Vasculitis: Resembling livedo racemosa (mottling of the skin in an irregular, netlike pattern), polyarteritis nodosa (produces painful, discolored nodules), or giant cell arteritis (causes inflammation of blood vessels)Erythema nodosum: Tender, red or darker-colored bumps, commonly presents symmetrically on the shins)Urticaria(hives): Sometimes itchy welts or bumps, red on lighter skin tones, skin-colored or darker-colored on darker skin tonesSkin blisters: Fluid filling a space between layers of the skin, causing a “bubble"Maculopapular rash: Mix of macules (flat, discolored areas of skin), and papules (small, raised bumps)Skin symptoms are often the first sign of VEXAS syndrome.
VEXAS Syndrome Rash
VEXAS syndrome often (more than 85% of the time) causes skin symptoms, such as:Neutrophilic dermatoses (resemblingSweet syndrome): Tender, firm, pigmented or purpuric (red or purple spots on lighter skin tones, brown to black on darker skin tones, that don’t change color when pressed) nodules, and plaques that may have a small depression in the middle (resembling a navel)Vasculitis: Resembling livedo racemosa (mottling of the skin in an irregular, netlike pattern), polyarteritis nodosa (produces painful, discolored nodules), or giant cell arteritis (causes inflammation of blood vessels)Erythema nodosum: Tender, red or darker-colored bumps, commonly presents symmetrically on the shins)Urticaria(hives): Sometimes itchy welts or bumps, red on lighter skin tones, skin-colored or darker-colored on darker skin tonesSkin blisters: Fluid filling a space between layers of the skin, causing a “bubble"Maculopapular rash: Mix of macules (flat, discolored areas of skin), and papules (small, raised bumps)Skin symptoms are often the first sign of VEXAS syndrome.
VEXAS syndrome often (more than 85% of the time) causes skin symptoms, such as:
Skin symptoms are often the first sign of VEXAS syndrome.
Who Diagnoses VEXAS Syndrome?
Steps to Diagnosis
Guidelines for the diagnosis of VEXAS syndrome have not yet been established. Often, a diagnosis is made retrospectively for research purposes.
Genetic testing is diagnostic for VEXAS syndrome. VEXAS syndrome may be tested for if a healthcare provider suspects it after observing symptoms. Healthcare providers are recommended to consider VEXAS syndrome in men older than 50 who present with:
VEXAS syndrome can resemble and/or occur alongside other systemic inflammatory conditions and may be missed initially. People with VEXAS syndrome have often had symptoms for four to five years before receiving a diagnosis.
Diagnostic tests and procedures that may be performed if VEXAS syndrome is suspected include:
Prognosis With Diagnosed VEXAS Syndrome
VEXAS syndrome is chronic and progressive. It can have complications such as:
Survival rates are still being researched. Survival rates may depend on how the condition manifests. A study of 116 people with VEXAS syndrome grouped participants into three clusters.
The five-yearsurvival rates(number of participants still alive five years after diagnosis or beginning treatment) for each of the clusters in the study were:
Other research shows an overall five-year survival rate of about 50%.
Research on VEXAS syndrome is still relatively new, and more is needed to determine survival rates, and ways to improve them.
Treatments to Manage VEXAS Syndrome
VEXAS syndrome can be challenging to treat, and often requires the cooperation ofdifferent specialist teams.
There is no standardized treatment protocol for VEXAS syndrome, and more research is needed to help find the best courses of treatment.
The two main approaches to treatment are:
Treatments that may be used in treating VEXAS syndrome include:
Allogeneichematopoietic stem cell transplantation (allo-HSCT) is a procedure that may be suggested for people with VEXAS syndrome that is not responding to medication. In this procedure,blood cell–producing stem cells from a donor are given to the recipient, usually after treatment to eradicate the recipient’s blood-producing cells.
Allo-HSCT may be particularly beneficial for people who are in the early stages of VEXAS syndrome, who are high risk, and who have poor clinical response.
Clinics and Interdisciplinary Care
VEXAS syndrome typically requires a treatment plan that involves healthcare providers from several specialties. If you aren’t sure where to start, ask your primary care provider or the healthcare provider who diagnosed your VEXAS syndrome for a referral to specialists for treatment.
Summary
VEXAS syndrome can affect several organs and systems and cause symptoms, includinginflammation of the skin, joints, vessels, eyes, and cartilage. Genetic testis is diagnostic for VEXAS syndrome.
There is currently no standard protocol for treating VEXAS syndrome. Some treatments that may be suggested include glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs), biologically targeted drugs, and allogeneic hematopoietic stem cell transplantation.
14 Sources
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