VEXAS syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

VEXAS syndrome is a disorder involving episodes of fever and abnormal inflammation. VEXAS is an acronym that stands for the technical terms of key descriptors of the condition. Normally, inflammation is an immune system response to injury or foreign invaders (such as bacteria). In people with VEXAS syndrome, part of the immune system called the innate immune response is turned on (activated) abnormally, when there is no injury or foreign invader, which causes fevers and inflammation-related damage to tissues and organs. Based on this process, VEXAS syndrome is classified as an autoinflammatory disease.

VEXAS syndrome typically affects older adults, primarily males, with signs and symptoms of the condition developing in a person's fifties, sixties, or seventies. People with VEXAS syndrome often have inflammation of the joints (arthritis), skin (dermatitis), cartilage in the ear and nose (chondritis), or blood vessels (vasculitis). Inflammation can also develop in other tissues, including in the lungs and eyes. Affected individuals may also have enlarged lymph nodes.

Blood cell abnormalities are common in VEXAS syndrome. Most affected individuals develop a shortage of red blood cells (a condition called anemia), and the red blood cells that are present are abnormally large (macrocytic). People with VEXAS syndrome can also have a shortage of blood cells called platelets (a disorder known as thrombocytopenia); platelets are needed for normal blood clotting. Some affected individuals develop myelodyspastic syndrome, a condition in which immature blood cells fail to develop normally; this condition may progress to a form of blood cancer calledleukemia.

ORPHANET DEFINITION A rare autoinflammatory syndrome characterized by adult onset of rheumatologic manifestations such as recurrent fever, skin and pulmonary inflammation, ear and nose chondritis, vasculitis, deep vein thrombosis, and arthralgia. Laboratory examination reveals progressive hematologic abnormalities including macrocytic anemia and thrombocytopenia, as well as elevated inflammatory markers. Bone marrow biopsy shows hypercellularity and signs of bone marrow dysplasia. The disease primarily occurs in males and is caused by somatic mutations on chromosome Xp11.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 37.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding terms used in the source

These definitions explain medical words used above. A definition is not evidence that another condition is present, and it does not predict how a symptom will develop. Ask the clinician which terms apply to the actual examination or test result.

Macrocytic anemia

A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).

Adult onset

Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later.

Progressive

Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age.

Recurrent

Applies to a sign, symptom or manifestation that occurs multiple times separated by intervals in which the sign, symptom, or manifestation is not present.

Affected

This term applies to a family member who is diagnosed with the same condition as the individual who is the primary focus of investigation (the proband).

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Adult; Elderly

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 37.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Which doctor should you see?

The suggested department for discussing VEXAS syndrome is Rheumatology, with a rheumatologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Are the findings inflammatory, structural or due to another mechanism?
• Is there evidence that other organs need assessment?
• How will function and any treatment-related risks be monitored?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for VEXAS syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.