Clinical Phenotype and Prevalence of VEXAS Syndrome in Internal Medicine (FIND-VEXAS)

FIND-VEXAS Project (Friuli Internal Medicine Network for Detection of VEXAS Syndrome): Clinical Phenotype and Prevalence of VEXAS Syndrome in Internal Medicine

The FIND-VEXAS project is a multicenter, cross-sectional observational study conducted in Internal Medicine departments in the Friuli Venezia Giulia region of Italy.

The study aims to estimate how frequently VEXAS syndrome occurs among adults older than 50 years who are admitted to Internal Medicine units with otherwise unexplained systemic inflammation or hematologic abnormalities, such as fever, elevated inflammatory markers, macrocytic anemia, thrombocytopenia, or other cytopenias.

Participants will be assessed using clinical information, physical examination findings, routine laboratory tests, and imaging data. Patients with findings suggestive of VEXAS syndrome will be selected for confirmatory genetic testing of the UBA1 gene using blood or bone marrow samples.

In addition to estimating the prevalence of genetically confirmed VEXAS syndrome, the study will describe the clinical manifestations, hematologic abnormalities, inflammatory profile, and organ involvement of patients with suspected or confirmed disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Vexas Syndrome
• Intervention / Treatment: Diagnostic test: UBA1 Genetic Testing

Detailed Description

VEXAS syndrome is an adult-onset autoinflammatory disease caused by acquired somatic mutations in the UBA1 gene. The condition is characterized by systemic inflammation, cytopenias, and multiorgan involvement, which may affect the skin, lungs, joints, cartilage, and blood vessels. VEXAS syndrome may also overlap with hematologic disorders, including myelodysplastic syndromes.

The disorder mainly affects men older than 50 years, a population frequently admitted to Internal Medicine departments. Patients with VEXAS syndrome may initially present with nonspecific findings such as unexplained fever, persistently elevated C-reactive protein or erythrocyte sedimentation rate, macrocytic anemia, thrombocytopenia, other cytopenias, or systemic inflammation without an identifiable infectious, neoplastic, or other clear cause.

The FIND-VEXAS project is a multicenter, cross-sectional observational study involving Internal Medicine departments affiliated with the FADOI Friuli Venezia Giulia network. The planned study duration is 24 months. Eligible participants will be adults older than 50 years who are admitted with unexplained inflammatory and hematologic abnormalities.

Participating centers will use routinely available clinical, laboratory, and imaging information to identify patients with features suggestive of VEXAS syndrome. The assessment may include medical history, physical examination, standard blood tests, and radiological examinations performed as part of routine clinical care. A structured screening pathway will be used to support diagnostic suspicion and identify patients who should undergo molecular confirmation.

Blood or bone marrow samples from patients with suspected VEXAS syndrome will be sent to the Immunology Laboratory at IRCCS Burlo Garofolo in Trieste, which will act as the regional reference center for UBA1 sequencing. Suspected cases identified across participating Internal Medicine departments will therefore be centralized for genetic confirmation.

The primary objective is to estimate the prevalence of genetically confirmed VEXAS syndrome in the Internal Medicine setting. Additional objectives are to describe the clinical presentation, hematologic features, inflammatory profile, and patterns of organ involvement among patients with suspected or genetically confirmed VEXAS syndrome.

The study is expected to improve recognition of VEXAS syndrome through clinically applicable screening criteria and to strengthen collaboration between Internal Medicine departments and specialized Immunology and Hematology laboratories.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Giacomo Emmi, MD, PhD; Phone Number: +393286852815; Email: giacomo.emmi@chuv.ch
• Study Contact Backup: Name: Maria Letizia Urban, MD, PhD; Phone Number: +393478732241; Email: marialetizia.urban@units.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults older than 50 years admitted to participating Internal Medicine departments of the FADOI Friuli Venezia Giulia network with otherwise unexplained systemic inflammation and/or hematologic abnormalities, including fever, elevated inflammatory markers, macrocytic anemia, thrombocytopenia, other cytopenias, or systemic inflammatory manifestations without a clear etiology. Clinical, laboratory, and imaging data routinely available during hospital care will be used to identify participants with features suggestive of VEXAS syndrome. Selected suspected cases will undergo confirmatory UBA1 genetic testing.

Description

Inclusion Criteria:

• Age older than 50 years.
• Admission to a participating Internal Medicine department within the FADOI Friuli Venezia Giulia network.
• Presence of otherwise unexplained systemic inflammation and/or hematologic abnormalities.
• At least one of the following clinical or laboratory findings:
• unexplained fever;
• elevated C-reactive protein and/or erythrocyte sedimentation rate;
• macrocytic anemia;
• thrombocytopenia or other cytopenias;
• systemic inflammatory manifestations without a clearly identified cause.
• Availability of clinical, laboratory, and imaging data required for assessment according to the study screening pathway.
• Provision of informed consent, where required by the approved study protocol and applicable regulations.

Exclusion Criteria:

• Systemic inflammation adequately explained by an active infection.
• Systemic inflammation adequately explained by a solid malignancy.
• Clinical or laboratory abnormalities with another clearly established etiology.
• Insufficient clinical or laboratory information to assess eligibility according to the study screening pathway.
• Inability or refusal to provide informed consent, where consent is required.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients With Suspected VEXAS Syndrome; Adults older than 50 years admitted to participating Internal Medicine departments with otherwise unexplained systemic inflammation and hematologic abnormalities, including fever, elevated inflammatory markers, macrocytic anemia, thrombocytopenia, or other cytopenias. Participants will be assessed using routinely available clinical, laboratory, and imaging data. Patients meeting the predefined criteria for suspected VEXAS syndrome will undergo molecular testing for UBA1 mutations

Diagnostic test: UBA1 Genetic Testing; Blood or bone marrow samples from participants with clinical features suggestive of VEXAS syndrome will be analyzed for somatic mutations in the UBA1 gene. Molecular testing will be performed centrally at the Immunology Laboratory of IRCCS Burlo Garofolo in Trieste.; Other Names: Molecular confirmation of VEXAS syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Genetically Confirmed VEXAS Syndrome	Proportion of enrolled participants with a somatic pathogenic mutation in the UBA1 gene confirming the diagnosis of VEXAS syndrome. Prevalence will be calculated as the number of genetically confirmed VEXAS cases divided by the total number of participants included in the study and evaluated according to the study screening pathway.	Through study completion, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Characteristics of Participants With Suspected or Genetically Confirmed VEXAS Syndrome	Frequency and distribution of clinical manifestations among participants with suspected or genetically confirmed VEXAS syndrome, including fever and involvement of the skin, lungs, joints, cartilage, and blood vessels.	At study inclusion
Hematologic Characteristics of Participants With Suspected or Genetically Confirmed VEXAS Syndrome	Frequency and distribution of hematologic abnormalities, including macrocytic anemia, thrombocytopenia, other cytopenias, and associated hematologic disorders such as myelodysplastic syndrome.	At study inclusion
Inflammatory Profile of Participants With Suspected or Genetically Confirmed VEXAS Syndrome	Description of inflammatory laboratory findings, including C-reactive protein and erythrocyte sedimentation rate values, in participants with suspected or genetically confirmed VEXAS syndrome.	At study inclusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Collaborators: IRCCS Burlo Garofolo; FADOI-Friuli Venezia Giulia Network)
• Investigators: Principal Investigator: Giacomo Emmi, MD, PhD, CHUV Service d'immunologie et allergie, Lausanne, Switzerland; Study Chair: Francesco Zaja, University of Trieste; Study Chair: Fabio Fiammengo, FADOI-Friuli Venezia Giulia Network); Study Chair: Alberto Tommasini, IRCCS Burlo Garofolo; Study Chair: Maria Letizia Urban, University of Trieste

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 13, 2026
• First Submitted That Met QC Criteria: July 13, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 13, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Prevalence; incidence; Systemic Inflammation; VEXAS Syndrome; UBA1 Mutation
• Additional Relevant MeSH Terms: VEXAS syndrome
• Other Study ID Numbers: FIND-VEXAS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pseudonymized individual participant data will not be shared with external researchers or third parties. Access to the data will be restricted to authorized investigators involved in the study and to the study personnel responsible for data management and statistical analysis. Data will be processed in accordance with the approved study protocol, the informed consent provisions, and the General Data Protection Regulation (GDPR).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No