top of page
Search

The role of 18FDG-PET imaging in VEXAS syndrome: a multicentric case series and a systematic review of the literature

Summarized by: Sophie GEORGIN LAVIALLE

Reference: Bixio R, The role of 18FDG–PET imaging in VEXAS syndrome: a multicentric case series and a systematic review of the literature, Internal and Emergency Medicine, 2024 Nov;19(8):2331-2345.

Rôle de l’imagerie TEP au 18FDG dans le syndrome VEXAS

Summary:

Introduction:

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is an autoinflammatory disease associated with somatic mutations in the UBA1 gene. Patients typically present with systemic symptoms (fever, weight loss, skin rashes, lung involvement, chondritis, vasculitis, etc.), macrocytic anemia, and often a myelodysplastic syndrome. Given the clinical heterogeneity and lack of established diagnostic criteria, 18F-fluorodeoxyglucose PET (18FDG–PET) imaging may help with diagnosis and disease monitoring.


Patients and Methods:

This article reports a multicenter Italian case series of 8 patients, combined with a systematic review of the literature, totaling 35 cases.


Results:

All patients were male, with a median age of 70 years. The most common mutations were Met41Thr, Met41Val, and Met41Leu. The main indication for PET imaging was to investigate inflammatory foci or rule out malignancy.

PET scan analysis showed a high prevalence of bone marrow hypermetabolism (77%), followed by lymph nodes (35%), lungs (29%), spleen, large vessels, and cartilage (23% and 20% respectively). In six cases, PET imaging performed before diagnosis already showed increased bone marrow uptake. In some patients, follow-up PET scans after treatment (glucocorticoids or JAK inhibitors) revealed a reduction or even disappearance of hypermetabolic foci.

The authors also provide a summary diagram of the main lesions (see next page).


Conclusion:

Although no specific uptake pattern was identified, bone marrow hypermetabolism may precede clinical manifestations, suggesting a potential role for PET imaging in the early diagnosis and monitoring of VEXAS syndrome. Additionally, PET scans can assist in excluding differential diagnoses, especially malignancies and infections.

 
 
 

Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX

First author: Hadjadj et al.

Link to article: DOI: 10.1136/ard-2024-225640


Efficacy and safety of targeted therapies in VEXAS syndrome

Summary:


Study Objective:

To assess the efficacy and safety of targeted therapies in VEXAS syndrome, an adult-onset autoinflammatory disease associated with somatic mutations in the UBA1 gene.


Methodology:

A multicenter retrospective study including 110 patients who received at least one targeted therapy. Complete response (CR) and partial response (PR) were defined based on specific clinical and biological criteria.


Results:

A total of 110 patients received 194 targeted therapies: 78 (40%) JAK inhibitors (JAKi), 51 (26%) IL-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) TNFα blockers, and 12 (6%) other targeted therapies.


At 3 months, the overall response rate (CR and PR) was 24% with JAKi, 32% with IL-6 inhibitors, 9% with IL-1 inhibitors, and 0% with TNFα blockers or other targeted therapies.


At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors.


Treatment-free survival was significantly longer with JAKi compared to other targeted therapies.


Among patients who discontinued treatment, reasons included primary failure, secondary failure, serious adverse events, or death, with varying rates depending on the therapy.


Conclusions:

JAK and IL-6 inhibitors show clinical benefits, while other therapies demonstrate lower efficacy. These findings require confirmation in prospective trials.

 
 
 

VEXAS syndrome: a Spanish national research project to better understand this rare disease.

Article title : VEXAS syndrome through a rheumatologist's lens: insights from a Spanish national cohortservices de rhumatologie espagnols
First author: García-Escudero P

First author: Rheumatology

Auteur du résumé: Philippe Mertz


Le syndrome VEXAS : une recherche nationale espagnole pour mieux comprendre cette maladie rare.


Introduction

VEXAS syndrome (Vacuoles, E1 enzyme, X‑linked, Autoinflammatory, Somatic) is a recently described, severe autoinflammatory disease associated with somatic variants in the UBA1 gene. It primarily affects men over 50 and combines systemic inflammatory manifestations with hematologic abnormalities. The aim of this study was to describe the clinical and genetic features of VEXAS seen in patients followed in Spanish rheumatology departments and to analyze genotype–phenotype correlations.


Methods

This was a multicenter retrospective study conducted in 126 Spanish hospitals, including 39 patients diagnosed between December 2020 and January 2024. Clinical, laboratory, and genetic data were collected and analyzed.


Key results

All patients were men, with a mean age of 73 years (range 40–92) at diagnosis. Initial working diagnoses included seronegative polyarthritis (9/39), relapsing polychondritis (6/39), Sweet’s syndrome (4/39), polymyalgia rheumatica (4/39), systemic lupus, and medium‑vessel vasculitis (3/39 each). The most frequent clinical features were skin involvement (87%), followed by polyarthritis (82%) and fever (79%). Renal involvement affected 20% of patients, a higher rate than previously reported cohorts, and polyarthritis also appeared more frequent than in earlier series.

Genetically, notable correlations emerged. The UBA1 M41V variant was significantly associated with renal involvement, whereas M41T correlated with thrombocytopenia and an increased rate of thromboembolic events. The study also identified a potentially pathogenic novel UBA1 variant (c.209T>A; p.L70H).

Regarding treatment, all patients received corticosteroids, with better responses observed after diagnostic confirmation and dose adjustments. Interleukin‑6 inhibitors and JAK inhibitors, notably ruxolitinib, showed the highest response rates, reaching 75% and 76% respectively. In contrast, anti‑TNF agents and hypomethylating agents were largely ineffective.


Conclusion

This study confirms that VEXAS remains under‑recognized in rheumatology, particularly among older men presenting with polyarthritis, unexplained cytopenias, or steroid dependence. It also underscores that genotype influences clinical expression, with certain variants associated with more severe disease or specific complications such as renal or thromboembolic involvement. Finally, the results support JAK and IL‑6 inhibitors as key therapeutic strategies in this condition.

In clinical practice, these findings support considering VEXAS promptly in any man over 50 with seronegative polyarthritis and atypical systemic features, cytopenias, or steroid dependence, to avoid diagnostic delay and better tailor therapy.



 
 
 
bottom of page