# Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: A comprehensive review of cases across different ethnicities

Yixiang Yves-Jean Zhu, David Benjamin Beck, Yannick Dieudonné, Sophie Georgin-Lavialle

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## To cite this version:

Yixiang Yves-Jean Zhu, David Benjamin Beck, Yannick Dieudonné, Sophie Georgin-Lavialle. Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: A comprehensive review of cases across different ethnicities. European Journal of Internal Medicine, 2025, 10.1016/j.ejim.2025.05.023. hal-05094190

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Original Article

# Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: A comprehensive review of cases across different ethnicities

Yixiang Yves-Jean Zhu<sup>a,1,†</sup>, David Benjamin Beck<sup>b</sup>, Yannick Dieudonné<sup>c</sup>,
Sophie Georgin-Lavialle<sup>a,1,2,*</sup>

ARTICLE INFO

Keywords:

Autoinflammatory diseases

Epidemiologic methods

Ubiquitin-proteasome system

Somatic mutation

Geographic distribution

A B S T R A C T

**Objectives:** Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is an autoinflammatory disease associated with somatic mutations in the *UBA1* gene. Although the disease has been described in many different countries, no studies have investigated the origin of patients to determine if the disease is universal across an- cestries. The aim of this study is to investigate the distribution of VEXAS syndrome across continents and ethnicities.

**Methods:** A literature review of all reported cases of VEXAS syndrome was conducted between October 2020 and April 2025 using the term 'VEXAS' with the all-field filter in the Pubmed and Web of Science databases. Epidemiological and clinical data were collected for included patients. If the country of origin was not described, it was assumed to be the same as the country of clinical evaluation. A subgroup analysis was performed for patients whose country of origin or ethnicity was documented by the authors.

**Results:** 674 cases of VEXAS syndrome were collected, with patients described from four continents and 32 countries. Considering the subgroup of patients with documented country of origin, 451 patients were from four continents and 19 countries. Of these, ethnicity was recorded for 372 patients with the presence of Caucasian, Central or East Asian, South Asian, Middle Eastern, Central American and South American ethnicities.

**Conclusion:** The results support a broad global distribution of the disease and highlight the importance of investigating the disease regardless of the patient's origin and ethnicity in cases of compatible symptoms.

1. Introduction

Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is a recently described somatic autoinflammatory disease [1]. A genetic mutation in the *UBA1* gene results in a deficiency of the encoded ubiquitin activating enzyme E1 involved in ubiquitina- tion. The ubiquitination defect leads to an accumulation of intracellular stress, followed by the production of pro-inflammatory cytokines, resulting in the symptoms observed in the disease. In the presence of a suspicious clinical picture, the diagnosis is based on the presence of a pathogenic variant of *UBA1*.

The clinical features presented by patients are multisystemic,

typically involving the skin [2], the eyes [3], the lungs [4], the musculoskeletal system and the blood count [5]. Although initially described in elderly males, the disease has also been diagnosed in women [6], reaching 4.3% (5/116) of patients in a large cohort [7], and in patients under the age of 30 [8,9]. The possibility of young or female patients adds to the difficulty of diagnosis and highlights the need to look for the disease in any combination of suspicious symptoms, regardless of the age or sex of the patient. Since the description of VEXAS syndrome, numerous cases have been described in the literature from several countries around the world. This suggests that this disease may occur across all ancestries, with no ethnic predominance, and that VEXAS syndrome should also be considered in the setting of suspicious

<footnote><sup>a</sup> Sorbonne University, AP-HP, Tenon hospital, Department of Internal Medicine, DMU3ID, Paris, France</footnote>

<footnote><sup>b</sup> Center for Human Genetics and Genomics New York University Grossman School of Medicine, New York City, USA</footnote>

<footnote><sup>c</sup> Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Department of Clinical Immunology and Internal Medicine, Strasbourg, France</footnote>

<footnote>* Corresponding author at: Department of Internal Medicine, Tenon Hospital, 20, rue de la Chine, 75020 Paris, France, Sorbonne University Assistance Publique-Hôpitaux de Paris, Centre de référence des maladies auto-inflammatoires et des amyloses inflammatoires (CEREMAIA).</footnote>

<footnote>E-mail address: sophie.georgin-lavialle@aphp.fr (S. Georgin-Lavialle).</footnote>

<footnote n="1">¹ Centre de référence des maladies auto-inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA).</footnote>

<footnote n="2">² ERN RITA.</footnote>
<figure><img src="image_4.png" /><figcaption>Fig. 1. Prisma Chart describing the methodology used for the review of the literature.</figcaption></figure>

symptoms, regardless of the ethnicity of the patient.

We present here data from a literature review to determine whether or not VEXAS syndrome has a ubiquitous distribution.

## 2. Methods

A review of the literature was conducted using the PubMed and Web of Science/Medline databases. The term 'VEXAS' was used in the all-fields filter to capture all articles published on the syndrome between its description in October 2020 and April 2025. Duplicate articles, inaccessible articles and articles not written in English or in French were excluded prior to screening. Based on the title and abstract, articles unrelated to VEXAS syndrome and articles that were not case reports, case series or cohorts were excluded. Based on full text, articles describing patients who had already been described in other articles, articles in which the patients described had not undergone genetic research, and cohorts for which individual epidemiological data were not provided were excluded. For the articles included in the review, the country and continent of origin of the patients, age at onset of symptoms and sex were analyzed. If the country of origin of the patients was not described, it was assumed that the patients were from the same country as the country of clinical assessment. Cohorts without individual epidemiological data were excluded without assuming the origin of the patients if not described, as it was considered more likely that a different origin from the country of clinical assessment would have been specified in a case report or small case series than in a large cohort. A subgroup analysis was performed by excluding reports in which the country of origin of the patient was assumed to be the country of clinical assessment, and retaining only articles in which the country of origin or ethnicity of the patient was documented.

Besides the epidemiological data, the main clinical, biological and genetic features were recorded for each patient when it was available, grouped according to continent of origin: the involved pathogenic mutation, including Met41Val variant of UBA1, or Met41Leu, or Met41Thr, or exon 3 splice mutation, or any other mutation described as likely pathogenic or pathogenic according to the InFever database [10]; fever; other general symptoms including asthenia, weight loss and night sweats; chondritis; arthritis; cutaneous rash including oedematous plaques, papules, macules, subcutaneous nodules, purpuric lesions; ocular involvement including conjunctivitis, scleritis, episcleritis, uveitis, periorbital inflammation; radiological lung involvement, including interstitial pneumopathy, alveolar opacities, fibrosis or pleurisy, unprovoked deep vein thrombosis and pulmonary embolism; anemia; macrocytosis; thrombocytopenia and myelodysplastic syndromes. In large cohorts, the absence of a description of one of these features led to data censoring. For case reports or series, the absence of mention of one of the main features of VEXAS syndrome was interpreted as most likely absent and therefore considered negative, as we recorded only the most important and significant features of the disease.

The existence of a dependency between each variable collected and the patient's continent of origin was assessed using the chi-square test. Statistical tests were performed using GraphPad Prism version 8.3.2 (Graphpad Software, La Jolla, CA, USA).

## 3. Results

A total of 1036 articles were retrieved. After excluding 480 duplicates, 55 non-English or non-French articles and 21 inaccessible articles, 480 articles were screened. Of the 480 articles screened, 117 articles that were not case reports/series or cohorts and 115 articles that were
<caption>**Table 1**</caption>

Detailed epidemiological, genetic, clinical, and biological characteristics of patients according to their geographic origin, considering both assumed and documented origins. *χ² test not applicable due to insufficient data.

<table><thead><tr><th></th><th>Europe<br>(n = 335)</th><th>America<br>(n = 199)</th><th>Asia<br>(n = 111)</th><th>Oceania<br>(n = 28)</th><th>p-value</th></tr></thead><tbody><tr><td><strong>General features</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age at onset of symptoms (years): median and range</td><td>68<br>(43-88)</td><td>64<br>(23-88)</td><td>69<br>(29-80)</td><td>69<br>(56-88)</td><td></td></tr><tr><td>Female patients</td><td>2</td><td>5</td><td>0</td><td>0</td><td></td></tr><tr><td><strong>UBA1 mutations</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Met41Val mutation</td><td>19.5 %<br>(49/<br>251)</td><td>24.1 %<br>(39/162)</td><td>24 %<br>(25/<br>104)</td><td>22.2 %<br>(4/18)</td><td>0.9518</td></tr><tr><td>Met41Leu mutation</td><td>21.9 %<br>(55/<br>251)</td><td>21.6 %<br>(35/162)</td><td>28.8 %<br>(30/<br>104)</td><td>22.2 %<br>(4/18)</td><td>0.5982</td></tr><tr><td>Met41Thr mutation</td><td>35.9 %<br>(90/<br>251)</td><td>51.9 %<br>(84/162)</td><td>35.6 %<br>(37/<br>104)</td><td>55.6 %<br>(10/18)</td><td>0.0336</td></tr><tr><td>Splice site mutation</td><td>7.2 %<br>(18/<br>251)</td><td>1.9 % (3/<br>162)</td><td>10.6 %<br>(11/<br>104)</td><td>0 % (0/<br>18)</td><td>0.012</td></tr><tr><td>Other mutations</td><td>3.6 %<br>(9/251)</td><td>4.3 % (7/<br>162)</td><td>1 % (1/<br>104)</td><td>0 % (0/<br>18)</td><td>/*</td></tr><tr><td><strong>Clinical features</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Fever</td><td>58.1 %<br>(144/<br>248)</td><td>49.7 %<br>(95/191)</td><td>75.7 %<br>(84/<br>111)</td><td>46.4 %<br>(13/28)</td><td>&lt;0.0001</td></tr><tr><td>Other general symptoms</td><td>34.9 %<br>(59/<br>169)</td><td>37.2 %<br>(71/191)</td><td>26.8 %<br>(11/41)</td><td>50 %<br>(14/28)</td><td>0.254</td></tr><tr><td>Chondritis</td><td>40.3 %<br>(100/<br>248)</td><td>32.5 %<br>(62/191)</td><td>37.8 %<br>(42/<br>111)</td><td>25 % (7/<br>28)</td><td>0.2043</td></tr><tr><td>Arthritis</td><td>33.1 %<br>(56/<br>169)</td><td>40.8 %<br>(78/191)</td><td>32.4 %<br>(36/<br>111)</td><td>21.4 %<br>(6/28)</td><td>0.1287</td></tr><tr><td>Cutaneous eruption</td><td>69.8 %<br>(173/<br>248)</td><td>71.7 %<br>(137/<br>191)</td><td>77.5 %<br>(86/<br>111)</td><td>75 %<br>(21/28)</td><td>0.4929</td></tr><tr><td>Eye inflammation</td><td>35.3 %<br>(73/<br>207)</td><td>31.4 %<br>(61/191)</td><td>40.5 %<br>(45/<br>111)</td><td>50 %<br>(14/28)</td><td>0.1875</td></tr><tr><td>Radiological lung lesions</td><td>34.3 %<br>(71/<br>207)</td><td>40.8 %<br>(78/191)</td><td>52.3 %<br>(58/<br>111)</td><td>50 %<br>(14/28)</td><td>0.0143</td></tr><tr><td>Unprovoked venous thrombosis</td><td>25.8 %<br>(64/<br>248)</td><td>34.6 %<br>(66/191)</td><td>20.7 %<br>(23/<br>111)</td><td>39.3 %<br>(11/28)</td><td>0.0263</td></tr><tr><td>Anemia</td><td>82.7 %<br>(205/<br>248)</td><td>86.4 %<br>(95/110)</td><td>83.8 %<br>(93/<br>111)</td><td>67.9 %<br>(19/28)</td><td>0.1404</td></tr><tr><td>Macrocytosis</td><td>63.3 %<br>(157/<br>248)</td><td>79.1 %<br>(151/<br>191)</td><td>77.5 %<br>(86/<br>111)</td><td>50 %<br>(14/28)</td><td>&lt;0.0001</td></tr><tr><td>Thrombocytopenia</td><td>30.2 %<br>(51/<br>169)</td><td>42.9 %<br>(82/191)</td><td>36.6 %<br>(15/41)</td><td>50 %<br>(14/28)</td><td>0.0437</td></tr><tr><td>Myelodysplastic syndrome</td><td>46.2 %<br>(97/<br>210)</td><td>20.4 %<br>(39/191)</td><td>43.7 %<br>(31/71)</td><td>35.7 %<br>(10/28)</td><td>&lt;0.0001</td></tr></tbody></table>

not related to VEXAS syndrome were excluded. Of the remaining 248 full-text articles screened, 29 cohorts were excluded for lack of individual epidemiological data, 2 articles were excluded for lack of genetic research and 24 were excluded because patients were assumed to be described in other articles. A total of 193 articles describing 674 patients were included in the epidemiological analysis: 143 case reports [8,9, 11-151], 43 case series [5,152-192] and seven cohorts [193-199], including three cohorts [193,196,198] for which epidemiological data were not detailed in the publication but obtained from the authors. Two cohorts [193,194] were then excluded for analysis of clinical phenotype

because it reported patients from multiple continents without precision of phenotype by continent of origin. Of the included patients, the origin or ethnicity was known for 451, described in 76 studies. The PRISMA guidelines followed for the literature review are detailed in Fig. 1.

Patients with both assumed and documented origins were described across four continents and 32 countries (Fig. S1). Of these, 49.7 % (n = 335) were described on the European continent across 17 countries. 29.5 % (n = 199) were described on the American continent across five countries. 16.4 % (n = 111) were described on the Asian continent across eight countries. 4.2 % (n = 28) were described on the Oceanic continent across two countries. No patients from Sub-Saharan Africa were published, to date. The median age at disease onset for patients with assumed and documented origins (Fig. S2) ranged from 64 years for patients described in America to 69 years for patients described in Oceania and Asia. The most frequent mutation was Met41Thr (Fig. S3). Seven patients were female: four of them were reported to have no functional X chromosome [17,69,157,183], two of them didn't have aneuploidy identified [155], and this information was missing for the last patient [160]. Detailed epidemiological, genetic, and clinical features, along with the p-value of the dependency between continent of origin and clinical variables of included patients, are provided in Table 1.

Subgroup of patients with documented origins or ethnicity was described across four continents and 19 countries (Fig. 2A). Of these, 39.7 % (n = 179) were European: mainly Spanish (n = 88), followed by Italian (n = 82), French and German (n = 2 each), Polish, Romanian, Irish, Portuguese and Andorran (n = 1 each). 39.7 % (n = 179) were from the American continent: primarily from the United States of America (n = 167), then from Mexico (n = 7), Brazil (n = 4), and Colombia (n = 1). 18 % (n = 81) were Asian: mainly Japanese (n = 71), followed by Chinese (n = 4), Indian and Turkish (n = 2 each), Pakistani (n = 1) and one patient was described as Asian without specifying the country. Finally, 2.7 % (n = 12) were Australian.

For these patients, the median age at disease onset (Fig. 2B) was 68 years in European patients, ranging from 50 to 88 years; 64.5 years for patients from the American continent, ranging from 40 to 88 years; 72 years for patients from the Asian continent, ranging from 29 to 76 years; 69 years for patients from Australia, ranging from 67 to 73 years. The most frequent mutation was Met41Thr across all continents (Fig. 2C), found in 43.3 % (n = 39/90) of European patients, 48.7 % (n = 76/156) of patients from the American continent, 37.2 % (n = 29/78) of Asian patients, 57.1 % (n = 4/7) of Australian patients. The most frequent clinical features (Fig. 2D) for all patients were anemia, present in 85.7 % (n = 6/7) of patients from Australia to 93.5 % of European (n = 87/93), with macrocytic features ranging from 72 % (n = 67/93) of European patients to 86.4 % (n = 70/81) of Asian patients; and cutaneous eruption, present in 61.3 % (n = 57/93) of European patients to 100 % (n = 7/7) of Australian patients.

The clinical variables that showed a dependence according to continent of origin (Table 2) were fever (p = 0.0001), unprovoked venous thrombosis (p = 0.0048), and myelodysplastic syndrome (p < 0.0001).

Due to the heterogeneous and multiethnic population in several countries, particularly the United States of America or European countries, the ethnicity of 372 of these 451 patients was clearly documented by the authors: 280 were described as Caucasian, 76 as Central or East Asian, 12 as Central or South American, two as South Asian and two as Middle Eastern.

## 4. Discussion

Clinical knowledge of VEXAS syndrome is rapidly advancing thanks to the increasing number of reported cases since the initial description of the disease. Although the original clinical profile of VEXAS syndrome was that of a middle-aged or elderly men, it is increasingly being challenged by the description of female or young patients. Apart from these
<figure><img src="image_5.png" /><figcaption>**Fig. 2.** A) World map showing the distribution of patients with VEXAS syndrome according to their documented country of origin, along with the corresponding number of publications per country reporting them. B) Age at onset of symptoms by continent of origin for patients with documented origins. C) Pathogenic *UBA1* mutation found in each group according to continent of origin for patients with documented origins. D) Heatmap showing the frequency of clinical and biological variables associated with patients according to their geographical origin, for patients with documented origins. Splice: Splice-site mutation affecting the acceptor site of exon 3 in *UBA1*.</figcaption></figure>

two epidemiological characteristics, to our knowledge, no studies have looked at the origin of patients to determine whether the disease spares some populations or is more ubiquitous in nature.

The results show that patients with VEXAS syndrome have been described on most continents and in a large number of different

countries. Moreover, if patients have been described in almost all continents, they also have documented origins from almost all continents. When ethnicity was recorded, mainly to avoid bias due to multi-ethnic populations, most patients were described as Caucasian, but multiple Asian, Middle Eastern and Central or South American ethnicity were
<caption>**Table 2**</caption>

Detailed epidemiological, genetic, clinical, and biological characteristics of patients according to their geographic origin, considering only documented origins. *χ² test not applicable due to insufficient data.

<table><thead><tr><th></th><th>Europe<br>(n = 179)</th><th>America<br>(n = 179)</th><th>Asia<br>(n = 81)</th><th>Oceania<br>(n = 12)</th><th>p-value</th></tr></thead><tbody><tr><td><strong>General features</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age at onset of symptoms (years): median and range</td><td>68<br>(50-88)</td><td>64.5<br>(40-88)</td><td>72<br>(29-76)</td><td>69<br>(67-73)</td><td></td></tr><tr><td>Female patients</td><td>0</td><td>2</td><td>0</td><td>0</td><td></td></tr><tr><td><strong>UBA1 mutations</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Met41Val mutation</td><td>21.1 %<br>(19/90)</td><td>23.1 %<br>(36/<br>156)</td><td>20.5 %<br>(16/78)</td><td>28.6 %<br>(2/7)</td><td>0.9356</td></tr><tr><td>Met41Leu mutation</td><td>28.9 %<br>(26/90)</td><td>21.8 %<br>(34/<br>156)</td><td>32.1 %<br>(25/78)</td><td>14.3 %<br>(1/7)</td><td>0.2828</td></tr><tr><td>Met41Thr mutation</td><td>43.3 %<br>(39/90)</td><td>48.7 %<br>(76/<br>156)</td><td>37.2 %<br>(29/78)</td><td>57.1 %<br>(4/7)</td><td>0.3463</td></tr><tr><td>Splice site mutation</td><td>4.4 %<br>(4/90)</td><td>1.9 %<br>(3/156)</td><td>9 %<br>(7/<br>78)</td><td>0 %<br>(0/<br>7)</td><td>/*</td></tr><tr><td>Other mutations</td><td>2.2 %<br>(2/90)</td><td>4.5 %<br>(7/156)</td><td>1.3 %<br>(1/78)</td><td>0 %<br>(0/<br>7)</td><td>/*</td></tr><tr><td><strong>Clinical features</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Fever</td><td>47.3 %<br>(44/93)</td><td>49.1 %<br>(84/<br>171)</td><td>72.8 %<br>(59/81)</td><td>100 %<br>(7/7)</td><td>0.0001</td></tr><tr><td>Other general symptoms</td><td>35.7 %<br>(5/14)</td><td>36.8 %<br>(63/<br>171)</td><td>27.3 %<br>(3/11)</td><td>71.4 %<br>(5/7)</td><td>0.2634</td></tr><tr><td>Chondritis</td><td>46.2 %<br>(43/93)</td><td>30.4 %<br>(52/<br>171)</td><td>44.4 %<br>(36/81)</td><td>28.6 %<br>(2/7)</td><td>0.0357</td></tr><tr><td>Arthritis</td><td>28.6 %<br>(4/14)</td><td>43.3 %<br>(74/<br>171)</td><td>38.3 %<br>(31/81)</td><td>28.6 %<br>(2/7)</td><td>0.5833</td></tr><tr><td>Cutaneous eruption</td><td>61.3 %<br>(57/93)</td><td>70.8 %<br>(121/<br>171)</td><td>72.8 %<br>(59/81)</td><td>100 %<br>(7/7)</td><td>0.0875</td></tr><tr><td>Eye inflammation</td><td>38.2 %<br>(21/55)</td><td>33.3 %<br>(57/<br>171)</td><td>37 %<br>(30/81)</td><td>71.4 %<br>(5/7)</td><td>0.2129</td></tr><tr><td>Radiological lung lesions</td><td>34.5 %<br>(19/55)</td><td>40.4 %<br>(69/<br>171)</td><td>50.6 %<br>(41/81)</td><td>71.4 %<br>(5/7)</td><td>0.0971</td></tr><tr><td>Unprovoked venous thrombosis</td><td>26.9 %<br>(25/93)</td><td>33.9 %<br>(58/<br>171)</td><td>14.8 %<br>(12/81)</td><td>57.1 %<br>(4/7)</td><td>0.0048</td></tr><tr><td>Anemia</td><td>93.5 %<br>(87/93)</td><td>86.7 %<br>(78/90)</td><td>88.9 %<br>(72/81)</td><td>85.7 %<br>(6/7)</td><td>0.4649</td></tr><tr><td>Macrocytosis</td><td>72 %<br>(67/93)</td><td>79.5 %<br>(136/<br>171)</td><td>86.4 %<br>(70/81)</td><td>85.7 %<br>(6/7)</td><td>0.1295</td></tr><tr><td>Thrombocytopenia</td><td>35.7 %<br>(5/14)</td><td>43.9 %<br>(75/<br>171)</td><td>45.5 %<br>(5/11)</td><td>42.9 %<br>(3/7)</td><td>0.9462</td></tr><tr><td>Myelodysplastic syndrome</td><td>57.7 %<br>(30/52)</td><td>20.5 %<br>(35/<br>171)</td><td>43.9 %<br>(18/41)</td><td>42.9 %<br>(3/7)</td><td><strong>&lt;0.0001</strong></td></tr></tbody></table>

also described. We are also aware of unpublished genetically proven cases of VEXAS in patients of North African ancestry.

This observation supports a broad distribution of the disease, which may therefore affect all populations. However, no cases have been described on Sub-Saharan African countries. It is unlikely that African ancestries or other ancestries without reported cases provide protection against VEXAS syndrome although this has not been studied directly; it is more likely that a combination of factors including reporting biases, disease recognition and test availability have impacted diagnostic rates in different regions. These findings highlight the importance of raising awareness of the disease in all countries of the world and of promoting widespread access to UBA1 genetic sequencing.

The age of symptom onset was consistent across patients described from all four continents, with the Met41Thr mutation being the most commonly observed. This latter observation is consistent with findings from a large cohort of VEXAS syndrome patients, in which the Met41Thr variant is also the most frequently reported [7]. One possible explanation is that the Met41Leu variant has been associated with a milder disease course and a more favorable prognosis [7,200]. Moreover, this variant has been identified in asymptomatic carriers [201], suggesting that it may be underdiagnosed compared to other variants, such as Met41Thr, due to its less pronounced clinical presentation and incomplete penetrance. Another hypothesis is that the Met41Thr variant may be more strongly associated with the classical phenotype of VEXAS syndrome, while other variants could be linked to incomplete or atypical forms of the disease. This may result in more frequent genetic testing and diagnosis in patients harboring the Met41Thr variant. However, as our understanding of the syndrome expands—particularly regarding its phenotypic spectrum—this trend may evolve. It is important to emphasize that VEXAS syndrome is a recently identified disease. Despite the increasing number of case reports, the predominance of the Met41Thr variant should be interpreted with caution and confirmed in larger, prospective cohorts.

Several female patients with VEXAS syndrome were identified in the present study. Although UBA1 is located on the X chromosome, the occurrence of VEXAS in women is a known possibility [6]. This can be explained by mechanisms such as constitutional monosomy X or acquired skewed X-chromosome inactivation, which, when combined with a pathogenic UBA1 variant, may lead to the development of the syndrome in female patients. In the current study, most female patients identified had absence of a functional X chromosome. As for the euploid female patients, they had symptoms compatible with VEXAS syndrome, especially dermatological and hematological involvement, raising the hypothesis of other mechanisms such as skewed X inactivation. Therefore, genetic testing should be considered in any patient presenting with compatible clinical features, regardless of sex.

Several clinical variables appear to be dependent on the patient's continent of origin, which may indicate a difference in clinical presentation depending on the patient's origin. This may also be due to reporting differences that are distinct between countries or alternatively differences in follow-up times between studies. It is important to note that the selected variables group multiples sub-variables together to ensure homogeneity of the collected data, and that the data are influenced by publication bias inherent in the methodology of a literature review. Therefore, whether or not there is a difference in the clinical presentation of VEXAS syndrome depending on the patient's origin needs to be confirmed in subsequent prospective studies analyzing the exact ethnic origin of patients with homogeneous collection of clinical data. Moreover, the present study did not explore potential variations in treatment strategies based on patients' origins, as it was not its objective. Further dedicated studies are needed to assess disparities in treatment access and management practices across countries and continents.

The study has several limitations. Firstly, the country of origin of a large number of patients was assumed to be the same as the country of clinical assessment. Although this is imperfect for determining the exact origin of patients, it provides an estimate of the distribution of the disease and confirms that the disease has at least been described in a large number of countries from different continents. Furthermore, the results of the subgroup analysis considering only patients with documented origin are similar and also show a description of patients in four continents and several countries. Secondly, even if only documented country of origin is considered, there is still a bias due to the multiethnic populations, especially in European countries and the USA. However, this bias is limited by the recording of patients' ethnicity where available, which shows that even if the majority of patients are Caucasian, several ethnicities from different continents are represented among patients with VEXAS syndrome, also arguing for a wide distribution of the disease. Finally, the results are biased by the availability of the medical
system and access to genetic testing, which differ between countries, probably explaining why the majority of patients have been described in European countries or in the USA, and that most of them are Caucasian. In particular, to our best knowledge, access to genetic testing is limited in African countries and is the most likely reason for the lack of description of the disease in these countries. However, the purpose of this study was not to precisely describe the incidence of the disease in each country and ethnicity, but to raise awareness of the worldwide distribution of the disease and to highlight the need, firstly, to seek genetic confirmation of the disease in the case of compatible signs, not only regardless of the sex or age of the patient, but also regardless of the country of origin and ethnicity of the patient, and, secondly, to improve access to genetic testing.

## 5. Conclusion

This literature review investigated the country of origin and ethnicity of a large cohort of 674 reported cases of VEXAS syndrome. Patients were reported from several countries on four continents and of different ethnicities, suggesting a worldwide distribution of the disease and the need for genetic screening for UBA1 in the presence of a suspicious clinical picture, regardless of the patient's origin and ethnicity. The results highlight the importance of raising awareness of the disease worldwide and promoting access to genetic sequencing, particularly in countries where no cases have been reported to date.

## Declaration of competing interest

The authors declare they have no conflict of interest in this work.

## Funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

## Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ejim.2025.05.023.

## References

[1] Beck DB, Ferrada MA, Sikora KA, Umbrello AK, Collins JC, Pei W, et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 2020;383(27):2628-38.

[2] Zakine E, Papageorgiou L, Bourguiba R, Mekinian A, Terrier B, Kosmider O, et al. Clinical and pathological features of cutaneous manifestations in VEXAS syndrome: a multicenter retrospective study of 59 cases. J Am Acad Dermatol 2023;88(4):917-20.

[3] Abumanhal M, Leibovitch I, Zisapel M, Eviatar T, Edel Y, Ben Cnaan R. Ocular and orbital manifestations in VEXAS syndrome. Eye 2024;38(9):1748-54.

[4] Borie R, Debray MP, Guedon AF, Mekinian A, Terriou L, Lacombe V, et al. Pleuropulmonary manifestations of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Chest 2023;163(3):575-85.

[5] Obiorah IE, Patel BA, Groarke EM, Wang W, Trick M, Umbrello AK, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1. Blood Advances 2021;5(16):3203-15.

[6] Echerbault R, Bourguiba R, Georgin-Lavialle S, Lavigne C, Ravaiau C, Lacombe V. Comparing clinical features between males and females with VEXAS syndrome: data from literature analysis of patient reports. Rheumatology (Oxford) 2024;63 (4):1501-4.

[7] Georgin-Lavialle S, Terrier B, Guedon AF, Heiblig M, Comont T, Lazaro E, et al. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients. Br J Dermatol 2022;186(3):564-74.

[8] Sanchez-Hernandez BE, Calderon-Espinoza I, Martin-Nares E. Challenging the paradigm: a case of early-onset VEXAS syndrome. Rheumatology (Oxford) 2024; 63(3):e99-100.

[9] Guerineau H, Kohn M, Al Hamoud A, Sellier J, Osman J. Cabannes-Hamy A. Could it be VEXAS? Ann Hematol 2024;103(6):2169-71.

[10] Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C, et al. Infevers: an evolving mutation database for auto-inflammatory syndromes. Hum Mutat 2004;24(3):194-8.

[11] Al-Hakim A, Cull A, Topping J, Nadat F, Milek J, Alhefzi R, et al. Recovery of bone marrow function in VEXAS syndrome-potential role for Romiplostim. Hemasphere 2023;7(8):e934.

[12] Alhomida F, Beck DB, George TI, Shaffer A, Lebiedz-Odrobina D, Kovacsovics T, et al. Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome-clinical presentation of a newly described somatic, autoinflammatory syndrome. JAAD Case Rep 2021;14:111-3.

[13] Ang T, Tong JY, Selva D. Orbital inflammatory disease due to VEXAS syndrome: an entity to consider. Ophthalmic Plast Reconstr Surg 2024;40(1):116-7.

[14] Argobi Y. VEXAS syndrome with cutaneous nodules. Dermatol Reports [Internet] 2021. Dec 28 [cited 2023 Feb 13]; Available from, https://www.pagepress.org/journals/index.php/dr/article/view/9414.

[15] Austestad J, Madland TM, Sandnes M, Haslerud TM, Benneche A, Reikvam H. VEXAS syndrome in a patient with myeloproliferative neoplasia. Case Rep Hematol. 2023;2023:6551544.

[16] Balu B, Ding Y, Junkins-Hopkins JM. VEXAS syndrome: diagnostic clues for dermatologists. Int J Dermatol 2023;62(9):e484-6.

[17] Barba T, Jamilloux Y, Durel CA, Bourbon E, Mestrallet F, Sujobert P, et al. VEXAS syndrome in a woman. Rheumatology (Oxford) 2021;60(11):e402-3.

[18] Beecher MB, Tong JY, Halliday LA, Hissaria P, Selva D. Recurrent orbital inflammation associated with VEXAS syndrome. Orbit 2022;41(6):566-9.

[19] Belicard F, Belhomme N, Bouzy S, Saillard C, Nedelec F, Mear JB, et al. Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome in the intensive care unit: a case report. J Med Case Rep 2023;17(1):314.

[20] Bert-Marcaz C, Briantais A, Faucher B, Corazza G, Ebbo M, Attarian S, et al. Expanding the spectrum of VEXAS syndrome: association with acute-onset CIDP. J Neurol Neurosurg Psychiatry 2022;93(7):797-8.

[21] Compton LA, Jones HA, Vinyard CA, Lee YS, Walter MJ, Yokoyama CC. Progressive, edematous plaques, mild pancytopenia, and inflammation. JAAD Case Rep 2023;42:109-12.

[22] Cordts I, Hecker JS, Gauck D, Park J, Härtl J, Günthner R, et al. Successful treatment with azacidine in VEXAS syndrome with prominent myofasciitis. Rheumatology (Oxford) 2022;61(5):e117-9.

[23] Dehghan N, Marcon KM, Sedlic T, Beck DB, Dutz JP, Chen LYC. Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: fevers, myalgia, arthralgia, auricular chondritis, and erythema nodosum. Lancet 2021; 398(10300):621.

[24] Djerbi N, Zimmermann K, Roncador M, Becker MO, Manz MG, Balabanov S. Intrapatient competition of VEXAS syndrome and CML clones. Blood Adv 2023;7 (22):6815-8.

[25] Euvrard R, Fournier T, Georgescu D, Bourbon E, Sujobert P, Lega JC, et al. VEXAS syndrome-related AA amyloidosis: a case report. Rheumatology (Oxford) 2021;61 (1):e15-6.

[26] Fahmy LM, Schreidah CM, Lapolla BA, Magro CM. Geskin LJ. VEXAS syndrome presenting as refractory cutaneous Kikuchi disease-like inflammatory pattern responding to tofacitinib. JAAD Case Rep 2023;38:136-40.

[27] Fanlo P, Román ML, de S, Fonollosa A, Ilarramendi J, Heras H, Grayson P. Episcleritis and periorbital edema secondary to VEXAS syndrome. Arch Soc Esp Oftalmol (Engl Ed) 2023;98(10):607-10.

[28] Fenu EM, Bagg A. VEXAS'd by lymphadenopathy: an unusual case of extramedullary hematopoiesis. Blood 2023;141(22):2784.

[29] Fukuda N, Kanai D, Hoshino K, Fukuda Y, Morita R, Ishikawa Y, et al. Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report. BMC Nephrol 2024;25(1):18.

[30] Guerrero-Bermúdez CA, Cardona-Cardona AF, Ariza-Parra EJ, Arostegui JI, Mensa-Vilaro A, Yague J, et al. Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS syndrome) with prominent supraglottic larynx involvement: a case-based review. Clin Rheumatol 2022;41(11):3565-72.

[31] Goyal A, Narayanan D, Wong W, Laga AC, Connell NT, Ritter SY, et al. Tocilizumab for treatment of cutaneous and systemic manifestations of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome without myelodysplastic syndrome. JAAD Case Rep 2022;23:15-9.

[32] Grambow-Velilla J, Braun T, Pop G, Louzoun A, Soussan M. Aortitis PET imaging in VEXAS Syndrome: a case report. Clin Nucl Med 2023;48(2):e67-8.

[33] Grey A, Cheong PL, Lee FJ, Abadir E, Favaloro J, Yang S, et al. A case of VEXAS syndrome complicated by hemophagocytic lymphohistiocytosis. J Clin Immunol 2021;41(7):1648-51.

[34] Grosse A, Salehi T, Callary M, Hecker JR, Hissaria P. VEXAS syndrome causing fever of unknown origin. Med J Aust 2022;217(3):129-30.

[35] Hage-Sleiman M, Lalevée S, Guermouche H, Favale F, Chaquin M, Battistella M, et al. Dominance of an UBA1 mutant clone over a CALR mutant clone: from essential thrombocyemia to VEXAS. Haematologica 2021;106(12):3245-8.

[36] Haines P, Pullarkat S, Said J. VEXAS syndrome: vacuoles in myeloid, erythroid, and lymphoid lineages. Int J Lab Hematol 2024;46(1):8-9.

[37] Harrison I, Cohen O, Yi L, Singh A, Gradecki S, Zlotoff B, et al. Neutrophilic eccrine hidradenitis associated with VEXAS syndrome: a case report. Int J Dermatol 2023;63(6):759-61.

[38] Himmelmann A, Brücker R. The VEXAS Syndrome: uncontrolled inflammation and macrocytic anaemia in a 77-year-old male patient. Eur J Case Rep Intern Med 2021;8(4):002484.

[39] Holmes A, Thant A, Correy R, Vilain R. Inflammatory pseudotumour arising secondary to VEXAS syndrome. Pathology (Phila) 2023;55(1):161-3.

[40] Horton RK, Zheng G. A case of VEXAS syndrome with subtle morphologic findings. Blood 2021;138(15):1378.
[41] Kao RL, Jacobsen AA, Billington CJ, Yohe SL, Beckman AK, Vercellotti GM, et al. A case of VEXAS syndrome associated with EBV-associated hemophagocytic lymphohistiocytosis. Blood Cells Mol Dis 2022;93:102636.

[42] Kataoka A, Mizumoto C, Kanda J, Iwasaki M, Sakurada M, Oka T, et al. Successful azacitidine therapy for myelodysplastic syndrome associated with VEXAS syndrome. Int J Hematol 2023;117(6):919-24.

[43] Legeas C, Sucareau J, Sraux A, Schoenlaub P. VEXAS syndrome: a first case without any haematological abnormalities. Joint Bone Spine 2023;90(1):105473.

[44] Lohaus N, Schaab J, Schaeer D, Balabanov S, Huellner MW. VEXAS syndrome with tracheal involvement but absence of vasculitis in FDG PET/CT. Clin Nucl Med 2023;48(9):e444-5.

[45] Loschi M, Roux C, Sudaka I, Ferrero-Vacher C, Marceau-Renaut A, Duployez N, et al. Allogeneic stem cell transplantation as a curative therapeutic approach for VEXAS syndrome: a case report. Bone Marrow Transplant 2022;57(2):315-8.

[46] Lötscher F, Seitz L, Simeunovic H, Sarbu AC, Porret NA, Feldmeyer L, et al. Case report: genetic double strike: VEXAS and TET2-positive myelodysplastic syndrome in a patient with long-standing refractory autoinflammatory disease. Front Immunol 2021;12:800149.

[47] Lucchino B, Delfino L, Patuzzo G, Finucci A, Ghellere F, Bortolotti ME, et al. SARS-CoV-2-induced venous thromboembolism in a patient with VEXAS syndrome. Rheumatol Adv Pract 2023;7(1):rkad012.

[48] Lytle A, Bagg A. VEXAS: a vivid new syndrome associated with vacuoles in various hematopoietic cells. Blood 2021;137(26):3690.

[49] Magnol M, Couvaras L, Degboé Y, Delabesse E, Bulai-Livideanu C, Ruyssen-Witrand A, et al. VEXAS syndrome in a patient with previous spondyloarthritis with a favourable response to intravenous immunoglobulin and anti-IL17 therapy. Rheumatology (Oxford) 2021;60(9):e314-5.

[50] Martin-Nares E, Vargas-Serafin C, Delgado-de la Mora J, Montante-Montes de Oca D, Grayson PC, Larios E, et al. Orbital and periorbital inflammation in VEXAS syndrome. Scand J Rheumatol 2022;51(4):338-41.

[51] Matsuki Y, Kawai R, Suyama T, Katagiri K, Kanazawa N, Inaba Y. A case of VEXAS syndrome with myositis possibly associated with macrophage activation syndrome. J Dermatol 2022;49(12):e441-3.

[52] Mayo-Juanatey A, Fernández-Llavarado MJ, Valera-Ribera C, Valls-Pascual E, Alegre-Sancho JJ. Use of sarilumab in VEXAS syndrome. Rheumatology (Oxford) 2024;63(2):646-7.

[53] Midtvedt Ø, Stray-Pedersen A, Andersson H, Gunnarsson R, Tveten K, Ali MM, et al. A man in his sixties with chondritis and bone marrow failure. Tidsskr Nor Laegeføren 2022;142(4):1-4.

[54] Myint K, Patrao N, Vonica O, Vahdani K. Recurrent superior orbital fissue syndrome associated with VEXAS syndrome. J Ophthalmic Inflam Infect 2023; 13(1):39.

[55] Oganesyan A, Jachiet V, Chasset F, Hirsch P, Hage-Sleiman M, Fabiani B, et al. VEXAS syndrome: still expanding the clinical phenotype. Rheumatology (Oxford) 2021;60(9):e321-3.

[56] Oka H, Sumitomo S, Nishikubo M, Yamashita D, Maruoka H, Shiroishi Y, et al. VEXAS syndrome with granulomatosis with polyangiitis manifestation: retained in remission using methotrexate and infliximab. Rheumatology (Oxford) 2022;64(3):e110-2.

[57] Pamies A, Ferras P, Bellaudi-Pallares N, Gimenez T, Raventos A, Colobran R. VEXAS syndrome: relapsing polychondritis and myelodysplastic syndrome with associated immunoglobulin A vasculitis. Rheumatology (Oxford) 2022;61(3): e69-71.

[58] Pathmanathan K, Taylor E, Balendra J, Lim A, Carroll G. VEXAS syndrome: favourable clinical and partial haematological responses to subcutaneous abatacept therapy with 30-month follow-up. Rheumatology (Oxford) 2022;61(7): e174-7.

[59] Pozdnikova H, Virede A, Kadakia A, Imburgio S, Bajwa R, Gupta V, et al. A double hit to ubiquitination leading to a new diagnosis of VEXAS syndrome. J Med Cases 2023;14(9-10):327-31.

[60] Rieu JB, El Kassir A, Largeaud L, Dion J, Comont T, Mansat-De Mas V. Characteristic vacuolisation of granulocytic and erythroid precursors associated with VEXAS syndrome. Br J Haematol 2021;194(1):8.

[61] Robert M, Berleur M, Gaudemer A, Crow YJ, Frémont ML, Sacré K. VEXAS syndrome: expanding the clinical and molecular spectrum. Joint Bone Spine 2023;90(3):105531.

[62] Ronsin C, Benard L, Mourtada A, Perrin F, Boukerroucha Z. Acute tubointerstitial nephritis revealing VEXAS syndrome. Kidney Int 2022;101(6): 1295-7.

[63] Sakuma M, Tanimura A, Yasui S, Ishiguro K, Kobayashi T, Ohshiro Y, et al. A Case of polychondritis-onset refractory organizing pneumonia with cytopaenia diagnosed as VEXAS syndrome: the disease course of 7 years. Rheumatology (Oxford) 2021;60(10):e356-9.

[64] Sharma A, Naidu G, Deo P, Beck DB. VEXAS syndrome with systemic lupus erythematosus: expanding the spectrum of associated conditions. Arthritis Rheumatol 2022;74(2):369-71.

[65] Shaukat F, Hart M, Burns T, Bansal P. UBA1 and DNMT3A mutations in VEXAS syndrome. A case report and literature review. Modern Rheumatology Case Reports 2022;6(1):134-9.

[66] Skowron F, Klepfisch L, Guillaume L, Godeneche J, Facile A, Gombert M, et al. VEXAS syndrome following COVID-19 mRNA vaccination. J Eur Acad Dermatol Venereol 2023;37(6):e585-7.

[67] Stiburkova B, Pavelkova K, Belickova M, Magaziner SJ, Collins JC, Werner A, et al. Novel somatic UBA1 variant in a patient with VEXAS syndrome. Arthritis Rheumatol 2023;75(7):1285-90.

[68] Strasser B, Haushofer A. The first case of VEXAS syndrome in Austria. Clin Chem Lab Med 2023;61(10):e187-8.

[69] Stubbins RJ. Lost in translation: cytoplasmic UBA1 and VEXAS syndrome. Blood 2022;140(13):1455-7.

[70] Thomas V, Campagne J. Vexas: a new syndrome not always associated with hemopathy. eJHaem 2022;3(1). 235-235.

[71] Thomas VT, Penmethcha M. Myelodysplastic syndrome associated with auto-immune inflammatory disease in VEXAS syndrome. J Hematol 2011;10(6):274-6.

[72] Topilow JS, Ospina Cardona D, Beck DB, Ferrada MA, McMahan ZH, Paik JJ. Novel genetic mutation in myositis-variant of VEXAS syndrome. Rheumatology (Oxford) 2022;61(12):e371-3.

[73] Tozaki N, Tawada C, Niwa H, Mizutani Y, Shu E, Kawase A, et al. A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment. Front Med (Lausanne) 2022;9:1046820.

[74] Tsoourloudis I, Georgiadi EC, Vatalis G, Kotsi P. Case report of a patient with VEXAS syndrome. Medicine (Baltimore) 2023;102(52):e36738.

[75] van Leeuwen-Kerkhoff N, de Witte MA, Heijstek MW, Leavis HL. Case report: up-front allogeneic stem cell transplantation in a patient with the VEXAS syndrome. Br J Haematol 2022;199(3):e12-5.

[76] Varadarajan A, Verghese RM, Tirlangi PK, Dass J, Soneja M, Seth T. VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). QJM 2023;116(4):313-5.

[77] Wilke MVMB, Morava-Kozicz E, Koster MJ, Schmitz CT, Foster SK, Patnaik M, et al. Exome sequencing can misread high variant allele fraction of somatic variants in UBA1 as hemizygous in VEXAS syndrome: a case report. BMC Rheumatol 2022;6(1):54.

[78] Wilson NR, Jain P, Gomez JA, Lu H, Pemmaraju N. Concurrent myelodysplasia and monoclonal B lymphocytosis in VEXAS syndrome. Leuk Res 2022;120: 106909.

[79] Yildirim F, Erdogan M, Yalcin Mutlu M, Akkuzu G, Ozgur DS, Karaalioglu B, et al. VEXAS syndrome with severe multisystem involvement: rapid recovery after splenectomy. Int J Rheum Dis 2023;26(3):559-62.

[80] Yoon JG, Lee S, Kim S, Kim MJ, Chang YH, Park JK, et al. The first Korean case of VEXAS syndrome caused by a UBA1 somatic variant. Ann Lab Med 2023;43(2): 217-20.

[81] Ciprian G. Adverse reaction to COVID-19 mRNA vaccination in a patient with VEXAS syndrome. Cureus 2022;14(3):e23456.

[82] De D, Baskaran N, Shah S, Bishnoi A, Bhatia P, Sharma P, et al. Cutaneous manifestations of VEXAS syndrome: multiple changing faces in the same patient. Int J Dermatol 2023;62(12):e355-8.

[83] Salles M, Fusta X, Lidia C, Esquius M, Miguez S. Systemic lupus erythematosus in the elderly finally diagnosed with VEXAS syndrome. Clin Exp Rheumatol 2023 Jul 14;41(7):1417-8.

[84] Vu KT, Wolfe RM, Lambird JE, Maracaja DLV. A case of VEXAS syndrome presenting with unusual bone marrow granulomas: a diagnostic dilemma. BMC Rheumatol 2023;10(1):18. 7.

[85] Estes J, Malus M, Wilson L, Grayson PC, Maz M. A case of VEXAS: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic with Co-existing DNA (Cytosine-5)-methyltransferase 3A mutation complicated by localized skin reaction to Tocilizumab and Azacitidine. Cureus 2023;15(6):e39906.

[86] Monzoni M, Bosi A, Fabris S, Lionetti M, Salero S, Migliorini AC, et al. Clinical, morphological and clonal progression of VEXAS syndrome in the context of myelodysplasia treated with Azacytidine. Clin Hematol Int 2022;4(1-2):52-5.

[87] Rivera EG, Patnaik A, Salvemini J, Jain S, Lee K, Lozeau D, et al. SARS-CoV-2/ COVID-19 and its relationship with NOD2 and ubiquitination. Clin Immunol 2022;238:109027.

[88] Valor-Méndez L, Sticherling M, Zeschick M, Atreya R, Schmidt FD, Waldfahrer F, et al. VEXAS syndrome mimicking lupus-like disease. Rheumatology (Oxford) 2023;62(9):e271-2.

[89] Wang CX, Yokoyama CC, Rosman IS, Musiek AC. Extensive reactive cutaneous histiocytic infiltrate resembling non-Langerhans cell histiocytosis as the presenting sign of underlying vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. JAAD Case Rep 2024;43:20-3.

[90] Wiesik-Szewczyk E, Zegadlo A, Sobczynska-Tomaszewska A, Korzeniowska M, Jahnz-Rozyk K. Case report: VEXAS as an example of autoinflammatory syndrome in pulmonology clinical practice. Front Med (Lausanne) 2024;11: 1340888.

[91] Fan BE, Sum CLL, Leung BPL, Ang MK, Lim XR, Lee SSM, et al. VEXAS syndrome and thrombosis: findings of inflammation, hypercoagulability, and endothelial dysfunction. Semin Thromb Hemost 2024;50(3):391-9.

[92] Fan BE, Cao L, Gallardo CA, Lee SMS, Koh LW, Goh LL, et al. Myeloid and lymphoid vacuolation in VEXAS syndrome. Am J Hematol 2021;96(8):1056-7.

[93] Lee SMS, Fan BE, Lim JHL, Goh LL, Lee JSS, Koh LW. A case of VEXAS syndrome manifesting as Kikuchi-Fujimoto disease, relapsing polychondritis, venous thromboembolism and macrocytic anaemia. Rheumatology (Oxford) 2021;60(9): e304-6.

[94] Khosravi-Hafsiejani T, O'Connor M, To F, Sreenivasan G, Shojania K, Au S. The spectrum of skin disease in VEXAS syndrome: a report of a novel clinicohistopathologic presentation. J Eur Acad Dermatol Venereol 2022;36(6):e435-7.

[95] Racz T, Burciu S, Torok T, Damian L, Rednic S, Simon SP. VEXAS syndrome diagnosis starting from ultrasound findings: a case report. Med Ultrason 2024;26 (2):246-9.

[96] Raman A, Damodaran A. Clinical images: ureteritis in VEXAS syndrome. ACR Open Rheumatol 2024;6(6):333.
[97] Allison DR, Dholaria B, Kishtagari A, Mohan S, Steigelfest E, Shaver AC, et al. Distinct bone marrow findings associated with a noncanonical UBA1 variant in VEXAS syndrome. Am J Hematol 2024;99(7):1400-2.

[98] Bellman P, Gonzalez-Lugo JD, Shahzad M, Amin MK, Khalid MF, Suleman N, et al. Successful treatment with fludarabine and cyclophosphamide in a VEXAS syndrome patient with associated myelodysplastic syndrome: a case report and systematic review. Front Oncol 2024;14:1383730.

[99] Diaz MJ, Liu VY, Motaparthi K. Noninflammatory extrafacial edema as a clue to the diagnosis of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. JAAD Case Rep 2024;47:96-8.

[100] Pereira da Costa R, Sapinho G, Bandeira M, Infante J, Marques T, Mimoso Santos C, et al. Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine. Front Immunol 2024;15:1403808.

[101] Philip R, Cadro V, Aouba A, Chantepie S, Bracquemart C, Dumont A. VEXAS syndrome: a new mimicker of idiopathic multicentric Castleman disease. Joint Bone Spine 2024;91(4):105731.

[102] Sofi FA, Naqati SM, Ahmad M, Bindroo M. VEXAS syndrome presenting as diffuse alveolar haemorrhage. BMJ Case Rep 2024;17(3):e259474.

[103] Zisapel M, Seyman E, Molad J, Hallevi H, Mauda-Havakuk M, Jonas-Kimchi T, et al. Case report: cerebral sinus vein thrombosis in VEXAS syndrome. Front Med (Lausanne) 2024;11:1377768.

[104] Archambeaud A, Le Dreau C, Bigot A, Kosmider O, Taleb A, Boucher L, et al. Trismus as a new feature of VEXAS syndrome. Rheumatology (Oxford) 2024;63(7):keae135.

[105] Rimbert N, Retout A, Muraine M, Thorel D. Acute orbital inflammation in VEXAS syndrome: case report. J Fr Ophthalmol 2024;47(6):527-9.

[106] Agwan S, Zhang L, Baker T, Lane M, Godbolt D, Mackintosh J. A vexing case of a 73-year-old man with fevers, orbital cellulitis, and asymptomatic interstitial lung disease. Respiro Case Rep 2024;12(9):e01152.

[107] Al-Nusair J, Lim O, Alhusari L, Elghezawi A, Abdallah M, Alshal M, et al. The challenging and unique diagnosis of VEXAS syndrome: a case report. J Investig Med High Impact Case Rep 2025;13:23247096251325416.

[108] Ataş Ü, Alhan FN, Beypinar D, Şahin S, Keskek ŞÖ. A case of VEXAS syndrome presenting with unexplained headache. Turk J Haematol 2025;42(1):66-7.

[109] Berger M, Schumacher F, Wollsching-Strobel M, Kroppen D, Stanzel S, Majorski D, et al. A clinical phenotype of VEXAS syndrome with pleural effusion, infiltrates, and systemic inflammation in a 76-year-old patient: a case report. J Med Case Rep 2024;18(1):314.

[110] Bergonzi G, Campochiaro C, Tomelleri A, Del Poggio A, Bonacchi R, Ferré L, et al. VEXAS associated acute disseminated encephalo-mylitis (ADEM)-like syndrome: a case report and review of the literature. Curr Res Transl Med 2025;73(3): 103370.

[111] Bryan C, Fidler L. A vexing diagnosis: a case report on VEXAS syndrome. Can J Respir Crit Care Sleep Med 2025;9(2):47-50.

[112] Burgei J, Alsheimer K, Lantry J, Hehn B. Mediastinal lymphadenopathy due to VEXAS syndrome. BMJ Case Rep 2024;17(8):e58979.

[113] Cáceres-Nazario B, Rivenbark J, Saha M, Mathews S, Rubinstein S. Novel use of siltuximab in a patient with VEXAS syndrome. Ann Hematol 2025;104(2): 1259-67.

[114] Ceccardi A, Dameri M, Ravera F, Gilardi N, Stabile M, Lombardo I, et al. JAK2 is a critical therapeutic target in VEXAS syndrome: the importance of clinical suspicion and the use of methotrexate. Ann Hematol 2024;103(11): 4789-91.

[115] Chen D, Stubbins R, Smrke A, Kevin KO YC, Gardner PJ. Kaposi sarcoma posthematopoietic stem cell transplant for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. JAAD Case Rep 2025;58:56-9.

[116] Colman B, Smolyansky E, Parmar H, Puvanakumar P, Fraser R, Ramachandran P, et al. Orbital inflammatory manifestations in a patient with VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) syndrome. J Neuroophthalmol 2025;45(1):96-9.

[117] de Oliveira FR, Lima AS, Faria CR, Quaresma TO, Mourani MM, Wichert-Ana L, et al. Complex somatic mutation landscape in myeloid cells in a patient with VEXAS syndrome: first Brazilian case report. Hematol Transfus Cell Ther 2025;47(1):103686.

[118] De Santis M, Tonutti A, Motta F, Todisco G, Manes N, Milanesi C, et al. Approaches for the diagnosis and treatment of VEXAS syndrome: the importance of clinical suspicion and the use of methotrexate. Ann Hematol 2024;103(11): 4789-91.

[119] Gupta A, Hussain A. Orbital compartment syndrome as a novel manifestation of VEXAS (Vacuole, E1 Enzyme, X-Linked, Autoimmune, Somatic Syndrome). Ophthal Plast Reconstr Surg 2024;40(5):585-6.

[120] Han Z, Fan H, Guo Q, Li Y, Liu S, Gao S, et al. Death with cerebral infarction in a patient with VEXAS syndrome. Rheumatology (Oxford) 2024;64(3):1545-7.

[121] Heeney A, Wu R, Fitzgerald C, Orfali N, Akasheh N, Magee C. VEXAS syndrome as a cause for multifocal, relapsing head and neck inflammation. Clin Case Rep 2024;12(7):e9126.

[122] Jain H, Roy D, Mavidi S, Haldar S, Mondal S, Bhattacharya P, et al. Elderly onset spondyloarthropathy and VEXAS syndrome: a case report. Mediterr J Rheumatol 2024;35(3):490-3.

[123] Kablar L, Corkill M, Menezes CN. VEXAS syndrome: a novel autoinflammatory disorder in an elderly male patient. Intern Med J 2024;54(8):1424-5.

[124] Kälber KA, Hoffmann J, Blank N. VEXAS syndrome in a male patient with fever and rash. Dtsch Arztebl Int 2024;121(17):565.

[125] Kashino K, Tsuchida N, Maeda A, Uchiyama Y, Kirino Y, Matsumoto N, et al. VEXAS syndrome initially presenting as relapsing polychondritis and progressing

into neutrophilic dermatosis with systemic symptoms over a 5-year period. Int J Dermatol 2024.

[126] Kelly G, Lobo Y, Godbolt A. Therapeutic challenges in the management of VEXAS syndrome: a case report. Australas J Dermatol 2025;76(2):e118-20.

[127] Knab T, Gaisl T, Steinack C, Kallweit T, Ulrich S, Roeder M. Pulmonary manifestation of VEXAS syndrome. BMJ Case Rep 2024;17(7):e258140.

[128] Langlois V, Curie A, Demas A, Etancelin P, Sauvère G, Leclancher A, et al. Central nervous system vasculitis in VEXAS syndrome: a rare involvement. Clin Neurol Neurosurg 2024;242:108351.

[129] Lechtenboehler R, Mauschitz MM, Holz FG, Finger RP, Wintergerst MWM. A case of VEXAS syndrome with therapy refractive macular involvement. Can J Ophthalmol 2025;60(2):e70-2.

[130] Lee NS, Lu TY. Fatigue and chronic anaemia: could it be VEXAS syndrome? Aust J Gen Pract 2025;54(4):219-21.

[131] Lim JWW, Chua CKT. Case report: lower limb pseudocellulitis due to calf myositis in VEXAS syndrome. Int J Rheum Dis 2024;27(7):e15270.

[132] Longley MJ, Gaffney RG, Smith JS, DeSimone MS, Weinblatt ME, Merola JF. VEXAS in a patient with hypereosinophilia and Sweet's-like lesions. JAAD Case Rep 2024;53:71-4.

[133] Loupret T, De Coster L, Lemacon C, Gadon E, Bertin P, Vergne-Salle P. Non-hematological triggers of VEXAS syndrome: a case report and literature review. Curr Res Transl Med 2025;73(1):103444.

[134] Miranda S, Roias C, Rua J, Salvador F. Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome: a diagnostic and therapeutic conundrum. Cureus 2025;17(2):e79338.

[135] Moreira-Gomes P, Costa R, Granja B, Rosa G, Matos P, Costa C, et al. VEXAS syndrome: an unusual dermatological presentation with histiocytic infiltration. Int J Dermatol 2025;64(1):e38-41.

[136] Ng TTW, Van Vliet C, Bui J, Wood BA. Histiocytoid Sweet syndrome as a manifestation of myelodysplasia cutis/cutaneous VEXAS syndrome. Am J Dermatopathol 2025;47(4):280-4.

[137] Niedochodowiez G, de Faria A, Marechal M, Cournac JM, Ohlmann C, Bugier S, et al. Orbitopathy and bilateral posterior scleritis in VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome. J Fr Ophtalmol 2024;47(4): 104151.

[138] Oka H, Sumitomo S, Shiroishi Y, Taguchi H, Takeuchi R, Maruoka H, et al. Case Report: disseminated nontuberculous mycobacterial infection in a VEXAS syndrome patient—Possible association with variant allele frequency. Int J Rheum Dis 2025;28(1):e13738.

[139] Oun H, Gordon W, Leach M, Bain BJ. Where hematology meets rheumatology—VEXAS syndrome. Am J Hematol 2024;99(7):1407-8.

[140] Porges T, Rosenberg E, Wolach O, Sagy I, Sharf Y, Levi I. Case report: VEXAS syndrome with excellent response to treatment with azacitidine. Ann Hematol 2024;103(12):5935-9.

[141] Rieu JB, Rigolot L. S56F UBA1 variant: a VEXAS syndrome subtype that follows its own path. Blood 2024;144(24):2558.

[142] Rubinstein H, Nguyen K, Caterson H. Thyroiditis as a novel manifestation of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Intern Med J 2024;54(11):1921-2.

[143] Soluicj J, Nguyen P, Bardy P, Ly Y, Lawton E. A case of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome presenting as progressive multisystem involvement with parenchymal infiltrates following infection with Epstein Barr virus. Respiro Case Rep 2024;12(10):e70037.

[144] Squalli K, Wolff L, Vanderheynst F. A case of VEXAS with microcytic anaemia: don't be misled by an associated condition! Acta Clin Belg 2024;79(2):140-2.

[145] Tan IJ, Ferrada MA, Ahmad S, Fike A, Quinn KA, Groarke EM, et al. Skin manifestations of VEXAS syndrome and associated genotypes. JAMA Dermatol 2024;160(6):e241657.

[146] Tancer S, Rodgers K, Fullen D, Kahlenberg JM. Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a patient with subacute cutaneous lupus (SCLE). BMJ Case Rep 2025;18(1):e261174.

[147] Tsuchiya J, Nunokawa T, Sogabe S, Chinen N. Aortitis in VEXAS Syndrome. Intern Med 2025;64(8):1195-8.

[148] Xing L, Liang W, Li Y, Xiao J, Li Z, Zhang F. Concurrent inhibited erythropoiesis in a case of VEXAS syndrome. Ann Hematol 2025;104(2):1255-8.

[149] Zaidi M, West F, Ellis Z, Yates RA, Davis H. Vacuoles, E1 Enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome: a case report. Cureus 2025; 17(2):e78373.

[150] Zhukovsky S, Rets A, Braaten T, Patel AB. VEXAS without vacuoles: linking genotype to phenotype. EJHaem 2024;5(5):981-6.

[151] Ziliotti R, Seitz L, Gasser M, Seitz P. Temporal phlebitis in VEXAS syndrome. Rheumatology (Oxford) 2024;63(8):2243-4.

[152] Al-Hakim A, Kulasekararaj A, Norouzi M, Medlock R, Patrick F, Cargo C, et al. S56F UBA1 variant is associated with haematological predominant subtype of VEXAS. Br J Haematol 2023;203(2):331-5.

[153] Baur V, Stoevesandt J, Hueber A, Hüffmeier U, Kneitz H, Morbach H, et al. VEXAS-Syndrome, a newly described autoinflammatory systemic disease with dermatologic manifestations. J Dtsch Dermatol Ges 2023;21(12):1456-63.

[154] Beaumesnil S, Boucher S, Lavigne C, Urbanski G, Lacombe V. Ear, nose, throat, and bronchial involvements in VEXAS Syndrome: specifying the spectrum of clinical features. JAMA Otolaryngol Head Neck Surg 2022;148(3):284-6.

[155] Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, et al. Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population. JAMA 2023;329(4):318-24.
[156] Bourbon E, Heiblig M, Gerfaud Valentin M, Barba T, Durel CA, Lega JC, et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 2021;137(26):3682-4.

[157] Cherniawsky H, Friedmann J, Nicolson H, Dehghan N, Stubbins RJ, Foltz LM, et al. VEXAS syndrome: a review of bone marrow aspirate and biopsies reporting myeloid and erythroid precursor vacuolation. Eur J Haematol 2023;110(6): 633-8.

[158] Ciferska H, Gregová M, Klein M, Šenolt L, Soukupová Maaloufová J, Pavelka K, et al. VEXAS syndrome: a report of three cases. Clinical and Experimental Rheumatology [Internet] 2021. Nov 12 [cited 2023 Feb 13]; Available from, https://www.clinexprehumatol.org/abstract.asp?a=18113.

[159] Diarra A, Duployez N, Fournier E, Preudhomme C, Coiteux V, Magro L, et al. Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience. Blood Advances 2022;6(3):998-1003.

[160] Delplanque M, Auoba A, Hirsch P, Fenaux P, Graveleau J, Malard F, et al. USAID associated with Myeloid neoplasm and VEXAS syndrome: two differential diagnoses of suspected adult onset still's disease in elderly patients. JCM 2021;10 (23):5586.

[161] Gurnari C, Mannion P, Pandit I, Pagliuca S, Voso MT, Maciejewski JP, et al. UBA1 Screening in sweet syndrome with hematological neoplasms reveals a novel association between VEXAS and chronic myelomonocytic leukemia. Hemasphe 2022;6(10):e775.

[162] Karadeniz H, Cerit M, Avanoğlu Güler A, Tufan A, Kanthi Y. Venous inflammation might be one of the features of VEXAS syndrome and associated thrombosis. Rheumatology (Oxford) 2023;62(9):e269-70.

[163] Koster MJ, Kourtelis T, Reichard KK, Kermani TA, Beck DB, Cardona DO, et al. Clinical heterogeneity of the VEXAS syndrome. Mayo Clin Proc 2021;96(10): 2653-9.

[164] Kreutzinger V, Pankow A, Boyadzheva Z, Schneider U, Ziegeler K, Stephan LU, et al. VEXAS and Myelodysplastic syndrome: an interdisciplinary challenge. J Clin Med 2024;13(4):1049.

[165] Lacomb V, Beucher A, Urbanski G, Le Corre Y, Cottin L, Croué A, et al. Distinction between clonal and paraclonal cutaneous involvements in VEXAS syndrome. Exp Hematol Oncol 2022;11(1):6.

[166] Li P, Venkatachalam S, Ospina Cordona D, Wilson L, Kovacsovic T, Moser KA, et al. A clinical, histopathological, and molecular study of two cases of VEXAS syndrome without a definitive myeloid neoplasm. Blood Adv 2022;6(2):405-9.

[167] Mohammed TO, Alavi A, Aghazadeh N, Koster MJ, Olteanu H, Mangaonkar AA, et al. Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a presentation of two cases with dermatologic findings. Int J Dermatol 2023;62(5):e313-5.

[168] Muratore F, Marvisi C, Castrignanò P, Nicoli D, Farnetti E, Bonanno O, et al. VEXAS syndrome: a case series from a single-center cohort of Italian patients with vasculitis. Arthritis Rheumatol 2022;74(4):665-70.

[169] Nguyen JK, Routledge D, van Der Weyden C, Blombery P, Angel CM, Johnson D, et al. VEXAS syndrome: a dermatological perspective. Australas J Dermatol 2022; 63(4):488-92.

[170] Poulter JA, Collins JC, Cargo C, De Tute RM, Evans P, Ospina Cardona D, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. Blood 2021;137 (26):3676-81.

[171] Pinto R, F, Lamas A, G Oliveira DE, Oliveira M, Faria R. VEXAS Syndrome: a call for diagnostic awareness based on a case series of seven patients. Acta Med Port 2023;36(5):379-80.

[172] Riescher S, Graveleau J, Aubert H, Le Turnier P, Lebris Y, Gaborit B, et al. Le VEXAS, un déficit immunitaire auto-inflammatoire ? La Revue de Médecine Interne 2021;42:A384-5.

[173] Sakuma M, Blombery P, Meggendorfer M, Haferlach C, Lindauer M, Martens UM, et al. Novel causative variants of VEXAS in UBA1 detected through whole genome transcriptome sequencing in a large cohort of hematological malignancies. Leukemia 2023;37(5):1080-91.

[174] Sockel K, Göte K, Ganster C, Bill M, Georgi JA, Balaian E, et al. VEXAS syndrome: complete molecular remission after hypomethylating therapy. Ann Hematol 2024;103(3):993-7.

[175] Staels F, Betrains A, Woei-Ain JIN FJSH, Boeckx N, Beckers M, Bervoets A, et al. Case Report: VEXAS syndrome: from mild symptoms to life-threatening macrophage activation syndrome. Front Immunol. 2021;12:678927.

[176] Templé M, Duroyon E, Croizier C, Rossignol J, Huet T, Friedrich C, et al. Atypical splice-site mutations causing VEXAS syndrome. Rheumatology (Oxford) 2021;60 (12):e435-7.

[177] Islam S, Cullen T, Sumpton D, Damodaran A, Heath D, Bosco A, et al. VEXAS syndrome: lessons learnt from an early Australian case series. Intern Med J 2022; 52(4):658-62.

[178] Ribereau-Gayon E, Heiblig M, Bourbon E, Sujobert P, Harou O, Theillac C, et al. Atypical extensive lupus tumidus-like eruption as an early presentation of VEXAS syndrome. Int J Dermatol 2022;61(3):e89-e91.

[179] Salehi T, Callisto A, Beecher MB, Hissaria P. Tofacitinib as a biologic response modifier in VEXAS syndrome: a case series. Int J Rheum Dis 2023;26(11):2340-3.

[180] van der Made CI, Potjewijd J, Hoogstins A, Willems HPJ, Kwakernaak AJ, de Sevaux RGL, et al. Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of patients with VEXAS. J Allergy Clin Immunol 2022; 149(1):432-9. e4.

[181] Ospina Cardona D, Rodriguez-Pinto I, Iosim S, Bonet N, Mensa-Vilaro A, Wong MK, et al. Description of a novel splice site variant in UBA1 gene causing VEXAS syndrome. Rheumatology (Oxford) 2024;63(5):keae201. Mar 29.

[182] Riescher S, Lecomte R, Danic G, Graveleau J, Le Bris Y, Hello M, et al. Susceptibility to mycobacterial infection in VEXAS syndrome. Rheumatology (Oxford) 2024;63(5):keae087.

[183] Williams S, Stewart M, Fifi-Mah A, Dehghan N. VEXAS syndrome: clinical case series from a Canadian cohort. J Rheumatol 2024;51(3):444-7. Mar.

[184] Aalbers AM, van Daele PLA, Dalm VASH, Valk PJM, Raaijmakers MHGP. Long-term genetic and clinical remissions after cessation of azacitidine treatment in patients with VEXAS syndrome. Hemasphe 2024;8(8):e129.

[185] Bao A, Munjal A, Reddy PS, Park E, Synkowski DR, Jedrych JJ, et al. Concurrent autoimmune blistering diseases in VEXAS syndrome: a report of two cases. Clin Exp Dermatol 2024;49(5):573-7. May.

[186] Costa A, Pilo F, Pettinau M, Piga M, Carboni P, Piras E, et al. VEXAS syndrome: is it more a matter of inflammation or hematopoietic clonality? A case series approach to diagnosis, therapeutic strategies and transplant management. Ann Hematol 2025;104(1):253-62.

[187] Heiblig M, Plesa A, Tantot J, Jamilloux Y, Labussière-Wallet H, Sujobert P. Myeloid neoplasm inspired intensive therapy in VEXAS syndrome: a single-centre experience. Br J Haematol 2025;200(2):e71-4.

[188] Ko CJ, Odell I, Gehlhausen JR, Leventhal J, McNiff JM, Zubek A. VEXAS syndrome: histiocytoid cells with feathery cytoplasm as a clue to the diagnosis. J Cutan Pathol 2025;52(2):108-12.

[189] Mendoza LO, Leal VNC, Roa MEGV, Barros SF, Kalil J, Pontillo A. Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation. Clin Exp Immunol 2024;218(2):213-20.

[190] Mizes A, Ash MM, Richardson CT. VEXAS syndrome with p.Met41Leu UBA1 gene mutation misdiagnosed as tumid lupus: a series of 3 cases. JAAD Case Rep 2025; 57:78-85.

[191] Murillo-Chavez F, Antiochos B. VEXAS syndrome as a mimicker of ANCA-associated vasculitis. Rheumatol Adv Pract 2024;8(4):rkae116.

[192] Saur SJ, Obermaier B, Klein R, Hahn M, Fend F, Mattern S, et al. Altered IgG4 serum levels in VEXAS syndrome - a retrospective monocentric cohort study. Rheumatol Int 2025;45(4):79.

[193] Mascaro JM, Rodriguez-Pinto I, Poza G, Mensa-Vilaro A, Fernandez-Martin J, Caminal-Montero L, et al. Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism. Ann Rheum Dis 2023;82(12):1594-605.

[194] Vitale A, Caggiano V, Martin-Nares E, Frassi M, Dagna L, Hissaria P, et al. Orbital/ ocular inflammatory involvement in VEXAS syndrome: data from the international AIDA network VEXAS registry. Semin Arthritis Rheum 2024;66: 152430.

[195] Maeda A, Tsuchida N, Uchiyama Y, Horita N, Kobayashi S, Kishimoto M, et al. Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome. Rheumatology (Oxford) 2024;63(8):2056-64.

[196] Kirino Y, Maeda A, Asano T, Migita K, Hidaka Y, Ida H, et al. Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry. Rheumatology (Oxford) 2024;63(9):3207-12.

[197] Kalantari K, Sullivan MM, Herrera Hernandez LP, Bu L, Cornell LD, Nasr SH, et al. Acute kidney injury, an underrecognized feature of VEXAS syndrome. Rheumatology (Oxford) 2025;64(4):2027-33.

[198] Gurnari C, Pascale MR, Vitale A, Diral E, Tomelleri A, Galossi E, et al. Diagnostic capabilities, clinical features, and longitudinal UBA1 clonal dynamics of a nationwide VEXAS cohort. Am J Hematol 2024;99(2):254-62.

[199] García-Escudero P, López-Gómez M, López B, Dorta A, Frade-Sosa B, Lizaraburu M, et al. VEXAS syndrome through a rheumatologist's lens: insights from a Spanish national cohort. Rheumatology (Oxford) 2025;64(2):654-61.

[200] Ferrada MA, Savic S, Cardona DO, Collins JC, Alessi H, Gutierrez-Rodrigues F, et al. Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis. Blood 2022;140(13):1496-506.

[201] Corty RW, Brogan J, Byram K, Springer J, Grayson PC, Bick AG. VEXAS-defining UBA1 somatic variants in 245,368 diverse individuals in the NIH All of Us cohort. Arthritis Rheumatol 2024;76(1):168-77.