Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Prevalence of carotid web in a French cohort of cryptogenic stroke.

BACKGROUND AND PURPOSE: Carotid webs (CaW) may be an under-recognized cause of anterior circulation cryptogenic ischemic stroke (ACIS). Prevalence is still unknown in European patients with ACIS. OBJECTIVE: To evaluate the prevalence of CaW in ACIS and describe patients with CaW phenotype in a cohort of patients from a French stroke center. METHODS: We conducted a retrospective monocentric cohort study from 01/01/2015 to 31/12/2019 (Montpellier University Hospital, France), in consecutive anterior ischemic stroke (AIS) patients ≤65 years old from a prospective stroke database. Using ASCOD phenotyping, ACIS patients were selected and cervical CTA were reviewed to find CaW. RESULTS: Among 1053 consecutive AIS patients, 266 ACIS patients with CTA were included. Among patients included (mean age 50, women 58%), CaW was in the ipsilateral carotid (iCaW) in 21 patients: 7.9% (95%CI [4.6-11.1]), (mean age 51, 11 women, 16 Caucasian). iCaW were uncovered during study review of CTA in 6/21 (29%) patients. Comparison between patients with iCaW and those without iCaW showed no differences except that of a higher rate of intracranial large vessel occlusion (LVO) (62.4 vs 37.6%; p = 0.03). Patients with iCaW under conservative medical therapy had an annualized stroke recurrence rate (SRR) of 11.4% (95%CI [8.4-15.1]. CONCLUSIONS: iCaW was identified as a source of stroke in about 8% of a French population ≤65 years with ACIS. iCaW was associated with a higher rate of LVO and a high SRR under conservative medical therapy.

[New nosological and therapeutic perspectives in syndromic vascular malformations with a vein-lymphatic component]. / Nouvelles perspectives nosologiques et thérapeutiques pour les malformations vasculaires syndromiques à composante veino-lymphatique.

Vascular malformations are poorly recognized constitutional anomalies which arises during early childhood. Several classifications tried to draw a distinction across the different entities. Recent advances in molecular biology have contributed to the update of their nosology. Syndromic vascular malformations are an example: while Klippel-Trenaunay syndrome, Proteus or CLOVES syndrome share many common features, understanding of pathological mechanism and specially the role of the PIK3/AKT/mTOR pathway enables us to rethink their classification. Then, some syndromes associated with overgrowth and vascular malformation have been grouped under a single term: "PIK3CA-related overgrowth spectrum" (PROS), and this group continues to grow. This new approach suggests new treatment options. Rapamycin, a PIK3/AKT/mTOR pathway inhibitor, demonstrated its efficiency for some forms of PROS. Targeted therapies such as PIK3 or mTOR selective inhibitor are still in a developmental phase and results are encouraging. This is an example of personalized medicine with significant therapeutic benefit for some patients. However, genotype relation with therapeutic efficiency must be clarified and physicians should pay attention to possible negative effects of these drugs, especially for young patients.

[Gardner-Diamond syndrome in a young man: A case report and literature review]. / Syndrome de Gardner-Diamond : à propos d'un cas chez un homme jeune et revue de la littérature.

INTRODUCTION: Gardner-Diamond syndrome is a rare condition secondary to a sensitization to self-erythrocytes. It is predominantly seen in women and presents as a painful ecchymotic disorder. An underlying psychiatric disease or a triggering psychological stress is of important diagnostic value. CASE REPORT: We report a 24-year-old patient who presented with intermittent spontaneous painful ecchymosis since 5 years. Complementary investigations failed to identify an organic disorder. Gardner-Diamond syndrome was retained because of the clinical presentation, the negativity of diagnostic work-up and the identification of a psychological trauma. Patient management (pain, psychological support) is difficult, justifying a multidisciplinary approach. CONCLUSION: Gardner-Diamond syndrome is a rare and unrecognized disorder, which should be discussed in the presence of ecchymotic or purpuric lesions that do not have a diagnostic orientation. Early recognition of this disorder enables initiation of an appropriate management, but also limits unnecessary additional explorations.