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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').To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.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.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.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.

Transthyretin (TTR) cardiac amyloidosis results from the dissociation of the tetrameric, liver-synthetized transport protein, either because of a mutation (hereditary CA), or spontaneously due to ageing (wild type CA). Monomers self-associate into amyloid fibrils within the myocardium, causing heart failure, arrhythmias and conduction defects. This overlooked disease must be recognized in case of unexplained increased thickness of the myocardium, particularly in subjects of African descent, in patients with heart failure and preserved ejection fraction, and in those with aortic stenosis. Some extra-cardiac symptoms must also be considered as red flags: carpal tunnel syndrome, lumbar canal stenosis, recent deafness, peripheral neuropathy, or dysautonomia. Medical assessment includes an electrocardiogram, biological assessment including troponin, natriuretic peptide and monoclonal protein assay, echocardiography with 2-D strain study, MRI and bone scintigraphy. Once the diagnosis established, cardiologic management must avoid beta-blockers and other rate-slowing drugs, which are deleterious in restrictive cardiomyopathy, and restrain the use of renin-angiotensin system inhibitors, of little use and often poorly tolerated. Congestion must be treated with diuretics. Anticoagulants are often necessary due to the risk of arrhythmias and stroke. Pacemaker or defibrillator implantation should be determined in patients with high risk of sudden death. Until now, etiologic treatments were liver and/or heart transplantation in some rare cases. Tafamidis, a TTR stabilizer has recently been approved, and new therapeutic approaches targeting TTR at the transcriptional level are under investigation.

Summary Objective This study aims to evaluate the new kit FIDIS™ APS (Biomedical Diagnostics) for the quantitative determination of anticardiolipin (ACA), anti-β2-glycoprotein I (β2-GPI) and antiprothrombin antibodies using the multiplex bead-based Luminex® technology. Material Three hundred and eighteen sera were tested: 30 sera from patients with antiphospholipid syndrome (APS), 47 sera from patients with antiphospholipid antibodies without APS, 30 sera from blood donors and 211 sera received in the laboratory for ACL or anti-β2GPI antibody assay. Methods Results were compared with those obtained with our routine ELISA techniques. Conclusion For ACA and anti-β2GPI antibodies, there was a good agreement between the FIDIS™ and the ELISA results (overall agreement superior to 85 %). FIDIS™ APS allows simultaneous determination of ACA and anti-β2-GPI antibodies as recommended by the Sydney international consensus. Simultaneous determination of antiprothrombin antibodies will permit to evaluate their clinical value.

Background Pulmonary mucormycosis (PM) is a life-threatening fungal infection with an increasing incidence among patients with acute leukemia. In some immunocompromised hosts, the reversed halo sign (RHS) has been described on the pulmonary computed tomographic (CT) scan of patients with mucormycosis. Methods This study reports a single-center experience with PM exclusively in patients with acute leukemia. Clinical records, laboratory results, and CT scans were retrospectively analyzed to evaluate the clinical usefulness of the RHS for the early identification and treatment of PM, with regard to outcomes in these patients. Results Between 2003 and 2012, 16 cases of proven PM were diagnosed among 752 consecutive patients receiving chemotherapy for acute myeloblastic or lymphoblastic leukemia. At the time PM was diagnosed, all patients but one were neutropenic. The study of sequential thoracic CT scans showed that during the first week of the disease, the RHS was observed in 15 of 16 patients (94%). Initially, other radiologic findings (multiple nodules and pleural effusion) were less frequent, but appeared later in the course of the disease (6% and 12% before vs 64% and 55% after the first week). After the diagnosis of PM, median overall survival was 25 weeks (range, 3-193 weeks), and 6 patients (38%) died before day 90. Conclusions In the particular setting of neutropenic leukemia patients with pulmonary infection, the presence of the RHS on CT was a strong indicator of PM. It could allow the early initiation of appropriate therapy and thus improve the outcome.

Phenotypic heterogeneity is very frequently observed in dermatomyositis (DM) patients depending on muscular weakness severity and extra-muscular involvement including interstitial lung disease or neoplasia. Dermatomyositis specific auto-antibodies are observed in 30% of patients. Among them an autoantibody recognizing melanoma differentiation-associated protein-5 (MDA-5) has been reported mainly in asiatic patients. We described here the first European study. We report the first French retrospective series of MDA-5 positive DM. MDA-5 antibodies were detected by Immunodot (D-Tek®). Seventeen patients (11 women, 10 Afro-Caribbean) have been included. The mean age was 44.2 [16–71] at presentation. Only two patients had severe muscle weakness and five had increase CK level. Muscle biopsy was always abnormal (n = 7) showing infiltrates (n = 6) and/or endomysial fibrosis (n = 1). One patient had severe myocardial impairment. Interstitial lung disease was often present (12/14) and subacute in 9 patients. CTscan demonstrated a pattern of non specific interstitial pneumonitis (n = 13), and/or organized pneumonia (n = 8). All patients had skin manifestations (n = 14): ulcerations or skin necrosis (n = 6), hyperkeratosis (n = 3), facial erythema (n = 4) and Raynaud’s phenomenon (n = 4). All patients suffered from arthralgia. Six patients had polyadenopathy. During follow-up (mean 44.2 months), 5 patients have been admitted in intensive care unit for an acute respiratory failure and 2 patients died, from respiratory cause (n = 1) and infection (n = 1). One patient had a cavum carcinoma. MDA-5 positive DM patients have a homogeneous presentation. Muscular disease is not severe whereas extra-muscular involvement is at the foreground lesions and may lead to life threatening complications.

We report the first detection of Seoul virus (SEOV) in humans in Europe, causing severe disease in a pregnant woman in France in October 2012. The patient's laboratory test results mimicked that of pregnancy-induced liver pathologies such as acute fatty liver of pregnancy (AFLP) with severe renal failure. This led to an emergency delivery (at 27 weeks' gestation). On the basis of gene S (small) sequence analysis, the Seoul hantavirus strain detected was found to belong to the main SEOV phylogroup. .