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Patient I.1 died from PML; Patient III.1 developed severe early-onset inflammatory bowel disease and was successfully treated, at 9 years with allogeneic HSCT from haploidentical donor using a reduced-intensity conditioning regimen; Patient III.3 died of neonatal HLH; Patient III.4 is asymptomatic; Patient III.5 developed auto-inflammatory symptoms at 8 years and was successfully treated at 12 year with allogeneic HSCT from matched sibling donor using a reduced-intensity conditioning protocol. To the Editor X-linked inhibitor of apoptosis (XIAP) deficiency (also known as X-linked lymphoproliferative syndrome type 2/XLP-2), caused by I XIAP i mutations, is a rare primary immunodeficiency (PID) [[1]]. The main clinical features of XLP-2 are (i) elevated susceptibility to hemophagocytic lymphohistiocytosis (HLH) (most frequently in response to Epstein-Barr virus (EBV) infection), (ii) recurrent splenomegaly, and (iii) inflammatory bowel disease (IBD). [Extracted from the article]

Objectives Blood transcriptomic IFN signature is a hallmark of SLE. The impaired health-related quality of life (HRQOL) observed in SLE is poorly related to disease activity. The aim of this study was to test how IFN signatures were associated with HRQOL in SLE patients. Methods Among consecutive patients, blood transcriptomic profiles were analysed with a modular framework comprising 3 IFN modules: M1.2, M3.4 and M5.12. Disease activity was evaluated by the SLEDAI score, and HRQOL was assessed with the SF-36 questionnaire, which includes eight domains: physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health (MH) and physical component summary and mental component summary scores. Results A total of 57 SLE patients were evaluated, among whom 27 (47%) were clinically quiescent, 30 (53%) were flaring, and 19 (33%) had active lupus nephritis. All SF-36 domains were altered in SLE patients compared with the general French population (P < 0.0001). In multivariate analysis, taking into account flares, age, ethnicity, smoking and renal severity, social functioning was independently associated with the IFN score (P = 0.027). Analyses restrained to quiescent patients (n = 27) yielded greater associations between social functioning and the three IFN modules, and between MH and M3.4. Considering all quiescent visits (n = 51), the IFN score was independently correlated with social functioning (P = 0.022) and MH (P = 0.038). Conclusion This unexpected paradoxical association between IFN signature and some specific HRQOL domains argues against a pivotal role of IFNs in the persistently altered HRQOL of SLE patients. [ABSTRACT FROM AUTHOR]

Introduction/objectives: The aim of our study was to investigate possible differences in nailfold videocapillaroscopy (NVC) features between patients with dermatomyositis (DM), overlap myositis (OM), antisynthetase syndrome (ASS), and immune-mediated necrotizing myopathy (IMNM). Methods: We performed a cross-sectional monocentric study. All patients with inflammatory myopathies (IMs) over a 6-month period were analyzed by NVC for giant and ramified capillaries, tortuosities, capillary density, disorganization, and scleroderma pattern. Clinical, biological, and pathological characteristics were retrospectively recorded. Patients were classified as having DM, OM, ASS, or IMNM for comparison. Patients were also compared with a group of patients with systemic sclerosis (SSc). Results: NVC was analyzed in DM (n = 17), OM (n = 8), ASS (n = 12), and IMNM (n = 6). Vascular disorganization and avascular zones were observed only in DM (11.8%) and OM (62.5%). The percentage of patients with giant capillaries was higher in OM (n = 4/8) than in DM (n = 3/17) and absent in ASS and IMNM. Frequency of ramified capillaries, tortuosities, hemorrhages, or thrombosis was not different between subgroups. A scleroderma pattern was only observed in OM patients. Conclusion: In this limited series of patients, we observed that DM and OM NVC abnormalities are different from ASS and IMNM. We could not determine NVC specific patterns associated with myositis-specific antibody subtypes of DM because of the small number of patients. Key Points • Nailfold videocapillaroscopy abnormalities are different in subgroups of inflammatory myopathies. • Giant capillaries, disorganization, and major capillary loss are observed in overlap myositis and dermatomyositis but not in antisynthetase syndrome (ASS) or immune-mediated necrotizing myopathy. • Nailfold videocapillaroscopy abnormalities in overlap myositis (with the exclusion of ASS) are close to systemic sclerosis. [ABSTRACT FROM AUTHOR]

Purpose: Neonatal immune neutropenia is observed in rare cases in newborns from mothers with idiopathic or autoimmune neutropenia, secondary to passive transfer of maternal granulocyte auto-antibodies. Methods: We performed a literature review and report four supplementary cases from the French registry of neutropenia. Results: Only 14 cases (11 mothers, 14 newborns) have been reported. Granulocyte aggregation (GAT) and granulocyte indirect immunofluorescence test (GIFT) are the recommended laboratory procedures for antibody detection. Monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA)-confirmed antibody specificity. Antibody detection in newborns is not generally possible owing to extreme neutropenia. In half of the cases autoantibodies against neutrophils (AAN) were positive in maternal sera (7 out of 11). In some newborns tested, IgG+ AAN were also positive, with disappearance in parallel of spontaneous neutrophil count improvement. No correlation between maternal type of AAN and titer and neonatal neutropenia can be established. Neutropenia resolved spontaneously between 2 weeks and 4 months. Infections in newborns were observed in 43% of cases, with no deaths reported. Granulocyte colony-stimulating factor (G-CSF) was administered to some newborns (5 out of 14) in the case of infections. Low-dose G-CSF administered to childbearing women during pregnancy could be proposed to prevent neutropenia in newborns. Conclusions: From the few cases reported so far it is impossible to draw any conclusions regarding frequency, risk factors, and outcome, but the overall prognosis for newborns seems good. Because it can be associated with potentially severe neonatal infections, autoimmune neutropenia in childbearing mothers should be closely monitored in collaboration with gynecologists and pediatricians. [ABSTRACT FROM AUTHOR]

Abstract Background We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis. Results From all MDS patients 11% presented with AIMs. These were heterogeneous and the most frequent where polyarthritis (25%) and autoimmune cytopenias (17%). No difference for frequency and type of AIMs was observed for the WHO 2016 MDS subgroups (p =. 3). In the case control study WHO classification, karyotype abnormalities, IPSS-R and IPSS were similar in both groups. The overall survival from MDS diagnosis was better in the group with AIMs [10.3 ± 0.6 (IC95% 6.2–12.9) versus 4.8 ± 1.1 years (IC95% 4.2–8.7), p =.04 ]. The better survival was restricted to MDS with low or intermediate-1 IPSS [11.1 ± 1.5 (IC95% 9.9-NR) versus 8.7 ± 1.3 years (IC95% 4.8–10.3), p =.006 ]. The better survival was only observed when AIMs diagnosis was timely associated or appeared after MDS diagnosis (p =.04). Factors associated with a better overall survival and survival without AML were steroid dependence [respectively HR = 0.042, p =.003 , (IC95% 0.005–0.33) and HR = 0.07, p =.002 , (IC95% 0.013–0.39)], a diagnosis of AIMs and MDS timely associated [respectively HR = 0.05, p =.009 , (IC95% 0.006–0.478) and HR = 0.1, p =.008 , (IC95% 0.018–0.54)] or a diagnosis of AIMs after MDS [respectively HR = 0.024 , p =.009 , (IC95% 0.001–0.39) and HR = 0.04, p =.008 , (IC95% 0.003–0.43)]. Conclusion Autoimmune and inflammatory diseases associated to MDS are heterogeneous. AIMs diagnosed after or concomitantly to MDS seems associated with a better survival. Prospective studies are necessary to demonstrate that autoimmunity is associated to a better control of the MDS clone. Highlights • Autoimmune and inflammatory diseases associated with MDS are heterogeneous. • Autoimmune and inflammatory diseases are not associated to a specific MDS subtype. • MDS patients with Autoimmune and inflammatory diseases seems to have a better overall survival than other MDS patients. [ABSTRACT FROM AUTHOR]

It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents. Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT. Retrospective multicenter study in French national HHT Registry patients exposed to AT. We included 126 patients with 180 courses of AT. Median follow-up was 24 [11–52] months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 [1.12;4.87], p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 [1.93;6.66], p < 0.001) or transfusion (HR 3.15 [1.61;6.18], p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 [1.57;4.65], p < 0.001) or MBE (HR 4.62 [2.68;7.98], p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 [1.37;11.22], p = 0.011). Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT. • Similar tolerability of antiplatelet and anticoagulant therapies in HHT • Dual antiplatelet therapy is not tolerated in HHT and should be avoided • Risk factors in HHT patients for major bleeding events (MBE) occurrence or premature discontinuation under antithrombotics are ≥60 years old, previous history of MBE or gastrointestinal bleeding, hospitalizations for bleeding in the last 3 months to help guide clinicians prescribing antithrombotic medication • Direct oral anticoagulants, notably apixaban, appear well tolerated by HHT patients [ABSTRACT FROM AUTHOR]

Background: Alemtuzumab is a humanized monoclonal antibody directed at CD52 approved as a disease-modifying therapy for relapsing forms of multiple sclerosis (MS). Objective: To describe a case of a life-threatening autoimmune anemia occurring after a first course of alemtuzumab for relapsing-remitting MS in a 28-year-old male. Methods: Case report. Results: A 28-year-old male developed a life-threatening autoimmune anemia occurring 11 months after first alemtuzumab course. Conclusion: We report the third case of autoimmune hemolytic anemia following treatment with alemtuzumab in a young MS patient. Due to the severity of this adverse event, neurologists using this treatment should be alert. [ABSTRACT FROM AUTHOR]

Acute severe hepatitis is a rare complication of adult-onset Still's disease (AOSD). This condition is poorly characterized. We performed a review of the medical literature to describe clinical, biological, pathological, and treatment characteristics from AOSD patients with acute severe hepatitis. Their characteristics were compared with AOSD patients without severe hepatitis. Twenty-one cases were collected including a new case reported here. Patients with severe hepatitis were mostly young adults with a median age of 28 years (range: 20 to 55 years). Overall, patients with severe hepatitis had less arthritis, macular rash, sore throat, lymphadenopathy, or splenomegaly than patients without severe hepatitis. Cytopenia was more frequent in case of severe hepatitis. Most patients were treated with steroids, and the use of biotherapies has increased over the last decade. Despite treatment, 49% of patients required liver transplantation and 24% died. Key Points • Acute severe hepatitis in adult-onset Still's disease (AOSD) is associated with liver transplantation and/or death in, respectively, 43% and 24% of cases. • Severe hepatitis is the inaugural manifestation of AOSD in half of cases. Diagnosis is difficult when extra-hepatic clinical manifestations are lacking. • The mechanism of hepatic necrosis in AOSD with severe hepatitis is unknown. Liver biopsy is not specific and should not delay treatment initiation. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN. Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone. Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42–92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p <.05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p =.07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p <.05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival. Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse. [ABSTRACT FROM AUTHOR]