Quitterie Reynaud

Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis.

AIM To evaluate the magnitude of venous and arterial thrombosis risk associated with antiphospholipid antibodies (APLs) in adults without systemic lupus erythematosus (SLE). METHODS Case-control and cohort studies were selected from the MEDLINE and Cochrane Library databases. Two investigators independently extracted data on study design, patient characteristics, venous and arterial events and exposure to APLs, including lupus anticoagulant (LA), anticardiolipin (aCL), anti-β2 Glycoprotein I (β2GpI), anti-prothrombin (aPT), anti-phosphatidyl serine (aPS), and anti-phosphatidyl ethanolamine (aPE). RESULTS 30 studies were included (16,441 patients). The odds ratio (OR) for venous thrombosis was 6.14 (95% confidence interval [CI] 2.74-13.8) in LA-positive patients (5 studies, 1650 patients) and 1.46 (CI 1.06-2.03) in aCL-positive patients (12 studies, 5375 patients). None of the associations with more recently identified APLs was significant, but fewer studies were available. For arterial thrombosis, the OR for LA and aCL was 3.58 (CI 1.29-9.92) and 2.65 (CI 1.75-4.00) respectively. The associations between β2GpI, aPT and aPS and the risk of arterial thrombosis were also significant, the OR being 3.12 (CI 1.51-6.44), 2.95 (CI 1.31-6.66) and 6.00 (CI 3.07-11.7), respectively. Owing to the heterogeneity of cut-off values for each APL assay, we were unable to perform any sensitivity analysis to determine the optimal value. The presence of low-quality studies may have led to overestimation of the magnitude of the associations. CONCLUSIONS LA and aCL were significantly associated with an increased risk of thrombosis, especially arterial, in patients without SLE. Systematic thromboprophylaxis in high-risk patients with APL should be evaluated.

The clinical phenotype associated with myositis-specific and associated autoantibodies: A meta-analysis revisiting the so-called antisynthetase syndrome

OBJECTIVE To describe the clinical spectrum associated with aminoacyl-transfer RNA synthetase (ARS) autoantibodies in patients with idiopathic inflammatory myositis defined according to Peter and Bohans criteria. METHODS Cohort studies were selected from MEDLINE and Embase up to August 2013. Two investigators independently extracted data on study design, patient characteristics, and clinical features (interstitial lung disease [ILD], fever, mechanics hands [MH], Raynauds phenomenon [RPh], arthralgia, sclerodactyly, cancer and dermatomyositis-specific rash) according to the presence of myositis-specific (anti-aminoacyl-transfer RNA synthetase [ARS], anti-signal recognition particle [anti-SRP] and anti-Mi2) and myositis-associated (anti-PM/Scl, anti-U1-RNP and anti-Ku) autoantibodies. RESULTS 27 studies (3487 patients) were included in the meta-analysis. Arthralgia (75%, CI 67-81) and ILD (69%, CI 63-74) were the most prevalent clinical signs associated with anti-ARS autoantibodies. Anti-Mi2 and anti-SRP autoantibodies were associated with few extramuscular signs. ARS autoantibodies were identified in 13% of patients with cancer-associated myositis (5-25). Patients with non-anti-Jo1 ARS had greater odds of presenting fever (RR 0.63, CI 0.52-0.90) and ILD (RR 0.87, CI 0.81-0.93) compared to those with anti-Jo1 autoantibodies. The frequencies of myositis (RR 1.60, CI 1.38-1.85), arthralgia (RR 1.52, CI 1.32-1.76) and MH (RR 1.47, CI 1.11-1.94) were almost 50% higher in patients with anti-Jo1 compared to non-anti-Jo1 ARS autoantibodies. Patients with anti-PM/Scl differed from those with anti-ARS autoantibodies by a greater prevalence of RPh (RR 0.70, CI 0.53-0.94) and sclerodactyly (RR 0.47, CI 0.25-0.89). ILD was less frequent in patients with anti-U1-RNP autoantibodies (RR 3.35, CI 1.07-10.43). No difference was observed between anti-ARS and myositis-associated autoantibodies for other outcomes. CONCLUSIONS The presence of anti-ARS autoantibodies delimits a heterogeneous subset of patients with a high prevalence of myositis, MH, arthralgia in anti-Jo1 patients, and RPh and fever in non-anti-Jo1 patients. The clinical signs of populations positive for anti-PM/Scl and anti-ARS autoantibodies largely overlap, especially with regard to ILD, challenging the clinical delimitation of the antisynthetase syndrome.

Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies.

OBJECTIVE This study aims to evaluate the response to rituximab (RTX) treatment in auto-immune hemolytic anemia (AIHA) patients. METHODS Studies were selected from MEDLINE up to March 2014. Two investigators independently extracted data on study design, patient characteristics, clinical features (AIHA type, disease duration, previous treatments), dose-schedule of rituximab, duration of treatment follow-up, and toxicities. Pooled overall response rate (ORR) and complete response (CR) rates were evaluated to determine RTX efficacy and toxicity by calculating the weighted mean proportion with fixed or random-effects models in case of heterogeneity (p<0.1 or I(2)>50%). RESULTS Twenty-one studies encompassing 409 patients were included in the meta-analysis. The characteristics of the entire analyzed cohort reported were as follows: mean male proportion: 43%, mean age: 50 years, splenectomized patients range: 0-50%. Warm AIHA, primary AIHA and adults were mostly represented. With the random-effect model, the overall response rate (ORR) was 73% (95% CI 64-81%, 20 studies encompassing 402 patients). CR rate was 37% (95% CI 26-49%, 20 studies including 397 patients). The ORRs were close to 70% for warm AIHA (79%, 95% CI 60-90%, 11 studies, 154 patients), primary AIHA (67%, 95% CI 49-81%, 10 studies, 161 patients), and secondary AIHA (72%, 95% CI 60-82%, 8 studies, 66 patients). The ORR was 57% (95% CI 47-66%, 6 studies, 109 patients) for cold agglutinin disease (CAD). The CR rate was 42% (95% CI 27-58%, 11 studies, 154 patients) for warm AHAI, 32% (95% CI 17-51%, 11 studies, 176 patients) for primary AIHA, 46% (95% CI 30-62%, 9 studies, 87 patients) for secondary AIHA and only 21% (95% CI 6-51%, 7 studies, 118 patients) for CAD. Definitive response rates were evaluated during follow-up. CR rate was the highest within 2 to 4 months after RTX (13 studies, 203 patients, CR=70% [57-80%]). As for toxicities, 38 adverse events in 364 patients were noted (14% (95% CI 9-21%)). Sixteen events were infusion-linked side effects, mostly chills and fever, whereas twenty-two were severe. Only one opportunistic Pneumocystis jiroveci pneumonia was reported. Seventeen patients out of 364 (4.6%) died during follow-up. In univariate mixed-effect meta-regressions, ORR and CR were significantly associated with warm AIHA (p=0.002) and mean age (p<0.001), and marginally associated with disease type (p=0.06 and 0.005, respectively). CONCLUSIONS Rituximab seems to be a safe and effective therapy for AIHA in this meta-analysis of observational studies. The authors suggest that it could be used at an earlier point in therapy, before more toxic immunosuppressive drugs, or in place of splenectomy in some cases.

Idiopathic inflammatory myopathies and the lung.

Idiopathic inflammatory myositis (IIM) is a group of rare connective tissue diseases (CTDs) characterised by muscular and extramuscular signs, in which lung involvement is a challenging issue. Interstitial lung disease (ILD) is the hallmark of pulmonary involvement in IIM, and causes morbidity and mortality, resulting in an estimated excess mortality of 50% in some series. Except for inclusion body myositis, these extrapulmonary disorders are associated with the general and visceral involvement frequently found in other CTDs including fever, Raynauds phenomenon, arthralgia, nonspecific cutaneous modifications and ILD, for which the prevalence is estimated to be up to 65%. Substantial heterogeneity exists within the spectrum of IIMs, and each condition is associated with various frequencies and subtypes of pulmonary involvement. This heterogeneity is partly related to the presence of various autoantibodies encompassing anti-synthetase, anti-MDA5 and anti-PM/Scl. ILD is present in all subsets of IIM including juvenile myositis, but is more frequent in dermatomyositis and overlap myositis. IIM can also be associated with other presentations of respiratory involvement, namely pulmonary arterial hypertension, pleural disease, infections, drug-induced toxicity, malignancy and respiratory muscle weakness. Here, we critically review the current knowledge about adult and juvenile myositis-associated lung disease with a detailed description of therapeutics for chronic and rapidly progressive ILD. Interstitial lung disease is a leading cause of morbidity in dermatomyositis/polymyositis http://ow.ly/M1wB8

Retrospective observational study of French patients with cystic fibrosis and a Gly551Asp-CFTR mutation after 1 and 2 years of treatment with ivacaftor in a real-world setting

BACKGROUND Ivacaftor has been shown to improve lung function and body weight in patients with CF and a gating mutation. Real-world evaluation is warranted to examine its safety and effectiveness over the long term. METHODS A retrospective observational multicentre study collected clinical data in the year before and the 2years after ivacaftor initiation in patients with CF and a Gly551Asp-CFTR mutation. RESULTS Fifty-seven patients were included. Mean absolute change in FEV1% predicted improved from baseline to Year 1 (8.4%; p<0.001) and Year 2 (7.2%; p=0.006). Statistically significant benefits were observed with increased body mass index, fewer Pseudomonas aeruginosa and Staphylococcus aureus positive cultures, and decreased IV antibiotics and maintenance treatment prescriptions (including azithromycin, Dornase alpha and nutritional supplements). No significant adverse events were reported. CONCLUSION The clinical benefits of ivacaftor reported in previous clinical trials were confirmed in a real-world setting two years post-initiation, also reducing treatment burden.

Contraceptive practices and cervical screening in women with cystic fibrosis

STUDY QUESTION Is gynaecological management of women with cystic fibrosis (CF) adequate? SUMMARY ANSWER Gynaecological care (frequency of follow-up, cervical screening and contraceptive use among sexually active women) in women with CF fails to reach the recommended level. WHAT IS KNOWN ALREADY Little is known about gynaecological follow-up and cervical screening in CF. Only few studies have described contraceptive practices in cohorts of CF women. STUDY DESIGN, SIZE, DURATION We did a cross-sectional study in a cohort of 155 CF women attending the Lyon adult centre. Women attending the CF adult centre in 2014 completed a written questionnaire about their contraceptive choices, frequency of gynaecological follow-up and cervical screening. Other clinical data were collected from the CF adult centre registry. PARTICIPANTS/MATERIALS, SETTING, METHODS One hundred and twenty women (100%) answered the questionnaire, among whom two were post-menopausal (46 and 59 years of age), and five were pregnant. MAIN RESULTS AND THE ROLE OF CHANCE Seventy-four per cent of the women declared they had undergone gynaecological follow-up (89% of the women with transplantation), and only 55% reported having at least one previous Pap smear test. Among the transplanted patients, only 58% had had a Pap smear test, despite immunosuppressive treatment. The overall rate of contraception was only 64% and in diabetic women, it was 61%. Among contraception users; 65% used oral contraception, predominantly combined estrogen-progestagen (47%); among diabetic patients, 26% used progestin-only contraception. Intrauterine device accounted for 10% of patients using contraception, and tubal ligation only 4%. LIMITATIONS, REASONS FOR CAUTION This study is limited by its cross-sectional design. Despite an internal validation of the questionnaire showing an almost perfect agreement, the risk of recall bias has to be taken into account. WIDER IMPLICATIONS OF THE FINDINGS This study of practices highlights the importance of improved information regarding sexuality, fertility and reproductive health in young women with CF. A regular gynaecological follow-up and cervical screening is mandatory in this population. Better gynaecological care and contraceptive advice would help to avoid unplanned pregnancies, and optimize contraceptive selection in relationship to specific clinical conditions.

Immunomodulatory treatments for persistent and chronic immune thrombocytopenic purpura: A Prisma-compliant systematic review and meta-analysis of 28 studies

Background Corticosteroid sparing is required in 15% to 40% of adults with persistent or chronic primary immune thrombocytopenic purpura (ITP). Herein, the efficacy of immunomodulatory drugs (dapsone, interferon alpha, danazol, and hydroxychloroquine as second-third-line therapies in ITP is investigated. Methods MEDLINE was searched for studies that included patients with persistent or chronic primary ITP and published before the end of December 2014. Two investigators independently extracted data regarding study design, patient characteristics, dosage schedule, time to response, and occurrence of adverse events. The pooled overall response rate (ORR; platelet count >30 × 109 L−1) and the complete response rate (CRR; platelet count >100 × 109 L−1) were evaluated to determine drug efficacy by calculating weighted mean proportion using a fixed or random-effects model according to heterogeneity (I2 > 50%). The study was performed following the MOOSE and PRISMA guidelines. Results A total of 28 studies (415 patients) were included (dapsone: k = 7 studies, n = 80; danazol: k = 12, n = 224; interferon alpha: k = 8, n = 83; hydroxychloroquine: k = 1, n = 28). The mean patient age was 50 years (female sex 70%, splenectomy 47%). The ORR and CRR were 55% (95% CI: 44%–66%, I2 = 0%) and 21% (95% CI: 13%–31%, I2 = 0%), respectively, for dapsone; 42% (95% CI: 22%–65%, I2 = 63%) and 18% (95% CI: 10%–29%, I2 = 9%), respectively, for interferon alpha; and 58% (95% CI: 42%–72%, I2 = 67%) and 29% (95% CI: 19%–42%, I2 = 63%), respectively, for danazol. The ORR was 50% (95% CI: 32%–67%) for hydroxychloroquine (data not available for CRR). Meta-regression analysis found a correlation between the ORR for interferon alpha and the splenectomized status of the patient (P = .02) and between the CRR for danazol and disease duration (P < .001). In total, 73%, 51%, 30%, and 0% of patients who received danazol, dapsone, interferon alpha, and hydroxychloroquine experienced side effects, respectively. Conclusion The ORR was equivalent for hydroxychloroquine, danazol, and dapsone in ITP. Regarding their low CRR, patients at high risk of infection or at low risk of bleeding should benefit from these treatments. Thanks to their best efficacy and safety profiles, dapsone and hydroxychloroquine in patients with antinuclear antibodies should be preferred over danazol and interferon alpha.

Glucose trajectories in cystic fibrosis and their association with pulmonary function

BACKGROUND The prevalence of cystic fibrosis-related diabetes is increasing. This condition is potentially responsible for respiratory decline. METHODS At inclusion, then yearly (over three years), 111 children and 117 adults with cystic fibrosis had oral glucose tolerance and insulin tests at one (G1) and 2h (G2). KmL analysis identified homogeneous G1 and G2 glucose trajectories. A linear mixed model quantified the relationships between trajectories and FEV1 changes. RESULTS In children, there were three G1 and four G2 trajectories and FEV1 decrease was not significantly different between G1 or G2 trajectories. In adults, two G1 and four G2 trajectories were identified and FEV1 change was estimated at -0.85/year (95% CI: [-1.54; -0.17], p=0.01) whatever the G1 trajectory and found significantly faster in the high and increasing G2 trajectory (-2.1/year, [-3.9; -0.2], p=0.03). CONCLUSIONS In case of persistent G2 abnormality, physicians should be alert for clinical deterioration and intensify patient surveillance.

Long-term extrapulmonary comorbidities after lung transplantation in cystic fibrosis: Update of specificities

Lung transplantation (LT) is the standard therapeutic option for cystic fibrosis (CF) patients with end‐stage lung disease. Both conditions lead to extrarespiratory complications, such as diabetes, renal insufficiency, bone disease, and cancer. The purpose of this study was to provide an update of the nonrespiratory comorbidities following LT in adult patients with CF and their specificities regarding their multisystemic underlying condition despite their younger age compared to other patients undergoing LT. Diabetes, renal insufficiency, metabolic bone disease, hypertension, liver disease, and cancer are the comorbidities considered in this review. The increase in CF adults living with a lung transplant justifies an update of knowledge for this specific situation (the prevalence of these complications, underlying risk factors), to provide better medical care and establish early diagnosis strategies.

Rare and unusual presentation of Cladophialophora infection in a pulmonary transplant cystic fibrosis patient

A 35‐year‐old woman with severe cystic fibrosis was admitted for sudden loss of strength in both legs, revealing a myelitis. The medullary lesion biopsy revealed phaeohyphomycosis caused by Cladophialophora species. Myelitis caused by Cladophialophora bantiana is a rare disease associated with high mortality.