Viral load kinetics of Zika virus in plasma, urine and saliva in a couple returning from Martinique, French West Indies.

While the rapid spread of Zika virus (ZIKV) in South America has been declared a public health emergency few data are available on the kinetics of the virus load and the specific antibodies in individual patients. This report describes the kinetics of ZIKV decay in the body compartments and the kinetics of anti ZIKV IgG and IgM of two people returning from Martinique, French West Indies. ZIKV remained detectable in the plasma for roughly 2 weeks indicating that mosquito control measures should be prolonged accordingly. Remarkably, their urine samples consistently tested positive for even longer. The antibodies responses were different between the two patients but for both the rapid onset of IgM allowed a diagnosis from the end of the first week.

Mastocytosis among elderly patients: A multicenter retrospective French study on 53 patients.

Mastocytosis is a heterogeneous group of diseases with a young median age at diagnosis. Usually indolent and self-limited in childhood, the disease can exhibit aggressive progression in mid-adulthood. Our objectives were to describe the characteristics of the disease when diagnosed among elderly patients, for which rare data are available.The French Reference Center conducted a retrospective multicenter study on 53 patients with mastocytosis >69 years of age, to describe their clinical, biological, and genetic features.The median age of our cohort of patients was 75 years. Mastocytosis variants included were cutaneous (n = 1), indolent systemic (n = 5), aggressive systemic (n = 11), associated with a hematological non-mast cell disease (n = 34), and mast cell leukemia (n = 2). Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). The main biological features were anemia (79.2%), thrombocytopenia (50.9%), leucopenia (20.8%), and liver enzyme abnormalities (32.1%). Of the 40 patients tested, 34 (85%), 2 (5%), and 4 (10%) exhibited the KIT D816V mutant, other KIT mutations and the wild-type form of the KIT gene, respectively. Additional sequencing detected significant genetic defects in 17 of 26 (65.3%) of the patients with associated hematological non-mast cell disease, including TET2, SRSF2, IDH2, and ASLX1 mutations. Death occurred in 19 (35.8%) patients, within a median delay of 9 months, despite the different treatment options available.Mastocytosis among elderly patients has a challenging early detection, rare skin involvement, and/or limited skin disease; it is heterogeneous and has often an aggressive presentation with nonfortuitous associated myeloid lineage malignant clones, and thus a poor overall prognosis.

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.

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 Bohan's 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, mechanic's hands [MH], Raynaud's 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.