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Aims: The purpose of the study was to describe the pattern of 99mTc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin cardiac amyloidosis (TTR-CA).Methods: Fifty patients with TTR-CA underwent 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images.Results: The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial 99mTc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and - 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = - 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = - 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184).Conclusion: These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis. [ABSTRACT FROM AUTHOR]

L'un des critères de diagnostic de la sclérodermie systémique (ScS) est la présence d'auto-anticorps spécifiques, souvent associés à des caractéristiques cliniques particulières. Des études ayant récemment mis en évidence la présence d'ACPA dans la ScS, nous nous sommes proposé d'évaluer la prévalence des ACPA dans cette affection et leur influence sur la présentation clinique de la ScS. Une revue systématique de la littérature a été réalisée dans les bases de données PubMed et Cochrane, sur les articles publiés entre 1999 et mars 2017. Les termes de recherche étaient les suivants : « systemic sclerosis [MeSH] AND (ACPA OR anti-CCP OR rheumatoid factor OR cohort OR value diagnostic) ». Dans un premier temps, nous avons sélectionné des cohortes de plus de 50 patients atteints de ScS pour lesquels une identification des ACPA avait été réalisée afin de déterminer la fréquence de ces auto-anticorps. Nous avons ensuite inclus les études analysant les profils cliniques selon le statut ACPA. Des méta-analyses ont été prises en compte lorsqu'au moins deux études étaient disponibles. Nous avons d'abord identifié 13 études observationnelles incluant au total 1231 patients atteints de ScS. La prévalence moyenne des ACPA dans la ScS y était de 9,2 %. Nous avons ensuite identifié neuf études décrivant les aspects cliniques selon le statut ACPA. Nos méta-analyses ont révélé une association significative entre la positivité des ACPA et la présence d'arthrite (odds ratio [OR] 22,48 [10,71–47,21], d'érosions articulaires visibles à la radiographie (OR 14,79 [6,38–34,28]), d'une fibrose pulmonaire [OR 2,75 [1,21–6,24]), d'une atteinte de l'œsophage (OR 2,72 [1,05–7,07]) et d'une atteinte cutanée diffuse (OR 2,21 [1,21–4,03]). La prévalence des ACPA dans la sclérodermie est de 9,2 %. Notre méta-analyse met en évidence un risque accru d'arthrite érosive, de fibrose pulmonaire, d'atteinte de l'œsophage et d'atteinte cutanée diffuse chez les patients atteints de ScS avec ACPA positifs. Les évaluations de la ScS devraient inclure systématiquement une analyse des ACPA. [ABSTRACT FROM AUTHOR]

Abstract Objectives The purpose of our study was to determine the prevalence and risk factors associated with malnutrition, and selenium (Se) and vitamin C (vitC) deficiencies in systemic sclerosis (SSc) patients. Methods We included adult SSc patients fulfilling the 2013 ACR/EULAR criteria from the Toulouse University Hospital cohort who underwent a micronutrient workup (including vitC, Se or thiamine levels) between 2011 and 2016. Results: 82 patients were included, mostly women (76%), with a median age of 60 years. SSc was limited in 76% of the cases, with Scl-70 and centromere antibodies in 32% and 44%, respectively. Median disease duration was 7.4 years. Cardiac involvement was noticed in 19% and gastrointestinal tract in and 95%; 9% had pulmonary artery hypertension (PAH) and 63% had interstitial lung disease. Overt malnutrition was present in 14 (17%) patients. Micronutrient deficiencies included Se (35%), vitC (31%) and/or thiamine (6%). Malnourished patients had significantly a higher summed Medsger disease severity scales (7.5 vs. 5, P =.003), lower hemoglobin (10.6 vs. 12.9 g/dL, P <.0001) and vitC levels (3.6 vs. 10.6 mg/L, P =.003). Cardiac involvement was significantly associated with Se deficiency (OR 6.2, IC 95%[1.48–32.70], P =.05). The factors associated with vitC deficiency were malnutrition (OR 8.57, IC 95%[2.16–43.39], P =.003), modified Rodnan skin score ≤ 14 (OR 0.33, IC95[0.11–1], P =.05), PAH (27% in deficient vs. none in non-deficient patients, P =.0006) and esophagitis or Barrett's mucosa (OR 4.05, IC95[1.27–13.54], P =.02). Conclusions Se testing should be considered as soon as cardiac involvement is suspected. VitC testing should be considered in malnourished SSc patients, especially if skin involvement is extensive. Highlights • Micronutrient deficiency is frequent in SSc and is not associated with malnutrition. • SSc primary heart disease is associated with selenium deficiency. • Malnutrition and SSc severity is associated with vitamin C deficiency. • Routine micronutrient testing and targeted supplementation might be useful in SSc. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of systemic sclerosis (SSc) is partially determined by the presence of specific autoantibodies often associated with specific clinical features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate the prevalence of ACPA in SSc and to assess their influence on clinical presentation of SSc.Methods: A systematic literature search was performed using PubMed and Cochrane databases' publications between 1999 and March 2017. Search terms were: "systemic sclerosis [MeSH] AND (ACPA OR anti-CCP OR rheumatoid factor OR cohort OR value diagnostic)". In a first step, we selected cohorts with >50 SSc patients with ACPA identification, for ACPA frequency determination. In a second step, we included studies that analysed clinical profiles according to ACPA status. Meta-analyses were performed when at least two studies were available.Results: First, we identified 13 observational studies with a total of 1231 SSc patients. The mean prevalence of ACPA in SSc was 9.2%. Secondly, we identified nine studies reporting clinical aspects according to ACPA status. Our meta-analyses showed a significant association between ACPA positivity and the presence of arthritis (odds ratio (OR)=22.48 [10.71-47.21]), joint erosions seen on X-rays (OR=14.79 [6.38-34.28]), pulmonary fibrosis (OR=2.75 [1.21-6.24]), oesophagus involvement (OR=2.72 [1.05-7.07]), and diffuse skin involvement (OR=2.21 [1.21-4.03]).Conclusions: The prevalence of ACPA in scleroderma is 9.2%. Our meta-analysis shows an increased risk for erosive arthritis, pulmonary fibrosis, oesophagus involvement and diffuse skin involvement, in patients with ACPA-positive SSc. ACPA should be systematically included in SSc assessment. [ABSTRACT FROM AUTHOR]

Abstract: The clinical phenotype and evolution of antisynthetase syndrome (ASS) are heterogeneous. This study was therefore undertaken to identify subgroups of ASS patients with similar clinico-biological features and outcomes. This retrospective multicentric study included 233 consecutive patients with three different anti-aminoacyl-tRNA-synthetase antibodies (anti-ARS): anti-Jo1 (n =160), anti-PL7 (n =25) and anti-PL12 (n =48). To characterise ASS patients, bivariate, multiple correspondence (MCA), cluster and survival analyses were performed. Interstitial lung disease (ILD) and myositis were the most common ASS manifestations. However, their respective frequencies were correlated to anti-ARS specificity: ILD was more frequent (80% and 88% vs 67%, p =0.014) whereas myositis was less common (44% and 47% vs 74%, p <0.001) in patients with anti-PL7 and anti-PL12 compared to anti-Jo1. The MCA suggested that anti-PL7 and anti-PL12 phenotypes were close to one another and distinct from anti-Jo1. The clustering analysis confirmed these data, identifying subgroups strongly defined by the anti-ARS specificity and other clinical features. Cluster 1 (n =175, 86% of anti-Jo1) defined patients with the most diffuse phenotype, whereas patients from cluster 2 (n =48, 96% of anti-PL12 and anti-PL7) exhibited a disease more restricted to the lung. Patient survival was also conditioned by the anti-ARS specificity, and was significantly lower in patients with anti-PL7/12 rather than anti-Jo1 (p =0.012). Other factors associated with poor survival were mostly related to pulmonary involvement, including severe dyspnea (p =0.003) and isolated ILD (p =0.009) at diagnosis. In patients with ASS, the phenotype and the survival were correlated with the anti-ARS specificity. [Copyright &y& Elsevier]

Hereditary renal amyloidosis caused by a new variant lysozyme in a French family. Background. The number of proteins with mutations resulting in amyloidosis has continued to increase. Five proteins—transthyretin, fibrinogen α-A chain, apolipoprotein AI, lysozyme, apolipoprotein AII, cystatin C and gelsolin—can be associated with hereditary amyloidosis involving the kidney. Methods. A French family with a history of autosomal dominant hereditary amyloidosis with early sicca syndrome and nephropathy leading to renal failure after the fifth to, the seventh decade was studied. Several tissue specimens obtained from the proband and his relatives were examined. Immunohistochemistry was performed on paraffin embedded sections using the indirect immunoperoxidase technique. We searched for mutations in the five exons and flanking introns of the lysozyme gene. Results. Amyloid deposits from the bowel, labial salivary gland and kidney were intensively stained by anti-lysozyme antibody. Sequence analysis of lysozyme exon 2 from the affected individuals revealed a nucleotide substitution predicting a substitution of the amino acid at position 64 in the mature protein from tryptophane, an aromatic residue to the cationic residue arginine (W64R). Conclusion. We report a novel mutation (W64R) of the lysozyme that is associated with hereditary amyloidosis and prominent nephropathy. Since the treatment of hereditary amyloidosis greatly varies with the nature of the amyloid protein, thorough characterization of the latter is crucial for the management of the disease. [ABSTRACT FROM AUTHOR]