Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Publisher Copyright: Copyright © 2014 by the American College of Rheumatology.Results The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections. Conclusion The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA. Objective To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection. Methods International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present.publishersversionPeer reviewe

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

The immune system in neonates and infants: Mechanisms and clinical correlates

Immaturity of the neonatal immune system has been suggested in the past as the factor underlying the high rates of morbidity and mortality from infections in newborn infants and the impairment of the neonatal immune response to most vaccines. A biased TH1/TH2 differentiation favoring TH2- rather than TH1-polarization has been incriminated in the susceptibility of newborns to allergic reactions and microbial infections, respectively. Over the last decade, increasing evidence has been produced which indicates that the neonatal immune system has been shaped to accommodate the abrupt transition of the newborn infant from a sterile intrauterine environment into a world rich in foreign antigens, with the concomitant avoidance of harmful inflammatory responses. At the same time, neonatal immunity appears to have a high degree of plasticity and flexibility, allowing mature responses when the infant is faced with life-threatening infectious agents. Deviations from this equilibrium are responsible for many aspects of neonatal mortality. Improving the understanding of neonatal immune function, provides the possibility of developing targeted therapeutic interventions against infections, allergies and other pathological mechanisms related to intrauterine inflammation. In addition, the documented ability of newborn infants to achieve mature immune functions under certain conditions of antigen exposure has provided incentive for the development of novel approaches to enhancing the efficacy of neonatal vaccination. © Athens Medical Society

Disordered eating attitudes and emotional/behavioral adjustment in Greek adolescents

Purpose: The aim of this study was to examine the relationship between disordered eating attitudes and emotional/behavioral adjustment in Greek adolescents as well as the moderating role of gender and body mass index (BMI) in this relationship. Methods: Ninety adolescents, 11–18 years old, were assessed using anthropometric measurements; demographics, eating attitudes and level of emotional/behavioral adjustment were examined via self-reported questionnaires. Results: Disordered eating attitudes were prevalent in 17.8% of the sample. A significant relationship was found between disordered eating attitudes and Youth Self-Report (YSR) anxiety score (r =.22, p <.05). Gender significantly moderated the relationship between YSR anxiety symptoms and Eating Attitudes Test (EAT) scores (b =.59, p =.01) and this effect held true for the EAT bulimia subscale (b =.20, p =.03), but not for the dieting or the oral control subscales. Contrary to our hypothesis, BMI did not moderate the relationship between EAT and YSR anxiety sub-scores (b =.13, p >.05). Conclusion: Girls with elevated anxiety levels appear to be at risk for exhibiting disordered eating attitudes, especially bulimic behaviors. This finding highlights the importance of developing gender-based preventive interventions tailored to these specific emotional/behavioral aspects. Level of evidence: Level V, cross-sectional descriptive study. © 2017, Springer International Publishing AG, part of Springer Nature

Hereditary angioedema in Greek families caused by novel and recurrent mutations

This study constitutes the first molecular analysis of hereditary angioedema (HAE) in Greece, where 11 patients from three unrelated families with recurrent angioedema attacks and decreased C1 inhibitor antigenic levels were analyzed for SERPING1 mutations. Interestingly, one family displayed a novel SERPING1 alteration, characterized by the substitution of two consecutive nucleotides TC to AA, resulting in a termination codon (F225X). To the best of our knowledge, this is the first report of such a mutation in SERPING1, causing HAE. The second family displayed the nonsense mutation W482X, and the third the missense mutation M1V, already described in the literature. The type of mutation did not predict clearly the disease phenotype, since even members of the Same family displayed a variety of the frequency and the severity of angioedema attacks. Our study identified a novel mutagenesis mechanism for HAE pathogenesis, providing additional evidence for the genetic heterogeneity of the disease. (C) 2009 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved