Autoimmune thyroiditis in antinuclear antibody positive children without rheumatologic disease

<p>Abstract</p> <p>Background</p> <p>Children are commonly referred to a pediatric rheumatology center for the laboratory finding of an Anti-nuclear antibody (ANA) of undetermined significance. Previous studies regarding adult rheumatology patients have supported an association between ANA and anti-thyroid antibodies, with the prevalence of thyroid antibodies being significantly higher in patients referred to a rheumatology center for an ANA without evidence of connective tissue disease compared to the general population. The purpose of the present study was to determine the frequency of thyroid antibodies in children referred to a pediatric rheumatology center for a positive ANA without evidence of a connective tissue disease.</p> <p>Methods</p> <p>A retrospective chart review was performed on children who were referred to our pediatric rheumatology center between August 2003 and March 2007 for positive ANA with concurrent thyroid antibody and thyroid function tests performed who did not fulfill criteria for a specific connective tissue disease. Laboratory and clinical features were recorded and analyzed. Mean and standard deviation were used to describe continuous data. Chi-square or Fisher's exact tests were used to compare proportions between variables.</p> <p>Results</p> <p>One-hundred and four ANA-positive patients with concurrent thyroid studies were evaluated (88% female, 93% Caucasian, mean age 11.9 ± 4.0 years). Half of patients had an ANA titer ≥ 1:320. The ANA pattern was speckled in 60% of the patients. Thyroid antibodies were detected in 30% of the patients. Anti-Thyroglobulin (ATG) was detected in 29% and Anti-thyroid peroxidase (ATPO) in 21% of the patients; of these children, 14% had hypothyroidism. ANA pattern and titer were not associated with anti-thyroid antibody positivity.</p> <p>Conclusion</p> <p>Thyroid antibodies associated with chronic lymphocytic thyroiditis, ATG and ATPO, were detected significantly higher in ANA-positive children without a rheumatologic condition (30%) as compared to the general pediatric population (1.3 - 3.4%). ANA titer and pattern did not help predict the presence or absence of thyroid antibodies. Given the high frequency of thyroid antibodies and increased risk of developing hypothyroidism over time, routine evaluation of ATG and ATPO with thyroid function tests in ANA-positive children is recommended.</p

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background: Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. / Methods: We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. / Findings: In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. / Interpretation: Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. / Funding: UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

How an Ebstein-Barr Virus May Induce Acute Fulminant Myocarditis in a Young Immunocompetent Adult: Case Report

INTRODUCTION Fulminant myocarditis, especially those caused by the Ebstein-Barr Virus (EBV) is a rare disease (1). For the first time, we describe a case of fulminant myocarditis caused by EBV in a young, immunocompetent adult, co-infected with parvovirus B19. Keywords: Ebstein-Barr virus, fulminant myocarditi

Chronotropic incompetence can limit exercise tolerance in COPD patients with lung hyperinflation

S&eacute;bastien Hulo,1 Jocelyn Inamo,2 Aur&eacute;lie Dehon,3 Olivier Le Rouzic,4 Jean-Louis Edme,1 Remi Neviere51Universit&eacute; Lille, CHU Lille, EA 4483, IMPact de l&rsquo;Environnement Chimique sur la Sant&eacute; humaine, Lille, France; 2D&eacute;partement de Cardiologie &ndash; CHU Fort de France, Martinique &ndash; Facult&eacute; de M&eacute;decine &ndash; Universit&eacute; des Antilles, France; 3P&ocirc;le d&rsquo;Anesth&eacute;sie R&eacute;animation ADRU, CHU N&icirc;mes, N&icirc;mes, France; 4Universit&eacute; Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; 5Universit&eacute; Lille, Inserm, CHU Lille, Lille Inflammation Research International Center, Lille, FrancePurpose: Metabolic-chronotropic relationship is the only concept that assesses the entire chronotropic function during exercise, as it takes into account individual fitness. To better understand interrelationships between chronotropic incompetence (CI), dynamic hyperinflation (DH) and exercise limitation among Global initiative for chronic Obstructive Lung Disease (GOLD) stages of chronic obstructive pulmonary disease (COPD) disease severity, we evaluated cardiopulmonary responses to symptom-limited cycle exercise in stable patients.Patients and methods: We prospectively studied 47 COPD patients classified by GOLD stage severity. Pulmonary function tests and cardiopulmonary responses to symptom-limited incremental exercise were studied. CI was defined by regression line between percent heart rate (HR) reserve and percent oxygen uptake (V&rsquo;O2) reserve, ie, chronotropic-metabolic index (CMI). DH was defined from the knot resulting from the nonlinear regressions of inspiratory capacity changes from rest to peak (dynamic inspiratory capacity (ICdyn)) with percentage of maximal HR and CMI.Results: Aerobic capacity (median interquartile ranges) peak V&rsquo;O2, 24.3 (23.6; 25.2), 18.5 (15.5; 21.8), 17.5 (15.4; 19.1) mL&middot;kg-1&middot;min-1 and CMI worsened according to GOLD severity. The optimal knot of ICdyn was equal to &minus;0.34 L. The multivariate logistic regression showed a strong relationship between CI (outcome) and DH (odds ratio [confidence interval 95]) 25 (3.5; 191.6). Conclusion: COPD patients with DH have a poor cardiovascular response to exercise, which may be attributed to CI.Keywords: COPD, hyperinflation, chronotropic incompetence, exercis