Favorable outcomes with reduced steroid use in juvenile dermatomyositis

BACKGROUND: High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing. METHODS: We retrospectively reviewed the records at a single tertiary-care children\u27s hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis, and complications from treatment. RESULTS: Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (IQR 3-7.5). Myositis control was achieved in a median of 7.1 months (IQR 0.9-63.4). Cutaneous disease control was achieved in a median of 16.7 months (IQR 4.3-89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (IQR 0.5-1.74). The median duration of steroid treatment was 9.1 months, (IQR 4.7-17.4), while the median duration of any pharmacotherapy was 29.2 months (IQR 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%). CONCLUSION: Current accepted treatment paradigms for Juvenile Dermatomyositis include oral glucocorticoids beginning at 2 mg/kg/day and reduced over a prolonged time period. However, our results suggest that treatment using reduced doses and duration with early use of steroid-sparing agents is comparably effective in achieving favorable outcomes in Juvenile Dermatomyositis

Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease

Introduction: The effectiveness of canakinumab may change according to the different times it is used after Still's disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment.Methods: Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still's disease. Seventy-seven (51 females and 26 males) patients with Still's disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent.Results: No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment.Conclusion: Canakinumab has proved to be effective in patients with Still's disease, regardless of its line of biologic treatment

Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry

: To characterize clinical and laboratory signs of patients with still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. patients with still's disease classified according to internationally accepted criteria were enrolled in the autoInflammatory disease alliance (AIDA) still's disease registry. clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). at multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data

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

Expression of adhesion molecules ICAM-1 and VCAM-1 in the aorta of rats at early stages of atherosclerosis

Introduction: Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM-1), strongly participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherosclerosis. The aim of the study was to examine the expression of VCAM-1 and ICAM-1 in the aorta of rats at the early stages of atherosclerosis and the correlation with their concentration in the serum Materials and Methods: Forty four male rats, ten weeks of age, were divided in 4 groups. Groups A and C (n =12) were fed with rich cholesterol diet (enriched with 2% cholesterol) for 12 and 16 weeks respectively. Group B (regression group, n =12) was fed for the first 12 weeks with rich cholesterol diet and for another 4 weeks with normal diet. Group D (control group, n =8) was fed with normal diet for 12 weeks. After the euthanasia, we received the aorta of the animals. We measured the lipid profile, the concentration of soluble ICAM-1 and the immunohistochemical expression of ICAM-1 and VCAM-1 in the endothelium, media and vasa vasorum of the aorta Results: There were significant differences (p<0,05) in the expression of ICAM-1 between group C (maximum time of rich cholesterol diet) and all other groups in the three subjects of the aorta studied. There was regression of the expression of ICAM-1 in group B and significant differences (p<0,05) between group B and all the other groups, except group D in the expression of ICAM-1. There were no significant differences in the expression of VCAM-1 between any of the groups. The serum concentration of soluble ICAM-1 positively correlates with the expression of the molecule in the vasa vasorum (r=0,35, p <0,05) and the fibroblasts/smooth muscular cells (r=0,34, p<0,05) of the aorta. Conclusions: Rich cholesterol diet has an important role in the expression of ICAM-1 but not in the expression of VCAM-1 in the aorta of the rat, which is time dependent. The expression of ICAM-1 in the aorta regresses after the recess of rich cholesterol diet. Soluble ICAM-1 is a reliable mean of measuring the expression of ICAM-1 in the the aorta and mainly in the vasa vasorum and fibroblasts/smooth muscle cells.Εισαγωγή: Τα μόρια προσκόλλησης ICAM-1(Intracellular Adhesion Molecule-1) και VCAM-1 (Vascular Cell Adhesion Molecule-1) συμμετέχουν στην προσκόλληση των λευκοκυττάρων στο ενδοθήλιο και διαδραματίζουν σημαντικό ρόλο σε όλα τα στάδια της αθηροσκλήρωσης. Σκοπός της μελέτης είναι η διερεύνηση της έκφρασης των μορίων προσκόλλησης ICAM-1 και VCAM-1 στην αορτή επίμυων στα πρώιμα στάδια της πειραματικής αθηροσκλήρωσης και η συσχέτισή τους με τα επίπεδα των μορίων στον ορό. Υλικά και Μέθοδοι: Χρησιμοποιήθηκαν 44 αρσενικοί επίμυες ηλικίας 10 εβδομάδων, οι οποίοι χωρίστηκαν σε 4 ομάδες. Οι ομάδες Α και Γ (n=12) έλαβαν αθηρογόνο δίαιτα (εμπλουτισμός με 2% χοληστερόλη) για 12 και 16 εβδομάδες αντιστοίχως. Η ομάδα Β (υποστροφής, n=12) έλαβε τις πρώτες 12 εβδομάδες αθηρογόνο δίαιτα και άλλες 4 κανονική δίαιτα. Η ομάδα Δ (ελέγχου, n=8) έλαβε για 12 εβδομάδες κανονική δίαιτα. Ακολούθησε ευθανασία και λήψη της αορτής των πειραματόζωων. Προσδιορίστηκε το λιπιδαιμικό προφίλ, τα επίπεδα του διαλυτού ICAM-1 στο πλάσμα ενώ έγινε ανοσοϊστοχημικός προσδιορισμός των επιπέδων έκφρασης των ICAM-1 και VCAM-1 στο ενδοθήλιο, το μέσο χιτώνα και τα τροφοφόρα αγγεία της αορτής. Ακολούθησε στατιστική επεξεργασία των αποτελεσμάτων. Αποτελέσματα: Η ομάδα Γ (μέγιστος χρόνος λήψης αθηρογόνου τροφής) παρουσίασε στατιστικώς σημαντικά αυξημένες τιμές σε σχέση με όλες τις υπόλοιπες στην έκφραση του ICAM-1 στα στοιχεία του αορτικού τοιχώματος (p<0,05), ενώ η ομάδα Β παρουσίασε υποστροφή της έκφρασης του ICAM-1 και στατιστικά σημαντικές διαφορές με όλες τις ομάδες της μελέτης (p<0,05) εκτός της ελέγχου (Δ), η οποία δεν παρουσίασε σημαντική έκφραση του ICAM-1. Αντίθετα δεν παρατηρήθηκαν στατιστικά σημαντικές διαφορές στα επίπεδα έκφρασης του VCAM-1. Η συγκέντρωση του διαλυτού ΙCAM-1 και η μεταβολή της συγκέντρωσής του στο πλάσμα πασουσιάζει θετική συσχέτιση με την έκφραση του μορίου στα αγγεία των αγγείων (r=0,35, p<0,05) και τους ινοβλάστες λείες μυικές ίνες (r=0,34, p<0,05) της αορτής. Συμπεράσματα: Η αθηρογόνος δίαιτα επηρεάζει την έκφραση των επιπέδων ICAM-1,όχι όμως και του VCAM-1, στο αορτικό τοίχωμα των επίμυων σε σχέση με τη διάρκεια της δίαιτας. Η διακοπή της αθηρογόνου δίαιτας έχει σαν αποτέλεσμα την υποστροφή της έκφρασης του ICAM-1 στο αορτικό τοίχωμα των επίμυων. H μέτρηση του διαλυτού ICAM-1 στο πλάσμα αποτελεί αξιόπιστο δείκτη της έκφρασης του μορίου στην αορτή και κυρίως στα αγγεία των αγγείων και τους ινοβλάστες/λείες μυικές ίνες