ABSTRACT
Introduction: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is designated as a lethal adverse drug effect with characteristic sign and symptoms such as skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytes, lymph node enlargement, and liver or renal dysfunction. Incidences of the DRESS range from 1/1000-1/10,000 drug exposures and are associated with a mortality rate of 10%. Pathogenesis of DRESS relates to an abnormal immune response in a genetically vulnerable individual, i.e. presence of human leukocyte antigen (HLA)*5801 and HLA-B* 5701 genotype and slow acetylation metabolic pathways. Methods: 48 cases were associated with the “Sulfasalazine-induced DRESS syndrome” reported between January 1990- March 2015 in PubMed-MEDLINE and HighWire Press. The “RegiSCAR” scoring system was used to analyze the case reports. Using this system, cases were classified into 4 categories as “no”, “possible, “probable” and “definite”. Results: The vast majority of cases were classified as “probable/definite” DRESS cases (83%). Hypereosinophilia, atypical lymphocytes and fever were significantly associated with “probable/ definite” DRESS cases. Liver involvement and skin rash was described in almost all of the cases, including “possible cases”. DRESS was found fatal in two cases. Conclusion: Awareness of DRESS is essential for diagnosis with the presence of skin rash, liver involvement, fever, hyper eosinophilia and lymphadenopathy. Early identification, followed by a prompt withdrawal of the culprit drug is the most essential measure to avoid disease evolution and to restore wellness.
ABSTRACT
Aim: Metabolic syndrome (MetS) and all its components are independently characterized by the presence of low-grade chronic inflammation. The study aimed at controlling inflammation using sulfasalazine 500mg, once a day treatment in comparison to placebo in MetS patients. Study Design: Double blind, randomized, placebo controlled study. Place and Duration of Study: Sadbhavna Medical and Heart Institute, Patiala; and, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, between January-November 2014. Methodology: 50 eligible subjects (Male / Female = 45/5, n=25/group), fulfilling the National Cholesterol education Program-Adult Treatment Panel (NCEP-ATP III) diagnostic criteria of MetS, were randomly assigned to once daily drug or placebo tablets for 20 weeks. Blood pressure, serum high sensitivity C-reactive protein (hsCRP), tumor necrosis factor–alpha (TNF-α), lipid profile, fasting plasma glucose and insulin levels, homeostatic model assessment-insulin resistance (HOMA-IR), endothelial-dependent flow-mediated dilation (FMD) of brachial artery, right common carotid artery’s intima-media thickness (IMT) and artery stiffness indices [(Young elastic modulus (YEM), stiffness index (SI) and carotid arterial compliance (CAC)] by Doppler Ultrasound were assessed at baseline and after 20 weeks treatment. Tolerability of drug was also measured using hematological and biochemical analysis. Statistical significance was accepted at p ≤.05. Results: FMD improved as 25.66±6.47% versus 12.41±3.22%, p<0.01; and insulin resistance (HOMA-IR) decreased as 7.05±3.48 versus 11.32±6.08, p<0.01, from baseline in drug group as compared to placebo group, whereas endothelium-independent vasodilatation (p=0.23) and baseline brachial artery diameter (p=0.95) remained unchanged in both the groups. Serum triglycerides (p=0.04), hsCRP (p<0.01) and TNF-α (p<0.01) levels were considerably altered, but there was no effect on carotid IMT, YEM, CAC and SI (all p≥0.05). Biochemical and hematological safety variables were significantly altered, but were still found with-in the normal limits. Conclusion: Thus, sulfasalazine may prevent cardiovascular disease risk in MetS patients by reducing insulin resistance and endothelial dysfunction via halting inflammatory process. Moreover, it was found tolerable.