Comparison of cytokine gene polymorphism in drug-induced maculopapular eruption, urticaria and drug reaction with eosinophilia and systemic symptoms (DRESS).

BACKGROUND: Polymorphisms of genes controlling cytokine production have not been studied in the genetic susceptibility to cutaneous adverse drug reactions (CADR). OBJECTIVES: The objective was to determine whether polymorphisms in nine cytokine genes were associated to the occurrence of drug reaction with eosinophilia and systemic symptoms (DRESS) compared to drug-induced maculopapular eruption or urticaria and to controls without drug intolerance. METHODS: Results from 118 patients with a well-defined CADR were compared to 236 controls without drug intolerance living in the same area of France. We assessed nine polymorphisms: interleukin (IL)1-alpha-889C>T (rs 1800587), IL1-beta-511C>T (rs 16944), IL1-RN intron-2-VNTR (rs2234663), IL2-330T>G (rs 2069762), IL4-33C>T (rs 2070874), IL5-745C>T (rs 2069812), IL10-592C>A (rs 1800872), IL16-295T>C (rs 4778889) and tumour necrosis factor-alpha-308G>A (rs 1800629). RESULTS: Three polymorphisms exhibited a significant association with CADR (P < 0.05). The combination of the IL1-RN-A2 and IL1-beta-511C alleles was statistically different between cases and controls (P = 0.007) and the A2C haplotype was associated with susceptibility to CADR, particularly in drug reaction with eosinophilia and systemic symptoms (DRESS) patients (odds ratio = 3.22; 95% confidence interval = 1.23-8.41; P = 0.016). The frequency of the IL10-592A allele was higher in DRESS patients than in controls (dominant model CC vs. CA + AA: P = 0.035). These abnormalities were not evident in maculopapular eruptions or urticaria. CONCLUSIONS: This is the first study showing that IL1-cluster polymorphisms and haplotypes and the IL10-592A allele (a low IL10 producer) are associated with DRESS. These gene variants may decrease drug tolerance and promote herpes virus reactivation.

[Recurrent toxin-mediated perineal erythema in an 11-year-old child]. / Érythème périnéal récidivant toxinique chez un enfant de 11 ans.

INTRODUCTION: Recurrent perineal erythema is a rare toxin-mediated disease. We report the case of recurrent toxin-mediated perineal erythema in a child. CASE REPORT: An 11-year-old boy was hospitalized for erythematous pustular eruption involving the perineum and the axillary area. This erythema started a few days after the onset of pharyngotonsillitis and the patient's personal history involved another episode of pharyngotonsillitis which was followed by an identical cutaneous eruption. Laboratory analysis confirmed the diagnosis of recurrent toxin-mediated perineal erythema. The skin disorder quickly improved and antistreptococcal antibiotic treatment was initiated to eradicate bacteria. DISCUSSION: Recurrent toxin-mediated perineal erythema is a cutaneous disease mediated by superantigens which are toxins produced by staphylococci and streptococci. It is characterized by recurrent macular erythema involving the perineum. Streptococcus pyogenes is the most common cause of recurrent toxin-mediated perineal erythema, with Staphylococcus aureus being isolated most rarely. This observation emphasizes the possibility of atypical clinical presentation with pustular lesions, and dermatologists must be mindful of this aetiology in order to isolate bacterial toxins and to initiate appropriate antibiotics.

[Six cases of spring DRESS]. / Six cas de DRESS printaniers.

BACKGROUND: An association between herpes virus reactivations and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is accepted. We report six cases of DRESS with viral reactivation occurring within a single 1-month period. We attempted to find a common factor for these six cases and carried out clinical and virological examinations. Before and after this "epidemic", the mean number of cases of DRESS seen at the same centre was one per quarter, making the occurrence of six cases within a single month all the more remarkable and prompting us to seek an explanation. PATIENTS AND METHODS: All six patients had taken a partly causative medication from different drug classes three to six weeks prior to the start of symptoms and herpes virus was detected in the blood of all of these subjects at the time of DRESS onset (four reactivations and two primary infections), and one patient subsequently displayed herpetic meningoencephalitis 95 days after the initial episode, associated with recurrence of DRESS. DISCUSSION: There was no common denominator among these six DRESS patients in terms of either drug class or reactivation of a particular type of herpes virus, which raises the possibility of a single unidentified environmental agent. DRESS does not appear fully explainable in terms of a cellular response to drug antigens but seems rather to result from complex interactions between the drug-induced immune response, viral reactivation and antiviral immune response. Several investigators have reported sequential reactivation of herpes viruses in DRESS. A viral epidemic could thus cause a "DRESS epidemic" in patients on medication. CONCLUSION: These cases point to the possible existence of a shared initial environmental factor (infectious or not) that favours reactivation of herpes viruses and induces DRESS in patients on medication. Before and after this "DRESS epidemic", about one patient each quarter was admitted to hospital for DRESS.

A combination of CLA-DAG oil modifies the diabetic phenotype in male Zucker diabetic fatty rats.

A number of human and animal studies using conjugated linoleic acids (CLA) or diacylglycerol (DAG) oil have shown positive physiological effects on abdominal adiposity, plasma triglycerides, plasma glucose, and insulin sensitivity. A novel DAG composition containing CLA called CLA diacylglyceride (CLA-DAG) may offer potential as a therapeutic agent in reducing some of the symptoms associated with the diabetic phenotype and metabolic syndrome. This study was designed to investigate the effect of CLA-DAG oil on the diabetic phenotype in male Zucker diabetic fatty rats. Animals were assigned to one of four groups: control (C), rosiglitazone (ROS), CLA-DAG, or CLA as free fatty acid (CLA-FFA). After 11 weeks, body weight was higher and kidney weight was lower in the CLA-DAG and ROS groups compared with the C group. The ROS treatment increased the percentage of body fat as compared with all other groups. Final fasting blood glucose was lower in the CLA-DAG and ROS groups than in the C group. Plasma cholesterol was lower in the CLA-DAG group, and plasma triglycerides were lower in the ROS group compared with the C group. We also observed changes in transcript abundance of PPAR-gamma, PPAR-alpha, FAS, LPL, UCP2, UCP3, CPT1, RxR, ObRb, ApoAII, ApoD, and IRS1 in liver, muscle, and adipose tissue, suggesting treatment-induced effects on these genes. Collectively, these data suggest the need for further research on the therapeutic relevance of CLA-DAG oil in obesity and diabetes. Future research should also differentiate between CLA alone and DAG alone compared with the combination.