The HLA-B*15:02 polymorphism and Tegretol®-induced serious cutaneous reactions in epilepsy: An updated systematic review and meta-analysis.

Tegretol® [carbamazepine (CBZ)], an aromatic drug approved for epilepsy treatment, can induce adverse drug reactions (ADRs) after its administration. Several genetic studies of epilepsy have shown that genetic polymorphisms increase the risk of ADRs, and some interactions between CBZ and other treatments can also induce adverse effects. Thus, to avoid such interactions and to provide an overview of the genetic profiles involved in ADRs with CBZ, for the first time, a systematic review and meta-analysis focusing on epilepsy was performed, using Cochrane Library, Embase and PubMed databases to find studies published between January 1980 and October 2016. Of the eligible studies, those selected were related to the impact of genetic polymorphisms on ADRs in patients receiving antiepileptic treatment. The results of these selected studies are expressed as pooled odds ratios (ORs) with 95% confidence intervals (CIs), based on data from individual patients. Out of 807 articles, nine were included in the present meta-analysis to assess the association between human leukocyte antigen (HLA)-B*15:02 polymorphisms and CBZ-induced serious cutaneous reactions (SCRs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), in epilepsy. It was found that HLA-B*15:02 polymorphisms were significantly associated with CBZ SCR risk (OR: 27.325, 95% CI: 9.933-51.166), while subgroup analyses by ethnicity showed that the association was significant in Han Chinese (OR: 42.059, 95% CI: 9.587-184.514). The HLA-B*15:02 polymorphism was also strongly associated with the CBZ-SJS subgroup (OR: 152.089, 95% CI: 34.737-665.901) and significantly associated with the CBZ-SJS/TEN subgroup (OR: 13.993, 95% CI: 7.291-26.856). Also, the allele was overrepresented in the Han Chinese population (OR: 17.886, 95% CI: 8.411-38.034) within the CBZ-SJS/TEN subgroup. Although the number of studies available in other Asian ethnicities was insufficient for determining publication bias, it nevertheless showed a relationship between the HLA-B*15:02 polymorphism and SCRs. In addition, despite the small number of included studies, the results reveal strong evidence that the HLA-B*15:02 polymorphism can induce SCRs among Asian CBZ users. These findings should prompt physicians to individualize CBZ therapy for patients with epilepsy.

[Adverse events related to systemic treatment using Glucantime for cutaneous leishmaniasis: a report from Tunisia]. / Effets indésirables du traitement systémique de la leishmaniose cutanée par Glucantime: expérience Tunisienne.

Glucantime is the firstline treatment for cutaneous leishmaniasis in Tunisia. Adverse effects related to systemic administration of Glucantime are frequent. The purpose of this retrospective study was to review the files of 53 patients who were treated for cutaneous leishmaniasis using meglumine antimoniate at a dose of 60 mg/kg/day for 15 days during the period between 1998 and 2007. Adverse effects were observed in 5 men and 4 women with an average age of 40.8 years. Antimony intolerance occurred in 8 patients and stibio-intoxication occurred in 4. Glucantime was considered as the most likely cause of adverse effects in 6 patients and as the plausible cause in 3 patients. Fever was the most frequent complication of antimony intolerance followed by cough, myalgia, and cutaneous lesions. Hepatic cytolysis was the most frequent sign of stibio-intoxication. Asymptomatic elevation of amylase level to 108 UI/l was observed in one case. The most serious complication was acute toxic kidney failure on the 15th day of treatment. The incidence of adverse events to Glucantime ranges from 16% to 59%. The most severe complication is acute renal failure on the 15th day of treatment, as observed in one patient in this series. Patient status must be monitored by performing laboratory tests at the beginning and end of the treatment. Since cutaneous leishmaniasis observed in Tunisia is a self-healing dermatosis that never results in sequels, treatment with Glucantime should be discontinued in any patient who develops suspicious symptoms.

[Fixed drug eruption induced by sulfaguanidine]. / Erythème pigmenté fixe à la sulfaguanidine.

INTRODUCTION: Fixed drug eruption is a lesion induced by drugs. The family of drugs usually incriminated are sulfonamides, tetracyclines and pyrazols. We describe nine cases of fixed drug eruption induced by sulfaguanidine, a sulfonamide with local action. CASE REPORTS: All the patients presented one or more fixed drug eruption reactivation lesions induced by sulfaguanidine as self-medication for diarrhea. The number of lesions increased in 7 cases after reactivation. The delay in occurrence of the fixed drug eruption decreased during the different episodes. The lesions predominated on the hands in 8 cases of 9. DISCUSSION: The sulfaguanidine must be added to the list of drug-induced fixed drug eruptions with limited absorption from the gastrointestinal tract.

[Are sigma receptors implicated in ischemic injury?]. / Les récepteurs sigma sont-ils impliqués dans les lésions d'ischémie?

Sigma receptors are present in many organs and several functions are allotted to them but the specificity of their effect remains to be established. Indeed, all the molecules known to interact with these receptors also have affinities for other receptors. Recently, sigma-1 receptors were implied in the processes of cellular protection, several of their ligands showing a neuroprotector effect in various models of cerebral ischaemia. S-16950, a trimetazidine derivative, is a powerful anti-ischaemic drug on a hepatic model of ischaemia-reperfusion. It is structurally closely related to SA4503, a sigma receptor ligand showing also an anti-ischaemic action. Our study shows that S-16950 inhibits the binding of [3H]pentazocine, a selective sigma-1 receptor radioligand, to rat brain membranes with a high affinity (IC50 = 7 nM). This affinity is equivalent to the most potent sigma ligand such as haloperidol. Its affinity is 170 times higher for the sigma-1 subtype than for the sigma-2 subtype. The effect of Gpp[NH]p on S-16950 inhibition of [3H]pentazocine binding and the potentiation of the convulsivant effect of cocaine under the action of S-16950 suggest that this molecule may act as an agonist. These results indicate that S-16950 is a new sigma ligand and reinforce the assumption of a link between sigma receptors and a cytoprotective activity.