Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) are associated with over 200 medicines including lamotrigine, an antiepileptic drug. Previous studies have suggested the involvement of immune mechanisms in the development of drug-induced SCARs.

High-resolution HLA genotyping was performed for 65 patients of European ancestry treated with lamotrigine (22 cases with lamotrigine-induced SCARs and 43 controls on lamotrigine without SCAR-related symptoms). Association of HLA genetic variants with SCARs in these patients were evaluated by contrasting allele frequencies between the cases and the controls for each of 112 HLA four-digit alleles.

RESULTS:
Five alleles were observed with higher frequencies in the cases compared with the treated controls with exact P values less than 0.05.

In contrast to the study of carbamazepine-induced Stevens-Johnson syndrome in Han Chinese patients, none of the cases carried B*1502. Accounting for the large number of hypothesis tests conducted, none of the associations identified were statistically significant.

CONCLUSION:
No single major HLA-related genetic risk factor was identified for lamotrigine-induced SCARs in patients of European origin. Only suggestive evidence was obtained for B*5801, A*6801, Cw*0718, DQB1*0609, and DRB1*1301.

Confirmation of these results in a larger, independent sample is needed to determine whether any of the HLA alleles identified are truly associated with the development of lamotrigine-induced SCARs.


"High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients."
Pharmacogenet Genomics. 2009 Aug 6; Kazeem GR, Cox C, Aponte J, Messenheimer J, Brazell C, Nelsen AC, Nelson MR, Foot E



Related:
High-resolution HLA genotyping and severe cutaneous adverse
Cutaneous Adverse Reactions: Stevens-Johnson Syndrome
Review: severe cutaneous adverse reactions to drugs
In the pursuit of classifying severe cutaneous adverse reactions
Cutaneous adverse reactions to valdecoxib distinct from stevens ...
Study: cutaneous adverse reactions to valdecoxib distinct from ...

Submucosal tunneling using endoscopic submucosal dissection for peritoneal access and closure in natural orifice transluminal endoscopic surgery: a porcine survival study.

Endoscopy. 2009 Aug; 41(8): 707-11Yoshizumi F, Yasuda K, Kawaguchi K, Suzuki K, Shiraishi N, Kitano SBACKGROUND AND STUDY AIMS: Safe peritoneal access and gastric closure are the most important concerns in the clinical application of natural orifice transluminal endoscopic surgery (NOTES). We aimed to clarify the feasibility of a submucosal tunnel technique using endoscopic submucosal dissection (ESD) for transgastric peritoneal access and subsequent closure for NOTES. METHODS: Seven female pigs, each weighing about 40 kg were included in the study. The following procedures were performed: (i) after injection of normal saline into the submucosa, the mucosa was cut with a flex knife; (ii) the submucosal layer was dissected using an insulation-tipped electrosurgical knife to make a narrow longitudinal 50-mm submucosal tunnel; (iii) a small incision was made at the end of the tunnel and enlarged with a dilation balloon. After transgastric peritoneoscopy, the mucosal incision site was closed with clips. The following outcome measures were used: (a) evaluation of the technical feasibility of making a submucosal tunnel; (b) clinical monitoring for 7 days; (c) follow-up endoscopy and necropsy; and (d) peritoneal fluid culture. RESULTS: Natural orifice transluminal endoscopic peritoneoscopy with a submucosal tunnel was successfully carried out in all pigs. The pigs recovered well, without signs of peritonitis. Follow-up endoscopy showed healing of mucosal incision sites without open defects. Necropsy revealed no findings of peritonitis, confirming completeness of gastric closure; there was a thin scar in one pig and adhesion of the omentum in six pigs. Peritoneal fluid culture demonstrated no bacterial growth. CONCLUSIONS: The submucosal tunnel technique is feasible and effective for transgastric peritoneal access and closure.