Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs

Abstract

Background/Aim: Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Methods: Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Results: Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT were 58.4, 95.8, 93.3 and 69.9%, respectively. Conclusions: Considering the significant difference in LTT results between the case and control groups in patients receiving carbamazepine and phenytoin, and not observing such a difference in patients receiving phenobarbital and lamotrigine, LTT results are more valuable for the diagnosis of hypersensitivity reactions following the administration of carbamazepine and phenytoin. The LTT has good specificity but low sensitivity for the diagnosis of drug hypersensitivity reactions.

Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment

“…For this reason, these patients were re‐exposed to the drugs although the LTT was positive. False positive data have been previously reported in a few cases . Moreover, our sample size is too small to extract strong conclusions.…”

“…Particularly in DRESS, most information is derived from small studies involving few patients or case reports suggesting its usefulness . Pichler and Tilch reported positive results in more than 50% of DRESS cases.…”

“…Particularly in DRESS, most information is derived from small studies involving few patients or case reports suggesting its usefulness. 9,23,29,[31][32][33][34][35][36] Pichler and Tilch 15 reported positive results in more than 50% of DRESS cases. Nevertheless, the sensitivity and specificity of LTT specifically in DRESS have not thus far been established.…”

“…False positive data have been previously reported in a few cases. 14,34 Moreover, our sample size is too small to extract strong conclusions.…”

Recent Advances in Clinical Allergy and Immunology

“…When used as a tool to diagnose anticonvulsant drug hypersensitivity, the lymphocyte transformation test has a high specificity but a low sensitivity, and provides the most valuable results for the diagnosis of carbamazepine and phenytoin hypersensitivity [94]. A retrospective analysis of hypersensitivity reactions to proton pump inhibitors showed lansoprazole to be the most frequently implicated drug, followed by pantoprazole, esomeprazole, rabeprazole, and omeprazole, as well as anaphylaxis being the most frequent manifestation [95].…”