Cutaneous Adverse Drug Reactions (CADRs) between Aromatic and Non-Aromatic Antiepileptic Drugs: Clinical Presentation and Severity

Background: Drug hypersensitivity is the most common adverse effect of drug use. Major cutaneous adverse drug reactions (CADRs) represent the higher rates of morbidity and mortality, with up to 5.2% of cases. Current reports revealed the non-aromatic antiepileptic drugs had increasing rates of CADRs from the past. Objective: To study the clinical presentations and the severity of CADRs due to aromatic and non-aromatic antiepileptic drugs. Materials and Methods: A retrospective cohort study was conducted with inpatients and outpatients with CADRs receiving antiepileptic drugs in Phramongkutklao Hospital between January 2009 and December 2018. Results: Among 77 patients with CADRs, 61 patients received aromatic antiepileptic drugs and 16 patients took non-aromatic antiepileptic drugs. Among the patients with aromatic antiepileptic drugs 52.46% developed minor cutaneous drug reactions. The rest, 47.54%, developed major cutaneous drug reactions including Steven-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN) 13.11% and drug rash with eosinophil and systemic symptoms (DRESS) 31.15%. Among the patients with non-aromatic antiepileptic drugs, 62.5% developed minor cutaneous drug reactions. The rest, 37.5%, developed major CADRs including SJS/TEN 12.5% and DRESS 25%. Of the patients receiving aromatic antiepileptic, the major CADRs group showed significant higher level of eosinophil compared with minor CADRs (10.35% and 2.1%, respectively, p<0.001). The study showed significant higher alkaline phosphatase (ALP) levels in 138.5 IU/L among patient with major CADRs who received aromatic antiepileptic drugs compared with minor CADRs in 87 IU/L (p=0.006). No significant difference of laboratory was found among CADRs patients in non-aromatic group. Conclusion: Aromatic antiepileptic drugs tended to cause more severe cutaneous drug reactions than non-aromatic antiepileptic drugs, especially DRESS. The internal organ involvements were significantly identified in the aromatic antiepileptic group regarding to serum eosinophil and ALP level. Keywords: Adverse skin reaction, Aromatic antiepileptic drugs, Non-aromatic antiepileptic drug