A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives
A-73-year-old female patient visited our clinic with multiple round well-demarcated dark pigmented lesions with desquamation. She took medications because of common cold eighteen days ago. Medications were bepotastine besilate (Talion®; Mitsubishi Tanabe Pharma, Japan), levocetirizine (Xyzal®; UCB Korea Co., Ltd, Korea), acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®; Samil Pharm. Co., Ltd, Korea), dihydrocodeine bitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®; Chong Kun Dang Pharmaceutical Corp., Korea) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®; Hanbul Pharm Co., Ltd, Korea). After taking these medications, the patient experienced generalized itching and multiple erythematous macules with several bullae formation in about two h. These cutaneous lesions were spontaneously resolved after stopping taking medications and changed to pigmented lesion with desquamation. The patient had already experienced similar adverse reactions twice after taking bepotastine besilate, levocetirizine, acetaminophen, Actifed®, Codening®, Antad®, dexibuprofen and roxithromycin one and a half years ago. Multiple cutaneous erythema and bullae occurred and were resolved after two weeks with localized pigmentation.\nThe patient was a house wife and had diabetes mellitus and penicillin induced acute hypersensitivity. She denied alcohol intake and smoking.\nIn laboratory findings, complete blood cell counts were as follows; white blood cell 8,600/mm3 (neutrophil 76.6%, lymphocyte 15.7%, monocyte 8.8%, eosinophil 4.5%, basophil 0.6%), hemoglobin 11.9 g/dL, platelet 207,000/µL. C-reactive protein was 1.0 mg/dL. Hepatic enzymes, blood urea nitrogen and serum creatinine were within normal ranges. Patch test was done with suspected drugs such as bepotastine besilate, levocetirizine, acetaminophen, Codening®, codein, Actifed® and Antad® at both normal skin and pigmented skin. Petroleum (Vaseline®) was used to make appropriate concentration to test and control. All drugs were made to 10% concentration except codein 5% and additional Actifed® 1% concentration []. After 48 h, patch was removed and readings were performed 48 h after initial patch applying. At the normal skin site where levocetirizine had been applied, erythema was presented (). At the pigmented skin site where levocetirizine had been applied, infiltration and vesicle were presented (). We additionally performed patch test for other antihistamines including levocetirizine (5% and 10% of Pet.), cetirizine (10% of Pet.), hydroxyzine (10% of Pet.), ebastine (10% of Pet.), loratadine (10% of Pet.) and fexofenadine (10% of Pet.). Erythema was observed at patch test sites of cetirizine and hydroxyzine which were piperazine derivatives (). But the patch tests of ebastine, fexofenadine and loratadine which were piperidine derivatives showed negative response (). The open oral challenge test with fexofenadine was done. The patients took 120 mg fexofenadine a day for 3 days as the open oral challenge test, and there was no adverse reaction.\nThe patient was diagnosed as levocetirizine-induced fixed drug eruption which was confirmed by patch test. She has cross-reactions with other piperazine derivatives such as cetirizine and hydroxyzine. We recommended that the patients avoid taking these antihistamines. Fexofenadine could be an alternative drug without adverse reaction to patient.