A 4-year-old male patient presented to the hospital with a skin eruption, which had exacerbated on his hands and feet after taking Ucerax (hydroxyzine, Korea UCB Co., Seoul, Korea) or Leptizine (levocetirizine, Han Wha Pharma Co., Chuncheon, Korea) for treating urticaria. The patient had begun to exhibit urticaria resembling small grains with pruritus at the skin folds and torso since 10 months. He was then diagnosed with cholinergic urticaria and administered antihistamine drugs. The patient had repeated episodes of such rashes and was administered antihistamine drugs upon recurrent diagnosis of cholinergic urticaria and chronic urticaria. However, the patient’s parents discontinued antihistamine administration as the skin rashes appeared to expand and were prolonged whenever antihistamines were administered, and the rashes would disappear approximately 2 days or more after discontinuing antihistamine administration. The rashes would begin to appear on the hands and feet within an hour or two after drug administration. Although antihistamine administration led to increased pigmentation and number of hives, no severe pruritus was observed.

The patient had a history of facial urticaria, which erupted after consuming watermelons, as well as other histories of intermittent facial skin eruptions after consuming cucumbers and bananas, although the symptoms were resolved without any treatment. However, the patient had been eating these foods as there were no skin eruptions upon consumption recently. In addition, the patient had a history of eruption after taking a cold medication.

When the patient visited the hospital, no visible skin lesion was observed as he had discontinued medication for 2 weeks. In order to verify the cause of skin eruption as well as determine a safer antihistamine drug for the patient, a drug provocation test was performed.

Laboratory test performed 2 years ago, when rashes erupted after consuming food, revealed a total white blood cell (WBC) count of 8,000/μL (neutrophil, 4,880/μL, 61%; eosinophil, 390/μL, 5%) and total IgE in plasma of 122.40 IU/mL (reference value, 1.31–165.3 IU/mL). Allergy blood test results were as follows: watermelon (Unicap RF 329)=1.07 KU/L, Banana (Unicap F92)=0.67 KU/L, and cucumber (Unicap F244)=1.0 KU/L. At the time of drug induction test, peripheral blood test revealed a WBC count of 6,900/μL (neutrophil, 3,795/μL, 55%; eosinophil, 330/μL, 5%), hemoglobin level of 11.9 g/dL, hematocrit of 37.1%, and platelet count of 242,000/μL. Total IgE in plasma of 340.7 IU/mL (reference value, 1.5–158.0 IU/mL).

The drugs that were considered in the provocation tests were injectable antihistamines and antihistamine syrups, which are commonly used types of antihistamines, as well as injectable H₂ antagonists. The following drugs were selected: injectable antihistamines, including chlorpheniramine maleate 4 mg/2 mL (Peniramin, Yuhan, Seoul, Korea) and ranitidine HCl 50 mg/2 mL (Curan, Ildong Pharm, Seoul, Korea), and antihistamine syrups, including levocetirizine HCL 0.5 mg/mL (Serenzal, Samil Pharm, Seoul, Korea), ketotifen fumarate 0.2 mg/mL (Zaditen, Novartis Korea, Seoul, Korea), loratadine 1 mg/mL (Clarityne, Bayer Korea, Seoul, Korea), and mequitazine 0.5 mg/mL (Primalan, Bukwang Pharm, Seoul, Korea). The drug provocation tests included a skin prick test using antihistamine syrups and injectable antihistamines, and then oral provocation tests were performed using drugs that showed a negative result in the skin prick test and levocetirizine, which is a suspected medication considering the patient’s medical history. Furthermore, intradermal tests were performed for the injectable H₁ antihistamines and H₂ antagonists. The skin prick test was performed by placing a single drop of each of the 4 antihistamine syrups, positive control liquid (histamine), and negative control liquid (0.9% saline) on the upper forearm followed by a skin prick with a disposable lancet. Each allergen sample and control liquid was left for 20 minutes on the skin, after which the size of urticaria and skin eruptions was observed. While ketotifen showed a negative reaction in the skin prick test, all other drugs showed wheal reaction (Table 1). The intradermal test was performed by injecting Peniramin, Curan, and negative control liquid (0.9% saline) into the surface of skin with a 26-G needle to create 2-mm blisters, and results were noted at 20 minutes after the injections. Both Peniramin and Curan induced wheal with a diameter greater than 2 mm (Table 1). According to the method used by Kim et al. [4], the oral provocation test was performed by administering half of the standard dose and standard dose, after which changes in blood pressure, pulse, and appearance of any other symptoms in a 2-hour period were observed. At 120 minutes after administering 0.5-mg ketotifen, which showed a negative result in the skin prick test, 1 or 2 macula appeared, yet without pruritus. Subsequently, 30 minutes after administering an additional 1 mg, the number of macula increased, but the total number appeared to be less than 5 and there were no more changes observed up to 120 minutes. On the other hand, the number and size of macula around the wrist and ankle gradually increased during the 30-minute to 120-minute period after the administration of levocetirizine 1.2 mg (2.5 mL) (Fig. 1). According to the test result, the patient was diagnosed with drug-induced skin eruption caused by levocetirizine and was advised to avoid taking similar antihistamine agents and agents that affect the H₂ receptor, such as Curan, as cross-reactions caused by these agents can cause similar skin eruptions.

This study was approved by the Institutional Review Board of Kangwon National University Hospital (KNUH-2018-09-005). As a retrospective case report, written consent was waived.