Background: Ten percent efinaconazole nail solution (EFCZ solution) is a new topical triazole antifungal drug, and we sometimes encounter patients with allergic contact dermatitis (ACD) caused by EFCZ solution in our outpatient clinic. However, no previous reports have summarized the patch test (PT) results obtained for individual ingredients in several patients with EFCZ solution-induced ACD.

Objectives: This study aimed to 1) confirm the causative agent of EFCZ solution-induced ACD based on PT of individual ingredients and 2) analyze the optimal concentration and vehicle for such PT on the basis of previous studies.

Patients and Methods: We clinically diagnosed eight patients with EFCZ solution-induced ACD from Sep. 2014 to Aug. 2021, and performed 48-hour closed PT using EFCZ solution and its ingredients. Readings were done on days (D) 2, 3, and 7 according to the International Contact Dermatitis Research Group criteria.

Results: Six of the 8 patients underwent PT with EFCZ solution, and all showed + to +++ reactions on D3. The results for the main component, EFCZ, were + to +++ on D3 in all patients. Two patients were patch tested with both 10% EFCZ in ethanol and 10% EFCZ in petrolatum, which produced similar reactions. One patient had an allergic reaction to ethanol.

Conclusions: The causative agent of EFCZ solution-induced ACD was EFCZ in all patients. For PT, we recommend EFCZ solution as is, its 10-fold dilution and 1% and 0.1% EFCZ in petrolatum.

A-55-year-old man who have been working in a Sake (Japanese rice wine) brewer for 27 years, came to the outpatient clinic because cough, dyspnea, and wheeze gradually worsen. These symptoms occurred immediately after exposure to Aspergillus oryzae in the brewing process since age 43. A dust mask was required to reduce these symptoms, but that work was interrupted by exacerbation of these symptoms. These symptoms disappeared when he was away from the on-site work. The SMART therapy using combined inhaler of budesonide (ICS) with formoterol (LABA) was effective to reduce these symptoms. In serological test total IgE antibody and Aspergillus specific IgE antibodies increased, whereas Aspergillus precipitating antibody and Asp f 1 (a major allergen of Aspergillus fumigatus) specific IgE antibody were negative. Eosinophilia in peripheral blood was not observed, and FeNO was not increased. Values of peak expiratory flow was reduced by 20.8% after exposure to Aspergillus oryzae in that work. Lung function test including reversibility test was intact, but FEV₁ was fluctuated up to 400mL (15.9%) in the clinical course. Based on these variable clinical manifestations, laboratory data, and lung function test findings, this case was diagnosed as adult-onset atopic (Aspergillus-sensitized) bronchial asthma without allergic bronchopulmonary aspergillosis. Involvement of eosinophilic inflammation is unknown. Allergen may be considered to be Aspergillus oryzae, because these symptoms do not occur in any environment without exposure to Aspergillus oryzae. This patient is the first case of occupational asthma related to Aspergillus oryzae in a Japanese rise wine brewer.

We describe here the case of a 7-year-old male patient with Stevens-Johnson syndrome (SJS), which was suspected to be caused by treatment with tipepidine hibenzate (Asverin^®). The day after taking tipepidine hibenzate and L-carbocysteine (Carbocysteine^® DS) for relief of a cold, he began presenting with the following symptoms: fever above 38°C, wheezing, and decreased oxygen saturation. Two days later, mucous membrane rashes, such as erosions on the lips, eye mucosa, vulva, and blisters on the trunk appeared, and SJS was thus diagnosed. Because pseudomembrane formation and corneal epithelial defect in the eyes were also observed, steroid pulse therapy was administered early in the course of the disease, and the patient recovered without sequelae.

A drug-induced lymphocyte stimulation test performed to determine the cause of the disease was positive for fixed-dose combination therapy with tipepidine hibenzate plus L-carbocysteine and for tipepidine hibenzate alone. It has now been three years since the onset of the disease, and no sequelae have been observed. Although tipepidine hibenzate is a drug frequently used for pediatric patients, it should be administered with caution because of its potential to cause SJS.