In total, 50 patients (aged ≥18 years) consistent with the diagnosis of urticarial dermatitis and who showed unsatisfactory therapeutic response to systemic steroid or antihistamines at local clinic were prospectively enrolled at the dermatologic clinic of Pusan National University Hospital between January 2012 and April 2013. Urticarial dermatitis was defined by the strict criteria of previously published studies12. Requirements for a diagnosis of urticarial dermatitis included both clinical and histopathologic characteristics which were outlined by Kossard et al.2 in 2006. Clinical criteria were both eczematous and urticarial lesions lasting longer than 24 hours. Histologic criteria were as follow: dermal inflammation with eosinophils limited to the papillary dermis with minimal spongiosis (Fig. 1). Detailed medical history recording, histopathologic examination, direct immunofluorescence and blood analysis were carried out to confirm the diagnosis. Differential diagnoses (e.g., eczema, urticaria, urticarial vasculitis, herpes gestationis or dermatitis herpetiformis, etc.) were ruled out by patients' medical history, physical exam, histopathologic findings or laboratory evaluation at their first visit. Written informed consent was obtained from all subjects after explaining the nature of the study, which was conducted according to the ethical standards of the Bioethical Committee of Pusan National University Yangsan Hospital (IRB no. 05-2015-075) and it was also performed in accordance with the Declaration of Helsinki.

To characterize the itch profile, a face-to-face structured questionnaire concerning pruritus (location, cutaneous lesions other than wheals, intensity, frequency, and diurnal variation) was conducted. The questionnaire also included the affective descriptors and consequent events resulting from the itch itself with the purpose of evaluating the quality of life matters and social activities. Respondents expressed their agreement with each statement by checking the corresponding boxes.

All patients received low-dose cyclosporine (1~3 mg/kg/d) for at least 2 weeks. If patient reports a marked improvement in symptoms in response to cyclosporine, we adjusted the dose of medication to 1 mg/kg/d. Otherwise, if there wasn't any apparent improvement, authors instructed patients to take the same dose of cyclosporine. The use of topical corticosteroids and antihistamines was prohibited for all patients who were enrolled throughout the study. At every visit, the intensity of pruritus, extent of erythema and interference with daily activities and sleep were evaluated. The evaluation of pruritus intensity and interference with daily activities and sleep (over the last 24 hours) were classified and evaluated with a 4-point scale as 0=none, 1=mild, 2=moderate, and 3=severe. The extent of erythema as a measure of clinical response to cyclosporine was defined as the percentage of area covered by erythematous lesions at every visit and it was divided into a 4-point scale as 0=≤30%, 1=31%~50%, 2=51%~75%, and 3=>75%. Any patient with adverse effects were recorded at each clinical visit. Cyclosporine was discontinued when patients experienced a complete clearance of clinical signs and symptoms and followed-up for 2 months more after stopping medication of cyclosporine.

PASW Statistics ver. 18.0 (IBM Co., Armonk, NY, USA) was used for all statistical analyses. Friedman test was performed to analyse the therapeutic efficacy of cyclosporine. Authors refer to statistically significant as p<0.05 in this study.

A total of biopsy-proven 50 patients completed the clinical assessments including the questionnaire. The mean age±standard deviation of the respondents was 52.5±17.7 years. Among the respondents, 17 were men (34.0%) and 33 were women (66.0%). Thirty-five patients had no known comorbidities, whereas 6 and 3 patients had a history of hypertension and diabetes, respectively.

Among the 50 patients with urticarial dermatitis, 40 patients (80.0%) complained of an itch considered moderate to severe, and 46 patients (92.0%) reported often or always experiencing an itching sensation. Most patients experienced exacerbation of the itch in the evening (74.0%), with the extremities (upper, 86.0%; lower, 94.0%) being the most commonly involved sites. Additional characteristics of pruritus in our patients are listed in Table 1. The affective descriptors and consequent events were analysed in Table 2. More than half of the patients reported having experienced reduced social contact, quality of life and daily activities due to pruritus. Difficulties in falling asleep and frequently waking were often observed. However, patients with urticarial dermatitis seldom need sleeping pill and lose their appetite.

The mean duration of treatment with cyclosporine was 4.3±2.7 weeks. The mean dose of cyclosporine was 2.96 mg/kg/d for the first 2 weeks, and 1.63 mg/kg/d and 1.04 mg/kg/d for 2 to 4 weeks and 4 to 6 weeks, respectively. The mean intensity score of pruritus was significantly reduced after 4 and 6 weeks of treatment (p=0.002, and <0.0001, respectively) compared with that of baseline. The interference with sleep was also significantly decreased at weeks 4, and 6 (p=0.020 and 0.012, respectively). Furthermore, erythema extent and interference with daily activities were reduced with statistical significance (p<0.0001 and p=0.005, respectively) after 2 weeks of cyclosporine therapy (Fig. 2, Table 3).

Only 6.0% (n=3) of all patients reported adverse events including general weakness, irregular menstruation and nausea during the treatment. However, none of the adverse events was severe enough to stop using cyclosporine.

All patients were available for follow-up telephone surveys 8 to 10 weeks after discontinuation of cyclosporin. Three patients had continued to take cyclosporin for 4 weeks and did not notice any relapse of symptoms or signs of the disease, whereas 2 patients who took medication only for 2 weeks experienced relapse within 10 weeks. Forty eight out of 50 patients remained free of the disease for at least 8 weeks after the discontinuation of cyclosporine.