This cross-sectional study examined children from the general pediatric population who were 4 to 13 year-old and attended 3 kindergartens and 6 elementary schools as part of the Seongnam Atopy Project in Korea from June to July of 2015 (SAP2015). We distributed questionnaires to the parents of 5,196 children and received 4,434 completed questionnaires in return (response rate: 85.3%). A total of 358 subjects completed the questionnaire incorrectly (e.g. missing values or absence of written consent) and were excluded. Therefore, 4,076 (78.5%) children were finally included in this study. This study was approved by the Institutional Review Board of the CHA Bundang Medical Center. Written consent was obtained from all parents or guardians following a detailed explanation of the study.

Based on previous studies,121121 “lifetime urticaria” was defined by an affirmative answer to the question: “Has your child had a problem with burning, itching or a rash resembling a mosquito bite or swelling on the skin during his/her lifetime?” Among those with lifetime urticaria, “current urticaria” was defined by an affirmative answer to the question: “In the past 12 months, has your child had a problem with burning, itching, or a rash resembling a mosquito bite or swelling on the skin?” Current urticaria was defined as acute or chronic urticaria according to its duration,322 “Chronic continuous urticaria” was defined by the presence of daily symptoms or outbreaks occurring 3 or more times a week and lasting more than 6 weeks.2 “Chronic recurrent urticaria” was defined by the presence of repeated development of symptoms with intervals of at least a week between each relapse and lasting more than 6 weeks.7 We defined “ever diagnosed with urticaria” by an affirmative answer to the question: “Has your child ever been diagnosed with urticaria at least once by a doctor”. We defined “current treatment” based on an affirmative answer to the question: “Has your child undergone treatment for urticaria during the past year?” Control subjects were children who did not experience urticaria during their lifetimes.

We used the modified urticaria activity score (UAS)23 to assess disease severity. In particular, the severity of urticaria was assessed by asking: “How many wheals were there when your child's urticaria was most severe?” Wheals were classified as none, mild (20 or fewer wheals per 24 hours), moderate (20 to 50 wheals per 24 hours), or intense (50 or more wheals per 24 hours or large confluent areas of wheal). Pruritus was classified as none, mild (present but not annoying or troublesome), moderate (troublesome but not interfering with normal daily activities or sleep), or intense (very troublesome and interfering with normal daily activities or sleep).

We asked about the presence of factors that might induce urticaria, such as exposure to specific foods, drugs, cold exposure (cold water or air), hot air (after a shower or exercise), common cold, changes in the environment, and stress.11

We performed blood sampling to measure white blood cell count, vitamin D, total eosinophil count (TEC), and total IgE levels (Phadia AB, Uppsala, Sweden). We also used skin prick tests (SPTs) in 503 children to assess allergic sensitization to 22 common allergens using extract and control solutions from Lofarma (Milan, Italy): Dermatophagoides pteronyssinus (Der p.), Dermatophagoides farina (Der f.), birch, oak, elm, hop, egg, milk, peanut, wheat, walnut, cod, pork, mussel, shrimp, apple, peach, kiwi, orange, tomato, strawberry, and celery. A subject was considered atopic if there was 1 or more positive reactions (wheal diameter > 3 mm) to any allergen in the SPT.

A modified Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to determine the prevalence of sign and/or symptoms and the diagnosis of allergic diseases. This questionnaire consists of 3 main sections: (1) general characteristics, including sex, birth year, height, and weight; (2) history of sign and/or symptoms related to asthma, allergic rhinitis (AR), atopic dermatitis (AD), and food allergy (FA), and family history, including parental asthma, allergic rhinitis, and atopic dermatitis; and (3) environmental factors. The environmental factors were: number of family members living together; presence, number, and birth order of other siblings; total days of activity per week out of physical education class (0, 1-2, 3-6, and 7 days/week), type of delivery (vaginal delivery vs C-section), birth weight, breast feeding, weaning period, attendance at a daycare center (among attendees: age at initial attendance and duration of attendance), exposure to secondary smoke, type of residence (detached house vs apartment), age of the residence (<6 vs ≥6 years), floor number in the residence, presence of mold on the walls or ceiling of the residence, type of ventilation, pet ownership, furniture less than 1 year old, change of residence since birth, remodeling of the residence (replacing wallpaper, flooring or ceiling, etc), distance of the residence to the main road (<50, 50-100, 100-200, >200 m), parental education, and parental income (<$3,360 vs ≥$3,360/month).

Statistical analysis was performed using SPSS version 22.0 (IBM Co, Armonk, NY, USA). The relationships of different parameters with urticaria were determined using Student's t test for continuous variables and Pearson's χ² test for dichotomous variables. A linear-by-linear (Mantel-Haenszel test) association trend test was used to test the presence of a linear trend of the proportion of urticaria and sex according to age in current urticaria. The agreement between current urticaria and treatment history in the past 12 months, lifetime urticaria, and diagnosis by a physician were analyzed by calculation of κ coefficients. Multivariate logistic regression analysis, after adjustment for age, sex, BMI z-score, and personal history of atopic dermatitis, was used to identify independent risk factors of acute and chronic urticaria (continuous and recurrent types). For all analyses, a P value of <0.05 was considered significant.

Fig. 1 shows the classification of the study subjects based on our criteria for the diagnosis of different types of urticaria. A total of 917 subjects (22.5%, mean age: 9.4±1.7 years) had a wheal or angioedema at some time during their lifetimes, and 624 of them (15.3%) had current urticaria. We further classified subjects with current urticaria as having acute urticaria (n=567, 13.9%), chronic continuous urticaria (n=27, 0.7%), or chronic recurrent urticaria (n=30, 1.1%).

Table 1 shows the characteristics of the 4,076 study subjects. These results indicate that subjects who ever had urticaria were more likely to have asthma, AR, or AD, and that their parents were also more like to have asthma, AR, or AD. The cases and controls had no significant differences in sex, age, height, or BMI z-score.

The percentage of subjects with current urticaria among the total subjects decreased significantly with age (P=0.009). However, within each age group, the sex ratio of subjects with current urticaria (P=0.070) did not differ from that of subjects with chronic urticaria (P=0.735). The κ for agreement between lifetime urticaria and ever diagnosis was 0.389 (P<0.001), and the κ for agreement between current urticaria and current treatment was 0.315 (P<0.001).

Table 2 shows the characteristics of the 624 subjects with current urticaria, which included 567 subjects with acute urticaria and 57 with chronic urticaria. These 2 groups had similar demographics, hematologic profiles, allergic profiles, and parental histories. Interestingly, there was a parental history of AR in 64.5% of those with acute urticaria, 40.7% of those with chronic continuous urticaria, and 69% of those with chronic recurrent urticaria (P=0.036, data not shown). The 25-hydroxyvitamin D levels of subjects with acute urticaria, those with chronic urticaria, and controls were 20.5±5.1, 22.9±4.9, and 20.0±5.1 ng/mL, respectively; there was no significant between-group difference (P=0.183). The percentages of positive skin prick tests in subjects with acute urticaria, those with chronic urticaria, and controls were 58.7%, 54.6%, and 48.3%, respectively; there was no significant between-group difference. The maximum UAS for wheals was significantly higher in subjects with chronic urticaria than in those with acute urticaria (P=0.028) (Fig. 2A), but this relationship was not observed for pruritus (P=0.204) (Fig. 2B). There was no significant difference in the maximum UAS between subjects with chronic recurrent urticaria and those with chronic continuous urticaria (data not shown).

Food was the most frequent cause of urticaria (n=236, 37.8%), followed by changing environment (n=172, 27.6%). There was a significant difference in cold exposure as a cause of urticaria between those with acute and chronic disease (6.7% vs 14%, P=0.043) (Fig. 3). However, there was no significant difference in environmental change including sunlight exposure, exposure to allergen, contact, irritants, pressure, warm exposure, stress, infection, or drug.

We calculated the adjusted odds ratios (aORs) for acute and chronic urticaria relative to controls after adjustment for age, sex, BMI z score, and atopic dermatitis (Table 3). The results showed that parental history of asthma (aOR=1.71, 95% CI=1.15-2.54, P=0.007), parental history of AR (aOR=1.71, 95% CI=1.38-2.10, P<0.001), parental history of AD (aOR=2.07, 95% CI=1.56-2.76, P<0.001), remodeling of the house (aOR=1.32, 95% CI=1.07-1.65, P<0.011), and moving into house (aOR=1.47, 95% CI=1.17-1.84, P<0.001) increased the risk for acute urticaria. Living in a new house was the only factor that increased the risk of chronic urticaria (aOR=2.12, 95% CI=1.17-3.84, P=0.013).

We also calculated the aORs for chronic recurrent urticaria and chronic continuous urticaria relative to controls after adjustment for the same confounders (Table 4). The results showed that living in new house (aOR=2.38, 95% CI=1.02-5.54, P=0.044) and high income (aOR=4.24, 95% CI=1.24-14.56, P=0.022) significantly increased the risk of chronic continuous urticaria (Table 4). No risk factors were significantly associated with increased risk of chronic recurrent urticaria.