Background

The key function of the skin is to provide a barrier between external environmental factors and the internal body environment. Transepidermal water loss (TEWL) has been successfully used to measure skin barrier function. High TEWL is associated with skin dysfunction, whereas low TEWL is related to healthy skin [1]. High TEWL has been associated to atopic dermatitis (AD) and allergic sensitization in infancy [2,3,4,5]. During puberty, however, individuals undergo profound physiological changes, which affect both skin function [6] and sex-specific risk of atopy [7]. We therefore hypothesized that the association of TEWL and atopic sensitization to allergens may change with these profound alterations in adolescence. Using the data of the PASTURE study, we aimed to investigate the association between TEWL and allergic sensitizations at 16 years of age using a cross-sectional study design.

Study design

PASTURE is a longitudinal birth cohort conducted in children from rural areas of five European countries (Austria, Finland, France, Germany, and Switzerland) [8]. The study was designed to evaluate risk and preventive factors for atopic diseases and was approved by the local research ethics committees in each country [9, 10]. Written informed consent was obtained from the children’s parents and adolescents at age 16 years. Pregnant women were invited to participate during their third trimester of pregnancy and were then classified into farm and non-farm groups. The children from the participating women were recruited at birth. Information was obtained through questionnaires in interviews or self-administered questionnaires from mothers. Current study population is a subsample of the German arm at age 16 years.

Outcome

Serum specific immunoglobulin E (IgE) and skin prick test (SPT) was assessed at age 16 years. Serum specific IgE was assessed using the semiquantitative Allergy Screen test panel for atopy (Mediwiss Analytic, Moers, Germany). SPTs were performed on the anterior part of the forearm using a Stallerpoint® (Stallergenes, Antony, France). Different types of sensitization were defined as having at least one IgE specific ≥ 0.7 IUml−1 or SPT as a wheal diameter ≥ 3 mm as follows: i) seasonal: alder, birch, hazel, grass, rye grass, mugwort, plantain, or alternaria; ii) perennial: cat, dog, horse, Dermatophagoides (D.) Pteronyssinus, or D. farinae; iii) inhalant: seasonal or perennial; iv) food: hen’s egg, cow’s milk, peanut, hazelnut, carrot, wheat flour, or soy; and v) any: seasonal, perennial or food. Asthma at 16 years was defined as a physician’s diagnosis of asthma or recurrent obstructive bronchitis ever until the age of 16 years. Children were labeled as having atopic dermatitis ever when the parents and/or adolescents reported in the questionnaires that the child had atopic dermatitis diagnosed by a doctor until 16 years of age. Allergic rhinoconjunctivitis (ARC) ever at 16 years was defined as parental and/or adolescent reported symptoms (itchy, runny, or blocked nose without a cold accompanied by red itchy eyes) and/or physician’s diagnosis ever of allergic rhinitis until the age 16 years.

Transepidermal water loss measurement

TEWL measurements were performed only in the German arm at the 16-year visit. TEWL was measured on the crook of either right or the left arm using a TEWAMETER® TM 300 (Courage + Khazaka electronic, Cologne, Germany). Additionally, it was taken care that no signs of atopic dermatitis were found at the skin area where TEWL measurement was carried out.

The subjects were instructed neither to wash this area on the day of the study visit nor to use cream or lotion. Three measurements were carried out for 30 s each. For each measurement, the mean value over these 30 s was calculated. The final TEWL value was calculated as the mean of the mean values of all three measurements. The mean TEWL, temperature and humidity were 11.9 ± 4.4 g/m2/h, 24.1 °C and 36.1%, respectively. TEWL was further transformed by dividing the original variable by the interquartile range (IQR 4.8) and the new continuous variable was included in the regression models. For the present study, we included 78 adolescents with data on TEWL and/or IgE/SPT.

Statistical analyses

The associations between TEWL and the different types of sensitization as well as the outcomes (asthma, AD, and ARC) were assessed by logistic regression adjusting for most relevant exposure (growing up on a farm). The results are presented as odds ratios (OR) per-interquartile-range of the probability of increased TEWL along with the 95% confidence interval [95%CI]. The test for differences between the groups was carried out by χ2/Fischer exact test for categorical variables and Mann–Whitney U test for continuous variables. A P-value of 0.05 was considered significant. All the analyses were performed in SAS (v9.4 software; SAS Institute, Cary, NC).

Results

Characteristics of the study population

Any sensitization at the age of 16 years was reported in 67.1% of the adolescents. Subjects with any sensitization had higher TEWL values and had more often ARC than subjects without any sensitization (Table 1). Perennial sensitization was reported in 39.7% of the adolescents. Subjects with perennial sensitization were more often seen in non-farmers, had higher TEWL values and had more often ARC (Table 1). In our study we did not find association between TEWL and farming status (farm vs non-farm: 11.9 ± 3.5 vs 11.8 ± 5.1; P-value = 0.33) or with other sensitization types (seasonal vs no seasonal: 11.9 ± 4.0 vs 11.7 ± 4.6; P-value = 0.75, inhalants vs no inhalants: 12.7 ± 4.9 vs 10.7 ± 3.5; P-value = 0.11, and food vs no food: 11.8 ± 3.5 vs 11.7 ± 4.6; P-value = 0.49).

Table 1 Basic characteristic
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Effect of TEWL on allergic sensitization

In adjusted logistic regression TEWL was positively associated with any sensitization (adjusted odds ratio [OR] per IQR of the probability of increased TEWL [95% confidence interval], P‑value: 2.64 [1.12–6.19], 0.03; Fig. 1a). TEWL was furthermore significantly associated with ARC (1.92 [1.04; 3.54], 0.04), but not with asthma or atopic dermatitis (Fig. 1b). The low number of included subjects with asthma (N = 10), ARC (N = 22), and AD (N = 8) and TEWL measurements did not allow to assess with any certainty whether the association between TEWL and any sensitization was stronger in those with asthma, ARC or AD.

Fig. 1
figure 1

Association between transepidermal water loss (TEWL) with different types of sensitization and outcomes at 16 years: a Associations of TEWL with different types of sensitization (any: [Cases/Total: 47/70], perennial [27/68], seasonal [28/69], inhalants [39/70], and food [17/66]) at age 16 years. Model is adjusted for farming status. The forest plot represents the odds ratios (OR) per interquartile range of the probability of increased TEWL along with the 95% confidence interval (95%CI). b Associations of TEWL with outcomes (asthma [Cases/Total: 10/78], atopic dermatitis [8/78], and allergic rhinoconjunctivitis [22/77]) at age 16 years. Model is adjusted for farming status. The forest plot represents the OR per interquartile range of the probability of increased TEWL along with the 95%CI

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When dissecting any sensitization into perennial and seasonal, only perennial sensitization (3.30 [1.42; 7.43], 0.005; Fig. 1a) was positively associated with TEWL. This may contradict the strong association with ARC, which is often also termed hay fever. Moreover, 66.7% of the adolescents in this analysis with ARC were sensitized to at least one perennial allergen.

Conclusion for the practitioner

The findings of the present study add to our understanding of the association between TEWL and allergic sensitization (any and perennial sensitization) in adolescence. Interesting was the finding of the perennial sensitization where 66.7% of the adolescence with ARC were sensitized to at least one perennial allergen. Even though the profound physiological changes occurring during adolescence did not change the association between TEWL and ARC in our study. These results are similar to the studies conducted in infants showing TEWL to predict allergic sensitization [2,3,4,5]. In our study, we could not find any association between TEWL and AD which could be due to the lower number of adolescents with AD (N = 8) in the present study. Additionally, 75% of the children with AD reported to have itchy rash with scratching and rubbing of the skin during last 12 months. Our results point to a possible role of epidermal barrier impairment in the sensitization to perennial allergens in ARC. Because of low numbers of included subjects, we could not investigate the role of filaggrin mutations in this population.

The strength of our study is the inclusion of adolescents recruited from the general population in Bavaria, Germany. However, the present study has several limitations. One of the limitations is the small study sample in the current analyses. Due to the low numbers, we were not able to associate TEWL measured at age 16 years with the age of onset of diseases and transient symptoms. Moreover, TEWL may be different for distinct age groups, which could have led to false positive or false negative results when associating TEWL to “ever doctor’s diagnosed disease”. Another weakness is the cross-sectional design of the current analyses, which makes is difficult to determine whether the exposure or the outcome occurred first. Hence, we could only speculate on causality in our study. However, by excluding the adolescents with any or perennial sensitization at 10.5 years (using the data from the examination at 10.5 years) did not alter the results. Nevertheless, it will be interesting to investigate the association between skin barrier dysfunction and incident clinical manifestation such as ARC in adolescence.

In the present study, we show the association of defective skin barrier function measured as TEWL with perennial sensitization and ARC. These results potentially indicate an important role of measuring TEWL in adolescents in clinical practice. Further larger longitudinal studies are necessary to prove if a causal relationship between high TEWL and ARC exists which will ensure the importance of TEWL measurement as a screening tool for allergy diseases as prevention strategies.