Prevalence, incidence and predictive factors for hand eczema in young adults – a follow-up study

Background Hand eczema is common in the general population and affects women twice as often as men. It is also the most frequent occupational skin disease. The economic consequences are considerable for society and for the affected individuals. Methods To investigate the prevalence and incidence of hand eczema and to evaluate risk factors for development of hand eczema in young adults. Subjects and methods; This is a prospective follow-up study of 2,403 young adults, 16 – 19 years old in 1995 and aged 29 – 32 years, 13 years later, in 2008. They completed a postal questionnaire that included questions regarding one-year prevalence of hand eczema, childhood eczema, asthma, rhino-conjunctivitis and factors considered to affect hand eczema such as hand-washing, washing and cleaning, cooking, taking care of small children and usage of moisturisers. These factors were evaluated with the multinominal logistic regression analysis. Results The one-year prevalence of hand eczema was 15.8% (females 20.3% and males 10.0%, p < 0.001). The incidence was 11.6 cases per 1000 person-years (females 14.3 and males 5.2, p < 0.001). Childhood eczema was the most important risk factor for hand eczema. The odds ratios were 13.17 when having hand eczema 1995 and 2008 compared to 5.17 in 2008 (p < 0.001). A high frequency of hand washing was important in predicting hand eczema only when having 1-year prevalence 2008, OR 1.02 (p = 0.038). Conclusions After 13 years an increased 1-year prevalence of hand eczema was found. The significant risk factors for hand eczema changed over time from endogenous to exogenous factors.


Background
Hand eczema is common in the general population. In a recent review of studies in the general population from mostly European countries, the 1-year prevalence rates ranged from 6.5% to 17.5% [1]. Hand eczema is 1.5 -2 times more common in females compared with males [2,3]. Swedish estimates of 1-year prevalence of hand eczema in different age-groups have varied from 6.5% to 11.8% [4][5][6]. Among Swedish 20-29 year-olds, the 1year prevalence of hand eczema was reported to range from 7.5% to 10.8% [3,4]. Furthermore, hand eczema is the most common occupational skin disease [7].
Occupation-related hand eczema has many negative consequences. The economic costs are considerable for affected individuals and for society [8,9]. Hand eczema has been shown to have an unfavourable long-term prognosis [10] and to impair quality of life [11]. These consequences could be reduced by identifying and preventing risk factors.
Several exogenous risk factors for hand eczema have been reported: occupational exposure, use of detergents and wet work at home [4,[12][13][14]. The identification and evaluation of risk factors for the development and persistence of hand eczema are important especially among young adults. During this period of life, type of occupation, household work and childcare are factors that are important to study because they might be related to the development of hand eczema. Taken together, these circumstances justify follow-up studies in early adulthood.
The aim of the present study was to investigate the prevalence and cumulative incidence of hand eczema and to evaluate factors that can influence the development and recurrence of hand eczema in young adults.

Study group
This is the 13 year prospective follow-up study of a cohort of pupils in upper secondary school, [16][17][18][19] years old at the baseline assessment, and consequently they were 29-32 years old at follow-up. In 1995, 2,572 pupils in the four secondary schools in Växjö completed a selfadministrated questionnaire regarding hand eczema, the response rate was 98.6%. Växjö is a town in southern Sweden with approximately 70,000 inhabitants [15,16]. In 1995, 74% of 16 -19 years-olds attended secondary school in the study area, which was consistent with the overall attendance rate in Sweden. The 13-year follow-up of this cohort was performed in 2008. At both occasions the questionnaire was mailed in springtime. Swedish personal identification numbers were used to get updated addresses from the Swedish Population Address Register (SPAR). Addresses were found for 2,403 of the original 2,572 participants ( Figure 1); 169 were unreachable: 106 had personal identification numbers not matching the SPAR register, 35 had emigrated, 21 had moved without providing a forwarding address, five were deceased, and two were not traceable for reasons of secrecy.

Questionnaire
In 1995 the questionnaire was based on the Toulihampi questionnaire [17]. The questionnaire in 2008 was based on the Nordic Occupational Skin Questionnaire 2002 (NOSQ-2002), [18]. The questions regarding hand eczema were almost the same in the two questionnaires and the answer alternatives were exactly the same. Some additional questions constructed by the investigators were included in the 2008 questionnaire (See Additional file 1).
Topics surveyed by the questionnaire were: hand eczema, childhood eczema, asthma and rhino-conjunctivitis, household size and family structure, occupation and everyday activities, hand washing and skin care.

Distribution of the questionnaire
A self-administrated postal questionnaire and a pre-paid return envelope were distributed in late May 2008. A postcard was sent at the beginning of June as a first reminder. At the end of August, a second reminder was sent which included a copy of the questionnaire, a pencil and a prepaid return envelope. Finally, a postcard was sent in the middle of September as a third and final reminder.

Data analysis and statistics
One-year prevalence of hand eczema was estimated from reported hand eczema at present or having had hand eczema some time during the last 12 months (See Additional file 1). The question regarding the 1-year prevalence was previously validated [19,20]. The question on point prevalence was validated, and sensitivity (73%) and specificity (99%) were calculated [15]. To estimate the true 1-year prevalence for this cohort, a calculation of the 1-year prevalence in relation to sensitivity and specificity was made by using the formula: P = (P * + (specificity-1))/(sensitivity + (specificity-1)). P is the estimated true 1-year prevalence in the population and P* is the 1-year prevalence in the sample [5,15,21].
The cumulative incidence was calculated on the individuals reporting having 1-year prevalence or ever having had hand eczema 2008 minus those who had 1-year prevalence or ever had had hand eczema in 1995. The cumulative incidence is presented as the percentage of new cases of hand eczema in the cohort. Incidence rate is presented as new cases per 1000 person-years, i. e. the cumulative incidence/13 years × 1000. Four groups were constructed with the intention to analyse risk factors and the development of hand eczema over time. The groups were constructed as follows: those who reported having a 1-year-prevalence in 1995 and in 2008 are in group HX9508, those who reported having a 1-year-prevalence in 1995 but not in 2008 are in group HX95, those who reported having a 1-year-prevalence in 2008 but not in 1995 are in group HX08, and those who reported that they never had hand eczema are in group NoHX. The reliability over time of self-reported childhood eczema in 1995 and then reporting the same in 2008 was determined by calculating positive predictive value (PPV); i.e. the percentage positive agreement in 2008 among the yes-respondents from 1995. The negative predictive value (NPV); i.e. the agreement of no-answers in 1995 and 2008 was also calculated.
Potential exogenous risk factors for developing hand eczema such as household size, time required for household work, frequency of hand washing, skin protective habits, working hours outside home and leisure activities were investigated by dividing the cohort into two groups. The respondents who had 1-year prevalence of hand eczema 2008, i.e. the merged groups HX9508 and HX08, denominated the HX group, and the group that reported never having had hand eczema, the NoHX group. Furthermore, hand eczema was also studied in the two hand eczema groups separately regarding these factors.
Regarding occupation, the respondents were asked not only to tell their profession, but also to give information about work tasks.
The groups HX9508, HX95 and HX08 were compared to the group NoHX using a multinominal logistic regression model. The endogenous factors childhood eczema, asthma and rhino-conjunctivitis as reported in 2008 were used. The response choices in this calculation were Yes/No. Exogenous factors such as hand-washing (times a day), usage of moisturisers (dichotomised Daily/ Some time each week, some time each month, never), cooking, cleaning/washing laundry, and taking care of children 0-4 years of age (hours a day) were investigated.
Categorical data were presented as numbers and/or proportions in groups; quantitative data were presented by mean, median and quartiles. Nominal data were tested with the Chi-squared test. When the number of expected values was insufficient, Fisher's exact test was used. When comparing groups over time, McNemar's test was used. Ordinal and interval data were tested with Kruskal-Wallis H test and Mann-Whitney U-test in independent group comparisons. In the multinominal logistic regression analysis odds-ratios, 95% confidence intervals and p-values were given for all the covariates. If data was missing for any covariate, the individual was not included in the analysis. A p-value <0.05 was considered significant in all calculations. All statistical analyses were performed with SPSS 20.0 for Windows.

Ethics
The study was approved by the The Regional Ethical Review Board in Lund, (application no 156/2008).

Results
The flow-chart of the cohort is shown in Figure 1. Out of the 2,403 participants from the original cohort who received a questionnaire in the mail, 1,516 responded to the questionnaire, which was a response rate of 63%; 56% of the respondents were females. Significantly more females than males answered the questionnaire, 69.4% of the reachable original female cohort and 56.4% of the males (p < 0.001). However, in 2008 there were no significant differences between the respondents and nonrespondents in reporting 1-year prevalence of hand eczema in 1995 (p = 0.677). No significant differences were found within the genders in reported hand eczema in 1995 (females, p = 0.490; males, p = 0.297).

Incidence of hand eczema
In 1995 in total 13.3% (202/1516) reported they had or had had hand eczema, 139 females, (16.2%) and 63 males (9.6%), p < 0.001. In 2008 an additional 198 individuals reported themselves having or having had hand eczema. Thus the cumulative incidence over the 13 years was 15.1% (198/1314), for the females 18.6% and for the males 10.7%, p < 0.001. The incidence rate was estimated as 11.6 cases per 1000 person-years, 14.3 for females and 5.2 for males (p < 0.001).

Hand eczema and exogenous factors
The results regarding potential exogenous risk factors for developing hand eczema are shown in Table 2. The individuals in the HX group reported a significantly higher frequency of hand washing compared to the NoHX group, mean 15.4 versus 11.7 times per day (p < 0.001). The females in the HX group had a significantly higher number of daily hand washing compared to the females in the NoHX-group, 17.4 versus 14.5 times per day (p < 0.001).
Concerning skin care, daily use of moisturisers was reported by 60.5% in the HX group (females 67.6% males 41.5%), and by 30.6% in the NoHX group (females 47.4% and males 12.7%). The differences were significant between the two groups and between the genders within the groups (p < 0.001). Regardless of hand eczema, females used moisturisers significantly more often than males; 52.9% female versus 16.2% male daily users (p < 0.001), However, having hand eczema raised the reported usage of moisturizers by a factor 1.4 for females and 3.3 for males.
The exogenous factors were analysed between all four groups, in total as well as between genders (HX9508, HX95, HX08 and NoHX) and within genders in all groups, Table 3. In total as well as within females, the HX08 group had a significantly higher frequency of hand washing at home and at work than the NoHX group (p < 0.001). Regarding time spent at ordinary work; the HX08 group worked significantly less than the NoHX group (p = 0.001). The HX08 group spent significantly more time cooking, cleaning and doing laundry than the  Significant differences (p < 0.05) between groups, totals and/or genders are marked with bold letters. a: significant differences within females or within males in different groups, b: significant difference between totals, c: significant difference between females and males in a group, < or >: the group or the gender has significantly lower or significantly higher frequency than the compared group. Chi-squared test.  Significant differences (p < 0.05) between groups, totals and/or genders are marked with bold letters. a: significant differences within females or within males in different groups, b: significant difference between totals, c: significant difference between females and males in a group, < or >: the group or the gender has significantly lower or significantly higher frequency than the compared group. Mann-Whitney U test.  Significant differences (p < 0.05) between groups, totals and/or genders are marked with bold letters. a: significant differences within females or within males in different groups, b: significant difference between totals, c: significant difference between females and males in a group, < or >: the group or the gender has significantly lower or significantly higher frequency than the compared group/groups. Kruskal-Wallis Test and Mann-Whitney U test.

Factors predicting hand eczema
The analysis of endogenous and exogenous factors was performed with multinominal logistic regression. The results are shown in Table 4. Having had childhood eczema was the most significant predictor for 1-year prevalence of hand eczema 2008 with odds ratios of 13.17 in the group HX9508 and 5.17 in the group HX08 compared to the group NoHX. The frequency of daily hand washing was significantly associated with the 1year prevalence of hand eczema only in the HX08 group. The daily usage of moisturisers was significantly associated with 1-year prevalence of hand eczema in the groups HX9508 and HX08. High odds ratios, 1.40, for predicting 1-year prevalence of hand eczema was found for female gender in the group HX9508. In the group HX08 the higher odds ratio for females was 1.19. However, none of these differences were significant.

Discussion
In this study comprising 1,516 young adults, the 1-year prevalence of hand eczema was more than 15%. One third of these individuals also had 1-year prevalence at the baseline 1995. The 1-year prevalence, and not the point prevalence, was used in all calculations because it better reflects the persistency, the relapsing course and the seasonal variations of the disease [2,19]. The increase in the one-year prevalence between the two occasions is in accordance with previous large Swedish crosssectional studies with respect to the age groups [3][4][5]22].
The estimated incidence of hand eczema in our study was 11.6 cases per 1000 person-years, 14.3 among females and 5.2 among males. Our figures are in the upper amplitude compared to an earlier population based study from Sweden, which showed between 11.4 and 3.7 cases/1000 person-years among 20-29 year-old females and males, respectively [23]. One explanation could be that our study is prospective, and underreporting is to be expected in retrospective questionnaire studies [24]. Based on 7 European hand eczema studies performed among 16-77 years-olds, the median incidence rate of hand eczema was 9.6 cases/1000 person-years (range 4.6-11.4) among women and 4.0 cases/1000 personyears (range 1.4-7.4) among men [1], which is also slightly lower than our current findings, probably due to age-differences. To the best of our knowledge there are no comparable studies of the cumulative incidence in this age group. The cumulative incidence of hand eczema in our study across 13 years was 15.1% (18.6% for females and 10.7% for males). This can be considered to be a high proportion [15]. When using a questionnaire for estimating the true occurrence of a disease it is important to know the sensitivity and specificity of the question used. The question on 1-year prevalence of hand eczema underestimates the occurrence. [25]. However, regarding childhood eczema the occurrence has been found to be overestimated especially if the true prevalence is low [5,19]. Based on prevalence as well as incidence, the occurrence of hand eczema is approximately twice as common among females compared to men, which is similar to other population-based studies [1,26,27].
The advantage of a longitudinal cohort study compared with a cross-sectional study is that it enables the estimation of both cumulative incidence and incidence rate. Another advantage of performing a follow-up study is the possibility to compare the development of hand eczema over time in relation to different risk factors.
The four groups (HX9508, HX95, HX08 and NoHX) were used to investigate the relationship between childhood eczema and the incidence of hand eczema. The assumption was that a smaller proportion of individuals who had hand eczema in 2008 but not in 1995 reported childhood eczema. However, there were no significant differences between the three hand eczema groups concerning childhood eczema. Furthermore, it was found that a higher proportion of individuals who had hand eczema at both occasions reported childhood eczema.
Thus, in this cohort childhood eczema was the most important predicting factor regardless of the debut of hand eczema. In 2008, around 30% of our sample reported childhood eczema (females 36%, males 20%). In a large population-based Swedish study performed from 2002-2003, among 21-30 years-olds, childhood eczema was reported by 30.1% of females and 20.8% of males, [4,28,29]. The corresponding figures in the 31-40 year-olds were 21.8% and 16.2% [30]. Thus, in our study, the prevalence of childhood eczema was higher. Similar to other studies, the relationship between having had hand eczema and reporting childhood eczema was highly significant [31]. The agreement in self-reports of childhood eczema at the two occasions was high. This high reliability over time in this age-group can be useful to know when hand eczema is diagnosed. However, the lower rate of reported childhood eczema in 2008 can be explained by recall bias as was found in a study comprising respondents aged 31 to 42 years [32]. For the individuals who reported only rhino-conjunctivitis, there was no significant association with one-year prevalence of hand eczema. Also, there was no association with asthma only, but there were very few respondents. Thus in our study no additional information concerning risk for hand eczema was obtained by asking about asthma or rhino-conjunctivitis. These results are in accordance with Meding et al. who showed that asthma and rhino-conjuntivitis in adults were only associated with hand eczema at an age below 30 years [23]; in another study, including adolescents, a marginally significant association with inhalant allergy was found [33]. Analyses of exogenous factors showed that the individuals with hand eczema only in 2008, reported a significantly higher frequency of hand washing compared to the individuals without hand eczema.
Females with hand eczema spent significantly more time doing household activities than men with hand eczema (Table 3). Hand washing was more frequent among females with hand eczema than females without hand eczema as well as compared with men with hand eczema. In the multinominal regression analyses hand washing in the group HX08 was the only significant exogenous risk factor associated with hand eczema. In the majority of hand eczema studies hand washing is found to be the most significant risk factor for developing hand eczema [34]. In our cohort, other exogenous risk factors such as cooking, washing and cleaning and taking care of young children did not have any significant association with hand eczema. Furthermore, female gender was not a significant risk factor. However, it is well known that females have hand eczema more often than men. This can be explained by the high exposure to water and other skin irritants. Experimental as well as epidemiological studies [14,35] have demonstrated that female skin is not more sensitive to irritants than male skin [35] which is in line with our findings.
An interesting finding was the high odds-ratio in daily use of moisturisers in the two groups with current 1year prevalence of hand eczema (HX9508 and HX08). This pattern was not seen in the group having had hand eczema in 1995 (HX95).
When self-administrated questionnaires are used, it is important for the results to be adjusted based on sensitivity and specificity of validated questions. This is especially important in diseases that are common and affect the general health and well-being of individuals, such as hand eczema. The development of specific instruments like questionnaires implicates problems. In this case the questions regarding childhood and hand eczema were not validated in 1995 but 2,535 of the 2,572 pupils (98.6%) were clinically examined, and the sensitivity of 73% and the specificity of 99% were found [15]. The question regarding the 1-year prevalence of hand eczema, which was used in the present study and in the first study, was previously validated [19]. Thus, the true one-year prevalence of hand eczema can be estimated from our data and is 20.6% for all; 26.8% among females and 12.5% among males.
The answers to the open questions on occupation as well as work tasks gave no further information regarding risk factors for developing or maintaining hand eczema. This circumstance seems to be a common problem in questionnaire studies [3]. In a study regarding occupational exposure to water as a risk factor for hand eczema, it was found that the title of an occupation gave misclassified results; exposure time and frequency of water use were more appropriate measures [36]. For result validity, it is important to have high response rates in general population studies [37][38][39]. The response rate in this study was almost two thirds of the individuals who received a questionnaire in the mail. Females were significantly more willing to participate than the males. There were, however, no significant differences within the female or the male groups regarding having had 1year prevalence of hand eczema at the two occasions. The response rate was similar to the annual national public health questionnaire performed by Swedish National Institute of Public Health [40]. express our gratitude to Steven Schmidt for valuable comments and for revising the English text.