The epidemiology of hand eczema in the general population prevalence and main findings*

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1 Contact Dermatitis 2010: 62: Printed in Singapore. All rights reserved 2010 John Wiley & Sons A/S CONTACT DERMATITIS Review Article The epidemiology of hand eczema in the general population prevalence and main findings* Jacob P. Thyssen 1, Jeanne D. Johansen 1, Allan Linneberg 2 and Torkil Menné 3 1 National Allergy Research Centre, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, 2 Research Centre for Prevention and Health, Glostrup Hospital, University of Copenhagen, and 3 Department of Dermato-Allergology, Gentofte University Hospital, Denmark Numerous studies have investigated the prevalence and risk factors of hand eczema in the general population. These studies are of high value as they tend to be less biased than studies using clinical populations and as they are important for healthcare decision makers when they allocate resources. This study aimed to review the epidemiology of hand eczema in the general population. Literature was examined using Pubmed-Medline, Biosis, Science Citation Index, and dermatology text books. On the basis of studies performed between 1964 and 2007, the point prevalence of hand eczema was around 4%, the 1-year prevalence nearly 10%, whereas the lifetime prevalence reached 15%. Based on seven studies, the median incidence rate of hand eczema was 5.5 cases/1000 person-years (women = 9.6 andmen= 4.0). A high incidence rate was associated with female sex, contact allergy, atopic dermatitis, and wet work. Atopic dermatitis was the single most important risk factor for hand eczema. Hand eczema resulted in medical consultations in 70%, sick leave (>7 days) in about 20%, and job change in about 10%. Mean sick time was longer among those with allergic hand eczema than those with atopic and irritant hand eczema. Moderate to severe extension of hand eczema was the strongest risk factor for persistence of hand eczema. Other risk factors included early onset of hand eczema and childhood eczema. The aetiology of hand eczema is multifactorial and includes environmental as well as genetic factors. Future studies should focus on unresolved areas of hand eczema, for example, genetic predisposition. Key words: general population; hand eczema; hand dermatitis, nickel allergy; public health; regulation. John Wiley & Sons A/S, Accepted for publication 3 November 2009 Like contact allergy (1), hand eczema is one of the most frequent dermatological disorders (2 4). In the past, numerous studies have investigated the prevalence and risk factors of hand eczema in the general population. These studies are of high value as they tend to be less biased than studies using clinical populations and as they are important for health care decision makers when they allocate resources. The present article aims to review the epidemiology of hand eczema in the general population. Hopefully, it may serve as a stepping *The content has not been published previously and is not otherwise submitted for publication. stone for future research but also prove useful for clinicians who on daily basis advise their patients about risk factors and prognosis. Materials and Methods Literature was examined using Pubmed-Medline, Biosis, Science Citation Index, and dermatology text books. Search terms included hand eczema, hand dermatitis, general population, unselected, healthy, prevalence, incidence, risk factor, and epidemiology. In addition, the databases were searched by the use of the related articles function and by searching the publications by specific authors in the scientific area. Finally, references were localized by

2 76 THYSSEN ET AL. Contact Dermatitis 2010: 62: the use of reference lists in selected articles. Prevalence estimates from included studies were ranked and the median selected as an average estimate of the prevalence of contact allergy in the general population. Furthermore, a weighted average prevalence with 95% confidence intervals (CIs) was conducted [(n 1 % 1 + n 2 % 2 + n n % n )/n 1 + n 2 + n n )]. For these analysis, we only included data from the baseline study in follow-up studies (5, 6) and chose to exclude one African study based on 4 15 year olds (7), as environmental exposure was expected to be markedly different. Data analysis was performed using Microsoft Excel 2002 (Redmond, Seattle, WA, USA). Results from general population studies that did not specifically address hand eczema were excluded (8, 9). Results Prevalence The median and weighted average prevalences of hand eczema are shown in Table 1. The point prevalence of hand eczema was around 4%, the 1-year prevalence nearly 10%, whereas the lifetime prevalence reached 15%. Few studies have investigated the development in the prevalence of hand eczema over time. In , Meding and Swanbeck found that the point prevalence of hand eczema among subjects aged years from Gothenburg, Sweden was between 5.4% and 6.3% (15, 16). This was considerably higher than the point prevalence estimated by Agrup (2.3%) in when she questioned individuals in Southern Sweden (10). The authors speculated that the increase could be explained by a general increase in the prevalence of atopic dermatitis as well as by the differences in the study samples used for comparison (industrial versus rural population) (10, 22). Thirteen years later, in 1996, Meding and Järvholm questioned 2218 subjects aged years from Gothenburg, Sweden and found that the 1-year prevalence had decreased from 11.8% to 9.7% (P < 0.01). The decrease was mainly observed in young age groups, whereas the prevalence in middle-aged men and women was almost similar in the two study periods (22). The authors speculated that the decrease was explained by high unemployment rates among especially young people in Sweden in the early 1990s (22). The decreasing prevalence of hand eczema occurred despite an overall increase in the prevalence of self-reported childhood eczema (22). Two repeated cross-sectional studies performed in Denmark 8 years apart found an increasing prevalence of self-reported hand eczema among year olds, which was independent of sex, age, patch test reactivity, and atopic dermatitis status (30). Thus, the overall prevalence increased from 17.0% in 1990 to 26.6% in 1998 [odds ratio (OR) = 1.78; 95% CI = ] (30). However, when the prevalence of self-reported hand eczema was compared between 18 and 69 year olds questioned in 1990 and 2006, an overall similar prevalence was identified, that is, 20.6% in 1990 and 21.8% in 2006 (18). When stratified by age group and sex, no significant changes between 1990 and 2006 were observed (18). Incidence Several studies have investigated the incidence of hand eczema in the general population (Table 2). Based on data from seven studies, the median incidence rate was 5.5 cases/1000 person-years (range ). Stratified by sex, the median incidence rate of hand eczema was 9.6 cases/1000 person-years (range ) among women and 4.0 cases/1000 person-years (range ) among men. A Danish 9-year follow-up study found statistically significant increased incidence rate ratios among twins with contact allergy, atopic dermatitis, and wet work, whereas no association was found for sex, age, and life-style factors (43). Furthermore, the study showed that the incidence of hand eczema was twice as high among monozygotic twins with a co-twin with hand eczema when compared to dizygotic twins with a co-twin with hand eczema, emphasizing the importance of genetic factors in the development of hand eczema (43). Meding et al. found that the incidence rate was highest among year-old women (11.4 cases/1000 personyears), whereas the incidence rate was 6.3 and 4.8 cases/1000 person-years among women aged years and years, respectively (23). Among men, the incidence rate increased gradually with age (23). Similarly, Lind et al. found that the incidence of hand eczema was higher in women under 25 years (12.2 cases/1000 personyears) in comparison to year-old women (8.8 cases/1000 person-years) and women above 34 years (4.8 cases/1000 person-years) (42). Sex All studies found statistically significant higher prevalences of hand eczema among women than among men (Table 1) (5, 21, 32, 44), except for one British study from 1976 that found a higher prevalence in men of middle social class due to frequent manual work (4). The sex difference is generally explained by different environmental exposure (domestically as well as occupationally) and not by a genuine difference in skin susceptibility between men and women (45 47). Also, the higher

3 Contact Dermatitis 2010: 62: HAND ECZEMA IN THE GENERAL POPULATION 77 Table 1. Studies that have investigated the prevalence of hand eczema in the general population (the list may not be exhaustive) 1-year prevalence (%) Lifetime (period) prevalence (%) Point Author Year Country ntotal nwomen nmen Age (years) prevalence (%) Total Women Men Total Women Men Agrup (10) Sweden Johnson (11) USA Peltonen (12) Finland Menné (13) 1978 Denmark Kavli (14) 1979 Norway Lantinga (5) 1979 The Netherlands Lantinga (5) 1982 The Netherlands Meding (15, 16) Sweden Meijer (17) 1995 Sweden Thyssen (18) 1990 Denmark Smit (19) 1992 The Netherlands Dotterud (20) 1994 Norway Bryld (21) 1996 Denmark Meding (22, 23) 1996 Sweden Fung (2) Hong Kong Matilla (24) Finland Örtengren (25) 1997 Sweden Yngeveson (26) 1995 Sweden Yngveson (6) 1997 Sweden Meding (27) 1997 Sweden Brisman (28, 29) 1998 Sweden Nielsen (30) 1998 Denmark Montnémery (31) 2000 Sweden Mortz (32) 2001 Denmark Meding (33) 2001 Sweden Bø (34) Norway Josefson (35) 2003 Sweden Fowler (36) 2003 USA Ogunbiyi 2005 Nigeria Lerbaek (37) 2005 Denmark Thyssen (18) 2006 Denmark Hald (38) 2006 Denmark

4 78 THYSSEN ET AL. Contact Dermatitis 2010: 62: Table 1. Continued 1-year prevalence (%) Lifetime (period) prevalence (%) Point Author Year Country ntotal nwomen nmen Age (years) prevalence (%) Total Women Men Total Women Men Moberg (39) 2006 Sweden Dotterud (40) 2007 Norway Svedman (41) 2007 Sweden Lind (42) 2007 Sweden Total Median prevalence Weighted average prevalence ( ) ( ) ( ) ( ) ( ) ( ) ( ) Positive answer to the question have you any skin changes on the hands (apart from warts). Determined at clinical examination. Publication year. After age 15 years. With 95% confidence intervals. prevalence of atopic dermatitis among women is though to contribute (22, 48, 49). A Swedish study found that the sex-related risk of hand eczema was only of significance in respondents aged below 30 years of age (23). The authors speculated that the overall sex difference observed in most prevalence studies is probably to be explained by different incidence rates between young men and women, as prevalence studies do not take exposure time into account (23). Apparently, a significantly higher prevalence of hand eczema in females may already be observed among year olds (32). However, as a Norwegian study found identical prevalences of hand eczema in 7 12-year-old male and female school children (20), the sex difference may mainly be observed in teenagers and young individuals. Age The prevalence of hand eczema is different across age groups. Thus, surveys and investigations have repeatedly shown that the frequency of self-reported hand eczema peak among young women and decrease with age (4, 14, 27, 44, 50). Among participants in a Swedish health survey, the self-reported 1-year prevalence of hand eczema decreased significantly from 12% among women aged years to less than 6% among women aged years (27). Among men, the 1-year prevalence did not depend as much on age group (27). However, both a large Norwegian and British survey found a decreasing trend with age among men (4, 44). Meding et al. found that 35% of women and 27% of men reported that their first occurrence of hand eczema was observed before age 20 (23). Hald et al. found that the median age at first onset of hand eczema was 26 years among women and 28 years among men (38). This was in accordance with a Swedish survey which found that the mean age at onset of hand eczema was 27 years among adults (51). However, a recent Swedish study including 5034 women found a considerably lower mean age at onset of hand eczema (21.2 years) (42). Atopic dermatitis and atopy General population studies have repeatedly found that atopic dermatitis is the most important risk factor for hand eczema (6, 20, 22, 32, 35, 52, 53). A Norwegian study found that 90% of school children with hand eczema also reported atopic dermatitis (20), which suggests that hand eczema in children is closely associated with hand eczema. A Danish study including 1438 adolescents found that hand eczema was significantly associated with atopic dermatitis as well as inhalant allergy (32).

5 Contact Dermatitis 2010: 62: HAND ECZEMA IN THE GENERAL POPULATION 79 Table 2. Studies that have investigated the incidence of hand eczema in the general population (the list may not be exhaustive) Incidence cases/1000 person-years Author Year Country Age (years) n total n women n men Total Women Men Lantinga (5) 1982 The Netherlands Yngveson (6) 1997 Sweden Meding (23) 1996 Sweden Brisman (28) 1998 Sweden Meding (33) 2001 Sweden Lerbaek (43) 2005 Denmark Lind (42) 2007 Sweden Recalculated from article. Meding and Järvholm also found that a history of respiratory atopy was associated with hand eczema even when subjects who reported childhood eczema were excluded from the analysis (49). Brisman et al. found that the incidence of hand eczema was 24.2/1000 person-years among women who reported childhood eczema, but only 9.5/1000 person-years among those who did not report childhood eczema (28). Also, large Danish and Swedish studies have found increased incidence rates among subjects who reported atopic dermatitis (23, 43). Of note, Meding et al. found that atopic dermatitis was only a risk factor in subjects aged below 30 years (23). Thus, the effect of atopic dermatitis seemed to level off with increasing age. Whether the association between hand eczema on the one hand and atopic dermatitis or atopy on the other hand is explained by null mutations in the filaggrin gene, by an altered immune response, or by their combination is currently unknown. Future studies should aim to investigate the distribution of these risk factors. Genetic factors Bryld et al. found that hitherto unrecognized hereditary factors independent of atopic dermatitis were associated with hand eczema in twins (21, 52). Genetic contribution to hand eczema appeared stronger in younger age groups (21). The authors speculated whether the inherited liability depended on additional excessive environmental exposure (21). In a later follow-up of the same twin cohort, the earlier results were confirmed as 41% of the variance in liability to develop hand eczema was explained by genetic factors other than atopic dermatitis (54). No effect of genetic factors on age at onset was found (54). Lerbaek et al. also found that genetic factors accounted for approximately 30% of the variance in liability regarding frequency of eruptions (54). In further twin studies, they investigated whether null mutations in the filaggrin gene complex were associated with hand eczema (55). They found no statistically significant association among 183 twins, which could be due to a lack of statistical power as well as an unfavourable control group (55, 56). Nickel allergy A possible association between hand eczema and nickel contact allergy has been repeatedly debated. In pioneering work, Agrup found positive patch test reactions to nickel in 56 (12.1%) of 462 females, with a history of allergic hand eczema (10). In 49 individuals, nickel was found to be the main cause or a contributory cause of the hand eczema (10). Peltonen found that hand eczema was more common in nickel allergic subjects (20.5%) than subjects without hand eczema (not given) (12). Menné etal. studied the association in a sample of women from the general population and found that nickel allergic woman had an increased risk of developing hand eczema, but also that women with hand eczema had an increased risk of developing nickel allergy (13). Meier et al. found no association between hand eczema and nickel allergy among 520 Swedish men doing military services (17); however, this may not be the best study group in which to test for this association. Meding et al. showed that nickel allergy and hand eczema were significantly associated among both sexes as 30% of those who reported nickel allergy also reported hand eczema (27). Of note, the authors observed that combined nickel allergy and atopic dermatitis increased the risk of hand eczema more than each of these conditions alone (27). Mortz et al. found that nickel allergy was associated with hand eczema in yearold Danes (OR = 2.36; CI 95% = ), as the prevalence of nickel allergy was 22.4% among those with hand eczema and only 9.4% among those without (57). Bryld et al. found that contact allergy and nickel allergy were risk factors for the development of hand eczema in a sample of twins from the general population (52). Furthermore, this association was stronger among subjects with strong patch test reactions (3+) when compared to those with weaker test reactions (52). In their follow-up

6 80 THYSSEN ET AL. Contact Dermatitis 2010: 62: study, Lerbaek et al. found a high prevalence of contact allergy (31.9%) among those who reported hand eczema, whereas the overall prevalence of selfreported contact allergy was 10.1% (54, 58). Josefson et al. made an interesting follow-up study of 735 school girls who had been nickel patch tested 20 years earlier (35). They found no difference in the frequency of self-reported hand eczema after age 15 years and no difference in the 1-year prevalence of hand eczema between the two groups (35). The authors confirmed their initial finding when they performed clinical examination as well as patch testing in 369 of these women (59). However, curiously, they found an increased risk of hand eczema in women with nickel allergy but without a history of childhood eczema (59). Josefson et al. found that women who had a positive nickel patch test reaction 20 years ago did not consult their doctor more often than those who had a negative patch test reaction at that time (35). Recently, the third Glostrup allergy study found that the prevalence of concomitant nickel allergy and a history of hand eczema decreased among year-old women from 9.0% in 1990 to 2.1% in 2006 (P <0.01) and that the association between nickel allergy and a history of hand eczema decreased in this age group between 1990 (OR = 3.63; 95% CI = ) and 2006 (OR = 0.65; 95% CI = ) (18). Life-style factors Few studies have investigated the association between life-style factors and hand eczema. No association was found between hand eczema and tobacco smoking in a Danish twin study (43), a Swedish questionnaire study performed in hairdressers, bakers, dental technicians, and a control group (29), or in a large Norwegian questionnaire study including adults (34). However, Montnémery et al. found a weak association between hand eczema and tobacco smoking (OR = 1.35; 95% CI = ) in an adjusted analysis including data from 9316 respondents (31). Also, a recent Danish study which included patch test results from 3460 participants in an adjusted analysis showed that the prevalence of hand eczema was significantly higher among both previous smokers, current light or heavy smokers when compared with never smokers (60). Finally, no studies have so far found an association between alcohol consumption and hand eczema (34, 43, 60). Socio-economic factors A large Norwegian survey with responders showed that individuals with lower education reported significantly more hand eczema than those with the highest education and that hand eczema was significantly more prevalent among respondents with middle household income when compared with the highest income groups (44). Also, the study suggested that men who lived alone tended to report hand eczema more often than those who lived with someone (44). Climatic conditions Kavli et al. reflected on the possible influence of climatic condition on the prevalence of hand eczema as they found a higher prevalence in Tromsø, Norway when a comparison was made to data from Lund, Sweden (14). Despite finding a lower humidity in Northern Norway than in Southern Sweden, no causality was established. Health-related quality of life Meding and Swanbeck questioned 1238 subjects with hand eczema and found that more than 80% had experienced negative psychosocial interference due to their hand eczema (e.g. sleep or mood disturbances, change of daily activities, or cessation of hobbies) (61). Women reported psychosocial effects of having hand eczema more frequently than men (84.9% versus 74.1%, P<0.001) (61). Nearly half of the respondents reported that they suspected other people to believe that hand eczema was a contagious disease (61). Also, half reported frequent itching (61). Health-related quality of life refers to the perception of the effects of a disease and its impact on the patient s daily functioning (39); however, only little research has addressed this topic. Moberg et al. found a poor quality of life among subjects with hand eczema in a survey including year olds (39). Thus, independent of age group and sex, subjects with hand eczema had a consistently lower EQ-5D index than subjects who did not report hand eczema (39). The EQ-5D index for subjects with hand eczema was similar to that of individuals with asthma and psoriasis (39). Occupation Meding and Swanbeck investigated the impact of occupational exposure for the development and severity of hand eczema among subjects (61, 62). The authors found that the 1-year prevalence of hand eczema was not significantly higher for people in gainful employment when compared with those without a job (62). Furthermore, among respondents who worked full-time or parttime, the 1-year prevalence of hand eczema was highest among those who reported nursing and

7 Contact Dermatitis 2010: 62: HAND ECZEMA IN THE GENERAL POPULATION 81 medical work (15.9%) or service work (15.4%), the latter being statistically significant when compared to all respondents (62). These occupational groups also had the highest prevalences of irritant hand eczema (62). Among all respondents who had a job, cleaners had the highest 1-year prevalence of hand eczema (21.3%) (62). Finally, daily occupational exposure to water, detergents, chemicals, or dirt resulted in a higher prevalence of hand eczema than among subjects who reported no exposures (62). Among subjects who reported hand eczema, no association was found between having contact allergy and belonging to a certain occupational group, except for female office workers who had higher frequencies of colophony allergy (62). Finally, Meding and Swanbeck did not find any association between specific occupations and the number of self-reported medical consultations when investigating 1238 subjects with hand eczema (61). In another Swedish questionnaire study, Montnémery et al. also found that highrisk occupations, such as nursing, were associated with hand eczema; however, their adjusted analysis showed no increased risks (31). Finally, Josefson et al. found no association between high-risk occupations, such as medical and nursing work, and self-reported hand eczema in a follow-up study of 731 women (35). Wet work In 1990, Meding et al. showed that 67% of participants in a health survey reported washing their hands between 5 and 14 times per day (27). Women reported hand washing more often than men and a statistically significant association between reporting frequent hand washing and hand eczema (within the past year) was observed (27). However, a large Danish twin study was not able to find an association between wet work and hand eczema (52). The authors speculated that wet work was only a risk factor for a subgroup of people and not for the population as a whole (52). Recently, Anveden et al. showed that among year-old employees from the general population in Sweden, 16.3% reported that total water exposure exceeded 30 min/day (63). Kitchen workers, nurses, hairdressers, and cleaners were highly exposed (63). Women reported more occupational water exposure than men, regarding both exposure time and frequency (63). Water exposure was most pronounced among the youngest women, which is interesting as this group was also intensely exposed at home (63). This finding was repeated in another Swedish survey where young women reported longer occupational water exposure than older women (51). The latter study interestingly found that subjects with hand eczema reported the same level of exposure when compared with controls without hand eczema (51). However, they reported a significantly higher use of protective gloves (51). The authors speculated whether this finding could explain the bad prognosis of hand eczema (51). Medical consultations, sick leave, and job change Occupational and medical consequences of having hand eczema have been thoroughly investigated. Lantinga et al. found that hand eczema in 67 (48%) of 142 subjects with hand eczema justified medical attention (5). Meding and Swanbeck found that 69% of 1238 subjects with hand eczema had consulted a doctor for their hand eczema and that 21.9% had consulted a doctor more than five times (61). Furthermore, 21.4% reported sick leave on at least one occasion (minimum 7 days) due to their hand eczema (61). The mean duration of sick leave was 18.9 weeks among those who reported sick leave (61). The mean total time on sick leave among subjects with allergic contact dermatitis (28.6 weeks) was higher than for those with irritant dermatitis (13.0 weeks) and atopic hand eczema (11.8 weeks) (61). No sex differences were found regarding sick leave. A total of 8% reported change of occupation because of hand eczema. They mostly reported service work, production work, as well as nursing and medical work (61). Subjects reporting job change also had a higher number of medical consultations and periods of sick leave as well as longer duration of sick leave in comparison to those who did not change their jobs (61). A large Norwegian survey found a high 1-year prevalence of hand eczema in both sexes, but also a surprisingly low prevalence of sick leave within the past 3 years due to hand eczema (0.7% of men and 1.4% of women) (14). Young women had the highest prevalence of sick leave being two to three times higher than among young men. In older age groups, the prevalence of sick leave was similar among men and women (14). In a twin followup study, Lerbaek et al. found that 12.4% of 185 subjects who reported hand eczema on themselves or their twin had been on sick leave because of their hand eczema (58), and that 3.2% had been on sick leave for more than 6 weeks (58). Low socio-economic group and atopic dermatitis were significant risk factors for reporting sick leave (58). Hand eczema resulted in job change in 8.5% (58). Also, the authors found that 63.4% had consulted their doctor because of hand eczema and that 15.6% did this on more than five occasions (58). Recently, a Danish questionnaire study found that among 564 subjects who reported hand eczema within the past 12 months, hand eczema resulted in medical

8 82 THYSSEN ET AL. Contact Dermatitis 2010: 62: consultation at their general practitioner in 67% and at a dermatologist in 44% (38). Finally, Josefson et al. showed that 15.5% of Swedish women with hand eczema changed their job as a result of their skin condition (35). Clinical severity Among 1238 subjects with hand eczema, the extent of involvement was investigated and showed that severe dermatitis occurred in 15% (men = 19% versus women = 12%), moderate dermatitis in 15% (men = 15% versus women = 15%), and mild dermatitis in 12% (men = 14% versus women = 12%) (50). The extent of involvement was most severe in subjects with atopic hand eczema and allergic contact dermatitis (50). Treatment with topical corticosteroids was reported in 50.9% of the participants with hand eczema, mainly group III (potent) (25%) (61); 84.7% reported treatment with emollient creams whereas only 0.3% reported ultraviolet (UV) treatment (61). Lerbaek et al. performed clinical examination on 274 (41.5%) of 659 twins who reported hand eczema themselves or a co-twin with hand eczema almost 9 years earlier (58). They identified 188 twins with antecedent or present hand eczema and focused their investigation on these (58); 41% had one or more clinical signs of hand eczema and examination showed that erythema as well as scaling were the most prevalent observations (58). Eczema was most often located on the palms and fingers (not fingertips). The mean of the hand eczema severity index (HECSI) score was 4.9, but if only subjects with clinical signs of hand eczema were included the mean HECSI score reached 12.0 (58). Severity was comparable between men and women. Finally, among 96 twins who reported hand eczema within the last year prior to the first clinical examination, 67% still reported hand eczema within the last year prior to the second examination (58). A recent Danish questionnaire study found that among 564 subjects who reported hand eczema within the past 12 months, 50% reported duration less than half the time whereas approximately 30% reported symptoms half the time or more (38). Self-rated severity of hand eczema using a photographic guide showed that 23% rated their hand eczema as moderate to severe (38). Among year-old Danes with hand eczema, 64.7% reported eczema on their fingers or finger webs, 51.1% on the back of their hands, and 16.5% on the palms (32). A Norwegian study found that 66% of 7 12-year-old school children with hand eczema had dermatitis on the back of their hands only (typically those with concomitant atopic dermatitis), whereas around 20% had hand eczema on their palms only (20). A Danish twin study found that the most frequent self-reported symptoms in subjects with hand eczema were itching/cracking (15%) and vesicles (15%) (21). Finally, Fowler et al. investigated the severity of hand eczema in unselected Americans and showed that 17 (54.8%) of 31 subjects reported moderate to severe hand eczema (36). Hand eczema subtypes Lantinga et al. pioneered the clinical description of hand eczema among subjects from the general population as they examined 1992 subjects in 1979 and again in 1982 (5). Irritant dermatitis was the most prevalent subtype (32 48%) followed by irritant plus allergic dermatitis (14 15%), allergic dermatitis (14 22%), and irritant plus atopic dermatitis (6 8%) (5). The authors found that irritant hand eczema had a lesser tendency to heal than combined irritant and allergic dermatitis (5). Meding and Swanbeck examined 1238 subjects who reported hand eczema in and found irritant dermatitis in 36%, allergic dermatitis in 16%, atopic dermatitis in 16%, pompholyx in 6%, hyperkeratotic dermatitis in 3%, nummular eczema in 2%, and unclassified eczema in 21% (50). The female/male ratio was highest for allergic dermatitis (5.4) and irritant dermatitis (2.4) (50). Furthermore, the study showed that irritant hand eczema was more common in subjects with occupational exposure (50) and that the hand eczema subtype influenced the number of medical consultations as 34.5% of subjects with atopic hand eczema and 34.9% of those with allergic contact dermatitis had consulted a doctor more than five times in comparison to only 11.9% of those who had irritant dermatitis (61). Finally, longer duration time was found for subjects with atopic dermatitis (15.5 years) when compared with allergic dermatitis (12.8 years) and irritant dermatitis (10.3 years) (50). Prognosis Several studies have investigated the prognosis of hand eczema. Anvenden et al. found that the mean duration of hand eczema was 12 years from onset to interview (51), which was similar to 11.6 years found by Meding and Swanbeck in (50). No difference between men and women was found (50). In , Meding et al. performed a follow-up study on 868 subjects who reported hand eczema in (64, 65). They found that 66% experienced hand eczema during the 15 year follow-up period, and that 44% had symptoms within the past 12 months (64). Only 12% reported continuous hand eczema

9 Contact Dermatitis 2010: 62: HAND ECZEMA IN THE GENERAL POPULATION 83 during the 15 years (64). Seventy-four percent (women = 78% versus men = 66%, P<0.01) of those who reported symptoms considered that their hand eczema had improved since (64). Some 33% had consulted a doctor due to their hand eczema, 6% reported sick leave periods of at least 7 days, 3% reported a change to another occupation due to their hand eczema, and 2% reported sickness pension (64). Finally, 96% reported impairment of their social life due to hand eczema (64). In general, no difference was observed between men and women (64). Statistically significant predictive factors for the persistence of self-reported hand eczema at least half the time since as well as for the occurrence of hand eczema within the past 12 months included (65) the age of onset before 20 years, positive history of childhood eczema, and moderate to severe extension of hand eczema in (65). Also, in an unadjusted analysis, contact allergy and medical consultation in were significantly associated with persistence of eczema (65). Analysis showed that moderate to severe extension of hand eczema was the strongest risk factor for persistence (65). However, the authors found that future studies should focus on extent rather than morphology when predicting the long-term prognosis (66). Finally, Meding et al. found that nickel allergy or contact allergy was associated with persistence of hand eczema after 15 years (65). General Discussion This review showed that the 1-year median prevalence of hand eczema in the general population was 9.7% (11.4% among women and 5.4% among men) and that the 1-year weighted average prevalence was 9.1% (10.5% among women and 6.4% among men). Most studies included in this review used the question have you had hand eczema on any occasion during the past 12 months? to estimate the 1-year prevalence of hand eczema. Meding et al. have previously validated this question among car mechanics, dentists, and office workers and found that its sensitivity was 53 59% and its specificity 96 99% (67). Although it has not been validated in the general population, the figures are likely to be similar. Thus, the true 1-year prevalence of hand eczema found in this review may be 30 60% higher, reaching 12 15% (67). Of note, the 1-year prevalence estimates showed in Table 1 were in some studies based on slightly different questions [e.g. have you suffered during the last 12 months from allergic eczema on the hands (14) and have you ever had or do you currently have eczema or any other rash on your fingers, fingerwebs, palms, backs of hands, or wrists? in combination with questions on time of occurrence (26, 68)]. Despite the interstudy differences in the questions used to diagnose hand eczema (both point, 1-year, and lifetime), the prevalence estimates seemed generally valid for comparison; for example, Yngveson et al. found that the specificity of the point prevalence estimate was 99% and that the sensitivity was 73% (26, 68). Figure 1 shows the development in the 1-year prevalence of hand eczema over time among Scandinavians. Data from an American questionnaire study were excluded as the response rate was only 36.5% (36), which potentially could skew the results. Also, a Nigerian study performed among school children (7) was excluded as environmental exposures and climatic conditions in Central Africa are much different from those in Scandinavia. Studies on younger age groups were included in the figure as the 1-year prevalence of hand eczema is already significant at a low age (Table 1). Figure 1 suggests that the 1-year prevalence has remained relatively stable, despite a general increase in the prevalence of atopic dermatitis in western societies (69 71). However, Fig. 1 may possibly hide an overall increase in the prevalence of hand eczema as it has not been stratified by sex and age group. As recruitment of young people to general population studies is becoming increasingly difficult (72), it is possible that a true increase in the 1-year prevalence of hand eczema is hidden by a decline in the proportion of young individuals in the included studies. For these reasons, a good way to study the changes in the prevalence of hand eczema in the general population would be to focus on young age groups. Table 1 shows that most general population studies on hand eczema have been performed in Scandinavia. There may be several putative explanations for this finding: (i) contact allergy and hand eczema have traditionally been a topic of interest for Scandinavian dermatologists (10, 73, 74), (ii) the use of unique personal identified for administrative purposes in Scandinavian countries favour epidemiological studies, and (iii) hand eczema is a more common disorder in Scandinavian countries, due to their northerly geographical location, that may increase skin dryness and the liability to develop dermatitis. We speculate that climatic factors may be of significant importance, in particular the cold weather. However, when investigating meteorological differences between European countries, we found no national differences in the relative humidity but we found that temperature is much lower during winter time in Scandinavia when compared to Southern European countries ( As only very few general population studies have been performed outside of Scandinavia, we are at this time unable

10 84 THYSSEN ET AL. Contact Dermatitis 2010: 62: Percentage (%) Study year Fig. 1. The development in the 1-year prevalence of hand eczema among Scandinavians as assessed by general population studies performed between 1979 and Each column indicates an individual study. to determine whether hand eczema is indeed more common in Scandinavia. Table 3 shows the main findings from investigations on hand eczema in the general population. Hand eczema was clearly associated with female sex, childhood eczema, and young age, whereas weaker evidence was found for wet work, occupation, contact allergy, and tobacco smoking. It is evident that general population studies may be suboptimal when one investigates the risk of, for example, wet work and occupational exposures, as an effect is diluted due to low power. Occupational exposure is clearly a risk factor of hand eczema as determined by various occupational studies on selected groups (19, 28, 42, 75). The association between nickel allergy and hand eczema seemed to have weakened over time, probably as a result of regulatory regulations on nickel exposure (18). Although a definite cause-effect relationship has not been established in the general population, it is undisputable that excessive nickel exposure on the hands will result in allergic hand eczema in most nickel sensitized individuals (76). The review showed that hand eczema is a chronic disorder that in many cases lasts for more than 10 years. Furthermore, it seems that moderate to severe disease is observed in 30% and that 20% are affected to a degree where they have longer periods of sick leave, and finally that 10% experience job change due to their hand eczema. Moderate to severe extension of disease as well as allergic and atopic hand eczema seems to be associated with persistence of hand eczema. This review interestingly found that the prognosis for allergic hand eczema was poorer than for irritant hand eczema. The finding underscores the importance of regulatory initiatives that have been passed within the EU to reduce allergen exposure. In a population of 500 millions, these initiatives have so far resulted in decreasing prevalences of, for example, nickel allergy (77 79), methyldibromo glutaronitrile (80), and chromate allergy (81). The positive impact on health and society resources is significant and globally unique. Furthermore, a change in the production of rubber gloves has resulted in decreasing prevalences of thiuram allergy (82 84). Also, it has been shown that direct interventions in the work environment can reduce skin problems (85 88). In a large Danish company producing wind turbine systems, a high prevalence of epoxy dermatitis was noted (88). Intervention resulted in a reduction in the incidence of eczema from 68 cases per year/1000 employees to cases per year/1000 employees (88). The value of intervention among Danish hairdressers is currently being investigated. A recent German study found a poor adherence to preventive skin programmes among male metal workers (89). The above-mentioned examples of hand eczema prevention should be further perpetrated in the future to reduce the prevalence of hand eczema.

11 Contact Dermatitis 2010: 62: HAND ECZEMA IN THE GENERAL POPULATION 85 Table 3. Main findings from population-based studies (performed between 1964 and 2007) investigating the epidemiology of hand eczema in the general population The point prevalence of hand eczema was 3 4%, the 1-year prevalence 10%, and the lifetime prevalence 15%. The prevalence of hand eczema seemed stable over the study period. Based on seven studies, the median incidence rate of hand eczema was 5.5 cases/1000 person-years (women = 9.6andmen= 4.0). A high incidence rate was associated with female sex, contact allergy, atopic dermatitis, and wet work. Hand eczema was more common in women than men, mainly because of different domestic and occupational environmental exposures as well as higher prevalences of atopic dermatitis. The prevalence and incidence of hand eczema in women peaks in the 20s and 30s. About one third of men and women report their first hand eczema before the age of 20. Atopic dermatitis is the single most important risk factor for hand eczema, but it is mainly of significance in young individuals. Genetic factors other than atopy are of importance in the development of hand eczema. Lately, filaggrin null mutations have been suggested as a risk factor. Nickel allergy is a risk factor for hand eczema. However, regulatory interventions on nickel exposure as well as other environmental changes seem to have reduced the association between nickel allergy and hand eczema. Hand eczema may be associated with tobacco smoking but not with alcohol consumption. Hand eczema seems to be more common among subjects with lower education and middle household income. Hand eczema has a negative psychosocial interference in nearly all affected subjects. Climatic conditions may possibly affect the prevalence of hand eczema although no studies have ever sufficiently investigated this topic. Occupational exposure to various offenders such as water, detergents, and dirt are associated with hand eczema. Although general population studies are generally unfavourable when one wishes to estimate the impact of occupational exposure, nursing, medical, and service work were associated with hand eczema. Wet work has been associated with hand eczema but several studies have also rejected an association. Subjects with hand eczema report the same amount of wet work, but also have a significantly higher use of protective gloves. Occupational water exposure is more frequent among women than men. Hand eczema results in medical consultations in 70%, sick leave (>7 days) in about 20%, and job change in about 10%. Mean sick time is longer in those with allergic hand eczema than those with atopic and irritant hand eczema. Up to one third of subjects with hand eczema have moderate to severe disease and around half use topical steroids group III at some point. Mean duration time of hand eczema exceeds 10 years. Fifty percent report hand eczema within the past 12 months and 10% still have hand eczema after 15 years. Irritant hand eczema is more prevalent than allergic and atopic hand eczema. Irritant hand eczema is associated with occupational exposure, whereas atopic and allergic hand eczemas are associated with medical consultations and persistence. Moderate to severe extension of hand eczema is the strongest risk factor for persistence of hand eczema. Other risk factors include early onset of hand eczema and childhood eczema. Taken together, the aetiology of hand eczema is multifactorial and includes environmental as well as genetic factors. We are just beginning to learn about the possible effect of null mutations in the filaggrin gene complex (55, 56, 56, 90 92). 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