LAUSR

Contact allergy occurs due to cutaneous interaction with environmental allergens that result in T-cell–mediated inflammation. Exposures to allergens could, therefore, be presumed to be the sole determinant of contact allergy. However, many contact allergens are ubiquitous in the environment and multiple human and animal studies have demonstrated interindividual variability in the development of contact allergy under uniform conditions of allergen exposure. Consequently, there exists a need to consider the factors influencing the development of contact allergy in relation to interindividual susceptibility. Interindividual susceptibility to many diseases is driven by genetic factors, which can be investigated by classic studies of heritability. For contact allergy, Menné and Holm examined the frequency of nickel allergy in 115 female twin pairs, identifying an increased pairwise concordance rate among monozygotic (0.32) compared with dizygotic (0.14) twin pairs and estimating a heritability for nickel contact allergy of 60%. Bryld et al also examined nickel contact allergy among 630 Danish female twin pairs, demonstrating a slightly increased odds of nickel contact allergy (adjusted odds ratio 1.28, 95% confidence interval 0.33-5.00) in monozygotic compared with dizygotic twin pairs. Although this study did not demonstrate statistical significance, it is important to note that proband selection was based on the presence of hand eczema and thus, selection bias may have affected the results. Similar heterogeneity has been observed in family studies of contact allergy. Walker et al experimentally sensitized parents and children in 99 families with dinitrochlorobenzene and p-nitrosodimethylaniline, observing that sensitization of children by p-nitrosodimethylaniline, but not dinitrochlorobenzene, was more frequent in the presence of concomitant parental sensitization (51% vs 29%, P < .01). Likewise, Forsbeck et al patch tested 404 relatives of 94 patients with confirmed contact allergy to a series of common contact allergens, demonstrating that patch test positivity was seen more frequently only in female relatives (30%) compared with healthy controls (18%). Such observations of heritability in contact allergy could be used as evidence to refute the relevance of genetic predisposition to its development. However, studies of heritability are per se imperfect due to concerns regarding the definition of heritability, while contact allergy is a highly heterogeneous entity, in which a myriad of environmental parameters, including allergen exposure, are known to affect whether a specific contact allergy develops. It seems more logical, therefore, to consider the development of allergen-specific contact allergy as a distinct complex trait, with allergy to each substance being determined by a unique combination of genetic and environmental factors. Nevertheless, major insights into key genetic determinants of contact allergy might be gained by examining those who demonstrate increased risk of contact allergy, irrespective of allergen structure or