Atopic dermatitis and the hygiene hypothesis: a case-control study.
BACKGROUND: The notion that lack of exposure to infection in early life leads to development of atopic disease has come to be known as the hygiene hypothesis. It has arisen from observations of the rapidly rising prevalence of atopic diseases in recent decades and the lower prevalence of atopy with rising birth order. Direct evidence for the hypothesis to date is inconsistent. METHODS: A case-control study set in Norfolk, UK of 602 children aged 1-5 years. Cases and controls were defined using the UK Diagnostic Criteria for atopic dermatitis (AD) and a range of direct and indirect methods were used to measure exposure to infection during infancy. Odds ratios (OR) for the effect of these measures were calculated using logistic regression with adjustment for possible biological and social confounding factors. RESULTS: Reduced odds of AD were associated with rising birth order (OR for one older sibling 0.59, 95% CI: 0.42, 0.84 and for >or=2 older siblings 0.49, 95% CI: 0.31, 0.77). None of the measures of infection reduced the odds of AD significantly, either in the unadjusted or adjusted analyses. None of the measures of infection explained the protective effect of older siblings. CONCLUSIONS: Increased exposure to infection does not explain the reduced risk of AD in second and subsequent siblings. More generally, these data cast doubt on the hygiene hypothesis as a causal explanation for AD in young children.