Atopic dermatitis (AD) is a clinical syndrome characterized by an itchy rash with a variety of morphological cutaneous features that change with age, in association with a positive family history and concomitant presence of other atopic diseases (atopic asthma, hay fever, and occasionally urticaria) (Williams, 1997). The atopic immunological state is characterized by a propensity to develop type 1 IgE mediated responses in response to certain antigens, but the cutaneous immuno-pathology of atopic dermatitis is characterized by the presence of a T cell and inflammatory cell infiltrate resembling the pattern seen in type IV hypersensitivity reactions (rather than the type 1-like response seen in urticaria). The onset of the rash is typically in early life, peaking at age four years and tending to improve with age, although a large proportion of subjects may develop other forms of eczema later in life (Williams, 1997). Drawing the boundary between mild atopic dermatitis and normality is difficult. Patients may have the symptoms and signs only when provoked by environmental factors, and symptoms may often be mild and patients unaware of the physical signs. Various standardized diagnostic criteria have been proposed but have not been used in most genetic studies (Williams, 1997). Therapy is suppressive with the mainstay being emollients (the skin appears dry) and immunomodulators such as corticosteroids or calcineurin inhibitors and antibacterials for episodes of secondary infection.
The incidence of atopic dermatitis, like other atopic disorders such as asthma and allergy to peanuts appears to have increase threefold over the last 40 years (Williams, 2000). The disease is more common in many developed populations and is affected by sib position: sibs with a higher birth order have a lower rate of disease (Williams, 2000).
That atopic dermatitis runs in families along with the other major atopic diseases was recognized in the original description of atopy (Larsen, 2004). Patients with severe atopic dermatitis have a parent affected in between one-third and two-thirds of cases and in families with one or more first-degree relatives affected, 25-45% of children have atopic dermatitis (Larsen, 2004).
The best population-based twin studies come from Schultz Larsen and colleagues in Denmark; studies which have been repeated over time and provide additional information on secular trends (Larsen, 1993; 2004). They report an increase in the cumulative incidence (up to age 7 years) of atopic dermatitis from 0.03 for a 1960-4 birth cohort to 0.12 for the 1975-9 birth cohort. Pairwise concordances for the most recent cohorts were 0.75 and 0.25 for MZ and DZ twins respectively. They additionally have shown that the risk of AD if the dizygotic partner has the disease is equal to the risk seen in non-twin siblings. In reviewing these results, Larsen comments that the concordance rates are much higher in these studies than in those conducted in Sweden earlier in the century although differences in study design render conclusions based on these differences problematic (Larsen, 1993; 2004). Finally some studies suggest that the risk of developing atopic dermatitis is greater when the mother rather than the father is affected. This could be due to imprinting but other explanations in terms of more shared environment and effects on the fetus are also possible (see Larsen, 2004).
Sib and other family studies have identified a number of loci, some of which show overlap with those implicated in psoriasis. The genes underpinning the linkage are not known. Special mention should be made of the gene underlying Netherton's syndrome (OMIM 256500, SPINK5).
Netherton's syndrome is an autosomal recessive disorder characterised by a characteristic rash, hair abnormalities, and the atopic state. It is due to a number of mutations in the SPINK5 gene that encodes a serine protease inhibitor. Recent studies have shown that a particular variant of the SPINK5 gene is associated with atopy and atopic dermatitis (Walley et al., 2001) (see Chapter 26).
Studies of serum IgE may be viewed as an intermediate phenotype and twin studies suggest that the heritability of IgE in adults is 0.59 and 0.79 in children (Bazarel etal., 1974).
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