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Key Points

  • Disease summary:

    • Atopic dermatitis (AD) is a complex trait, resulting from the interaction of multiple genetic and environmental factors.

    • The specific clinicopathologic definition of “atopic” dermatitis is debated; however, atopic dermatitis, synonymous with atopic eczema, is characterized by elevated levels of circulating IgE and coassociation with the other atopic disorders, asthma, allergic rhinitis, and food allergies.

    • AD is an itchy inflammatory skin disease that follows a chronic relapsing and remitting course. It usually begins in childhood and approximately 90% of cases resolve before adulthood. Diagnosis is based on clinical features (Table 111-1).

    • Moderate-to-severe AD is associated with significant morbidity as a result of pruritus and sleep deprivation. There is an associated reduction in quality of life of the affected child and their close family which is similar in severity to type I diabetes.

  • Differential diagnosis:

    • Irritant dermatitis, allergic contact dermatitis, seborrheic dermatitis, impetigo (Staphylococcus aureus infection) and scabies; severe congenital immunodeficiency and Netherton syndrome may also present as a widespread eczematous rash with failure to thrive

  • Monogenic forms:

    • No monogenic form of AD is known to exist, however, common loss-of-function mutations in the gene encoding the skin barrier protein filaggrin (FLG) cause the dry scaly skin condition ichthyosis vulgaris and approximately 70% of ichthyosis vulgaris cases have AD.

  • Family history:

    • Atopic diseases show strong familial clustering, but a child whose parents have AD is more likely to develop AD than a child whose parents have asthma or allergic rhinitis, suggesting that skin-specific genes may influence phenotype.

  • Twin studies:

    • Monozygotic twins have a 70% to 80% concordance rate for AD, compared to approximately 20% in dizygotic twins.

  • Environmental factors:

    • The prevalence of AD has risen dramatically over the past 20 to 30 years, illustrating the importance of environmental effects, but the key environmental factors remain to be defined. The “hygiene hypothesis” proposes that lack of early life exposure to infectious agents has increased the prevalence of atopic disease.

  • Candidate gene studies:

    • Many different candidate genes have been investigated for association with AD because of their biologic roles in systemic atopic inflammation, cutaneous inflammation, or skin barrier function (Table 111-2). A Few have been replicated in independent studies, most notably FLG, the gene encoding the skin barrier protein filaggrin, in which loss-of-function mutations increase AD risk (odds ratio ~4).

  • Genome-wide associations:

    • Two independent genome-wide association studies have been published to date. Some disease-associated genetic variants (single-nucleotide polymorphisms [SNPs]) provide insight into disease pathogenesis but testing for SNPs is not yet clinically validated to diagnose or guide management of AD.

  • Pharmacogenomics:

    • Carriage of one or more loss-of-function mutations in FLG increases the risk of severe and persistent AD. Testing for common thiopurine methyltransferase (TPMT) variants to guide the choice of azathioprine dose has proven validity in AD.

Table 111-1The UK Working Party’s Diagnostic Criteria for Atopic Dermatitis

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