Atopic Dermatitis Phenotypes Impact Expression of Atopic Diseases Despite Similar Mononuclear Cell Cytokine Responses

Abstract

Background: The atopic march refers to the co-expression and progression of atopic diseases in childhood, often beginning with atopic dermatitis, although children may not progress through each atopic disease. Objective: We hypothesized that future atopic disease expression is modified by atopic dermatitis phenotype, and that these differences result from underlying dysregulation of cytokine signaling. Methods: Children (n=285) were enrolled into the Childhood Origins of ASThma birth cohort and followed prospectively. Rates of atopic dermatitis, food allergy, allergic rhinitis, and asthma were assessed longitudinally from birth to 18 years of age. Associations between atopic dermatitis phenotype and food allergy, allergic rhinitis, asthma, allergic sensitization, exhaled nitric oxide, and lung function were determined. Peripheral blood mononuclear cell responses (IL-5, IL-10, IL-13, IFN-γ) to dust mite, phytohemagglutinin, Staphylococcus aureus Cowan I, and tetanus toxoid were compared among atopic dermatitis phenotypes. Results: Atopic dermatitis at year 1 was associated with an increased risk of food allergy (p=0.004). Both persistent and late-onset atopic dermatitis were associated with an increased risk of asthma (p=<0.001), rhinitis (p<0.001), elevated total IgE (p=<0.001), percentage of aeroallergens with detectable IgE (p<0.001), and elevated exhaled nitric oxide (p=0.002). Longitudinal analyses did not reveal consistent differences in PBMC responses among dermatitis phenotypes. Conclusion: Atopic dermatitis phenotype is associated with differential expression of other atopic diseases. Our findings suggest peripheral blood cytokine dysregulation is not a mechanism underlying this process, and immune dysregulation may be mediated at mucosal surfaces or in secondary lymphoid organs. Keywords: Atopic dermatitis; allergic sensitization; atopic dermatitis phenotypes; atopic march; progression of atopic disease.