Dichotomic nature of atopic dermatitis reflected by combined analysis of monocyte immunophenotyping and single nucleotide polymorphisms of the interleukin-4/interleukin-13 receptor gene: the dichotomy of extrinsic and intrinsic atopic dermatitis.

Patients with atopic dermatitis display substantial immunologic abnormalities, among which elevated total IgE is considered as a hallmark; however, a subgroup of atopic dermatitis patients exhibits normal IgE levels, but mechanisms contributing to the so-called "intrinsic" or "nonallergic" form of atopic dermatitis are obscure. In order to unravel similarities and differences of both atopic dermatitis subtypes, the phenotype of monocytes, total serum IgE levels, and serum levels of cytokines regulating the IgE production from nonatopic individuals and patients with allergic rhinitis, and extrinsic and intrinsic atopic dermatitis were measured. Concomitantly, genomic DNA probes of all subjects were analyzed for single nucleotide polymorphisms of candidate genes of structures involved in the regulation of the IgE synthesis, such as interleukin-4 and the interleukin-4R/interleukin-13R. Our data show that the surface expression of the high- and low-affinity receptor for IgE (FcepsilonRI and FcepsilonRII/CD23) and the interleukin-4Ralpha chain were significantly elevated in monocytes from patients with extrinsic atopic dermatitis. Furthermore, serum levels of interleukin-13 were significantly increased in patients with intrinsic atopic dermatitis. In addition, the frequency of the interleukin-4Ralpha polymorphism C3223T and the interleukin-4 polymorphism C590T tended to be higher in extrinsic atopic dermatitis than in intrinsic atopic dermatitis. Altogether our findings indicate that intrinsic atopic dermatitis patients exhibit phenotypic and immunologic features, which differ from those of patients with extrinsic atopic dermatitis or other atopic disorders.