**Part 3**

**Diagnosis and Clinical Management** 

158 Atopic Dermatitis – Disease Etiology and Clinical Management

Yim, M., Kim, Y., Ko, H., Lee, W., Choe, B. & Ahn, J. (2010). Molecular analysis of

*Dermatology*, Vol.22, No.1, (February 2010), pp.41-47, ISSN 1013-9087

*Malassezia* microflora on the skin of the patients with atopic dermatitis. *Annals of* 

**10** 

*Italy* 

**Atopic Dermatitis: From Pathophysiology** 

Atopic eczema/dermatitis syndrome (AEDS) is a chronic inflammatory skin disease, very common in childhood (1). The prevalence of AEDS is estimated to 15–30% in children and 2–10% in adults while the incidence has shown a 2- to 3-fold increase in the past 3 decades in developed countries (2). This results in a significant socio-economic impact, that in the United States was estimated in a range from \$364 million to \$3.8 billion US dollars per year, usually considering only the direct but not the indirect costs (3). The disease is sustained by a complex interaction between genetic and environmental factors and is characterized by a skin barrier dysfunction resulting in epidermal damage and altered permeability to allergens and microbes (4). Depending on the association or not to IgE sensitization, AEDS may be defined as atopic or nonatopic. The two forms are clinically similar but show some differences regarding the histology, the kind of cells involved, and

The pathophysiologic mechanisms leading to AEDS originate from an initial skin defect at epidermal level, above all in the *stratum corneum*, which is the first of the four epidermal layers. The *stratum corneum* (from the Latin words for horned layer) is composed of large, flat cells containing keratin, a protein that helps keep the skin hydrated by preventing water evaporation, and surrounded by lamellae sheets rich in hydrophobic lipids, including ceramides, sphyngosynes and free fatty acids. Keratin is produced by the keratinocytes of the basal layer, which also keep the Langerhans cells and the intradermal lymphocytes in position with the epidermis. They also work to modulate the immune response by secreting cytokines such as TGF-beta and alpha, and a number of interleukins (6). A major advance in the understanding of epidermal barrier dysfunction which occurs in AEDS was the identification of the fundamental role of filaggrin (7). Filaggrin, which derives from the highly phosphorylated polypeptide profilaggrin, the main constituent of the keratohyalin substance in the granular layer, is a structural protein associated to filaments which are bound to keratin fibres in epidermal cells. Recent studies found that loss-of-function mutations in the gene encoding filaggrin, particularly the R501X and 2282de14 mutation, are

**1. Introduction** 

the cytokine pattern (5).

**2. Pathophysiology of AEDS** 

associated with the development of atopic dermatitis (8-10).

**to Diagnostic Approach** 

Nicola Fuiano1 and Cristoforo Incorvaia2 *1Paediatric Allergy Service, ASL Fg, Torremaggiore 2Allergy/Pulmonary rehabilitation, ICP Hospital, Milan* 
