1. From: Darlenski et al. Exp Rev Dermatol 2011

2. Genetic background Epidermal barrier impairment Environmental factors Immunologic disturbances Bieber T. Curr Allergy Asthma Rep. 2009 Elias P. JID 2009 Atopic dermatitis

3. Epidermal barrier impairment Inflammation / itch Secretion of I inflammatory cytokines (IL-1, TNFα) by keratinocytes Penetration of irritants

4. Skin irritation in atopic dermatitis The increased use of detergents is one of the most common causes for the atopic dermatitis exacerbation (Meding B. Br J Derm 1987) Higher irritant susceptibility in atopic subjects ( Löfller H. Cont Derm 1999) The increasing prevalence of atopic dermatitis is most probably due to the increasing use of detergents nowadays (Cork MJ et al. JACI 2006, JACI 2009)

5. Controversy on contact sensitization in atopic dermatitis (AD) АД АD: Тh-2 ↔ contact allergy: Тh-1 Lower DNCB sensitization in AD (Rees J. Arch Dermatol 1990) Epidemiology data (Spiewak R. Ann Allergy Asthma Immunol 2005) Нарушената бариера улеснява пентрацията на хаптените Filaggrin mutations associated with contact allergy (Novak N et al. JID 2008) Epidemiology data (Klas P. Contact Derm 1996) AD = healthyAD↑ > healthy↓

6. Corneocyte Genetic factors Mutations in the genes encoding filaggrin and SC proteases Polymorphism in the IL-1; TNF-α genes Stratum corneum Irritant А А А А Secretion/synthesis of pro-inflammatory cytokines Increased expression of MHC molecules Increased expression of ICAM Increased skin permeability/penetration APC MHC ICAM А А Т Increased APC (Langerhans cells) density Irritation and sensitization in AD

7. Key issues Subjects with active atopic dermatitis (AD) show increased skin susceptibility to irritants, including subjective skin irritation (stinging) Epidermal barrier impairment could be the basis for the increased response of the skin to irritant stimuli in atopic subjects. Mucosal atopy most probably does not play a role in the exaggerated response to cutaneous irritants. Data on contact hypersensitivity in atopic subjects is controversial Filaggrin mutations are associated with contact allergy to nickel and particular types of hand dermatitis Patch testing should be routinely performed in atopic subjects; however, the result must be interpreted cautiously. Contact allergy to certain allergens is more common in atopic subjects. As AD is a disease that can be provoked by external factors (such as contact allergy), patch testing may be helpful in disclosing contact hypersensitivity as a factor worsening the course of AD. This, in turn, would result in different therapeutic implications, for example, allergen avoidance.