Objectives: 1. To identify the loss of function mutations of genetic variants in the gene encoding filaggrin as a strong predisposing factor for AD
2. To identify the “brick and mortar” model and tight junctions role as epidermal barrier
3. To identify the progressive activation of TH2 and TH22 cytokines in AD
4. To review the concept of “outside-in” and “inside-out” hypothesis

Introduction: Atopic Dermatitis (AD) is a chronic, pruritic, inflammatory skin disease. It is one of the most common inflammatory skin disease in Malaysia. The prevalence of AD is estimated to be 15-25% of children & 3-7% of adults. In most patients, AD developed before the age of 5 and typically clears by adolescence. Primary symptom is pruritus (itch). About 20-30% of patients have moderate-to-severe disease

Materials / method: In 2006, 2 independent loss of function of genetic variants (R501X and 2282del4) in the gene encoding filaggrin (FLG) were found to be strong predisposing factors for AD. The gene, FLG, is located in the epidermal differentiation complex on chromosome 1q21. The epidermal barrier function is largely dependent on the stratum corneum (SC). In the stratum granulosum, keratinocytes produce keratohyaline granules (filaggrin, loricrin, keratin filaments) and Lamellar bodies (lipids, corneodesmosin, kallikrein). Tight junctions within the mid stratum granulosum (SG2) form the innermost line of defense

Results: Guttman showed in 2012 that there was marked activation of TH2 and TH22 immune pathways in acute phase of atopic dermatitis. The largest gene expression increases are associated with TH2- and TH22-associated products, including IL-31, IL-22, S100A7, S100A8, and S100A9. (Inside-out hypothesis). Skin barrier dysfunction and excessive immune responses are 2 sides of the same coin in AD pathogenesis. It may not matter which starts first but it is the immune dysfunction that perpetuates the phenotype toward chronic disease.

Conclusion: Atopic dermatitis is a complex disease with a genetic barrier defect as well as an immunologic defect involving Th2 and Th22 cells. Both play an important role in the pathogenesis of atopic dermatitis.

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