J Korean Med Assoc.  2014 Mar;57(3):218-225. 10.5124/jkma.2014.57.3.218.

Pathogenesis of atopic dermatitis

• Choi EH
• Yoon NY

• KMID: 2064878
• DOI: http://doi.org/10.5124/jkma.2014.57.3.218

Abstract

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with severe pruritus, and the first step of atopic march since it often precedes asthma or allergic rhinitis. Since its etiology or pathogenesis is very complex and frequently changing, physicians cannot easily understand it in entirety. New insights into the genetics and pathophysiology of AD emphasize the crucial function of the skin barrier as well as abnormal immune response. In this review, the pathogenesis of AD is explained as the combined features of impaired skin barrier and abnormal immune response rather than each independent concept. Understanding the whole pathogenesis of AD may lead to early intervention and prevention of atopic march as well as proper clinical treatment.

Keyword

Atopic dermatitis; Skin barrier; Hypersensitivity; Filaggrin; Thymic stromal lymphopoietin

MeSH Terms

Asthma
Dermatitis, Atopic*
Early Intervention (Education)
Genetics
Hypersensitivity
Pruritus
Rhinitis
Skin
Skin Diseases

Figure

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  Figure 1 Life cycle of filaggrin. Filaggrin exists as profilaggrin within keratohyaline granules in the granular layer of epidermis. It is degraded to filaggrin during the terminal differentiation process. Then, going up to the upper part of stratum corneum (SC), filaggrin degrades into amino acids and plays a crucial role in maintaining SC hydration and pH by forming natural moisturizing factor including pyrrolidone carboxylic acid or urocanic acid (From Choi EH, et al. J Skin Barrier Res 2013;15:13-23, with permission from Korean Society for Skin Barrier Research) [4].

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  Figure 2 Two main pathogenesis of dry skin in atopic dermatitis. First pathway is a reduced natural moisturizing factor (NMF) in the stratum corneum (SC) due to filaggrin deficiency which caused by inherited FLG mutation or lesional Th2 inflammation. Second is a decreased SC hydration as well as increased transepidermal water loss (TEWL) and epidermal proliferation due to disrupted SC intercellular lamellae which caused by deficiency of ceramide (esp, ceramide 1 having long chain) in SC. KC, keratinocytes.

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  Figure 3 Complex interaction among skin pH, filaggrin, serine protease and serine protease inhibitor in skin inflammation of atopic dermatitis (AD) patients. Acute barrier disruption in non-atopy healthy people induces serine protease (SP) activation transiently, but inhibited immediately with serine protease inhibitor (SPI), therefore reaches to barrier recovery (top blue dotted box). On the other hand, in the case of AD patients with SPINK5 or FLG gene mutation, uncontrolled SP activity could induce the activation of protease-activated receptor-2 (PAR-2), in turn thymic stromal lymphopoietin (TSLP) followed by aggravation cycle to skin allergic inflammation (bottom red dotted box). LB, lamellar body, LC, Langerhans cell.

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  Figure 4 Combined pathogenesis of atopic dermatitis including dysfunctions of skin barrier and immune response. Skin barrier is composed of corneocytes (brick), intercellular lipid lamellae (mortar) and corneodesmosomes (rivet) in stratum corneum and tight junctions in upper stratum granulosum. If these structures have inherited or acquired defect, exogenous allergens, microbes, or pollutants can easily penetrate skin barrier. And then abnormal responses of innate immune and adaptive system induce allergic inflammation in the patients with atopic dermatitis.

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