Atopic dermatitis (ATOD), also known as eczema, is a common chronic pruritic inflammatory skin disease with a strong genetic component. Onset typically occurs during the first 2 years of life (review by Soderhall et al., 2007).
... Atopic dermatitis (ATOD), also known as eczema, is a common chronic pruritic inflammatory skin disease with a strong genetic component. Onset typically occurs during the first 2 years of life (review by Soderhall et al., 2007). - Genetic Heterogeneity of Atopic Dermatitis Many inflammatory diseases, such as atopic eczema, are genetically complex, with multiple alleles at several loci thought to be involved in their pathogenesis. Several susceptibility loci for atopic dermatitis have been identified: ATOD1 on chromosome 3q21, ATOD2 (605803) on chromosome 1q21, ATOD3 (605804) on chromosome 20p, ATOD4 (605805) on chromosome 17q25.3, ATOD5 (603165) on chromosome 13q12-q14, ATOD6 (605845) on chromosome 5q31-q33, ATOD7 (613064) on chromosome 11q13.5, ATOD8 (613518) on chromosome 4q22.1, and ATOD9 (613519) on chromosome 3p24.
Atopic dermatitis commonly begins in infancy or early childhood (Kay et al., 1994; Taylor et al., 1984). Eighty percent of cases of ATOD have elevations of the total serum IgE (147050) concentration. The hallmarks of atopic dermatitis are ... Atopic dermatitis commonly begins in infancy or early childhood (Kay et al., 1994; Taylor et al., 1984). Eighty percent of cases of ATOD have elevations of the total serum IgE (147050) concentration. The hallmarks of atopic dermatitis are a chronic relapsing form of skin inflammation, a disturbance of epidermal barrier function that culminates in dry skin, and IgE-mediated sensitization to food and environmental allergens. Bieber (2008) reviewed the natural history of ATOD. The new occurrence of inflammatory diseases after organ transplantation suggests that genetic predisposition may be confined to the particular organs or physiologic systems. A new occurrence of asthma after bone marrow transplantation from a donor who had asthma (Agosti et al., 1998) or new asthma in a recipient who had lungs transplanted from an asthmatic donor (Corris and Dark, 1993) suggests that expression of some inflammatory disorders is a result of both systemic (often immune) influence and end-organ specificity, each under distinct genetic control. Turner et al. (1998) described an 18-year-old woman who had had an intensely itchy rash on her right leg since childhood. There were no exacerbating factors. Her itch improved with sunlight. Topical corticosteroids gave only a small benefit. The patient also had hayfever, but was otherwise well. Her eczema was in an uninterrupted distribution down the inner aspect of her right leg in a pattern of Blaschko described by Jackson (1976) and thought to be the path of migration of a clone of embryonic keratinocytes. Histology of a biopsy specimen showed features typical of eczema and supported a diagnosis of linear eczema (dermatitic nevus). The rest of her skin was normal. She was found to be atopic with multiple positive prick tests (on normal skin), including house dust mite, feathers, and grass, and a raised IgE of 308 IU. In this patient, Turner et al. (1998) suspected that an aberrant clone of cells with either genetic (or epigenetic) change allowed expression of the atopic eczema phenotype in the mutated area only. As conventional treatments were largely unsuccessful and the area of involvement was small, Turner et al. (1998) excised the most itchy area of skin on her thigh as split skin. This produced only transient relief. Full skin thickness was excised from another area, and grafted with split skin from a donor area on her thigh. She had lasting relief for 6 years, although the itch persisted in her untreated skin.
Soderhall et al. (2007) analyzed the ATOD1 candidate gene COL29A1 in 46 unrelated children with atopic dermatitis and 2 controls and identified 13 common and 6 rare sequence variations causing nonsynonymous amino acid substitutions. All coding SNPs were ... Soderhall et al. (2007) analyzed the ATOD1 candidate gene COL29A1 in 46 unrelated children with atopic dermatitis and 2 controls and identified 13 common and 6 rare sequence variations causing nonsynonymous amino acid substitutions. All coding SNPs were genotyped in 199 ATOD families originally studied by Lee et al. (2000); 4 SNPs showed a positive association with ATOD, but that association did not account for the previously observed haplotype association. In situ hybridization and immunohistochemical analysis of normal human skin detected COL29A1 expression in the epidermis with strongest staining in suprabasal viable layers. However, in situ hybridization of the skin of patients with ATOD demonstrated an absence of COL29A1 expression in the most differentiated upper spinous and granular layers, although overall COL29A1 expression levels remained the same between patients and controls. Soderhall et al. (2007) concluded that ATOD patients displayed an abnormal distribution of COL29A1 mRNA and protein in skin and suggested that COL29A1 is involved in the pathogenesis of ATOD. Among 100 patients with atopic dermatitis and 264 controls, Vasilopoulos et al. (2007) observed an association between risk for ATOD and a 344C-T SNP in the CSTA gene (184600) on 3q21 (OR = 2.13, p = 0.006). The C allele was more common among patients, indicating that the T allele may offer a protective effect. In vitro functional expression studies showed that the 344C allele produced mRNA that was 2.2-fold less stable than the 344T mRNA. Vasilopoulos et al. (2007) noted that since CSTA is a cysteine protease inhibitor of dust mite proteases that breaks down epidermal barriers, a decrease in CSTA mRNA may contribute to a defective epidermal barrier among patients with atopic dermatitis.
Atopic dermatitis is one of the most common diseases in childhood, affecting 10 to 20% of children in industrialized societies (Beasley and The International Study of Asthma and Allergies in Childhood Steering Committee, 1998).