Table 1. Pathogenesis and the Molecular Basis of Eczema.

 TEWL: transepidermal water loss, FLG: filaggrin, AD: atopic dermatitis, CLDN-1: Claudin-1, PCR: polymerase chain reaction, SNP: single nucleotide protein, TH2: T helper 2 cells, mRNA: messenger RNA, TJ: tight junction

Author (Year)	Purpose of Study	Study Characteristics	Outcomes and Results	Conclusions
Kelleher M et al., 2015 [10]	To see if a noninvasive evaluation of skin barrier function on the second day after birth and at two months predicts the onset of Atopic Dermatitis at one year. In addition, researchers wanted to see if increases in transepidermal water loss (TEWL) preceded the onset of clinical Atopic Dermatitis.	From July 2009 to October 2011, a total of 1903 newborns were enrolled in the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study. The TEWL was measured at birth (day 2), 2 months, and 6 months. At 6 and 12 months, the presence of AD was confirmed, and the severity of the condition was determined using the Scoring Atopic Dermatitis clinical instrument at 6 months and 12 months. A total of 1300 newborns had their FLG mutations genotyped.	18.7% of the children had AD at 6 months, and 15.53% at 12 months. In a logistic regression model, the day 2 upper quartile TEWL measurement was strongly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.81; P.05).	Clinical Atopic Dermatitis is preceded by a loss of skin barrier function at birth and at two months. These findings have implications for the best timing of therapies for the prevention of Atopic Dermatitis, in addition to offering crucial mechanistic insights into disease development.
Rodriguez E et al., 2009 [15]	To better refine FLG risk profiles within the broad and inclusive eczema diagnosis and to provide a more accurate estimation of FLG effect magnitude and also to get a more precise and clear estimation of the asthma risk associated with FLG null alleles.	meta-analysis	strong associations with eczema	FLG mutations confer a high eczema risk, and their risk profiles are refined, revealing a link with more severe diseases. Additionally, a significant risk factor for asthma, FLG mutations could help define the asthma endophenotype that is associated with eczema.
De Benedetto A et al., 2011 [19]	screened two American populations for single nucleotide polymorphisms in the claudin-1 gene and examined the expression/function of the TJ protein claudin-1 in epithelium from AD and nonatopic people (CLDN1).	Illumina's BeadChips were used to produce expression profiles of nonlesional epithelium from extrinsic AD patients, nonatopic individuals, and psoriasis patients. The use of tissue staining and quantitative PCR to confirm dysregulated intercellular proteins was used. In Using chambers, epithelial bioelectric characteristics were determined. Using a knockdown technique in primary human keratinocytes, the functional importance of claudin-1 was examined. In two separate groups with Atopic dermatitis, 27 haplotype-tagging SNPs in CLDN1 were examined.	Only patients with Atopic dermatitis had significantly lower expression of the TJ proteins claudin-1 and claudin-23, which was confirmed at the mRNA and protein levels. The expression of Claudin-1 was found to be inversely associated with TH2 biomarkers. They discovered a significant deterioration in the bioelectric barrier function in the epidermis of those with Atopic Dermatitis. They found that inhibiting claudin-1 expression in human keratinocytes reduces TJ function while increasing keratinocyte proliferation in vitro. Finally, CLDN1 haplotype-tagging SNPs in two North American groups found correlations with Atopic dermatitis.	Tight junction dysfunction contributes to barrier failure and immunological dysregulation in Atopic Dermatitis patients, and this may be mediated in part by claudin-1 decreases.