MedicalResearch.com Interview with: Adam Friedman, MD, FAAD Associate Professor of Dermatology Residency Program Director Director of Translational Research Department of Dermatology George Washington School of Medicine and Health Sciences Medical Research: What is the background for this study? What are the main findings? Dr. Friedman: Given pruritus is not only a hallmark symptom of atopic dermatitis, and in fact is even part of the diagnostic criteria, we sought to evaluate whether factors known to cause itch or inhibit said pruritogens in other disease states are over or under expressed in skin from patients diagnosed with atopic dermatitis. Over the past 10 years considerable attention has been paid to the complexity of the immune dysregulation and plethora of inflammatory and neurogenic factors involved in the activity and progression of this disease. Our study showed significant differences between atopic dermatitis skin and normal skin.  Specifically, we found significantly elevated levels of several well-known components of both the inflammatory and pruritus cascade including interleukin-2, BLT1 (the receptor for leukotriene B4, recently implicated in atopic dermatitis), 5-lipoxygenase and Matrix Metalloproteinase-7.  Interestingly, for the first time to our knowledge, α-2 macroglobulin, a ubiquitous protein found in the skin that binds a host of proteases, growth factors (TGF-b, PDGF, b-NGF) and inflammatory cytokines (TNF-α, IL-1b, IL-2, IL-6, IL-8), was found to be significant unregulated in atopic skin. Because it has a known an important role in the modulation of inflammation, as its binding acts to inhibit the majority of these mediators, this overexpression may in fact be a compensatory mechanism for ongoing disease. Importantly, when activated through chloramination by, for example, bleach, it can very effeectively scavenge these pro-inflammatory mediators. Thus leading to the second goal of this study. One of the driving forces for selecting the various "itch or anti-itch factors" is that all can be augmented by hypochlorous acid, which is what bleach disassociates into when mixed with water. Bleach baths have been used for years as an adjuvant to treatment in atopic dermatitis.  When mixed with water, sodium hypochlorite (NaOCL) produces hypochlorous acid (HOCl), a compound stable between pH 3 and 6. HOCl is known to have antimicrobial properties, and therefore it was believed that bleach baths lowered bacterial burden on the skin and prevented and treated localized skin infections and colonization by organisms such as Staphylococcus aureus. Recent studies have found that HOCl intact has potent anti-inflammatory properties, and therefore we sought to expand this data by evaluating whether factors augmented by HOCl are overexposed in atopic dermatitis skin, giving some insight into how bleach bathes or HOCl products may aid in disease and symptom management. (more…)

MedicalResearch.com Interview with: Emma Guttman-Yassky, MD, PhD Department of Dermatology Icahn School of Medicine at Mount Sinai Medical Center New York, NY 10029 Medical Research: What is the background for this study? What are the main findings? Dr. Guttman-Yassky: Atopic dermatitis/AD is the most common inflammatory skin disease. Increased knowledge about the molecular phenotype of atopic dermatitis has contributed to development of novel therapeutics, including trials with targeted therapeutics. Genomic skin data from these trials largely rely on microarrays that are based on hybridization of labeled RNA/cDNA to single stranded DNA sequences that translate to expression levels. We have recently shown that the atopic dermatitis transcriptome (defined as differentially expressed genes [DEGs] between lesional and non-lesional skin) is reversible with broad and specific therapeutics. For future mechanistic studies within clinical trials, it is important to determine the agreement between microarrays and RNA-seq and to evaluate whether RNA-seq offers additional benefits. This is the first report of the lesional atopic dermatitis phenotype by RNA-seq, and the first direct comparison between the microarray and RNA-seq platforms in this disease. Both platforms robustly characterize the AD transcriptome. Through RNA-seq, we unraveled novel atopic dermatitis disease pathology, including increased expression of the novel TREM-1 signaling pathway and IL-36 cytokine, which might have a pathogenic role in atopic dermatitis. Importantly, good agreement with real time PCR, which serves as the "gold standard" for detection of gene expression was observed for both technique. Overall good agreement was observed with RT-PCR for both RNA-seq and microarrays, but key atopic dermatitis immune cytokines (such as interleukin 13, and interleukin 22), which are highly elevated in atopic dermatitis lesions were only detected by RT-PCR. Overall, both RNA-seq and microarrays can similarly characterize the lesional AD transcriptome and serve as valuable tools for molecular tissue studies within large clinical trials and a core atopic dermatitis pathology is common to microarray and the RNA-seq transcriptomes. RNAseq might play a complementary role for unravelling novel disease pathology, although analyses tools for RNAseq are still being developed. (more…)