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The Future of Precision Medicine in the Treatment of Atopic Dermatitis

The Future of Precision Medicine in the Treatment of Atopic Dermatitis

Biomarkers in AD
Biomarkers are best described as biologic indicators that link disease endotype with a phenotype. AD-specific biomarkers provide insights into pathogenesis of disease, help to stratify severity of disease, and can be used as targets to develop pathway-specific treatments.4 Despite the predominance of AD in childhood, current research primarily aims to identify biomarkers in adults. It is well known that pediatric and adult AD have different clinical profiles, including distribution of the affected skin areas, expression of TH22/TH17, and the fact that a significant percent of childhood AD does not continue into adulthood.8 This heterogeneity of AD and variations in immune profiles may be detected using biomarkers to separate the disease into different clinically relevant subtypes. In a recent study, noninvasive sampling with tape-stripping of the stratum corneum was performed and biomarkers, both previously reported and novel, were identified.8 The authors recommended further studies of these biomarkers, especially in early AD, as potential targets of predicting disease severity or comorbidities. Less invasive, cost-effective, simple, less time-consuming, and age-specific biomarkers are the most desirable.

Importance of the Skin Barrier in AD Prevention
Defects in proteins making up the epidermal skin, such as FLG, triglycerides, keratins, and loricrin, can lead to defects in the skin barrier, which can subsequently lead to increased exposure to allergens, sensitization, and finally a systemic allergic response. Transepidermal water loss (TEWL) is currently the most useful noninvasive marker of skin barrier function; patients with AD have an increased TEWL, which indicates a loss of integrity of their epidermal barrier. FLG deficiency in patients with AD contributes to the breakdown of the skin barrier, as the inflammatory threshold for irritants and haptens is reduced. TEWL can be a marker of current skin barrier disruption but also a predictive measure: TEWL at 2 days of age and 2 years of age foretold the development of AD at 1 year of age.9 Moisturizers, the cornerstone of daily management of AD, may also be preventive, as moisturizers have been shown to reduce the rates of AD development by decreasing rate of TEWL and maintaining a more intact epidermal barrier in susceptible individuals.9 By using simple, noninvasive measures such as TEWL and serum biomarkers to identify those individuals at risk for developing atopy, personalized medicine has the potential to become a prophylactic tool, helping to avoid the development of AD altogether.

The improved understanding of the pathophysiology of AD, development of biomarkers, and emergence of targeted therapies promises potential breakthroughs in the management and prevention of AD.

Inclusion criteria for trials investigating AD are based on disease severity rather than AD endotypes. To utilize precision medicine and optimize the response to targeted therapies, molecular, clinical, genetic, and epigenetic factors will need to be taken into consideration in future research trials. With the emergence of novel therapies from current clinical trials, dermatologists will be able to implement them into their clinical practice and switch from a generalized “one-drug-fits-all” approach to more personalized “patient-endotype-specific” management.

Dr Balogh is a research fellow at the Wake Forest School of Medicine, department of dermatology, Center for Dermatology Research, in Winston-Salem, NC. Ms Muradova is a medical student at University of South Florida, Morsani College of Medicine, in Tampa, FL. Dr Strowd is an assistant professor at the Wake Forest School of Medicine, department of dermatology.

Disclosure: Dr Strowd has received research, speaking, and/or consulting support from Galderma, Pfizer, Regeneron, Sanofi, and Actelion. The remaining authors report no relevant financial relationships.

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8. McAleer MA, Jakasa I, Hurault G, et al. Systemic and stratum corneum biomarkers of severity in infant atopic dermatitis include markers of innate and T helper cell-related immunity and angiogenesis. Br J Dermatol. 2019;180(3):586-596. doi:10.1111/bjd.17088

9. Kim BE, Leung DYM. Significance of skin barrier dysfunction in atopic dermatitis. Allergy Asthma Immunol Res. 2018;10(3):207-215. doi:10.4168/aair.2018.10.3.207

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