From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine

Abstract

: Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD. Thus, early therapy of AD to restore the impaired skin barrier, modified microbiome, and target type 2 inflammation, depending on the (endo)phenotype, in a tailored approach is crucial. We discuss what we can learn from the comorbidities and the implications for preventive and therapeutic interventions from precision dermocosmetics to precision medicine. The stratification of AD patients into biomarker-based endotypes for a precision medicine approach offers opportunities for better long-term control of AD with the potential to reduce the systemic impact of a chronic skin inflammation and even prevent or modify the course, not only of AD, but possibly also the comorbidities, depending on the patient’s age and disease stage.

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

“…Categorization based upon biomarker endotypes could differentiate newborn, children, and adult atopic dermatitis patients into groups characterized by different biochemical forms of skin barrier dysfunction, immune dysfunction, and microbial dysbiosis. Thereafter, individualized therapy directed towards the specific abnormalities that each patient exhibits could be initiated [ 32 ].…”

“…In summary, atopic dermatitis has several immunologic pathways that contribute to its pathogenesis; hence, it should be an excellent candidate for the application of precision dermatology to provide targeted therapy for the individual patient. Similar to psoriasis, a machine-learning-based test could potentially be developed to predict the response to topical or systemic agents such as inhibitors of PDE4, IL-4, IL-13, IL-31, and JAK [ 25 , 32 ].…”

“…In atopic individuals, in addition to elevated immunoglobulin E and eosinophilic responses, the Th2 cytokines IL-4, IL-5, and IL-13 have a pathogenic role; also, IL-31 participates in dermatitis-associated pruritus. Non-immunologic components in atopic dermatitis pathogenesis include epidermal barrier dysfunction secondary to filaggrin deficiency and skin microbiome alterations [27][28][29][30][31][32].…”

Blockage of the IL-31 Pathway as a Potential Target Therapy for Atopic Dermatitis

“…Before initiating treatment-targeted strategies, our first step should include a detailed evaluation of the severity and extension of AD in order to establish a baseline disease burden [ 19 ]. Thus, early treatment strategies focused on the restoration of the skin barrier and microbiome and/or the targeting of Th2 inflammation, depending on the (endo)phenotype, is not only crucial for disease control but can also contribute to avoiding possible associated comorbidities and improvement in the quality of life of AD patients and their caretakers [ 20 , 21 ]. All these approaches together lead us to future opportunities for the patient to achieve an acceptable social, educational, and professional routine.…”

Skin-associated adipocytes in skin barrier immunity: A mini-review

“…As the largest organ and outermost layer of the human body, the skin serves as the first-line defense against various external pathogenic factors, including physical, chemical, and biological stresses, and plays a pivotal role in preventing dehydration. Maintenance of these functions relies primarily on a sound skin barrier; any functional or structural defect of the skin barrier may induce various skin diseases such as atopic dermatitis (AD) ( 1 ) and psoriasis ( 2 ). In addition to the skin physical barrier, which mainly consists of keratinocytes and their products, skin barrier immunity is also recently found to play an important role in maintaining integrity of skin barrier ( 3 ).…”