Connecting the Dots: From Skin Barrier Dysfunction to Allergic Sensitization, and the Role of Moisturizers in Repairing the Skin Barrier

June 2019 | Volume 18 | Issue 6 | Journal Article | 581 | Copyright © June 2019


Tamara Lazic Strugar MD,a Alyce Kuo BS,a Sophie Seité PhD,b Ma Lin MD PhD,c Peter Lio MDd

 

aIcahn School of Medicine at Mount Sinai, New York, NY

bLa Roche-Posay Dermatological Laboratories, Levallois-Perret, France

cBeijing Children's Hospital of Capital Medical University, China

dMedical Dermatology Associates of Chicago, IL

Abstract
The skin is one of the largest immunologic organs in the body and a continuous target for allergic and immunologic responses. Impairment of the skin barrier increases the likelihood of external antigens and pathogens entering and creating inflammation, which can potentially lead to skin infections, allergies, and chronic inflammatory diseases such as atopic and contact dermatitis. Functionally, the skin barrier can be divided into four different levels. From outermost to innermost, these highly interdependent levels are the microbiome, chemical, physical, and immune levels. The objective of this review is to provide an update on current knowledge about the relationship between skin barrier function and how dysfunction at each level of the skin barrier can lead to allergic sensitization, contact dermatitis, and the atopic march, and examine how to best repair and maintain this barrier through the use of moisturizers.

J Drugs Dermatol. 2019;18(6):581-586.

INTRODUCTION

The skin is one of the largest immunologic organs in the body and a continuous target for allergic and immunologic responses. Rising incidences of allergies have been reported worldwide. While the cause of this rise is not totally clear, it has been attributed to factors such as poor nutrition, stress, use of antibiotics, and growing up in clean urban homes while exposed externally to high air pollution.1-5 The skin barrier is the first interface between the environment and our immune system. This interface is constantly exposed to endogenous and exogenous factors including ultraviolet radiation, pollution, and damaging skincare products. Impairment of the skin barrier increases the likelihood of external antigens, irritants, and pathogens passing into the skin and driving inflammation, potentially leading to skin infections, allergies, and chronic inflammatory skin diseases such as atopic dermatitis (AD) and contact dermatitis (CD).6 This phenomenon has been referred to as “transcutaneous sensitization”, and is highly dependent on skin barrier dysfunction.7

Skin Barrier Anatomy
Anatomically, the skin barrier can be divided into the epidermis and the dermis. The epidermis primarily consists
of keratinocytes arranged in several layers, with the stratum corneum (SC) at the top, a layer of cornified keratinocytes that physically prevents invaders from entering. The dermis contains collagen and elastin fibers, fibroblasts, proteoglycans, and nerve endings. Functionally, the skin barrier can be divided into four strata: the microbiome, chemical, physical, and immune layers (Figure 1). The microbiome layer consists of living microbial communities. The chemical layer includes natural moisturizing factors (NMF), human β-defensins, and the acid mantle, which maintains an acidic surface pH.8 Tight junctions and the SC constitute important parts of the physical layer, which also produces some of the compounds of the chemical layer. Sensing danger signals through pathogen- and damage-associated molecular patterns, resident immune cells of the immune layer work to clear invasions, repair the barrier, and maintain homeostasis. While each layer has unique functions, it also works interdependently in upholding overall integrity of the skin barrier.9

The Skin Microbiota and Dysbiosis
Like the gut microbiota, the healthy skin microbiota is fairly stable.10,11 It is populated by commensal organisms including bacteria, viruses, fungi, and mites, with the Staphylococcus, Cutibacterium, and Corynebacterium genus dominating. It is thought that commensal bacteria regulate potentially pathogenic species. As the outermost layer, microbial communities are first responders to changes in the environment and transmit signals to the immune system.9,12 Dysbiosis, or disruption of balance in the microbiome layer, has been extensively studied in the context of AD, the first