Journal of Dermatitis

The Impact of Microanatomy and Changing Physiology of Stratum Corneum the Skin Barrier, on Evolution of Atopic Dermatitis

Virendra N Sehgal^* Department of Dermato Venereology (Skin/VD) Center, Sehgal Nursing Home, Panchwati-Delhi, India
^*Correspondence: Virendra N Sehgal, Department of Dermato Venereology (Skin/VD) Center, Sehgal Nursing Home, India, Tel: 91-11-2767-0373, Fax: 91-11-2767-0373, Email: ,

Received: 04-May-2018 Published: 09-Jan-2019

Introduction

Atopic Dermatitis (AD) is a pre-eminent age oriented entity with a continuous clinical spectrum ensuing in infancy, to March to childhood, adolescent, adult and senile/elderly [1] characterize by pruritus, with or without lichenification and xerosis. The entity has been in the reckoning ever since its inception, and is a matter of an intriguing dialogue, especially for its etio-pathogenesis, which has thus far been largely speculative. The emergence of stratum corneum, a formidable skin barrier, as a target tissue has added refreshing dimensions in the on-going research to find plausible explanation for the sequence of events in AD. A substantive work on its micro-anatomy [2,3] and related physiological components/changes (Figure 1) is startling [4].

Figure 1. Diagrammatic display of stratum corneum, granular layer, spinous layer, basal cell layer with their respective proteins configuration.

Graphic is displaying the layers of epidermis and their proteins configuration. The accumulated data thus far seems conducive. In fact, the current status is directionally accrued to offer adequate work job for continuing research, and endeavour to provide an impetus is made, in the following text.

Microanatomy and Physiology of Stratum Corneum

Stratum corneum, the horny layer [1] (latin) is a fascinating, outermost layer of the epidermis [2,3] stratum lucidum, stratum granulosum, stratum spinosum and stratum basale are its other layers. Stratum corneum is formed by 15-20 layers of flattened dead cells with no nuclei (anucleated) and organelles; the corneocytes (Figure 2) their cytoplasm contains birefringent filamentous scleroprotein, the keratin.

Figure 2. Microanatomy of stratum corneum depicting the layers of epidermis. It is composed of three lipid components: Ceramides, Cholesterol, and fatty acids.

It forms a formidable barrier to protect underlying tissue(s) from Infection; Dehydration; Chemicals and Mechanical stress.

Desquamation, the process of cell shedding, is a regular feature for balancing the proliferating keratinocytes that are formed in the stratum basale. These cells have the potential to migrate through the epidermis towards the surface, which may take about 14 days for the process to complete.

The advent of stratum corneum [5], an impeccable skin barrier, has emerged as a prime factor in the evolving pathogenesis of the atopic dermatitis. The skin barrier functions6 emanate from the sequence of events namely:-

• Transformation of living keratinocytes to non-living corneocytes.

• Cell membrane is replaced by a layer of ceramides covalently linked to structural proteins, the cornified envelope, surrounding the cells in the stratum corneum [6].

• Thus, facilitating cellular adhesion with adjacent cells in the epidermis by the modified desmosomes.

• The complexes thus formed are degraded by proteases, permitting cell to be shed. Hence, desquamation as well as cornified envelope are its essential pre-requisite [7,8]. Furthermore, up-regulation of serine protease activity may cause adverse structural changes in consequence to degradation of certain proteins, which are the part component of epidermal structure and its functions, thus interfering in the formation of the stratum corneum intercellular lipid membrane, regulating epidermal water flux and gradient, resulting in induction of TH2 (Subset Type pattern) of inflammation, the hallmark profile of atopic skin. Therefore mentioned formulation supplemented by alteration in lipid ratios and changes in lipid-directed enzymes may play a decisive role in the impairment of barrier functions, associated with atopic dermatitis.

• A dense network of keratin, a protein forming the cells of stratum corneum, helps keep the skin hydrated by preventing water evaporation and also by absorbing water. It possesses ‘spring back’ or stretchy properties, a weak glutenous protein bond pulls the skin back to its natural shape.

Filaggrin

Filaggrin [9], filament aggregating protein, is a unique filament-associated protein that binds to keratin fibers in epithelial cells. 10 to 12 filaggrin units are post-translationally hydrolized from a large pro-filaggrin precursor protein during terminal differentiation of epidermal cells. Thus, filaggrin is a key protein that facilitates terminal differentiation of the epidermis, and formation of the skin barrier. Besides, it’s specifically contributes to its physical strength, hydration status, skin pH, and buffering capacity among other physio-chemical properties. Impairment or loss of functions of filaggrin, the epidermal barrier protein is, therefore, a major pre-disposing factor in the pathogenesis of AD. In humans, pro-filaggrin is encoded by the FLG gene, which is part of the S100 fused-type protein (SFTP) family within the epidermal differentiation complex on chromosome 1q21 [10,11].

Filaggrin, is a key component of the stratum corneum that is derived from a larger precursor protein and contributes to its physical strength, hydration status, skin pH, and buffering capacity among other physio-chemical properties [12].

Glimpses into the structure and function of stratum corneum, the skin barrier is a salient overture for comprehending the upheaval in it functions in atopic dermatitis, in particular. It is, therefore, relevant to recall its clinical presentations namely; early age of onset, atopy, personal and/or family history, Immunoglobulin E reactivity and xerosis [13]. Moreover, AD seem to possess a clinical spectrum span from infantile, childhood, adolescent, adult and senile (elderly), xerosis being the common denominator with or without lichenification [1].

Currently, it is classified into Extrinsic atopic dermatitis (eAD ) [14] IgE associated allergic atopic dermatitis, and Intrinsic atopic dermatitis (iAD) non-allergic atopic eczema/dermatitis syndrome (AEDS) [15] The former have elevated Th2- and decreased Thl-expressing cells in the peripheral blood, with elevated interleukin, IL-4 and IL-13 expression. AD seems to be controlled by genetic factors [16]. The Immune System [17] and its dysfunction [18] is a subject of intriguing investigation, and is sequentially recounted; IgE Interactions between IgE-bearing antigen-presenting cells, T-cell activation, mast-cell degranulation, keratinocytes, eosinophils, and a combination of immediate and cellular immune responses are the hallmark of extrinsic atopic dermatitis (eAD) [19] Moreover, Inflammatory dendritic epidermal cells, a distinct dendritic cells population, could induce the Th2. It is, therefore, worthwhile to name genetic disorders which may have pre-disposition to hay fever, allergic rhinitis, bronchial asthma, including atopic dermatitis the atopic-diathesis. Pre-eminent amongst them are Agammaglobulinemia/X-linked hypogammaglobulinemia (XLA) [20] (X-linked recessive), Anhidrotic ectodermal dysplasia [21,22] (X-linked recessive), Cystic fibrosis(CF) [23-25] (Autosomal recessive), Hurler's syndrome [26] (Autosomal recessive), Hyper IgE syndrome (HIES) [27] (Autosomal dominant or autosomal recessive), Netherton's syndrome [28] (Autosomal recessive), Wiskott-Aldrich syndrome/thrombocytopenia [29], (X-linked recessive), and Down syndrome(DS,DNS) trisomy21 [30] (Autosomal dominant, Autosomal recessive).

Topical Therapy, Evolving Scenario’s Application in Day-to-Day Practice

Although, several treatment options are in vogue, its treatment continues to loom large, because its etiopathogenesis is largely seem to be enigmatic [31,32] nevertheless, the endeavors to unfold it are relentlessly continuing. The advent of stratum corneum [31-33] the impeccable skin barrier has taken the central stage. Accordingly, its micro-anatomy (structure) and physiology (function) has added refreshing dimensions. The alterations in its patho-physiology have been a definitive step forward, enshrining the role of flaggrin [34] and serine proteases [35] in particular. The changing pattern in the former may impede its physical strength, hydration status, skin pH, and buffering capacity amongst other physio-chemical properties. Filaggrin [36,37], the epidermal barrier protein is, therefore, a major pre-disposing factor in the pathogenesis of AD. In addition, up-regulation of serine protease activity may cause adverse structural changes due to degradation of certain proteins, the part component of epidermal structure and its functions, thus interfering in the formation of the stratum corneum intercellular lipid membrane, regulating epidermal water flux and gradient, resulting in induction of TH2 (Subset Type pattern) of inflammation. Simultaneous, immune system [38] and its dysfunction through IgE mediated sequence of events capped by genetic [39] undertones may initiate and/or perpetuate the clinical expression of AD. Hence, the preceding rumblings responsible for the clinical connotation of AD, may bring to the fore newer modalities to counter the intricate often difficult to treat condition. Thus, atopic dermatitis treatment envisages [40]

Eliminating inflammation and infection; Hydrating the skin; Controlling pruritus, and Avoiding exacerbative factors.

Addition of moisturizer to a low-potency corticosteroid lotion in separate regimens is effective in treating the signs and symptoms of mild-to-moderate atopic dermatitis [40,41].

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