Approaching Atopic Dermatitis Treatment Differently: From Skin Barrier Preservation to Allergen-Specific Immunotherapy

Abstract

AD & skin barrier dysfunction Under normal conditions, skin provides an effective barrier between the organism and the environment, preventing the invasion of pathogens and blocking chemical and physical assaults, as well as controlling and tuning water and solute loss [13]. Skin barrier alterations in AD have been extensively described by Elias and Schmuth [14]. Alteration in skin barrier function plays a major role in the pathogenesis of AD [15]. A deficit in lipid components (i.e., ceramide) has been described in AD. A deficit in filaggrin synthesis has been demonstrated in up to 30% of AD patients [16]. Filaggrin is crucial for efficient hydration of the skin [17]. The antimicrobial barrier is also compromised in AD. This alteration could favor colonization of lesional and non lesional skin by Staphylococcus aureus. In fact, in AD, in contrast to psoriasis, a reduced synthesis of antimicrobial peptides has been observed [18]. This alteration of a component of innate immunity could be one of the mechanisms responsible for the increased incidence of bacterial skin infections observed in AD patients. AD is characterized by dry skin, even skin that is nonlesional. In addition, AD is characterized by an increase in trans epidermal water loss [19]. In healthy skin, the ceramide complex, an important component of the skin barrier, serves as the major water-retaining molecule in the extra cellular space of the cornified stratum, contributing to a normal hydration of the skin. The barrier function of these complex structures is provided by a matrix of structural proteins, which are bound to ceramides [20]. A normal and efficient skin barrier is essential in order to prevent or reduce the penetration of allergens, micro-organisms and irritants. For this reason, a restoration of altered skin barrier Atopic dermatitis (AD) is a common inflammatory, itching skin disease [1]. Epidemiological studies show that one in every four children suffers from AD. In addition, 3% of the adult population are affected worldwide [2]. The clinical picture of AD is dominated by chronic eczematous skin lesions in typical localizations [3]. Itchy skin and rashes are the most common symptoms of AD. Skin lesions are often observed on the face, inside the elbows and behind the knees, and on the hands and feet [4]. Furthermore, clinically unaffected skin in AD is abnormal. In fact, skin is frequently dry and shows a greater response to irritants than normal healthy skin [5]. Microscopic studies reveal a perivascular T-cell infiltrate in unaffected AD skin that is not seen in normal healthy skin [6]. There is a marked infiltration of activated CD41 memory T cells in acute AD [7]. APCs in lesional and nonlesional skin bear IgE molecules [8]. Mast cell degranulation can be observed. Eosinophil cells can also contribute to the inflammatory condition. In the chronic phases of the disease T cells remain present, although in smaller numbers than seen in acute AD [9]. Chronic AD skin lesions undergo tissue remodelling caused by chronic inflammation. Although AD may occur at any age, it most often begins in infancy and childhood. The etiology of AD remains unknown so far, but the disease seems to be a result of a combination of genetic and environmental factors [10]. Children are more likely to develop this disorder if their mother or father, or both, have had AD or have had other allergic conditions such as allergic rhinitis or asthma [11]. While some people outgrow skin symptoms, approximately three-quarters of children with AD go on to develop hay fever or asthma in the following years [12].