Prospective, Randomized, Double Blind Comparative Study on the Use of Two Creams in Xerosis Atopic Probands Biomedical Findings With Vitreoscilla Filiformis

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease and often coexists with other atopic diseases, such as allergic rhinitis, conjunctivitis and asthma (Biedermann and Röcken 1999, Biedermann et al. 2001, 2004, 2006; Leung et al., 2000, 2003a, 2003b). Even though the immune pathology of AD is not precisely understood, today the new concept of atopic dermatitis pathology is based on a large set of data. In most patients with AD, dry skin and dysfunction of the epidermal barrier is found. As an important prove of concept, the loss of function mutation of the epidermal protein filaggrin impairing skin barrier function was found and can be detected in about 15% of kaukasian AD patients (Palmer et al., 2006). As a consequence, patients with AD are predisposed to develop sensitizations dominated by a Th2 immune phenotype (Hudson, 2006).

Independently of the filaggrin study, it was demonstrated earlier that a disrupted barrier function of the stratum corneum is present in atopics not only in involved skin, but also in uninvolved dry skin facilitating permeation of various environmental substances into the skin (Berardesca et al., 1990; Werner et al., 1985; Watanabe et al., 1991; Loden et al, 1992). As a biomarker, an increased level of transepidermal water loss (TEWL) can be demonstrated (Tagami et al., 1985; Ghadially et al., 1996). Various functional and morphological studies on atopic xerosis that clinically appeared without inflammation demonstrated that cellular inflammation is already present in atopic skin and a key and initial step in the development of atopic dermatitis (Watanabe et al., 1991; Uehara et al., 1984). In fact, barrier dysfunction, atopic immune dysregulation, and atopic dermatitis pathogenesis are not independent events, but closely linked (Biedermann 2006; Hudson 2006). Th2 lymphocytes dominate the atopic immune phenotype and are the underlying cell type responsible for the induction if IgE antibodies (Biedermann et al. 1999, 2004). Barrier dysfunction predisposes for the development of Th2 lymphocytes and Th2 cells are the first cell type invading atopic skin initiating inflammation and the inflammatory vicious circle of inflammation (Biedermann 2002; 2004; Lametschwandtner et al. 2004; Günther et al. 2005). Next to Th2 lymphocytes, in atopic dermatitis skin lesions, infiltrates of eosinophils and cells of the mononuclear phagocyte lineage are found.

The altered skin structure of people with atopic predisposition allows increased penetration of allergens and irritative substances (Roll et al., 2004; Hudson 2006). Many studies have shown that the extent of S. aureus colonization correlates with AD disease activity (Cho et al., 2001; Biedermann 2006). In more than 90% of AD patients, a massive skin colonization with S. aureus (up to 107cfu/cm2 of lesional skin) can be found (Matsui et al., 2000). A prerequisite for bacterial colonisation are the genuine barrier dysfunction, mechanical disruption of the barrier and trigger of inflammation (scratching), alkaline pH, decreased IgA secretion through sweat production, predominant Th2 cells inhibiting anti-infectious immune responses, and reduced antimicrobial peptides, all representing important pathophysiological features leading to the disruption of the primary skin defense system (Biedermann et al. 2001; Biedermann&Röcken 2001,; Biedermann et al. 2002; Biedermann 2006; Howell, 2005; Rieg 2005).

Among several microbes colonising the skin, the bacterium Staphylococcus aureus (S. aureus) may play the most important role in the pathogenesis of dermatitis of atopic people (Biedermann 2006). This colonization is observed not only in the involved inflammatory skin but also in the non involved dry skin. The ratio Staphylococcus aureus / Staphylococcus epidermidis is inverse in comparison to healthy skin. Many studies have shown that the extent of S. aureus colonization correlates with AD disease intensity (Cho et al., 2001).

Reduced expression of antimicrobial peptides was demonstrated for AD skin and favours colonization with S. aureus (Ong et al. N. Engl. J. Med. 2002; Howell et al.. Immunity. 2006;24:341-8; Rieg et al. JI 2006). In addition, dry skin may by itself allow colonization with bacteria such as S. aureus. Decreased levels of sphingosine, which has antimicrobial properties and the fact that S. aureus itself stimulates the hydrolysis of ceramides by bacterial derived ceramidase in atopic skin add the dysfunction of the immune barrier in AD (Arikawa et al., 2002; Kita et al, 2002). The cell membrane of S. aureus contains adhesins for epidermal and dermal laminin and fibronectin allowing attachemment of S. aureus. to the skin and these docking positions for S. aureus are uncovered in lesional skin (Cho et al, 2001). The precise mechanism by which S. aureus gains access to the dermis is unknown, but it is suggested that again IL-4, produced by T helper type 2 cells, induces fibronectin synthesis, which in combination with plasma exsudation of fibrinogen, allows S. aureus to bind to the skin. Moreover, S. aureus is able to encase itself in a kind of biofilm composed of a hydrated matrix of polysaccharides (glycocalix) and proteins, which supports cell adhesion (Akiyama et al., 2003). After colonization, S. aureus contributes to skin inflammation e.g. by secreting toxins and an array of so called pathogen associated molecular pattern (PAMP) that bind their pathogen recognition receptors such as Toll- like receptors and directly triggering inflammation (Biedermann 2006). Moreover, S. aureus PAMPs also influence T cell mediated skin inflammation by indirectly regulating skin homing of T cells and orchestrating chronic inflammation in AD skin (Biedermann 2006; Biedermann et al. 2006).