Background-Bacterial infection with Staphylococcus aureus is a known trigger for worsening of atopic dermatitis (AD); the exact mechanisms by which bacterial infection worsens dermatitis are unknown.

Although platelet-activating factor (PAF) is a well-known acute inflammatory mediator, little is known regarding the role of PAF in chronic inflammation. Phorbol esters are known to stimulate PAF production. Moreover, the ability of repeated applications of phorbol esters to induce a sustained inflammatory response is crucial to their tumorigenic activity. We therefore examined whether PAF acts as a mediator of phorbol ester-induced inflammation and tumorigenesis. While PAF receptor knockout mice (PAFR(-/-)) showed an expected but modest reduction in the acute inflammatory response to phorbol 12-myristate 13-acetate (PMA), these mice exhibited a surprising increase in inflammation following chronic PMA application. This increased inflammation was documented by a number of findings that included: increased skin thickness, increased myeloperoxidase activity and expression and increased expression of known inflammatory mediators. Interestingly, vehicle-treated PAFR(-/-) mice also exhibited modest increases in levels of inflammatory markers. This suggests that the platelet activating factor receptor (PAFR) acts to suppress chronic inflammation in response to other stimuli, such as barrier disruption. The idea that chronic PAFR activation is anti-inflammatory was documented by repetitive topical PAFR agonist administration that resulted in reduced myeloperoxidase activity in skin. We next utilized a 7,12-dimethylbenz(a)anthracene/PMA carcinogenesis protocol to demonstrate that PAFR(-/-) mice exhibit significantly increased tumor formation and malignant progression compared with wild-type control mice. These studies provide evidence for two important, unexpected and possibly interrelated pathological roles for the PAFR: first, the PAFR acts to suppress PMA-induced chronic inflammation; secondly, the PAFR acts to suppress neoplastic development in response to chemical carcinogens.

Background/Objectives Patients with atopic dermatitis (AD) are predisposed to infection with Staphylococcus aureus which worsens their skin disease; it has been postulated that the relative lack of antimicrobial peptides due to aberrant allergic inflammation in AD skin could mediate this enhanced bacterial susceptibility. We sought to characterize the amounts of S. aureus and biological products found in infected AD lesions and whether treatment with topical corticosteroids and oral cephalexin as only antimicrobial improved outcomes. Methods 59 children with clinically and S. aureus-positive impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically using the Eczema Area and Severity Index, and wash fluid was obtained from the lesion for quantitative bacterial culture and antibiotic sensitivities, and measurement of bacterial products and cytokines. Subjects were re-evaluated two weeks following treatment. Results Improvement in the clinical and inflammatory characteristics of impetiginized lesions were noted, even in the 15% of lesions infected with MRSA. In a subgroup of subjects whose lesions did not contain S. aureus two weeks after initiating treatment, beta-defensin levels were elevated at both visits in comparison to normal skin. Conclusions These studies indicate that treatment of uncomplicated impetiginized pediatric AD with topical corticosteroids and the antibiotic cephalexin results in significant clinical improvement, even in subjects infected with MRSA. We propose that the inhibition of abnormal inflammation by the treatment regimen resulting in the increased relative levels of defensins is involved in the improvement of AD, and that systemic antibiotics do not appear to be necessary in secondary impetiginized AD.

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SummaryBackground-Bacterial infection with Staphylococcus aureus is a known trigger for the worsening of atopic dermatitis (AD). Staphylococcal superantigens have been theorized to potentially contribute to this worsening of AD seen with infection.