Article

Clinical practice. Atopic dermatitis

Center of Evidence-Based Dermatology, Queen's Medical Center, University of Nottingham, Nottingham, United Kingdom.
New England Journal of Medicine (Impact Factor: 54.42). 07/2005; 352(22):2314-24. DOI: 10.1056/NEJMcp042803
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    • "Conventional strategies for treatment of AD chiefly rely on local administration of a moisturizing agent and/or immunosuppressants as pallative care [37]. The former sustains and reinforces the barrier function of epidermal tissues, while the latter suppresses the activity of effector cells to stop inflammation. "
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    ABSTRACT: In the skin lesions of atopic dermatitis (AD), keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP), causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP. Expression of TSLP receptors in skin tissues and keratinocytes was assessed by immunohistochemistry and quantitative RT-PCR, and in vitro studies were also performed to examine the functional relevance of ΔNp63 in the expression of TSLP receptors and the constituting autocrine and/or paracrine pathway of TSLP under the condition of stimuli to innate receptors sensing cell damage. The results showed that normal keratinocytes in the upper epidermis preferentially expressed TSLP receptors and conversely lacked ΔNp63, which has an inhibitory effect on the expression of TSLP receptors. Interestingly, the epidermis of AD lesions was found to abundantly contain keratinocytes with low or undetectable levels of ΔNp63 (ΔNp63lo/-). Moreover, in the absence of ΔNp63, keratinocytes readily presented TSLP and other cytokines by stimuli through Toll-like receptor 3 (TLR3). Together with the evidence that extrinsic TSLP itself augments TSLP production by keratinocytes without ΔNp63, the results indicate that ΔNp63lo/- keratinocytes generate TSLP through a putative autocrine and/or paracrine pathway upon TLR3 stimulation within AD lesions, since moieties of damaged cells and pathogens stimulate TLR3.
    PLoS ONE 08/2014; 9(8):e105498. DOI:10.1371/journal.pone.0105498 · 3.23 Impact Factor
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    • "There is currently no cure for AD, so disease management is focused on trigger avoidance and alleviation of symptoms. First-line maintenance therapy includes nonpharmacological treatment with various emollients and skin barrier repair agents, which have been shown to improve skin appearance and dryness and/or to reduce the need for pharmacological treatment [1, 9]. When flares occur, anti-inflammatory agents are used to control the inflammatory aspects of the disease. "
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    ABSTRACT: Atopic dermatitis (AD) is an inflammatory skin disease commonly affecting children and managed by pediatricians, primary care physicians, allergists, and dermatologists alike. For many years, the only available topical pharmacological treatment was topical corticosteroids. This changed in 2000-2001, when topical formulations of two calcineurin inhibitors (tacrolimus and pimecrolimus) were approved for short-term or chronic intermittent treatment of AD in patients ≥2 years of age, in whom other treatments have been ineffective or contraindicated. These topical calcineurin inhibitors (TCIs) quickly became a popular treatment option due at least in part to concerns over adverse events associated with prolonged topical corticosteroid use, especially in children. However, based on theoretical concerns about a possible risk of lymphoma associated with TCI use, a Boxed Warning was placed on both products in 2006. Since then, despite an extensive body of evidence, no causal relationship has been demonstrated between TCI use and an increased risk of lymphoma; however, the US FDA has concluded that a link cannot be ruled out. In fact, based on post-marketing surveillance of spontaneous, literature, and solicited reports, we report here that the lymphoma incidence in the topical pimecrolimus-exposed population is up to approximately 54-fold less than that seen in the general US population. This review summarizes the mechanism of action of TCIs, the factors that prompted the Boxed Warning, and recent TCI safety and efficacy data. Based on these data, both topical corticosteroids and TCIs should have defined roles in AD management, with TCIs favored for sensitive skin areas (e.g., face) and instances where topical corticosteroids have proven ineffective, thereby minimizing the risk of adverse effects with both drug classes.
    Paediatric Drugs 04/2013; 15(4). DOI:10.1007/s40272-013-0013-9 · 1.72 Impact Factor
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    • "The disease is characterized mainly by the presence of dry itchy skin accompanied by chronic or relapsing eczema with an early onset primarily in individuals with a familial history of atopic disorders. In infancy, eczema typically develops on the face and scalp as well as on the extensor aspects of the arms and legs [2]; later in childhood flexural eczema occurs, whereas in adulthood skin changes are more often confined to the face and neck, as well as the hands, although some suffer from more widespread eczema [1]. In adults, hand eczema sometimes is the only symptom, which may however take a chronic course [3]. "
    The Open Allergy Journal 10/2012; 5(1):62-64. DOI:10.2174/1874838401205010062
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