Are the concepts of induction of remission and treatment of subclinical inflammation in atopic dermatitis clinically useful?
Atopic dermatitis (AD) treatment is often initiated by symptoms or visible erythema. The role of induction of remission or treatment of inflammation that is not visible is unclear.
We investigated whether (1) the notion of subclinical inflammation is scientifically sound, (2) treatment corrects subclinical inflammation, and (3) different strategies for initial clearance of AD affect long-term disease control.
We conducted a systematic review based on searching MEDLINE, Embase, the Cochrane register of randomized controlled trials, and the Global Resource of Eczema Trials from inception to the end of October 2012.
Twenty of 26 included studies presented evidence of subclinical inflammation, with a continuum of changes in skin barrier dysfunction, the proinflammatory cytokine milieu, and lymphocytic infiltration from normal-appearing skin to posttreatment lesional skin to active skin lesions in patients with AD. Such subclinical inflammation is improved, with proactive treatment aimed at maintaining remission. Failure to achieve control of AD symptoms with initial therapy was associated with a higher risk of relapse in 14 randomized controlled trials (fluticasone: risk ratio, 1.31; 95% CI, 1.02-1.68; tacrolimus: risk ratio, 1.36; 95% CI, 1.12-1.66). Three trials on systemic therapy/phototherapy suggested that induction of remission resulted in long-term remission without maintenance therapy in approximately 15% of patients.
Induction of remission followed by maintenance therapy might prove to be an integral part of a disease-modifying strategy for treating atopic diseases.
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ABSTRACT: Moderate to severe forms of atopic dermatitis (AD) have a substantial impact on the quality of life of patients and their relatives, carrying a significant socio-economic burden. They often require a systemic therapy and ciclosporine A (CsA) is the only medicinal product approved for this indication in a limited number of European countries. However, due to the safety profile of CsA and its approval conditions, this treatment can only be prescribed for a limited period of time. Thus, moderate to severe forms of AD represent a significant unmet medical need and are subject to off-label prescriptions. Besides giving some insights into the approval procedures for medicinal products in the European Union, this short review is aimed to provide some relevant background information for off-label prescription in AD. It also provides a clinical algorithm for the off-label prescription of systemic immunosuppressants in AD, discusses the apparent dilemma between approval and guidelines, and finally suggests practical rules to be considered in the context of off-label prescription.This article is protected by copyright. All rights reserved.Allergy 07/2014; 70(1). DOI:10.1111/all.12498 · 6.00 Impact Factor
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ABSTRACT: Serum levels of thymus and activation-regulated chemokine (TARC/CCL17) have served as a reliable biomarker of disease progression of atopic dermatitis (AD). However, it remains to be scientifically explained why serum TARC levels correlate well with the degree of AD progression.Journal of Dermatological Science 08/2014; 76(2). DOI:10.1016/j.jdermsci.2014.08.009 · 3.34 Impact Factor
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ABSTRACT: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It often precedes the development of food allergy and asthma. Recent insights into AD reveal abnormalities in terminal differentiation of the epidermal epithelium leading to a defective stratum corneum, which allows enhanced allergen penetration and systemic IgE sensitization. Atopic skin is also predisposed to colonization or infection by pathogenic microbes, most notably Staphylococcus aureus and herpes simplex virus. Causes of this abnormal skin barrier are complex and driven by a combination of genetic, environmental, and immunologic factors. These factors likely account for the heterogeneity of AD onset and the severity and natural history of this skin disease. Recent studies suggest prevention of AD can be achieved through early interventions to protect the skin barrier. Onset of lesional AD requires effective control of local and systemic immune activation for optimal management. Early intervention might improve long-term outcomes for AD and reduce the systemic allergen sensitization that leads to associated allergic diseases in the gastrointestinal and respiratory tract.Journal of Allergy and Clinical Immunology 10/2014; 134(4):769–779. DOI:10.1016/j.jaci.2014.08.008 · 11.25 Impact Factor