Long‐term reduction in local inflammation by a lipid raft molecule in atopic dermatitis

Dölle, Sabine; Hoser, Dana; Rasche, Claudia; Loddenkemper, Christoph; Maurer, Marcus; Zuberbier, Torsten; Worm, Margitta

doi:10.1111/j.1398-9995.2010.02341.x

Cited by 19 publications

(15 citation statements)

References 35 publications

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“…215 This part industry-sponsored within-person trial by Dolle and colleagues 215 compared a solution containing miltefosine against a hydrocortisone solution for 3 weeks. The dose for both treatments was gradually increased from two drops per lesion once a day for the first week to two drops per lesion twice a day for the second and third weeks.…”

Section: Studiesmentioning

confidence: 99%

Scoping systematic review of treatments for eczema

Nankervis

Kim

Delamere

et al. 2016

Programme Grants Appl Res

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BackgroundEczema is a very common chronic inflammatory skin condition.ObjectivesTo update the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) systematic review of treatments for atopic eczema, published in 2000, and to inform health-care professionals, commissioners and patients about key treatment developments and research gaps.Data sourcesElectronic databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Skin Group Specialised Register, Latin American and Caribbean Health Sciences Literature (LILACS), Allied and Complementary Medicine Database (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the end of 2000 to 31 August 2013. Retrieved articles were used to identify further randomised controlled trials (RCTs).Review methodsStudies were filtered according to inclusion criteria and agreed by consensus in cases of uncertainty. Abstracts were excluded and non-English-language papers were screened by international colleagues and data were extracted. Only RCTs of treatments for eczema were included, as other forms of evidence are associated with higher risks of bias. Inclusion criteria for studies included availability of data relevant to the therapeutic management of eczema; mention of randomisation; comparison of two or more treatments; and prospective data collection. Participants of all ages were included. Eczema diagnosis was determined by a clinician or according to published diagnostic criteria. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. We used a standardised approach to summarising the data and the assessment of risk of bias and we made a clear distinction between what the studies found and our own interpretation of study findings.ResultsOf 7198 references screened, 287 new trials were identified spanning 92 treatments. Trial reporting was generally poor (randomisation method: 2% high, 36% low, 62% unclear risk of bias; allocation concealment: 3% high, 15% low, 82% unclear risk of bias; blinding of the intervention: 15% high, 28% low, 57% unclear risk of bias). Only 22 (8%) trials were considered to be at low risk of bias for all three criteria. There was reasonable evidence of benefit for the topical medications tacrolimus, pimecrolimus and various corticosteroids (with tacrolimus superior to pimecrolimus and corticosteroids) for both treatment and flare prevention; oral ciclosporin; oral azathioprine; narrow band ultraviolet B (UVB) light; Atopiclair™ and education. There was reasonable evidence to suggest no clinically useful benefit for twice-daily compared with once-daily topical corticosteroids; corticosteroids containing antibiotics for non-infected eczema; probiotics; evening primrose and borage oil; ion-exchange water softeners; protease inhibitor SRD441 (Serentis Ltd); furfuryl palmitate in emollient; cipamfylline cream; andMycobacterium vaccaevaccine. Additional research evidence is needed for emollients, bath additives, antibacterials, specialist clothing and complementary and alternative therapies. There was no RCT evidence for topical corticosteroid dilution, impregnated bandages, soap avoidance, bathing frequency or allergy testing.LimitationsThe large scope of the review coupled with the heterogeneity of outcomes precluded formal meta-analyses. Our conclusions are still limited by a profusion of small, poorly reported studies.ConclusionsAlthough the evidence base of RCTs has increased considerably since the last NIHR HTA systematic review, the field is still severely hampered by poor design and reporting problems including failure to register trials and declare primary outcomes, small sample size, short follow-up duration and poor reporting of risk of bias. Key areas for further research identified by the review include the optimum use of emollients, bathing frequency, wash products, allergy testing and antiseptic treatments. Perhaps the greatest benefit identified is the use of twice weekly anti-inflammatory treatment to maintain disease remission. More studies need to be conducted in a primary care setting where most people with eczema are seen in the UK. Future studies need to use the same core set of outcomes that capture patient symptoms, clinical signs, quality of life and the chronic nature of the disease.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

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Section: Studiesmentioning

confidence: 99%

Scoping systematic review of treatments for eczema

Nankervis

Kim

Delamere

et al. 2016

Programme Grants Appl Res

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“…At this end, modeling by systems biology approaches are needed to propose adapted algorithm based on a hierarchical classification of each BM value, to finely tune the emerging new molecular picture of AD. This will ultimately lead to a personalized management using newly developed prevention (115)(116)(117)(118) and therapeutic approaches (119)(120)(121).…”

Section: Perspectivesmentioning

confidence: 99%

Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine

Bieber

2012

Allergy

169

125

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Atopic dermatitis (AD) is a paradigmatic inflammatory chronic skin disease. As for other chronic skin diseases, (i) the spectrum of the clinical phenotype and severity as well as (ii) the genetic background and (iii) the underlying mechanisms strongly suggest a high degree of pathophysiological heterogeneity yet leading to a similar clinical pattern, that is, the eczematous skin lesion, but showing distinct progression patterns. This review suggests to exploit the recent knowledge about AD for a novel approach proposing a tentative first molecular taxonomy of this disease based on the genotype and endophenotype. The consequences in terms of personalized prevention and management are delineated.As an evolution of the biomedical research and our genetic and pathophysiological understanding of complex diseases, we are currently experiencing a new trend in the classification of diseases moving from the purely phenotypic definition to a molecular taxonomy. It is expected that in future medicine, every disease will be characterized by three main groups of information: (i) the genotype, including epigenotypic information, (ii) the endophenotype (1) that comprises all available biomarkers (BMs), and (iii) the clinical phenotype (Fig. 1). Among all chronic inflammatory diseases, atopic dermatitis (AD) represents a paradigmatic condition because of its genetic and pathophysiological complexity (2) and finally the result thereof: the wide spectrum of clinical phenotype (3). This wide spectrum includes at one end the very minor forms such as atopic stigmata or simply dry skin with minimal itching and the erythrodermic and most severe form of AD at the other end. Due to the recent progress in the research of genetic, immunologic, and environmental factors (the so-called exposome) leading to AD, we are just starting to understand the complexity of the mechanisms underlying the variety in the clinical phenotype and to make first attempts to link the genotype and endophenotype to distinct clinical forms and courses of this disease such as the atopic march. After exposing a brief update of the clinical phenotype and pathophysiological aspects, this review introduces the concept of molecular taxonomy for AD and the consequences for its future management in the context of stratified or personalized medicine.

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“…Currently, a number of emollients that should substitute missing or defective components of the skin barrier, for example ceramides and lipids, have been studied in clinical trials (104)(105)(106). The application of a lipid raft-modulating agent, miltefosine, resulted in a sustained improvement in AD and increase of regulatory T cells in the skin (107). In a murine model, dietary sphingolipids were found to increase ceramide synthesis and thus recover damaged skin barrier (108).…”

Section: Translating Research Into Therapy For Admentioning

confidence: 99%

Update in clinical allergy and immunology

Gunten

Marsland

Garnier

et al. 2012

Allergy

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In the recent years, a tremendous body of studies has addressed a broad variety of distinct topics in clinical allergy and immunology. In this update, we discuss selected recent data that provide clinically and pathogenetically relevant insights or identify potential novel targets and strategies for therapy. The role of the microbiome in shaping allergic immune responses and molecular, as well as cellular mechanisms of disease, is discussed separately and in the context of atopic dermatitis, as an allergic model disease. Besides summarizing novel evidence, this update highlights current areas of uncertainties and debates that, as we hope, shall stimulate scientific discussions and research activities in the field.Research progress goes ahead fast, and each issue of Allergy distributes a dozen of new and interesting papers providing actual research results, opinions and reviews in different fields of allergy and clinical immunology. Over time, it becomes difficult to keep an overview on the novelties and trends given by these articles. Here, we give an update aiming to summarize interesting papers published in Allergy over the last years and putting them in context with recently published work in the field. As we were not able to cover all fields, we selected three research subjects: (i) Hygiene hypothesis: the role of the microbiome in allergy; (ii) Pathogenic mechanisms of allergic diseases and their potential therapeutic implications; (iii) Atopic dermatitis (AD): skin barrier and allergic inflammation. In our view, the selected papers provide new insights in clinically and pathogenetically important research as well as novel targets and strategies for therapy that might become starting points for future research.

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Long‐term reduction in local inflammation by a lipid raft molecule in atopic dermatitis

Abstract: We demonstrate that miltefosine is locally active in patients with AD and led to a sustained clinical improvement in local skin inflammation. Moreover, the increased frequency of FoxP3(+) cells in the skin of patients with AD suggests its immunomodulatory properties.

Cited by 19 publications

References 35 publications

Scoping systematic review of treatments for eczema

Scoping systematic review of treatments for eczema

Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine

Update in clinical allergy and immunology

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