Wednesday, October 8, 2014
In the October 2014 issue of Journal of Allergy and Clinical Immunology, Brough et al show that early environmental peanut exposure from house dust increases the risk of peanut allergy in children with impaired skin barrier. Children were assessed for peanut allergy and had genetic studies to determine whether they could produce normal filaggrin levels. Dust samples were collected and analyzed for peanut concentration to determine in which groups of children environmental peanut exposure influenced the development of peanut allergy. In normal children environmental peanut exposure did not influence the development of peanut allergy. In contrast, in filaggrin deficient children the risk of peanut allergy increased as peanut concentration in the house dust increased. To read the full article, please click here: http://bit.ly/1qkfHeY
Thursday, October 2, 2014
Atopic eczema (AE, syn. atopic dermatitis) is a major medical condition that causes substantial burden to patients, their families, and society. Various different interventions exist, many of which have been assessed in randomized controlled trials (RCTs). However, there is a lack of core outcome sets for atopic eczema (AE) which is a major obstacle for advancing evidence-based treatment. There are several different instruments identified to assess clinical signs of AE and the global Harmonizing Outcome Measures for Eczema (HOME) initiative has already defined clinical signs, symptoms, quality of life, and long-term control of flares as core outcome domains for AE-trials. To resolve the current lack of standardization of the assessment of clinical signs of AE, the HOME initiative followed a structured process of systematic reviews and international consensus sessions to identify one core outcome measurement instrument to assess clinical signs in all future AE-trials (J Allergy Clin Immunol 2014; 134(4): 800-807).
The authors determined that from 16 different instruments identified to assess clinical signs of AE, only the Eczema Area and Severity Index (EASI) and the objective Scoring Atopic Dermatitis Index (objective SCORAD) were identified as sufficiently tested for inclusion in the core outcome set. The EASI has adequate validity, responsiveness, internal consistency, and intra-observer reliability. The objective SCORAD has adequate validity, responsiveness, and inter-observer reliability, but unclear intra-observer reliability to measure clinical signs of AE. In an international consensus study, patients, physicians, nurses, methodologists, and pharmaceutical industry representatives agreed that EASI is the preferred core instrument to measure clinical signs in all future AE-trials. The EASI was chosen as the core outcome measure for clinical trials because (1) it only includes the 4 essential signs, (2) assesses the severity of AE signs at multiple body sites, rather than at a single representative site for each sign, and (3) gives the extent of AE lesions sufficient weighting.
The HOME initiative recommends that all investigators, pharmaceutical industry, and regulatory authorities observe this consensus and include the EASI in all future atopic eczema trials to enable improved evidence-based decision making and scientific communication in the future. This does not preclude the use of other scales in trials (such as SCORAD) in addition to the core outcome measure. Better training materials for use of EASI are in preparation and will be freely available via the HOME website (). Furthermore, the process of standardization and selection of measurement instruments for the assessment of the other core outcome domains of AE, i.e. symptoms such as pruritus and sleeping problems, quality of life and long-term control of flares, is currently underway.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and often precedes the development of food allergy and asthma. The defective skin barrier in AD is thought to allow the absorption of allergens through the skin. This promotes systemic allergen sensitization, contributing to the development of food allergy and asthma, as well as skin infections such as Staphylococcus aureus and herpes simplex virus (HSV). This month’s JACI focuses on the importance of both genetic and acquired causes of epithelial skin barrier dysfunction in driving the natural history of AD. In their review, Donald Leung and Emma Guttman-Yassky summarize current insights into AD that may lead to new treatment approaches, including several articles published in this month’s journal (J Allergy Clin Immunol 2014; 134(4): 769-779).
The causes of AD are complex and driven by a combination of genetic, environmental and immunologic factors which likely account for heterogeneity of AD onset, severity and natural history of the disease. While there is currently no cure for AD, recent studies suggest prevention of AD can be achieved by early interventions that protect the skin barrier such as emollients and topical anti-inflammatory treatments. Importantly, the control of lesional AD may improve long term outcomes not only in AD, but in allergic diseases of the gastrointestinal and respiratory tracts as well, due to the reduction of associated allergen sensitization.
Although current treatment options for AD are limited, the authors explain that in addition to Th2 antagonists (i.e. the anti IL-4R drug dupilumab), determining the key role of TSLP-receptor signaling and IL-22 that involve clinical trials with agents that target TSLP, Th22, and TH17/IL-23 will be of interest. Furthermore, the selection of therapeutics for patients with differing degrees of disease severity and /or phenotypes should be guided by defining the extent of activation in the skin and blood. For example, anti IL-23/IL-17 might provide beneficial responses particularly in intrinsic AD patients. The individual contributions of the TH22, Th17, and Th2 immune pathways to the disease phenotype will be clarified through clinical trials coupled with mechanistic studies that are currently in progress. This comprehensive review highlights the importance of translational medicine, from animal models to clinical trials, and how this approach is advancing AD research.
Questions for the authors:
Recently, both basic science and clinical research have provided novel insights into the prevention, identification, and treatment options for AD. Do you anticipate these findings to improve outcomes for not only AD but other allergic diseases as well?
Yes, because the principle underlying causation of allergic diseases likely have in common a defective epithelial barrier and abberant immune response. This is modulated by different resident cells in each organ.
AD is most often a first step in a series of atopic diseases in the Atopic March that often leads to rhinitis, food allergy, and asthma. Could removing the first step in the Atopic March reduce the global burden of atopic disease?
Possibly. The studies in the current issue of JACI support the concept that skin barrier dysfunction enhances sensitization via environmental allergen exposure. A natural progression of this concept would be to correct the skin barrier defect to determine whether elimination of AD could prevent food allergy, asthma and allergic rhinitis.