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World J Dermatol. Aug 2, 2017; 6(3): 42-51
Published online Aug 2, 2017. doi: 10.5314/wjd.v6.i3.42
Atopic eczema treatment now and in the future: Targeting the skin barrier and key immune mechanisms in human skin
David C Bell, Sara J Brown
David C Bell, Sara J Brown, Skin Research Group, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
Author contributions: Bell DC performed the majority of the writing and produced the figures and table with advice from Brown SJ; Brown SJ edited and supplemented the text and provided advice in the development of the figures and table.
Conflict-of-interest statement: Bell DC has no conflict of interest to declare; Brown SJ receives funding from the Wellcome Trust (Senior Research Fellowship in Clinic Science reference 106865/Z/15/Z); she provides consultancy advice for CXR Biosciences.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sara J Brown, Professor of Molecular and Genetic Dermatology, Wellcome Trust Senior Research Fellow in Clinical Science, Honorary Consultant Dermatologist, Skin Research Group, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, James Arrott Drive, Dundee DD1 9SY, Scotland, United Kingdom. s.j.brown@dundee.ac.uk
Telephone: +44-1382-383210
Received: February 15, 2017
Peer-review started: February 15, 2017
First decision: March 7, 2017
Revised: March 14, 2017
Accepted: April 4, 2017
Article in press: April 5, 2017
Published online: August 2, 2017
Processing time: 159 Days and 2.6 Hours
Abstract

The skin facilitates a number of key roles but its functioning can be impaired by disease. Atopic eczema is a chronic inflammatory disease where the skin barrier has become leaky, and inflammation occurs. It affects up to 20% of children and 3% of adults worldwide, manifesting as red itchy patches of skin with varying severity. This review aims to investigate the leaky skin barrier and immune mechanisms from the perspective of potential novel treatments. The complexity of atopic eczema as a disease is what makes it difficult to treat. Genome-wide association studies have highlighted possible genetic variations associated with atopic eczema, however in some cases, individuals develop the disease without these genetic risk factors. Loss of function mutations in the filaggrin gene are one of these associations and this is plausible due to its key role in barrier function. The Th2 immune response is the link with regards to the immune mechanisms as atopic inflammation often occurs through increased levels of interleukin (IL)-4 and IL-13. Eczematous inflammation also creates susceptibility to colonisation and damage by bacteria such as Staphylococcus aureus. Potential novel treatments are becoming ever more specific, offering the hope of fewer side effects and better disease control. The best new treatments highlighted in this review target the immune response with human beta defensin 2, phosphodiesterase-4 inhibitors and monoclonal antibodies all showing promise.

Keywords: Atopic eczema; Novel treatment; Filaggrin; Skin barrier; Immune dysfunction

Core tip: Atopic eczema (atopic dermatitis) is an itchy inflammatory skin disease with complex aetiology, including impairment in barrier function and concomitant inflammation. Increased understanding of the molecular mechanisms in eczema pathogenesis has opened up opportunities for new therapeutic targets. This review summaries current understanding and highlights some novel treatments in development.