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The reason why eczema (atopic dermatitis) first arises in children, and why it often leads to allergies and asthma, are key questions that are being addressed in Ireland by world-leading researchers.
Eczema affects up to 20 per cent of children in Ireland and often leads on to other conditions, but there is no effective treatment. Throughout the 20th Century and early 21st Century, the dermatological community worldwide believed eczema in children arose because of a fault in the immune system. The problem was, no-one could identify an immune system fault linked to eczema; the scientists hit a roadblock.
The breakthrough which cleared the way for a new understanding of eczema came when a team of researchers in Ireland, led by Prof Alan Irvine, a principal investigator funded by the National Children’s Research Centre (NCRC) based at Our Lady’s Children’s Hospital, Crumlin, and Trinity College Dublin (TCD), began to investigate whether eczema was caused by our genes, rather than a misfiring immune system, which was widely assumed.
The identification of a defective FLG gene at the root of eczema is crucial to stopping the allergic march, because eczema is often the first step in that march
Beginning in 2006, Prof Irvine and colleagues began to build large-scale, multi-site studies of eczema in children. The goal was to find out how the condition arose in young children in its ‘purest form’, how it developed as the children grew, and why it often led to the development of allergies and asthma.
The size of the network built across Ireland, Northern Ireland, Scotland and England made it the largest study of moderate-to-severe cases of atopic dermatitis in children anywhere in the world.
The key finding that emerged was ground-breaking and it changed how eczema was understood around the world. Prof Irvine reported along with his long-time collaborator Prof Irwin McLean in Dundee University, UK, that they had identified errors in a gene that was called filaggrin (known as FLG), which was linked to eczema in children.
Children with FLG mutations were found to be at a higher risk for developing atopic dermatitis, leading to a breakdown in the function of the skin. The children with the FLG mutation, they also reported, were found to be at significant risk of going on to develop food allergies, such as a peanut allergy.
The importance of FLG was that because, when functioning properly, it ‘tells’ the cell to produce filaggrin, a protein needed to hold the skin together. Filaggrin is not produced in children with a defective FLG gene and, as a result, the skin of such children cannot perform its role of providing a physical barrier against infection. This is why children with errors in their FLG gene are far more vulnerable to eczema.
When the FLG paper was published in leading scientific journal Nature Genetics, the story was picked up by many of the world’s leading media, including The New York Times. The coverage of the research in the medical press and the mainstream press changed how dermatologists, GPs, nurses and health professionals viewed eczema’s roots.
It was a massively impressive start to the eczema research project set up by Prof Irvine and his collaborators, but they did not intend to rest on their laurels.
In the past decade, they have built on this early success by going on to show that eczema is the first step in an ‘atopic march’, which leads later in life to allergies and asthma. About half of all children with eczema will develop asthma, and an even higher number, about 70 per cent, will develop hay fever later on.
The identification of a defective FLG gene at the root of eczema is crucial to stopping the allergic march, because eczema is often the first step in that march — stop eczema, and the ‘march’ never starts. This is why it is so important that children are tested as early as possible for the FLG gene.
Prof Irvine is continuing his research into the skin barrier and the genetic basis of eczema, and is working hard to ensure his discoveries translate into new treatments for children. The fact that eczema is linked to a defect in a particular gene is good news, in the sense that new gene repair therapies, which could be developed in the future, could halt or reverse eczema in children when its occurrence is first spotted.
The question of why asthma is linked to eczema led Prof Irvine to collaborate with Prof Padraic Fallon, Professor of Translational Immunology at TCD, and a leading asthma researcher. The link-up between Prof Irvine, a consultant working at the coalface with children, and Prof Fallon, a top laboratory-based scientist, was a powerful one.
The incidence of asthma among Irish children is the fourth-highest in the world, which makes it a significant public health issue here. Many asthmatic children in Ireland have first developed eczema, and thus understanding how the two are linked is crucial.
Prof Fallon and Prof Irvine are the leaders of the NCRC-funded PRiTI (paediatric research in translational immunology) programme, which is funded from 2011 to 2016. A key aim of the PRiTI is to better understand the genetic basis for why allergies and immunological diseases of childhood initially develop. PRiTI has already produced important findings in asthma, eczema, ulcerative colitis and sepsis.
Prof Fallon’s laboratory is the testing ground for how asthma is linked to eczema, using mice models. The link with Prof Irvine is crucial because this provides him with access to the world’s largest, multi-site study of the root causes of childhood eczema, as well as access to Prof Irvine’s own research expertise and insights he has gained from treating children with eczema.
Together, the two men make a dynamic team. Prof Fallon’s says his collaboration with Prof Irvine is a perfect one because it links his lab work with asthma in the real world.
The work in mice can identify, as a first step, he says, whether a gene is relevant at a particular stage in the development of asthma.
With childhood asthma, it is easier — and faster — to do the initial research on mice than it is in humans, which is what Prof Fallon is doing. Working in this way, he has identified some abnormally-functioning genes.
“This finding opens up the possibility of developing new drugs which act on the genes linked with asthma before the disease develops,” said Prof Fallon. “We are also working now on developing some other new therapeutic targets, which could help to treat childhood asthma,” he added.
Prof Fallon said that while he does not expect a ‘cure’ for asthma anytime soon, it is realistic to expect that life will be far better and less hazardous for children with asthma in the near future. Irish children will still continue to get asthma — due to the complex interaction of genes and environment — he said, but what we will be far better at in future will be identifying asthma earlier and treating it with effective new drugs, so that the condition becomes more manageable.
The finding that abnormal genes are also linked with childhood asthma means that it is possible that drugs or therapies could be developed in the future that target the abnormal gene, enable it to better function, and improve lung capacity in the 7 per cent of Irish children under 18 years who are affected by asthma.
Eczema expert advice meeting
The Irish Skin Foundation (ISF) has announced the line-up for its ‘Eczema Expert: Advice for Life’ meeting, which will be held during Eczema Awareness week (this week) to help anyone caring for eczema to learn more about managing the condition.
The meeting will cover general information on eczema, emollient therapy, childhood eczema, wet-wrap and Tubifast therapy and a mother’s perspective on eczema. Exhibitors will also be present on the day.
Join the ISF at the Red Cow Moran Hotel, Naas Road, Dublin 22, on 17 September 2016, from 10am to 1:30pm.
The workshops will cover:
10:00: Registration, tea, coffee and exhibitor stands.
10:20: Opening and welcome address.
10:30: ‘What you need to know about eczema’, followed by Q&A with Dr Grainne O’Regan, Consultant Paediatric Dermatologist, Our Lady’s Children’s Hospital, Crumlin.
11:00: ‘Emollients — their importance and how to use them’, followed by Q&A with Ms Annamma Raju, Clinical Nurse Specialist, Tallaght Hospital, Dublin.
11:30: ‘A parent’s perspective — hints and tips on caring for a child with eczema’, Ms Jeannette Brazel, Irish Skin Foundation.
12:00 noon: ‘Wet-wrap/paste bandage/Tubifast demonstration — how to use them to best effect’, Ms Annamma Raju, Clinical Nurse Specialist, Tallaght Hospital, Dublin.
Also from 12:00 noon: Exhibitor stands.