Successive flare-ups of the most common form of eczema may trigger an immune system overreaction, causing it to become a long-term condition in people.
This is the conclusion of a new study using mathematical modelling to analyse how the most common form of eczema, atopic dermatitis (AD), progresses. Scientists have previously been unable to determine why some people show signs of improvement while others progress to having a long-term and more severe condition.
AD is a medical condition primarily affecting children, where patches of skin become rough and inflamed with blisters, causing itching and bleeding. It is a long-term (chronic) condition in most people, although it can improve over time, and children can grow out of it by adulthood.
AD can be triggered by a combination of factors such as stress, detergents, weather, allergies to certain foods, and genetic factors may play a role.
Now, a bioengineer from Imperial College London and her colleagues have collated data from previous studies on AD and developed a mathematical model that suggests how AD may progress to becoming chronic. The team's model showed that repeated flare-ups of AD trigger an immune system overreaction in the body, and when triggered this can't be reversed.
This creates a cycle where the threshold for triggering further AD outbreaks becomes lower, the flare-ups are more severe, and the condition progresses to becoming long-term. Severe flare-ups happen as a result of the complex interactions between the body's immune system, the skin's protective barrier, and environmental factors such as stress.
The team examined approximately 500 clinical and experimental studies, and carried out research involving mice, to develop their mathematical model. It modelled four different types of AD, ranging from no symptoms to severe flare-ups. They also looked at how genetic factors affect the skin and the immune system.
The researchers stress that theirs is a general model of AD. However, they believe it suggests preventing an immune system overreaction from being triggered may be the key to preventing AD from becoming more severe.
Two recent clinical trials demonstrated that babies who received moisturising treatments, known as emollients, which were applied directly to the skin to reduce water loss and cover it with a protective film, were less like to develop AD. The authors of today's study also explained the possible mechanism behind these observed preventive effects.
The emollients provide an effective barrier, preventing the itching and scratching cycle that can progress the condition further. They also demonstrated that these preventive effects are applicable not only for babies with genetic markers that indicate a predisposition to AD but for those without genetic markers as well.
Dr Reiko Tanaka, co-author of this study from the Department of Bioengineering at Imperial College London, said: "I am a bioengineer, not a clinician, but I have a daughter who suffers from eczema so I know the discomfort and frustration that people go through with this skin condition. What is more frustrating for AD sufferers is that no one knows who will progress to the long-term condition.
"Our mathematical modelling is helping us to make a clearer connection between a systemic reaction to AD and its progression. More work needs to be done to verify our results in patients. However, we think a crucial preventative measure may be the use of ointments on all babies early on. It doesn't matter which moisturising treatment is used as long as a barrier on the skin is created, which may stop the AD cycle from triggering a systemic reaction."
This approach to using mathematical models to understand the underlying causes of diseases or conditions is called systems medicine. Dr Tanaka and her colleagues now hope to develop a model that can be tailored to each patient based on their individual clinical data. This could enable doctors to tailor each treatment to the specific needs of the patients, optimising its effectiveness, lessening the severity and impact of the condition.
The research is published in the Journal of Allergy and Clinical Immunology and was carried out in conjunction with the Japanese research institute RIKEN and Trinity College Dublin.
Article: Mathematical Modeling of Atopic Dermatitis Reveals "Double switch" Mechanisms Underlying Four Common Disease Phenotypes, Elisa Domínguez-Hüttinger, PhD, Panayiotis Christodoulides, MEng, Kosuke Miyauchi, PhD, Alan D. Irvine, MD, DSc, Mariko Okada-Hatakeyama, PhD, Masato Kubo, PhD, Reiko J. Tanaka, PhD, Journal of Allergy and Clinical Immunology, doi: 10.1016/j.jaci.2016.10.026, published online 5 December 2016.