Multi-band optical coherence tomography platform for the development of novel atopic dermatitis treatments.

Lead Research Organisation: University of Sheffield
Department Name: Electronic and Electrical Engineering

Abstract

Atopic dermatitis (AD - also known as eczema) is a skin disease that is greatly underestimated both in its prevalence and in its negative effects both on sufferers. The physical sensation of trying to sleep whilst experiencing a severe eczema "flare" has been likened to putting on a wet-suit that is stuffed with stinging nettles, zipping it up and then lying down to try to sleep. AD first affects the very young, with symptoms often appearing in the first 6 months of life and persisting through school years. Having open, weeping sores on the skin can cause children to have serious emotional problems at school and the lack of sleep from severe nighttime itching leaves children exhausted, unable to concentrate and thus unable to keep up. In severe attempted suicide is not uncommon, even in children under 10 years of age. The burden on carers is similar to that from children who need e.g. to be fed through a tube at home. Yet AD is a very common condition, affecting up to 30% of children in the UK and up to 10% of all adults. The UK has one of the highest rates of AD in the world and the disease is the commonest reason for consulting a GP about a skin complaint. AD is a "disease of the modern world": rates of AD have increased dramatically since the 1940's, suggesting that an increase in external irritants is a major factor. AD belongs with asthma and hay fever in being primarily an "allergic" reaction. The financial burden of AD on the health service arises because it is the first step along the "atopic march", where a child with AD very often progresses on to one of these other conditions.
Despite its potential severity and high prevalence, AD has been neglected as a priority for developing treatments. The most commonly prescribed treatments (moisturizing creams and steroid creams) are over 50 years old. Steroid creams are very effective for calming inflammation and itching but come with serious problems. Sufferers can become dependent on them (steroid addiction) but at the same time they gradually damage the skin ("skin thinning"). Many carers suffer from "steroid phobia" and under-treat children; this causes AD flares to be poorly controlled which then requires even more steroid cream to be used later.
The last 5 years has seen this regretable situation begin to completely transform however. New treatments are being brought to market which control inflammation and itching with potentially far fewer side-effects than steroid creams. The companies developing these treatments urgently require objective tools that can assess the skin before, during and after use so that they can reliably measure how well the treatments suppress AD flares and avoid causing skin damage. During a previous EPSRC project we applied an emerging imaging tool, optical coherence tomography (OCT), to AD patients and normal volunteers and found it to be potentially an ideal tool for this purpose. Such was the interest in our work from major drug companies that we are actively collaborating with them to use existing OCT techniques to evaluate 3 new types of AD treatment. At the same time at Sheffield we have a unique collaboration between dermatologists and OCT engineers who can see even greater potential for more advanced OCT techniques to be applied. This HIPS project is a unique partnership between clinicians, engineers and drug companies which will develop cutting edge OCT tools and assess their effectiveness in assessing new AD treatments. The potential impact in healthcare is enormous because of the huge demand for these new treatments. If successful we will develop an advanced OCT scanner that can immediately be used to help in the clinical evaluation of new and emerging treatments for this highly distressing disease.

Planned Impact

Atopic dermatitis (AD - a.k.a eczema) affects up to 30% of children in the UK and up to 10% of adults, giving the UK one of the highest prevalence rates in the world. Its prevalance has increased over 3-fold in the post-war era and it now represents the commonest dermatological cause of a GP referral. It generally appears during the first 6 months of life and is the first step along the "atopic march" leading to other allergic conditions such as asthma and hay fever. AD is a chronic, relapsing condition in which the skin intermittently "flares". During a flare the skin becomes intensely itchy, dry and inflamed. Excessive scratching leads to open, oozing sores that easily become infected and then require intensive courses of antibiotics to resolve. As antimicrobial resistance grows, the risks to the general health of sufferers from recurrent skin lesions will grow also.
The direct costs to the NHS from AD are estimated to be £1 billion annually. In addition, AD levies indirect costs on sufferers and their carers which can be extreme. It has been estimated that the impact on the quality of life for juvenile sufferers of AD is second only to cerebral palsy because the chronic nature of the condition requires major adjustments in lifestyle (avoiding common wash products, house dust mites and other allergens; moisturizing the skin multiple times per day; wearing tight-fitting scratch-resistant dressings at night) that are ongoing. Other studies have estimated the stress placed on carers as being similar to caring for children with major disabilities that require home enteral feeding. The psycho-social impact of AD can be profound on young sufferers especially. The presence of open sores on exposed skin can lead to poor self-esteem and social exclusion. Disturbed sleep due to night time itching can lead to tiredness and poor concentration at school, so that AD sufferers fall behind academically. In severe cases of juvenile AD, attempted suicide in children as young as 8 is not uncommon.
Despite its prevalence and negative effects AD has been neglected by the pharmaceuticals industry. Many AD dermatologists have had to resort to prescribing drugs intended for other diseases "off-label". The mainstay treatment for AD flares, topical corticosteroids (TCS), were introduced in the 1950's and act in a very non-targetted way on the immune system. Because AD is a chronic, relapsing condition the long-term use of TCS is problematic. Potent TCS can be safely used for short periods, but prolonged use causes epidermal atrophy (skin thinning), telangiectasia and dermal striae (scars due to tearing of dermal collagen). Fortunately this situation is dramatically changing and major pharmaceuticals companies are investing heavily to bring new, more targeted, drugs to the AD market. Pfizer recently acquired Crisaborole, a small-molecule PDE4 inhibitor, by buying Anacor for US$5.2 billion. Regeneron/Sanofi recorded annual sales of Dupilumab, an IL-4/IL-13 human monoclonal antibody, of nearly US$500 million in 2017 and projections suggest US$3 billion annually is likely. Such drugs have the potential to be "blockbusters" because the chronic nature of AD requires their long-term use.
Our OCT technology platform thus has the potential to make a huge impact in this renaissance of AD treatment options. It is widely accepted that existing clinical scoring of AD is inaccurate and that more objective biomarkers will help to establish efficacy, stratify the most responsive patients and demonstrate safety. We are already collaborating with several major drug developers to use our existing OCT techniques to aid their drug evaluation process. Our proposed platform will thus fit directly into an established clinical evaluation workflow, giving the potential for major impact.

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