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Targeted therapies set to reduce impact of the most severe psoriasis cases Psoriasis is an incurable condition that can have a painful and psychologically disabling effect on patients’ lives. Expert, Professor Christopher Griffiths from the University of Manchester, discusses how it’s being tackled and how patients will be better able to manage in the years to come. ow does psoriasis H present, and what causes it to come on? Psoriasis typically presents as red, scaly patches on the skin called ‘plaques’. These usually appear on the scalp, the outer part of the elbows and the knees and the lower back. However, it can involve any part of the skin surface and very severe cases can affect all of the skin. In children, psoriasis often occurs in little teardrop formations on areas such as the trunk. This early onset – or guttate – psoriasis can occur quite suddenly in a lot of cases following a throat infection. In terms of the ‘why’, genetics and family links play a huge role, but there are other environmental triggers that can cause the onset of psoriasis. Smoking, alcohol, stress and being overweight aren’t root causes but have been shown to
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exacerbate the onset of psoriasis and its severity.
INTERVIEW WITH:
hat treatments are W prescribed to someone diagnosed with the psoriasis? Firstly, topical creams or ointments are prescribed and applied directly to the skin. They usually contain vitamin D and may be combined with a steroid. This, alongside emollients and moisturisers, can be all that some people need. More ser ious cases t y pica l ly requ i re ‘photot herapy ’, wh ich involves doses of ultraviolet (UV) light administered to the skin. UV light reduces inflammation quite significantly, but only produces temporary benefit. At the moment there is no cure and we can only suppress the symptoms.
PROFESSOR CHRIS GRIFFITHS OBE Foundation Professor of Dermatology, The University of Manchester and Consultant Dermatologist, Salford Royal NHS Foundation Trust
ow has treatment H changed in the last 10-15 years?
Conventional treatments historically included drugs that act as immune system suppressants. They tackle the parts
of the immune system that we now know are related to the onset of psoriasis. They work in around 50% of people and can reduce symptoms by 75% in some cases, but side effects, such as nausea, liver toxicity and high blood pressure make them less than ideal. What breakthroughs have there been recently? The key discovery has been that psoriasis is driven by the immune system. We now have drugs called biologic therapies, which target the specific areas of the immune system linked to the onset of psoriasis. People with very severe psoriasis can have their lives transformed for the better by these drugs – their impact can be huge.
ow do you see H treatment changing in the coming years? We’l l see g reater upta ke of t he t a rgete d biolog ic therapies, certainly. Drugs that act as broad immune suppressants have done a good job in many cases, but they’re nowhere near as effective at clearing psoriasis as the new generation of drugs. Drug therapies will become more targeted to the individual as we come to better understand people’s responses to medicines – known as personalised medicine. Combined with lifestyle modification such as weight loss and stopping smoking are a powerful way of managing even the most severe cases of psoriasis. WRITTEN BY: JAMES ALDER
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1. Difficult-to-treat psoriasis ifficult-to-treat psoriasis occurs D on areas of the body such as the face, genitals, scalp, palms of the hands, soles of the feet and in the body creases (also called ‘flexures’) for example the armpits and under the breasts. Psoriasis in these areas can be difficult to treat completely and because the condition is visible, it can have a greater impact on the person.
2. Erythroderma rythroderma is a rare form E of psoriasis that affects nearly all the skin on the body and can cause intense itching or burning. It can lead to more serious illness, sometimes requiring hospital admission.
3. Guttate psoriasis uttate psoriasis (sometimes G referred to as ‘raindrop psoriasis’) is a form of psoriasis in which small red spots occur over the body, arms and legs. It is more common in children and young people, and can be triggered by a type of throat infection called a streptococcal throat infection. This type of psoriasis may not be long-lasting.
4. Plaque psoriasis laque psoriasis is the most P common form of psoriasis. Raised, red, plaques typically occur on the elbows, knees, scalp and lower back, but it can be more widespread.
5. Psoriatic arthritis soriatic arthritis is a type of P arthritis with swelling, pain and stiffness of one or more joints which may occur in people with psoriasis and needs diagnosing by a rheumatologist.
6. Pustular psoriasis ustular psoriasis is a rare form P of psoriasis in which pus-filled blisters appear on the skin. It is not infectious, and the pus is not a sign of infection. © NICE 2019 For further information, see: www.nice.org.uk/guidance/cg153 NICE guidance is prepared for the National Health Service in England. NICE accepts no responsibility for the use of its content in this publication.
Registered Charity Numbers: 257414 and SC 039886
Responses to survey with 250 young people with psoriasis by the Psoriasis Association 2018’
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Everyday tasks can be painful with eczema
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ost people have heard about eczema, but few realise just how difficult and painful it can be. The skin is of ten u nbea rably itchy a nd uncomfortable, and the relentless daily challenge to care for it can be exhausting. For some people with eczema, doing everyday tasks like cooking or even bathing can be extremely painful, because the skin is so cracked, sore and raw. Alongside the painful physical symptoms, many children and adults experience related sleeplessness, low selfesteem, bullying, anxiety, and other mental health problems. Eczema is a serious, debilitating, long-term medical condition that has a huge impact on millions of children, adults and their families. The most common form, atopic eczema, affects one in five children and up to one in ten adults in the
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UK. Around a third of those with eczema have either moderate or severe symptoms. Eczema and dry skin Using emollients is essential to help repair and protect the body’s natural skin barrier and reduce the itch associated with eczema. Skin is made up of several layers, each containing skin cells, water, oils and fats. Together these help maintain a nd prote c t t he c ond it ion of the skin. If you have eczema, your skin is less able to retain water. Gaps open up between the skin cells and the protective barrier doesn’t work as well as it should. Moisture is lost from the deeper layers of the skin, allowing bacteria or irritants to pass through more easily. Emollients are therefore needed to repair and protect the skin barrier, to
stop the skin from drying out and being damaged. How should emollients be used? Emol l ients shou ld be used for moisturising the skin several times a day, and for washing, even when the skin isn’t red and inf lamed. Emollients come in various forms, lotions, creams, gels and ointments. You’re likely to need more than one kind of emollient, depending on the dryness of your skin, the part of the body affected and the time of year. NHS emollient rationing Having a good skincare routine is crucial if people are to self-manage their eczema well, and in doing so reduce the need for more expensive medical treatments. It is not always straightforward to find the right emollient, with such a
WRITTEN BY: ANDREW PROCTOR Chief Executive, National Eczema Society
If you have eczema, your skin is less able to retain water. Gaps open up between the skin cells and the protective barrier doesn’t work as well as it should. wide range of products available. Different emollients suit different people and finding the best ones for you usually involves some trial and error. The best emollients are the ones that people are willing to use regularly because they work best for them. This is why National Eczema Societ y is so concer ned about moves by the NHS to restrict the availability and range of emollients on prescription, for both children and adults. We hear from many people that they are having their emollient prescriptions changed, reduced or stopped. NHS England prescribing guidance on leave-on emollients says
that emollients can be prescribed for people with eczema. Even so, this is not always followed. The Society has produced its own guidance for people on how to advocate with their GP or nurse for access to emollients on prescription, citing the research evidence and clinical guidelines. T he S o c ie t y i s a l s o hu g e l y concerned about the latest moves to stop making bath emollients and therapeutic silk garments available on prescription too, including for people with more severe eczema. D espite st rong fe e dback f rom patients and compelling research ev idence, decision ma kers are seemingly not listening.
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Atopic eczema and its impact on quality of life Atopic eczema (or atopic dermatitis) is the most common form of eczema, causing skin inflammation and intense irritation.
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czema is most common in babies and children but can also persist into adulthood, affecting around 1.5 million people in the UK. It can have a significant impact on quality of life. E c z ema of ten st a r t s a s d r y, scaly patches and most people w ith eczema tend to have dr y skin generally, indicating that the barrier function of the skin is not working properly.
reaction when the individual is exposed to them. Individual triggers of eczema vary, but can include: • Changes in temperature • Chemicals and soaps • Food allergy/intolerance • Certain fabrics • Viral and bacterial infections
Triggers of atopic eczema
• C o nt a c t a l l e r g e n s i n t h e environment (such as house dust mites and pet dander)
Once the skin barrier is broken, i r r ita nt s such a s soaps a nd detergents can further damage the skin barrier, exacerbating the eczema. Allergens (such as food and airborne allergens) can penetrate the upper layers of the skin and potent ia l ly lead to an a l lerg ic
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Treating atopic eczema Currently, there is no cure for eczema so, following a management plan, using emollients to maintain
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the barrier function of the skin and avoiding irritants are essential. It is important to be aware of the signs of bacterial infections (weeping and crusting), as eczema makes the skin more prone to infection. Impact on quality of life Eczema is often seen as ‘just a skin condition’ but can affect ever y aspect of life. The physical pain a nd d iscom for t caused by t he condition can be difficult to deal with, causing distress, anxiety and embarrassment. Some of t hese impacts were outlined in Allergy UK’s 2017 adult eczema survey: • 8 8% of patients said that the management of their eczema impacts on their daily lives
WRITTEN BY: AMENA WARNER Head of Clinical Services, Allergy UK
• O ver 70% feel depressed as a result of their condition • 7 3% state that their social life is impacted • 7 0% report that their sleeping habits are affected If you are concerned that you or your child may have eczema, seek advice from a healthcare professional. An accurate and timely diagnosis is i mpor ta nt for t he ef fec t ive management of this condition.
Read more at healthawareness.co.uk
Visit www.allergyuk.org for more information and advice on identifying eczema triggers and managing the condition. Allergy UK also has a dedicated Helpline which can be contacted on: 01322 619898 Allergy UK’s Seal of ApprovalTM is a globally recognised endorsement scheme for products scientifically tested to benefit allergic conditions, including ‘Allergy Friendly’ cosmetics and skincare products.
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elanoma cell spreading. Actin, the cell’s cytoskeleton, in grey; M focal adhesions, or how a cell attaches to its environment, in blue/green. (Credit: ICR/Lucas Dent)
etastatic mouse melanoma cells spreading on a collagen M matrix and imaged by Total Internal Reflection Fluorescence (TIRF) microscopy. Actin in green, focal adhesions in blue, and tubulin in red. (Credit: ICR/ Chris Bakal & Oliver Inge)
human melanoma cell invading a collagen matrix. In the A lab we engineer gels that mimic tissues in the body to see how cancer cells look and move during metastasis. We often use collagen gels because this is the most abundant tissue in the body. (Credit: ICR/Vicky Bousgouni & Dave Robertson)
Beating melanoma with cutting-edge science New technology is giving my team an unprecedented understanding of how cancer cells grow and spread. I work on a skin cancer called melanoma – the fifth most common cancer in the UK, with around 16,000 newly diagnosed cases each year.
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cient ists at t he ICR have long been at the forefront of research to better understand melanoma, and our research is behind the discovery of some of the most important new treatments for the disease. The difference between a fatal and non-fatal cancer is usually its ability to spread around the body – in a process called metastasis. We’re aiming to understand what makes some cancer cells, including melanomas, leave their original site and make that journey to other tissues and other parts of the body. We know a melanoma cell’s ability to change its shape is a crucial factor in its ability to spread. Metastatic cells can take on many shapes, squeezing through tissues and finding their way into places they should not naturally be. In my team, we aim to develop treatments that ‘freeze’ the shape of cancer cells. We u s e a s oph i s t ic ate d microscopy, such as the ‘lattice light sheet’ microscope to illuminate melanoma cells in ultra-fine detail, and to generate many images at very high speed. We combine this
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microscopy with sophisticated artificial intelligence methods to allow computers to understand how the shape of cancer cells influences t hei r abi l it y to s pre ad rou nd the body. We have recently discovered genes that allow melanoma cells to ‘shapeshift’, and used Big Data integration methods to develop a ‘postcode’ s ystem t hat maps protei n s i n metastatic melanoma cells. Drug discovery successes ICR scientists have also made breakthroughs that have h e l p e d t r a n s fo r m t r e a t m e n t of melanoma. One of the ICR’s most high-profile successes of re c ent ye a r s w a s re s e a rch to understand how mutations in a gene called BRAF could help cause the disease. Researchers at the ICR played a major role in characterising the BRAF gene and its role in cancer, increasing our understanding of malignant melanoma. Our work in the laboratory led to the discover y of t wo BR A F-
WRITTEN BY: PROFESSOR CHRIS BAKAL Professor of Cancer Morphodynamics, The Institute of Cancer Research, London
We’re aiming to understand what makes some cancer cells, including melanomas, leave their original site and make that journey to other tissues and other parts of the body. in hibiting dr ugs that are now mainstays of treatment for advanced melanoma, buying extra months or years for many thousands of patients around the world. One of these drugs was discovered by a team which included Dr Olivia Rossanese – who is now the Head of Biology in our Division of Cancer Therapeutics, working to find the next generation of cancer drugs. O u r s u c c e s s at t h e IC R i n discovering new dr ugs is underpinned by gaining a de e p er u nder s t a nd i n g of t he b iolo g ic a l p r o c e s s e s at wo rk in cancer. What’s really important for us
is to understand the underlying mechanisms and genetic alterations in cancer that lead to uncontrolled tumour growth and spread. And when we beg in to understand those mechanisms, we really have a good idea of what the targets are for therapeutics. Immunotherapy treatments for melanoma ICR researchers are also leaders in the field of immunotherapy. Recent clinical trials involving our researchers have led to the approval of new i m mu not he r apie s for patients on the NHS and worldwide
to treat advanced melanoma and other cancers. These treatments have included a highly innovative viral immunotherapy made up of a genetically modified form of herpes simplex virus type-1. P rofessor Kev in Har r ing ton, P rofessor of Biolog ica l Cancer Therapies at the ICR and Consultant Clinical Oncologist at The Royal Marsden, was the UK leader of the definitive trial that showed the benefits of this drug, which uses a genetically altered virus to burst cancer cells from within and attract the immune system to tumours. Research at the ICR has led to vital new drugs to treat melanoma, and a better understanding of its biology than ever before. Together with my colleagues, I am determined to keep on building on what is known about this disease, and find more new ways to treat it.
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‘ I take my pill every morning, and I get on with my life’
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h r i s t i n e O ’C o n n e l l , 4 7, from south-west London, was diagnosed with breast cancer in December 2012. After undergoing intensive treatment, she thought cancer was well and truly behind her – until a scan revealed a secondary tumour in her brain. She has now started a targeted treatment to keep the disease at bay. The drug works by blocking two proteins, CDK4 and CDK6, which help cancer cells divide. It was assessed in clinical trials which the ICR helped lead. Now, than ks to the targeted treatment, which avoids many of the side effects of traditional chemotherapy, Christine is able to keep up her passion, cycling: “I’ve seen first hand the difference a targeted treatment can make. My cancer is currently stable. I take my pill every morning, and I get on with my life.
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“I still cycle three to four times a week, which I could never have done had I been on conventional therapy. This year I did the Etape du Tour, an amateur event that follows the route of one of the stages of the Tour de France, and completed the 365km ride from Manchester to London in a day, as well as a 600km ride from Paris to Amsterdam. I’m not stopping there though! “My treatment allows me to live a good life with cancer – and I want all cancer patients to have this hope and optimism for the future.”
Supported by
The cutting-edge drug discovery programme outsmarting cancer evolution Researchers at The Institute of Cancer Research, London, are poised to outsmart cancer with the world’s first anti-evolution ‘Darwinian’ drug discovery programme.
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ince 2005, scientists at The Institute of Cancer Research (ICR) – a charity and worldleading research institution – have discovered 20 drug candidates, 10 of which have entered clinical trials. One of the ICR’s drugs is now standard treatment for prostate cancer on the NHS and is extending the lives of hundreds of thousands
of men worldwide. However, while progress in developing targeted t re at ment s now a l lows m a ny patients to live longer, with fewer drug-related side effects, some cancer cells evolve and adapt to survive and resist treatment. To facilitate an ambitious research programme to tackle this challenge, the ICR is constructing a state-ofthe-art facility at a second site in Sutton. The Centre for Cancer Dr ug Discover y will bring together drug discover y a nd e volut ion a r y scientists to explore how t o o ut s m a r t cancer by using its s u r v iv a l i n s t i nc t against itself. The £7 5 m i l l ion building will house a series of pioneering
projects, with a focus on overcoming or redirecting the process of cancer evolution. The aim is to achieve long-term control and effective cures, just as comparable approaches h ave ac h ie ve d w it h d i s e a s e s like HIV. In this fantastic new facility, t he ICR w i l l overcome cancer drug resistance in innovative new ways, creating a new generation of treatments that will make a difference to millions of people with cancer. CEO Paul Workman says: “With further research, we can find ways to ma ke ca ncer a ma nageable disease in the long term and one t hat is more often curable, so patients can live longer and with a better quality of life. For more information, visit: icr.ac.uk/letsfinishcancer
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