Current Research

The Psoriasis Association is currently funding a number of psoriasis research projects, from improving UVB treatment to investigating the impact of flare-ups.

To find out more about an individual project, please click on the title to read the project summary provided by the researchers. Please see the glossary for an explanation of scientific terms used in the summaries.

Identifying immune determinants of clinical response to ustekinumab in psoriasis.

Dr Paola Di Meglio, King’s College London

Biological drugs, such as ustekinumab (Stelara®), have a significant positive impact on the lives of people with psoriasis. Nevertheless, these expensive drugs do not work in every individual, and are still prescribed by trial-and-error. This process can be very frustrating for patients, and is not cost-effective for the NHS.

In order to prescribe the best possible drug to each individual with psoriasis, doctors need to be able to categorise people according to specific biological markers (“biomarkers”) that predict the likelihood that the drug will work. The Psoriasis Association-endorsed Psoriasis Stratification to Optimise Relevant Therapy (PSORT) is a multicentre study aimed at identifying biomarkers predictive of response to biologic drugs.

As part of PSORT, we are looking specifically at the white blood cells as potential predictive biomarkers. We aim to analyse cells already obtained from the blood of patients receiving ustekinumab, and measure a number of biological markers associated with them. Moreover, we will apply mathematical and statistical techniques to understand whether any of the biological markers measured can predict whether or not each individual patient will do well on ustekinumab.

Our findings will eventually be integrated with other datasets currently produced by PSORT (e.g. genetic data) to produce a clinically useful tool (“stratifier”) to guide psoriasis management, for the benefit of people with psoriasis, and to reduce costs for the NHS.

Impact of autophagy and nucleophagy deregulation in psoriasis

Dr Daniele Bergamaschi, Queen Mary University of London

Autophagy is a detox process naturally supporting the epidermis in cleansing and replacing damaged cells in exchange of energy. This is a crucial mechanism as one of the main skin functions is to protect the organism from UV exposure and infections.

When keratinocytes are surrounded by inflammatory cells for a prolonged time, they lose their ability to detox and replace damaged cells. Inflamed skin cells release toxic substances (Reactive Oxygen Species) which reduce their healthy ability to purify themselves thus preventing them to transform their shape and size. We have recently shown that when skin cells detox, they also gradually lose their nucleus with a process called Nucleophagy. This mechanism is not correctly functioning in the few skin diseases including psoriasis.

In this project we will further determine the effects of inflammation on the autophagy machinery in healthy human and psoriatic epidermis and will establish the consequences of having a deregulated form of this metabolic process. This will be achieved by measuring where the protein involved in the autophagy process of the skin are expressed and whether they are correctly functioning. As a model we will use cell lines isolated from normal and psoriatic skin and with them we will also reconstruct in 3D psoriatic-like artificial skin to perform experiments of drug treatment.

This research project will significantly improve our understanding of how this detox metabolic mechanism can impact on development of psoriasis and may lead to the identification of novel therapeutic and preventative targets for this common skin condition.

Investigation of the prevalence of liver fibrosis in patients with psoriasis using Transient Elestography and evaluation of the relationship between liver fibrosis and methotrexate

Dr Parastoo Babakinejad, Royal Victoria Hospital, Newcastle

Patients with psoriasis appear to have higher rates of liver fibrosis in comparison to the general population. The prevalence of liver fibrosis in the psoriasis population in the UK has not been defined. The higher rates of risk factors for liver fibrosis such as obesity, alcohol and diabetes are important; however there have been concerns that methotrexate can contribute to liver fibrosis. Despite the increasing importance of biologic therapies, methotrexate remains the most commonly used systemic agent in the UK. The majority of patients needing systemic therapy will try methotrexate first as per NICE guidance. 

This study aims to investigate the prevalence of liver fibrosis in a group of patients with psoriasis by measuring liver stiffness measurement (LSM) using Transient Elastography. The cumulative methotrexate dose in addition to other important factors including BMI, waist circumference and alcohol intake will be recorded. A univariate analysis will be performed to investigate the relationship between all measured factors and LSM. The relationship between the cumulative dose of Methotrexate and liver fibrosis will be addressed.

The ultimate goal is to use the prevalence data to perform a power calculation to determine the number of participants required to conduct a study to determine which factors can predict the risk of liver fibrosis and whether or not methotrexate is an independent risk factor for liver fibrosis in patients with psoriasis. Using this data a risk prediction model can be built to allow optimal and safe prescribing of methotrexate.

The impact of flare-ups on psychological wellbeing, treatment adherence, and life engagement in people living with psoriasis

Ms Ella Guest, University of the West of England

The transient and unpredictable nature of psoriasis can make it a difficult condition to manage. In addition to physical symptoms such as pain, itching, and discomfort, which are often visible to others, psoriasis can also impact considerably on psychosocial wellbeing. Although effective treatments for physical symptoms are available, evidence suggests that many patients find it difficult to adhere to their treatment regime, making them more susceptible to distressing flare-ups. Concurrently, previous research has found patients to perceive current information and support to be insufficient to help them effectively manage their condition. Compared to other areas of healthcare, qualitative research is relatively scarce, with little specific investigation into how people manage flare-ups. 

In the recent priority-setting exercise by the Psoriasis Association, the list of top 10 research questions included: “What’s the best way to treat sudden flare-ups of psoriasis?” The proposed study will investigate the impact of psoriasis flare-ups on patients’ psychological wellbeing and life engagement, barriers and facilitators to managing flare-ups, and patients’ information and support needs using an in-depth qualitative approach. Individual semi-structured telephone interviews will be conducted with approximately 30 individuals living with psoriasis, aged 16 years+. 

The findings will provide guidance as to what types of support may be most helpful, when, and for whom; identify how information and signposting by health professionals could be improved; and provide practical suggestions for supporting treatment adherence, allowing individuals to assert more control over their condition, reduce their likelihood of developing co-morbid disorders, and support them to cope with flare-ups. 

Investigating genetic control of the psoriasis transcriptome to define and validate drug and disease endotypes

Professor Nick Reynolds, Newcastle University

The genetics underlying psoriasis differs from person to person. Currently we have no way of knowing which treatment will work best for each patient and so treatments are prescribed by trial and error. As a result, only 50% of patients remain on their original drug 3 years later, which is not ideal for the patient and is wasteful of NHS resource. We need to find the right treatment, at the right time for the right patient: an approach known as personalised or stratified medicine. Our Consortium (PSORT) aims to develop tests based on blood samples or a small skin biopsy that predict individual patient responses to biologic drugs. This project builds upon the extensive clinical and sample resource already collected by PSORT.  

Developments in gene sequencing mean that we can now sequence all the messenger RNA molecules present in the skin or blood of an individual at reasonable cost. We will combine this information with the genetic makeup of individuals to produce markers of clinical response. Such complex data requires high-level computer analysis combined with biologic and clinical interpretation. As bioinformatics (a discipline involving method development and analysis of biological data) is a rapidly growing and developing field, this represents an ideal PhD project.  

Our established collaborative network provides an excellent training environment for a PhD studentship and will develop cutting-edge transferable skill sets for the next generation of researchers. Key outcomes will include biomarkers that can be developed into clinical tests that predict individual patient response to biologic drugs.  

Latest results summary

Currently we have no way of knowing which treatment will work best for each patient and so treatments are prescribed by trial and error. As a result, only 50% of patients remain on their original drug 3 years later, which is not ideal for the patient and is wasteful of NHS resource. We need to find the right treatment, at the right time for the right patient: an approach known as personalised or stratified medicine.  Our Consortium (PSORT) aims to develop tests based on blood samples or a small skin biopsy that predict individual patient responses to biologic drugs. This project builds upon the extensive clinical and sample resource already collected by PSORT. 

Developments in gene sequencing mean that we can now sequence all the messenger RNA molecules present in the skin or blood of an individual at reasonable cost. This is called RNA sequencing (RNASeq) and through bioinformatic analysis using computer programming we can work out the gene expression signatures (or patterns) within psoriasis plaques. We can also work out whether these patterns group together across patient groups or separate out into distinct groups. We are interested to test whether gene patterns before treatment predict clinical response 12 weeks late. We are also interested so see whether the two drugs (adalimumab and ustekinumab) affect the patterns of gene expression particularly early on (at week 1) before any improvement is seen clinically in psoriasis. This may provide clues and insights into how the drugs are actually working to clear psoriasis. 

Our work so far has uncovered gene expression signatures within psoriasis plaques that shed light on the mechanisms by which two biological drugs commonly used in psoriasis treatment, adalimumab and ustekinumab, clear the disease. Importantly we have also found that the patterns of gene expression at baseline within psoriasis (before drug treatment) predicts the response to biologic drugs.  Moreover, these patterns of gene expression distinguish between the response of individual patients to the 2 different drugs studied (adalimumab and ustekinumab). We need to check that these findings are reproducible by repeating these studies in our replication cohort.  Taken together and if confirmed, these results are an important step towards the main goal of the PSORT consortium: the development of scalable biomarkers that predict clinical response to individual biological drugs in psoriasis. Our next step will be to replicate these findings in a second cohort of patients. We are also planning a sophisticated analysis that will link other genetic markers to gene expression changes induced by these drugs.

Investigating the therapeutic benefits of exercise in patients with psoriasis.  

Dr Helen Young, University of Manchester 

Psoriasis, a common skin disease which confers immense suffering on those it afflicts, is associated with an increased risk of developing cardiovascular disease (CVD). The severity of psoriasis and the number of individuals affected by the disease are increased by obesity. Patients with psoriasis are often embarrassed about exposing their skin in front of others, which leads to exercise avoidance.  Lack of physical exercise and obesity are risk factors for the development of CVD. 

Individuals with psoriasis have much to gain by regular exercise including an improvement in psoriasis itself, a reduced risk of CVD, weight management and enhanced wellbeing.  Based on our research in this field, which was supported by a Psoriasis Association PhD studentship, we worked with individuals with psoriasis to develop an exercise programme that can be followed by sufferers – even on their worst day. This project will test our exercise programme in clinical practice and measure the improvement in psoriasis, CV health and overall well-being in patients.  We will also use a laboratory-based technique called transcriptomic analysis to investigate how exercise exerts its beneficial effects in the body. We will learn more about psoriasis and how to treat it effectively. 

An attentional bias approach to understanding and reducing the psychosocial burden of psoriasis 

Dr Henning Holle, University of Hull  

People with psoriasis often experience social rejection. A big risk in this context is that psoriasis can lead to a spiral of increasing social isolation, driven by a fear of negative social reactions. Every time a person with psoriasis experiences such a negative social reaction, the link between fear, avoidance and further social withdrawal is reinforced. At the same time, the person may become more likely to always carefully monitor the environment for signs that others might reject them, for example, by showing facial expressions of disgust. In the medical literature this state is known as hypervigilance, which can lead to a cascade of negative thoughts and emotions, increased anxiety and exhaustion. 

The present research project aims to determine whether people with psoriasis can learn to escape the vicious and mutually reinforcing cycle of fear and increased attention towards potential social threats. In a first step, we will systematically document the degree to which people with psoriasis show hypervigilance or increased monitoring for different types of information (disease-related words, facial expressions of disgust, bodily expressions of disgust). Once we have determined this, we will investigate in a second step whether people with psoriasis can be trained to allocate attention in a more balanced way, and whether such a training can increase resilience, reduce anxiety and thereby help to reduce the psychosocial burden of psoriasis. 

The role of IL-1 and IL-36 in palmar plantar pustulosis (PPP)

Dr Francesca Capon, King's College London

What is already known about the problem that the project will address?

Palmar plantar pustulosis (PPP) is a severe form of psoriasis manifesting with the appearance of painful pustules on the palms and soles. These lesions can be preceded or accompanied by plaque psoriasis and/or psoriatic arthritis. PPP is a disabling condition that has a profound effect on quality of life, as affected individuals can find it very difficult to walk or carry out everyday tasks. At the same time, very little is known about the causes of the disease, which as a consequence is extremely difficult to treat.

What do you hope to find out?

The aim of our research is to achieve a better understanding of the causes of PPP, as that is essential for the development of effective treatment. Our group has already discovered two genes that malfunction in affected individuals, causing excessive production of an inflammatory molecule known as IL-36. Importantly, we also demonstrated that IL-36 drives the release of a protein called IL-1, which can be blocked by existing drugs. This was a breakthrough, which suggested that PPP could be treated with known IL-1 inhibitors.

It is important to bear in mind, however, that the genetic defects we have discovered are only found in 10-15% of individuals with PPP. Therefore, it is still not clear whether abnormal release of IL-36 and IL-1 is a general feature of the disease.

With this project, we plan to identify novel PPP genes and to establish whether they also cause excessive IL-36 and IL-1 production. If we find that the newly identified defects do not alter IL-36/IL-1 levels, we will seek to clarify what are the alternative mechanisms whereby they cause disease.

Latest results summary

The focus of this project is on palmar plantar pustulosis (PPP), a severe variant of psoriasis that manifests with the appearance of painful skin pustules on the hands and feet. The hypothesis driving our study is that PPP is caused by the excessive accumulation of two related proteins called IL-1 and IL-36. To demonstrate that this is the case, we are examining the DNA of affected individuals, looking for changes in genes that influence IL-1 and IL-36 production.

In the last 12 months, we have concentrated our efforts on a gene called CARD14, which in the past has been linked to IL-36. We examined the DNA of 160 PPP sufferers and found that 14 of them carried CARD14 defects. Of interest, DNA changes that cause CARD14 to malfunction have previously been observed in individuals affected by other rare and severe forms of psoriasis (erythrodermic psoriasis and generalised pustular psoriasis). We are now investigating whether the mutations that we have identified and those reported by others can enhance the production of IL-1 and IL-36. This will shed new light on a common mechanism contributing to the onset of different forms of psoriasis.

Mutation burden of narrowband UVB

Professor Eugene Healy, Southampton University

Ultraviolet radiation (UV) in sunlight is an effective treatment for psoriasis.  Narrowband UVB (NB-UVB) is a form of “artificial sunlight” which is used widely by dermatologists to treat patients with psoriasis.  It is known that UV can cause skin cancer, but the long-term safety of NB-UVB in relation to skin cancer development is unknown.  It has been highlighted that, in order to determine the long-term safety of NB-UVB, large studies in multiple dermatology centres involving several thousand new patients per year would need to be conducted and that those patients would need to be followed up at least for 10 years or more.  In the meantime, patients with psoriasis and dermatologists do not know what is a suitable safe limit of NB-UVB treatments for people with psoriasis to have over the course of their lifetime.

All of the cells in our body contain the genes that we are born with.  These genes are written in the DNA in all our cells, including our skin cells.  Exposure of the skin to UV causes specific damage to the DNA in skin cells and leads to mutations (i.e. errors in the DNA) that affect the ability of the genes to work properly.  When a skin cell divides these changes are passed on to its daughter cells.  Over time, these daughter cells and their descendants (which are collectively known as a clone) may eventually accumulate thousands of mutations which may cause the skin cells to become abnormal and form skin cancers.  Recent advances in genetic technology have allowed scientists to map groups of cells carrying altered genes which drive the formation of cancer in normal skin.  In the proposed study, we plan to use this technology (called next generation sequencing) to detect how many groups of cells carrying DNA changes linked to cancer are induced by NB-UVB treatment for psoriasis.  Based on these findings, we will calculate the additional risk of cancer in a psoriasis patient resulting from multiple courses of NB-UVB and thus estimate the long-term safety of NB-UVB.

Latest results summary

Narrowband UVB (NB-UVB) is used as a treatment for psoriasis but it is also known that ultraviolet radiation has the potential to cause skin cancer. To identify how many courses of NB-UVB a patient can receive over their lifetime without being at significant risk of developing skin cancer, the changes in genes within the DNA in skin cells after a course of NB-UVB are being investigated.

Skin samples have been collected from 20 individuals with psoriasis before their NB-UVB treatment to date.  Of these 20 samples, so far 13 have provided a subsequent skin biopsy sample after the course of NB-UVB treatment (the others are still receiving their course of NB-UVB). These samples will be sent to the Wellcome Sanger Institute in Cambridge in the near future to identify changes in genes via Next Generation Sequencing (NGS).

Experiments have been conducted to ensure that the DNA from these skin samples is of sufficient quantity and quality for NGS. In preparation for the analysis of genes relevant to skin cancer in the NGS data that will be generated from the skin samples, publicly-available online genetic databases such as COSMIC (i.e. Catalogue of Somatic Mutations in Cancer) and genetic data obtained via a systematic literature search have been collated. Bioinformatics tools have been used to organise and analyse the data (while at the same time allowing the PhD student to gain bioinformatic skills and experience in this type of analysis).  Statistical tools have been employed to identify significant cancer-causing genes (known as driver genes) in this data. This information will be utilised in the analysis of the NGS data that will be generated from the above skin samples taken from individuals who have received a course of NB-UVB, with the results of that analysis allowing us to determine the long-term safety of treatment with NB-UVB.

The risk of cancer in psoriasis patients treated with biologic therapies compared with conventional systemic therapies: results from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

Dr Richard Warren, University of Manchester

Patients with severe psoriasis (more than 10% of the body surface affected) are often offered two broad types of long-term systemic treatment: conventional systemic treatments, such as methotrexate, ciclosporin and acitretin; and biologics, such as Humira, Stelara, and Enbrel. Biologic therapies target the immune system and may affect the body’s ability to fight cancer. It is not known whether being treated with biologic therapies carries an increased risk of cancer in psoriasis patients compared to treatment with conventional systemic treatments. Very few studies have compared the safety of these two treatment options and have been limited by short duration with only small numbers of patients. As cancers develop relatively rarely, we need to compare large groups of psoriasis patients receiving biologic and conventional systemic treatments respectively.

A pilot study to compare the response of psoriasis to narrow-band UVB phototherapy in the morning and afternoon

Dr Henry Grantham, Royal Victoria Infirmary, Newcastle Upon Tyne

Psoriasis is a very common skin disease. We often think of psoriasis as a disease of just the skin, but research shows that people who have psoriasis may have different body clock rhythms from the general population. We know that people without psoriasis are more sensitive to phototherapy with ultraviolet B light at different times in the day. What we don’t know is if this is also true for people who have psoriasis.

The main aim of this research question is to see if patients' psoriasis is more sensitive to ultraviolet light at different times of the day.

We also aim to see whether the participants in our study have different body clock (circadian) rhythms to the general population. We will do this in multiple ways, such as looking at the levels of a few chemicals in the body that respond to body clock rhythms (melatonin and cortisol), asking questions about participants' sleep (by questionnaire), measuring sleep (with a wrist-worn motion sensor), and asking the patients to fill in questionnaires about depression.

We will recruit 15 patients who have been prescribed phototherapy for the treatment of their psoriasis. The study will last nine days per patient and after this they will proceed to their prescribed course of phototherapy.

Not just skin deep: circulating lipids in a "localised" disease

Dr Timothy M Millar, Southampton General Hospital

People with psoriasis have a greater risk of clogged arteries and heart disease than the general population. People with psoriasis show more bad cholesterol and less of the good kind circulating in the blood. This can lead to fatty plaques growing on the inside of the blood vessel wall which are filled with white blood cells.

Plaque psoriasis shows large numbers of white blood cells in the skin and an over growth of blood vessels. We believe that the plaque form of psoriasis and the fatty plaques seen in the blood vessels have striking similarities.

From our earlier research, we have shown that some types of fat found in the blood can control new blood vessel growth. New blood vessel growth is part of how plaques form in psoriasis and more blood vessels mean more white blood cells. These white blood cells in turn can cause blood vessels to grow causing a vicious circle of continued plaque flares.

We have also shown that some white blood cells have the potential to be activated by blood fats and that when fats are removed, more white cells die. While some current treatments for psoriasis show effects on blood lipids they still have side effects which could be improved on. Together with other chemicals which are raised in psoriasis, these blood fats could provide a simple target to help treat the skin disease and also reduce the risks from clogged arteries.

It is likely that our approach would provide an additional treatment to those already in place. It would mean that traditional treatments can be scaled back which would benefit patients with potentially fewer side effects. There is also the added benefit of reducing blood vessel diseases and improving quality of life through gains in fitness. These fat restricted nutritional approaches are achievable today but knowledge of the best mix of dietary fats is a medium term goal. More long term outcomes would be small drug treatments targeting fat dependent processes.

An innovative mixed methods study investigating altered emotional processing in psoriasis patients

Dr C. Elise Kleyn, University of Manchester

Psoriasis is a chronic, inflammatory skin disease which affects 2-3% of the UK population. As a result of the appearance of their skin, patients with psoriasis commonly experience negative social interactions and reactions from others including facial expressions of disgust.

Our group were the first to use brain scanning (magnetic resonance imaging) to demonstrate that patients with psoriasis process facial expressions of disgust differently to individuals without skin disease. It was demonstrated that patients with psoriasis have a diminished signal in the insula, an area of the brain known to be important in disgust processing. This differential response may reflect a coping mechanism, adopted by patients to ‘block out’ the aversive reactions of others and protect themselves from stressful emotional responses. 

More recent, (unpublished) work, by the group suggests that an individual’s response to disgust may vary depending on the length of time a patient has had psoriasis and the age at which they were diagnosed. However, it is not known when this mechanism develops, or its wider implications on patients’ quality of life.

This novel study will pilot the integration of different techniques, including in-depth patient interviews and state-of-the art brain scanning, to further understanding of this proposed coping mechanism in psoriasis. Addressing this current gap in knowledge will inform the development of personalised clinical and psychological interventions to support people living with psoriasis.

Neuropsychological morbidity in psoriasis

Dr Elise Kleyn, University of Manchester

Psoriasis is a chronic skin disease for which there is currently no cure. It afflicts far more than the skin and there is limited knowledge of the mechanisms or way in which psychological effects as well as other brain effects are caused.

We were the first to use brain scanning techniques to show that patients with psoriasis process facial expressions of disgust differently to individuals without skin disease.

This PhD project will use state-of-the-art brain scanning, questionnaires and laptop-based tasks to investigate whether treating psoriasis lesions effectively will change altered processing of disgust in patients. Patients’ reactions to pictures of their own psoriasis lesions and those of others will also be studied in a separate group of patients who have had psoriasis for varying lengths of time.

Understanding the brain-skin connection is key to developing new approaches to help treat the psychological and other brain effects of psoriasis.

The Psoriasis Association is the UK's leading national charity and membership organisation for people affected by psoriasis – patients, families, carers and health professionals Read More >

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