Current Research

Dr Esther Burden-Teh, University of Nottingham

“They couldn’t decide whether it was a fungal infection.”

“I had psoriasis for about six and a half months before someone correctly diagnosed me.”

These are the experiences of some children and young people who have psoriasis who took part in

the healthtalk.org project. They found the delay in getting a diagnosis to be frustrating and

upsetting.

Psoriasis is a skin condition that can cause red, flaky patches on any part of the body including the

face, scalp, hands and genitals. Psoriasis can affect adults and children, but psoriasis in children is

often confused with other common skin diseases.

Diagnostic criteria can help doctors make a diagnosis. Criteria are a list of skin changes to look for

and questions to ask when the patient is seen in clinic. We have developed a version that patients

can complete themselves but we don’t know how well it works so we need to test it.

Before starting a large study across several hospitals, it is important to test the design. Therefore, a

practice study, called a pilot study, will take place first.

In this practice study, one hundred children and young people will be invited to complete an online

diagnostic criteria questionnaire before they have their dermatology appointment. We will compare

their responses to the diagnosis given by the doctor. We will also collect information on what makes

them more, or less, likely to fill in the questionnaire.

Dr Ella Guest, University of the West of England

Individuals with psoriasis can experience negative attitudes and discrimination from the general population, which can affect their psychological wellbeing (e.g., low mood, anxiety, depression, appearance concerns) and life engagement (e.g., avoidance of activities that draw attention to their skin, romantic relationships) and make it more difficult to manage their condition. Given that most of these challenges stem directly from the attitudes and behaviours of society, which are influenced by the (mis)representation of psoriasis in the media, it is important that charitable organisations have tools to raise awareness of psoriasis, increase knowledge of the condition, and reduce misconceptions towards it. Social media provides a cost-effective and wide-reaching platform for population-level campaigns and is regularly used by the Psoriasis Association; however, the effectiveness of current campaigns has not been assessed. Limited current research suggests including personal stories, educational information, and presenting psoriasis in a positive light may effectively reduce negative attitudes; however, this research is in its infancy. Therefore, further evidence-based research is needed to target negative attitudes towards psoriasis and develop an effective social media campaign intervention. Therefore, in collaboration with adults with psoriasis, this PhD would use a mixed-methods approach to understand experiences of misconceptions and negative attitudes using qualitative interviews and co-produce and evaluate a social media intervention that the Psoriasis Association can use to improve the lives of people with psoriasis by targeting the general public.

Dr Paola Di Meglio, King’s College London

The focus of this proposal is a cellular protein called Aryl Hydrocarbon Receptor (AHR) which responds to dietary, light and microbial stimulation by switching off inflammation in the skin. Importantly, a compound called tapinarof, which works by instructing AHR to switch off inflammation, has been tested as topical medication in people with psoriasis, with good efficacy in around 50% of them. However, it is currently unclear how much AHR there is in the skin of people with psoriasis, what determines the amount, and whether that amount is enough for tapinarof to work as an anti-inflammatory drug. Moreover, some evidence suggests that the amount of AHR in the skin may differin people of different ethnicities. We aim to study the skin of people with and without psoriasis who define their ethnicity according to the UK Census 2021 categories as Asian or White to find out:1)What affects the amount of AHR present in skin cells and whether it varies according toethnicity2)How much AHR is present in their skin3)If the anti-inflammatory effect of tapinarof depends on the amount of AHR present in the skin and whether it varies according to ethnicity. Taken together, these experiments will enhance our understanding of how environmental factors influence psoriasis and treatment in people of different ethnic groups. Moreover, they can provide further opportunities to find novel effective medications or lifestyle intervention to improve the lives of people living with psoriasis.

Dr Zenas Yiu, the University of Manchester

The newer injectable biologic therapies that target interleukin(IL)-17 and 23 are more effective for the treatment of psoriasis compared with the older biologics such as ustekinumab, a IL-12/23blocker, and TNF inhibitors. However, we do not yet know whether these newer treatments lead to more, less, or different types of serious infections in people with psoriasis in the routine clinical setting.

We will perform two studies to investigate this. Our first study will be a review of existing data on this topic, where we will look for all the relevant available evidence comparing the infection risk of IL-17 and IL-23 inhibitors with the older biologics. This will help us understand the strengths and flaws of current research and focus our further research on any gaps in knowledge that exist. If these studies are similar enough, we will combine this data together. We anticipate that the current evidence for the newer biologics will not be as robust.

Our second study will use a large national, well-established, long-term ongoing database of people with psoriasis on biologic therapies. We will test whether people on the newer IL-17 and IL-23inhibitorshave any difference in risk of serious infection, which are those that lead to hospital admission and require intravenous antibiotic treatment, or death, compared with the older biologics, and analyse whether there is any specific type of infection that is more common inpatients on individual biologic therapies.

These studies will provide both psoriasis patients and their doctors with an accurate estimate of the risk of infection while on the newer biologic therapies which will allow them to make well-informed decisions to choose a particular biologic treatment

Dr Elaine Clarke, Sheffield Hallam University

Many people living with psoriasis can find it difficult to use topical treatments as prescribed. People often dislike their topical psoriasis treatments and receive little practical support to use them, so may not use them exactly as their doctor instructed. This can mean that the topical treatments do not relieve symptoms as well as they should, which can be distressing and make self-management of psoriasis difficult. It is therefore important that we work with people living with psoriasis to develop new ways of supporting people to use their topical treatments.

Self-compassion—being sensitive to your own distress and wanting to reduce it—may be helpful for this. We know that in people living with some long-term conditions, self-compassion is linked with people using their medication as prescribed. Furthermore, when people are helped to become more self-compassionate, they tend to act in healthier ways, including taking better care of themselves. However, we do not yet know whether self-compassion is linked with use of topical treatments in people with psoriasis. We also do not know whether people with psoriasis would consider help to become more self-compassionate as a relevant and acceptable way of supporting them to use their topical treatments. We propose to investigate the link between self-compassion and use of topical treatments in people living with psoriasis, and to use the findings from this work to co-develop new self-help materials to support people to use their topical treatments as prescribed.

We propose to carry out two pieces of work. In the first, we will conduct a survey of people living with psoriasis to investigate the link between self-compassion and use of topical psoriasis treatments. In the second piece of work, we will invite people living with psoriasis who are prescribed topical treatments to take part in co-production workshops. We will work together as a group, incorporating the survey findings, to co-design new self-help materials (e.g. information sheets or a self-help booklet) to support people to use their topical treatments as prescribed. These new co-produced materials will be given to the Psoriasis Association to share with the public.

Dr Zenas Yiu, the University of Manchester

Biologic therapies for psoriasis, which are targeted injection treatments made of manufactured antibodies, are very effective and have transformed the level of success patients with psoriasis can achieve in clearing the skin. These medicines are made using living cell lines and are costly.

Biosimilar is a term used to describe a me-too medicine designed to work in the body in the same way as a biologic medicine already available for use by patients, also called originators. Biosimilars do not need to go through as much testing; makers of biosimilars only need to show there are no major differences between their product and the originator. The costs of biosimilars are usually much lower, offering the NHS cost savings whilst opening opportunities to treat more people in the future.

However, biologics have complex chemical designs, and it is difficult to make a biosimilar that is exactly the same as the originator. Although trials have not shown any difference between biosimilars and originators, we do not yet know whether this is the same in routine clinical practice.

We designed a study using data from the British Association of Dermatologists Biologics and Immunomodulator Register, a large multicentre registry of patients with severe psoriasis based in the UK and the Republic of Ireland, with the objectives to firstly describe the current use of biosimilars for the treatment of psoriasis in the UK; and secondly to generate evidence to show whether biosimilars have the same effectiveness and safety compared to originators under routine clinical practice settings.

Latest results summary

Tumour necrosis factor-alpha inhibitors (TNFi) are injectable treatments that are very effective for the treatment of moderate to severe psoriasis. These medicines were previously costly. Biosimilars, which are treatments that are manufactured so that they are like the original drug (originators),are much cheaper. However, the development process and regulatory pathway of biosimilars are not the same as orginators. Some people are therefore concerned that small differences between biosimilars and originators might have unwanted poorer treatment effects or safety problems when used with patients in clinic.

We performed a systematic review, which is a reproducible, rigorous, and transparent search of the evidence, and found reassuring data to suggest that the treatment effect and safety of biosimilars were no different to originators in people starting these drugs or in people switching to biosimilar drugs. However, we also found that this data was limited because most of the evidence was based on clinical trials, which are carried out over short periods of time in selected groups of patients. We did not find any high-quality studies investigating the use of biosimilars in routine settings.

We conducted a second study looking at the use of biosimilars using data from the British Association of Dermatologists Biologics and Immunomodulator Register (BADBIR), a large multicentre registry of patients with severe psoriasis based in the United Kingdom (UK) and the Republic of Ireland (RoI) and showed that the rate of switching to or starting TNFi biosimilars increased over time and varied across the UK and the RoI. Biosimilar use was found to be more common in male patients or patients with low disease severity.

For the next phase of the project, we will conduct a multi-centre international study in collaboration with research teams across the world to compare the effectiveness and safety of biosimilars to originators for the treatment of psoriasis in real-world settings.

Dr Satveer Mahil, King’s College London

Psoriasis research has delivered powerful drugs (called biologics) which act by influencing the immune system. ‘Remission’ (achieving clear skin with no/low risk of psoriasis recurrence upon stopping therapy) is now achieved more frequently than ever before. However, biologics are still continued lifelong at standard doses. This is costly and burdensome, with regular injections, blood tests, risk of infections and side effects.

We therefore need to identify patients in remission, in whom clear skin could be maintained with less frequent dosing (‘dose tapering’) or by stopping treatment.

1. Identify the immune cell types driving remission.

• We obtained skin biopsies before and after biologic treatment in patients in remission. We will examine individual immune cells present in these samples, using an innovative technique called single-cell sequencing.

2. Confirm that these immune cells are also observed in publicly available studies.

• We will validate the above findings by comparing our individual cell data with results of traditional studies, comprising information from a mixture of cells.

3. Demonstrate the presence of these immune cells in skin and blood collected from a new group of patients receiving biologics.

• We will use experimental techniques to detect the immune cells defined in the previous stages of the study.

The above steps will define the cells driving remission in people receiving biologics. This will identify patients suitable for dose tapering, which may reduce the burden of long-term biologics use and improve outcomes in psoriasis.

Latest results summary

Biologic drugs have revolutionised outcomes in psoriasis, with a growing number of patients achieving clear skin (‘remission’). However, the cells and molecules in skin that drive remission to biologics remain poorly understood.

We used skin samples donated by people with psoriasis to investigate changes in the skin before and during early biologic treatment. We performed a technique called single cell sequencing. By studying individual cells, this powerful technology helped to identify a new cell type that may coordinate the early effects of biologic treatment. We followed up our findings using skin samples from independent donors with psoriasis. We used a method called RNA scope to find out where these cells are located in skin. We found that the new cell type was located near to the upper layer of the skin and decreased in abundance by day 14 of biologic treatment.

Our study has uncovered a new cell type that are ‘early responders’ to biologic drugs, potentially driving early skin clearance in response to treatment. This information may help us to select individuals most likely to respond well to treatments available already, and design better treatments for the future.

Dr Thiviyani Maruthappu, Queen Mary University of London

The APPLE Study (Asking People with Psoriasis about their Lifestyle and Eating) aims to help address one of the commonest questions that people living with psoriasis ask, whether changes in diet may or may not be helpful for their skin. Therefore, developing evidence-based dietary guidance is a key priority. This study aims to address this unmet need by firstly, examining the current diet patterns of people living with psoriasis around the UK, in addition to lifestyle factors such as sleep and exercise. This questionnaire survey will enquire whether people with psoriasis have observed whether particular foods trigger their psoriasis or whether any dietary changes may have helped. Secondly, a small trial will compare two popular evidence-based diets – the Mediterranean diet and “Intermittent Fasting” to observe whether either of these are helpful in improving psoriasis and potentially associated risk factors for heart disease such as high blood pressure and cholesterol levels. By examining the amount of inflammation in the blood as well as the extent of skin involvement at the beginning and end of the study, we will be able to see if either of these diet affects inflammation. The study brings together a unique group of UK experts for the first time, dermatologists, scientists and nutritionists to provide a robust approach in exploring the relationship between diet and psoriasis. The PhD candidate will be a Registered dietician who, at the end of the study, will have developed expertise in the specific needs and challenges faced by people living with psoriasis.

Professor Miriam Wittmann, University of Leeds

We now have a range of medicines available to treat psoriasis. These therapies work in many but not all patients and some patients have to stop medication due to side effects. Unfortunately, we still do not have tests available to tell us which therapy works best for which patients. The answer to this question is of high importance. At present, many patients experience a phase of “trial and error” before a good therapy is identified. Failure to respond to treatment leads to frustration, depression and potential side effects from ineffective drugs.

Our project aims to predict therapy response to the commonly used drugs methotrexate and adalimumab. Our approach is different from already existing ones. Along with clinical data we also will collect information from affected skin but will not need biopsies. Instead we use a non-invasive tape stripping. We have used this method before and have optimised it so we can now detect thousands of proteins from each sample.

Due to the large amount of data collected it is impossible to analyse this information manually. We will therefore input all of the different and complex data into a “machine learning” computer program. Machine learning can be very powerful. Through many millions of calculations the computer is able to find “patterns” within very complex data. In our case we will look for the best “pattern” to predict response to methotrexate and adalimumab. We will share the program that we develop so that other researchers can use it to predict response to other drugs.

Latest results summary

Choice of therapy for moderate-to-severe plaque psoriasis is currently dominated by a trial and error. This project aims to identify means of predicting, before treatment, whether a patient will respond to a given systemic treatment by clinical data and skin samples. Direct sampling of a lesion classically involves an invasive skin biopsy but this project will use adhesive tape strips as a painless means of sampling. This will allow for many more patients to be recruited, allowing for the reasonable application of Artificial Intelligence (AI) analysis methods.

Recruitment has been delayed due to the pandemic, but is now proceeding at a rate of approximately 12 patients per month with a total of 35 so far. In the meantime, data from another project – focused on psoriatic arthritis – has been used to develop relevant methods and skills. Data gathered in these two trials is similar in structure and will likely face the same challenges in terms of format and missing data. Currently, recruitment is ongoing and processing of samples already collected is in progress. In addition, proteins of interest for measurement in the samples are being identified.

Professor Silvia Bulfone-Paus, University of Manchester

Psoriasis is a common, chronic, and as yet incurable inflammatory skin disease. Our project seeks to investigate the contribution of specific skin immune cells, namely mast cells and CD8 T lymphocytes (CD8 T cells), to the development of psoriasis. The latter have long been known to play a critical role in psoriasis, while the former cells have mainly been studied in the context of psoriasis-associated itch. Instead, here we explore whether mast cell-CD8 T cells interactions actually can drive the disease and are thus an important, new therapeutic target.

In psoriasis plaques, both mast cells and CD8 T cells are higher in number than in normal, healthy skin and appear to interact closely with each other. Furthermore, by isolating mast cells from skin biopsies and comparing their gene expression in healthy skin and in psoriasis plaques we have identified a number of secreted products or mediators of mast cells whose expression is increased in psoriasis and can regulate CD8 T cell activities.

Therefore, the overall goal of our project is to characterize the biological significance of mast cells-CD8 T cell interactions and how these may contribute to the development of psoriasis and their response to treatment. We also study how their activities are affected by biologic therapy targeting a key immune system molecule – interleukin (IL) 17. This knowledge will suggest novel strategies for therapeutic intervention, e.g. by manipulating mast cell mediators in psoriatic plaques so as to block the activation of CD8 T cell and thus reduce skin inflammation.

Latest results summary

The focus of this project is on mast cells and CD8 T cells, two immune cells that are enriched in psoriasis lesions. The hypothesis driving our study is that mast cells are critical modulators of pathogenic CD8 Tcell activities in psoriasis.This builds on work that has already been done in our lab that showed the increased gene expression of MC mediators that are capable of modulating CD8+ T cell activity in psoriasis skin. Our first aim was to identify the subpopulation of CD8+T cells that are dysregulated in psoriasis. To demonstrate that, we have designed a panelwith23 cell surface and intracellular markers and have optimized it. To establish a baseline, we analysed the blood samples from 8 healthy donors. In parallel, we have confirmed the spatial co-localization of mast cells and CD8 T cells in both healthy and psoriasis skin samples. In future, we will apply the established system to samples from psoriasis patients. We would like to investigate the alternation in mast cells and CD8 T cells as well as their connection with disease severity. We will also set up in vitro cell culture system to explore the mechanism and the factors that regulate the bidirectional interactions between these two cells.

Dr Francesca Capon, King’s College London

Several studies have demonstrated that smokers are at increased risk of psoriasis. At the same time, it is not clear whether giving up cigarettes can improve disease symptoms. Our study will address this important question by:

- Identifying the changes that occur in the skin of smokers affected by psoriasis

- Demonstrating that these alterations can be reversed by quitting smoking

Thus, our specific objectives will be:

- To identify changes in chromosome conformation in psoriatic skin. Smoke can affect the way that genes and proteins are packaged together into chromosomes. As this can influence the activity of genes that contribute to inflammation, we will compare chromosome conformation in individuals with psoriasis and healthy volunteers.

- To demonstrate that the chromosome changes observed in psoriatic skin are linked to smoke. We will grow skin cells in a dish, in the presence of chemical substances that are found in cigarette smoke. We will then determine whether these chemicals can induce the same changes we observed in the skin of affected individuals.

- To show that giving up cigarettes can reverse the chromosome changes induced by tobacco. We will obtain skin biopsies from psoriasis sufferers who have agreed to stop smoking. We will determine whether their chromosomes are reverting to a normal conformation and whether this correlates with an improvement in disease symptoms.

Taken together, these experiments are expected to provide a scientific rationale for introducing stop-smoking programmes in the treatment of psoriasis.

Latest results summary

We initially focused our attention on palmoplantar pustulosis, as this is a severe disease variant that mostly affects smokers. While the Covid-19 epidemic has disrupted our research activity and limited access to our laboratories, we have been able to investigate whether genetic factors synergise with cigarette smoking in causing PPP. We initially examined a gene called CARD14 which is known to malfunction in many diseases that affect the skin. We have demonstrated that individuals who carry genetic defects in CARD14 are at increased risk of developing PPP, whether they smoke or not. We are now expanding our analysis to all the genes that are found in our DNA. Our preliminary results indicate the existence of additional genetic defects predisposing to the onset of PPP. Once we have characterised them, we will investigate whether they have a stronger effect in smokers.

Dr Alison Havelin, Royal Victoria Infirmary, Newcastle

Psoriasis is a chronic skin disease affecting 2% of the UK population. It is a visible, often stigmatising disease and can have a significant impact on patients’ quality of life. UVB (ultraviolet B light) is one of the few psoriatic treatments that can lead to complete psoriasis clearance and a period completely free of psoriasis (remission) after treatment has stopped. For patients, this means living a life without the burden of applying messy topical therapies or taking potentially harmful medications to control their disease. The achievement of improved clinical remission with UVB is therefore highly attractive.

UVB is more effective in some patients than others, with 2/3 of patients achieving good clearance. The response to UVB is variable and currently there is no accurate way of predicting which patients will do better than others.

A typical UVB treatment course requires patients to attend hospital 3 times weekly for 6-10 weeks. Our recent study identified a subgroup of patients who were less likely to achieve clearance of their psoriasis, by analysing their response after just 3 weeks of treatment.

We hypothesis that by identifying these “slow-responders” early and changing their phototherapy regimens from three times per week to five times per week, they will have a better chance of clearing. To the best of our knowledge, this has never been studied before.

The optimisation of UVB treatments based on individual responses allows us to develop personalised treatment plans. This would benefit patients by reducing the need for potentially toxic systemic treatments and would result in better utilisation of NHS resources.

Latest results summary

This study was delayed due to Covid-19. All participants have now completed their UVB courses and follow ups and the study is at the write up stage.

Dr David Hill, the University of Sunderland

Psoriasis is a chronic skin complaint characterised by raised red patches of skin called plaques. These plaques are caused by the over-production of skin cells, which in contrast to normal skin cells that die and become replaced by healthy cells from below, fail to die off correctly leading to thickened skin and impaired skin barrier function. As a result, psoriatic plaques can often become inflamed and painful. Unfortunately, despite the development of new immuno-therapies there remains no cure. Therefore, to develop more effective therapies for psoriasis we need a better understanding of the underlying causes of the disease.

Our preliminary data and results from previous studies suggest that psoriasis skin has increased expression of a protein called fatty acid binding protein 5 (FABP5), which is responsible for controlling the breakdown of a class of growth-regulators called endocannabinoids, and has been linked to increased growth of several cancers. We propose that endocannabinoids, which suppress the growth of normal skin cells, are degraded in the skin of psoriasis patients leading to increased cell production and defective skin barrier formation. Our research aims to investigate how frequently levels of FABP5 are increased in psoriasis by staining a small cohort of affected and unaffected skin biopsies with antibodies that detect FABP5. We will also reconstruct full-thickness skin in the lab from normal skin cells that we have genetically modified to increase levels of FABP5, which will tell us whether high FABP5 is sufficient to cause psoriasis. Finally, because psoriasis skin likely has reduced levels of endocannabinoids, we will investigate the effect of cannabinoid treatment (and specific FABP inhibition) on the growth and behaviour of FABP5-expressing skin cells.

Patients and health practitioners are increasingly looking at cannabis and cannabis-derived compounds as realistic and viable sources of medicine due to their excellent safety profile and changing legal status. However, the lack of preclinical evidence regarding disease-specific mechanisms and efficacy is a cause for concern. This study will allow us to better understand the role of cannabinoid signalling in psoriasis, which will form a rational basis for conducting future in-patient clinical trials.

Latest results summary

This study was delayed due to Covid-19. The study is now at the write up stage.

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.

Latest results summary

Biological drugs, such as ustekinumab (Stelara®), have a significant positive impact on the lives of people with moderate-to-severe psoriasis. Nevertheless, ustekinumab does not work in every individual. To prescribe the best possible drug to each individual with psoriasis, doctors need to be able to classify people according to specific biological markers (“biomarkers”) that predict the likelihood that a specific drug will work. In this PhD project, we are analysing white blood cells in the blood of people with psoriasis receiving ustekinumab and measuring a number of biological markers associated with them. In the first year of the project, we have developed a laboratory test to measure the effect of ustekinumab in specific white blood cells and applied this test to the first 10 samples from people with psoriasis. Moreover, we have applied mathematical and statistical techniques to understand whether any of the biological markers measured can predict whether each individual will do well on ustekinumab. Preliminary data suggest that some types of white blood cells may be more sensitive to the effect of ustekinumab and this may be associated with whether the drug works or not. Next steps will involve increasing the number of samples and analysing more biological markers with the aim to further verify and expand our findings. Taken together, our project has the potential for identifying biomarkers in the blood of people with psoriasis to predict response to ustekinumab, for the benefit of people with psoriasis, and to reduce costs for the NHS.

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.

Latest results summary

In this part of the project, we have been trying to study and characterize the differences between human normal and psoriatic skin keratinocytes. These cells were isolated from either normal or psoriatic skin samples and immortalized in the lab, allowing us to measure important parameters in a simple live model. For example, we have been growing them in the lab and tested their ability to detox. Our data shows that psoriatic skin cells have a reduced capacity to eliminate their damaged or surplus cytoplasmic material. We are now investigating when exactly this defect is picked up by psoriatic cells and whether we can reproduce the same defect if we chronically expose normal skin cells with inflammatory stimulants. We are also imaging human skin samples from both healthy and psoriatic patients. We stain our samples with immunofluorescent protein tags which show us where in the skin certain detox pathway proteins are expressed. When we compared the amount and location of these detox proteins between healthy and psoriatic skin samples, we have noticed few differences about where these molecules shift or their expression changes within the separate layers of the skin upon chronic inflammation. Following this information, we have developed a 3D psoriatic-like organotypic skin model, to further investigate how inflammation can affect the skin detox ability.

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.

Latest results summary

This study was delayed due to Covid-19 and has been extended.

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.

Latest results summary

This study was delayed due to Covid and has been extended.

We know that living with psoriasis can make it difficult to exercise and stay fit. In this PhD studentship we want to find out if exercise can help psoriasis or make psoriasis easier to live with or improve heart health in people who have psoriasis. To do this we have created a 10-week group walking exercise programme, during the first year of the project. Other people who have psoriasis have helped us do this. Despite some delays due to lockdown and HM Government restrictions volunteer participants have been recruited.

Professor 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.

Latest results summary

Biologic therapies are injectable treatments for people with severe psoriasis who no longer respond to treatment with traditional oral systemic agents. There are some fears that people with psoriasis treated with biological therapies might have an increased risk of developing cancer compared with people treated with the older systemic therapies.

The first study of this project reviewed all the published evidence to date pertaining to the risk of developing the skin cancer, known as melanoma, after receiving treatment with biologic therapy for either psoriasis or conditions treated with the same biologics. Due to the small number of studies in psoriasis, we were unable rule out an increased risk of melanoma in patients treated with biologic therapy. These findings have only highlighted the urgent need to clarify if treatment with biologic therapy is a risk factor for cancer.

The next step of the project will aim to address this research question by exploring if the people with psoriasis, in the UK and the Republic of Ireland, treated with biologic therapy are at an increased risk of developing common cancers (breast, prostate, lung, colorectal and melanoma) compared with people treated with only non-biologic systemic therapies. The study will utilise data from The British Association of Dermatologists Biologics and Immunomodulators Register; known as BADBIR.

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.

Latest Results Summary

Humans, like in all living creatures, have an internal clock, or circadian rhythm. This means that expression of our genes and proteins changes throughout the day. Over the past few years, research into this has grown to become a huge discipline that aims to streamline and personalise medical treatment for people. In the same year the Nobel Prize was awarded for circadian rhythms, Professor Reynolds and I were awarded a Small Project Grant by The Psoriasis Association to set up, to our knowledge, the first research project looking into circadian rhythms in the skin of people with psoriasis. We also aimed to look into whether ultraviolet light affects psoriatic skin differently in the morning and afternoon, to see whether phototherapy – which is an ultraviolet light treatment given to people with psoriasis in hospitals – is better at a certain time of the day.

To this end, we have used the money to train a cohort of dermatology research nurses in how to administer UV light, how to read the results and how to take skin samples (our main source of research data). It hasn’t always been smooth, however! The field is always evolving, and so we have had to adapt our research to take into account new information. The Covid-19 pandemic has unfortunately been a big set-back for our study, initially halting all recruitment for six months. Once again, we had to modify our study, to make it safer for participants so we can continue to recruit. The pandemic has also changed our focus to analysing the data we have so far. Although it is from only five patients, we have forty skin samples – half of which are being analysed for gene changes and half for protein changes.

Ultimately, this is a pilot study, which means it aims to inform future research, but so far it has generated quite a lot of exciting data which we will share with you when we can. We are very grateful to you all for making this possible, and still look forward to a future where doctors personalise your treatment based upon your internal clock.

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.

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.