Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Baroness Hodge of Barking Excerpts

Wednesday 13th July 2016 Westminster Hall

[Dame Margaret Hodge (Barking) (Lab)]

I beg to move,

That this House has considered awareness and funding for treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis.

It is a delight to move a motion under your chairmanship for the first time, Mrs Gillan, and I am grateful to the Speaker for selecting this issue for debate. I am also grateful to the Minister and look forward to having a positive exchange with him.

I had never heard of Stevens-Johnson syndrome or toxic epidermal necrolysis—my pronunciation of some of these medical terms may leave a little to be desired—until my constituent Nadier Lawson, who had suffered from the condition, contacted me. She has set up an awareness group, SJS Awareness UK, which is based in my constituency. It was because of her and that group that I asked for the debate.

SJS—and its much more severe form, TEN—is a severe reaction that affects the skin. It is caused by a whole range of standard medicines that we all use regularly. The reaction is most commonly caused by drugs used to treat epilepsy; some antibiotics, such as penicillin and sulphonamides; over-the-counter drugs such as ibuprofen; and medications that are commonly used to treat HIV and gout. The adverse reaction triggered by those drugs is devastating. I have seen pictures of children and adults who have had such a reaction, and they are truly shocking. People start with a skin rash, which rapidly develops into excruciating blistering across their skin, which starts to peel off. The condition particularly attacks the mucus membranes in the body—in the mouth, eyes, nasal passages and guts—and is similar to having third-degree burns on the skin. The condition is classified according to how much of the body surface is blistered: if it is less than 10%, the condition is called Stevens-Johnson syndrome; if it is 11% to 30%, it is called overlap syndrome; and if it is over 30%, it is called toxic epidermal necrolysis.

The initial symptoms that people experience are non-specific. Someone can take a pill one day and feel nothing for up to a week or two but then start to feel unwell and develop a rash, which is often assumed to be chicken pox, and may experience flu-like symptoms. A key problem associated with the condition is that all too often, it takes far too long to identify. Obviously, the first thing to do is to stop taking the medication that is causing the condition. Failure to identify the condition early enough can lead to terrible lasting effects, including permanent damage to the eyes—resulting at its most extreme in blindness—and lungs, loss of nail beds, arthritis and chronic fatigue syndrome. At the very worst, people die. Around one in 10 people with SJS, the mildest form of the condition, and up to a quarter of those with TEN, the most severe form of the condition, die.

I have a whole lot of case studies, but I thought it worth reading out just one, which was given by a young man who came to an event that I held in the House to bring together people who had experienced the condition. He is called Stuart Doyle, and he wrote and said this:

“Nine years ago I had a TENS reaction. I burned from the inside out and lost around 95% of my skin, all through second and third degree burns with permanent scarring. My finger and toenails burned off and have never grown back. The enamel on my teeth burned away. Mouth, throat, lungs and stomach all burned. My eyes burned and ulcerated, then fused to my upper and lower eyelids. My tear film was destroyed, as was my tear production and I lost all saliva production too. I also had inner ear burning and am now partially deaf in one ear. My genitals burned.”

I will skip a bit and give just a summary of what he said and wrote. He continued:

“I spent six weeks in a ketamine-induced coma, which I was placed in just two days after I arrived at my first hospital. I arrived with what seemed to be meningitis, it was textbook and it was moving fast. Two days later my oxygen SATS had dropped to the point where brain damage had begun its process. They acted quickly; they had already started treating me, my son, and my partner for meningitis. It wasn’t until after the lumbar puncture results came back, that they realised it was not what they first thought it was.

The high doses of anti-biotics were stopped, by this point my throat and lungs had begun burning and blistering and a rash now covered more than half of my body. It was the lungs and throat burning that had begun to close up my airways and provoked the need for a ventilator to keep my brain intact. The ketamine-induced coma was to try and get my heart rate back down from the 180 beats per minute mark caused by the pain of the internal burning. If they’d not done that, I’d have certainly died from cardiac arrest there and then. I was to stay in the coma on full life support for six weeks; my total hospital stay was three months. I woke up in a different city.”

He goes on to describe how the condition has impacted his life, saying:

“I hoped I’d die, I wished every night for 3 years after my reaction that I’d not wake again. I had more surgeries than I can recall, my eyes were in a terrible state.”

This is the treatment that he requires today:

“My eyes require a tremendous amount of work. My day starts before 6am and ends around midnight. I have to change my lenses at least 20 times a day, put in more than 100 drops, both lubricants and steroids, and then there is the ever present pain. But, it’s totally worth the effort and I am so lucky, and grateful for all the work that my doctors put in to get me to here.”

He then says:

“The hardest thing about my new life, is the chronic pain”.

[Jim Shannon (Strangford) (DUP)]

I congratulate the right hon. Lady on raising awareness of this issue. As far as I am aware, this is the first time that this condition has been brought to the attention of Westminster Hall and the Minister. The background information about the condition indicates that it can be triggered by normal medicines such as paracetamol. Is it time for the Minister and the NHS to address the issue by raising awareness of the condition among GPs, consultants and everyone else? The condition affects only one or two people in every million, but it is an important issue.

[Dame Margaret Hodge]

I completely agree. We are raising awareness through the debate, and I hope that the Minister will take action so we can get early identification and therefore prevent people from suffering the condition’s worst impacts.

The condition is rare, and therein lies the problem. I would appreciate it if the Minister addressed the following issues. There is a lack of awareness among many medical professionals, who just do not come across the condition. Insufficient attention is paid to the condition and its symptoms in the education and training of all health professionals. Survivors whom I have talked to all talk about that. A young man, Laurence McCalla, went to my local hospital, Queen’s hospital. They gave him antibiotics; it took about 24 hours to identify the condition. At one point he had 20 doctors and consultants looking at him, because it was new to them and they wanted to learn from it as a case study. Another lad, from Worcester, said:

“There is one big thing that stands out the most from this though. It astonishes me that so many doctors I have seen do not know about it.”

Debbie Hazel was misdiagnosed three times, as doctors thought she had chicken pox. She says:

“One of the problems was the lack of knowledge doctors have about the condition.”

The mum of a 13-year-old son, who lives in Surrey, says:

“My son was so ill and I couldn’t hold him or kiss him. He was screaming because his skin was so raw. I felt helpless. Nobody could tell us what was happening because nobody knew.”

My first ask to the Minister, therefore, is for a commitment that the condition, and its symptoms and treatment, should be taught to medical students, nurses and pharmacists as part of their educational courses. SJS Awareness, the organisation in my constituency, has a fantastic poster about the symptoms and how to spot the condition. Those posters could, if the Minister were to help us, be distributed to all GPs. Early diagnosis, and therefore awareness, would not just alleviate suffering; it would save lives.

Guidance has also been prepared on the clinical pathway by the British Association of Dermatologists. What steps will the Minister take to ensure that that guidance is followed throughout the country so that identification and treatment of the condition is not a postcode lottery? SJS Awareness has asked me to ask the Minister whether we could have an SJS awareness week for the general public. We are talking about such regularly used medicines—Optrex, ibuprofen, penicillin. They are standard medications, which we do not even think about using. We need to raise our awareness about the potential side effects.

Finally, because the condition is rare, money for research on it is limited. However, there is a cost to the NHS from not understanding the condition or recognising it early and understanding how to treat it. I understand the cost of treating skin reactions is about £500 million a year and it simply makes economic sense, as well as being a question of people’s lives, of course, to use research to get better at understanding why some people have such a reaction to drugs. An interesting key finding on genetic testing is that, in China, there is a gene in the population that predisposes people to different types of skin reaction, putting them at a higher risk from the drug carbamazepine. I do not know whether the Minister has come across that. In China and Taiwan, doctors test for the gene before they administer the drug. If we did more work here, we could manage that.

We also want research on new and better ways of treating severe reactions. From what I gather, more treatment should happen in burns units; often that is not understood and people are put into the intensive care unit and given the wrong medication. Finally, it is very important that we should have research on better understanding the features of drugs that make them more liable to cause the reactions in question. Those are three hugely important areas of research. I hope that the Minister can give us some comfort on that point.

People who saw the title of today’s debate would not have had a clue what I was going to talk about, yet the condition could affect any one of us, because we all take the medications concerned—they are standard. I have a file full of tragic cases of people affected by Stevens-Johnson syndrome, yet many people would not have a clue what we are debating. I ask the Minister, therefore, to do some practical things: to help us to raise awareness; to improve the training and development of all medical professionals, so that they understand the syndrome; and to get money for research so that we can understand the causes and prevent recurrences of this terrible condition in our population.

[The Parliamentary Under-Secretary of State for Life Sciences (George Freeman)]

It is a pleasure to serve under your chairmanship, Mrs Gillan, not least because on other occasions you have been a doughty champion of campaigns on rare diseases. It is also a pleasure to respond to the debate. I congratulate the right hon. Member for Barking (Dame Margaret Hodge) on obtaining it and thank her for raising the issue. It is my great privilege as the Minister for rare diseases to be educated every time we have such a debate. A process of huge preparations is triggered in the Department, so already, just by raising the issue, the right hon. Lady has struck a blow and alerted the machine to the condition and its causes. However, I want to go further.

Perhaps, as this is the day when we say farewell to the Prime Minister, I may pay tribute to his personal leadership in the field of medical research, and to his unleashing of UK leadership, building on what happened under previous Administrations. The Labour Government did a lot of great work setting up the National Institute for Health Research, but because of the Prime Minister’s experience with genetic conditions in his family he has been an incredible champion of genomics and of rare disease science and research. As he leaves I want to state that that is one of his great legacies. It has been my privilege to be his first Minister for Life Sciences, with the purpose of driving forward that quiet revolution and UK leadership.

I also want to pay tribute to SJS Awareness. As with so many rare conditions, it is charities and patient groups, the patients and victims of diseases, who take the early steps in speaking up, raising money, rattling tins, having raffles and raising awareness, which in the end lead, as I see often, to huge progress and advances in research and treatment. I encourage them to continue and not to give up. I hope that what I will say will send a good signal.

The truth is that the debate on this condition shows up a wider issue throughout the biomedical research community. The more we know about disease and how patients respond to drugs, the more we realise how many conditions there are. We discover them literally each month through the UK genome project, at a faster and faster pace, and that is changing the way drug discovery works, and the way the system thinks of conditions. The old model of diagnosing on a standard understanding of X number of conditions with clear symptoms no longer holds. We must, as the right hon. Lady said, think about how we will help a new generation of clinicians to have at their fingertips the genomics, data and informatics to be able to recognise conditions and triage patients into the right treatment.

The Government take the issue of rare disease treatment incredibly seriously, and that is why we have worked with NHS England on launching the UK rare diseases strategy. There are now 51 recommendations. It is not just a brochure; it is a serious document with commitments and an action plan. Although the number of rare disease patients suffering from a particular condition may be small—the one that we are considering affects about 150 patients a year—collectively more than 3 million people in the UK suffer from rare diseases, so they are not rare; they are very common, and they are experienced by a huge number of people. It is only fair that the system should recognise that, and start to adjust and adapt towards the mainstreaming of provision for people with rare diseases.

Research is, of course, vital, which is why the £1 billion a year that we spend on the National Institute for Health Research, the £850 million for the Medical Research Council and the £1.4 billion spent by the Association of Medical Research Charities and its members is so important. That underpins UK leadership in this space, and it is even more important for rare conditions such as Stevens-Johnson syndrome. There are some encouraging research projects under way which I want to highlight, partly because I think they give hope to patients and charities.

The National Institute for Health Research clinical research network is supporting the MOLGEN trial. It is actively recruiting patients from across 80 NHS trusts who have experienced adverse drug reactions. That study has already recruited 1,740 participants and plans to continue recruiting patients until February 2019 with an eventual aim of accurately predicting those patients at risk of developing severe reactions, including Stevens-Johnson syndrome.

Further research that is likely to benefit those with the syndrome include the 10-year study of chronic eye inflammation, including SJS, which is being taken forward by the NIHR clinical research network in the west midlands. That has recruited 224 patients to date and will continue until 2021. The MRC Centre for Drug Safety Science at the University of Liverpool is doing powerful work in this field and has already been instrumental in identifying some of the genetic markers that indicate that a patient group are at an increased risk of developing the condition. The progress we are making in genetics generally, in terms of deep science, diagnosis and genetics for new cures, holds real hope. Being realistic, that is not hope for those patients who are in that excruciating agony that the right hon. Lady powerfully described in the words of one of her constituents.

While patients with SJS are more likely to be identified earlier and receive the best forms of clinical management, we want to prevent the condition in the first place by understanding the underlying genetic causes. That is why we are so committed to the 100,000 Genomes Project. For those who are not aware of it, it was led and inspired by the Prime Minister. I describe it as the NASA of UK biomedical research. It is our world-leading project to take 100,000 entire, fully sequenced genomes from NHS volunteers and combine them with phenotypic hospital data to form a global reference library for understanding the genetic predispositions for both disease and drug reactions. It is that combination of the living medical record of patients at scale with their genomic information at scale that allows us to understand those genetic mutations, which are often not associated with a particular condition so are not studied. When we have the whole genome at scale we can see, for example, the reason why 20% of patients respond to a certain drug in a certain way is that all of them have a genetic variation, which we had not realised, in a sequence that nobody had realised was associated with that disease.

Although we are only partially through sequencing the first genomes, we are already identifying extraordinary insights into rare diseases. I saw recently, when meeting the informatics team at Genomics England, a man who had presented with a rare blindness disease. It presents in teenage years with early onset blindness and can lead to mortality at around the age of 40. He has two young boys. He volunteered for the programme and the scientists quickly identified five possible variations that may have accounted for the condition, of which they were able to knock out four that had nothing to do with the eye. One was a pathway related to the eye and on that information alone they were able to recognise that that pathway is one that is implicated in the disease, for which there is already a treatment that is available at pence as a generic. With the patient’s consent they decided to try it and the drug arrested the condition.

That is an extraordinary breakthrough that was based on genomics simply allowing us to understand, initially quite randomly, how to prevent that condition, though we have not got a cure for it. We have identified in the haystack of the pharmacopeia of drugs one that has already worked. The genome programme is already identifying early treatments that are giving patients with rare diseases real hope. I am delighted to say that while the programme is a bit behind on the recruitment and sequencing of cancer genomes, for a whole series of operational reasons, it is steaming ahead on rare diseases. The UK is driving world leadership in that space. I was recently in Washington and met the White House precision medicine team, which is looking to us for a steer on how to use genomics to drive rare disease treatment and diagnosis.

[Dame Margaret Hodge]

To be specific about SJS, are there volunteers who have the condition, or relatives of volunteers who have it, in that sample? I do not know what is appropriate; I am not a great scientist, but that would seem to me to be a very useful way of progressing on this particular rare disease, though I recognise it is one of many. Does the Minister know?

[George Freeman]

The right hon. Lady read my mind. I do not have that information at my fingertips but I have already asked that question and I will happily ask Genomics England to ensure that she and I have that answer. I will touch on the point she made about awareness because I think there is an opportunity for us to use the genomic programme to trigger greater awareness among those who suffer from rare diseases, and possibly to drive up recruitment rates for the programme.

Let me touch on the NHS rare diseases advisory group, which recently noted that SJS is a devastating disease with a very high mortality rate, and endorsed the proposal for a highly specialised service for SJS and toxic epidermal necrolysis. The intention is for a nationally commissioned service to standardise treatment around the country in a small number of expert centres. Those proposals include a network of centres for both treatment and research and for using the diagnostic material to support that research. The establishment of a national service should make it possible to implement the national guidelines for patient care that were published by the British Association of Dermatologists just last month.

The Government absolutely recognise the long-term impact of SJS on survivors and their families. That is why we are putting not just research but patient support and a patient voice at the heart of the UK strategy for rare diseases. It is crucial that people who suffer from conditions like these are able to both feel that their suffering is not in vein and that they are being listened to and supporting research, and also that they are helping to drive new care pathways.

I will address the specific questions the right hon. Lady asked. She talked about lack of awareness and training. She is absolutely right that that is a major issue for our health system because the more we discover those rare diseases, the more we have a real challenge to keep our medical students up to date. In the old days we trained medics for the conditions that we understood but, because of the pace of discovery now, we have discovered new diseases that were not known when their textbooks were published before they have even finished a year at medical school. That is a challenge for the whole system and I will raise that important point with the relevant agencies who are in charge of training to ensure that they are address it.

[Dame Margaret Hodge]

I take that point but I draw to the Minister’s attention the fact that this disease was identified in 1922; it is not entirely new. Early identification means the drug that is causing the problem is withdrawn and the more appropriate treatment can be started. I hope the Minister can go a little bit further.

[George Freeman]

Many of these conditions have been known about for years, but it is only now that we are really beginning, through genomics and infomatics, to get a handle on how we might track, spot earlier and use big data to analyse cause and effect and develop new medicines that could intervene. Some of these conditions that have been thought of as never treatable are now becoming treatable because of the pace of biomedical progress. We need to inform our trainee clinicians not to think, “Well, I’m sorry. You’ve got a diagnosis; there is nothing we can do about it. People have suffered for 80 years.” There is a genomics programme, an accelerated access review for new medicines and an early access to medicines scheme, and we are beginning to accelerate getting new cures through into treatment. I will raise the issue of greater awareness of rare disease and what is available for them with the agencies responsible for training medical students.

The right hon. Lady raised the idea of an awareness week, which I think is an excellent idea. The truth is there are many rare diseases and I foresee a clamour for every rare disease to have a week, for which there would not be enough weeks in the year. It may be that one has a rare dermatological conditions awareness week, which would heighten awareness. There may be different ways to do that but her idea is first class. She also talked about money for research; she would not be doing her job if she did not. The Government spend a considerable amount of money on research. The NIHR has a policy of not identifying particular diseases and earmarking money to them but, following the debate, I will raise with the NIHR how much is being spent that would be relevant for sufferers of SJS. I know it is taking steps to amend its research criteria in the years ahead so that it is responding to the progress made in the genomics programme and others.

The right hon. Lady made an excellent point about gene testing. The reason I am so inspired by that quiet revolution is that we are now at a point at which we can start to gene test patients, profile them and get targeted medicines to them. That is already happening with cancer and some other diseases. For the new drugs we have launched in the NHS this year for Hep C, it turns out we can profile which patients will respond in six weeks, in eight weeks or in 12 weeks. That is driving a new model of reimbursement that sits at the heart of my accelerated access review.

Lastly, the right hon. Lady raised the important issue of side effects and the wider science of drug side effects, which the Government are investing in through a whole series of programmes in the Department of Health and NHS England. Understanding side effects can be a cue to the science of new cures. I hope she is reassured that we are taking that seriously and I will follow up—or will ensure my successor follows up, if I am no longer in post after today—the points she has sensibly raised.