Mysteries of myositis unravelled
Published on 15 November 2011
Myositis is a rare, little-known muscle condition that can have a devastating effect on patients’ lives. Current therapies have only limited success. Now new research aims to unravel its causes, leading to better treatment.
Stacey Farrington has more reason than most to hope that Arthritis Research UK’s new research into myositis has a practical, positive outcome.
Until two years ago, the mother-of-three from Wigan, now aged 30, had a normal active lifestyle, enjoying spending time with her family and working as a doctor’s receptionist.
Then she went down with what she thought was flu and wrongly diagnosed variously as glandular fever and a viral infection.
She was perpetually weak and tired, had night sweats and often struggled to breathe. Matters came to a head when she woke up and found she could not get out of bed. Finally admitted to hospital, tests and scans revealed that she had a condition called dermatomyositis, which affects the skin and muscles.
Unfortunately for Stacey, as for many sufferers of myositis, diagnosis did not bring automatic relief. The drugs – steroids, intravenous immunoglobulin and immunosuppressants – reduced her symptoms a little, but didn’t provide the “miracle” she wanted. She developed swallowing problems and for a time had to be fed through a tube.
She is currently hoping that a new drug regime of mycophenolate will kick in, but is having to come to terms with the fact that she has to adapt to living with a chronic condition and that life as she knew it before may never be the same again. Husband John has had to give up work to look after her as she is unable to do very much for herself due to ongoing muscle weakness and difficulties with swallowing and breathing. Weight loss has also been a problem. “I kept thinking, OK, I have this condition, they give me tablets; it will get better,” says Stacey. “But after about a year down the line you realise that will not happen.”
Stacey’s rheumatologist, Dr Robert Cooper at Salford Royal Foundation Trust (formerly Hope Hospital), says that her lack of a good response to existing treatments is not uncommon in myositis patients, although most do show some improvement and some even achieve a full remission, albeit on life-long treatment.
“Myositis has been relatively neglected in terms of research”
Dr Cooper is the principal investigator of a new-five year Arthritis Research UK £450,000 programme grant, which aims to understand better the causes of myositis – in particular by examining which genes govern which individuals get the disease; which genes govern whether affected patients will do well or badly; and which genes govern treatment response.
“The fact that the drugs work so poorly reflects our lack of understanding of what causes myositis, and this has slowed down the development of more effective new drugs,” he explains. Another big problem he and his team face is the small number of myositis patients on which to base their research, as there are probably no more than 2,500 existing cases in the UK. “Most rheumatologists will see only five or six patients in their whole career, which makes it very difficult to recruit the hundreds or even thousands of cases needed to do robust genetic research into myositis,” he says.
Colleague and fellow rheumatologist Dr Hector Chinoy, who co-runs the dedicated adult-onset myositis clinic at Salford Royal with Dr Cooper – the biggest in the country – concurs. “The fact that the condition is so rare means that it has been relatively neglected in terms of research, but although myositis is less common than other rheumatic conditions, it can still destroy patients’ lives or render them dependent,” he says.
Over the past decade the myositis research team has grown to now include Dr Lucy Wedderburn from the Institute of Child Health in London, who heads up a UK team nationally recruiting juvenile dermatomyositis cases of which there are now around 250, and leading autoantibody expert, Bath-based rheumatologist Professor Neil McHugh. Both are co-applicants on the programme grant. “Our results correlating genetic and antibody findings have begun to give important clues into disease mechanisms, and illustrate the power of this collaboration between Manchester, Bath and London,” explains Dr Cooper. These developments have enabled the UK-based team to establish important collaborations with specialist colleagues around Europe and, more recently, with those in the US. Thus, the European Myositis Consortium has to date recruited about 1,000 cases, with similar case numbers being available in the US.
“The fact that the drugs work poorly reflects our lack of understanding of myositis”
Adds Dr Chinoy, who is the clinical point of contact for European rheumatologists: “There’s a realisation that to conduct meaningful research studies of sufficient statistical power it’s essential to collaborate when dealing with rare diseases.”
As a result of the collaboration, blood samples from patients seen by around 60 UK and EU rheumatologists are sent to team members Professor Bill Ollier and Dr Janine Lamb at the University of Manchester’s Centre for Integrated Genomic Medical Research (CIGMR) for DNA genetic analysis. Serum samples are then sent from CIGMR to the Bath autoantibody laboratory, to enable the vital link up with antibody analysis. The Manchester-based part of the team is also building up a bio-repository of muscle and other tissues during the next five years as part of the programme grant, which will enable future studies and spin-offs from these genetic and antibody research efforts.
Research so far has identified a number of genetic variations and antibodies that can predict severity of disease, and even which patients are most likely to develop cancer. However, more genes and more antibodies are still waiting to be discovered.
“We have through the Bath lab the facilities to identify new antibodies, and examine if sufferers with shared antibodies have common clinical symptoms or changes in their muscles,” says Dr Cooper. “Preliminary work suggests that we have discovered new, previously unknown genetic variations which we will now need to study in detail.”
The team aims to be able to monitor outcomes, including responses to treatment and complications, such as interstitial lung disease, and to see how genetic variations and related anti-bodies relate to signs of disease, type of disease, the age it develops, and so on.
The genetics research could also have a strongly practical application. “If we could predict if someone with myositis was going to get lung disease or cancer-associated myositis, we could be more aggressive with treatment and more accurate with investigations from the start, so we have the potential to change how we would treat different sub-types of disease,” explains Dr Cooper. “At the same time we don’t want to risk giving people powerful and potentially dangerous drugs that they don’t need.”
New drugs can’t come soon enough for Stacey Farrington. However, Stacey is taking hope and inspiration from another myositis sufferer, Jason Jeffries (pictured above), who lives in nearby Atherton in north Manchester. For eight years Jason struggled with polymositis, suffering severe aching and weakness in his muscles, but is now happily in full remission.
“It was the worst eight years of my life,” says Jason, now a healthy and toned 42-year-old. “It felt like my muscles were constantly burning, and on top of that there was this terrible weakness. I couldn’t even pick up a cup of tea, or get tablets out of a blister pack, I was so weak. I got very depressed; it really got me down.”
After all the usual drug treatments, and unsuccessfully experimenting with complementary therapies, Jason’s symptoms started to reduce two years ago. He still comes to Salford Royal every six months for check-ups and remains on low dose steroids, but now leads a normal life.
“My little girl said to me recently: ‘I wish it could be like before mummy got ill"
Stacey is keeping her fingers crossed that the same will happen for her. Her eyes fill with tears when she says: “You look like there is nothing wrong with you; so it’s hard to explain to people. My little girl said to me recently: ‘I wish it could be like before mummy got ill.’ Myositis changes your life.”
What is myositis?
Myositis is a rare auto-immune condition that affects the muscles and the skin, and in severe cases, the heart, lungs and gut. It can also affect the muscles in the throat, making it difficult to swallow.
Polymyositis affects many muscles in the body, especially the shoulders, hips and thighs, while in addition dermatomyositis also causes skin rashes on the face and the back of the hands. Some people with myositis are also at an increased risk of cancer.
Steroids, immunosuppressant drugs such as methotrexate, and immunoglobulin infusions are the most common treatment, but they are not always effective.
Clinically and genetically myositis shares features with rheumatoid arthritis, lupus and scleroderma.