A diagnostic challenge
Published on 01 January 2011
There are some types of arthritis that appear to defy logic and provide a serious challenge to the diagnostic skills of the medical profession. Sjögren’s syndrome (pronounced Shurgren’s) is one of those. Jane Tadman reports on a new clinical trial that could help sufferers of this curious condition.
Dry eyes, dry mouth, dry, itchy skin, joint pain, fatigue and lung, liver or heart complications. Not the most obvious set of symptoms for a medic to make sense of.
For the patient who has to endure such a combination of symptoms without a very effective treatment and without practically any public awareness of the condition, life can be difficult. And just getting diagnosed is usually the first hurdle to overcome.
Angela Mullally from Birmingham was in her early 40s when she started feeling very weak and tired, with pains in her joints and muscles in her arms, shoulders and legs. She also developed telltale dryness in her eyes and mouth, but despite a history of Sjögren’s in her family, she didn’t make the connection between symptoms. Unfortunately, neither did her GP, steadfastly sticking to his diagnosis of stress for some time.
Angela was a housekeeper at the National Exhibition Centre in Birmingham at the time but managed to keep working until her late 50s, struggling with the effects of a perpetually dry mouth and eyes and having to keep by her what she calls her “spare parts” – eye drops, mouth gel and a bottle of water in order to keep herself hydrated.
The extreme fatigue was just as bad. “I had a busy, very physical job and would come in and flop – the fatigue was unbelievable,” says Angela, now 62. Intermittent fatigue is still a problem, and she also more recently became very breathless when walking uphill, which was found to be another common complication of Sjögren’s – inflammation of the lungs which has led to fibrosis (scarring). Her dry eyes drive her to distraction, making reading and driving very difficult.
But for a brief time five years ago, Angela enjoyed her best period of good health since developing Sjögren’s back in 1993. By then she was being treated by Dr Simon Bowman, who has a special interest in the syndrome, at Selly Oak Hospital. Dr Bowman ran a small pilot trial of the B-cell drug, rituximab (now licensed to treat severe rheumatoid arthritis), and Angela was among 17 patients to take part.
“The trial compared rituximab against steroids, and I thought I might be on the steroids because I felt really well,” says Angela. “It was during December and January and that winter I was really busy and active and could get about – I even went dancing! My mouth and eyes were still bad but I didn’t have swollen or painful joints and I had a great three months. It gave me a glimpse of what I used to be like.”
In fact, Angela was on rituximab. The pilot study ended and Angela went back to what is now normal for her – ups and downs, dryness, regular bouts of fatigue and joint pain. But now, five years on, Simon Bowman has been awarded almost £1m from Arthritis Research UK to run a full-scale clinical trial of 110 Sjögren’s patients around the country, comparing rituximab against placebo in improving dryness and fatigue.
“Those of us in the rheumatology community with an interest in Sjögren’s have been talking about doing a trial like this for some years, so I’m delighted that we are finally getting to do it,” said Dr Bowman, who will be collaborating with Arthritis Research UK Professor of Rheumatology at Leeds University, Paul Emery; Professor Costantino Pitzalis of Queen Mary, University of London, and other colleagues; plus the Leeds Clinical Trials Unit, and aiming to recruit patients from several UK hospitals.
Many of the patients will come from a register of 300 Sjögren’s patients funded by the Medical Research Council and set up by a colleague of Dr Bowman, Dr Wan-Fai Ng in Newcastle.
To qualify for the trial, patients must have a significant level of fatigue, oral dryness, a number of antibodies found in the blood of the majority of Sjögren’s sufferers called anti-Ro and anti-La, and typically some systemic involvement.
“There is good background research to suggest that rituximab is worth looking at, and that this is a sensible trial to be doing,” adds Dr Bowman. “Our earlier pilot study showed that treating patients with a single course of the drug showed some improvement in fatigue, and an earlier Dutch study which looked at 30 patients also had resulted in improvement in fatigue levels and also the dryness symptoms.”
If the five-year trial is a success, Dr Bowman hopes that the manufacturers of rituximab, Roche, will take it forward to a commercial trial with a view to gaining a UK licence. There is a link between lymphoma and Sjögren’s, with patients at increased risk of developing lymphoma. Rituximab was first licensed to treat non-Hodgkin’s lymphoma.
Angela Mullally is keeping her fingers crossed that she may be able to get onto the trial, after her earlier experience, although as the trial is blinded there is a 50 per cent chance she will be taking the placebo, not the active drug.
Meanwhile, she is keeping as active and busy as she possibly can, doing yoga, T'ai chi and swimming regularly, which helps her joint pain and breathing, and maintaining a very positive attitude to her debilitating condition.
“Some days I’m fine; other times I just have to lie down, but I don’t give up. I don’t believe in giving up; you’ve got to make the best of things,” says Angela. “I try not to think about Sjögren’s too much; I don’t want to end up in a wheelchair or in the house 24 hours a day, and it’s a psychological thing for me–I think the more I keep moving the better I will be. Life is far too short and I’ve got too many things to do.”
What is Sjögren’s syndrome?
- It is an autoimmune disorder in which the body’s immune system attacks the tear glands in the eye and salivary glands in the mouth.
- It is sometimes described as the “rheumatoid arthritis of the glands”.
- Some people with Sjögren’s also have dramatic systemic involvement – swollen glands, skin rashes, neuropathy (losing feeling in the hands and feet), fevers and lung inflammation leading to fibrosis.
- About 10% of people with either rheumatoid arthritis or lupus also develop a degree of secondary Sjögren’s.
- Extreme fatigue is another common symptom.
- It is 15 times more common in women than men.
Read more about Sjögren’s syndrome.