Liz Linehan reports on a controversial approach to a crippling disease of the joints
MORE than a million people in Britain are suffering from severe diseases caused by the body attacking itself. One of
the commonest is caused by eating too much bread, potatoes and pasta. Excessive carbohydrate encourages abnormal
growth of bacteria in the bowel triggering the crippling disease. People who are vulnerable have inherited a special
tissue type. They produce antibodies which erode bone and joints causing ankylosing spondylitis, illustrated below.
Now a team of doctors and scientists in London had discovered that avoiding carbohydrates can lead to remission.
Clues suggest that other diseases such as rheumatoid arthritis are caused in a similar way. Most people with rheumatoid
arthritis belong to another common tissue type and are sensitive to a bacterium, Proteus, which commonly causes bladder infections. The prospect of preventing the disease and perhaps of reversing it in the early stages is now at hand.
This is just the beginning; motor neurone disease, pernicious anaemia, myasthenia gravis and certain forms of diabetes may also be triggered by infections. Eventually it may be possible to halt these diseases too.
NINE years ago, Janet Djelal began to "hurt" all over. She was then 30 years old, a mother of two, living in north London. "Everything seemed to be hurting. I had pain in my back, down the back of my legs, and I couldn't move certain joints properly. I had recurrent attacks of conjunctivitis and cystitis. I looked awful and felt awful all the time and no one could tell me why."
Her physical symptoms were accompanied by depression, and a lack of energy and motivation — "I didn't want to go anywhere or do anything."
Janet's symptoms were labelled "psychological" but her health failed to improve and one night she experienced severe chest pain and breathing problems. A doctor was called out and he said she was having an asthma attack, something she had never before suffered from. By now, anxious and frightened, she turned for help elsewhere. After a private examination and various tests, she was referred to hospital. The doctors discussed her symptoms at length. "Suddenly somebody seemed" to know what I was talking about. The relief was tremendous."
Ankylosing spondylitis (AS) was diagnosed, a chronic arthritic disease which initially affects the spine, but which can involve other joints and tissues including the lungs, heart and eyes. It is characterised by periods of inflammation and pain, and remissions of weeks, months, even years Its progress in each patient varies greatly, as do the symptoms.
To relieve the pain and reduce inflammation, Janet was initially prescribed non-steroidal anti-in-flammatory drugs, the conventional treatment for management of the disease. Less conventional is the low-starch diet she now follows as one of a number of patients being treated by Dr Alan Ebringer, who is in charge of AS research in the department of rheumatology at the Middlesex Hospital, and an immunologist at King's College. London.
Dr Ebringer believes that the disease is a form of reactive arthritis caused by bacterial infection in the colon or rectum. By diet alone, or in conjunction with drug therapy, the extent of the infection and disease can be controlled. He has now treated more than 200 patients in his clinic at the Middlesex and claims success in halting the progress of AS in the majority.
There are more than 80,000 people in the UK being treated for AS, but according to the National Ankylosing Spondylitis Society (NASS). around 750,000 people are sufferers. "Many dismiss their symptoms as 'just a bit of back pain' or a 'touch of arthritis'," says NASS director and AS sufferer Fergus Rogers. "They remain ignorant of the true cause of their symptoms. Long periods of misdiagnosis or — as in Janet's case — no diagnosis at all, are the norm, as many GPs confuse the AS with other back problems."
The onset of AS is most common in the 15-30 age group and affects three times more men than women. Most of them first visit their doctor complaining of lower back pain and "early morning stiffness". The disease usually starts in the sacroiliac joint, between the sacral bone at the base of the spine and the pelvis. Inflammation develops and there is "wearing" down of the bone. Once the inflammation subsides, though, there is a reactive bone growth which can cause fusion between previously mobile joints.
If it progresses to the vertebrae — spondylos is the Greek for vertebra — this fusion can result in "bamboo spine", when it becomes fixed and rigid. In severe cases there is a complete loss of posture and the typical Victorian representation of the AS sufferer is that of a shuffling hook-backed figure, bent almost double.
The hip, knee and ankle joints may be affected, leading to more pain and loss of mobility. Chest and neck pain are common if the vertebrae corresponding to these areas become affected. Often the initial stages of the disease are the worst, when depression, fatigue and weight loss can accompany debilitating pain. Although drug therapy, physiotherapy and daily exercises can keep the worst deformities can be kept at bay, life as a "spondy" is not easy.
But where exactly does the diet fit in and how can it help? Dr Ebringer and co-workers in the departments of biochemistry and microbiology at King's College, London, have identified a bacterium in the bowel called Klebsiella which triggers the disease.
"Klebsiella thrives on a diet rich in starch," says Dr Ebringer. "If you cut out starchy carbohydrates such as rice, potatoes and flour products, then you reduce the number of Klebsiella in the gut, and subsequently the production of antibodies to the bacteria which cause the inflammation. Klebsiella levels can also be controlled by the drug salazopyrine which has anti-inflammatory activity".
Patients going to Dr Ebringer's clinic are given instructions for a low-starch diet. Dr Ebringer admits the diet is only a rough guide. It was drawn up on the assumption that starch in most people's diet comes from bread, flour products and potatoes. These foods should be avoided if possible. Pasta, rice and other starchy products should also be avoided. (Meat, fish milk, cheese, eggs, fruit and vegetables may all be eaten without restriction.)
Dr Ebringer's theory as to the cause of AS and his treatment are controversial and he has many critics among medical colleagues. Dr Frank Dudley Hart, former head of rheumatology at the Westminster Hospital, and now a consulting physician there, says (theories as to the cause of AS abound and there are indications of a link with the gut. "But there is still not enough evidence to sup-port these theories conclusively."
Janet Djelal, who has followed the diet for three years now, has little need of more evidence. " When I first started I couldn't see any difference, but I realise now that I wasn't following it closely enough. Once I stuck to it religiously I noted real improvement after six months or so. Movement became easier and the lethargy and depression lifted. The best way I can describe it is that after years of pain and stiffness, I suddenly feel 'well-oiled'."
National Ankylosing Spondylitis Society advises sufferers, 6 Grosvenor Crescent, London SW1X 7ER.
PETER COWLING held a dish up to the light and saw a faint white line. It marked the place where serum fixed in agar gel had reacted with an extract of bacteria from the human bowel. Cowling, a third-year student at King's College, London, examined the line with excitement. This was the result he hoped for but did not dare to expect.
The faint white line provided the missing clue to the cause of two diseases which between them affect more than a million people in Britain, These diseases, rheumatoid arthritis and ankylosing spondylitis (AS), another painful disease of the joints, start when the body reacts to bacteria in the bowel or some other part of the body, triggering a process of self-destruction.
The test on the laboratory dish demonstrated a similarity between human tissue and the bowel bacterium, Klebsiella. It showed that the body's immune system could mistake human tissue for the bacterium, and so in trying to get rid of the infection the body attacks itself. The similarity of body tissue to the bacterium was predicted by the immunologist Dr Alan Ebringer, but had not previously been observed. The basic idea was simple, but the Implications of it were immense.
"Peter Cowling, was asked by Dr Ebringer to screen our departmental collection of bacteria to see if any of the bacteria had a similarity to the human tissue type B27," recalls Professor Pitt, Emeritus Professor of Microbiology at King's College. "Just one type of bacteria was found to cross-react with the test-serum, out of 40 or so types of organisms screened — that was the exciting and significant thing."
It had been known for some time that 98 per cent of people suffering from ankylosing spondylitis have the B27 tissue type. Dr Ebringer began his experiments because he believed that there must be an organism, which could have been a virus, which triggered the disease.
The experiment showed that ail the organisms which reacted with B27 were bowel bacteria: Salmonella, Klebsiella, Shigella, and Yersinia. The last two types of bacteria cause diarrhoeah diseases and it has been known for a long time that people who suffer a severe infection of these sometimes develop arthritis afterwards. But Klebsiella, which is a normal resident of the bowel, had not been linked with arthritis.
Once Dr Ebringer knew what to look for it was a simple matter to test for Klebsiella in the faeces of patients with AS. The tests showed that patients with active disease had more Klebsiella in their stools than normal people, and more than patients whose disease was inactive. During active phases of the disease the patients could also be shown to have antibodies to Klebsiella in their blood. These studies showed that healthy males had more Klebsiella in their bowel than healthy females. This seems to explain why AS is almost three times as prevalent in men than women.
These experiments, and others, suggested that AS is an auto-immune disease. The immune system, which normally protects the body from infection, is precipitated into attacking tissues of its own body with devastating effect. In people with AS, Dr Ebringer believes this destructive process is triggered by a reaction to bowel bacteria.
A bacterium could be involved in rheumatoid arthritis in the same way
There are a number of other chronic degenerative diseases that doctors know, or suspect, of being auto-immune in origin. Motor neurone disease is such a condition, so is systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, pernicious anaemia and certain forms of diabetes. In most cases it is not known if there is any factor like bowel bacteria which triggers the destructive reaction.
However, Dr Ebringer and his co-workers have discovered that another bacterium could be involved in rheumatoid arthritis in the same way that Klebsiella is in AS. A high proportion of people who suffer from rheumatoid arthritis have the HLA-DR4 tissue.
Money was short and so the task of identifying that bacterium was given to another King's microbiology undergraduate, Yvonne Macafee. She screened the departmental collection for a bacterium that would react with serum which had been prepared to react against human white blood cells of the HLA-DR4 tissue type. Again only one microbe was found to react. This time the culprit was found to be Proteus, a bacterium that causes urinary tract infections.
Following up this observation, Dr Ebringer found that patients with active rheumatoid arthritis had much higher levels of anti-bodies to Proteus in their blood than healthy people. Trials with patients at the Royal Hampshire Hospital in Winchester have further supported these observations, and a group in Dublin have also reported raised antibody levels to Proteus in rheumatoid arthritis patients.
Once the Proteus/rheumatoid link was established, it could be used to explain other features of the disease. Two-thirds of sufferers are women, almost certainly because they are anatomically more vulnerable to urinary tract infections. Some men have been found to develop the disease after respiratory tract infections — could it be that the infecting organism is Proteus, asks Professor Pirt.
Dr Ebringer's work has met with much opposition and his efforts to gain acceptance for these challenging theories are a classic tale of one man taking on the "establishment". It is a confrontation that has been watched with Interest and no little detachment by Professor Pirt. Now Dr Ebringer's early work is supported by studies from several centres in other countries. The most recent from Finland.
The work, which was mainly carried out by PhD students over the last 12 years, is now gaining acceptance and acknowledgement from the profession as an exciting discovery. AS is an area that is crying out for further investigation
associated with HLA-B27 - Reiter's syndrome (a type of arthritis with urethritis and eye inflammation), uveitis (an inflammatory eye conditio!.} and reactive arthritis which occurs following infection elsewhere in the body. It seems likely that the dreaded Klebsiella or similar bacteria may be responsible for these conditions too.
Liz Lachan 
A 'bamboo spine' built of bony bridges
PEOPLE with ankylosing spondylitis suffer increasing stiffness and pain in the spine and buttocks. The man illustrated above has suffered from the disease for many years and his spine has become fused in the bent position so that he can only see ahead with great difficulty. In the most extreme cases people with the disease may need the help of prismatic spectacles to see ahead with any comfort The detail of vertebrae (illustrated) shows how bridges form between the bones until they eventually fuse to make a '"bamboo spine". Bones in the pelvis may also fuse causing pain and difficulty in sitting still. Erosions often occur in the heel and other joints too.
