Viruses, bacteria or even drugs can be the hidden triggers of inflammatory bowel disease, and many other intestinal illnesses can be mistaken for it.
Inflammatory bowel disease affects hundreds of thousands of people around the world each year. It is, according to conventional medicine, incurable and its cause is unknown (BMJ, August 6, 1994). The number of reported cases is increasing worldwide each year (Canada Health Rep, 1990; 71: 343-59), especially among children.
Generally speaking, IBD is thought to be autoimmune in nature, causing the immune system to attack and inflame the body’s own tissues. For diagnostic purposes, doctors divide IBD into two separate categories: Crohn’s disease and ulcerative colitis (UC). Crohn’s involves all the layers of the bowel but can affect any part of the gastrointestinal tract from the mouth to the anus, while ulcerative colitis affects only the colon/rectum.
While Crohn’s and ulcerative colitis are usually categorized as two separate diseases (BMJ, 1994; 309: 355), there is also an argument that they are better described as two examples of the same process, which merely affects different areas in the intestine to a differing degree. No single test is sufficient to diagnose either disease, and sufferers are often put through an endless round of endoscopic, radiological, histologic assessments, laboratory testing and bowel studies in order to come up with a definitive diagnosis (Postgrad Med J, 1995; 112: 46-8; and 54: 57-8). In 10-15 per cent of patients it is almost impossible to differentiate between the two diseases.
Each type may have different causes (Gastroenterol Clin North Am, 1995; 71: 475-507), making the selection of appropriate treatment difficult. Diagnosis can also be made difficult by the fact that both diseases mimic several other infections of the intestines, as well as other conditions (see box below).
While the death rate from IBD is dropping, the risk is still greater than that of the general population (Gastroenterol, 1996; 110: 1339-45). In a retrospective study of death certificates in Rochester, New York from January 1973 to December 1989, Crohn’s was the direct cause of death in 25 per cent of cases and in 6 per cent of cases of UC (AM J Gastroenterol, 1995; 90: 927-32).
But what makes someone suceptible to IBD in the first place? Certainly there is a genetic link which is stronger among sufferers of Crohn’s. If someone in your family is a sufferer, you are anywhere from 3.5 to 10 times more likely than the general population to contract the disease yourself (Acta Chir Scand Suppl 1990; 559 (Crohn’s Disease-EP/GE): 1-42; N Eng J Med, 1991; 324: 84-8).
The use of non-steroidal anti-inflammatory drugs (NSAIDs) is another possible explanation. Research in Jersey showed that in 38 per cent of new cases of inflammatory bowel disease, the disease developed while the patient was taking NSAIDs (Lancet October 8, 1994).
Viral and bacterial links with IBD have also been explored at length, particularly in relation to Crohn’s (Ann Med, 1993; 25: 557-61). Studies have shown that the human herpesvirus 6 (HHV 6), Epstein-Barr virus and cytomegalovirus seem to play a much greater role in the development of UC (J Med Viriol, 1992; 38: 183-90). But the weight of research into bacterial causes centres around Crohn’s disease and the presence of Mycobacterium paratuberculosis.
This bacterium is known to cause chronic enteritis in many animals and may also be responsible for the disease in humans, especially in those with inherited or acquired susceptibility. Its presence is more common in those with Crohn’s than with ulcerative colitis.
One study showed that two-thirds of tissue samples from those with Crohn’s had evidence of the bacterium, but only 5 per cent of those with ulcerative colitis did (Gut, 1992; 33: 890-6).
Professor John Hermon-Taylor at St George’s Medical School in London has been investigating the condition for many years (Appl Environ Microbiol, 1996; 62: 3446-52).
According to his research, M paratuberculosis was found in up to one in four samples of whole pasteurized milk randomly obtained from retail outlets, suggesting that it cannot be wholly destroyed by the pasteurizing process.
Another study confirms the findings that pasteurization process does not completely destroy M paratuberculosis (App Environ Microbiol, 1996; 62: 631-6). Its presence in Crohn’s patients may explain in part why Crohn’s sufferers can react so badly to milk and other dairy products
It is further claimed that if M paratuberculosis is responsible for intestinal disease, filing the whole range of disorders under the banner of Crohn’s may be misleading. Intestinal tuberculosis, also a mycobacterial disease, is very similar to Crohn’s (J Gastroenterol Hepatol. 1996; 11: 183-6; BMJ, 1975; 4: 395-7), but the treatment of the two conditions is very different.
For instance, corticosteroids a mainstay of Crohn’s treatment may make intestinal tuberculosis worse (J Gastroenterol Hepatol, 1996; 11: 532-4).
That said, the cause of Crohn’s remains elusive, and other researchers claim that the link between Mycobacterium, while strong, is not convincingly established (Scand J Gastroenterol, 1990; 175 (Suppl): 93-6). Mycobacterium can be difficult to culture in the laboratory, and some still doubt that it plays a part in causing Crohn’s (Gut, 1995; 37: 660-7).
Dr Andrew Wakefield at the Royal Free Hospital, London, has been conducting research into Crohn’s for many years. Recently, he suggested that, instead of being an ulcerative disease, Crohn’s may be caused by restricted blood flow in the blood vessels which feed the lining of the gut.
What causes the constriction in the first place is not known. It could be that small tumours, or granulomas, form within the walls of the blood vessels causing vascular injury (Gastroenterol, 1991; 100: 1279-87). But Wakefield’s belief is that the missing link between granulomas and vascular constriction is a persistent measles virus (Gastroenterol, 1995; 108: 911-6; J Med Virol, 1997; 51: 90-100; J Med Virol, 1993; 39: 345-53).
According to his research, exposure to the measles virus in the womb or shortly after birth greatly increases the risk of contracting Crohn’s later in life (Lancet, 1996; 348: 515-17). In a review of four counties’ health records in Sweden, Wakefield and his colleagues identified all those who were born between 1945 and 1954 who had Crohn’s diagnosed before the age of 30 (Lancet, 1994; 344: 580-10). Yearly reports showed that five measles epidemics had affected all four counties over the trial period. The number of cases of Crohn’s significantly exceeded the researchers’ expectations: 57 versus 39. For those with ulcerative colitis the actual number, 42, was close to what they expected: 47.
According to Wakefield it could be the measles vaccine and not the circulating virus which may be responsible for the rising rates of Crohn’s in children. When a large study in Scotland looked at data from 1968 to 1983, it discovered that cases of Crohn’s in children have risen by more than seven times from four per million to 29 per million (Gut, 1989; 30: 618-22). Other studies point to the fact that during that time, although cases of live measles dropped drastically, the measles vaccine was introduced and widely used (Lancet, 1995; 345: 1071-73).
It could be that the measles vaccine may be one vastly under-reported cause of Crohn’s. But retrospective analyses are hard to perform accurately (Lancet, 1996; 347: 263), and it would be difficult to find a large enough group of children today who have not been vaccinated whom researchers could use as controls in a large prospective trial (Lancet, 1995; 345: 1363-4; J Gastroenterol, 1995; 344: 48-51; Gut, 1996; 38: 211-5).
While the true cause remains unproven, there is similar uncertainty about treatment.
Surgery is a mainstay of the conventional approach and it can help but at a price. Surgeons may take out as much as 50 per cent of the small intestine, but it should be viewed as a relief of symptoms rather than a cure (Int Surg, 1992; 10: 2-8). It can also cause malabsorption, diarrhea and other nutritional disturbances. In a study of 62 patients with Crohn’s aged 55 years or over surgery helped restore good health, but nearly half of the patients required a permanent stoma (surgically-created opening in the abdomen) (Postgrad Med J, 1997; 73: 225-9).
In another group of 212 patients, surgery resulted in high death rates (28.3 per cent); and 60 patients had at least one complication, mainly of a septic nature. The mortality rate was 3.3 per cent, with infection, deep vein thrombosis and pulmonary embolism being the most common cause of death. Those who were nutritionally compromised because of the disease had a significantly higher rate of complications (39.7 per cent), as did those who required emergency surgery (44.4 per cent). This suggests that taking the time to improve health before surgery will result in significantly better results (Neth J Surg, 1990; 42: 105-9).
While the initial result of surgery is good, as many as 38 per cent of patients will be re-operated on within 10 years and 54 per cent within 15 years (Tidsskr Nor Laeegeforen, 1994; 114: 1603-5).
Steroids are the primary treatment for Crohn’s (Gastroenterol, 1984; 86: 249-66). But steroids such as cyclosporin can cause kidney damage even at low initial doses which cannot be reversed by later dose reduction (Dig Dis Sci, 1993; 38: 1624-30) Also, steroid dependency occurs in more than a third of users and steroid resistance in 20 per cent taking the drugs for the first time (Gut, 1994; 35: 360-2; Lancet, 1995; 345: 859).
Steroid use is, of course, associated with development of the bone disease osteoporosis. This is particularly true in patients with both Crohn’s and ulcerative colitis since the disease often results in a secondary malabsorption of calcium and vitamin D. In one study, patients with Crohn’s had diminished bone density of the hip by 64 per cent and of the spine by 44 per cent. In UC patients, hip density was diminished by steroid use by 43 per cent and density of the spine by 48 per cent (J Bone Miner Res, 1995; 10: 250-6). Steroid use was the only significant predicting factor for reduced bone density.
Anti-diarrheal and antispasmodic preparations and sedatives are often prescribed for symptom relief. Bowel inflammation is often controlled with sulphasalazine or the newer 5 amino salicylic acid (5-ASA) compounds, anti-bacterial drugs and adrenocortical steroids and the immunosuppressive compounds 6-mercaptopurine (6-MP), azathioprine and cyclosporin.
Immunosuppressives such as 6-MP and azathioprine are often used to wean patients from steroids. They are used mainly as maintenance therapy and to close fistulas (where two normally unconnected tissues join up), though the action can take some time to show its effect. These drugs are associated with side effects such as liver damage or bone marrow suppression, and their action is still not well understood. One study has shown that after four years of remission on these drugs, the risk of relapse appeared to be similar, whether the therapy was maintained or stopped (Lancet, 1996; 347: 215-19).
Cyclosporin use, in addition to any other treatment, does not improve symptoms or reduce the individual’s requirements for other forms of therapy (N Eng J Med, 1994; 330: 1846-51).
Today we are beginning to realize that treatment for IBD should reflect an individual programme rather than a general drug/surgery regime. There are many studies to support the use of nutritional therapy, whether dietary or intravenous, in the treatment of IBD.
In one of the most important and controversial studies, Dr AM Riordan and colleagues demonstrated that an elemental diet (see below) was as effective as steroid treatment for Crohn’s disease, though most patients relapsed soon after resumption of their normal diet (Lancet, 1993; 342: 1131-4).
During the trial, 136 of the patients with Crohn’s were all started on an elemental diet a protein free diet which includes a liquid nutrient preparation and other treatment was withdrawn. After 14 days, patients were randomized into two groups, either being treated with elemental diet and placebo, or steroids with dietary advice for healthy eating. Both groups were followed for up to two years by physicians who were unaware of group assignment. In addition, the diet group were asked to introduce a new food each day providing they did not react adversely to that food.
The results showed the common allergens cereals, dairy products and yeast were associated with Crohn’s. The researchers concluded that the process of food allergy testing could provide an effective strategy for the long-term management of CD.
Some of the improvement on this restrictive diet may be because it is a diet low in histamine which is found in high amounts in yeast and dairy products.
Diamine oxidase is the agent which metabolizes histamine in the gut. Patients with Crohn’s disease seem to have up to 50 per cent less diamine oxidase in their guts than healthy controls (Agents Actions, 1990; 30: 267-70). This element cannot be given as a supplement. Therefore, a histamine-free diet excluding fish, cheese, hard-cured sausage, pickled cabbage and alcohol is the best way to help those who are intolerant (Lancet, 1994; 343: 113).
In the commentary which followed this trial, several doctors rejected the idea of diet easing or curing the disease, claiming that it only made people feel better about having it (Lancet, 1994; 343: 112). Others believe dietary toxicity as well as environmental pollution should be urgently addressed since many of these pollutants contain chemicals which are known to deplete the immune response (BMJ, 1994; 309: 1090).
As the debate continues, it should be noted that earlier trials have come to the same conclusions as Dr Riordan about the importance of diet (Lancet, 1985; ii: 177-80; Arch Dis Child, 1987; 62: 123-27; Lancet, 1990; i: 816-19).