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Crohn's Disease

Crohn’s disease is a chronic inflammatory bowel disease (IBD). It is a long-term condition that causes inflammation of the lining of the digestive system. The symptoms are similar to other bowel conditions such as irritable bowel syndrome (IBS) and another IBD ulcerative colitis. Crohn’s disease commonly occurs in the ileum (the lower part of the small intestine), but it can affect any part of the bowel. In fact it can occur anywhere along the entire alimentary tract from the mouth to the anus. In most cases though, Crohn’s disease occurs in sections of the bowel which become inflamed, ulcerated and thickened. Symptoms can include diarrhoea, abdominal pain, fatigue (extreme tiredness), unintended weight loss and blood and mucus in the faeces. There may be long periods lasting for weeks or months where there are mild or even no symptoms, this is known as remission. Remission may be followed by periods where symptoms are particularly disruptive and/or distressing, these are known as flare-ups.


According to the National Association for Colitis and Crohn’s Disease, the disease affects about one in every 1,000 people in the UK. There are currently at least 115,000 people living with Crohn’s disease in the UK. It can affect people of all ages, including children but most cases first develop between the ages of 16 and 30. A large number of cases also develop between the ages of 60 and 80. It affects slightly more women than men, but in children more boys are affected than girls. Crohn’s disease is more common in white people than in black or Asian people. It is most prevalent among Jewish people of European descent. Over time, inflammation may damage parts of the digestive system, resulting in additional complications, such as stricture (narrowing of the intestine) and fistula (a channel that develops between the anal canal and the skin near the anus). These problems usually require surgical treatment. The condition can lead to delay of growth and puberty in children, as well as affecting fertility and sexual relationships in adults.


There is currently no cure for Crohn’s disease so the aims of treatment are to stop inflammation, relieve symptoms, induce and maintain remission and avoid surgery wherever possible. In the last decade, there have been a number of new drugs licensed for the condition; glucocorticosteroids can be offered to induce remission and azathioprine or mercaptopurine can be offered as maintenance treatment. The National Institute for Health and Care Excellence (NICE) guidance suggests that the first treatment offered to reduce symptoms is usually corticosteroids (steroid medication). If this doesn’t help, immunosuppressants (medication to suppress the immune system) and medication to reduce inflammation may be used. In some cases, surgery may be required to remove the inflamed section of the intestine. Once the symptoms under control, further medication may be used to help maintain remission.


Although the exact cause of Crohn’s disease remains unclear, research suggests that a combination of factors may be responsible including:


  • Genetics – genes that you inherit from your parents may increase your risk of developing Crohn’s disease
  • The immune system – the inflammation may be caused by a problem with the immune system (the body’s defence against infection and illness) that causes it to attack healthy bacteria in the gut
  • Previous infection – a previous infection may trigger an abnormal response from the immune system
  • Smoking – smokers with Crohn’s disease usually have more severe symptoms than non-smokers
  • Environmental factors – Crohn’s disease is most common in westernised countries, such as the UK, and least common in poorer parts of the world, such as Africa, which suggests the environment (particularly sanitation) has a part to play

It has been proposed that an environmental factor leading to Crohn’s disease is a pathogenic bacterium. The most popular candidate is the infectious bacterium Mycobacterium avium subspecies paratuberculosis (MAP). MAP infection is widespread in domestic livestock and is present in retail pasteurised cow’s milk in the UK and potentially elsewhere and water supplies are also at risk. The overall prevalence of MAP infection in US dairy herds was reported by a USDA survey (1991-2007) to be 68.1 per cent and it is suggested that MAP infection in farmed animals is also widespread in many areas of Western Europe and elsewhere. As MAP contaminates and persists in natural watercourses and the environment, it is found in dairy products, it can survive milk pasteurisation and it is present in meat from infected animals and there are concerns that water supplies may be contaminated, it is inevitable that human populations are widely exposed. MAP is a robust and versatile pathogen which has been shown to cause chronic inflammation in the intestines of many species of animal, including primates. MAP causes a chronic gastrointestinal infection called Johne’s disease in cattle and other ruminants. The rising incidence of Crohn’s disease reported from several former low incidence countries in Asia shows that, as with Johne’s disease, Crohn’s disease is spreading worldwide.


A substantial body of evidence supports the causal link between MAP and Crohn’s disease. Researchers at the University of Wisconsin used a range of modern molecular techniques to search for and confirm the presence of MAP in patients with IBDs including Crohn’s. The results showed MAP was present in around 20 per cent of Crohn’s patients compared to less than seven per cent of controls (without Crohn’s). Although these results did not provide the substantive evidence initially anticipated the researchers concluded that MAP (or some similar species) infects a subset of IBD patients. In another study, Professor John Hermon-Taylor and colleagues at St George’s Hospital Medical School in London tested a group of patients with and without Crohn’s disease for MAP. Using improved molecular biology techniques that increased the sensitivity of the tests, this time 92 per cent of patients with Crohn’s disease tested positive compared to 26 per cent of the controls. These patients were from the UK, Ireland, US, Germany and United Arab Emirates, suggesting exposure to this pathogen occurs on an international basis. They concluded that the discovery that MAP is present in the majority of Crohn’s patients would suggest a causal link between this bacterium and the condition. Since then, additional reports have confirmed MAP as a predominant feature of Crohn’s disease. MAP can be notoriously difficult to detect in humans but when validated methodologies have been used, most people with Crohn’s disease have been found to be infected with MAP.


But how does MAP infection occur? The answer may lie under our very noses, depending on what we are drinking. MAP can survive the pasteurisation process, indeed an FSA-commissioned survey in 2002 found MAP in two per cent of pasteurised milk on sale in the UK. However, researchers from the Department of Surgery at St George’s Hospital Medical School in London detected MAP in 22 of 312 (seven per cent) of samples of whole pasteurised cow’s milk obtained from retail outlets throughout central and southern England from September 1991 to March 1993. Alarmingly this study revealed the presence of peak periods in January to March and in September to November, when up to 25 per cent of samples tested positive for MAP. Taken together with data on the prevalence of MAP infection in herds in the UK, the known secretion of MAP in milk from infected animals and the inability of laboratory conditions simulating pasteurisation to ensure the killing of all these slow-growing organisms, the authors of this study concluded that there is a high risk, particularly at peak times, that residual MAP will be present in retail pasteurised cow’s milk in England.


In response to concerns about the presence of MAP in retail milk, the FSA devised a strategy to control MAP in milk at all stages of the food chain. This strategy aims to ensure hygienic milking practices and effective pasteurisation of milk and reduce the level of MAP in dairy herds. Of course the overall aim is to reduce the likelihood of consumers being exposed to MAP. However, this strategy does not consider alternative routes of exposure. In 2006 the strategy was reviewed and FSA Board Members were informed of progress, provided with an update on developments and told that no action was required. The report concluded “the Agency is not aware of any developments to suggest that its current advice on the drinking of milk needs updating at this time. The Agency and DH [The Department of Health], together with their expert committees, continue to keep evidence on the possible link between MAP and Crohn’s disease under review”.


MAP is a robust organism which can survive for months or even years in the environment which is a cause of much concern as infected animals excrete huge numbers of MAP in their faeces. In South Wales, researchers sampled river water from the Taff which runs off the hills and through the city of Cardiff and detected MAP in 32.3 per cent of the samples. The hills are grazed by livestock in which MAP is endemic. Previous research in Cardiff has shown a steep increase in the incidence of Crohn’s disease. Given that inhalation is a probable route of MAP infection in cattle, it was suggested that the pattern of clustering of Crohn’s disease in Cardiff may be due to people inhaling aerosols carrying MAP from the river. Other locations around the world, with similar geographic characteristics to the landscape in Cardiff, have since been identified as having higher rates of Crohn’s disease. In New Zealand, a high incidence of Crohn’s disease has been reported in the Canterbury region of South Island where Christchurch is the principal city. Rivers run from the mountains in the northwest across rich agricultural pastures and then around either side of Christchurch before entering the sea. A small river meanders through the city itself. As stated, these features resemble the situation in Cardiff. Similarly, a higher incidence of Crohn’s disease has been observed in the US, in Winnipeg, Minnesota. The city straddles the junction of two large rivers; the Red River and the Assiniboine River. The 'hot spot' of Crohn’s disease in Winnipeg is probably due to local exposure to high levels of waterborne MAP brought down from the agricultural river catchments of the US Midwest, meeting those from the provinces of Manitoba, Saskatchewan and Alberta. Avoiding dairy products alone may not be enough to ensure avoiding exposure to MAP, although if everyone reduced their intake of animal products there would be fewer cattle and therefore less MAP present in the environment.


Some evidence from clinical trials suggests that anti-MAP treatment may be able to heal Crohn’s disease in some people. When anti-MAP treatment works in so-called ‘responders’ receiving treatment with drug combinations (including rifabutin and clarithromycin) the clinical and pathological improvements can be dramatic. Furthermore, some of the clinical benefit resulting from treatment with immunosuppressants (such as mercaptopurine or methotrexate) may actually be a consequence of their anti-MAP action. However, MAP infections are difficult to eradicate, the organisms are generally resistant to drugs conventionally used in the treatment of tuberculosis. 


The hypothesis that MAP causes Crohn’s disease remains controversial and is disputed by some. Professor Ryan Balfour Sartor, from the Department of Medicine at the University of North Carolina in the US says that we must determine whether MAP infection causes human disease or whether this environmental contaminant innocently lodges in ulcerated mucosa. He asks if MAP might be analogous to Helicobacter pylori in peptic ulcer disease, gastritis and gastric cancer, where host genetics and microbial virulence factors determine immune responses that mediate clinical disease in a small minority of patients exposed to a widespread infectious agent. He says that this controversy has persisted far too long and needs to be resolved.


For patients that have developed Crohn’s disease avoiding foods that precipitate the symptoms has proved to be a successful way of avoiding drug (corticosteroid) therapy. In the Lancet in 1993, researchers from a Cambridge hospital reported that altering the diet was as effective in producing remission of Crohn’s disease as corticosteroid treatment thus providing an alternative therapeutic strategy to treating Crohn’s. The research showed that the food intolerances were predominantly to cereals, dairy products and yeast. The foods that trigger symptoms differ for each person with Crohn’s disease and no single diet has been established to alleviate the symptoms. Types of food and drink that have been associated with worsening symptoms include:


  • Milk and dairy products
  • Alcohol
  • Spicy foods
  • Fatty foods
  • High-fibre foods

Not all patients respond equally to dietary changes, many simply remove symptom-provoking foods that affect them, such as dairy, wheat, corn and certain fruits and vegetables. In a review of the evidence coupled to existing dietary information provided patient-centred IBD-related organisations, scientists from the Department of Complementary and Alternative Medicine at John A Burns School of Medicine at the University of Hawaii in Manoa are attempting to create new ‘global practice guidelines’ that will consolidate the existing information regarding diet and IBD. They include nutritional deficiency screening, avoiding foods that worsen symptoms, eating smaller meals at more frequent intervals, drinking adequate fluids, avoiding caffeine and alcohol, taking vitamin/mineral supplements, eliminating dairy if lactose intolerant, limiting excess fat, reducing carbohydrates and reducing high-fibre foods during flare ups. They say that mixed advice exists regarding probiotics and note that enteral nutrition (the delivery of nutritionally complete food directly into the stomach) is recommended for Crohn’s disease patients in Japan, which differs from practices in the USA and UK. Manipulating the diet rather than relying on drug therapy may be particularly important as corticosteroid treatment in patients with Crohn’s disease has been linked to osteoporosis.


Stress and smoking can also influence the course of Crohn’s disease. 


 


For references, please see the White Lies report.


 

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