Inflammatory bowel disease (2003)

Inflammatory bowel disease may potentially cause lifelong disability and is associated with an increased risk of colorectal cancer (Table 1, Figure 1). The two major forms of idiopathic inflammatory bowel disease are ulcerative colitis and Crohn's disease. These disorders commonly occur early in life; 15–20% present in childhood before the age of 16 years, and are increasing in prevalence. There is a very considerable geographical difference in incidence, with an apparent north/south divide, particularly with respect to Crohn's disease, which is 10–20 times higher in Scandinavia than it is in Greece (2, 3). Cumulative frequency of colorectal cancer in patients with extensive ulcerative colitis and extensive Crohn's disease [1]. Ulcerative colitis. Incidence/100 000 of the population, corrected for age and sex [6]. Crohn's disease. Incidence/100 000 of population corrected for age and sex [6]. The cause of inflammatory bowel disease remains unknown, but there is growing evidence of familial susceptibility to an intestinal antigen, which may be transmittable (Table 2). The risk of developing either condition is influenced by a number of environmental factors including smoking. The type of immunological response that occurs results in two phenotypically and genotypically distinct disorders, but there is an overlap in 5–10% of patients, especially when they present acutely, and these cases may be referred to as indeterminate colitis. For this reason, the disorders will be described separately. The impact of these disorders on admission rates is shown in Table 3. The difference in healthcare consumption for ulcerative colitis and Crohn's disease with respect to consultations, admissions, operations, endoscopy and radiology costs from a European survey are shown in Table 4. A study in the Netherlands indicates the impact of inflammatory bowel disease, especially of Crohn's disease, on age-adjusted employment and work disability, as well as loss of employment from sick leave (Table 5). Ulcerative colitis affects only the large bowel. The inflammatory process is confined to the inner gut lining (mucosa). The incidence of this disorder in Europe from data corrected for age and sex is shown in Figure 2. In 10–30% of cases of ulcerative colitis, the first manifestation of the disease is an acute attack of bloody diarrhoea. These patients may be acutely unwell and there is a real risk that the bowel may perforate, causing potentially fatal peritonitis if there is no response to intensive drug therapy. In a third of these patients with fulminating colitis, an operation to remove the diseased colon is required, either during the first hospital admission or within a year of diagnosis. These urgent operations often result in a temporary stoma, or bag, being fashioned. Fortunately, the majority of patients with ulcerative colitis can be treated by medication alone. All patients with colitis, but particularly severe disease involving most of the colon, is associated with colon cancer development. The risk is significant and warrants screening for colon cancer by colonoscopy every 3 years after diagnosis. The average cost over 10 years for surveillance colonoscopy is in the order of €2500. Thus, from time to time, operations are needed to treat or protect against a high risk of cancer. The overall lifetime likelihood of needing an operation for ulcerative colitis is between 10 and 15%. These operations are generally performed in two or three stages and cost on average €25 000–30 000 per patient. Fortunately, in this disease, an ileostomy rarely needs to be permanent because modern operations now make it feasible to remove the diseased bowel and join it together whilst preserving normal bowel continence by the construction of a pouch. The impact of this disorder on quality of life is considerable. There is a lifelong fear of cancer (risk over years shown in Figure 1) and the possibility of an ileostomy bag, which most people find repugnant. On account of the increased risk of colitis among family members (Table 2), there is a natural concern that siblings or children may become affected by this disease or its partner, Crohn's disease. There is also a public health fear that certain dietary products or environmental factors might exacerbate the disease. The medication required to prevent relapse normally has to be taken indefinitely, which is a burden on health costs, the average cost per annum being €1500. Furthermore, additional treatments needed in cases of relapse have potential serious side-effects, as well as being expensive. These side-effects include heart disease, diabetes, increased susceptibility to infections, hypertension, bone-marrow suppression and kidney failure. Some patients with ulcerative colitis have associated skin disorders, liver failure, joint manifestations and eye diseases, which may be associated with chronic disability. All patients with ulcerative colitis require lifelong medical supervision, and are seen on average 1.6 times per year (Table 4). The economic burden at the moment differs very considerably between countries in Europe. The incidence of Crohn's disease in various locations in Europe is shown in Figure 3. There is considerable geographical variation, with a much higher incidence in northern than in southern Europe, and the incidence appears to be increasing (Figure 4). Although it is less common than ulcerative colitis, it has a far greater impact on quality of life, and overall costs are therefore larger (Table 4). Crohn's disease may cause severe colitis, which is sometimes indistinguishable from ulcerative colitis but with a tendency to form disease and infection around the anus. Unlike ulcerative colitis, Crohn's disease is not confined to the lining of the bowel but burrows through the bowel wall to form abscesses and fistulas (abnormal connections between the lumen of the bowel and other organs or the surface of the skin), and it may also present as bowel obstruction. It may affect any part of the bowel, as well as the mouth, oesophagus, appendix and worst of all the anorectum. In the latter, it has a devastating impact by causing fistulas around the anus or into the female genital tract. The disease may result in strictures, narrowing and recurrent abscesses, which often results in bowel incontinence and embarrassing psychosexual problems as well as general ill-health. Changes in the incidence of Crohn's disease per 100 000 population from sequential studies in various geographical locations (Nunes & Ahlquist 1988) [13]. The mainstay of medical treatments for Crohn's disease are drugs, dietary manipulation and lifestyle modifications. Drug therapy rarely cures the disease but may delay or prevent surgical intervention. As in ulcerative colitis, medications can be associated with potentially dangerous side-effects. Low residue diets may alleviate incomplete obstruction and may reduce the need for operation, but diets are often unpalatable and compliance can be poor. Smoking is known not only to increase the risk of developing Crohn's disease, but also the risk of requiring initial and repeated operations (Table 6, Figure 5) [14]. Effects of smoking on the prognosis of Crohn's disease: 5 and 10 year cumulative recurrence rates for smokers compared with non-smokers [7]. As in ulcerative colitis, there is a comparable risk of bowel cancer. Table 1. However, in Crohn's disease many have so much trouble from the inflammation in the bowel itself that the disease is removed before cancer develops. Approximately 75–90% of all patients with Crohn's disease require surgical operations. Patients with Crohn's disease have a lifetime risk of approximately three operations, which can range from between one and 10 procedures during their lifetimes at an average cost of €15 000 per operation. The avoidance of a permanent ileostomy is much less likely in Crohn's disease than in ulcerative colitis. Approximately 35% of patients having an operation eventually need a permanent ileostomy. There are clusters of cases in tight geographical communities and a strong family history, which might imply genetic susceptibility to a transmittable agent. Specific gene mutations are found in over 70% of patients with Crohn's disease. The impact of Crohn's disease on lifestyle is considerable. It often affects children and may permanently compromise musculoskeletal development, either from the medication or malnutrition. Crohn's disease may compromise educational milestones because of illness, hospital admissions and operations. The toll of Crohn's disease on sexual activity, marriage and family life can be devastating. An ileostomy, fistulas into the vagina, chronic infections, malnutrition, drug therapy with metabolic side-effects, may result in infertility, prevent normal sexual relationships, cause psychological scarring and lifelong anxiety [5]. Social deprivation and missed employment opportunities are frequent consequences of chronic ill health, bowel incontinence and ileostomy or medication. The social and economic burden from repeated out-patient consultations, operations, hospital admissions and drug medication is much greater in Crohn's disease than it is in ulcerative colitis (Table 4). If causative agents are discovered there is then the prospect of developing immunization strategies against these diseases. This, however, remains aspirational. Anti-smoking campaigns will reduce the burden of Crohn's disease. Genetic susceptibility should allow targeted members of the public at risk to be offered dietary advice, surveillance and possibly specific immunological therapy that will prevent the complications of inflammatory bowel diseases developing. Any such programme will require significant initial investment.