Immunopathogenesis of chronic inflammatory bowel disease

The aetiology and pathogenesis of chronic inflammatory bowel disease are unknown. However, there is circumstantial evidence that immune mechanisms may play a significant role in mediating the gut lesion and various systemic manifestations. The role of the cellular immune system, soluble mediators, including proinflammatory and immunoregulatory cytokines, humoral immunity and mucosal complement activation will be discussed.     

Occupational and chronic inflammatory bowel disease in Denmark

It has been suggested that some occupational groups have a high risk of contracting chronic inflammatory bowel diseases. A cohort, comprising 2,273,872 male and female Danes aged 20-59 on 1 January 1981, and a cohort similarly defined as of 1 January 1986 were followed up for hospitalizations due to chronic inflammatory bowel disease until 31. December 1990. From 1981 to 1990, 6296 first time admissions occurred. Among 15 groups previously found to be at high or low risk only female office staff and health personnel had statistically significantly increased standardized hospitalization ratios. Occupations with non-daytime work did not have an increased risk. Occupations with predominantly sedentary work had a standardized hospitalization ratio of 125 (95% confidence interval 116.9-133.1) compared to occupations without sedentary work. Self-employed had low hospitalization rates, while 'other salaried staff' and "not economically active" had high rates.     

Thromboembolic complications in inflammatory bowel disease

Thromboembolic complications during the course of inflammatory bowel disease are infrequent but are mainly found in young patients and are associated with a high morbimortality. The etiopathogenesis of these complications has been widely debated and the existence of coagulation alterations and fibrinolysis have been suggested. Nonetheless, the mechanism must be complex since not only do not all the patients with these alterations present this complication but neither do all the patients with thromboembolism have recognized coagulation disorders. The most common clinical presentation is deep vein thrombosis with pulmonary embolism with arterial thrombosis being rare. Five patients with Crohn's disease and two with ulcerative colitis who presented a total of new thromboembolic episodes, six arterial (1 in primitive iliac artery, 1 in common femoral artery, 1 in humeral-axillary artery, 2 in internal carotid and 1 in superior mesenteric artery) and three of venous localization (1 in brachyocephalic-subclavian trunk, 1 axillary and 1 iliac-femoral/pulmonary thromboembolism) are reported. An updated review of the etiopathogenesis, presentation, treatment and prophylaxis of the thromboembolic complications of inflammatory bowel disease is presented.     

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.     

Medical therapy of inflammatory bowel disease

In the past years the advances in therapy of IBD have been characterized mainly by the more widespread use of immunosuppression. Especially azathioprine is currently used in Crohn's disease with methotrexate as the second-line immunosuppressive drug. Cyclosporin may become a drug of choice to treat severe ulcerative colitis but its effect in the long term is probably insufficient. Topically acting glucocorticosteroids have emerged as a valuable safer alternative to standard glucocorticosteroids (GCS) in right ileocolonic Crohn's disease but GCS have no role in maintenance therapy. The most significant development in recent years is the introduction of immunomodulatory treatments using cytokines and anticytokines. The first data show that anti-TNF monoclonal antibodies, especially cA2, not only may result in rapid control of active Crohn's disease but also achieve rapid tissue healing. Repeated administration of cA2 maintains remission. Immunomodulation therapy creates great expectations since early reset of the immunostat might be able to control inflammation in the long term. Safety will be a key issue.     

Surgery for inflammatory bowel disease in Singapore

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.     

Colorectal cancer in idiopathic inflammatory bowel disease

The development of colorectal cancer is the most serious long-term problem faced by patients with extensive ulcerative colitis and Crohn's colitis, with an incidence 20-fold higher and an average age of onset 20 years younger than colorectal cancer in the general population. This report summarizes the epidemiology, pathology, and recent advances in the molecular pathogenesis of colorectal cancer in inflammatory bowel disease and of its acknowledged precursor, mucosal dysplasia. It also reviews the rationale behind the use of endoscopic surveillance for dysplasia as a means of reducing cancer mortality, as well as some of the issues involved in its effective implementation.     

Conventional drug therapy in inflammatory bowel disease

The conventional treatment of inflammatory bowel disease should center around the liberal use of one of the many available forms of 5-ASA. Sulfasalazine should be used initially with the newer mesalamine-only containing drugs being reserved for sulfasalazine-intolerant patients or for those patients who require larger doses of medication. The choice of the delivery method should be made with the knowledge of the extent of disease and the potential coverage areas of the individual delivery methods. Systemic and topical glucocorticoids are an invaluable adjunct to 5-ASA therapy, but their use must be directed with the goal of remission induction. The tapering of glucocorticoids should be as prompt as the maintenance of remission allows, with a useful general guideline of decreasing the dose by 1 mg per day. Immunosuppressive therapy, including azathioprine and 6-mercaptopurine, holds promise for refractory cases of inflammatory bowel disease and for their potential steroid sparing properties; antibiotic therapy with metronidazole and ciprofloxacin in the absence of documented infectious disease offers additional routes to control disease. The majority of patients require a combination of drugs to attain remission. Only further study will reveal the ideal regimen for each of the different subsets of inflammatory bowel disease.     

The immune system in inflammatory bowel disease

The activation of naive CD4+ T cells requires two discrete signals: a signal delivered by the T cell receptor following recognition of antigen and an accessory signal transduced when costimulatory receptors interact with their ligands. Particularly important in the development of an immune response to foreign antigens is the T cell molecule CD28, which delivers a potent costimulus when engaged by ligands, B7-1 and B7-2, on antigen-presenting cells. It is interesting that blockade of B7 molecules, which disrupts interactions with CD28 and prevents delivery of the CD28 costimulus, also alters the immune responses to self antigens and prevents the development of clinical disease in murine models of systemic and organ-specific autoimmunity. Herein we review the roles of CD28 and its B7 ligands in the pathogenesis of autoimmunity, discuss efforts to treat animal models of autoimmunity by modifying the CD28 signal, and consider the mechanisms by which manipulation of the CD28 signal alters the course of experimental autoimmune disease.     

Foetal outcome in women with inflammatory bowel disease treated during pregnancy with oral mesalazine microgranules

BACKGROUND: Little information is available about the safety of high doses of mesalazine during pregnancy. AIM: To study the fate of pregnancy and foetal outcome in women taking 1-4 g/day of mesalazine microgranules for inflammatory bowel disease. PATIENTS AND METHODS: Case reports were collected from the Pharmacovigilance Department of Ferring SA, France, from a survey conducted in three gastroenterology units, and from a teratology information service. The evolution of pregnancy and foetal outcome were assessed by questionnaire. RESULTS: The study covered a total of 123 pregnancies (126 foetuses). Ninety-six women took mesalazine during the first trimester, 85 during the second and 83 during the third. The mean daily dose was 2.1+/-0.8 g; 86 women received <3 g/day (low-dose group), 37 women received > or =3 g/day (high-dose group). The following abnormalities were observed in the low-dose and high-dose groups, respectively: ectopic pregnancy (1/0), spontaneous abortions (1/1), foetal death (0/1), premature deliveries (3/5, P < 0.05), congenital malformations (3/1) and one case of lethal oxalosis. Abnormalities were not considered to be related to mesalazine. CONCLUSIONS: The use of oral mesalazine microgranules during pregnancy is safe at doses < or =2 g/day, and probably also at a dose of 3 g/day.     

Pre-illness dietary factors in inflammatory bowel disease

BACKGROUND: The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them. AIM: To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls. METHODS: Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods. RESULTS: A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD. CONCLUSIONS: An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.     

Risk indicators for inflammatory bowel disease

We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.