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PubMed2006

Prevention of colorectal cancer in inflammatory bowel disease: value of screening and 5-aminosalicylates.

Colorectal cancer is a serious complication of inflammatory bowel disease. Given this fact, it is necessary to examine the opportunities for current and future approaches to colorectal cancer prevention. The value of surveillance colonoscopy and chemoprevention of colorectal cancer with 5'-aminosalicylic acid has been evaluated in the recent literature. The current state of knowledge in the epidemiology of and new approaches to the prevention of cancer and dysplasia in inflammatory bowel disease were reviewed. It is concluded that there is significant preclinical and clinical evidence to suggest that 5-aminosalicylate drugs reduce the risk of colorectal neoplasia. However, the minimal dosage to achieve this chemopreventive effect remains unclear. There is also indirect evidence to suggest that surveillance colonoscopy is beneficial for patients with inflammatory bowel disease, particularly in those with long-standing pancolitis or primary sclerosing cholangitis-associated inflammatory bowel disease. However, definitive proof from prospective clinical trials is not available.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

A randomized, placebo-controlled trial of calcium supplementation for decreased bone density in corticosteroid-using patients with inflammatory bowel disease: a pilot study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high prevalence of osteoporosis. A number of studies have found that corticosteroid use is associated with the development of osteoporosis in these patients. Calcium supplementation may be of benefit in corticosteroid-induced osteoporosis and calcium may be a nutrient that patients with IBD lack. AIM: To test the benefit of calcium supplementation on bone density in a pilot study over a 1-year period, in a group of corticosteroid-using patients with IBD, in a randomized, double-blind, placebo-controlled treatment study. METHODS: Corticosteroid-using patients with IBD including males over the age of 18 years and premenopausal females, were randomized to receive either calcium carbonate 1000 mg plus vitamin D 250 IU (Oscal) or an identically matched placebo. Dual energy X-ray absorptiometry measurements of bone density were obtained at entry and at 1 year. At entry, and every 3 months thereafter, serum was collected for the measurement of haemoglobin, biochemistry and bone hormones. Simultaneously a 24-h urine collection was analysed for calcium excretion and creatinine clearance, and a 4-day food record was collected to document dietary calcium and vitamin D ingestion. RESULTS: We found a high prevalence of moderately severe decreased bone density in corticosteroid-using patients with IBD. The dose of prednisone in the year prior to study entry was inversely correlated with bone density at the hip (R = -0.67, P = 0.004). At study entry serum osteocalcin was inversely correlated with corticosteroid dose in the year prior to the study (R = -0.64, P = 0.02) and at study end, directly correlated with the percentage change in spine bone density (R = 0.59, P = 0.01). The dietary calcium intake of these patients was close to the current RDA (recommended daily intake) for premenopausal, post-adolescent adults. Calcium supplementation with small extra doses of vitamin D conferred no obvious benefit to bone density at the end of 1 year. There was no correlation between oral calcium ingestion and bone mass measurements. Both the treatment and placebo groups' bone density remained relatively stable at 1 year, suggesting that bone loss in corticosteroid-using patients may peak early into the use of the corticosteroids. CONCLUSIONS: Calcium supplementation (1000 mg/day) conferred no significant benefit to bone density at 1 year in patients with corticosteroid-using IBD patients with osteoporosis. Future investigations should explore other therapeutic avenues that may have greater effects on increasing bone density in patients who already have considerable osteoporosis.

Absorptiometry, Photon↗
PubMed1991

Metabolism of vitamin A in inflammatory bowel disease.

The aim of this study was to determine serum retinol levels in patients with inflammatory bowel disease and to attempt to elucidate the mechanism of changes in vitamin A metabolism in these disorders. It was found that in 15 patients with active ulcerative colitis, 14 patients with active Crohn's disease and in 3 operated patients with recurrent Crohn's disease serum retinol levels and retinol-binding protein were significantly lower than in controls. Concentrations of vitamin A did not depend on the localization of inflammatory bowel disease, previous ileal resections, duration of the disease or age and sex of the patients. During successful treatment of active ulcerative colitis normalization of serum retinol levels without substitution of vitamin A was observed. Repeated determinations in patients with Crohn's disease who had low serum retinol levels in an active phase of disease revealed normal vitamin A levels in an inactive phase. The absorption of vitamins A and E in patients with inflammatory bowel disease was normal. The normal serum retinol concentrations in patients with diarrhea due to irritable bowel syndrome, and in those with anorexia nervosa exclude the influence of diarrhea and body weight itself on vitamin A levels. The results of this study indicate that serum retinol levels in patients with active inflammatory bowel disease are secondary to the decreased serum retinol-binding protein concentrations, and probably depend on the increased protein catabolism in these disorders.

Adult↗
PubMed2001

Review article: does the use of immunosuppressive therapy in inflammatory bowel disease increase the risk of developing lymphoma?

Recent case reports have raised concerns regarding the risks of non-Hodgkin's lymphoma in patients with inflammatory bowel disease treated with immunosuppressive agents. This evidence-based review examines this issue from data derived from the use of immunosuppression in other conditions (and inflammatory bowel disease). We conclude that, in transplant (cardiac and renal) recipients, immunosuppression increases the risk of non-Hodgkin's lymphoma. For non-transplant patients (with psoriasis and rheumatoid arthritis), debate remains as to whether the observed increase in the incidence of non-Hodgkin's lymphoma is due to drug or disease. For inflammatory bowel disease per se, population studies show no significant increase in the risk of non-Hodgkin's lymphoma, with a relative risk of 1.3 (95% confidence interval, 0.9-1.7) compared to expected rates, and several studies of immuno- suppression in inflammatory bowel disease do not appear to confirm a significant rate of lymphoma incidence. Reported cases of lymphoma from single centres should be viewed with caution as evidence of increased risk. If any association exists, it is likely to be of minimal clinical significance compared to the established and more frequent risks of myelosuppression and infection, and is unlikely to outweigh the benefit of immunosuppression in inflammatory bowel disease.

Arthritis, Rheumatoid↗
PubMed2006

Evidence-based medications for the treatment of the inflammatory bowel diseases.

PURPOSE OF REVIEW: Evidence-based medicine is an increasingly important tool to aid the clinician in the treatment of patients. This is particularly true for diseases such as the inflammatory bowel diseases, for which the pathogenesis is unknown and an extensive range of treatment options is available. High quality data may not be available for all decisions, but it is essential that clinicians are aware of well-grounded data that are available. RECENT FINDINGS: The body of data supporting the use of biological therapies in inflammatory bowel disease continues to grow and diversify. Regulatory requirements and academic expectations are evolutionary forces that are resulting in continuous improvement in the quality of studies. SUMMARY: This review will update the reader on several significant analyses that have been published recently. It is intended to raise awareness of the data, helping clinicians to evaluate new treatments and to revisit older treatments with a critical eye.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease.

Initiation and perpetuation of the inflammatory intestinal responses in inflammatory bowel disease (IBD) may result from an exaggerated host defense reaction of the intestinal epithelium to endogenous lumenal bacterial flora. Intestinal epithelial cell lines constitutively express several functional Toll-like receptors (TLRs) which appear to be key regulators of the innate response system. The aim of this study was to characterize the expression pattern of TLR2, TLR3, TLR4, and TLR5 in primary intestinal epithelial cells from patients with IBD. Small intestinal and colonic biopsy specimens were collected from patients with IBD (Crohn's disease [CD], ulcerative colitis [UC]) and controls. Non-IBD specimens were assessed by immunofluorescence histochemistry using polyclonal antibodies specific for TLR2, TLR3, TLR4, and TLR5. Primary intestinal epithelial cells (IEC) of normal mucosa constitutively expressed TLR3 and TLR5, while TLR2 and TLR4 were only barely detectable. In active IBD, the expression of TLR3 and TLR4 was differentially modulated in the intestinal epithelium. TLR3 was significantly downregulated in IEC in active CD but not in UC. In contrast, TLR4 was strongly upregulated in both UC and CD. TLR2 and TLR5 expression remained unchanged in IBD. These data suggest that IBD may be associated with distinctive changes in selective TLR expression in the intestinal epithelium, implying that alterations in the innate response system may contribute to the pathogenesis of these disorders.

Amino Acid Sequence↗
PubMed2001

Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3).

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine, commonly diagnosed as either ulcerative colitis (UC) or Crohn's disease (CD). Epidemiological studies have consistently shown that both genetic and environmental factors influence the pathogenesis of IBD. A number of genome scans have been conducted in cohorts of IBD families with affected sibling pairs (ASPs) to identify chromosomal regions that harbour IBD susceptibility genes. Several putative linked loci have been identified, including two loci on chromosomes 16 and 12, IBD1 and IBD2, which have subsequently been replicated by independent region-specific studies. We have conducted both a replication study on another linkage region, chromosome 6p (IBD3), and extension studies on two other regions, chromosomes 3p and 7q. Microsatellite markers across each region were genotyped in 284 IBD ASPs from 234 families. A nonparametric peak multipoint LOD score of 3.0 was observed near D6S291, replicating the previous linkage to chromosome 6p (IBD3). Nominal evidence of linkage was observed at both the 3p and 7q regions.

Chromosome Mapping↗
PubMed2003

Superior mesenteric vein thrombosis after colectomy for inflammatory bowel disease: a not uncommon cause of postoperative acute abdominal pain.

PURPOSE: Thromboembolism is a significant cause of morbidity and mortality in inflammatory bowel disease. Several prothrombotic conditions have been investigated in inflammatory bowel disease. The aim of this study was to evaluate the incidence of symptomatic postoperative superior mesenteric vein thrombosis in inflammatory bowel disease patients undergoing colonic resections and to identify and characterize their clinical presentation. METHODS: Between January 1999 and December 2001, 83 consecutive patients undergoing total colectomy for inflammatory bowel disease were studied retrospectively. Patients who developed new-onset postoperative acute abdominal pain were evaluated by CT scan of the abdomen. A complete coagulation profile, including thrombin time, platelet count, protein C, protein S, antithrombin III, homocysteine level, factor V Leiden mutation, plasminogen, and prothrombin G20210A mutation, was obtained in patients diagnosed with superior mesenteric vein thrombosis. RESULTS: Four patients (4.8 percent; 3 females; 3 patients with ulcerative colitis and 1 with Crohn's colitis) developed symptomatic postoperative superior mesenteric vein thrombosis. Two of these patients had extension of the clot into the portal vein. Their presenting symptom was abdominal pain, with a median interval of ten days from the index surgery. The hematologic workup was negative in three patients, with one heterozygous for prothrombin G20210A mutation. All patients were treated with systemic anticoagulation for at least six months. One ulcerative colitis patient was diagnosed after abdominal colectomy and underwent an uneventful ileal pouch-anal anastomosis after systemic anticoagulation. CONCLUSION: Postoperative superior mesenteric vein thrombosis is a more frequent occurrence than previously reported in patients with inflammatory bowel disease. Direct surgical trauma to the middle colic veins, with resulting thrombosis, is likely to be the precipitating factor in a borderline intrinsically hypercoagulable environment. All patients became asymptomatic after systemic anticoagulation and recovered uneventfully.

Abdomen, Acute↗
PubMed2004

Experience with the use of low-dose methotrexate for inflammatory bowel disease.

BACKGROUND: Thiopurine drugs (azathioprine and 6-mercaptopurine) are well established in the treatment of patients with inflammatory bowel disease. However, some patients are intolerant or resistant to thiopurine drugs and their management remains a challenge. Several studies have suggested methotrexate is effective for the induction and maintenance of remission in Crohn's disease. OBJECTIVE: This study was conducted because the overall data on clinical efficacy of methotrexate in inflammatory bowel disease remain limited and there are no data regarding fistulating Crohn's disease or concomitant use of methotrexate with thiopurine drugs in inflammatory bowel disease. METHODS: This study was a retrospective review of medical notes. Clinical response was defined as sustained withdrawal of oral steroids or fistula improvement. New episodes of steroid therapy, infliximab or surgery during the first 6 months were considered as failure to achieve clinical response. RESULTS: Seventy-two patients were studied (66 Crohn's disease and six ulcerative colitis). The mean dose of methotrexate used was 18.2 mg/week. Clinical response was achieved in 22 of 54 patients (40.7%) who completed 6 months of methotrexate treatment. For patients with Crohn's disease, fistula improvement was achieved in eight of 18 (44.4%) patients compared with 11 of 30 (36.7%) receiving methotrexate for steroid withdrawal. Clinical response was achieved in six of 15 patients (40%) treated with methotrexate and azathioprine at the same time compared with 16 of 39 patients (41%) treated with methotrexate alone. CONCLUSIONS: Methotrexate is reasonably effective in clinical practice as a steroid sparing agent in inflammatory bowel disease. The efficacy in fistulating Crohn's disease justifies its use as an immunomodulator in these patients. Combined azathioprine and methotrexate treatment appears to offer no advantage over methotrexate alone.

Adolescent↗
PubMed1982

Sulfasalazine intolerance. A retrospective survey of the reasons for discontinuing treatment with sulfasalazine in patients with chronic inflammatory bowel disease.

Sulfasalazine is of proven therapeutic value in chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease in the colon) of mild and moderate degrees. However, owing to adverse effects (allergy, dyspepsia), this drug often has to be withdrawn. The present work analyzes, in 704 patients with chronic inflammatory bowel disease, the frequency of such side effects that over a 15-year period necessitated withdrawal of sulfasalazine (Salazopyrin). A total of 17% of the patients developed dyspeptic manifestations, whereas extraintestinal manifestations, mainly exanthema and fever, occurred in 13%. Out of 121 patients with dyspeptic troubles, 107 had Salazopyrin replaced by EN Salazopyrin (dragées), and in 102 of them dyspepsia did not recur. Salazosulfadimidine (Azudimidine) was given to 48 patients who had developed extraintestinal manifestations when receiving sulfasalazine. Only 29% of these patients developed intolerance to this drug too. Generally, dyspepsia occurred within the first days after institution of treatment, extraintestinal manifestations after 1 to 3 weeks.

Colitis, Ulcerative↗
PubMed1996

[Quality of life in chronic inflammatory bowel diseases. Validation of a questionnaire and first French data].

UNLABELLED: Inflammatory bowel diseases have an important impact on the daily life of patients. This impact can be measured by the evaluation of the health related quality of life. The aim of this study was to develop and to validate a questionnaire of quality of life in a French population. METHODS: The questionnaire comprised 70 items and was completed in 15 min. It was made up of a) a general questionnaire of 36 items (SF-36) exploring daily physical and social functioning, mental and general health, body pain and vitality. A sleep module of 6 items was added. b) a specific questionnaire of 28 items (RFIPC), exploring the concerns of the patients. The questionnaire was self-administered to 101 patients with Crohn's disease (57 F. 44 M. mean age: 35 years, acute disease: 28%, inpatients: 27%), 96 patients with ulcerative colitis (38 F. 58 M. mean age: 39 years, acute disease: 53%, inpatients: 21%). Each patient was sex and age matched with a healthy control. RESULTS: The psychometric analysis confirmed the validation of the questionnaire for the item's convergent validity, internal consistency (Cronbach's coefficient being > 0.70), analyses of discrimination. Scores of each scale of SF-36 were worse in patients than in controls. Scores of patients with active disease were worse than those of patients with quiescent disease. Scores were comparable in patients with Crohn's disease and with ulcerative colitis except for score of pain which was worse in acute Crohn's disease. The most important concerns of patients were the uncertain nature of the disease, energy level and having surgery. CONCLUSION: This study allowed the validation of a questionnaire for the evaluation of the quality of life in French patients with inflammatory bowel disease and provides first indications which need to be confirmed by future epidemiological studies.

Adult↗
PubMedDate not supplied

Normal absorption of oral prednisolone in children with active inflammatory bowel disease, including cases with proximal to distal small bowel involvement.

In order to determine whether oral prednisolone efficiency in inflammatory bowel disease may be limited by impaired absorption, seven patients were studied. These were children with active disease, localized or extensive on the small and/or the large bowel. Serum prednisolone concentrations were compared within each subject after oral and intravenous administration of the same dose. Absorption was found complete, and its rate similar to that in nine normal adults. Thus prednisolone malabsorption did not limit treatment efficiency. In one patient, an alternative explanation was poor compliance with the treatment. Less complete studies in nine other children with active inflammatory bowel disease suggested the same conclusion. Prednisolone malabsorption in children with inflammatory bowel disease, if it exists, could only be transitory or exceptional.

Administration, Oral↗
PubMed2001

Epidemiology of inflammatory bowel disease in Spain. A systematic review.

BACKGROUND AND OBJECTIVES: Incidence and prevalence of Inflammatory Bowel Disease (IBD) differ considerably depending on the geographical region studied. In Spain, both Ulcerative Colitis (UC) and Crohn's Disease (CD) seem to have experienced an important change in terms of incidence during the past decades. Our aim was to systematically review the experience in Spain regarding the epidemiology of IBD, in particular its incidence, its geographical differences and its evolution over time. METHODS: A bibliographical search till January 2000 was conducted in Internet using the PubMed search motor and the following descriptors or key words: "Crohn's disease", "Ulcerative colitis", "Inflammatory bowel disease", "Spain" and "Spanish". Only publications providing data on IBD incidence among Spanish patients were included. References from articles that fulfilled the selection criteria were also reviewed. The endpoints considered in the review were IBD incidence rate, its geographical differences, and its evolution over time. RESULTS: UC incidence reported by different studies performed in Spain ranges from 0.6 to 8 cases/10(5)/year, with a mean value of 3.8. CD incidence rates in Spain ranges from 0.4 to 5.5 cases/105/year, with a mean value of 1.9. Some studies have shown differences in IBD incidence between regions in our country. Many studies have reported an increase in IBD incidence in Spain over time, although such increase is more evident in the case of CD. CONCLUSIONS: UC incidence in Spain ranges from 0.6 to 8 cases/105/year, with a mean value of 3.8. CD figures range from 0.4 to 5.5 cases/105/year, with an average rate of 1.9. IBD incidence seems to be relatively different depending on the geographical region studied. Finally, several authors have demonstrated an increase in IBD incidence in Spain over time, although such increase seems to be more evident in the case of CD. Consequently, IBD in Spain is no longer considered a rare disease, but a relatively frequent one.

Humans↗
PubMed1991

Familial occurrence of inflammatory bowel disease.

BACKGROUND AND METHODS: We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders. In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, asking whether their first- and second-degree relatives had this disorder. Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohn's disease) provided adequate information. RESULTS: As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohn's disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex. The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohn's disease was not significant in the relatives of patients with ulcerative colitis. The risk of ulcerative colitis in first-degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first-degree relative belonged and of the sex of the patient and the relative. The risk of ulcerative colitis in first-degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50, but the risk seemed to be independent of the current age of the relatives. The prevalence of the same disease as that of the patient (either ulcerative colitis or Crohn's disease) among second-degree relatives was increased; the prevalence of the other disease was not increased. CONCLUSIONS: The 10-fold increase in the familial risk of ulcerative colitis and Crohn's disease strongly suggests that these disorders have a genetic cause.

Adult↗
PubMed1991

Changes in phenotypically distinct mucosal macrophage populations may be a prerequisite for the development of inflammatory bowel disease.

Previous studies have demonstrated the presence of much more marked macrophage heterogeneity in colonic mucosa affected by the idiopathic inflammatory bowel diseases (ulcerative colitis and Crohn's disease) than in normal mucosa. This study examines the morphology, distribution and phenotypic expression of mucosal macrophage-like cells in biopsies from patients with idiopathic inflammatory bowel disease in comparison with disease control samples from patients with colonic infection or ischaemia. Approximately 80% of macrophage-like cells in histologically normal mucosa co-express the antigens recognized by the monoclonal antibodies RFD1 (an interdigitating cell marker) and RFD7 (a marker for mature tissue macrophages). In idiopathic inflammatory bowel disease, the normal colonic macrophage population is partly replaced by cells staining positively with RFD7 alone, and, to a lesser extent, with RFD1+ dendritic cells. Sections from patients with infections and ischaemia exhibited epithelial HLA-DR positivity and infiltration of the lamina propria by a more heterogeneous population of macrophages than that seen in histologically normal mucosa. However, the displacement of the normal colonic macrophage phenotype by RFD7+ tissue macrophages occurred to a significantly greater extent in idiopathic inflammatory bowel disease than in disease control mucosa. A pathognomonic feature of the ulcerative colitis and Crohn's colitis sections was the clustering of RFD9+ epithelioid cells at the bases of disrupted crypts and adjacent to areas of mucosal damage. It is concluded that a degree of macrophage heterogeneity and macrophage infiltration can occur as a non-specific response to colonic mucosal damage. The distinctive feature of idiopathic inflammatory bowel disease mucosa is the almost complete replacement of the normal colonic mucosal macrophage population by tissue macrophages and epithelioid cells, and this phenomenon may be important in promoting the development of a chronic inflammatory state.

Adolescent↗
PubMed1987

Corticosteroids in inflammatory bowel disease. A review.

Corticosteroids have been used for decades in the treatment of inflammatory bowel disease. Despite considerable information on the clinical response to corticosteroids in inflammatory bowel disease, much less is known concerning corticosteroids' effects on the underlying immunopathology of the disease. In this review, we discuss the known immunologic actions of corticosteroids: their effects on eicosanoid production and on modulating the humoral and cellular immune response. After reviewing the postulated immunological aberrations in inflammatory bowel disease, we speculate on the specific immunologic effects of corticosteroids in this disease.

Adrenal Cortex Hormones↗
PubMed2003

Severe inflammatory bowel disease: medical management.

The majority of patients with inflammatory bowel disease (IBD) have mild or moderate disease. However, a minority have a severe attack requiring hospital admission. Acute severe colitis (ulcerative colitis and Crohn's colitis) continues to be a medical emergency requiring careful joint management by physicians and surgeons. Extensive Crohn's jejuno-ileitis can also present major management problems, particularly in children. The evidence base for the management of this potentially severe form of Crohn's disease is limited and thus treatment has to be largely tailor-made for individual cases. Acute intestinal failure occurs in Crohn's disease in a variety of clinical settings, but the most challenging problem in the acute phase is the management of the major losses of fluid and electrolytes.

Colitis↗
PubMedDate not supplied

Incidence of inflammatory bowel disease in the French West Indies (1997-1999).

OBJECTIVES: To investigate the incidence of inflammatory bowel disease in the French West Indies. METHODS: From January 1st 1997 to December 31st 1999 all patients observed with clinical symptoms suggestive of inflammatory bowel disease attending gastroenterologists practicing in Guadeloupe and Martinique were included. Patients were interviewed with a standard questionnaire to record data used by an expert to establish the final diagnosis of definite, probable or possible Crohn's disease, ulcerative colitis, unclassifiable chronic colitis or acute colitis, according to the EPIMAD registry. RESULTS: Sixty-six cases of ulcerative colitis (47.48%) including 12 cases of ulcerative proctitis (18.18% of the ulcerative colitis cohort), 55 of Crohn's disease (39.57%), 11 of unclassifiable chronic colitis (7.91%), and 7 of acute colitis (5.04%) were recorded. The crude annual incidence (per 100,000 inhabitants) based on definite and probable cases only was 2.44 for ulcerative colitis and 1.94 for Crohn's disease. The female/male ratio and median age at time of diagnosis were 1.61 and 29 years for Crohn's disease and 1.46 and 34 years for ulcerative colitis respectively. The median time from symptom onset to diagnosis was 2 months for both diseases. CONCLUSIONS: The observed incidence of inflammatory bowel disease In the French West-Indies is lower than in metropolitan France. These data will serve as a basis to assess disease evolution.

Adolescent↗