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Review article: nutrition and adult inflammatory bowel disease.

Major advances in the understanding of the aetio-pathogenesis and genetics of inflammatory bowel disease have been accompanied by an escalation in the sophistication of immunomodulatory inflammatory bowel disease therapeutics. However, the basic 'triple' therapy (5-aminosalicylates, corticosteroids, azathioprine) and nutrition have maintained their central role in the management of patients with inflammatory bowel disease over recent decades. This review provides an overview of the supportive and therapeutic perspectives of nutrition in adult inflammatory bowel disease. The objective of supportive nutrition is to correct malnutrition in terms of calorie intake or specific macro- or micronutrients. Of particular clinical relevance is deficiency in calcium, vitamin D, folate, vitamin B12 and zinc. There is justifiably a growing sense of unease amongst clinicians and patients with regard to the long-term use of corticosteroids in inflammatory bowel disease. This, rather than arguments about efficacy, should be the catalyst for revisiting the use of enteral nutrition as primary treatment in Crohn's disease. Treatment failure is usually related to a failure to comply with enteral nutrition. Potential factors that militate against successful completion of enteral nutrition are feed palatability, inability to stay on a solid-free diet for weeks, social inconvenience and transient feed-related adverse reactions. Actions that can be taken to improve treatment outcome include the provision of good support from dietitians and clinicians for the duration of treatment and the subsequent 'weaning' period. There is evidence to support a gradual return to a normal diet through exclusion-re-introduction or other dietary regimen following the completion of enteral nutrition to increase remission rates. We also review the evidence for emerging therapies, such as glutamine, growth factors and short-chain fatty acids. The future may see the evolution of enteral nutrition into an important therapeutic strategy, and the design of a 'Crohn's disease-specific formulation' that is individually tailored, acceptable to patients, cost-effective, free from adverse side-effects and combines enteral nutrition with novel pre- and pro-biotics and other factors.

Butyrates↗

Magnetic resonance imaging of inflammatory bowel disease: evaluation in a rabbit model.

PURPOSE: To correlate intestinal contrast enhancement and wall thickening with the degree of inflammation in an experimental model of inflammatory bowel disease. MATERIALS AND METHODS: Inflammatory bowel disease was elicited in 39 New Zealand White rabbits by rectal instillation of 2,4,6-trinitrobenzene sulphonic acid (TNBA). Magnetic resonance imaging (MRI) was used to determine bowel wall thickness and intestinal contrast enhancement after the administration of 0.1 mmol/kg of gadodiamide intravenously. MR measurements were compared with the complete histopathologic analysis. RESULTS: MR measurements of bowel wall thickness correlated well with histopathologic measurements in vitro (r = 0.85, P < 0.0001) and with histopathologic evidence of chronic inflammatory bowel disease (P < 0.02). Chronic inflammation was characterized by increased intestinal contrast enhancement (137 +/- 25%) when compared to normal bowel (86 +/- 7%, P = 0.04). CONCLUSION: Contrast-enhanced MRI accurately reflects inflammatory bowel disease in the rabbit model.

Animals↗

Technetium-99m autologous phagocyte scanning: a new imaging technique for inflammatory bowel disease.

A method to determine the extent of active inflammatory bowel disease using selective labelling of autologous neutrophils and monocytes by phagocytosis of a technetium-99m (99mTc) stannous oxide colloid is described. Unlike leucocyte scanning techniques using Indium-III (IIIIn), the 99mTc colloid scan uses a cheap, readily available isotope, which specifically labels phagocytes. Scan results in 20 patients with inflammatory bowel disease were compared with barium examinations and colonoscopic appearances. There was close agreement in 15 of 20 patients as to the extent of mucosal disease. In four cases the scan showed more extensive disease than was suggested by barium examination. The scan showed terminal ileal Crohn's disease in three patients in whom the barium studies of the ileum had been reported as normal. In four patients with inactive disease and normal barium examinations no activity was seen on the scans. The 99mTc phagocyte scan is a sensitive, reliable means of determining the extent of active inflammatory bowel disease and can be used to quantify disease activity.

Adolescent↗

Tumor necrosis factor-alpha is not elevated in children with inflammatory bowel disease.

Chronic undernutrition and high-dose daily corticosteroid therapy are well-accepted causes of growth failure in children with inflammatory bowel disease. Occasionally, children are seen with minimal gastrointestinal symptoms but in whom severe anorexia and profound growth impairment are evident. Recent observations that elevated serum levels of tumor necrosis factor-alpha (TNF) in cachexia associated with a number of disease states have suggested a similar possible role in inflammatory bowel disease. Accordingly, we determined TNF levels in 45 children and adolescents with inflammatory bowel disease (18 ulcerative colitis, 27 Crohn's disease) at varying times during their clinical course and compared them to values obtained from a group of 25 children with functional bowel disease. No differences were noted in serum TNF levels between the children with inflammatory bowel disease and the control population. Values were generally within the range of the lower limit of detection of the assay. In the children with inflammatory bowel disease, there was no significant correlation between TNF levels and disease activity or growth parameters. Our observations suggest that elevated TNF levels are not associated with inflammatory bowel disease in children.

Adolescent↗

Ultrasonographic findings correspond to clinical, endoscopic, and histologic findings in inflammatory bowel disease and other enterocolitides.

OBJECTIVE: To compare results obtained by abdominal ultrasonography with clinical findings, including endoscopic and histologic findings, to evaluate the location and activity of inflammatory bowel disease, including disease controls in children. METHODS: Ninety-two ultrasonographic scans and 41 colonoscopic examinations with biopsies were performed in 78 patients (1 month to 17.8 years of age) with Crohn's disease (n = 26), ulcerative colitis (n = 21), inflammatory bowel disease of indeterminate type (n = 2), and disease controls (other intestinal disorders, including infectious and ischemic lesions; n = 29). Laboratory parameters for inflammatory bowel disease were determined, and disease activity was assessed by a combination of clinical and laboratory data. Bowel wall thickness and echo texture were recorded in a standardized way by ultrasonography and compared with endoscopic and histologic findings in a segment-by-segment comparison. RESULTS: Sensitivity and specificity of ultrasonography in detecting patients with severe macroscopic lesions depicted on endoscopy were 77% and 83%, respectively. Sensitivity and specificity of ultrasonography in detecting patients with severe histologic inflammation were 75% and 82%. There was a statistically significant correlation between maximal bowel wall thickness and disease activity score (P < .01). CONCLUSIONS: Abdominal ultrasonography may be helpful in evaluating the location, severity, and inflammatory activity of inflammatory bowel disease in children and young adults.

Adolescent↗

Enteral feeding in inflammatory bowel disease.

PURPOSE OF REVIEW: Treatment algorithms for inflammatory bowel disease are changing rapidly. Increased and earlier use of immunomodulatory drugs and availability of biologic agents have reduced dependence on corticosteroids and made mucosal healing a realistic goal. It is timely to debate the role of enteral nutrition in this evolving therapeutic armamentarium for Crohn's disease, and to examine the mechanisms of its anti-inflammatory effects in light of current understanding of disease pathogenesis. RECENT FINDINGS: Clinical studies have suggested that response to enteral nutrition is associated with decreased mucosal inflammation in Crohn's disease, that isolated Crohn's colitis is less responsive and that exclusive enteral nutrition is required. Basic research has demonstrated that lipids in the intestinal lumen can alter signalling of the mucosal immune system by intestinal epithelial cells. Exclusive enteral nutrition is associated with alteration of enteric microflora. SUMMARY: Enteral nutrition is an efficacious treatment of active inflammation involving the ileum; recent-onset disease may be particularly responsive. The significance of effects on enteric flora deserves further exploration in view of the importance of microbes to disease pathogenesis.

Crohn Disease↗

Hepatobiliary complications of inflammatory bowel disease.

Clinically significant liver and biliary disorders occur in approximately 5 percent of persons with inflammatory bowel disease. The most common hepatobiliary disorders encountered in patients with inflammatory bowel disease are fatty liver, sclerosing cholangitis and gallstones. In addition, chronic hepatitis, cirrhosis, biliary cancer and amyloidosis sometimes occur. Family physicians should be alert for these gastrointestinal problems in patients with inflammatory bowel disease.

Biliary Tract Diseases↗

Capacity for work and employment record of patients with inflammatory bowel disease.

The literature on the vocational effects of inflammatory bowel disease is scanty. This paper describes the effects in a sample of 170 patients, supplemented with data obtained from the Ileostomy Association. Work capacity is affected by diarrhoea, urgency (including the problem of access to toilets), fatigue, and hospitalization. Rare complications, such as arthritis, represent special difficulties. The fashioning of an ileostomy has, as a general rule, a positive effect on the ability of the patient to work and, overall, inflammatory bowel disease should not prevent the vast majority of patients from successfully following a chosen career.

Employment↗

[Molecular genetic detection of polyclonal immune response in autoimmune thyroiditis and inflammatory bowel diseases].

Southern blot hybridization techniques were used to analyze the arrangements of the immunoglobulin and the T cell antigen receptor genes in lymphocytes of patients with Graves disease and Hashimoto's thyroiditis as well as in patients with Crohn's disease, chronic ulcerative colitis, and with other gastrointestinal disease. The results indicate that the immune response of autoimmune thyroid disease and inflammatory bowel disease is of polyclonal origin.

Adolescent↗

Doppler sonography in the diagnosis of inflammatory bowel disease.

Over the past few years, thanks to its ability to reveal neovascularization and inflammatory hyperemia, Doppler sonography has proved to be a valuable method for the assessment of disease activity in inflammatory bowel disease. Hypervascularization has been detected by Doppler imaging both in splanchnic vessels, in terms of flow volume and velocity, or resistance and pulsatility index on spectral analysis, and in small vessels of the affected bowel wall in terms of vessel density. In particular, power Doppler has been shown to be a highly sensitive method for evaluating the presence of flow in vessels that are poorly imaged by conventional color Doppler, and in detecting internal fistulas complicating Crohn's disease. Recently, the use of ultrasound contrast agents, such as Levovist, has been shown to improve the image quality of color Doppler by increasing the backscattered echoes from the desired regions, thus making it possible to better monitor the response to treatment and discriminate between active inflammatory and fibrotic bowel wall thickness in Crohn's disease. Additionally, Levovist-enhanced power Doppler sonography has proved to be highly sensitive and specific in the detection of inflammatory abdominal masses associated with Crohn's disease. In clinical practice, used in combination with second harmonic imaging and new generations of stable contrast agents, Doppler sonography appears to be a non-invasive and effective diagnostic tool in the diagnosis and follow-up of Crohn's disease and ulcerative colitis.

Colitis, Ulcerative↗

Outpatient management of inflammatory bowel disease. Let's keep it as simple as possible.

Inflammatory bowel disease is a conglomeration of disorders of unclear etiology and pathogenesis. Confirming the diagnosis of active disease may be difficult but is critical to judicious therapy. Sulfasalazine (Azulfidine) and its newer derivatives mesalamine (Asacol, Rowasa) and olsalazine sodium (Dipentum) are used for treatment of mild disease and maintenance. Corticosteroid therapy controls moderate disease in most patients, but withdrawal may be difficult. Immunosuppression or surgery may be necessary in severe or refractory cases. The risk of cancer as a complication of inflammatory bowel disease is often exaggerated but cannot be ignored.

Abdominal Pain↗

[Chronic inflammatory bowel disease--pathogenic concepts and therapeutic perspectives].

Chronic inflammatory bowel disease (IBD) is considered to be a consequence of inappropriate upregulation of immune reactions evoked by the colonic microflora. Abnormalities observed in IBD may be explained, at least in part, by an unfavourable balance between pro- and anti-inflammatory cytokines. Conventional drug treatment of IBD may soon be replaced by more selective inhibitors that act centrally in the inflammatory process. Immunoneutralisation with chimeric anti-tumour necrosis factor-alpha (TNF alpha) antibodies reduces treatment refractory IBD, including fistular Chrons' disease, but recombinant human TNF alpha-receptor fusion proteins may be equally effective with potentially fewer side effects. This view also applies to chimeric antibodies directed against cytokines or adhesion molecules. Potentially more promising are antisense oligonucleotides and matrix-metalloproteinase inhibitors. Whether sustained remission can be achieved probably depends on successful unravelling of the aetiology of IBD.

Antibodies↗

High prevalence of antibodies to intestinal epithelial antigens in patients with inflammatory bowel disease and their relatives.

STUDY OBJECTIVE: To assess whether healthy members of families of patients with inflammatory bowel disease share an immune reactivity to gut epithelial cell antigens. DESIGN: Assessment of immune reactivity against epithelial-cell-associated components (ECAC). METHODS: Detection of specific anti-ECAC serum antibodies by antibody-dependent cellular cytotoxicity (percent specific lysis) and by immunoblotting (Western blots). PATIENTS: Index cases (131) and first-degree relatives in 17 families with 2 or more affected members, and 13 with only 1 member affected. MAIN RESULTS: Compared with a gastrointestinal disease control group (0.5% +/- 0.8%), specific lysis against ECAC-C (colon-derived) among patients with inflammatory bowel disease was significantly greater in both multiply affected (8.4% +/- 8.2%; P less than 0.01) and singly affected (5.2% +/- 5.4%; P less than 0.05) families. In contrast, specific lysis by patients with other inflammatory processes of the small and large bowel (1.1% +/- 1.4%) or autoimmune disease (0.7% +/- 1.0%) did not differ from that of the gastrointestinal disease control group. Among relatives of patients with inflammatory bowel disease (index cases), specific lysis was also significantly higher than in the control group (4.8% +/- 5.5% for multiply affected, P less than 0.01, and 4.3% +/- 5.5% for singly affected, P less than 0.05). Relatives of patients with chronic inflammatory liver disease had a level of lysis (0.6% +/- 0.9%) similar to that of controls. The prevalence of antibodies to ECAC-C was 69.7% among patients with chronic inflammatory bowel disease, and 55.7% among relatives; both prevalences were significantly higher than that of the control group (8.0%, P less than 0.001). Using small-bowel-derived ECAC, the prevalence of antibodies among patients with inflammatory bowel disease and relatives was also significantly higher than that of controls. Reactivity of sera was directed to a 160- and a 137-kilodalton macromolecule. CONCLUSIONS: Immune sensitization to intestinal epithelial antigens is common in families with chronic inflammatory bowel disease; its high frequency among asymptomatic relatives suggests it may represent a primary phenomenon, perhaps predisposing individuals to gut tissue injury.

Adolescent↗

Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987-1990).

Idiopathic inflammatory bowel disease was the diagnosis for 58 dogs and 26 cats, with signs of persistent gastroenteritis, failed responses to dietary trials, and histologic evidence of cellular infiltrates unrelated to other causes of gastrointestinal tract inflammation. Clinical signs of large intestinal dysfunction, watery diarrhea, vomiting, and anorexia with weight loss were common. Nonspecific hematologic, biochemical, and radiographic abnormalities frequently were observed. Mucosal biopsy specimens, obtained endoscopically, were histologically evaluated for severity of mucosal epithelial damage. Mucosal erythema, friability, enhanced granularity, and ulceration or erosion were the predominant endoscopic lesions. Inflammatory bowel disease lesions of moderate severity predominated in the stomach, duodenum, and colon. Lymphocytic/plasmacytic infiltrates were limited to the lamina propria in biopsy specimens from all regions of the gastrointestinal tract. Inflammatory bowel disease commonly is associated with chronic gastroenteritis in dogs and cats.

Animals↗

Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16.

A number of localizations for the putative susceptibility gene(s) have been identified for both Crohn's disease and ulcerative colitis. In a genome wide scan, Hugot et al. (1996) identified a region on chromosome 16 which appeared to be responsible for the inheritance of inflammatory bowel disease in a small proportion of families. Subsequent work has suggested that this localization is important for susceptibility to Crohn's disease rather than ulcerative colitis (Ohmen et al. 1996; Parkes et al. 1996). We investigated the contribution of this localization to the inheritance of inflammatory bowel disease in 54 multiplex Australian families, and confirmed its importance in a significant proportion of Crohn's disease families; we further refined the localization to a region near to D16S409, obtaining a maximum LOD score of 6.3 between D16S409 and D16S753.

Australia↗

Thiopurine S-methyltransferase (TPMT) genotype does not predict adverse drug reactions to thiopurine drugs in patients with inflammatory bowel disease.

BACKGROUND: Azathioprine and mercaptopurine (MP) are well established treatments for inflammatory bowel disease but they have severe adverse effects that prevent their use in some patients. The likelihood and type of adverse effect may relate to thiopurine methyltransferase (TPMT) enzyme activity and genotype. AIM: To compare the TPMT genotype frequencies in patients with inflammatory bowel disease who have had severe adverse effects to those who tolerate azathioprine or MP (controls). METHODS: Patients with inflammatory bowel disease who had been treated with azathioprine or MP in Christchurch between 1996 and 2002 were identified. Patients with adverse effects, and controls, were invited to provide a peripheral blood sample for analysis of TPMT genotype. The genotype frequencies were then compared between the two groups. RESULTS: Fifty-six patients were identified with adverse effects requiring cessation of therapy, of which 50 were genotyped. Reactions included allergic-type (25%), hepatitis (33%), nausea/vomiting (14%), bone marrow suppression (10%), pancreatitis (6%) and other (12%). Five of 50 patients with reactions had TPMT genotype *1/*3, one had *3/*3, and the rest had the wildtype genotype *1/*1. The patient with genotype *3/*3 had severe pancytopenia requiring hospitalization. Three of 50 controls had the *1/*3 genotype and the rest were *1/*1. CONCLUSIONS: The TPMT allele frequency in our population with inflammatory bowel disease is similar to that reported elsewhere. There was a slight trend for more frequent TPMT mutations in the patients with adverse reactions, but this was not statistically significant. Most patients with reactions did not have gene mutations.

Adolescent↗

Ten years experience with intravenous hyperalimentation and inflammatory bowel disease.

A retrospective analysis was conducted on 74 patients with inflammatory bowel disease who were treated with intravenous hyperalimentation at the Hospital of the University of Pennsylvania between the years 1967-1976. Intravenous hyperalimentation can ameliorate the inevitable protein-calorie malnutrition present in patients with inflammatory bowel disease. Combined with complete bowel rest, intravenous hyperalimentation can effectively function as the primary treatment or as an adjunct to the surgical management of the complications of inflammatory bowel disease. Intravenous hyperalimentation can be safely administered to these severely ill patients, almost certainly improving survival rates in the patients treated.

Adult↗

Inflammatory bowel disease in pediatric patients.

Optimal management of chronic idiopathic inflammatory bowel disease requires determination of disease localization and intensity. Scintigraphy with the use of 99mTc-HMPAO-White Blood Cells (99mTc-HMPAO-WBC) is a relatively new noninvasive nuclear medicine procedure. We have evaluated more than 230 children and have found a high correspondence between the disease distribution shown by the 99mTc-HMPAO-WBC scan and that shown by endoscopic, radiologic, or surgical methods. Additionally the 99mTc-HMPAO-WBC scan has the ability of identifying extra intestinal site of inflammation, such as appendicitis and others. The erythrocyte sedimentation rate, the most frequently used indicator of disease activity in the clinical setting, has better correlation with the scan scores than the clinical activity index. The 99mTc-HMPAO-WBC scan is reliable in differentiating Crohn's disease from ulcerative colitis. Some patients because of unequivocal demonstrable small bowel uptake are reclassified from ulcerative colitis to Crohn's disease. The medication regimen is frequently altered because of the intensity of uptake displayed by the 99mTc-HMPAO-WBC scan. It is a practical and safe study even in an acutely ill patient who may not tolerate endoscopic or radiological study. At our institution, the 99mTc-HMPAO-WBC scan is now part of the initial evaluation, and follow-up of patients with inflammatory bowel disease. In conclusion the 99mTc-HMPAO-WBC is excellent for the detection, localization and characterization of inflammatory bowel disease in children. Compared with the other methods of investigation this study requires no bowel preparation, is noninvasive and has excellent diagnostic accuracy.

Child↗