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Pericarditis is an uncommon extraintestinal manifestation of inflammatory bowel disease. Clinical presentations range from asymptomatic pericardial effusions to cardiac tamponade. Our patient with ulcerative colitis presented with acute pericarditis that provided an opportunity to review the literature on cardiac involvement in inflammatory bowel disease.
Anorexia is a major complication of inflammatory bowel disease (IBD). We postulated that chronic intestinal inflammation with increased proinflammatory cytokines elevates serum leptin concentration, thereby contributing to anorexia. This hypothesis was studied in interleukin-2-deficient (IL-2(-/-)) mice, a model of IBD with elevated proinflammatory cytokine production. IL-2(-/-), wild-type pair-fed and wild-type control male mice (8 wk old) were fed regular laboratory mouse food for 2 wk. The IL-2(-/-) and pair-fed groups consumed less food and lost weight. Serum leptin concentrations in the IL-2(-/-) mice in the fed state were lower than controls, but not different from pair-fed mice, and paradoxically increased in the starved state to levels significantly higher than both starved control and pair-fed groups. This result did not change when serum leptin was adjusted for amount of body fat. These data show abnormal leptin responses in IL-2(-/-) mice with increased leptin concentrations disproportionate to fat mass and prevention of the normal decline in leptin with food restriction.
PURPOSE OF REVIEW: Oral tolerance refers to the ability of the mucosal immune system to actively inhibit systemic immune responses to fed antigens. Recently, clinical trials have used oral tolerance as a therapy for certain chronic inflammatory and autoimmune diseases such as multiple sclerosis and type I diabetes. Inflammatory bowel disease is now widely thought to be caused by the breakdown of oral tolerance through a combination of genetic and environmental factors. Therefore, it seems incongruous that clinicians would try to use oral tolerance therapy to alleviate the symptoms of inflammatory bowel disease. Yet, armed with the results of select animal models, trials have begun for oral tolerance therapy for Crohn's disease. This review will outline the recent advances in understanding oral tolerance, explore the relation between oral tolerance and inflammatory bowel disease, and comment on the likelihood of successful oral tolerance therapy for inflammatory bowel disease. RECENT FINDINGS: The results of an oral tolerance trial in Crohn's disease patients in Israel have shown some promising results, whereas the results of studies of experimentally induced oral tolerance in patients with inflammatory bowel disease from the authors' laboratory have shown that feeding a neoantigen in an attempt to induce oral tolerance is not successful in patients with inflammatory bowel disease. SUMMARY: The fundamental difference in the mechanisms of oral tolerance in mice and humans requires a more focused effort to understand the human mucosal immune system before oral tolerance therapy for autoimmune and chronic inflammatory disorders reaches its full potential.
OBJECTIVE: To investigate the relationship between inflammatory bowel disease (IBD) patients' disease-related worries and concerns and their disease-related data, sociodemographic variables and perceived information level with respect to IBD. STUDY DESIGN: Prospective evaluation of disease-related concerns. SETTING: Out-patient IBD clinic of a university hospital. STUDY POPULATION: The study included 105 patients with IBD (72 with Crohn's disease and 33 with ulcerative colitis). MEASUREMENTS: Worries and concerns were measured using the standardized 25-item rating form of IBD patient concerns; actual disease activity was assessed by physicians using the Crohn's disease and clinical activity indices. Sociodemographic and other disease-related data were collected using a structured questionnaire. Patients' perceived information level was measured using a visual analogue scale. RESULTS: The issues of greatest concern to our patients were, in descending order of importance, having an ostomy bag (mean score +/- SD 63.6 +/- 38), the effects of medication (53.1 +/- 34), having surgery (51.6 +/- 36), the uncertain nature of the disease (46.5 +/- 32) and energy level (41.5 +/- 34). Patients with ulcerative colitis scored higher with respect to concern about loss of bowel control (P < 0.03). Disease-related worries and concerns correlated poorly with disease-related data (actual disease activity, severity of the course of IBD, diagnosis, disease duration or location, medication) but showed a significant negative correlation with patients' perceived information level about IBD (t = 0.2, P < 0.004). Lower information-level scores were associated with greater concerns. CONCLUSION: We conclude that the patients' information level about IBD and disease-related concerns have to be considered in clinical practice. Better information about IBD and psychosomatic counselling for patients who show high levels of concern may improve their quality of life and clinical care.
An adolescent had marked systemic features suggestive of inflammatory bowel disease. Giardia lamblia trophozoites were present in endoscopic biopsy specimens from the terminal ileum and from the duodenum. His illness rapidly and completely resolved after metronidazole therapy. Giardiasis must be included in the differential diagnosis of inflammatory bowel disease in children.
BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. Our aim was to evaluate the current practices of examination, prevention and treatment of osteoporosis in IBD patients in a routine clinical setting. METHODS: A total of 154 consecutive patients with IBD (63 female, 91 male; 36 ulcerative colitis, 115 Crohn's disease, 3 indeterminate colitis), referred to two gastroenterological units for scheduled follow-up examinations, were included. Patient charts were evaluated regarding bone densitometry already performed and any prophylactic or therapeutic interventions in cases of low bone mineral density. RESULTS: Bone mineral density (BMD) measurements had been performed only in 38 patients (25%). BMD was abnormally low in 27 of the examined patients (71%), 20 of whom had osteopenia and seven had osteoporosis. Among the subgroup of patients on long-term steroid therapy (77 patients), 30 had been referred to bone densitometry during the course of disease, and 21 of them were found to have low bone mineral density. Preventive measures were prescribed in 12 patients (9% of the whole study population). In the majority of the patients with low bone mineral density, calcium and vitamin D were used as treatment. CONCLUSIONS: Despite the high prevalence of osteopenia and osteoporosis in patients with IBD, only a minority of these patients were included in a structured program in accordance with modern guidelines for diagnosing and preventing this extraintestinal complication in a routine clinical setting.
We conducted a survey on the quality of life and social consequences for patients with inflammatory bowel disease. Questionnaires of 41 patients with Crohn's disease, 28 patients with ulcerative colitis and 7 patients with overlap colitis were evaluated. All the patients had been hospitalized in the past. 15 patients (20%) were unable to work due to inflammatory bowel disease. 9 (12%) of these 15 patients received a disability pension. 11 patients (15%) had to change a place of work and 16 (21%) had had financial problems due to inflammatory bowel disease. 4 patients (5%) had had to give up a partnership due to the disease. For 16% of the patients their perceived quality of life during the past 4 weeks was poor or very poor, while 35% of the patients perceived their overall quality of life as poor or very poor since the beginning of the disease. We conclude that inflammatory bowel disease affects job and financial matters rather than partnerships. The quality of life is judged by many patients as considerably diminished.
Linkage studies from five groups worldwide have confirmed the presence of an inflammatory bowel disease susceptibility locus on chromosome 12q. Beta 7 integrin is a strong candidate gene within this region, and is involved in lymphocyte homing to the gut and retention of intra-epithelial lymphocytes. Monoclonal antibodies to beta7 integrin ameliorate colitis in animal models. We obtained genomic sequence for beta7 integrin, and screened all 16 exons and 1.7 kb of 5' promoter region for polymorphisms in 24 individuals. Fourteen single nucleotide polymorphisms were identified in total and, of these, two common (frequency > or =10%) intronic and two amino acid changing polymorphisms were assessed for potential disease associations. Data were available from 102 multiply affected inflammatory bowel disease families (affected sibling pairs) and 362 simplex (one affected proband) families containing 254 ulcerative colitis, 13 indeterminate colitis and 300 Crohn's disease trios (parents + affected child). No significant associations with any disease phenotype were found with the transmission disequilibrium test. Beta 7 integrin is unlikely to be involved in the genetic susceptibility to inflammatory bowel disease, and therefore future studies on chromosome 12 should focus on other positional candidate genes.
UNLABELLED: Pancreatitis in inflammatory bowel disease (IBD) in children is anecdotal. In adults, symptomatic pancreatitis occurs in 2% and asymptomatic in 8 to 21%. PATIENTS AND METHODS: The aim of our study was to review retrospectively the frequency of pancreatitis in 124 pediatric patients (54.8% boys, 45.2% girls; 97 with Crohn disease, 16 with ulcerative colitis and 11 with undetermined colitis). Diagnostic criterion of pancreatitis was an increase of amylasemia > or = +2 SD of the normal with or without evocative clinical symptoms. RESULTS: Symptomatic or asymptomatic pancreatitis was found in 27% (respectively 14.5 and 12.5%). Pancreatitis was significantly more frequent in girls as compared to boys (P = 0.04). Symptomatic pancreatitis was moderate and non complicated, often recurrent. It occurred mainly during active and severe diseases (P = 0.006). The localizations of IBD were not discriminant. Strong relation with drug was found in 25% of pancreatitis mainly due to azathioprine or 5-aminosalicylic acid, and salazopyrin. Duodenal localisation of Crohn disease or hepatobiliary complications were found associated with pancreatitis in 18% and 15% respectively. CONCLUSION: These data suggest the high incidence of symptomatic and asymptomatic pancreatitis in children with IBD, the importance of its regular monitoring but also its multifactorial causes. Precise diagnosis of pancreatitis in pediatric IBD has to be done in order to avoid inappropriate drug pancreatitis diagnosis.
BACKGROUND: Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. AIM: To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease. METHODS: Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease. RESULTS: The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively. CONCLUSIONS: The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.
Initial standard medical treatment for inflammatory bowel disease (IBD) includes a 5-aminosalicylic acid (5-ASA) compound (oral, local or combined) and corticosteroids (oral, local or combined). In both ulcerative colitis and Crohn's disease 5-ASA has proved effective in the acute phase of the disease. As maintenance treatment, it is effective in ulcerative colitis and in some instances also in Crohn's disease. Steroids can be used in active IBD, but their effectiveness as maintenance treatment has never been proven, although in practice low-dose steroids are used for chronic treatment. When the above-mentioned preparations are unsuccessful, other medications could be tried. Flagyl could be used when the colon is involved in Crohn's disease or when anal fistulation develops, but it often fails to maintain its effect after only a few weeks. For refractory IBD more potent immunomodulators are needed. 6-Mercaptopurine and azathioprine have been shown to be effective in ulcerative colitis and Crohn's disease with a response rate between 60 and 70%. Their optimal effect is only reached after 3-4 months. These drugs are therefore not of value for treatment in the acute phase of the disease. 6-Mercaptopurine or azathioprine can be used best in combination with steroids in situations where dose reduction of the latter drug repeatedly leads to relapse. They have therefore a steroid-sparing effect and initiate cessation of the long-term severe side-effects of steroids. Another possibility is the use of methotrexate in patients with refractory ulcerative colitis or Crohn's disease.
Unfractioned heparin was recently reported to be beneficial in the treatment of inflammatory bowel disease. The available uncontrolled data show that it may be effective in steroid-resistant ulcerative colitis with a percentage of complete clinical remission of over 70% after an average of 4-6 weeks of therapy. The administration of unfractioned heparin is not currently justified by the very limited available data. The worsening of rectal bleeding is infrequent in treated ulcerative colitis patients and only rarely does it require blood transfusion or a colectomy. Low molecular weight heparin was used in a single trial in patients with steroid-refractory ulcerative colitis, with results similar to those observed with unfractioned heparin. Since a prothrombotic state has been described in inflammatory bowel disease, and microvascular intestinal occlusion seems to play a role in the pathogenesis of inflammatory bowel disease, it is reasonable that part of the beneficial effects of unfractioned heparin in inflammatory bowel disease may result from its anticoagulant properties. However, beyond its well-known anticoagulant activity, unfractioned heparin also exhibits a broad spectrum of immunomodulating and anti-inflammatory properties, by inhibiting the recruitment of neutrophils and reducing pro-inflammatory cytokines. Moreover, it can restore the high-affinity receptor binding of basic fibroblast growth factor and this would aid healing of the ulcerated mucosa. In conclusion, unfractioned heparin may represent a safe therapeutic option for severe, steroid-resistant ulcerative colitis, although randomized, controlled trials are needed to confirm these data.
Recent developments concerning nutritional complications of inflammatory bowel disease include a better understanding of disease-associated anorexia and increasing recognition of the interaction of nutrition and cytokines in the pathogenesis of growth impairment of children. Decreased bone mineral density is a multifactorial complication and an increased focus of research. Enteral nutrition continues to play an important role in the therapy of Crohn's disease. The mechanisms whereby specific nutrients, such as n-3 fatty acids, antioxidants, and butyrate, ameliorate inflammation are being elucidated in in-vitro studies, but beneficial effects have yet to be translated into the clinical sphere.
Intestinal permeability was assessed in patients with inflammatory bowel disease by measuring the urine excretion of 51chromium-labeled ethylenediaminetetraacetate over periods up to 24 h after oral administration. Twenty-eight control subjects and 10 patients with ulcerative colitis excreted less than 2.6% of the test dose in 24 h. Ten patients with small bowel Crohn's disease excreted 3.3%-14.0%, and 10 of 11 patients with ileocolonic involvement had increased excretion. At the same time, 5 of 11 patients with Crohn's colitis were clearly outside the normal range, suggesting small bowel involvement. The 24-h urine excretion of 51chromium-labeled ethyl-enediaminetetraacetate after oral administration appears to be a sensitive, noninvasive test for assessing small intestinal integrity, and may be a valuable adjuvant in the differential diagnosis of inflammatory bowel disease.
For targeting local and systemic inflammatory processes in inflammatory bowel disease (IBD) therapeutic agents of first choice (e.g. aminosalicylates, corticosteroids) have been developed in special galenic forms to accomplish the topical delivery of the active compounds to the terminal ileum (Crohn's disease) and/or the colon (Crohn's disease and ulcerative colitis). However, it has to be realized that intestinal physiology (e.g. motility, intraluminal pH profiles), extent and pattern of IBD as well as drug disposition demonstrate large interindividual differences resulting in variable clinical response rates between about 35% and 75%. 5-Aminosalicylate (5-AS) can be delivered to the colon either by azo-prodrugs (e.g. sulfasalazine, olsalazine or balsalazide) or by direct rectal administration of 5-AS in form of enemas, foam or suppositories. Such formulations will be only effective in patients with ulcerative colitis (UC). Various slow/controlled release preparations of 5-AS have been developed for oral use. Some of them (e.g. Pentasa, Salofalk) release sufficient 5-AS already in the small bowel which could provide some additional benefit in Crohn's disease (CD). As urinary and faecal recoveries of total 5-AS are similar for all oral formulations, no major clinical differences can be expected. Extent of the disease, profile of adverse effects and patient's acceptance provide some guidance for selection of the particular agent. Rectal installation of several glucocorticosteroids has been employed for many years. More recently scientific and clinical interest has been focused on budesonide which is extensively presystemically metabolized in the intestinal wall and the liver. Therefore, its systemic availability is low (10-15%) independent whether budesonide is administered orally as controlled release formulation in patients with CD or rectally as enema in patients with UC. Numerous pharmacokinetic and clinical studies have documented the anticipated topical delivery and clinical efficacy of this corticosteroid without serious side effects such as cushingoid features. It can be assumed that for any novel therapeutic principle in IBD the approach of topical delivery will be also tried.
To investigate the pathogenesis of diarrhea in inflammatory bowel disease, electrolyte transport was examined in vitro in stripped colonic mucosa taken from the sigmoid or descending colon in colectomy specimens. Compared with previously reported values from normal colon, the electrical potential difference, short circuit current, and mucosal resistance were significantly lower in diseased mucosa. This reduction was associated with a significantly lower net sodium absorption in diseased mucosa, owing to a reduced mucosa to serosa unidirectional flux. Net chloride flux was similar to normal, but unidirectional fluxes were reduced. In mucosa from patients treated with corticosteroids, fluxes were similar to normal, while in untreated patients they were markedly impaired. It is concluded that there is a defect in active sodium absorption in inflammatory bowel disease that may contribute to the diarrhea. A secretory process, inhibited by sulphasalazine, cannot be excluded however.
BACKGROUND: It is a common experience for people to dream of events about which they are either anxious or concerned. We therefore hypothesised that the dreams of patients with irritable bowel syndrome may reflect their worries about their problem especially as hospital out-patients with this disorder tend to exhibit some anxiety. In addition, dreaming about, for instance bowels, in patients with irritable bowel syndrome in excess of that observed in other gastrointestinal disorders may be of importance. AIM: To establish whether patients with irritable bowel syndrome dream about bowel-related issues more than controls or patients with inflammatory bowel disease. PATIENTS AND METHODS: A total of 57 patients with irritable bowel syndrome and 57 patients with inflammatory bowel disease were compared with 60 healthy controls. All subjects completed a structured questionnaire concerning sleeping habits and dream characteristics as well as an assessment of anxiety and depression. RESULTS: There were no differences in the sleeping habits between any of the groups. However, significantly more patients with irritable bowel syndrome and inflammatory bowel disease dreamt about their bowels (22% inflammatory bowel disease patients, 18% irritable bowel syndrome patients vs 3% of controls, p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) and soiling themselves (16% of inflammatory bowel disease patients, 14% of irritable bowel syndrome patients vs 2% of controls; p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) than controls. CONCLUSION: Chronic gastrointestinal disorders, of both a functional and organic nature, may influence the nature of dreams. In those patients who dream about their symptoms, it would be interesting to know whether this affects the course of their disease, either positively or negatively, in any way.
Familial and epidemiologic studies of inflammatory bowel disease indicate a strong genetic predisposition that is modified by certain environmental factors. Abnormal submucosal immune activation may be important in the etiology of the disease. Yersinia enterocolitica infection, various "gay bowel syndromes" and other recently described enteric infections often mimic Crohn's disease. An initial barium study is useful in documenting the extent of disease and complications. Endoscopic biopsy confirms the surface appearance and histologic features of inflammatory bowel disease. Newer photodocumentation techniques are expected to improve the comparability of endoscopic observations. Complications of inflammatory bowel disease occur frequently, may involve any organ system and may precede the onset of bowel symptoms.