Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease

BACKGROUND & AIMS: New serologic markers of inflammatory bowel disease may be useful for differentiating between Crohn's disease and ulcerative colitis and for disease stratification. We profiled sugar-binding antibodies to identify novel antiglycan antibodies that may be associated with inflammatory bowel disease. METHODS: Serum samples were obtained from patients with diagnosed Crohn's disease or ulcerative colitis and from control patients. The presence of antiglycan antibodies was evaluated using either a glycan array (GlycoChip; Glycominds, Ltd, Lod, Israel) in patients with Crohn's disease (n = 72) or ulcerative colitis (n = 56) and in healthy controls (n = 41) or using an enzyme-linked immunosorbent assay in patients with Crohn's disease (n = 124), ulcerative colitis (n = 106), and in control patients (n = 101). RESULTS: Inaddition to antibodies against mannan, antibodies to laminaribioside (Glc[beta1,3]Glc[beta]) and chitobioside (GlcNAc[beta1,4]GlcNAc[beta]) had the highest discriminative capability between Crohn's disease and ulcerative colitis (P < .001 and P < .05, respectively). Importantly, 44% (12/27) of anti-Saccharomyces cerevisiae antibody-negative Crohn's disease patients were positive for antilaminaribioside or antichitobioside. In patients with inflammatory bowel disease positive for antibodies against either laminaribioside, chitobioside, or mannan, the diagnosis of Crohn's disease was suggested with a sensitivity of 77.4% and specificity of 90.6%. Having at least 2 of these antibodies increased the specificity to 99.1%. In Crohn's disease, higher levels of antibodies against laminaribioside or mannan were significantly associated with small intestinal disease (P = .03 and P < .0001, respectively). CONCLUSIONS: Antilaminaribioside and antichitobioside carbohydrate antibodies are novel serologic markers associated with Crohn's disease. These antibodies may contribute to the diagnosis and improved stratification of Crohn's disease.     

Non-invasive evaluation of activity in inflammatory bowel disease by power Doppler sonography

BACKGROUND: To study the vascularization in the diseased bowel wall by power Doppler sonography in patients with inflammatory bowel disease. PATIENTS AND METHODS: The diseased bowel wall was investigated in 99 patients with inflammatory bowel disease (60 patients with Crohn's disease and 39 patients with ulcerative colitis) either with active disease or in remission by B-mode and power Doppler sonography. Disease activity was determined by clinical indices. Twenty healthy age and sex matched individuals served as controls. RESULTS: Bowel wall was thickened in active Crohn's disease (mean 7 mm, range 4-14) and ulcerative colitis (mean 5 mm, range 2-15) as compared to healthy controls (mean 2 mm, range 1-3), p < 0.001. In contrast to healthy controls blood vessels were detected in the bowel wall in 100 % of patients with active Crohn's disease and 91 % with active ulcerative colitis. Vascularization was significant decreased in patients with quiescent versus active disease in ulcerative colitis (p < 0.05), while in Crohn's disease there was no significance between active and remission phase. CONCLUSIONS: Thickened and hypervascularized bowel wall are characteristic findings in inflammatory bowel disease. A combination of B-mode and power Doppler sonography offers an additional noninvasive procedure for the determination of activity in patients with inflammatory bowel disease.     

Inflammatory bowel disease in the rural Indian subcontinent: a survey of patients attending mission hospitals

39 missionaries working at 38 separate mission hospitals or clinics in Bangladesh. India, Nepal and Pakistan completed questionnaires about their clinical practice during the previous year, 1980. Data were collected about gastrointestinal disorders, including coeliac disease, tropical sprue, bloody diarrhoea, amoebiasis, typhoid, cholera, inflammatory bowel disease and diverticular disease. More than 386,000 out-patients and over 56,000 in-patients were treated with an estimated 12,272 cases of bloody diarrhoea, 7,310 of amoebiasis, 2,113 of typhoid and 872 cases of intestinal tuberculosis, 74 cases of inflammatory bowel disease were diagnosed, of which 56 were ulcerative colitis and the remainder were said to have Crohn's disease. Surgery was performed in 28 hospitals, but only 10 (26%) had a histology service. Inflammatory bowel disease appears to be a relatively more common cause of diarrhoea in the Indian subcontinent than in sub-Saharan Africa (z = 5.47, p less than 0.001). The proportion of patients with bloody diarrhoea who have ulcerative colitis Crohn's disease was similar throughout the region. The rate of cases having ulcerative colitis rather than Crohn's disease was greater in India (z = 3.1, p less than 0.005), and in Bangladesh (z = 3.2, p less than 0.005), than in Pakistan (z = 1.28, NS) or Nepal and Bhutan (z = 0, NS). The relative risk of Indians developing ulcerative colitis rather than Crohn's disease is 2.6 (95% confidence limits 1.4-4.8, NS). This may reflect diagnostic difficulties in distinguishing Crohn's disease from intestinal tuberculosis, but it may also shed light on similar differences now being reported in migrant groups in Western Europe.     

Evaluation of serological markers to differentiate between ulcerative colitis and Crohn's disease: pANCA,ASCA and agglutinating antibodies to anaerobic coccoid rods

BACKGROUND: Accurate diagnosis of inflammatory bowel disease, in particular the differentiation between ulcerative colitis and Crohn's disease, is important for treatment and prognosis. Several serological markers have been used as non-invasive diagnostic tools in inflammatory bowel disease patients both to differentiate ulcerative colitis from Crohn's disease and to define patient subgroups. AIM: To evaluate the diagnostic accuracy of three serological tests in differentiating ulcerative colitis from Crohn's disease by single or combined use. METHODS: Sera from 51 patients with clinically well-defined ulcerative colitis and 50 patients with clinically well-defined Crohn's disease were analysed. Detection assays for the presence of perinuclear anti-neutrophil cytoplasmatic antibodies (pANCA), antibodies against (ASCA) and serum agglutinating antibodies to anaerobic coccoid rods were studied. Sensitivity, specificity, predictive values and likelihood ratios of each of these serological tests were determined. RESULTS: In supporting the diagnosis of ulcerative colitis, the sensitivity and specificity of the pANCA test were 63% and 86%, respectively. The ASCA test (immunoglobulin A or immunoglobulin G positive) for diagnosing Crohn's disease had a sensitivity of 72% and a specificity of 82%. The sensitivity of antibodies to anaerobic coccoid rods in diagnosing Crohn's disease was 52%, whereas specificity was 90%. A combination of pANCA-positive and ASCA-negative results in the case of ulcerative colitis showed a sensitivity and specificity of 51% and 94%, respectively. However, for ASCA-positive and pANCA-negative results in the case of Crohn's disease, sensitivity was 64% and specificity was 94%. The combination of all three tests increased positive predictive value and specificity to 100% for both ulcerative colitis and Crohn's disease. In Crohn's disease patients, positive pANCA was correlated with colonic involvement. No correlation was found between the presence of any of these antibodies and disease activity, duration and behaviour or medical treatment. CONCLUSIONS: The value of these serological tests in differentiating ulcerative colitis from Crohn's disease is limited when used separately but, by combining two or more tests, the positive predictive value and specificity can be improved substantially. These tests might be of help in studying disease heterogeneity, and may contribute to defining various subgroups of patients with different pathogeneses.     

Pulmonary function tests, high-resolution computed tomography findings and inflammatory bowel disease

AIM: The association between inflammatory bowel disease and pulmonary involvement has not been clearly established. The aim of this prospective study was to define the features of pulmonary function tests and high resolution computed tomography in inflammatory bowel disease patients and the relation between these and disease activity. METHOD: Fifty-two patients with inflammatory bowel disease (20 with Crohn's disease and 32 with ulcerative colitis) were enrolled. The standard pulmonary function tests and thorax high resolution computed tomography findings were investigated with respect to inflammatory bowel disease activity. Crohn's disease activity index and the Rachmilewitz endoscopic activity index for ulcerative colitis were used to assess disease activity. Medications used and smoking status were also documented. RESULTS: Among the patients with ulcerative colitis, 6.25% had an obstructive and/or restrictive ventilatory defect compared with 25% of the patients with Crohn's disease. Fifty percent of the patients with ulcerative colitis and 60% of the patients with Crohn's disease showed abnormal findings in high resolution computed tomography. Pulmonary function tests and high resolution computed tomography abnormalities did not differ significantly between Crohn's disease and ulcerative colitis. No significant difference related to inflammatory bowel disease activity was found (P > 0.05). CONCLUSION: Findings of high resolution computed tomography and the pulmonary function tests did not differ between ulcerative colitis and Crohn's disease. Bowel disease activity did not seem to affect these measurements.     

Cytomegaloviral enterocolitis

PURPOSE: Cytomegaloviral enterocolitis is an uncommon disorder that can complicate inflammatory bowel disease. It is more common in patients with acquired immunodeficiency syndrome and can occur in patients on immunosuppressive therapy for autoimmune or inflammatory diseases and in allograft recipients. Mortality rates of up to 71 percent have been reported for cytomegaloviral enterocolitis. The aims of this study were 1) to identify the presentation, underlying medical conditions, treatment, and outcome of patients with cytomegaloviral enterocolitis and 2) to determine the prevalence of this infection in patients undergoing intestinal resection for inflammatory bowel disease. METHODS: A retrospective chart review of patients with pathologic evidence of cytomegaloviral enterocolitis from 1985 through 1996 was performed. To determine the prevalence of this condition, the hospital discharge database was searched for the diagnoses of ulcerative colitis and Crohn's disease in patients who underwent bowel resection. RESULTS: 93 patients (mean age, 44 years; 66 percent males) had cytomegaloviral infection in the small intestine (n = 6), large intestine (n = 86), or appendix (n = 1). Patients with acquired immunodeficiency syndrome (n = 42), with ulcerative colitis (n = 11), with Crohn's disease (n = 11), receiving organ transplant (n = 12), receiving bone marrow transplant (n = 8), and in other immunosuppressed states (n = 11) comprised this study. Seventeen patients (18 percent) underwent intestinal resection, and the remaining 76 patients were treated medically. Abdominal pain (77 vs. 37 percent; P < 0.01) and gastrointestinal bleeding (65 vs. 34 percent; P < 0.05) were more common presenting symptoms in patients who required resection than patients in the medically managed group. Mortality was 17.6 percent in the surgically managed group and 14.5 percent in the patients who were managed medically. The median duration of ulcerative colitis in patients with coexisting cytomegaloviral infection was 12 months. The prevalence of cytomegaloviral enterocolitis was 4.6 percent in patients with ulcerative colitis and 0.8 percent in patients with Crohn's disease. CONCLUSIONS: These data suggest that cytomegaloviral infection more frequently complicates ulcerative colitis than Crohn's disease. Furthermore, a short and fulminant course of ulcerative colitis may indicate coexisting cytomegaloviral infection. The overall low mortality in this retrospective study suggests that aggressive medical and surgical treatment improves survival in patients with cytomegaloviral enterocolitis.     

A population-based study of the frequency of corticosteroid resistance and dependence in pediatric patients with Crohn's disease and ulcerative colitis

BACKGROUND: The goal of this study was to examine the 1-year outcome after the first course of systemic corticosteroids in an inception cohort of pediatric patients with inflammatory bowel disease. METHODS: All Olmsted County (Minnesota) residents diagnosed with Crohn's disease (n = 50) or ulcerative colitis (n = 36) before 19 years of age from 1940 to 2001 were identified. Outcomes at 30 days and 1 year after the initial course of corticosteroids were recorded. RESULTS: Twenty-six patients with Crohn's disease (65%) and 14 with ulcerative colitis (44%) were treated with corticosteroids before age 19. Thirty-day outcomes for corticosteroid-treated Crohn's disease were complete remission in 16 (62%), partial remission in 7 (27%), and no response in 3 (12%), with 2 of these patients requiring surgery. Thirty-day outcomes for treated ulcerative colitis were complete remission in 7 (50%), partial remission in 4 (29%), and no response in 3 (21%). One-year outcomes for Crohn's disease were prolonged response in 11 (42%) and corticosteroid dependence in 8 (31%), whereas 7 (27%) were postsurgical. One-year outcomes for ulcerative colitis were prolonged response in 8 (57%) and corticosteroid dependence in 2 (14%), whereas 4 (29%) were postsurgical. CONCLUSIONS: Most pediatric patients with inflammatory bowel disease initially responded to corticosteroids. However, after 1 year, 58% of pediatric patients with Crohn's disease and 43% of pediatric patients with ulcerative colitis either were steroid dependent or required surgery. This finding emphasizes the need for early steroid-sparing medications in pediatric inflammatory bowel disease.     

Virulence properties of Escherichia coli strains isolated from patients with inflammatory bowel disease.

Escherichia coli strains cultured from 74 patients with inflammatory bowel disease at different stages of disease activity (Crohn's disease (40), ulcerative colitis (34)) and 18 healthy controls were studied in relation to haemolysin and verotoxin production and enteroadherence. Disease activity was assessed by standard clinical and laboratory tests. Haemolytic E coli were isolated from 18% of patients with Crohn's disease, 24% with ulcerative colitis, and 11% of healthy controls. None of these differences was significant. No verotoxin producing strains were detected among the 216 E coli isolates examined but the extract from five strains (Crohn's (4), ulcerative colitis (1) produced a distinctive cytopathic effort on Vero cell monolayers which was later shown not to be due to verotoxin. The adhesion indices of E coli isolates cultured were: mean (SEM) 42.2 (6.4) for Crohn's disease, 43.3 (6.2) for ulcerative colitis, and 11.3 (2.0) for normal controls (p less than or equal to 0.0001). Adhesive E coli were isolated from 62% of patients with Crohn's disease and 68% with ulcerative colitis but from only 6% of normal controls (p less than or equal to 0.0002). Neither haemolysin production nor enteroadherence was dependent upon disease activity, disease location, sulphasalazine treatment, or previous intestinal resection. These results indicate that only enteroadherent E coli were frequently associated with inflammatory bowel disease; their relation to the pathogenesis of these conditions, however, remains uncertain.     

Development of an assay for antibodies to Saccharomyces cerevisiae: Easy, cheap and specific for Crohn's disease.

OBJECTIVE: To develop a serological test to measure antibodies to Saccharomyces cerevisiae in patients with inflammatory bowel disease. METHODS: An ELISA to the mannan of S cerevisiae that is commercially available was developed. Sera were tested from randomly chosen sera specimens kept frozen at the University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba. Clinical diagnoses were kept blinded until the assay results were finalized. One hundred thirty-six sera were tested, including 51 with Crohn's disease, 32 with ulcerative colitis, one with indeterminate colitis and 16 other control subjects. Thirty-six samples were duplicates from patients already studied but were either run on separate days or drawn on different days. RESULTS: Using a cutoff of 15 binding units as a positive result, Crohn's disease was found to have a sensitivity of 53% but a specificity of 100% compared with ulcerative colitis. Compared with all other diagnoses (including ulcerative colitis), Crohn's disease had a sensitivity of 53% and a specificity of 96%. For patients with Crohn's disease only, those who were anti-S cerevisiae antibody (ASCA) positive (n=27) were significantly more likely to have proximal gastrointestinal disease and significantly less likely to have colonic or inflammatory type disease than those who were ASCA negative (n=24). The direct cost of this assay was $6.00 per positive test, and the total charge was set at $38.15. CONCLUSIONS: A reasonably inexpensive, easy and reproducible assay to assess for antibodies to S cerevisiae has been developed. Using a cutoff for positivity of 15 binding units, this test had a specificity of 100% for ruling out Crohn's disease and a lower (60%) sensitivity compared with ulcerative colitis. This test could identify a specific phenotype of patients with Crohn's disease as being more likely to have small bowel Crohn's disease and less likely to have colonic (isolated) or inflammatory disease, as opposed to fibrostenotic disease or penetrating disease. The test proved reliable when assaying samples drawn or assayed on different days.     

Evolving concepts on inflammatory bowel disease. Are we happy with the present nosology?

The term inflammatory bowel disease traditionally comprises ulcerative colitis, Crohn's disease and indeterminate colitis, an intermediate variant of the two major forms. The term is commonly used in the literature and in clinical practice even though it has never been revised in a Consensus Conference. The present nosology of inflammatory bowel disease seems not to be entirely satisfactory as it is limited to chronic diseases only and does not include several recently described idiopathic inflammatory bowel disorders. Although the aetiology of inflammatory bowel disease remains unknown, both ulcerative colitis and Crohn's disease are characterized by a similar pathogenesis which consists in a persistent intestinal inflammation resulting from disregulation of the gut mucosal immune system. The pathogenetic mechanisms could, therefore, provide a suitable criterion for the classification of idiopathic inflammatory bowel disease. A revised classification of inflammatory bowel disease is thus proposed. It seems reasonable to subclassify inflammatory bowel disease into acute and chronic forms. Acute forms should include the sudden attacks of ulcerative colitis and Crohn's disease with rapid and complete resolution and the so-called "acute self-limited colitis". The chronic forms should comprise, besides the classical forms of ulcerative colitis, Crohn's disease and indeterminate colitis, also other idiopathic inflammatory bowel conditions such as collagenous colitis, lymphocytic colitis and eosinophilic gastroenteritis.     

Kallikrein–kinin system in inflammatory bowel diseases: Intestinal involvement and correlation with the degree of tissue inflammation

BACKGROUND: Tissue kallikrein and its natural inhibitor, kallistatin, play opposite roles in the generation of bradykinin, a potent mediator of inflammation. Observations on experimental models and humans with ulcerative colitis suggest a pathogenetic role of the kallikrein-kinin system in inflammatory bowel diseases. AIM: To evaluate tissue kallikrein and kallistatin in intestinal tissue samples from Crohn's disease and ulcerative colitis patients with different degrees of disease involvement. PATIENTS AND METHODS: Full-thickness surgical intestinal samples were obtained from 144 subjects (38 normal controls, 32 inflammatory controls, 38 Crohn's disease, 36 ulcerative colitis) and tested for kallikrein and kallistatin by immunoperoxidase techniques. RESULTS: Compared with controls, kallikrein immunoreactivity was significantly weaker in goblet cells (p=0.0001) and significantly stronger in interstitium (p=0.0001) of the Crohn's disease and ulcerative colitis samples. Kallistatin colocalised with kallikrein, with almost no reactivity in goblet cells but strong reactivity in interstitium of inflammatory bowel disease patients (p=0.0001 versus controls). The kallikrein and kallistatin depletion of goblet cells and the increased interstitial kallikrein and kallistatin reactivity correlated with the degree of tissue inflammation (p=0.0001). Disease-free samples had normal kallikrein and kallistatin patterns. CONCLUSIONS: Kallikrein-kinin system is actively involved in inflammatory bowel disease as a result of the release of kallikrein in the intestinal extracellular space; this involvement correlates with the degree of tissue inflammation. The normal pattern observed in the disease-free samples seems to rule out a genetic defect of kallikrein and kallistatin in inflammatory bowel diseases.     

Utility of a Rapid Fecal Latex Agglutination Test Detecting the Neutrophil Protein, Lactoferrin, for Diagnosing Inflammatory Causes of Chronic Diarrhea

Objective: The utility of tests for fecal neutrophils in the setting of chronic diarrhea has not been established. The purpose of this study was to determine the causes of chronic diarrhea associated with fecal neutrophils.
Methods: One fecal specimen from each of 10 normal subjects, 26 patients with known microscopic colitis, 13 with celiac sprue, eight with Crohn's disease, four with ulcerative colitis, and 103 with chronic diarrhea of unknown origin, as well as 10 fecal specimens from a patient with chronic nongranulomatous enterocolitis were analyzed blindly for the presence of a neutrophil granule protein called lactoferrin using a commercial latex agglutination kit. Diagnostic evaluation of the 103 patients with chronic diarrhea was carried out to determine the diagnostic accuracy of this test for chronic inflammatory bowel disease.
Results: None of the normal control subjects, three of 39 patients with microscopic colitis or celiac sprue, all 10 specimens from the patient with enterocolitis, and all 12 control patients with ulcerative colitis or Crohn's disease had a positive fecal lactoferrin test. Eleven of 103 patients with chronic diarrhea presenting without a diagnosis had a positive test, and all were diagnosed with an inflammatory condition of the colon (five-, ulcerative colitis; four-, Crohn's disease; one-, ischemic colitis; and one-, microscopic colitis). Only one patient with inflammatory bowel disease had a negative lactoferrin test. The sensitivity, specificity, and positive and negative predictive values of the fecal lactoferrin test for ulcerative or Crohn's colitis were 90%, 98%, 82%, and 99%, respectively.
Conclusion: The major cause of fecal neutrophils in patients with chronic diarrhea is chronic inflammatory bowel disease of the colon. The latex agglutination test for fecal lactoferrin offers a highly sensitive, specific, and simple means for detection of fecal neutrophils in these patients.     

Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease. METHODOLOGY: Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay. RESULTS: VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls. CONCLUSIONS: The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.     

Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics

BACKGROUND & AIMS: In 1988, we reported the first twin study in inflammatory bowel disease. The aim of the current study was to follow up these twins regarding new cases of inflammatory bowel disease and Crohn's disease characteristics using the Vienna classification. METHODS: The official Swedish population register and the cause of death register were used to search for the twins. All living patients were interviewed. RESULTS: Three monozygotic twins earlier classified as healthy had been diagnosed with inflammatory bowel disease (ulcerative colitis, n = 2; Crohn's disease, n = 1). Retrospectively, all 3 were symptomatic at the original survey. This changed the pair concordance in monozygotic twins from 6.3% to 18.8% in ulcerative colitis and from 44.4% to 50.0% in Crohn's disease. A high degree of concordance regarding age at diagnosis, disease location at diagnosis and during the course, and disease behavior was found in concordant monozygotic twin pairs with Crohn's disease. Seven of 9 pairs were identical in 3 or more of these disease characteristics compared with an expected number of 1.5 (P = 0.000076). CONCLUSIONS: This study confirms that the genetic influence is stronger in Crohn's disease than in ulcerative colitis. A remarkable phenotype similarity within concordant pairs with Crohn's disease was found using the Vienna classification.     

Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease.

Previous studies suggesting increased reactive oxygen metabolite (ROM) production in inflammatory bowel disease have been restricted to peripheral blood and isolated intestinal phagocytes. In the current study, chemiluminescence and the effect of various scavengers, enzymes, and enzyme inhibitors were used to show that ROMs account for the increased production of oxidants by colorectal mucosal biopsy specimens in inflammatory bowel disease. Luminol-amplified chemiluminescence was increased in active ulcerative colitis [macroscopic grade 1: 25 photons.mg-1.min.10(-3) (median), 8-47 (95% confidence intervals), n = 40; grade 2: 89, 65-156, n = 30; grade 3: 247, 133-562, n = 13] and Crohn's disease [mild: 9, 3-84, n = 6; severe: 105, 25-789 (range), n = 5] compared with normal-looking mucosa (ulcerative colitis: 0.8, 0.4-1.4, n = 22, P less than 0.01; Crohn's disease: 0.8, 0.1-2, n = 6, P less than 0.05) and controls (0.6, 0.04-1.4, n = 52, P less than 0.01). In ulcerative colitis, luminol chemiluminescence correlated with microscopic inflammation (Spearman's p = 0.74, P = 0.0001) and was decreased by sodium azide (-89%, P less than 0.05), taurine (-31%, P less than 0.05), catalase (-23%, P less than 0.05), and dimethyl sulfoxide (-29%, P less than 0.05). Superoxide dismutase and oxypurinol decreased lucigenin chemiluminescence in ulcerative colitis by -63% (P less than 0.05) and -27% (P less than 0.05), respectively. Luminol chemiluminescence correlated with lucigenin chemiluminescence (Spearman's rho = 0.72, P = 0.003). These results suggest that neutrophil-derived oxidants (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorite) are generated in colorectal mucosa in active inflammatory bowel disease and support the hypothesis that production of such metabolites by neutrophils is of major pathogenetic importance.     

Ultrasonography in the detection of Crohn's disease and in the differential diagnosis of inflammatory bowel disease

The diagnostic accuracy of abdominal ultrasonography in inflammatory bowel disease (IBD) has been evaluated in a prospective, randomized, blind study. A total of 181 patients (89 with Crohn's disease, 57 ulcerative colitis and 35 controls) were examined. Sensitivity and specificity of diagnosis in Crohn's disease, corrected for prevalence, were 80.8 and 79.2%, respectively, and a very similar accuracy was found in the differential diagnosis of IBD. In conclusion, ultrasonography can play a role in detecting Crohn's disease and in the differential diagnosis of chronic IBD.     

Complications of inflammatory bowel disease

Complications in inflammatory bowel disease determine the severity of disease as well as the complexities of medical or surgical treatment opportunities. Therefore, in known inflammatory bowel disease, the prevention, the early detection and the adequate therapeutic response to certain complications are important goals in the follow-up of inflammatory bowel disease patients. Disease complications are separated into intestinal and extraintestinal complications. Intestinal complications are somewhat disease specific, which means that they occur exclusively in either Crohn's disease or ulcerative colitis (e.g., enteric fistulas are particularly found in Crohn's disease and toxic megacolon in ulcerative colitis). Most extraintestinal complications occur in both forms of inflammatory bowel disease (e.g., anemia, thromboembolic events or osteoporosis). The current knowledge on pathogenesis, diagnostic tools, prevention and treatment of certain intestinal and extraintestinal complications is reviewed.     

A case-control study of childhood environmental risk factors for the development of inflammatory bowel disease

OBJECTIVE : To clarify the relationship between childhood environment and the risk of subsequent development of Crohn's disease or ulcerative colitis. DESIGN AND OUTCOME MEASURES : A case-control study, assessing the risk of inflammatory bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression. SETTING : District general hospital (secondary care institution). PARTICIPANTS : Subjects with Crohn's disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control. RESULTS : Helicobacter seroprevalence was substantially reduced in Crohn's disease (OR 0.18; 95% CI, 0.06-0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38-2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01-0.51). Crohn's disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23-6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21-6.91). There was no association between hepatitis A seroprevalence and either disease. CONCLUSION : The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohn's disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohn's disease.     

The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study

BACKGROUND & AIMS: The aim of this study was to determine the 1-year outcome after the first course of corticosteroids in an inception cohort of patients with inflammatory bowel disease. METHODS: All patients in Olmsted County, Minnesota, diagnosed with Crohn's disease (n = 173) or ulcerative colitis (n = 185) from 1970 to 1993 who were treated with systemic corticosteroids were identified (4 denied research authorization). Immediate outcome (30 days) and 1-year outcome after the first course of corticosteroids were determined. RESULTS: Seventy-four (43%) patients with Crohn's disease and 63 (34%) with ulcerative colitis were treated with corticosteroids. Immediate outcomes for Crohn's disease were complete remission in 43 (58%), partial remission in 19 (26%), and no response in 12 (16%). Immediate outcomes for ulcerative colitis were complete remission in 34 (54%), partial remission in 19 (30%), and no response in 10 (16%). One-year outcomes for Crohn's disease were prolonged response in 24 (32%), corticosteroid dependence in 21 (28%), operation in 28 (38%), and lost to follow-up in 1 (1%). One-year outcomes for ulcerative colitis were prolonged response in 31 (49%), corticosteroid dependence in 14 (22%), and operation in 18 (29%). CONCLUSIONS: Most patients with Crohn's disease and ulcerative colitis initially respond to corticosteroids. At 1 year, 32% of patients with Crohn's disease and 48% with ulcerative colitis are corticosteroid free without operation.     

Association of Susceptibility Locus for Inflammatory Bowel Disease on Chromosome 16 with Both Ulcerative Colitis and Crohn's Disease

A susceptibility locus for inflammatory bowel disease (IBD) on chromosome 16 (IBD1) has been linked to Crohn's disease in genome-wide linkage studies. We performed a case–control study with two markers for this locus using leukocyte DNA from 127 Crohn's patients, 83 ulcerative colitis patients, and 74 control patients. Allele, genotype, and haplotype frequencies of the polymerase chain reaction products were determined using autoradiography. Haplotype frequencies differed for ulcerative colitis and Crohn's disease, particularly for haplotype CC (22% ulcerative colitis vs 10% Crohn's disease, P = 0.002 ² = 10.0) and haplotype CD (18% Crohn's disease vs 9% ulcerative colitis, P = 0.025 ² = 5.02). These data demonstrate the association of the IBD1 locus with both ulcerative colitis and Crohn's disease in a group of unrelated IBD patients. The use of such microsatellite markers when combined with others, might help distinguish ulcerative colitis from Crohn's disease in patients with ambiguous clinical and histological features.