Symptoms of 50 patients with the irritable bowel syndrome were compared with those of 49 with endoscopically proven peptic ulcer disease and 49 with radiologically or endoscopically proven inflammatory bowel disease using a questionnaire which was administered after the diagnosis was made. Symptoms of bowel dysfunction including pain related to bowel movements were more likely to occur in the irritable bowel syndrome than peptic ulcer disease. Only abdominal distension, straining at stool and scybala, however, were significantly more likely in the irritable bowel syndrome than inflammatory bowel disease. Four symptoms previously shown to be more common in irritable bowel syndrome than in organic abdominal disease were combined. The more of these symptoms that were present, the more likely were the patients to have the irritable bowel syndrome than peptic ulcer disease. Symptoms of gut dysfunction are highly discriminating between irritable bowel syndrome and peptic ulcer disease but less so between irritable bowel syndrome and inflammatory bowel disease.
AIM: To determine the incidence and characteristics of intestinal and extra-intestinal cancers among patients with inflammatory bowel disease in a Spanish hospital and to compare them with those of the local population.
METHODS: This was a prospective, observational, 7-year follow-up, cohort study. Cumulative incidence, incidence rates based on person-years of follow-up and relative risk were calculated for patients with inflammatory bowel disease and compared with the background population. The incidence of cancer was determined using a hospital-based data registry from Hospital Universitario de Fuenlabrada. Demographic data and details about time from diagnosis of inflammatory bowel disease to occurrence of cancer, disease extent, inflammatory bowel disease treatment, cancer therapy and cancer evolution were also collected in the inflammatory bowel disease cohort.
RESULTS: Eighteen of 590 patients with inflammatory bowel disease developed cancer [cumulative incidence = 3% (95%CI: 1.58-4.52) vs 2% (95%CI: 1.99-2.11) in the background population; RR = 1.5; 95%CI: 0.97-2.29]. The cancer incidence among inflammatory bowel disease patients was 0.53% (95%CI: 0.32-0.84) per patient-year of follow-up. Patients with inflammatory bowel disease had a significantly increased relative risk of urothelial carcinoma (RR = 5.23, 95%CI: 1.95-13.87), appendiceal mucinous cystadenoma (RR = 36.6, 95%CI: 7.92-138.4), neuroendocrine carcinoma (RR = 13.1, 95%CI: 1.82-29.7) and rectal carcinoid (RR = 8.94, 95%CI: 1.18-59.7). Colorectal cancer cases were not found.
CONCLUSION: The overall risk of cancer did not significantly increase in our inflammatory bowel disease patients. However, there was an increased risk of urinary bladder cancer and, with less statistical power, an increased risk of appendiceal mucinous cystadenoma and of neuroendocrine tumors. Colorectal cancer risk was low in our series.
Extra-intestinal cancer; Inflammatory bowel disease; Cancer risk; Background population; Urothelial carcinoma; Appendiceal mucinous cystadenoma; Neuroendocrine carcinoma; Rectal carcinoid
The Jewish population has an increased frequency of inflammatory bowel disease compared with their non-Jewish neighbours. Genetic factors have been implicated in the aetiology of this disorder and may contribute to ethnic differences. This study determined the familial empirical risks for inflammatory bowel disease in the first degree relatives of inflammatory bowel disease probands (for both Jews and non-Jews) for the purpose of accurate genetic counselling and genetic analysis. A total of 527 inflammatory bowel disease patients from Southern California (291 Jews and 236 non-Jews) were questioned about inflammatory bowel disease in their first degree relatives (a total of 2493 individuals). Since inflammatory bowel disease has a variable and late age of onset, age specific incidence data were used to estimate the life time risks and to make valid comparisons between the different groups. In the first degree relatives of non-Jewish probands, the life time risks for inflammatory bowel disease were 5.2% and 1.6% when probands had Crohn's disease and ulcerative colitis respectively. These values were consistently lower than the corresponding risks for relatives of Jewish patients -7.8% and 4.5% for Crohn's disease and ulcerative colitis probands respectively (p value for comparison between Jews and non-Jews: 0.028; between ulcerative colitis and Crohn's disease: 0.005). These data provide the requisite basis for genetic counselling for these disorders in the white American population. In addition, these different empirical risks for relatives of Jewish and non-Jewish probands allow rejection of single Mendelian gene models for inflammatory bowel disease, but are consistent with several alternative genetic models.
Crohn disease (CD) is a chronic inflammatory bowel disease that affects the entire gastrointestinal tract but is most frequently localized to the large and small bowel. Small bowel endoscopy helps with the differential diagnosis of CD in suspected CD patients. Early diagnosis of CD is preferable for suspected CD conditions to improve chronic inflammatory infiltrates, fibrosis. Small bowel endoscopy can help with the early detection of active disease, thus leading to early therapy before the onset of clinical symptoms of established CD. Some patients with CD have mucosal inflammatory changes not in the terminal ileum but in the proximal small bowel. Conventional ileocolonoscopy cannot detect ileal involvement proximal to the terminal ileum. Small bowel endoscopy, however, can be useful for evaluating these small bowel involvements in patients with CD. Small bowel endoscopy by endoscopic balloon dilation (EBD) enables the treatment of small bowel strictures in patients with CD. However, many practical issues still need to be addressed, such as endoscopic findings for early detection of CD, application compared with other imaging modalities, determination of the appropriate interval for endoscopic surveillance of small bowel lesions in patients with CD, and long-term prognosis after EBD.
Crohn disease; Capsule endoscopy; Balloon assisted endoscopy; Endoscopic balloon dilation
Indium leucocyte scanning and measurement of faecal Indium leucocyte excretion are techniques which have recently been introduced for assessing patients with inflammatory bowel disease. The methodology has recently been made more specific for acute inflammation by labelling pure granulocytes rather than the mixed leucocyte preparation. To determine the accuracy of this modified technique in detecting inflammatory bowel disease, we have prospectively compared Indium granulocyte scanning and faecal In granulocyte excretion with rectal histology and contrast bowel radiology as screening procedures in 100 patients with suspected inflammatory bowel disease. Thirty three patients were shown to have inflammatory bowel disease - 24 with Crohn's disease and nine with ulcerative colitis or indeterminate colitis. Overall the respective sensitivities for detecting inflammatory bowel disease were 97% for faecal Indium granulocyte excretion, 94% for Indium granulocyte scanning, 79% for radiology and 70% for rectal histology. The superiority of In granulocytes over radiology and rectal histology in detecting inflammatory bowel disease was, in the main, due to the difficulty in diagnosing Crohn's with conventional techniques. Although three of the patients with ulcerative colitis and indeterminate colitis had normal sigmoidoscopic appearances - all had abnormal rectal histology. No patient with a non-inflammatory bowel disorder had a positive In granulocyte scan or a raised faecal excretion. These results show that investigations using In granulocytes are accurate in identifying inflammatory bowel disease and offer important advantages over conventional procedures for detecting Crohn's disease.
Stools from 109 patients with inflammatory bowel disease (13.4%) contained Clostridium difficile or its toxin, an incidence similar to the stools of 99 control patients with diarrhoea (11.9%), but significantly higher than the stools of 77 control patients with a normal bowel habit (1.4%). Sixty-six per cent of the diarrhoea controls, but only 11% of the inflammatory bowel disease patients, reported recent antibiotic use: however, 67% of inflammatory bowel disease patients were taking sulphasalazine. The presence of Cl difficile in the stool was not related to the clinical assessment of inflammatory bowel disease relapse, but it was related to hospital admission. During the one year study, 31 of the 109 patients (28%) with inflammatory bowel disease had one or more stool samples that were positive for Cl difficile.
Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.
Conclusions about the relationship between the pathophysiology and treatment of inflammatory bowel disease and the physiology and management of pregnancy are based on the results of several large physician surveys and retrospective chart reviews. Patients with active disease fare worse than those with inactive disease. There is little evidence that pregnancy affects the course of inflammatory bowel disease or that inactive inflammatory bowel disease affects the course of pregnancy. Judicious medical therapy is effective in controlling inflammatory bowel disease during pregnancy. Sulfasalazine or steroid therapy should not be withdrawn in a patient who needs it to achieve or maintain a quiescent state of inflammatory bowel disease during the course of pregnancy. Immunosuppressive therapy should be avoided. Aggressive medical therapy with total parenteral nutrition in a team approach with a gastroenterologist, surgeon, and perinatologist usually avoids the need for surgical intervention during pregnancy with a good fetal outcome in a patient whose disease is active. Contraception against pregnancy need only be considered in those patients whose disease is so severe that operative therapy is imminent.
Invasive and non-invasive tests can be used to evaluate the activity of inflammatory bowel diseases.
The aim of the present study was to investigate the role of fecal calprotectin in evaluating inflammatory bowel disease activity and the correlation of fecal calprotectin with the erythrocyte sedimentation rate and C reactive protein values in inflammatory bowel disease.
Sixty-five patients affected with inflammatory bowel disease were enrolled. Twenty outpatients diagnosed with inflammatory bowel disease comprised the control group.
In the present study, all patients in the control group had an fecal calprotectin value lower than the cut-off point (50 mg/kg).
In conclusion, fecal calprotectin was found to be strongly associated with colorectal inflammation indicating organic disease. Fecal calprotectin is a simple and non-invasive method for assessing excretion of macrophages into the gut lumen. Fecal calprotectin values can be used to evaluate the response to treatment, to screen asymptomatic patients, and to predict inflammatory bowel disease relapses.
Inflammatory bowel diseases; Irritable bowel syndrome; Fecal calprotectin
Capsule endoscopy was conceived by Gabriel Iddan and Paul Swain independently two decades ago. These applications include but are not limited to Crohn’s disease of the small bowel, occult gastrointestinal bleeding, non steroidal anti inflammatory drug induced small bowel disease, carcinoid tumors of the small bowel, gastro intestinal stromal tumors of the small bowel and other disease affecting the small bowel. Capsule endoscopy has been compared to traditional small bowel series, computerized tomography studies and push enteroscopy. The diagnostic yield of capsule endoscopy has consistently been superior in the diagnosis of small bowel disease compared to the competing methods (small bowel series, computerized tomography, push enteroscopy) of diagnosis. For this reason capsule endoscopy has enjoyed a meteoric success. Image quality has been improved with increased number of pixels, automatic light exposure adaptation and wider angle of view. Further applications of capsule endoscopy of other areas of the digestive tract are being explored. The increased transmission rate of images per second has made capsule endoscopy of the esophagus a realistic possibility. Technological advances that include a double imager capsule with a nearly panoramic view of the colon and a variable frame rate adjusted to the movement of the capsule in the colon have made capsule endoscopy of the colon feasible. The diagnostic rate for the identification of patients with polyps equal to or larger than 6 mm is high. Future advances in technology and biotechnology will lead to further progress. Capsule endoscopy is following the successful modern trend in medicine that replaces invasive tests with less invasive methodology.
Capsule endoscopy; Cancer screening; Colon cancer; Artificial intelligence; Technology
Obesity is becoming increasingly more common among patients with inflammatory bowel disease. In this review, we will explore the epidemiological trends of inflammatory bowel disease, the complex interplay between the proinflammatory state of obesity and inflammatory bowel disease, outcomes of surgery for inflammatory bowel disease in obese as compared with non-obese patients, and technical concerns pertaining to restorative proctocolectomy and ileoanal pouch reservoir, stoma creation and laparoscopic surgery for inflammatory bowel disease in obese patients.
Obesity; Crohn's disease; ulcerative colitis; inflammatory bowel disease; laparoscopy; restorative proctocolectectomy
A non-invasive method of imaging and assessing inflammatory bowel disease is described. 111Indium labelled leucocyte scans were performed on 33 patients with a wide variety of inflammatory bowel diseases and 25 control patients. All patients with moderate or severe inflammatory bowel disease had positive scans with localisation of abnormal activity corresponding to the sites assessed to be diseased by radiology in either small or large bowel. No false positives were recorded in the control patients. Faecal excretion of 111In labelled leucocytes was increased in patients with inflammatory bowel disease according to disease severity and correlated with disease activity assessed by serum C-reactive protein levels (r = 0.74, p less than 0.001) or in those patients with Crohn's disease by Crohn's Disease Activity Index (r = 0.78, p less than 0.001). These data suggest that 111In labelled leucocytes may be used to provide a safe, non-invasive method of imaging diseased bowel and objectively assessing disease activity.
Background: Thromboxanes are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthase inhibitor, is anti-inflammatory and may have therapeutic benefits in patients with ulcerative colitis.
Aims: To investigate the immunohistochemical expression of thromboxane synthase in the colorectal mucosa of patients with inflammatory bowel disease.
Methods: Immunostaining of colonic biopsies from patients with inflammatory bowel disease (n = 13) and controls (n = 5) was performed using a monoclonal antibody to human thromboxane synthase. The extent of staining in cells of the lamina propria was compared in patient and control groups, and was assessed in relation to disease activity scored macroscopically and histologically.
Results: The percentage of cells in the lamina propria staining for thromboxane synthase was higher in patients with active inflammatory bowel disease than in those with inactive disease or in controls (p = 0.02 and p = 0.002, respectively). There was a direct correlation between disease activity, measured endoscopically and histologically, and the percentage of lamina propria cells staining for thromboxane synthase (R = 0.71, p = 0.001 and R = 0.72, p = 0.001, respectively).
Conclusions: Increased thromboxane synthase expression in lamina propria cells occurs in active inflammatory bowel disease. It is possible that this results in increased thromboxane synthesis, which may in turn contribute to mucosal inflammation and intramucosal thrombogenesis.
thromboxane; thromboxane synthase; ulcerative colitis; Crohn's disease
Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors.
There are several types of small bowel pathology that can lead to small bowel obstruction or intussusception. The etiology causing small bowel obstruction varies by age. Benign disease is the typical cause in children and adolescents while malignant or adhesive disease is far more common in older patients. Although cases of adult intussusception caused by benign processes are rare, there are reports of inflammatory fibroid polyps causing adult intussusception of the terminal ileum published in the literature.
We present the case of a 70-year-old man with a multiple year history of intermittent episodes of bowel obstruction who was found to have a giant ileal inflammatory fibroid polyp causing intermittent small bowel obstruction. The patient underwent operative intervention and has now been symptom-free for three years.
Small bowel lesions include both malignant and benign etiologies. The malignant etiologies include adenocarcinoma, carcinoid or lymphoma while benign lesions are typically lipomas, inflammatory polyps or adenomas. Inflammatory fibroid polyps are rare, benign lesions that can occur anywhere within the gastrointestinal tract. They are typically an incidental finding, but on rare occasions have been presented as the source of intussusception or obstruction.
Background—A large number of monozygotic and
dizygotic twin pairs with inflammatory bowel disease have been
reported. To date no twin pair has developed phenotypically discordant
inflammatory bowel disease. This case report is the first documented
occurrence of discordant inflammatory bowel disease occurring in
Case report—Twenty two year old identical male
twins presented within three months of each other with inflammatory
bowel disease that proved to be discordant in overall disease type,
disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time of
testing while twin 2 (Crohn's disease) was ANCA positive.
Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previously
associated with extensive colitis.
Conclusion—This case report confirms the important
role played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undetermined
environmental agents in dictating disease expression and phenotype.
monozygotic twins; ulcerative colitis; Crohn's
disease; inflammatory bowel disease
BACKGROUND—Measurement of 6-thioguanine nucleotide concentrations may be useful for optimising treatment with azathioprine and 6-mercaptopurine.
METHODS—We conducted a study of 170 patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine to determine the relationship between 6-thioguanine nucleotide concentrations and both disease activity, as measured by the inflammatory bowel disease questionnaire (active disease <170, remission ⩾170) and leucopenia. Blood was submitted for whole blood 6-thioguanine nucleotide concentration and leucocyte count.
RESULTS—Mean (SD) inflammatory bowel disease questionnaire score was 176 (32). There was no correlation between inflammatory bowel disease questionnaire scores and 6-thioguanine nucleotide concentrations (rs=−0.09, p=0.24). Median 6-thioguanine nucleotide concentrations in 56 patients with active disease and 114 patients in remission were similar (139 v 131 pmol/8×108 red blood cells; p=0.26). There was no correlation between 6-thioguanine nucleotide concentrations and leucocyte counts.
CONCLUSIONS—In patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine, 6-thioguanine nucleotide concentrations did not correlate with disease activity, as measured by the inflammatory bowel disease questionnaire, or leucocyte count. These findings are discrepant with most previous studies, possibly due to selection of responding patients who tolerated the medications. A prospective, randomised, dose optimisation trial using 6-thioguanine nucleotide concentrations is warranted.
Keywords: azathioprine; 6-mercaptopurine; thioguanine nucleotides; thiopurine methyltransferase; inflammatory bowel disease
Thrombophilia is a rare but potentially catastrophic phenomenon occurring in patients having tendency of thrombosis. It may lead to serious complications. The etiology of thrombophilia is thought to be multifactorial and related to both acquired and inherited factors. Inflammatory bowel disease is an acquired cause of thrombophilia. Thromboembolic events are seen during inflammatory bowel disease, especially during the active period of the disease. In inflammatory bowel disease, thrombus formation in portal, splenic and mesenteric veins are not common. Besides, the association of genetic disorders related to metabolism of homocysteine with inflammatory bowel disease has been evidenced, especially in Crohn disease and rarely in ulcerative colitis. We present a rare case of ulcerative colitis in association with combined portal, splenic and mesenteric vein thrombosis. The patient was recently diagnosed with the disease which was in the inactive period. Interestingly, our patient was also heterozygous for the mutation in methylenetetrahydrofolate reductase (MTHFR) gene.
Thrombophilia; Inflammatory Bowel Disease; Ulcerative Colitis; Portal Vein Thrombosis; Mesentery Vein Thrombosis; Splenic Vein Thrombosis; Methylenetetrahydrofolate Reductase Gene
The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction.
Background: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease.
Objective: To examine environmental risk factors prior to the development of inflammatory bowel disease in a paediatric population based case control study.
Methods: A total of 222 incident cases of Crohn’s disease and 60 incident cases of ulcerative colitis occurring before 17 years of age between January 1988 and December 1997 were matched with one control subject by sex, age, and geographical location. We recorded 140 study variables in a questionnaire that covered familial history of inflammatory bowel disease, events during the perinatal period, infant and child diet, vaccinations and childhood diseases, household amenities, and the family’s socioeconomic status.
Results: In a multivariate model, familial history of inflammatory bowel disease (odds ratio (OR) 4.3 (95% confidence interval 2.3–8)), breast feeding (OR 2.1 (1.3–3.4)), bacille Calmette-Guerin vaccination (OR 3.6 (1.1–11.9)), and history of eczema (OR 2.1 (1–4.5)) were significant risk factors for Crohn’s disease whereas regular drinking of tap water was a protective factor (OR 0.56 (0.3–1)). Familial history of inflammatory bowel disease (OR 12.5 (2.2–71.4)), disease during pregnancy (OR 8.9 (1.5–52)), and bedroom sharing (OR 7.1 (1.9–27.4)) were risk factors for ulcerative colitis whereas appendicectomy was a protective factor (OR 0.06 (0.01–0.36)).
Conclusions: While family history and appendicectomy are known risk factors, changes in risk based on domestic promiscuity, certain vaccinations, and dietary factors may provide new aetiological clues.
environment; children; inflammatory bowel disease; ulcerative colitis; risk factors
AIM: To investigate a possible genetic influence of claudin (CLDN)1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.
METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn’s disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease -families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.
RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95%CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95%CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.
CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.
Crohn’s disease; Genetic predisposition; Inflammatory bowel disease; Single nucleotide polymorphism; Tight junctions
The proportions and absolute numbers of helper and suppressor T-cells in 40 patients with inflammatory bowel disease and 22 control subjects were determined, using the monoclonal antibodies OKT 4 and OKT 8. There were no significant differences in helper or suppressor cell proportions among 15 steroid treated patients with active inflammatory bowel disease, 10 patients with inactive inflammatory bowel disease, 10 patients with other gastrointestinal diseases, or 12 normal control subjects. In contrast, 15 patients with active inflammatory bowel disease not treated with corticosteroids manifested increased proportions of helper cells and decreased proportions of suppressor cells (p less than 0.001), compared with all other patient groups and to normal controls. When absolute numbers of helper and suppressor subsets were measured, these alterations in proportions of helper and suppressor cells were primarily attributable to decreased counts of suppressor T-cells both in patients with active Crohn's disease and in those with ulcerative colitis (p less than 0.01). In four patients undergoing serial study, the helper/suppressor ratios appeared to rise and fall respectively with clinical exacerbations and remissions of disease. These data provide additional evidence for the involvement of cellular immune systems in these disease processes.
Background & Aims: Inflammatory bowel disease is thought to be rare in Libya. The aim is to determine the prevalence of juvenile onset inflammatory bowel disease in Libya. Setting: Al-Fateh childrens' hospital, Benghazi, Libya. Methods: This is a retrospective study of all cases diagnosed over 10 years (1997–2006) with either ulcerative colitis, Crohn's disease or indeterminate colitis. Inclusion criteria were age <15 years at time of presentation who were resident in the eastern part of the country and who diagnosed with inflammatory bowel disease. Clinical features were outlined using a proforma. Results: Sixteen cases were diagnosed with inflammatory bowel disease, of whom 11 were males (M:F ratio of 1.5:1). The prevalence and incidence rates in the year 2006 were 3.6 and 0.9 per 100,000 children, respectively. The incidence rate increased from 0.2 in 2002 to 0.9 in 2006 (Z score of 39.87, p= 0.00). The age at presentation ranged from 5 months to 14 years. Nine had Crohn's disease (6 males) and 6 had ulcerative colitis (4 males). One patient had indeterminate colitis. The most common clinical features were diarrhea in 10 (62.5%), abdominal pain, anorexia and weight loss in 9 (56.2%), anemia in 7 (43.75%) and vomiting in 6 (37%). Ileopancolitis was found in 3 patients whereas 6 patients had ileocecal disease. Conclusions: Childhood inflammatory bowel disease in this population is not so rare and it is increasing. The clinical pattern is similar to that reported by others.
Inflammatory bowel disease; Ulcerative colitis; Crohn's disease; Indeterminate colitis; Juvenile onset inflammatory bowel disease
Inflammatory bowel disease is the result of both genes and environment. Canadian First Nations people, despite living in a region with a high prevalence of inflammatory bowel disease, are relatively protected from this disease. We aimed to compare the carriage of genetic variants associated with inflammatory bowel disease in healthy First Nations and white people.
DNA was extracted from the venous blood of healthy First Nations (n = 340) and white (n = 285) participants from Manitoba. Genotyping was performed for 69 single nucleotide polymorphisms (SNPs) with known or suspected associations with inflammatory bowel disease. We compared the genotypes between groups by logistic regression, adjusting for multiple testing. We calculated a risk score for the NOD2 gene by adding the number of risk alleles at three important NOD2 SNPs (G908R, R702W and 3020insC).
We found genetic variation between white and First Nations participants at 45 of 69 SNPs. Notably, carriage of the ATG16L1 T300A mutation was lower in First Nations participants (p = 4.1 × 10−30). Cumulative carriage of important NOD2 variants was significantly lower among First Nations participants (3.9% v. 15.2%; p < 0.0001 for risk score) than among white participants. Risk variants in IL23R (p = 0.014) and IL12B (p = 1.2 × 10−16), among others, were more prevalent among First Nations participants than among white participants.
The low prevalence of variants associated with bacterial processing and handling in First Nations people may explain their relative protection from inflammatory bowel disease. Increased carriage of a number of risk variants, for example in the interleukin-23/Th17 pathway, is especially intriguing given their importance in other inflammatory diseases of high incidence in First Nations populations.
The inflammatory bowel diseases are considered an abnormal host immune response to an environmental stimulus. Evidence suggests a role for intestinal bacteria in initiating and/or providing an ongoing stimulus for inflammation in inflammatory bowel disease. Helicobacter pylori is the major cause of active chronic gastritis and peptic ulcers in humans and has been linked to gastric carcinoma and lymphoma. Studies in various animal models, particularly mice, have identified enterohepatic Helicobacter species that are capable of causing hepatitis and enterocolitis. We hypothesize that Helicobacter species may have a role in maintaining inflammation in humans with inflammatory bowel disease. In order to investigate this, biopsy specimens were obtained from patients with and without inflammatory bowel disease. DNA was extracted from the tissues and subjected to PCR with primers designed to detect the ribosomal DNA of members of the Helicobacter species. DNA from six biopsy samples from 60 inflammatory bowel disease patients tested positive. This included 5 of 33 ulcerative colitis patients that were positive compared to 0 of 29 age-matched controls (P < 0.04). Sequencing of the bands produced by PCR amplification revealed ≥99% homology with H. pylori. These results indicate that a member of the Helicobacter species may be involved in some cases of ulcerative colitis.