Fulminant colitis in inflammatory bowel disease

PURPOSE: The morphologic features of fulminant colitis may be nonspecific, making differentiation between ulcerative colitis and Crohn's disease difficult, even after colectomy. The aims of this study were 1) to identify histologic features that accurately differentiated ulcerative colitis, Crohn's disease, and indeterminate colitis in fulminant colectomy specimens; 2) to determine how frequently subsequent clinical course altered the pathologic diagnosis; and 3) to evaluate the natural history of histologically diagnosed indeterminate colitis. METHODS: Ninety-five fulminant colectomy specimens were evaluated, of which 85 had an original diagnosis of fulminant inflammatory bowel disease. Complete pathologic material and comprehensive clinical follow-up information was available on 67 cases of inflammatory bowel disease. These were re-evaluated in a blinded fashion, and histopathologic features were compared with the original diagnosis and reviewed in the light of subsequent clinical behavior to reach a final diagnosis. RESULTS: Evaluation of macroscopic features was not helpful in differentiating ulcerative colitis from Crohn's disease. Microscopic examination correctly diagnosed ulcerative colitis or Crohn's disease in only 58 of 67 (87 percent) cases. A further three cases (4 percent) were definitively classified after correlation with clinical data, leaving a residual six cases that were diagnosed as indeterminate colitis. Granulomas and lymphoid aggregates were the two most specific indicators of Crohn's disease. CONCLUSIONS: Histopathologic evaluation alone has limitations in the accurate classification of fulminant inflammatory bowel disease. Histologically diagnosed indeterminate colitis is a heterogeneous group that may include some patients who subsequently prove to have ulcerative colitis or Crohn's disease.Presented at the meeting of the United States and Canadian Academy of Pathology, Orlando, Florida, March 1 to 7, 1997.     

Microaggregate of immunostained macrophages in noninflamed gastroduodenal mucosa: a new useful histological marker for differentiating Crohn's colitis from ulcerative colitis

OBJECTIVE: In 10% of cases it may be difficult to differentiate Crohn's colitis from ulcerative colitis. Distinguishing the two conditions is important because they are distinct entities with different therapeutic implications. Noncaseating granulomas are usually considered diagnostic of Crohn's disease. We previously reported that the presence of a microaggregate of immunostained macrophages within the noninflamed gastroduodenal mucosa was a characteristic finding of Crohn's disease. The aim of this study was to determine whether a microaggregate of immunostained macrophages can be a reliable marker for differentiating Crohn's colitis from ulcerative colitis. METHODS: We investigated the presence of microaggregates of immunostained macrophages and epithelioid cell granulomas in biopsy specimens taken from the noninflamed gastroduodenal mucosa of 22 known Crohn's colitis patients and 23 established ulcerative colitis patients. The incidence of microaggregates and granulomas was compared between these two groups. RESULTS: Microaggregates and granulomas were detected only in the Crohn's colitis patients. In addition, the presence of microaggregates was more frequent than that of granulomas in Crohn's colitis patients (54.5% and 18.2%, respectively, 95% confidence interval for the difference: 10.0-62.7%). CONCLUSION: Detecting a microaggregate of immunostained macrophages in a biopsy specimen taken from noninflamed gastroduodenal mucosa seems to be a useful method for differentiating Crohn's colitis from ulcerative colitis.     

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.     

Two cases of inflammatory bowel disease with multiple myeloma

A significant increase has been reported in reticuloendothelial neoplasms in patients with inflammatory bowel diseases. We present two rare cases of multiple myeloma in patients with inflammatory bowel diseases. One was in a 58-year-old woman with ulcerative colitis, and the other was in a 59-year old woman with Crohn's disease. In both patients, multiple myeloma occurred during long-term observation of inflammatory bowel disease and during the inactive stage of intestinal inflammation. The multiple myeloma appeared to have resulted from monoclonal gammopathy of undertermined significance in both patients, and was diagnosed by characteristic serum and bone marrow findings. Our findings suggested that multiple myeloma should be particularly considered in women of middle or advanced age with ulcerative colitis or Crohn's colitis and serum monoclonal gammopathy. Received: October 29, 1998 / Accepted: April 4, 1999     

Measles is more prevalent in Crohn's disease patients. A multicentre Israeli study

The question whether there is a transmissible pathogenetic agent as a cause for Crohn's disease, remains unanswered. Measles virus has been the subject of many intensive studies, in the attempt to find a role for it in the pathogenesis of inflammatory bowel disease. Whether an early infection with measles virus may predispose to Crohn's disease in later life is still not clear. We conducted a large scale multicentre study, in order to obtain sufficient data to answer this question. To do so, we compared inflammatory bowel disease patients, with Crohn's disease or ulcerative colitis, with two matched control groups: clinical controls, and community controls. A total of 531 patients, 271 with ulcerative colitis and 260 with Crohn's disease were interviewed, as well as 903 matched controls. Blood from 104 inflammatory bowel disease patients and 50 controls was tested for antibodies to measles virus. We did not find any differences related to measles vaccination, either in Crohn's disease or in ulcerative colitis. Exposure to measles in childhood was more frequent in Crohn's disease patients than in their controls, the difference being statistically significant (p < 0.05) in relation to community controls. The presence of IgG antibodies to measles virus was higher in patients with Crohn's disease than in patients with ulcerative colitis or controls (p = 0.084). Another observation of interest was the finding that Crohn's disease patients who had measles in childhood, more frequently had large bowel disease than those who had not had measles. These data lead us to postulate that there may be a role for measles infection in Crohn's disease, even if, at present, this role remains unclear.     

Microsatellite Instability Is Uncommon in Intestinal Mucosa of Patients with Crohn's Disease

Patients with long-standing inflammatory bowel disease have an increased risk for colorectal carcinoma. Microsatellite instability occurs in colonic neoplasms and has been reported in colonic tissues from patients with ulcerative colitis. Patients with Crohn's disease also have an increased risk for colorectal cancer, although it is lower than that associated with ulcerative colitis. This study was designed to determine whether microsatellite instability occurs in Crohn's disease, and whether it occurs with similar frequency to that observed in ulcerative colitis. In all, 177 tissue samples from 33 patients with Crohn's disease were evaluated for microsatellite alterations. Microsatellite instability occurred in five different tissue samples from one of 33 Crohn's disease patients. Four of the five tissue samples showed microsatellite instability at more than one locus. We conclude that microsatellite instability is less common in Crohn's disease than ulcerative colitis and may reflect differences in cancer risk between these two forms of inflammatory bowel disease.     

Evolutionary changes in the pathologic diagnosis after the ileoanal pouch procedure

PURPOSE: Inadequate initial differentiation between ulcerative colitis and Crohn's disease may lead to a diagnosis of indeterminate colitis. Construction of an ileoanal pouch in these patients may result in significant morbidity and pouch failure when the ultimate diagnosis is Crohn's disease. METHOD: We prospectively studied 543 patients with idiopathic inflammatory bowel disease to determine whether a patient's pathologic diagnosis changed with time and how it affected outcome. RESULTS: Preoperative diagnosis was ulcerative colitis in 499 patients, indeterminate colitis in 42 patients, and Crohn's disease in 2 patients. Prior colectomy was performed in 58 percent of patients with ulcerative colitis and in all patients with indeterminate colitis and Crohn's disease. Postoperatively, the diagnosis changed in 20 patients with ulcerative colitis (13 to indeterminate colitis, 7 to Crohn's disease). Another two patients with indeterminate colitis showed evidence of Crohn's disease in the resected rectal specimen. As patients were followed up, an additional 13 patients were found to have Crohn's disease (5 indeterminate colitis, 8 ulcerative colitis). With the current diagnosis, perineal complications and pouch failure occurred, respectively, in 23 and in 2 percent of patients with ulcerative colitis, in 44 and in 12 percent of patients with indeterminate colitis, and in 63 and in 37 percent of patients with Crohn's disease. Pathologic diagnosis was altered in 35 patients (6 percent) overall, with a 12-fold increase in the diagnosis of Crohn's disease. Only 3 percent of patients with ulcerative colitis compared with 13 percent of patients with indeterminate colitis had a change in diagnosis to Crohn's disease (P =0.006; Fisher's exact test). CONCLUSION: Pouch-related complications, eventual pouch failure, and discovery of underlying Crohn's disease occurred in a significant number of patients with a diagnosis of indeterminate colitis. Until more accurate diagnostic differentiation is available, caution is advised in recommending the ileoanal pouch procedure to patients with indeterminate colitis.Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

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.     

A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5

BACKGROUND & AIMS: A genome-wide association scan of nonsynonymous DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16L1 with Crohn's disease. We investigated this association in independent U.K. cohorts of Crohn's disease and ulcerative colitis. METHODS: The T300A variant (rs2241880) was genotyped in an independent sample of 727 Crohn's disease and 877 ulcerative colitis cases, and in 579 controls. We then performed an extension analysis combining these data with the U.K. data from the initial study to give a total of 1236 U.K. Crohn's disease cases and 1235 controls to estimate disease risk and test for interaction with the CARD15 and IBD5 risk loci and for association with disease subtypes. RESULTS: The association of T300A was replicated in the independent sample of 727 Crohn's disease cases (P = .001), and was strongly associated in the extended analysis of 1236 Crohn's cases (P = 2.4 x 10(-6)). The 300A/A genotype conferred a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease. Analysis of the interaction of ATG16L1 with CARD15 and IBD5 indicated that all 3 loci contribute independently to disease risk. Homozygosity for the risk allele at all 3 loci conferred a combined risk of 20.4 (95% confidence interval: 8.71, 47.7) for Crohn's disease. The ATG16L1 risk genotype showed a modest but significant association with ulcerative colitis (P = .026). CONCLUSIONS: The association of ATG16L1 with Crohn's disease and possibly with ulcerative colitis supports a role for autophagy in the pathogenesis of inflammatory bowel disease.     

Two for one: coexisting ulcerative colitis and Crohn's disease.

Three cases of coexisting ulcerative colitis and Crohn's disease are presented. In the first case, the patient had a long-standing history of ulcerative proctitis before developing Crohn's colitis. In the two remaining cases, the patients presented initially with Crohn's disease of the ileum and, subsequent to resection, developed ulcerative colitis. Well-documented cases of patients diagnosed with both ulcerative colitis and Crohn's disease are rare. The literature on such cases is reviewed, and the controversy over whether ulcerative colitis and Crohn's disease are two distinct diseases is explored.     

Epidemiological aspects of inflammatory bowel disease in the Pamplona area.

OBJECTIVES: to analyze retrospectively our hospital records on patients diagnosed during the period from 1983 to 1993 as having Crohn's disease or ulcerative colitis, and to estimate the incidence and epidemiological characteristics of these diseases in the Pamplona health administration area. METHODS: 246 patients were diagnosed has having inflammatory bowel disease (147 with ulcerative colitis, 97 with Crohn's disease, and 2 with indeterminate colitis. RESULTS: mean incidence was 2.47 +/- 0.96 per 100 000 inhabitants for Crohn's disease, and 3.75 +/- 1.5 per 100 000 inhabitants for ulcerative colitis (p < 0.05). There was a nonsignificant increase in incidence during the study period. Age, sex, alcohol intake, smoking habit and familial aggregation were analyzed. CONCLUSIONS: mean estimated incidence of Crohn's disease and ulcerative colitis in our setting during 1983-1993 was similar to that reported more recently for other parts of Spain. In our setting, ulcerative colitis was significantly more frequent that Crohn's disease, and familial aggregation was lower among patients who had the former disease. Crohn's disease was diagnosed at earlier ages, and cigarette smoking was more frequent among patients with this disease.     

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease

PURPOSE: Appendectomy has been suggested as a possible protective factor in ulcerative colitis and as a risk factor in Crohn's disease. Tonsillectomy has also been associated with Crohn's disease. We performed a case-controlled study to investigate these associations in a homogeneous Greek population. METHODS: One hundred thirty-four consecutive cases of ulcerative colitis and 76 cases of Crohn's disease were included in the study. For each inflammatory bowel disease patient and a corresponding healthy control subject, matched for gender, age, and educational level, a standard record on various risk factors was completed by interview. The association between disease status and risk factors was assessed by Pearson's chi-squared test and the independent contribution of each risk factor was analyzed by means of logistic regression analysis. RESULTS: Appendectomy had been performed in 11 (8.2 percent) patients with ulcerative colitis, in 18 (13.4 percent) of their matched healthy control cases, in 19 (25.0 percent) patients with Crohn's disease, and in 10 (13.2 percent) of their matched healthy control cases. Odds ratio for development of ulcerative colitis after appendectomy was 0.6 (95 percent confidence interval, 0.26–1.27). Odds ratio for Crohn's disease was 2.2 (95 percent confidence interval, 0.94–5.12). Odds ratio for development of ulcerative colitis or Crohn's disease after tonsillectomy was 0.95 (95 percent confidence interval, 0.49–1.82) and 3.29 (95 percent confidence interval, 1.29–8.37), respectively. The logistic regression analysis showed that appendectomy and tonsillectomy have no independent association with the risk of developing ulcerative colitis, whereas in Crohn's disease both appendectomy and tonsillectomy have positive associations. Wellestablished risk factors, such as family history and smoking status, were also verified in this study. CONCLUSIONS: This case-control study, using multivariate logistic regression analysis, showed a less pronounced association between ulcerative colitis and appendectomy than previous reports. Our data also support the conclusion that tonsillectomy is a risk factor for developing Crohn's disease.Poster presentation at the World Congress of Gastroenterology, Vienna, Austria, September 6 to 11, 1998.     

Direct hospital costs for patients with inflammatory bowel disease in a Canadian tertiary care university hospital

OBJECTIVE: We set out to determine the direct costs of hospitalizations of patients with Crohn's disease and ulcerative colitis admitted to a university-affiliated tertiary care hospital and to contrast the costs of medical versus surgical inpatient care, Crohn's disease versus ulcerative colitis, and to identify dominant components of inpatient costs. METHODS: We used a patient-specific case costing system at Saint Boniface General Hospital, Winnipeg, Manitoba, for fiscal years 1994 and 1995. We extracted all inpatients whose hospital discharge abstracts included ICD-9-CM codes 555 (Crohn's disease) and 556 (ulcerative colitis) among the top eight discharge diagnoses, and performed a chart review on all cases to ensure that the hospitalization was for inflammatory bowel disease and the diagnoses were accurate. We analyzed cases based on their disease diagnosis, primary mode of therapy associated with the hospitalization (medical vs surgical), and their major diagnosis-related group (DRG). This study evaluated direct patient care costs only and costs are expressed in Canadian dollars. RESULTS: Of 362 hospital admissions, 325 were eligible and of these admissions 275 belonged to the digestive system DRGs. Seventy-one (37%) were admitted more than once during the 2 yr of the study, accounting for 202 (62%) of the total number of admissions. The mean cost per admission of all cases of Crohn's disease was $3,149 (95% confidence interval [CI], $2,665-$3,634) and for ulcerative colitis was $3,726 (95% CI $3,008-$4,445). Surgical therapy cases accounted for 49.8% of all admissions, 57.8% of all hospital days, and 60.5% of all costs. Patients treated surgically had more costly hospitalizations than those treated medically, particularly when analyzing only nontotal parenteral nutrition (TPN) cases. Surgical treatment admissions were significantly more costly for ulcerative colitis digestive DRG admissions than Crohn's disease. The nondigestive DRG admissions were more costly than the digestive DRGs in all categories although this was only statistically different among medically treated Crohn's disease. Patients treated medically were similarly costly whether they had Crohn's disease or ulcerative colitis. There was no significant difference in cost per admission among cases admitted multiple times, compared with those admitted only once. TPN cases accounted for 9.5% of cases but 27.1% of costs. TPN-associated hospitalizations were more costly than non-TPN-use hospitalizations but these costs were primarily driven by duration of stay rather than TPN use itself. For all cases, the top five cost categories in descending order were nursing unit bed-days, drugs and pharmacy, diagnostic lab tests, operating room, and diagnostic imaging and endoscopy. CONCLUSIONS: Using our system we could determine direct costs for inpatients with inflammatory bowel disease and the factors that determined increased costs. Medical therapy admissions were similarly costly between Crohn's disease and ulcerative colitis; however, surgical therapy admissions were costlier among ulcerative colitis patients. Admissions for nondigestive DRGs were more costly than those for digestive DRGs. TPN use identified a sicker group of patients who remained in the hospital longer than nonusers and, not surprisingly, these were the costliest patients.     

Thiol methyltransferase activity in inflammatory bowel disease

BACKGROUND: Luminal anionic sulphide may contribute to epithelial damage in ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification by the colonic mucosa and circulating erythrocytes. AIMS: To measure levels of TMT activity in erythrocytes of surgically treated cases of colitis or in rectal biopsies of defined groups of colitis. PATIENTS: Venepuncture blood was obtained from 37 blood donors and 27 subjects who had previously undergone a proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal disease, 33 post-colon resection for cancer, 14 with moderate to severe ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute Crohn's colitis, and six with radiation proctitis. METHODS: TMT activity was measured by high performance liquid chromatography with radioactive detection to measure (14)C methylmercaptoethanol formation, the reaction product of cell extracts incubated with mercaptoethanol and (14)C S-adenosylmethionine. RESULTS: Erythrocyte TMT activity of surgically treated cases of colitis was significantly elevated (p<0. 001) compared with control cases. TMT activity of rectal biopsies was significantly decreased (p<0.02) in acute but not quiescent ulcerative colitis, Crohn's colitis, or radiation colitis. CONCLUSIONS: Erythrocyte TMT activity was persistently elevated after proctocolectomy for Crohn's disease and ulcerative colitis. No primary defect of TMT activity was found in any case of unoperated colitis but mucosal activity was diminished with disease progression of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes in inflammatory bowel disease appear worthwhile.     

Increased expression of VEGF and CD146 in patients with inflammatory bowel disease

BACKGROUND: Angiogenesis has been suggested as an integral part of inflammatory bowel disease pathology. Vascular endothelial growth factor has long been considered to play a central, specific role in angiogenesis. Endothelial junction adhesion molecules, such as CD146, have recently been suggested to play a potent role in angiogenesis. CD34 is expressed on vascular endothelium, and it has been reported to be upregulated on endothelium in IBD. We investigated the expression of tissue vascular endothelial growth factor, CD34 and CD146 in the inflamed mucosa of patients with active inflammatory bowel disease compared with no inflamed mucosa of healthy controls. METHODS: Forty-two IBD patients [23 ulcerative colitis, 19 Crohn's disease] and ten healthy controls were included in the study. In colonoscopically obtained biopsies, CD34, CD146 and vascular endothelial growth factor expression were evaluated by immunohistochemistry. RESULTS: Vascular endothelial growth factor was detected in the mucosa of all groups, and its expression was significantly higher in both Crohn's disease and ulcerative colitis compared with controls (p<0.05). Immunohistochemical staining for CD146 in the inflamed mucosa was significantly higher in both Crohn's disease and ulcerative colitis compared with controls (p=0.002). A trend of higher CD34 expression in Crohn's disease and ulcerative colitis compared with controls was also found, but the difference among the three groups was not statistically significant (p=0.09). CONCLUSIONS: Inflamed mucosa of patients with active Crohn's disease and ulcerative colitis showed a markedly enhanced expression of VEGF and CD146, than normal mucosa of controls, indicating a possible role of angiogenesis in the pathogenesis of inflammatory bowel disease.     

Selective resistance of mucosal T-cell activation to immunosuppression in Crohn''s disease

BACKGROUND & AIMS: The inappropriately high state of T-cell activation found in Crohn's disease could be due to failure to respond to inhibitory signals. We tested the hypothesis that Crohn's disease mucosal T-cells are resistant to the immunosuppressive action of interleukin4. PATIENTS: Patients with Crohn's disease, ulcerative colitis, and other malignant and non-malignant conditions undergoing bowel resection. METHODS: The effect of interleukin-4 on lamina propria mononuclear cells from Crohn's disease, ulcerative colitis and control mucosa was assessed on various T-cell functions: interleukin-2-induced cytotoxicity, soluble interleukin-2 receptor and interleukin-2 production, and expression of mRNA for interleukin-2R and interferon-gamma. RESULTS: Cytotoxicity of control and ulcerative colitis cells was markedly decreased by interleukin-4, whereas Crohn's disease cells failed to be inhibited. Addition of interleukin-4 to interleukin-2-stimulated cultures decreased soluble interleukin-2R production significantly less in Crohn's disease and ulcerative colitis than control cells. In the same cultures, residual levels of interleukin-2 were significantly increased in control and ulcerative colitis, but not Crohn's disease cultures. Finally, Crohn's disease cells were significantly more resistant to interleukin-4-mediated inhibition of spontaneous and interleukin-2-induced expression of interleukin-2Ralpha and interferon-gamma mRNA compared to control cells. CONCLUSIONS: The effector function, receptor expression and cytokine production of Crohn's disease mucosal T-cells are resistant to interleukin4-mediated inhibition. Failure to respond to down-regulatory signals may contribute to persistent T-cell activation and chronicity of inflammation in Crohn's disease.     

Familial occurrence of inflammatory bowel disease in celiac disease

BACKGROUND: The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease. AIM: The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS: One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital records. Two hundred twenty-two controls matched for age and sex (111 from the general population and 111 from orthopedic wards) were also interviewed regarding the possible occurrence of IBD in first-degree relatives. The chi2 test was used to evaluate the difference in proportion of familial occurrence of IBD among individuals with celiac disease and controls. RESULTS: Among 600 first-degree relatives of patients with celiac disease, 10 cases of IBD were identified among first-degree relatives (7 cases of ulcerative colitis and 3 cases of Crohn's disease), whereas only 1 case of IBD was identified among the 1,196 first-degree relatives of control patients (p < 0.01). When ulcerative colitis and Crohn's disease were analyzed separately, only the prevalence of ulcerative colitis was statistically significant (p 相似文献   

Seasonal variations in onset of symptoms in Crohn''s disease

BACKGROUND: Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn's disease. AIM.: To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms. PATIENTS AND METHODS: Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets. Statistical analysis: chi-square test, odds ratio (95% confidence interval). RESULTS: Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn's disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring-summer compared to autumn-winter (odds ratio 1.39; 95% confidence interval 1.03-1.87; p<0.03). This variation was observed in Crohn's disease (odds ratio 1.59; 95% confidence interval 1.00-2.51; p<0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86-1.88; p=0.27). CONCLUSIONS: These data indicate that onset of Crohn's disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases.     

Geographic variation in the incidence of and mortality from inflammatory bowel disease

The geographic and temporal variations in mortality from Crohn's disease and ulcerative colitis were investigated. The validity of mortality data as indicators of morbidity was tested by comparing the death rates and incidences among different countries. Death rates from Crohn's disease and ulcerative colitis were high in England, Germany, and the Scandinavian countries, and low in the Mediterranean countries. There was a significant correlation between the incidence and mortality of both diseases among different countries. In addition, the incidence and mortality of Crohn's disease were correlated with those of ulcerative colitis. In countries with a low mortality rate from Crohn's disease, the death rates in men tended to be higher than those in women. In contrast, countries with high death rates from Crohn's disease showed female predominance. No such relationship existed for ulcerative colitis. The overall change in mortality rates during the last 20 to 30 years was characterized by a rise of Crohn's disease and a marked fall of ulcerative colitis. In countries with a high mortality rate from Crohn's disease, the death rates started to fall in recent times. The significant correlations between incidence and mortality show that the death rates from both diseases represent reliable indicators of the morbidity and that the severity of the two diseases is similar in different countries. The marked temporal and geographic variations in both incidence and mortality suggest that environmental factors play an important role in the etiology of both diseases. Supported by grant number So 172/1-1 from the Deutsche Forschungsgemeinschaft.