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Antineutrophil cytoplasmic autoantibodies in autoimmune liver and inflammatory bowel diseases.

Perinuclear antineutrophil cytoplasmic autoantibodies have been described in inflammatory bowel diseases and in primary sclerosing cholangitis. Because the data concerning their occurrence are conflicting, we have used indirect immunofluorescence on ethanol-fixed neutrophils to test the sera from a large population of 382 patients with various liver and digestive diseases: in particular, from 27 patients with primary sclerosing cholangitis, 105 patients with autoimmune chronic active hepatitis, 30 patients with primary biliary cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative colitis and 15% in Crohn's disease. They would not be helpful in the differential diagnosis between these two inflammatory bowel diseases. Within the group of autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies were detected in 44% of sera from patients with primary sclerosing cholangitis and in 36% of sera from patients with type I autoimmune active hepatitis, but not in primary biliary cirrhosis. When primary sclerosing cholangitis was associated with an inflammatory bowel disease, the prevalence of these autoantibodies was 60%. They were 88% specific for primary sclerosing cholangitis and 86% specific for type I autoimmune active hepatitis. Despite their moderate sensitivity and specificity in primary sclerosing cholangitis, they remain the only serologic marker of this autoimmune liver disease. Moreover, they turned out to be a more sensitive marker for inflammatory bowel disease with associated primary sclerosing cholangitis.

Adolescent↗

The prevalence of long bone fractures in pediatric inflammatory bowel disease.

INTRODUCTION: The association of inflammatory bowel disease (IBD) with decreased bone mineral density is well recognized. In the adult population, up to 50% of IBD patients are reported to have osteopenia, correlating with an increase in the incidence of fractures as compared with controls. The aim of this study was to determine the prevalence of fractures in a pediatric population with IBD as compared with healthy sibling controls (SC). PATIENTS AND METHODS: The families of 209 patients with IBD were sent a questionnaire asking them to compare their children with IBD to a healthy sibling (non-IBD). RESULTS: Surveys were returned by 132 of the 209 families (63%). The sample characteristics of this sample closely resembled the overall clinic population for age (mean 14.3 vs 14.7 years), gender (53% vs 59% male) and diagnosis (58.1 vs 57.8 Crohn disease). Completed surveys described 263 children. Of the 132 with IBD 73 (55%) had Crohn disease, 52 (39%) had ulcerative colitis and 7 (6%) had indeterminate colitis. There were 76/132 males (age range, 4-18 years) with IBD and 64/131 males (age range, 1-26 years) in the sibling controls. Mean ages of the IBD sample 14.3 +/-.3 was compared with 13.9 +/- in SC. Of the total group, 73/263 (28%) reported ever having a fracture, 44 (60%) were siblings (SC), and 29 (40%) had IBD. Of the 29 children with IBD, 17 (59%) reported having a fracture after diagnosis including 2 who had fractures both before and after diagnosis. The total number of fractures reported was 96 (55 SC:41 IBD). CONCLUSION: In this survey, we found no statistically significant difference in the prevalence of fracture in IBD patients compared with their normal siblings.

Adolescent↗

Assessment of hypothalamic-pituitary-adrenal axis function after corticosteroid therapy in inflammatory bowel disease.

OBJECTIVES: In patients with inflammatory bowel disease (IBD), little is known about the effect of long term corticosteroid therapy (CT) on the hypothalamic-pituitary-adrenal (HPA) axis function. Our aim was to assess HPA axis function in IBD, before the end of CT, during the tapering phase. METHODS: HPA axis function was assessed with cortisol (ng/ml) measurement before (T0) (normal > 100) and 60 min (normal > 210) after 0.25 mg tetracosactide (Synacthen immédiat) injection (T60) in 55 consecutive cases of IBD attacks. Abnormal response was defined as a T60 <210. The attacks were separated into two groups according to the result of the Synacthen test (ST). RESULTS: In all, 36 of 55 ST were abnormal. The time for recovery normal HPA axis function was 7.2+/-1.3 months. Duration of disease since onset, past history of surgical or immunosuppressive treatment, severity and extension of the attack, need for surgical or immunosuppressive treatment, total cumulative and mean daily corticosteroid dose, total duration of CT, and steroid dose at the time of ST were not significantly different in the two groups. In multivariate analysis a past history of CT was predictive of abnormal ST (OR = 8.4, 95% CI = 2.2-31.5, p = 0.0009). Among patients with a past history of CT, the time (months) elapsed between the last course of CT was significantly longer in those with normal ST than in those with abnormal ST (45.5+/-13.5 vs 15.4+/-6.0; p = 0.02), and in multivariate analysis a duration free of CT < 15 months was predictive of abnormal ST (OR = 15.00, CI = 1.23-183.00, p = 0.03). CONCLUSIONS: In all, 65% of the ST were abnormal. These results suggest that ST should be performed before corticosteroid withdrawal, especially in patients with recent past history of CT.

Adult↗

Etiology and pathophysiology of inflammatory bowel disease--environmental factors.

Environmental factors play an important role in the pathophysiology of inflammatory bowel disease. There is a strong and consistent association between smoking and Crohn's disease, and between nonsmoking and ulcerative colitis. Despite extensive research, the exact pathophysiological mechanisms for these associations remain unclear. In spite of this, some clinical trials with nicotine-patches showed beneficial effects for the treatment of ulcerative colitis. Associations of Crohn's disease and ulcerative colitis with other environmental factors are weaker like the association with use of oral contraceptives or those less well investigated such as the association with childhood hygiene. Most studies suggesting a potential pathogenetic role of Mycobacterium paratuberculosis or an effect of tuberculostatic therapy in Crohn's disease could not be reproduced by others. Perinatal or childhood infections by viruses like measles are heavily debated, but not proven to be causal for inflammatory bowel disease. Coagulation disorders have been described as protecting from inflammatory bowel disease, suggesting hypercoagulability to be a pathogenetic factor. Some studies described that appendectomy may prevent the onset of ulcerative colitis in man and mice. Other environmental factors such as hydrogen sulfide, tonsillectomy, diet, blood transfusions, and Listeria also require confirmation. There are, however, convincing data from genetic animal models and twin studies that environmental factors as the intestinal bacterial flora interact with susceptible hosts to cause inflammatory bowel disease. Inflammatory bowel diseases have multifactorial etiologies, which require a differentiated approach for treatment and prevention.

Animals↗

The relationship between inflammatory bowel disease and socioeconomic variables.

OBJECTIVES: Inflammatory bowel diseases (IBD) are chronic diseases associated with considerable morbidity. This morbidity may have an impact on the ability of patients to remain employed, on their marital status, and on their ability to complete a course of higher education. It has long been held that IBD patients are of a higher socioeconomic status and more educated than the general population. Our aim was to determine the relationship between IBD and employment, income, disability, education, and marital status in two population-based data sets based in the province of Manitoba, Canada. METHODS: Two studies are reported here. In study A, we surveyed persons with IBD, using the population-based University of Manitoba IBD Database, created in 1995-1996. We compared these IBD patients to the general population with respect to employment, education, and marital status using data from the 1996 National Population Health Survey. IBD patients were queried as to their socioeconomic status as of the time of diagnosis and also at the time of the survey (1995-1996). In study B, we used a database that linked health care and census variables to determine differences in employment, income, occupation, and marital status among individuals who met the administrative definition of IBD (created in forming the University of Manitoba IBD Database, based on ICD-9-CM codes 555 for Crohn's disease and 556 for ulcerative colitis) compared with the rest of working-age population. RESULTS: In study A we found that, compared with the general population, patients with IBD were more likely to be unemployed. Crohn's disease appeared to affect employment more than ulcerative colitis. IBD patients, however, had a low rate of reporting themselves as disabled (1.3%). Among those married when diagnosed with IBD, approximately 10% of men and up to 20% of women were no longer married 5 yr later. More patients with IBD were married in 1995 compared with the general population; however, more were also divorced. Fewer patients with IBD achieved postsecondary education. In study B, we found that individuals with IBD were twice as likely to be out of the labor force as were controls. Sedentary occupations were twice as likely to be associated with IBD. The income, education level, and marital status of IBD patients were not significantly different from those of controls. CONCLUSIONS: Individuals with IBD at some time in the course of their illness are more likely not to be working than are those in the general population. Based on employment status and job classification, as well as income and education, IBD patients are not of a higher socioeconomic status as previously reported. IBD patients are at least as likely as the general population to be married.

Adolescent↗

Basic coating polymers for the colon-specific drug delivery in inflammatory bowel disease.

During acute attacks of inflammatory bowel disease, the luminal pH of the colon decreases significantly. This drop in pH can be exploited by developing coated dosage forms with acid-soluble coating polymers to achieve topical drug delivery to the colon. Two batches of minitablets, a conventional and a swellable formulation, were prepared by direct compression and coated with different amounts of either Eudragit E or AEA in a small coating pan. The release of the model drug dexamethasone from the coated tablets was measured spectrophotometrically at pH 2.0, 4.0, 5.0, and 6.8 and different stirring rates (100-200 rpm) to simulate the influence of pH and hydrodynamic stress on drug release. In general, lag times of drug release, determined as the time points of a 5% drug release, were longer with AEA-coated cores compared to those coated with Eudragit E, resulting from a lower polymer dissolution rate and water permeability of this film. In low pH media, drug release was dependent on the stirring rate because the onset of drug release is determined by the time required for dissolution of the basic polymer films. At pH 6.8, lag times from nonswelling tablets coated with Eudragit E, for which drug release only begins after complete erosion of the polymer film, are not significantly affected by hydrodynamic stress. Drug release from AEA-coated cores is determined by the slow drug diffusion through the polymer film. Lag times from tablets with swelling properties, for which drug release is induced by disruption of the basic polymer films due to water penetration and subsequent core swelling, are not significantly affected by hydrodynamic stress. Additional coating layers such as an intermediate hydroxypropylcellulose (HPC) layer and an enteric outer layer do not influence the lag times of drug release, nor does a 2-hr pretreatment of the entire dosage form in acidic media.

Anti-Inflammatory Agents↗

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies in patients with inflammatory bowel disease.

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies (x-, c- and pANCA, respectively) are associated with a variety of inflammatory diseases, including inflammatory bowel disease (IBD). Anti-neutrophil cytoplasmic antibodies are more common in patients with ulcerative colitis (UC) than in patients with Crohn's disease (CD). Most publications only refer to p- and cANCA in relation to IBD. We have prospectively evaluated the reactivity of sera from 58 patients with IBD and 10 healthy controls against human neutrophils with emphasis on the distinction of the ANCA types. The sera were incubated with ethanol- and formaldehyde-fixed granulocytes to differentiate between c-, p- and xANCA. The results showed that 10 of 24 patients with UC were positive for ANCA, whereas only one of 34 patients with CD was ANCA positive. These results correspond to a sensitivity of 42%, a specificity of 97%, a negative predictive value of 91% and a positive predictive value of 75% in UC. Of the 11 ANCA-positive sera, two showed a cytoplasmic staining pattern, three showed a perinuclear and six an atypical staining pattern. The disease activity was not correlated to either the ANCA titre or to the presence of ANCA in the serum. In conclusion, ANCA are of limited value in differentiating between UC and CD. Because the majority of ANCA in patients with IBD are xANCA, these ANCA should be explored by not only incubating on ethanol-fixed granulocytes, but also on formaldehyde-fixed granulocytes.

Adolescent↗

Risk factors for thromboembolic complications in inflammatory bowel disease: the role of hyperhomocysteinaemia.

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolic events. Aim of this study was to examine the relationship of hyperhomocysteinemia and thrombosis in IBD patients and to assess the role of this factor in addition to other known prothrombotic abnormalities. IBD patients with a history of thrombosis (n = 22) and sex-, age-, and diagnosis-matched IBD controls (n = 23) were studied. Homocysteine (tHcy) was assessed before and after methionine loading. Plasma levels of protein C, protein S, antithrombin III, and fibrinogen and the presence of anticardiolipin and antiphospholipid antibodies were determined and genetic testing for factor V Leiden and the prothrombin gene mutation was performed. Results showed that fasting homocysteine levels in IBD patients with a history of arterial or venous thrombosis tended to be higher than in IBD controls, although not significantly. The increase in homocysteine levels after methionine loading was significantly higher in IBD patients in the arterial thrombosis group than in IBD controls (40.9 +/- 17.7 vs. 27.2 +/- 9.9 microM; P < 0.05). Among the other prothrombotic factors, only factor V Leiden was significantly associated with a history of venous thrombosis (20 vs. 0%). At least one risk factor was found in 64% of the IBD patients with previous thromboembolic complications. We conclude that there is an association between hyperhomocysteinemia and a history of arterial thrombosis in IBD patients. We confirm the high prevalence of factor V Leiden in IBD patients with a history of venous thrombosis. In the majority of IBD patients with previous thromboembolic complications, at least one prothrombotic risk factor is detected.

Adult↗

Endoscopic factors in the diagnosis of colorectal dysplasia in chronic inflammatory bowel disease.

BACKGROUND: Surveillance colonoscopy in inflammatory bowel diseases (IBDs) is advocated for early diagnosis of neoplasia but is imperfect because some patients develop cancer despite surveillance. We sought to determine if any endoscopic factors during surveillance colonoscopy were associated with the diagnosis of colorectal dysplasia before the development of cancer. METHODS: We reviewed the Mayo Clinic endoscopic database and medical records of patients with IBD who underwent surveillance colonoscopy between January 2002 and November 2003. Associations were sought between endoscopic factors and the diagnosis of dysplasia. Among 635 IBD patients, 24 (3.8%) had flat dysplasia and 12 (1.9%) had IBD-related polypoid dysplasia. In 28 patients (4.4%), sporadic tubular adenoma was identified. Colonoscopies in which flat dysplasia was identified varied in duration from 7 to 81 minutes (median, 24.5 min) compared with 3 to 70 minutes (median, 22 min) for those in which dysplasia was not found. RESULTS: Using logistic regression analysis, we found that every additional minute in total colonoscopy time increased the flat dysplasia diagnosis rate by 3.5% (P = 0.0157). There was a significant correlation between median surveillance colonoscopy duration per endoscopist and flat dysplasia diagnosis rate (P = 0.0066). The number of biopsies taken during the procedures with flat dysplasia ranged from 6 to 36 (median, 28) compared with 2 to 54 (median, 25) in those without flat dysplasia. There was no significant effect of biopsy number of dysplasia diagnosis. CONCLUSIONS: Our results show that the practice of surveillance colonoscopy varies greatly among endoscopists, and longer procedure duration is significantly associated with the likelihood of dysplasia diagnosis.

Adult↗

Decreased suppressor cell activity in inflammatory bowel disease.

Studies were performed on eleven patients with inflammatory bowel disease to determine if there was an alteration in concanavalin A (Con A) induced suppressor cell activity. Similar investigations were also performed on twenty-one control subjects and five patients with other inflammatory conditions. Supressor cells were generated by pre-incubation of peripheral blood mononuclear cells with a mitogenic concentration of Con A, followed by treatment with mitomycin C and alpha-methyl mannoside. Under these conditions, cells obtained from normal individuals are then capable of suppressing the Con A-stimulated blast transformation responses of fresh allogeneic lymphocytes in new cultures. We found that in twenty out of twenty-one control subjects, and all five patients with other inflammatory disorders, Con A-stimulated suppressor cell activity was demonstrable. Four patients with inflammatory bowel disease, whose disease was mildly active or was in clinical remission, had elicitable suppressor cell activity which fell within the normal range. In contrast, suppressor cell activity was markedly diminished or absent in seven patients with severe and active inflammatory bowel disease. These studies suggest that an alternation in Con A-stimulated suppressor cells exists in patients with active inflammatory bowel disease, which may contribute, in part, to the persistent inflammation in the gastrointestinal tract.

Adolescent↗

Inflammatory bowel disease in pregnancy.

This article provides the current state of knowledge on the interrelations between ulcerative colitis and Crohn's disease and pregnancy and its multiple concerns, including inheriting inflammatory bowel disease, fertility, influence of inflammatory bowel disease activity on pregnancy and vice versa, the safety of drug therapy, and risk factors. The author provides some conclusions and his recommendations.

Colitis, Ulcerative↗

[Good response to colchicine in amyloidosis secondary to inflammatory bowel disease].

Acquired systemic amyloidosis may develop during the course of a number of chronic inflammatory diseases, including inflammatory bowel disease. Amyloidosis, although rare, is life-threatening, especially when it involves the kidneys. It is important to recognize this complication, especially since colchicine has been proposed as a possible treatment.We present a 25-year-old female diagnosed at the age of 13 years with Crohn's disease with involvement of the terminal ileum and right colon. Surgery was performed because of inflammatory activity unresponsive to corticosteroid and immunosuppressive drugs. She subsequently presented nephrotic syndrome due to secondary amyloidosis, which responded well to colchicine treatment.

Adult↗

Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease.

BACKGROUND: Heparin therapy may be effective in steroid resistant inflammatory bowel disease. AIM: A randomized pilot study, to compare unfractionated heparin as a first-line therapy with corticosteroids in colonic inflammatory bowel disease. METHODS: Twenty patients with severe inflammatory bowel disease (ulcerative colitis, n=17; Crohn's colitis, n=3) were randomized to either intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks (n=8), or high-dose intravenous hydrocortisone for 5 days followed by oral prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5 days, non-responders in each treatment group were commenced on combination therapy. Response to therapy was monitored by: clinical disease activity (ulcerative colitis: Truelove and Witt Index; Crohn's colitis: Harvey and Bradshaw Index), stool frequency, serum C-reactive protein and alpha1 acid glycoprotein, endoscopic and histopathological grading. RESULTS: The response rates were similar in both treatment groups: clinical activity index (heparin vs. steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both treatments were well-tolerated with no serious adverse events. CONCLUSION: Heparin as a first line therapy is as effective as corticosteroids in the treatment of colonic inflammatory bowel disease. Large multicentre randomized comparative studies are required to determine the role of heparin in the management of inflammatory bowel disease.

Administration, Oral↗

Nutritional considerations and management of the child with inflammatory bowel disease.

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the bowel often associated with significant malnutrition, particularly in children because of increased nutrient demands due to growth. We discuss the increasingly prominent role of nutritional support in inflammatory bowel disease (IBD). Issues that are addressed include the etiology of malnutrition in IBD, assessment and monitoring of patient nutritional status and the use of nutrition in the management of growth failure and as primary medical therapy.

Child↗

Helicobacter pylori-positive gastritis in pediatric patients with chronic inflammatory bowel disease.

BACKGROUND: Gastritis is a common finding in patients with inflammatory bowel disease. However, the association of gastritis with Helicobacter pylori is unclear in these patients. METHODS: The prevalence of antibodies for H. pylori in serum was determined in 47 pediatric patients with inflammatory bowel disease (19 with Crohn's disease, 21 with ulcerative colitis, and 7 with unclassified disease). H. pylori antibodies of the IgG and IgA classes were measured by enzyme immunoassay in 24 patients at the time of diagnosis of inflammatory bowel disease and in 23 more patients during the follow-up of inflammatory bowel disease (mean follow-up, 3.5 years; range 1-10 years). Esophagogastroduodenoscopy was performed on 40 patients during the examination for inflammatory bowel disease. RESULTS: In contrast to earlier findings, no patient was determined to be positive for H. pylori, either in serologic or histologic examination. This negative finding was unexpected, because it is known that approximately 10% of asymptomatic Finnish children have antibodies for H. pylori in serum and approximately 10% of analyses of specimens obtained in gastric antral biopsies obtained at the Hospital for Children and Adolescents, Helsinki, Finland, are positive for H. pylori. CONCLUSIONS: Permanent colonization of the stomach with H. pylori is unusual in children with inflammatory bowel disease.

Adolescent↗

Apolipoprotein A-IV is an independent predictor of disease activity in patients with inflammatory bowel disease.

BACKGROUND: ApoA-IV, an apolipoprotein (apo) with antioxidant, antiatherogenic, and antiinflammatory properties, was recently demonstrated to inhibit dextran sulfate sodium (DSS)-induced experimental colitis in mice. We therefore hypothesized that apoA-IV may be associated with disease activity in patients with inflammatory bowel disease (IBD). METHODS: We addressed this question by testing for associations between apoA-IV genotypes, apoA-IV plasma levels, inflammatory parameters, and clinical disease activity in 206 patients with Crohn's disease (CD), 95 subjects with ulcerative colitis (UC), and 157 healthy controls. RESULTS: In CD patients, apoA-IV plasma levels were inversely associated with C-reactive protein (CRP) (P = 0.005) and disease activity (P = 0.01) in univariate analysis. In multiple logistic regression analysis, apoA-IV levels were identified as an independent predictor of elevated CRP (odds ratio [OR] 0.956, 95% confidence interval [CI]: 0.916-0.998, P = 0.04) and active disease (OR 0.957, 95% CI: 0.918-0.998, P = 0.04). In UC patients the apoA-IV gene variant 360 His (P = 0.03) but not apoA-IV levels (P = 0.15) were associated with increased disease activity in univariate analysis. This association, however, was lost in multiple logistic regression analysis (OR 3.435, 95% CI 0.995-11.853, P = 0.05). CONCLUSIONS: To our knowledge, this is the first study to demonstrate an association of apoA-IV with disease activity in patients with CD. Further studies are needed to define the relationship of apoA-IV to IBD.

Adult↗

[Assessment of usefulness of anti-Saccharomyces cerevisiae and anti-neutrophil cytoplasmic antibodies in patients with unspecific inflammatory bowel diseases].

UNLABELLED: Ulcerative colitis (UC) and Crohn's disease (CD) are the nonspecific inflammatory bowel diseases with unknown etiology. Existing diagnostic methods are in many cases insufficient for proper diagnosis and choice of treatment method. In 10% cases of inflammatory bowel disease indeterminate colitis (IC) is described. It includes cases with diverse clinical manifestations, range and histopathological picture. New methods to distinguish inflammatory bowel diseases, chose proper treatment and monitor their activity are searched. Anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmatic antibodies (pANCA) seem to be a new markers used in this end. OBJECTIVE: Comparison of ASCA and pANCA appearance in CD and UC searching of correlation between serum levels of antibodies, activity and clinical picture of disease and appearance of ASCA and pANCA in IC. MATERIAL AND METHODS: We examined 63 patients with UC aged 24 to 74 (30 men and 33 women), 14 patients with CD aged 27 to 64 (10 men and 4 women) and 11 patients with IC aged 21 to 53 (4 men and 7 women). Mean duration time of diseases respectively for UC, CD and IC was 7.9 (from 1.0 to 32), 9 (from 1 to 20) and 3.04 (0.5 to 7) years. Diagnosis in specific clinical picture was established with endoscopic and histopathologic examination. Disease activity was described according to Rachmilewitz scale in UC and in CD according to Crohn's disease activity index (CDAI). Control group consisted of 24 healthy men. Examination of pANCA, IgA and IgG ACSA was performed with ELISA kits respectively by Congent Diagnostics and Genesis Diagnostic. RESULTS: There were 39 of UC patients and of CD patients with active disease according to Rachmilewitz scale (above 3 points) and CDAI. We observed statistically more often pANCA in patients with UC (58%; n=31) than in patients with CD (28%; n=4) (p<0.05). Both IgA and IgG ACSCA occurred more often in patients with CD (57%; n=8) than in patients with UC (24%; n=15) (p<0.05). There were no significant differences between antibodies according to duration time, activity, location and treatment method of diseases. Obtained results besides the help with understanding of pathologic mechanisms, indicate for use of antibodies as an diagnostic tool in inflammatory bowel diseases.

Adult↗

Is there clustering of inflammatory bowel disease at birth?

Evidence points to possible cohort effects in inflammatory bowel disease, the possible role of perinatal infection as a risk factor for inflammatory bowel disease, and the occurrence of clusters of Crohn's disease. This evidence suggests the value of searching for birth date clustering among cases of inflammatory bowel disease. The authors looked for clustering by birth date and maternal residence at birth in a population-based series of 845 Crohn's disease patients and 1,330 ulcerative colitis patients born from 1924 through 1957 and diagnosed in the Uppsala Health Care Region, Sweden, until the end of 1983. Over this period, 43% of persons with Crohn's disease had been born within 6 days of another case, compared with 36% of controls simulated to account for monthly variation in births (p = 0.0002). The number of pairs of inflammatory bowel disease cases whose births occurred in the same county (close in space) and whose birth dates were also close in time was statistically significantly greater than expected for most birth dates 23-57 days apart. Results after 1944, when ascertainment was more complete, generally corroborate these findings and suggest some seasonality in the birth dates of ulcerative colitis cases. Results from the entire study period and after 1944 thus provide evidence for clustering by birth (including seasonality) among Crohn's disease cases and also, to a lesser extent, among ulcerative colitis cases.

Causality↗