The Occurrence of Gastritis in Microscopic Colitis and Inflammatory Bowel Disease.

Multiple studies have shown that Helicobacter pylori infection is associated with a lower prevalence of inflammatory bowel disease (IBD).1,2 Besides chronic active gastritis (CAG) resulting from gastric infection with H pylori, pathologists have noticed another form of CAG, which is unrelated to H pylori infection and seems to cluster in patients with IBD.3-5 The aim of the present study was to compare the prevalence of H pylori-negative and H pylori-positive CAG in patients with IBD, and microscopic colitis (MC).

Similar Time Trends of Hodgkin Lymphoma, Multiple Sclerosis, and Inflammatory Bowel Disease.

BACKGROUND: The Epstein-Barr virus (EBV) plays a role in the causation of Hodgkin lymphoma (HL) and multiple sclerosis (MS). A previous study showed that the time trends of mortality from Crohn's disease (CD) and MS shared striking similarities. It was hypothesized that such similarities would also involve the time trends of ulcerative colitis and HL. AIMS: To compare the time trends of CD and UC with those of HL and MS in 6 different countries. METHODS: Using the vital statistics of England, Canada, Netherlands, Scotland, Switzerland, and United States from 1951 to 2020, the time trends of mortality from these 4 diseases were compared. The time-dependent changes of death rates were subjected to a birth-cohort analysis. RESULTS: Similar trends were observed in all 6 countries. UC mortality rose among generations born during the nineteenth century and decreased among all generations born subsequently during the twentieth century. CD mortality was similarly characterized by a birth-cohort pattern with a rise and fall that were shifted by 20-30 years towards more recent generations when compared to UC. The birth-cohort pattern of UC was matched by a similar pattern of HL, whereas the birth-cohort pattern of CD was matched by a similar pattern of MS. CONCLUSIONS: The similarities in the ubiquitous birth-cohort patterns of UC, CD, HL, and MS suggest that these 4 diseases share a common environmental risk factor. Such risk factor may be linked to EBV or its acquisition during an early period of a patient's lifetime.

Cost-utility advantage of interventional endoscopy.

BACKGROUND: Gastroenterologists frequently face the dilemma of how to choose among different management options. AIM: To develop a tool of medical decision analysis that helps choosing between competing management options of interventional endoscopy and surgery. METHODS: Carcinoma-in-situ of the esophagus, large colonic polyps, and ampullary adenoma serve as three examples for disorders being managed by both techniques. A threshold analysis using a decision tree was modeled to compare the costs and utility values associated with managing the three examples. If the expected healing or success rate of interventional endoscopy exceeds a threshold calculated as the ratio of endoscopy costs over surgery costs, endoscopy becomes the preferred management option. A low threshold speaks in favor of endoscopic intervention as initial management strategy. RESULTS: If the decision in favor of surgery is focused exclusively on preventing death from a given disease, surgical intervention may seem to provide the best treatment option. However, interventional endoscopy becomes a viable alternative, if the comparison is based on a broader perspective that includes adverse events and long-term disability, as well as the healthcare costs of both procedures. For carcinoma-in-situ of the esophagus, the threshold for the expected success rate is 24% (range in the sensitivity analysis: 7-29%); for large colonic polyps it is 10% (5-12%), and for duodenal papillary adenoma it is 17% (5-21%). CONCLUSIONS: Even if a management strategy surpasses its alternative with respect to one important outcome parameter, there is often still room for the lesser alternative to be considered as viable option.

Trends of Colonic Neoplasia in US Outpatient Endoscopy Centers.

BACKGROUND: A variety of studies have shown rising trends in the occurrence of colorectal cancer in younger patients as opposed to falling trends among older patients aged 55 years or more. We hypothesized that the time trends of benign colonic precursor lesions would reveal similar patterns. AIMS: The present study was designed to test this hypothesis in a large nationwide sample of the US population undergoing colonoscopy in community-based endoscopy centers. METHODS: The Inform Diagnostics database is an electronic repository of histopathologic records of patients distributed throughout the USA. A cross-sectional study analyzed the detection rates of sessile serrated adenomas (SSA), hyperplastic polyps (HP), tubular adenomas (TA), traditional serrated adenomas (TSA), or adenocarcinomas (colorectal cancer, CRC) in 2,910,174 colonoscopies done 2008-2020. RESULTS: During the 13-year time period, the rate of SSA showed a significant rise, both in patients younger and older than 55 years. HP and TA both showed a significant decline during the same time period. The trends of CRC in the older age group decreased significantly between 2008 (or its peak in 2012) and 2020. The trends of CRC in the younger age group increased significantly between 2008 and its peak in 2017. CONCLUSIONS: The age-specific time trends of benign and malignant colonic neoplasia are characterized by dissimilar temporal patterns. Such dissimilarity could suggest that besides a set of shared risk factors that affect all types of colonic neoplasia alike, there is yet another set of environmental risk factors that specifically influence malignant transformation.

The test characteristics of a biased or ignorant diagnostician.

BACKGROUND: A human diagnostician may harbour a special bias towards favourable positive or negative test results. The aim of the present analysis is to describe in quantitative terms how bias can affect the test characteristics of a human tester. METHODS: Whereas an unbiased tester would give absolute (100%) preference to true positive or true negative test results, and no (0%) preference to any false positive or false negative test results, a biased tester may harbour some preferences towards false positive or false negative tests. Such bias can be phrased in terms of a separate sensitivity-specificity matrix. The bias matrix multiplied with the original test matrix yields the biased test matrix. Similarly, the extent of ignorance by a human tester about the diagnosis is modelled as a separate sensitivity-specificity matrix, which captures the concordance between positive and negative diagnoses made by an ignorant and expert diagnostician. RESULTS: Increasing bias or ignorance result in decreasing test performance with decreasing positive predictive values until the test completely loses its discriminatory power. With more pronounced bias towards false test results, any positive test outcome may even become misinterpreted as predicting the non-existence of a given diagnosis. CONCLUSIONS: The proposed model helps to understand in quantitative terms, how bias and ignorance can alter a diagnostician's interpretation of test outcomes and result in diagnostic errors.

Successful Hepatitis C Birth Cohort Screening and Linkage to Care in a US Community Health System.

CONTEXT: Birth cohort ("baby boomer") screening represents a well-validated strategy for the identification of asymptomatic hepatitis C-infected patients. However, successful linkage of newly diagnosed patients to antiviral therapy has been more difficult to accomplish. OBJECTIVE: To analyze the results of a systemwide birth cohort screening program in a US community health care system. DESIGN: We analyzed the data from an ongoing hepatitis C virus (HCV) screening and treatment program that was established at NorthShore University Health System in 2015. Hepatitis C virus screening by primary care providers was prompted through automated Best Practice and Health Maintenance alerts. Patient visits and screening orders were tracked using a customized HCV dashboard. Virologic, demographic, and treatment data were assessed and compared with those of a cohort of patients with previously established HCV infection. RESULTS: Since program inception, 61 8161 (64.3%) of the entire NorthShore baby boomer population of 96 001 patients have completed HCV antibody testing, and 160 patients (0.26%) were antibody positive. Of 152 antibody-positive patients who underwent HCV RNA testing, 53 (34.2%) were viremic. A total of 39 of 53 patients (73.6%) underwent antiviral therapy and achieved a sustained virologic response. Compared with patients identified through screening, a comparison cohort of patients with previously established HCV had more advanced fibrosis and significantly lower dropout rates. The COVID-19 pandemic was associated with a decrease in the number of outpatient visits of screening-eligible patients and with a reduction in HCV screening rates. CONCLUSION: Our data demonstrate the electronic medical records-assisted systemwide implementation of HCV birth cohort screening and successful linkage to antiviral therapy in a community-based US multihospital system.

Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease.

In a previous study, we found a variety of inverse associations between the occurrence of gastroesophageal reflux disease (GERD) and the occurrence of various forms of inflammatory bowel disease (IBD), as well as microscopic colitis (MC) and its 2 subtypes of lymphocytic and collagenous colitis.1 Two recent studies suggested a 5-fold increase in the occurrence of eosinophilic esophagitis (EoE) among IBD patients.2,3 The aim of the present study was to confirm these positive associations between EoE and IBD.

Sustained and cumulative impact of an electronic medical record-based alert on a hepatitis C birth cohort screening programme.

The study aimed to assess the effect of an electronic medical record-embedded best practice alert (BPA) on HCV age cohort screening in primary care clinics. HCV testing by primary care physicians was monitored prior and subsequent to the implantation of the BPA. Four intervals of 9 months duration were analysed in detail, including a pre-BPA baseline analysis and three annual post-BPA assessments. Pre- and post-BPA orders consistently followed a power law distribution, characterized by small groups of physicians placing the majority of test orders. Significant correlations were present between the numbers of tests orders by each physician, suggesting that 'high' and 'low' screening performances tended to be physician-specific. Testing rates increased markedly in response to the BPA, resulting in completion of screening in 56.8% (50,468 of 88,914%) of the entire age cohort within less than 3 years. In conclusion, HCV age cohort testing by primary care physicians follows a power-law distribution, with high-performing physicians contributing disproportionately to the overall effort. A simple BPA resulted in a sufficient increase in testing to allow testing of the entire target population within a reasonable time frame.

Evaluating key characteristics of ideal colorectal cancer screening modalities: the microsimulation approach.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, tests for the detection of biomarkers in stool, blood, or serum, including the fecal immunochemical test (FIT), ColoGuard, Epi proColon, and PolypDx, have recently been advanced. We aimed to identify the characteristics of theoretic, highly efficient screening tests and calculated the effectiveness and cost effectiveness of available screening tests. METHODS: Using the microsimulation-based colon modeling open-source tool (CMOST), we simulated 142,501 theoretic screening tests with variable assumptions for adenoma and carcinoma sensitivity, specificity, test frequency, and adherence, and we identified highly efficient tests outperforming colonoscopy. For available screening tests, we simulated 10 replicates of a virtual population of 2 million individuals, using epidemiologic characteristics and costs assumptions of the United States. RESULTS: Highly efficient theoretic screening tests were characterized by high sensitivity for advanced adenoma and carcinoma and high patient adherence. All simulated available screening tests were effective at 100% adherence to screening and at expected real-world adherence rates. All tests were cost effective below the threshold of 100,000 U.S. dollars per life year gained. With perfect adherence, FIT was the most effective and cost-efficient intervention, whereas Epi proColon was the most effective at expected real-world adherence rates. In our sensitivity analysis, assumptions for patient adherence had the strongest impact on effectiveness of screening. CONCLUSIONS: Our microsimulation study identified characteristics of highly efficient theoretic screening tests and confirmed the effectiveness and cost-effectiveness of colonoscopy and available urine-, blood-, and stool-based tests. Better patient adherence results in superior effectiveness for CRC prevention in the whole population.

The Meaning of Incidental Goblet Cells at the Gastroesophageal Junction.

BACKGROUND AND AIMS: The causes for the occurrence of goblet cells at the gastroesophageal junction (GEJ-GC) are unknown. The aim of our study was to compare the concurrent histologic changes of the stomach in (1) patients with GEJ-GC, but without Barrett's esophagus (BE) to those in (2) patients with BE and in (3) controls without GEJ-GC or BE. METHODS: We used an electronic database of histopathologic records from 1.3 million individual patients, who underwent esophago-gastro-duodenoscopy (EGD) in 2009-2018. We compared the prevalence of Helicobacter pylori-positive gastritis (HpG), gastric intestinal metaplasia (G-IM), chronic inactive gastritis (CIG), and reactive gastropathy (RG) among the 3 patient groups, using odds ratios and their 95% confidence intervals. RESULTS: Of all EGD patients, 4.0% harbored BE and 2.4% GEJ-GC. The average age of patients with GEJ-GC (60 ± 14) was significantly younger than the age of patients with BE (63 ± 12) and significantly older than the age of controls (55 ± 17). Female subjects were more common among GEJ-GC (54%) than BE (37%), but less common than among controls (63%). The 3 gastric histopathology changes associated with H. pylori were significantly more common in GEJ-GC than BE (for HpG 2.42, 2.29-2.56; for G-IM 1.82, 1.73-1.92; for CIG 1.31, 1.22-1.41). The corresponding differences between GEJ-GC and controls were less striking (for HpG 0.97, 0.93-1.01; for G-IM 1.15, 1.11-1.19; for CIG 0.90, 0.85-0.95). RG was slightly less common in GEJ-GC than BE (0.89, 0.86-0.92) and controls (0.94, 0.91-0.96). CONCLUSIONS: With respect to its demographic and histopathologic features, GEJ-GC likely represents gastric intestinal metaplasia as opposed to BE and should prompt gastric intestinal metaplasia screening and management.

Seasonal Variation of Duodenal Intraepithelial Lymphocytosis.

The increase of intraepithelial lymphocytes in architecturally normal duodenal mucosa is commonly referred to as duodenal intraepithelial lymphocytosis (DIL). The characteristic appearance of DIL corresponds with Marsh grade 1, that is, normal or mild increase in lamina propria inflammation of the duodenal mucosa, with no crypt hyperplasia or villous atrophy.1 Approximately 11% of DIL patients harbor clinical and serologic features suggestive of gluten sensitivity.2 An additional 2% of patients with DIL harbor concomitant microscopic colitis.3Helicobacter pylori gastritis may contribute to another 10%-15% of DIL, which may resolve following eradication of H pylori.4 In the majority of cases with DIL, however, its underlying cause has remained unknown.1 A study of the seasonal variations in the occurrence of DIL may provide additional clues about its yet unknown etiology.

Low Prevalence of Helicobacter pylori-Positive Peptic Ulcers in Private Outpatient Endoscopy Centers in the United States.

OBJECTIVES: During the past decades, the prevalence of gastric and duodenal ulcers, as well as Helicobacter pylori infection, has markedly declined. We hypothesized that the decline in H. pylori prevalence has decreased the fraction of H. pylori-positive gastric and duodenal ulcers. The present study was designed to test this hypothesis in a large US population undergoing esophagogastro-duodenoscopy in community-based endoscopy centers. METHODS: The Inform Diagnostics database is a national electronic repository of histopathologic records of patients distributed throughout the United States. A cross-sectional study among 1,289,641 individual esophagogastro-duodenoscopy patients analyzed the prevalence of peptic ulcers stratified by age, sex, ethnicity, H. pylori status, year of diagnosis, and ulcer type. The joint influence of multiple predictor variables on the occurrence of gastric and duodenal ulcers was analyzed using multivariate logistic regression analysis. RESULTS: Between 2009 and 2018, the general prevalence of H. pylori infection fell significantly from 11% to 9%. This decline was accompanied by a similar decline in the fraction of H. pylori-positive gastric ulcers from 17% to 14% and H. pylori-positive duodenal ulcers from 25% to 21%. Nowadays, only 17% of all patients with ulcer harbor H. pylori. The fraction of H. pylori-positive ulcers was significantly greater in duodenal than in gastric ulcers and in male than in female patients with ulcer. The prevalence of H. pylori was 2.6-fold higher among Hispanics and 3.2-fold higher among East Asians compared with the general population. The H. pylori prevalence fell from 24% to 22% among Hispanics and from 21% to 15% among East Asians. In East Asians and Hispanics, the fraction of H. pylori-positive gastric ulcers was 37% and 35%, respectively. DISCUSSION: H. pylori infection continues to fall in the general population. Nowadays, even among patients with ulcer only a small minority harbors H. pylori infection.

Interaction Between Ethnicity and Helicobacter pylori Infection in the Occurrence of Reflux Disease.

BACKGROUND AND AIMS: Few reports are available to reliably assess the ethnic distribution of Barrett metaplasia and reflux esophagitis. The present study served to analyze the joint influence of Helicobacter pylori infection and patient demographics on the diagnoses of Barrett metaplasia and reflux esophagitis. METHODS: The Inform Diagnostics database is a national electronic repository of histopathologic records of patients distributed throughout the United States. In a case-control study of 52,096 cases with Barrett metaplasia, 189,235 cases with reflux esophagitis, and 152,322 controls without any signs or symptoms suggestive of gastroesophageal reflux disease, we assessed the influence of age, gender, ethnicity, and H. pylori status on occurrence of Barrett metaplasia or reflux esophagitis. RESULTS: Barrett metaplasia was less common among East Asians (with odds ratio, 0.48; 95% confidence interval, 0.44-0.53) and Hispanics (0.60, 0.57-0.63) than other ethnic groups living in the United States. Reflux esophagitis was also less common among East Asians (0.86, 0.82-0.90), but more common among Hispanics (1.18, 1.14-1.21). Both types of esophageal disease were associated with a lower prevalence rates of gastric H. pylori infection than controls, with 0.48, 0.44-0.53 for Barrett metaplasia and 0.60, 0.57-0.63 for reflux esophagitis. The prevalence rates of gastric H. pylori and both esophageal diseases were greater in older than younger and male than female patients in all ethnic groups alike. CONCLUSIONS: Gastric H. pylori infection, ethnicity, gender, and age all influence the occurrence of Barrett metaplasia, and reflux esophagitis.

Upper Gastrointestinal Disease Influences the Occurrence of Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Compromise of the gastric acid barrier may facilitate bacterial invasion of the lower intestinal tract and influence the occurrence of inflammatory bowel disease (IBD). Our study tested the associations between histopathologic changes in the upper and lower gastrointestinal tract in patients undergoing bidirectional endoscopy. METHODS: The Inform Diagnostics database is a national electronic repository of histopathologic records of patients distributed throughout the entire USA. A case-control study among 302,061 patients, of whom 13,943 harbored IBD, evaluated whether the occurrence of Crohn's disease or ulcerative colitis was influenced by the presence of various upper gastrointestinal diagnoses associated with lowered gastric acid output. The influence of individual risk factors on the occurrence of colonic disease was expressed as odds ratios with their 95% confidence intervals. RESULTS: The odds ratio for Crohn's disease being associated with gastric H. pylori was 0.30 (0.24-0.37), with intestinal metaplasia 0.30 (0.24-0.39), with fundic gland polyps 0.42 (0.35-0.50), with gastric hyperplastic polyps 0.35 (0.23-0.51), with Barrett's metaplasia 0.19 (0.14-0.24), and with reflux esophagitis 0.46 (0.42-0.51). The odds ratio for ulcerative colitis being associated with gastric H. pylori was 0.58 (0.50-0.67), with intestinal metaplasia 0.39 (0.32-0.47), with fundic gland polyps 0.61 (0.53-0.71), with gastric hyperplastic polyps 0.64 (0.49-0.84), with Barrett's metaplasia 0.50 (0.43-0.59), and with reflux esophagitis 0.77 (0.71-0.84). CONCLUSIONS: A diminished gastric acid barrier function, as evidenced by various upper gastrointestinal diseases associated with lowered gastric acid output, may exert a protective influence against the development of inflammatory bowel disease.

Prevalence and concordant occurrence of esophageal, gastric, duodenal, and colonic eosinophilia.

Eosinophilic esophagitis, gastritis, duodenitis, and colitis are rare diseases. Few studies have been able to accumulate sufficiently large number of patients to analyze their clinical epidemiology. The aim of the present epidemiologic study was to examine the prevalence and concordant occurrence of gastrointestinal (GI) eosinophilia. Using a database of histopathologic records, a cross-sectional study among 302,061 patients undergoing bidirectional endoscopy evaluated the concordant occurrence of esophageal, gastric, duodenal, and colonic eosinophilia. The prevalence rates (PRs) of GI eosinophilia were expressed per 1,000 study subjects with their 95% Poisson confidence intervals (CIs). The concordant occurrence of various forms of GI eosinophilia was compared to their overall occurrence in the study population by calculating odds ratios (ORs) and their 95% CI. The database contained 3,008 patients with esophageal eosinophilia (PR = 9.96, 9.61-10.32), 366 patients with gastric eosinophilia (1.21, 1.09-1.34), 10 patients with duodenal eosinophilia (0.03, 0.02-0.06), and 124 patients with colonic eosinophilia (0.41, 0.34-0.49). The occurrence of esophageal eosinophilia was associated with an increased occurrence of gastric eosinophilia (OR = 3.58, 2.06-6.23), duodenal (40.22, 12.61-128.31), and colonic eosinophilia (8.12, 4.26-15.49). Similarly, we also found statistically significant associations between gastric eosinophilia and duodenal or colonic eosinophilia, and between duodenal and colonic eosinophilia. In the adult, as in the pediatric population, patients with any type of GI eosinophilia are at an increased risk for simultaneously harboring eosinophilia at multiple sites of their GI tract. With the exception of esophageal eosinophilia, however, other forms of GI eosinophilia are rarely diagnosed.

Associations of Microscopic Colitis With Other Lymphocytic Disorders of the Gastrointestinal Tract.

BACKGROUND & AIMS: Lymphocytic disorders of the upper and lower gastrointestinal tract seem to cluster in patients. We aimed to assess the frequency of comorbid occurrence of lymphocytic disorders in patients with microscopic colitis (MC). METHODS: We collected data from the Miraca Life Sciences Database, a large national electronic repository of histopathologic records of patients throughout the United States. In a population of 228,506 patients who underwent bidirectional endoscopy from January 2008 through July 2016, we studied the comorbid occurrence of celiac disease, duodenal intraepithelial lymphocytosis, lymphocytic gastritis, and lymphocytic esophagitis among 3456 patients with MC. Associations were described in terms of their odds ratios (OR) and 95% CIs. RESULTS: Any type of lymphocytic disorder occurred in 13.7% of patients with MC and 5.9% of patients without MC. The ORs of lymphocytic disorders in patients with MC were: 2.56 (95% CI, 2.32-2.82) for any type of lymphocytic disorder, 3.07 (95% CI, 1.25-7.52) for lymphocytic esophagitis, 15.05 (95% CI, 12.31-18.41) for lymphocytic gastritis, 1.73 (95% CI, 1.53-21.96) for duodenal intraepithelial lymphocytosis, and 6.06 (95% CI, 5.06-7.25) for celiac disease. Comorbidities were more common in patients with lymphocytic than collagenous colitis, with an OR of 1.74 (95% CI, 1.42-2.13). Patients with MC with comorbidities were significantly younger and had a lower proportion of men than patients with MC patients without comorbidities. Diarrhea was the predominant symptoms in all patients MC, irrespective of comorbidities. CONCLUSION: In a retrospective study, we identified lymphocytic disorders of the upper gastrointestinal tract that are significantly more common in patients with than without MC. These associations suggest the existence of an underlying etiology that is common to all lymphocytic disorders and that affects the upper and lower gastrointestinal tract.

Lesions of All Types Exist in Colon Polyps of All Sizes.

OBJECTIVES: Although large polyps are known to harbor more advanced neoplasia than small polyps, the extent of the relationship between size and type is not fully known. The study aim was to establish benchmarks for the prevalence of different histologic polyp types among varying size categories. METHODS: The Miraca Life Sciences Database is an electronic repository of histopathologic patient records from private practices throughout the United States. We extracted the records of 483,998 unique patients who underwent colonoscopy with polypectomy between January 2008 and December 2014. A total of 550,811 polyps were stratified by their endoscopic size measurement. Polyps of each size were further stratified as hyperplastic polyp (HP), tubular adenoma (TA), tubulovillous adenoma (TVA), sessile serrated adenoma/polyp, and adenocarcinoma. RESULTS: Of all 550,811 polyps, 447,343 (81%) were 1-9 mm in size, and 103,517 (19%) were 10 mm or larger. A fraction of 18,591/550,811 polyps (3.4%) harbored histologic features of advanced adenoma, such as TVA, high-grade dysplasia, or cancer. Of these, 4,725/18,591 (25%) occurred in polyps 1-9 mm and 13,868/18,591 (75%) occurred in polyps 10 mm or larger. The fractions of advanced adenoma were 0.6% (0.5-0.6%) in 1-5 mm polyps and 2.1% (2.0-2.2%) in 6-9 mm polyps, as compared to 13.4% (13.2-13.6%) in polyps 10 mm or larger. The frequency of HP significantly decreased with increasing polyp size, whereas the frequency of TA remained largely unaffected by polyp size. CONCLUSIONS: While advanced histopathology was found more frequently in colorectal polyps of larger than smaller size, one quarter of all advanced histopathology existed in polyps of <10 mm.

Similar birth-cohort patterns in Crohn's disease and multiple sclerosis.

BACKGROUND: The etiology of Crohn's disease and multiple sclerosis is unknown. Genetic susceptibility and environmental factors are believed to play a role in both diseases. OBJECTIVES: To compare the long-term time trends of the two diseases and thus gain insight about their etiology. METHODS: We analyzed mortality data of Crohn's disease and multiple sclerosis from Canada, England, Italy, the Netherlands, Switzerland, and the United States during the past 60 years. Age-period-cohort (APC) analyses based on logit models served to disentangle the separate influences of age, period, and cohort effects on the overall time trends. RESULTS: The long-term time trends of Crohn's disease and multiple sclerosis have been shaped by strikingly similar birth-cohort patterns. In both diseases alike, mortality increased in all generations born prior to 1910. It peaked among generations born between 1910 and 1930 and then declined in all subsequent generations. Similar birth-cohort patterns of Crohn's disease and multiple sclerosis were found in each country analyzed separately. CONCLUSION: The birth-cohort patterns indicate that the development of Crohn's disease and multiple sclerosis is influenced by exposure to environmental risk factors during an early period of life. These environmental risk factors may be similar or even identical in Crohn's disease and multiple sclerosis.