Edward V. Loftus

Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohns disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Risk Factors for Opportunistic Infections in Patients With Inflammatory Bowel Disease

BACKGROUND & AIMS We sought to identify and quantify the clinical factors that were associated with opportunistic infections in inflammatory bowel disease patients. METHODS We identified 100 consecutive IBD patients with opportunistic infections. For each case, 2 matched IBD patients who did not have a history of opportunistic infection were selected as controls. Conditional logistic regression was used to assess associations between putative risk factors and opportunistic infections, presented as odds ratios (OR) and 95% confidence intervals (CIs). RESULTS In univariate analysis, use of corticosteroids (OR, 3.4; 95% CI, 1.8-6.2), azathioprine/6-mercaptopurine (OR, 3.1; 95% CI, 1.7-5.5), and infliximab (OR, 4.4; 95% CI, 1.2-17.1) were associated individually with significantly increased odds for opportunistic infection. Multivariate analysis indicated that use of any one of these drugs yielded an OR of 2.9 (95% CI, 1.5-5.3), whereas use of 2 or 3 of these drugs yielded an OR of 14.5 (95% CI, 4.9-43) for opportunistic infection. The relative risk of opportunistic infection was greatest in IBD patients seen at older than 50 years of age (OR, 3.0; 95% CI, 1.2-7.2, relative to those 24 years or younger). No patient died from opportunistic infection. CONCLUSIONS Immunosuppressive medications, especially when used in combination, and older age are associated with increased risk of opportunistic infections. The absolute risk of opportunistic infection in IBD patients remains to be determined, as does any potential benefit of any preventive strategy.

Crohn's disease in Olmsted County, Minnesota, 1940–1993: Incidence, prevalence, and survival

BACKGROUND & AIMS Many centers worldwide have reported an increased incidence of Crohns disease, but population-based data in North America are sparse. We studied the incidence and prevalence of Crohns disease in Olmsted County, Minnesota, and examined temporal trends in incidence and survival. METHODS Residents diagnosed with Crohns disease between 1970 and 1993 were incidence cases, and residents with Crohns disease who were alive on January 1, 1991, were prevalence cases. Cases from previous studies were reconfirmed. Rates were adjusted using 1990 U.S. Census figures for whites. Incidence trends were evaluated with a Poisson regression model. Survival from diagnosis was compared with that expected for U.S. north-central whites. RESULTS Between 1940 and 1993, 225 incidence cases were identified, for an adjusted incidence rate of 5.8 per 100,000 person-years. On January 1, 1991, there were 145 residents with Crohns disease, an adjusted prevalence rate of 133 per 100,000, 46% higher than that seen in 1980. Incidence rates before 1964 were significantly lower than those of 1989-1993. Observed survival was less than expected (P = 0.007). CONCLUSIONS The incidence of Crohns disease has stabilized since the 1970s at a rate higher than that seen previously. Prevalence has increased by 46% since 1980. Overall survival is slightly decreased.

Update on the incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000.

Background We previously reported that the prevalence of Crohns disease (CD) and ulcerative colitis (UC) in Olmsted County, Minnesota, had risen significantly between 1940 and 1993. We sought to update the incidence and prevalence of these conditions in our region through 2000. Methods The Rochester Epidemiology Project allows population‐based studies of disease in county residents. CD and UC were defined by previously used criteria. County residents newly diagnosed between 1990 and 2000 were identified as incidence cases, and persons with these conditions alive and residing in the county on January 1, 2001, were identified as prevalence cases. All rates were adjusted to 2000 US Census figures for whites. Results In 1990–2000 the adjusted annual incidence rates for UC and CD were 8.8 cases per 100,000 (95% confidence interval [CI], 7.2–10.5) and 7.9 per 100,000 (95% CI, 6.3–9.5), respectively, not significantly different from rates observed in 1970–1979. On January 1, 2001, there were 220 residents with CD, for an adjusted prevalence of 174 per 100,000 (95% CI, 151–197), and 269 residents with UC, for an adjusted prevalence of 214 per 100,000 (95% CI, 188–240). Conclusion Although incidence rates of CD and UC increased after 1940, they have remained stable over the past 30 years. Since 1991 the prevalence of UC decreased by 7%, and the prevalence of CD increased about 31%. Extrapolating these figures to US Census data, there were ≈1.1 million people with inflammatory bowel disease in the US in 2000. (Inflamm Bowel Dis 2007)

Epidemiology of Inflammatory Bowel Disease

The incidence of IBD has either continued to increase or has stabilized at a high rate in most developed countries, whereas the incidence continues to rise in regions where IBD had been less common. The prevalence has continued to increase as a result of a combination of previously rising incidence and improved survival. Regardless of the exact prevalence, the burden of disease in North America and Europe is significant. Studying the patterns of geographic variation and age and gender distribution may yield important clues to the cause of IBD.

The Natural History of Adult Crohn's Disease in Population-Based Cohorts

OBJECTIVES:Natural history studies provide invaluable data on the disease course. First, they help define the end points for clinical trials that are designed to test drugs for the end point of disease modification in chronic disabling diseases. Natural history studies can also help to identify subsets of patients in whom the disease prognosis can be stratified according to clinical features. This comprehensive review summarizes our current knowledge of the natural history of Crohns disease in adults as reported in population-based studies that include long-term follow-up results.METHODS:We conducted a literature search of English and non-English language publications listed in the electronic databases of MEDLINE (source PUBMED, 1935 to December 2008).RESULTS:One-third of the patients had ileitis, colitis, or ileocolitis at the time of diagnosis. Disease location remained broadly stable over time. Up to one-third of the patients had evidence of a stricturing or penetrating intestinal complication at diagnosis, and half of all patients had experienced an intestinal complication within 20 years after diagnosis. Ten percent of the patients had prolonged clinical remission. Steroid dependency occurred in one-third of the patients, and surgery was required in one-third after initiation of steroid therapy. The annual incidence of hospitalizations was 20%. Half of the patients required surgery within 10 years after diagnosis. The risk of postoperative recurrence was 44–55% after 10 years.CONCLUSIONS:Crohns disease is a disabling condition over time. The impact of changing treatment paradigms with increased use of immunosuppressants and biological agents on its natural history is poorly known.

PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis

Background: Inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD) may have a high prevalence of rectal sparing, backwash ileitis, and colorectal neoplasia. Aims: To describe the clinical features and outcomes of PSC-IBD and compare these to a group of chronic ulcerative colitis (CUC) patients. Methods: The medical records of all patients with PSC-IBD evaluated at the Mayo Clinic Rochester between 1987 and 1992 were abstracted for information on endoscopic and histological features, colorectal neoplasia, surgery, and other clinical outcomes. Patients referred for colorectal neoplasia and those who did not undergo colonoscopy with biopsies were excluded. A control group of CUC patients matched for sex, duration of IBD at first clinic visit, and calendar year of first clinic visit was identified, and similar information was abstracted. Results: Seventy one PSC-IBD patients and 142 CUC patients without PSC were identified. Rectal sparing and backwash ileitis were more common in the PSC-IBD group (52% and 51%, respectively) than in controls (6% and 7%, respectively). Overall, colorectal neoplasia developed in 18 cases and 15 controls, including 11 cancers (seven cases and four controls). An increased risk of colorectal neoplasia or death was not detected in a matched analysis. Although the cumulative incidence of colorectal neoplasia was higher in cases (33%) than in controls (13%) at five years, this was of borderline statistical significance (p = 0.054, unmatched log rank test). Overall survival from first clinic visit was significantly worse among cases (79% v 97%) at five years (p<0.001, unmatched log rank test). Conclusion: PSC-IBD is frequently characterised by rectal sparing and backwash ileitis. Colorectal neoplasia develops in a substantial fraction and overall survival is worse. PSC-IBD may represent a distinct IBD phenotype.

Correlation of C-Reactive Protein With Clinical, Endoscopic, Histologic, and Radiographic Activity in Inflammatory Bowel Disease

Introduction: We sought to examine the relationship between C‐reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). Methods: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow‐through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohns disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. Results: One‐hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate‐severe clinical activity (OR, 4.5; 95% CI, 1.1‐18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4‐8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1‐104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. Conclusions: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.

Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival

BACKGROUND There is significant geographic variation in the reported incidence of ulcerative colitis. AIMS To update the incidence and prevalence of ulcerative colitis in Olmsted County, Minnesota, examine temporal trends, and determine overall survival. PATIENTS All Olmsted County residents diagnosed with ulcerative colitis between 1940 and 1993 (incidence cases), and all residents with ulcerative colitis alive on 1 January 1991 (prevalence cases). METHODS Incidence and prevalence rates were adjusted using 1990 US census figures for whites. The effects of age, sex, and calendar year on incidence rates were evaluated using Poisson regression. Survival from diagnosis was compared with that expected for US north-central whites. RESULTS Between 1940 and 1993, 278 incidence cases were identified, for an adjusted incidence rate of 7.6 cases per 100 000 person years (95% confidence interval (CI), 6.7 to 8.5). On 1 January 1991, there were 218 residents with definite or probable ulcerative colitis, for an adjusted prevalence rate of 229 cases per 100 000 (95% CI, 198 to 260). Increased incidence rates were associated with later calendar years (p<0.002), younger age (p<0.0001), urban residence (p<0.0001), and male sex (p<0.003). Overall survival was similar to that expected (p>0.2). CONCLUSIONS The overall incidence rate of ulcerative colitis in Olmsted County increased until the 1970s, and remained stable thereafter. Incidence rates among men and urban residents were significantly higher. The prevalence rate in Rochester in 1991 was 19% higher than that in 1980. Overall survival was similar to that of the general population.

The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: a systematic review.

To quantify, through systematic review, the epidemiology and natural history of Crohn’s disease in North America.