Incidence rates and disease course of paediatric inflammatory bowel diseases in Western Hungary between 1977 and 2011.

BACKGROUND: Limited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011. METHODS: 187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort. RESULTS: The incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977-1981 to 7.2 and 5.2 in 2007-2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%). CONCLUSIONS: The incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low.

Is current smoking still an important environmental factor in inflammatory bowel diseases? Results from a population-based incident cohort.

BACKGROUND: Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%. RESULTS: Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06). CONCLUSIONS: Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.

The risk of lymphoma and immunomodulators in patients with inflammatory bowel diseases: results from a population-based cohort in Eastern Europe.

BACKGROUND AND AIMS: Prior studies suggest a small but significantly increased risk of lymphoma in adults with inflammatory bowel disease (IBD), especially in patients treated with thiopurines. No data was available from Eastern Europe. The aim of this study was to analyze the incidence of lymphomas as related to drug exposure, in a population-based Veszprem province database, which included incident cases diagnosed between January 1, 1977 and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 36.5 years; CD: 506, age at diagnosis: 28.5.5 years). Both in- and outpatient records were collected and comprehensively reviewed. The rate of lymphoma was calculated as patient-years of exposure per medication class, of medications utilized in IBD. RESULTS: Of the 1420 patients, we identified three patients who developed lymphoma (one CLL, two low-grade B-cell NHL including one rectal case), during 19,293 patient-years of follow-up (median follow-up: 13 years). All three patients were male. None had received azathioprine or biologicals. The absolute incidence rate of lymphoma was 1.55 per 10,000 patient-years, with 3 cases observed vs. 2.18 expected, with a standardized incidence ratio (SIR) of 1.37 (95% confidence interval [CI]: 0.44-4.26). No cases have been exposed to either azathioprine or biologicals. CONCLUSIONS: The overall risk of lymphoma in IBD was not increased; only three cases were seen in this population-based incident cohort over a 30-year period. An association with thiopurine exposure was not found.

[The effect of early immunosuppressive therapy on the rate of resections performed in patients with Chron's disease, in Veszprém county, Hungary, a population-based cohort study]. / A korai immunszuppresszív kezelés hatása a reszekciós mutétek arányára Crohn-betegekben, Veszprém megyében, populációs alapú kohorszvizsgálat alapján.

UNLABELLED: Medical therapy for Crohn's disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn's disease over the past decades is scarce. AIMS: The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprém county database. METHODS: Data of 506 Crohn's disease patients were analyzed (age at diagnosis: 31.5 years, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups based on the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall azathioprine, systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1 and 5-year probabilities of azathioprine use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In multivariate analysis, decade of diagnosis (P<0.001), age at onset (P = 0.008), disease behavior at diagnosis (P<0.001), and need for systemic steroids (P<0.001) were significantly associated with the time to initiation of azathioprine therapy. Early azathioprine use was significantly associated with the time to intestinal surgery in Crohn's disease patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for azathioprine use (HR: 0.42,95% CI:0.26-0.67). CONCLUSIONS: This population-based inception cohort showed that reduction in surgical rates was independently associated with increased and earlier azathioprine use.

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

OBJECTIVES: Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). CONCLUSIONS: This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.

BACKGROUND: Recent trends indicate a change in the epidemiology of inflammatory bowel diseases (IBD), with previously low incidence areas now reporting a progressive rise in the incidence. Our aim was to analyze the incidence and disease phenotype at diagnosis in IBD in the population-based Veszprem Province database, which included incident patients diagnosed between January 1, 2002 and December 31, 2006. METHODS: Data of 393 incident patients were analyzed (ulcerative colitis [UC]: 220, age-at-diagnosis: 40.5 years; Crohn's disease [CD]: 163, age-at-diagnosis: 32.5 years; and indeterminate colitis [IC]: 10). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: Adjusted mean incidence rates were 8.9/10(5) person-years for CD and 11.9/10(5) person-years in UC. Peak onset age in both CD and UC patients was 21-30 years old. Location at diagnosis in UC was proctitis in 26.8%, left-sided colitis in 50.9%, and pancolitis in 22.3%. The probability of proximal extension and colectomy after 5 years was 12.7% and 2.8%. The disease location in CD was ileal in 20.2%, colonic in 35.6%, ileocolonic in 44.2%, and upper gastrointestinal in four patients. Behavior at diagnosis was stenosing/penetrating in 35.6% and perianal in 11.1%. Patients with colonic disease were older at diagnosis compared to patients with ileal or ileocolonic disease. In a Kaplan-Meier analysis, probability of surgical resection was 9.8%, 18.5%, and 21.3% after 1, 3, and 5 years of disease duration, respectively. CONCLUSIONS: The incidence of IBD in Veszprem Province in the last decade was high, equal to that in high-incidence areas in Western European countries. Early disease course is milder compared to data reported in the literature.

Risk of colorectal cancer and small bowel adenocarcinoma in Crohn's disease: a population-based study from western Hungary 1977-2008.

BACKGROUND AND AIMS: Limited data are available on the incidence and predictors of colorectal (CRC) and small bowel adenocarcinoma (SBA) in patients with Crohn's disease (CD) from population-based cohorts. Since data are completely missing from Eastern Europe, our aim was to analyze the incidence and risk factors of CD associated CRC and SBA in the population-based, Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. METHODS: The data of 506 incident CD patients were analyzed (age-at-diagnosis: 31.5, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: CRC was diagnosed in five patients (5/5758 person-year-duration) during follow-up, while no patients developed SBA in this cohort. Standardized incidence ratio (SIR) of CRC was not increased overall with five cases observed vs. 5.02 expected (SIR: 0.99, 95% CI: 0.41-2.39); however, there was a tendency for increased incidence in males (five cases observed vs. 2.56 expected; SIR: 1.95, 95% CI: 0.81-4.70). Age at onset of CD (p<0.001), male gender (p=0.022) and stenosing disease behavior at diagnosis (p<0.001) but not disease location were identified as risk factors for developing CRC in univariate analysis and Kaplan-Meier analysis. The cumulative risk for developing CRC after a disease duration of 20 years was 1.1% (95% CI: 0.6-1.7%). CONCLUSIONS: The incidence of CRC and SBA was not increased in this population-based CD cohort. Age at onset of CD, male gender and stenosing disease behavior at diagnosis were identified as risk factors of CRC.

IBD in the elderly population: results from a population-based study in Western Hungary, 1977-2008.

BACKGROUND AND AIMS: Limited data are available on the incidence and disease course of IBD in the elderly population. Our aim was to analyze the incidence and disease course of IBD according to the age at diagnosis in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. METHODS: Data of 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 SD 15.9 years; CD: 506, age at diagnosis: 31.5 SD 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: 106 (11.6%) of UC patients and 21 (4.2%) of CD patients were diagnosed with >60 years of age. In UC, the incidence increased from 1.09 to 10.8/10(5) in the elderly, while CD increased to 3.04/10(5) in 2002-2007. In CD, colonic location (elderly: 61.9% vs. pediatric: 24.3%, p=0.001, and adults: 36.8%, p=0.02) and stenosing disease (elderly: 42.9% vs. pediatric: 14.9%, p=0.005, and adults: 19.5%, p=0.01) were more frequent in the elderly. A change in disease behavior was absent in the elderly, while in pediatric and adult CD population it was 20.3% (p=0.037), 19.8% (p=0.036) after 5 years. In UC, extensive disease was more frequent in pediatric patients compared to the elderly (p=0.003, OR: 2.73, 95%CI: 1.38-5.41). In addition, pediatric (57.3%, p<0.001, OR: 6.58; 95%CI: 3.22-12.9) and adult (39.8%, p<0.001, OR: 3.24; 95%CI: 1.91-5.49) patients required more often systemic steroids during follow-up compared to the elderly (17%). Proximal extension at 10 years was 11.6%, but time to extension was not different according to the age at onset. CONCLUSIONS: Elderly patients represent an increasing proportion of the IBD population. Stenosing and colon-only disease were characteristic for elderly CD patients, while the disease course in UC was milder.

Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977-2001.

AIM: An investigation into inflammatory bowel disease and colorectal cancer in Veszprem Province was conducted from 1977 to 2001. METHODS: Both hospital and outpatient records were collected and reviewed comprehensively. The majority of patients were followed up regularly. RESULTS: The population of the province was decreased from 386,000 to 376,000 during the period. Five hundred sixty new cases of ulcerative colitis (UC), 212 of Crohn's disease (CD), and 40 of indeterminate colitis (IC) were diagnosed. The incidence rates increased from 1.66 to 11.01 cases per 100,000 persons for UC, from 0.41 to 4.68 for CD and from 0.26 to 0.74 for IC. The prevalence rate at the end of 2001 was 142.6 for UC and 52.9 cases per 100,000 persons for CD. The peak onset age in UC patients was between 30 and 40 years, in CD between 20 and 30 years. A family history of IBD was present in 3.4 % in UC and 9.9 % in CD patients. Smoking increased the risk for CD (OR=1.98) while it decreased the risk for UC (OR=0.25). Twelve colorectal carcinomas were observed in this cohort, the cumulative colorectal cancer risk after 10 years in UC was 2%, after 20 years 8.8%, after 30 years 13.3%. CONCLUSION: The incidence and prevalence rates of IBD have increased steadily in Veszprem Province, now equivalent to that in Western European countries. Rapid increase in incidence rates supports a probable role for environmental factors. The rate of colorectal cancers in IBD is similar to that observed in Western countries.

[Epidemiology of inflammatory bowel diseases in Veszprém county of Western Hungary between 1977 and 2001]. / A gyulladásos bélbetegségek epidemiológiája Veszprém megyében--25 éves felmérés eredményei (1977-2001).

INTRODUCTION: An epidemiological study of inflammatory bowel disease (IBD) in Veszprém county (located in western part of Hungary) was carried out from 1977 to 2001. METHODS: Both hospital and outpatient records of IBD patients were collected reviewed carefully. Most patients have been followed up regularly. RESULTS: The number of population has decreased during the observed period from 386,000 to 376,000. The county has both industrial and agrarian parts. 560 new ulcerative colitis (UC) cases, 212 Crohn's disease (CD), and 40 indeterminate colitides (IC) were diagnosed in the investigated period. Incidence rate increased from 1.66 (1977-1981) to 11.01 (1997-2001) in UC, and from 0.41 to 4.68 in CD, respectively. The incidence rate in IC rose from 0.26 to 0.74. The M/F ratio in UC was 1.06, in CD: 1.03, respectively, 41 UD patients and 13 CD patients died, the cause of death was disease related in 6 UC and in 6 CD patients. The average age at death in UC was not different from that observed in general population (66.4 years) but in CD (50.1 years) it was much earlier. The disease related mortality was low, 0.06/100,000 both in UC and CD. The prevalence rate at the end of 2001 was 142.6 for UC and 52.9/100,000 inhabitants for CD. Mean age at onset in UC was 38.9 +/- 15.5 years, in CD 31.7 +/- 12.8 years. We observed only one peak onset of the diseases, in UC it was between 30 and 40 years, in CD between 20 and 30 years. People living in towns were more liable to acquire the disease (ORUC = 1.27, ORCD = 1.13). The rate of smokers at the onset was 14.3% (OR = 0.25) in UC and 50.5% (OR = 1.98) in CD. Ex-smokers were 18.4% and 6.4%. Family history of IBD was present in 3.4% in UC and 9.9% in CD. The location of UC (according to the known largest extent) was proctitis in 112 cases, proctosigmoiditis in 162 cases, left sided colitis in 117 and subtotal or pancolitis in 169 cases. The location of CD was only ileal in 68 cases, ileocolonic in 87 cases, colonic in 57 cases. The behaviour of CD was non-stricturing-non-penetrating in 63 cases, stricturing in 54 cases, penetrating in 95 cases. 59.4% of the CD patients had at least one operation, 6.1% had more than 3 operations. CONCLUSION: The incidence and prevalence rates have increased steadily in Veszprém County, now it reaches that of most western European countries. There were no gender differences either in UC or CD. Smoking seemed to be a risk factor for CD, but it was preventive for UC. The rapid increase in incidence supports a role for environmental (e.g. diet, lifestyle changes) risk factors.