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Relevance of Yersinia Outer Membrane Proteins in Collagenous and Lymphocytic Colitis
AGA Abstracts
colonoscopy for long term ulcerative colitis during this study period,a total of 24 colorectal lesions in 23 patients(84.4% Male;age 55,SD11) were identified.Final histopathology confirmed 6 DALM lesions including two adenocarcinomas,8 sporadic adenomas including 7 tubular adenomas and 1 serrated adenoma and 9 nonneoplastic lesions(4 inflammatory and 5 hyperplastic).The morphology of DALM lesions according to Paris classification was Ip 1,Is 1,IIa 4 while all sporadic adenomatous lesions were sessile lesions(1s).The Kudo pit pattern assessment among all DALM lesions was of tubular, large pattern (3l) and among sporadic adenomatous lesions 6 lesions had tubular (3l) pattern and two oval pit pattern(2). The majority of dysplastic lesions were located in the left colon (9; 64.5%). The median size was 24 mm for DALM (7-40 mm) and 5 mm(3-6mm) for sporadic adenomas(p<0.01)CONCLUSION:Most DALM lesions were larger(>10mm),sessile and flat with characteristic large tubular pit mucosal patterns.This novel finding suggests that routine high quality white light endoscopy is capable of identifying characteristic endoscopic features in DALM lesions.Further prospective evaluation in a large number of patients is merited.
Mo1992 Trends in Emergency Department Abdominopelvic Computed Tomography Use, Admission Rates, and Urgent Diagnoses Among Patients With Crohn's Disease Caroline Kerner, Kathleen Carey, Angela M. Mills, Wei Yang, Marie B. Synnestvedt, Susan Hilton, Mark Weiner, James D. Lewis BACKGROUND: In the United States, abdominopelvic computed tomography (APCT) use in emergency departments (EDs) for patients with abdominal pain has increased despite stable rates of admission and detection of urgent diagnoses (Pines JM. Med Care 2009;47:7826). We hypothesized that similar trends would be seen among patients with Crohn's disease (CD). This population is at risk of excessive radiation exposure from diagnostic imaging, particularly APCT used in EDs; yet the impact of ED APCTs on CD outcomes is unknown. We examined the trend over time in APCT use, admission rates, and frequency of urgent APCT findings among ED patients with CD. METHODS: A retrospective chart review using an electronic database was performed of adults with a prior CD diagnosis presenting to two university EDs with a gastrointestinal chief complaint. The database was queried to determine patient characteristics and APCT use from 2001-2009. For eligible encounters between 2001-2003 and 2007-2009 that included an APCT, the radiology reports were reviewed to characterize the radiologic findings. Trends over time were assessed with Spearman's correlation coefficient. Patient characteristics and APCT findings were compared between 20012003 and 2007-2009 using robust variance estimate to compute p values. RESULTS: There were 2079 ED visits among 726 subjects (53% female; 70% Caucasian; mean age at first ED visit 38.8). 582 subjects (80%) had <3 ED visits during the study period. Abdominal pain was the chief complaint in 63% of visits. APCT use increased over time from 17 to 69% (p<0.0001) while admission rates were stable (p=0.14) (Figure). During the study period, 134 patients (25%) received >3 scans (range 3-23). There were no significant differences in gender (54% vs. 52% female, p=.73), race (60% vs. 65% Caucasian, p=.50), chief complaint (abdominal pain in 76% vs. 75%, p=.85), or admission rate (74% vs. 77%, p=.51) between 2001-2003 and 2007-2009. In 2001-2003 vs. 2007-2009 visits, patients were slightly older (mean age 41 vs. 37 years, p=.03), were more often taking aminosalicylates (50% vs. 34%, p=.02), less often taking biologic drugs (7% vs. 19%, p=.006), but were taking corticosteroids (32% vs. 26%, p=.22) and immunomodulators (20% vs. 14%, p=.15) with similar frequency. Importantly, after adjusting for differences in age and medication use, the proportion of APCTs with findings of intestinal perforation, obstruction or abscess was similar (25% vs. 27%, p=.41), as was the proportion with any urgent diagnosis including those unrelated to CD (30% vs. 33%, p=.26). CONCLUSION: Despite the dramatic increase over time in APCT use in ED patients with CD and gastrointestinal complaints, there was no significant change in admission rates or the proportion of APCT scans with intestinal perforation, obstruction, abscess or other urgent non-CD-related findings.
Mo1990 Relevance of Yersinia Outer Membrane Proteins in Collagenous and Lymphocytic Colitis Stephan Miehlke, Ahmed Madisch, Andrea Morgner, Manfred Stolte, Gustavo Baretton, Norbert Lehn, Wulf Schneider-Brachert Objectives: Collagenous colitis and lymphocytic colitis are two distinct forms of microscopic colitis with unknown etiology and similar clinical features. Infectious agents such as Yersinia enterocolitica are suspected to be involved in the pathogenesis of both diseases. We analyzed the serological response to Yersinia outer membrane proteins (YOP) in a large cohort of patients. Methods: Serum samples were collected from consecutive patients with symptomatic collagenous (n=76) and lymphocytic (n=54) colitis, and from asymptomatic control subjects with normal colonic histology matched for age and gender (n=39). Serum YOP antibodies were semiquantitatively assessed by a recombinant immunoblot in a blinded fashion. Results: There was a high prevalence of YOPD D IgG and IgA serum antibodies in patients with collagenous (84%, 45%) and lymphocytic (59%, 37%) colitis, and in control subjects (84%, 48%). YOP D IgM antibodies were detected in only 13% and 7.5% of patients, and in 20% of controls. In contrast, YOP H IgG antibodies were significantly more common in patients with lymphocytic (20.1%) and collagenous colitis (22.6%) compared to controls (2.6%) (p= 0.01). Conclusion: Our study demonstrates a higher prevalence of YOP H IgG serum antibodies in patients with microscopic colitis compared to controls suggesting a potential role of this Yersinia specific virulence factor in the pathogenesis of microscopic colitis. Mo1991 Serologic Response to Microbial Antigens Does Not Differ by Age of Diagnosis Sandra Quezada, Nadia Cheevers, Ankur Rustgi, Raymond Cross Background and Aims: Crohn's disease (CD) and ulcerative colitis (UC) comprise inflammatory bowel disease (IBD), a disease of the gastrointestinal tract that primarily affects young adults; however approximately 15% of patients are diagnosed at an advanced age. Serologic responses to enteric microbial antigens are felt to play a critical role in the pathogenesis of IBD. Previous studies have shown that older patients are less likely to have complicated CD compared to patients diagnosed at younger ages. Our aim was to compare serologic responses to microbial gut antigens by age of diagnosis in a tertiary referral cohort. Methods: Sera collected from patients diagnosed with CD or UC were tested for immune responses: ASCA IgA, ASCA IgG, Omp-C, Cbir-1, and p-ANCA. Demographics, disease behavior, disease extent/location and serologic responses were compared by age of diagnosis groups: <40 years, ≥40-59 years, and ≥60 years. Mean titers and proportion of patients with a positive response to each microbial antigen were compared among the three age at diagnosis groups. For each antigen, patients with antibody levels in the 1st, 2nd, 3rd, and 4th quartile of distribution were assigned a quartile score of 1, 2, 3, and 4 respectively. Individual quartile scores for each microbial antigen were added to create a quartile sum score for each patient (range 5-20) to represent cumulative quantitative immune response toward all 5 antigens. Results: A total of 51 patients with IBD were included. 20 patients were diagnosed under age 40, 20 were diagnosed between 40-59, and 11 were diagnosed at age 60 or over. 33 patients had CD and 18 had UC. There were no significant differences in any demographic variable by age at diagnosis. 82% of all patients had at least one positive response to a microbial antigen, 37% responded to two microbial antigens, 25% responded to three microbial antigens, 6% responded to four microbial antigens, and 2% responded to all five microbial antigens. The proportion of patients with a positive response to each microbial antigen did not differ by age of diagnosis. Mean titers to each microbial antigen did not differ by age of diagnosis. Mean quartile sum scores were: 12.8 ± 3.3 in those diagnosed under age 40, 10.6 ± 2.6 in those diagnosed between ages 40-59, and 12.2 ± 4.1 in those diagnosed at or over age 60 (p=0.11). Subgroup analyses of participants with only CD or UC did not reveal a significant difference in immune responses to microbial antigens, mean titers, or mean quartile scores. Conclusion: Serologic responses to gut microbial antigens did not differ by age of diagnosis among patients diagnosed with IBD. Our preliminary results suggest that immune responses to gut microbial antigens in patients with IBD diagnosed at older ages do not differ from those diagnosed at younger ages. Further studies are needed to confirm our results.
AGA Abstracts
Rates of Emergency Department Abdominopelvic CT Scan Use and Hospital Admission Rates over Time in Patients with Crohn's Disease Presenting With Gastrointestinal Complaints Mo1993 Prospective Noninvasive Analysis of Hepatic Fibrosis in Patients With Crohn's Disease: Correlation of Transient Elastography and Laboratory-Based Marker Johannes Brühl, Moritz Schirren, Christel Weiss, Christoph Antoni, Manfred V. Singer, Ulrich Böcker Objective: Hepatobiliary disorders, associated either with extraintestinal manifestations or consequences of treatment, are prevalent among patients with inflammatory bowel disease (IBD). Therefore, this study aimed to prospectively and noninvasively assess liver function with a focus on fibrosis in patients with Crohn's disease. Material and Methods: A total of 114 patients were recruited. Established markers of fibrosis, namely, Apri, Fibrotest, and Forns, sonography, and transient elastography were performed and correlated with disease parameters. In addition to descriptive statistical analysis Pearson's correlation coefficients were determined. T- and Mann-Whitney-U-test were applied and uni- and multivariate data analysis performed. Results: Ultrasound indicated hepatic steatosis in 33 patients, hepatomegaly in 10, and cirrhosis in 2. Liver stiffness as quantified by transient elastography was determined to be 5.06 ± 2.33 kPa (2.6-21.5). Results of noninvasive liver fibrosis markers were as follows: Fibrotest -1.65 ± 0.94, Apri 0.33 ± 0.22, and Forns 3.11 ± 2.00. Correlation coefficients were found to be: Fibrotest/transient elastography: r=0.35291; Apri/ transient elastography: r=0.38442; Forns/ transient elastography: r=0.33949; Fibrotest/Apri: r=0.52937; Fibrotest/Forns: r=0.42413; and Apri/Forns: r=0.56491. Correlation of inflammatory markers and noninvasive liver fibrosis tests, respectively, was generally negative, while correlation of parameters indicating liver damage and liver fibrosis tests, respectively, was generally positive. Conclusions: In a center-based, unselected cohort of patients with Crohn's disease the prevalence of advanced fibrosis, as determined noninvasively, was low.
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colonoscopy for long term ulcerative colitis during this study period,a total of 24 colorectal lesions in 23 patients(84.4% Male;age 55,SD11) were identified.Final histopathology confirmed 6 DALM lesions including two adenocarcinomas,8 sporadic adenomas including 7 tubular adenomas and 1 serrated adenoma and 9 nonneoplastic lesions(4 inflammatory and 5 hyperplastic).The morphology of DALM lesions according to Paris classification was Ip 1,Is 1,IIa 4 while all sporadic adenomatous lesions were sessile lesions(1s).The Kudo pit pattern assessment among all DALM lesions was of tubular, large pattern (3l) and among sporadic adenomatous lesions 6 lesions had tubular (3l) pattern and two oval pit pattern(2). The majority of dysplastic lesions were located in the left colon (9; 64.5%). The median size was 24 mm for DALM (7-40 mm) and 5 mm(3-6mm) for sporadic adenomas(p<0.01)CONCLUSION:Most DALM lesions were larger(>10mm),sessile and flat with characteristic large tubular pit mucosal patterns.This novel finding suggests that routine high quality white light endoscopy is capable of identifying characteristic endoscopic features in DALM lesions.Further prospective evaluation in a large number of patients is merited.
Mo1992 Trends in Emergency Department Abdominopelvic Computed Tomography Use, Admission Rates, and Urgent Diagnoses Among Patients With Crohn's Disease Caroline Kerner, Kathleen Carey, Angela M. Mills, Wei Yang, Marie B. Synnestvedt, Susan Hilton, Mark Weiner, James D. Lewis BACKGROUND: In the United States, abdominopelvic computed tomography (APCT) use in emergency departments (EDs) for patients with abdominal pain has increased despite stable rates of admission and detection of urgent diagnoses (Pines JM. Med Care 2009;47:7826). We hypothesized that similar trends would be seen among patients with Crohn's disease (CD). This population is at risk of excessive radiation exposure from diagnostic imaging, particularly APCT used in EDs; yet the impact of ED APCTs on CD outcomes is unknown. We examined the trend over time in APCT use, admission rates, and frequency of urgent APCT findings among ED patients with CD. METHODS: A retrospective chart review using an electronic database was performed of adults with a prior CD diagnosis presenting to two university EDs with a gastrointestinal chief complaint. The database was queried to determine patient characteristics and APCT use from 2001-2009. For eligible encounters between 2001-2003 and 2007-2009 that included an APCT, the radiology reports were reviewed to characterize the radiologic findings. Trends over time were assessed with Spearman's correlation coefficient. Patient characteristics and APCT findings were compared between 20012003 and 2007-2009 using robust variance estimate to compute p values. RESULTS: There were 2079 ED visits among 726 subjects (53% female; 70% Caucasian; mean age at first ED visit 38.8). 582 subjects (80%) had <3 ED visits during the study period. Abdominal pain was the chief complaint in 63% of visits. APCT use increased over time from 17 to 69% (p<0.0001) while admission rates were stable (p=0.14) (Figure). During the study period, 134 patients (25%) received >3 scans (range 3-23). There were no significant differences in gender (54% vs. 52% female, p=.73), race (60% vs. 65% Caucasian, p=.50), chief complaint (abdominal pain in 76% vs. 75%, p=.85), or admission rate (74% vs. 77%, p=.51) between 2001-2003 and 2007-2009. In 2001-2003 vs. 2007-2009 visits, patients were slightly older (mean age 41 vs. 37 years, p=.03), were more often taking aminosalicylates (50% vs. 34%, p=.02), less often taking biologic drugs (7% vs. 19%, p=.006), but were taking corticosteroids (32% vs. 26%, p=.22) and immunomodulators (20% vs. 14%, p=.15) with similar frequency. Importantly, after adjusting for differences in age and medication use, the proportion of APCTs with findings of intestinal perforation, obstruction or abscess was similar (25% vs. 27%, p=.41), as was the proportion with any urgent diagnosis including those unrelated to CD (30% vs. 33%, p=.26). CONCLUSION: Despite the dramatic increase over time in APCT use in ED patients with CD and gastrointestinal complaints, there was no significant change in admission rates or the proportion of APCT scans with intestinal perforation, obstruction, abscess or other urgent non-CD-related findings.
Mo1990 Relevance of Yersinia Outer Membrane Proteins in Collagenous and Lymphocytic Colitis Stephan Miehlke, Ahmed Madisch, Andrea Morgner, Manfred Stolte, Gustavo Baretton, Norbert Lehn, Wulf Schneider-Brachert Objectives: Collagenous colitis and lymphocytic colitis are two distinct forms of microscopic colitis with unknown etiology and similar clinical features. Infectious agents such as Yersinia enterocolitica are suspected to be involved in the pathogenesis of both diseases. We analyzed the serological response to Yersinia outer membrane proteins (YOP) in a large cohort of patients. Methods: Serum samples were collected from consecutive patients with symptomatic collagenous (n=76) and lymphocytic (n=54) colitis, and from asymptomatic control subjects with normal colonic histology matched for age and gender (n=39). Serum YOP antibodies were semiquantitatively assessed by a recombinant immunoblot in a blinded fashion. Results: There was a high prevalence of YOPD D IgG and IgA serum antibodies in patients with collagenous (84%, 45%) and lymphocytic (59%, 37%) colitis, and in control subjects (84%, 48%). YOP D IgM antibodies were detected in only 13% and 7.5% of patients, and in 20% of controls. In contrast, YOP H IgG antibodies were significantly more common in patients with lymphocytic (20.1%) and collagenous colitis (22.6%) compared to controls (2.6%) (p= 0.01). Conclusion: Our study demonstrates a higher prevalence of YOP H IgG serum antibodies in patients with microscopic colitis compared to controls suggesting a potential role of this Yersinia specific virulence factor in the pathogenesis of microscopic colitis. Mo1991 Serologic Response to Microbial Antigens Does Not Differ by Age of Diagnosis Sandra Quezada, Nadia Cheevers, Ankur Rustgi, Raymond Cross Background and Aims: Crohn's disease (CD) and ulcerative colitis (UC) comprise inflammatory bowel disease (IBD), a disease of the gastrointestinal tract that primarily affects young adults; however approximately 15% of patients are diagnosed at an advanced age. Serologic responses to enteric microbial antigens are felt to play a critical role in the pathogenesis of IBD. Previous studies have shown that older patients are less likely to have complicated CD compared to patients diagnosed at younger ages. Our aim was to compare serologic responses to microbial gut antigens by age of diagnosis in a tertiary referral cohort. Methods: Sera collected from patients diagnosed with CD or UC were tested for immune responses: ASCA IgA, ASCA IgG, Omp-C, Cbir-1, and p-ANCA. Demographics, disease behavior, disease extent/location and serologic responses were compared by age of diagnosis groups: <40 years, ≥40-59 years, and ≥60 years. Mean titers and proportion of patients with a positive response to each microbial antigen were compared among the three age at diagnosis groups. For each antigen, patients with antibody levels in the 1st, 2nd, 3rd, and 4th quartile of distribution were assigned a quartile score of 1, 2, 3, and 4 respectively. Individual quartile scores for each microbial antigen were added to create a quartile sum score for each patient (range 5-20) to represent cumulative quantitative immune response toward all 5 antigens. Results: A total of 51 patients with IBD were included. 20 patients were diagnosed under age 40, 20 were diagnosed between 40-59, and 11 were diagnosed at age 60 or over. 33 patients had CD and 18 had UC. There were no significant differences in any demographic variable by age at diagnosis. 82% of all patients had at least one positive response to a microbial antigen, 37% responded to two microbial antigens, 25% responded to three microbial antigens, 6% responded to four microbial antigens, and 2% responded to all five microbial antigens. The proportion of patients with a positive response to each microbial antigen did not differ by age of diagnosis. Mean titers to each microbial antigen did not differ by age of diagnosis. Mean quartile sum scores were: 12.8 ± 3.3 in those diagnosed under age 40, 10.6 ± 2.6 in those diagnosed between ages 40-59, and 12.2 ± 4.1 in those diagnosed at or over age 60 (p=0.11). Subgroup analyses of participants with only CD or UC did not reveal a significant difference in immune responses to microbial antigens, mean titers, or mean quartile scores. Conclusion: Serologic responses to gut microbial antigens did not differ by age of diagnosis among patients diagnosed with IBD. Our preliminary results suggest that immune responses to gut microbial antigens in patients with IBD diagnosed at older ages do not differ from those diagnosed at younger ages. Further studies are needed to confirm our results.
AGA Abstracts
Rates of Emergency Department Abdominopelvic CT Scan Use and Hospital Admission Rates over Time in Patients with Crohn's Disease Presenting With Gastrointestinal Complaints Mo1993 Prospective Noninvasive Analysis of Hepatic Fibrosis in Patients With Crohn's Disease: Correlation of Transient Elastography and Laboratory-Based Marker Johannes Brühl, Moritz Schirren, Christel Weiss, Christoph Antoni, Manfred V. Singer, Ulrich Böcker Objective: Hepatobiliary disorders, associated either with extraintestinal manifestations or consequences of treatment, are prevalent among patients with inflammatory bowel disease (IBD). Therefore, this study aimed to prospectively and noninvasively assess liver function with a focus on fibrosis in patients with Crohn's disease. Material and Methods: A total of 114 patients were recruited. Established markers of fibrosis, namely, Apri, Fibrotest, and Forns, sonography, and transient elastography were performed and correlated with disease parameters. In addition to descriptive statistical analysis Pearson's correlation coefficients were determined. T- and Mann-Whitney-U-test were applied and uni- and multivariate data analysis performed. Results: Ultrasound indicated hepatic steatosis in 33 patients, hepatomegaly in 10, and cirrhosis in 2. Liver stiffness as quantified by transient elastography was determined to be 5.06 ± 2.33 kPa (2.6-21.5). Results of noninvasive liver fibrosis markers were as follows: Fibrotest -1.65 ± 0.94, Apri 0.33 ± 0.22, and Forns 3.11 ± 2.00. Correlation coefficients were found to be: Fibrotest/transient elastography: r=0.35291; Apri/ transient elastography: r=0.38442; Forns/ transient elastography: r=0.33949; Fibrotest/Apri: r=0.52937; Fibrotest/Forns: r=0.42413; and Apri/Forns: r=0.56491. Correlation of inflammatory markers and noninvasive liver fibrosis tests, respectively, was generally negative, while correlation of parameters indicating liver damage and liver fibrosis tests, respectively, was generally positive. Conclusions: In a center-based, unselected cohort of patients with Crohn's disease the prevalence of advanced fibrosis, as determined noninvasively, was low.
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