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Histologic features in the presence of peritonitis in diverticular disease
Immunology, Microbiology, and Inflammatory Disorders A1093
April 1998
Conclusions: This confirms that prednisolone of 10mg or greater for three
• G4472
ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES (ANCA) IN MONOZYGOTIC TWINS DISCORDANT FOR INFLAMMATORY BOWEL DISEASE (IBD). J Subhani, RS Walmsley, *AC Dunn, *PC Chapman, *A Brownlee, *CM Lockwood, AJ Wakefield, RE Pounder. Department of Medicine, Royal Free Hospital School of Medicine, London UK. *University Department of Medicine, Addenbrooke's Hospital, Cambridge, UK. Introduction: ANCA occurs more frequently in relatives of patients with IBD, and it may be either a subclinical or genetic marker for IBD. This hypothesis is best tested in a group of monozygotic twins discordant for the disease (i.e. one twin affected, one unaffected). Methods: 22 monozygotic pairs (17 ulcerative colitis (UC), 5 Crohn's disease (CD)) were screened for ANCA by neutrophil granules ELISA. Positive sera were then investigated by indirect immunofluorescence (IIF). All patients were also tested for IgG anti-Bactericidal/Permeability Increasing protein antibodies (anti-BPI) by ELISA. Fifty blood donors acted as controls (Con). Results: Two of 50 controls were positive for ANCA by ELISA, one by IIF, and none had anti-BPI antibodies. IIF ( + / - ) Anti-BPI(+/-) 5/12 3/17 2/15 0/17 NS NS P = 0.003 P = 0.01 U vs Con P = 0.002 NS NS Affected CD 3/5 015 1/5 Unaffected CD 3/5 0/5 015 A vs U NS NS NS A vs Con P = 0.004 NS NS U vs Con P =0.004 NS his (A = Affected U = Unaffected Con = Controls)
Affected (A) UC Unaffected (U) UC A vs U A vs Con
ANCA (+/-) 9/8 6/11 NS P < 0.0001
In 4 ulcerative colitis and 3 Crohn's disease pairs both affected and unaffected twin were positive for ANCA by ELISA. Conclusions: ANCA is present in ulcerative colitis and Crohn's disease patients at a significantly higher prevalence than in the healthy population. That it is not present in all "unaffected" twins of ANCA positive probands indicates that it is not a genetic marker. However the prevalence of ANCA is significantly increased in "unaffected" monozygotic twins of IBD probands. If ANCA is assumed to be a marker of an underlying immunological process it may identify those who require close follow-up. G4473 B O N E MINERAL DENSITIES IN TWINS DISCORDANT FOR IBD. J Subhani, SM Montgomery, C Kaiairai, A Hilson, JW Buscombe, AJ Wakefield, RE Pounder, Royal Free Hospital School of Medicine, Pond St., London, UK.
Some IBD patients have lower Bone Mineral Density (BMD) than expected. BMD is determined by both genetic factors and events during life. Correcting for genetic determinants will accentuate these other influences. Aim: To identify these influences that act as risk factors for bone loss. Method: Same-sex twin pairs discordant for IBD had a DEXA scan, biochemistry, dietary calcium and lifestyle exposures affecting BMD, assessed. In addition the characteristics of the disease, drug treatment and operations were determined in the affected twins. The percentage change in BMD (hip) of the affected compared with the unaffected twin was entered as the dependent variable in a multiple linear regression, with possible predicting factors. Analyses were also conducted for Crohn's disease (CD) and ulcerative colitis (UC) subgroups. Results: 32 twin pairs were studied, mean age was 45 years (range 29-68 years), mean duration of IBD 15 years (4 - 47 years), 24 pairs were mon0zygotic, 11 had a Crohn's disease proband, 3 pairs were male, 20 twins were postmenopausai. In an unmatched analysis, gender and age, but not the presence of IBD alone, were predictors of BMD. The matched analysis are tabulated below: UNADJUSTED %BMD (hip) loss (95% CI) Crotm's disease 17 (3-31)
ADJUSTED (adjusting for all %BMD other factors and (hip) loss menopause status) (95% CI) Age under 37 year 19 (4-34)
Age under 37 years
16 (0-33)
Pred> 10 mg/d for > 3 months
14 (0-28)
Pred> 10 mg/d for > 3 months Body Mass Index lower by 4 in the affected twin
15 (0-30) BMI lower by 4
9 (5-13)
Age under 37 year
18 (12-25)
Factor
All
CD
10 (2-19)
months and Crohn's disease are risks for osteopenia. Whether a fall in BMI is a marker for CD severity or the mechanism by which bone loss occurs, remains undetermined. That "age <37 years" was a risk but not "young age at diagnosis", implies that BMD is susceptible during this period, but it can recover. The presence of IBD itself is not necessarily a risk factor for bone loss, but other consequences of the disease are. • G4474 CONCORDANCE RATES OF TWINS AND SIBLINGS IN INFLAMMATORY BOWEL DISEASE (IBD). J Subhani, SM Montgomery, RE Pounder, AJ Wakefield. IBD Study Group, Royal Free Hospital School of Medicine, London, UK. Introduction: Concordance rates for IBD in relatives of an affected proband
are useful in patient counselling. However their greater importance lies in the assessment of the relative contributions of genetics and environment to the aetiology of the disease. Methods: A twin registry was established by volunteer recruitment from an IBD patient support group and individual gastroenterologists' clinics. Consultants confirmed the diagnosis, and a validated questionnaire of the zygosity. From probands other affected siblings (including twins) were identified. Since the age of diagnosis varies widely in IBD, a correction for the lifetime risk of developing IBD, using Stromgren method, was used to calculate adjusted concordance rates. Comparing identical vs. non-identical twins concordance rates reveals the effect of different levels of genetic similarity. Comparing non-identical twins vs. siblings concordance rates may reveal the effect of shared vs. different early childhood exposures, with the same genetic similarity. Results: The registry has 249 twin pairs, including 120 ulcerative colitis (UC) twin probands (52 monozygotic) who had 137 non-twin siblings, and 129 Crohn's disease (CD) twin probands (48 monozygotic) who had 187 non-twin siblings. There were 52 concordant pairs (34 twin-twin, 18 twin-sib). In six cases the second affected member (3 twins, 3 non-twin siblings) had the opposite IBD phenotype e.g. UC rather than CD, or vice versa. In 10 cases the second affected member was of the opposite sex (4 twins, 6 non-twin siblings). The median time between diagnoses of the 34 concordant twin pairs was 5 years, range 0 - 21 years. IBD type
UC (pairs) CD (pairs)
PAIRWISE CONCORDANCE RATES Identical twins Non-identicaltwins Siblings adjusted adjusted adjusted 13.4% 16.5% 4.4% 5.3% 5.8% 6.8% 7/52 3/68 8/137 33.3% 42.2% 9.9% 12.0% 5.3% 6.0% 16/48 8/81 10/187
Conclusions: The concordance rate is significantly higher for identical twms compared with non-identical twins indicating a genetic component for both UC and CD. However there is evidence of environmental influences. The concordance rate in CD for non-identical twins is twice that for siblings, which may reflect the effects of shared early life-events. Three cases of identical twins manifesting different phenotypes of IBD (e.g. CD vs. UC) are described, indicating environmental modulators of disease expression. Both genes and environment are important in determining the risk and phenotype of IBD.
G4475 ItISTOLOGIC FEATURES IN THE PRESENCE OF PERITONITIS IN DIVERTICULAR DISEASE, C Subramony, S Bigler, RM Joseph, AA Mihas. University of Mississippi Medical Center, Jackson, MS. Back~,round: Recurrent diverticulitis resulting in peritonitis is a common complication that requires surgical intervention. The mucosal changes occuring in the diveriticula that lead to peritonitis are not well charecterized. The purpose of this study was to examine the histological changes in the diverticular mucosa in patients with peritonitis and compare them, to those seen in patients without peritonitis. Desien: Slides from 53 patients who had colon resections for diverticular disease were examined One to 5 diverticula were examined per patient. The presence of the following features were documented in each case: histologic evidence of peritonitis, mucosal ulcer, acute mucosal inflammation, lymphoid aggregates, granulomas and fecoliths. Results: Twenty patients (37%) showed evidence of peritonitis. The diverticular mucosa showed superficial ulceration in 10/20 patients (50%) with peritonitis and 7/33 (21%) patients without peritonitis. (Z2 =5.35, significant at p<0.05). Acute inflammation, characterized by the presence of neutrophils in the diverticular mucosa, was seen in 17/20 cases with peritonitis, but only in 11/33 cases without peritonitis (~2=13.2, p<0.001). Lymphoid aggregates in the mucosa were seen in 13/20 cases with peritonitis and 25/33 cases without peritonitis (Z2=0.67,NS). Fecaliths were seen in 2 cases, both with peritonitis, and granulomas were seen in 2 cases with peritonitis. Additionally, one case without peritonitis showed vascular necrosis with prominent mucosal and submucosal hemorrhage. Conclusions: Peritonitis in diverticular disease is often associated with superficial ulcers and acute inflammation of the diverticular mucosa.
April 1998
Conclusions: This confirms that prednisolone of 10mg or greater for three
• G4472
ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES (ANCA) IN MONOZYGOTIC TWINS DISCORDANT FOR INFLAMMATORY BOWEL DISEASE (IBD). J Subhani, RS Walmsley, *AC Dunn, *PC Chapman, *A Brownlee, *CM Lockwood, AJ Wakefield, RE Pounder. Department of Medicine, Royal Free Hospital School of Medicine, London UK. *University Department of Medicine, Addenbrooke's Hospital, Cambridge, UK. Introduction: ANCA occurs more frequently in relatives of patients with IBD, and it may be either a subclinical or genetic marker for IBD. This hypothesis is best tested in a group of monozygotic twins discordant for the disease (i.e. one twin affected, one unaffected). Methods: 22 monozygotic pairs (17 ulcerative colitis (UC), 5 Crohn's disease (CD)) were screened for ANCA by neutrophil granules ELISA. Positive sera were then investigated by indirect immunofluorescence (IIF). All patients were also tested for IgG anti-Bactericidal/Permeability Increasing protein antibodies (anti-BPI) by ELISA. Fifty blood donors acted as controls (Con). Results: Two of 50 controls were positive for ANCA by ELISA, one by IIF, and none had anti-BPI antibodies. IIF ( + / - ) Anti-BPI(+/-) 5/12 3/17 2/15 0/17 NS NS P = 0.003 P = 0.01 U vs Con P = 0.002 NS NS Affected CD 3/5 015 1/5 Unaffected CD 3/5 0/5 015 A vs U NS NS NS A vs Con P = 0.004 NS NS U vs Con P =0.004 NS his (A = Affected U = Unaffected Con = Controls)
Affected (A) UC Unaffected (U) UC A vs U A vs Con
ANCA (+/-) 9/8 6/11 NS P < 0.0001
In 4 ulcerative colitis and 3 Crohn's disease pairs both affected and unaffected twin were positive for ANCA by ELISA. Conclusions: ANCA is present in ulcerative colitis and Crohn's disease patients at a significantly higher prevalence than in the healthy population. That it is not present in all "unaffected" twins of ANCA positive probands indicates that it is not a genetic marker. However the prevalence of ANCA is significantly increased in "unaffected" monozygotic twins of IBD probands. If ANCA is assumed to be a marker of an underlying immunological process it may identify those who require close follow-up. G4473 B O N E MINERAL DENSITIES IN TWINS DISCORDANT FOR IBD. J Subhani, SM Montgomery, C Kaiairai, A Hilson, JW Buscombe, AJ Wakefield, RE Pounder, Royal Free Hospital School of Medicine, Pond St., London, UK.
Some IBD patients have lower Bone Mineral Density (BMD) than expected. BMD is determined by both genetic factors and events during life. Correcting for genetic determinants will accentuate these other influences. Aim: To identify these influences that act as risk factors for bone loss. Method: Same-sex twin pairs discordant for IBD had a DEXA scan, biochemistry, dietary calcium and lifestyle exposures affecting BMD, assessed. In addition the characteristics of the disease, drug treatment and operations were determined in the affected twins. The percentage change in BMD (hip) of the affected compared with the unaffected twin was entered as the dependent variable in a multiple linear regression, with possible predicting factors. Analyses were also conducted for Crohn's disease (CD) and ulcerative colitis (UC) subgroups. Results: 32 twin pairs were studied, mean age was 45 years (range 29-68 years), mean duration of IBD 15 years (4 - 47 years), 24 pairs were mon0zygotic, 11 had a Crohn's disease proband, 3 pairs were male, 20 twins were postmenopausai. In an unmatched analysis, gender and age, but not the presence of IBD alone, were predictors of BMD. The matched analysis are tabulated below: UNADJUSTED %BMD (hip) loss (95% CI) Crotm's disease 17 (3-31)
ADJUSTED (adjusting for all %BMD other factors and (hip) loss menopause status) (95% CI) Age under 37 year 19 (4-34)
Age under 37 years
16 (0-33)
Pred> 10 mg/d for > 3 months
14 (0-28)
Pred> 10 mg/d for > 3 months Body Mass Index lower by 4 in the affected twin
15 (0-30) BMI lower by 4
9 (5-13)
Age under 37 year
18 (12-25)
Factor
All
CD
10 (2-19)
months and Crohn's disease are risks for osteopenia. Whether a fall in BMI is a marker for CD severity or the mechanism by which bone loss occurs, remains undetermined. That "age <37 years" was a risk but not "young age at diagnosis", implies that BMD is susceptible during this period, but it can recover. The presence of IBD itself is not necessarily a risk factor for bone loss, but other consequences of the disease are. • G4474 CONCORDANCE RATES OF TWINS AND SIBLINGS IN INFLAMMATORY BOWEL DISEASE (IBD). J Subhani, SM Montgomery, RE Pounder, AJ Wakefield. IBD Study Group, Royal Free Hospital School of Medicine, London, UK. Introduction: Concordance rates for IBD in relatives of an affected proband
are useful in patient counselling. However their greater importance lies in the assessment of the relative contributions of genetics and environment to the aetiology of the disease. Methods: A twin registry was established by volunteer recruitment from an IBD patient support group and individual gastroenterologists' clinics. Consultants confirmed the diagnosis, and a validated questionnaire of the zygosity. From probands other affected siblings (including twins) were identified. Since the age of diagnosis varies widely in IBD, a correction for the lifetime risk of developing IBD, using Stromgren method, was used to calculate adjusted concordance rates. Comparing identical vs. non-identical twins concordance rates reveals the effect of different levels of genetic similarity. Comparing non-identical twins vs. siblings concordance rates may reveal the effect of shared vs. different early childhood exposures, with the same genetic similarity. Results: The registry has 249 twin pairs, including 120 ulcerative colitis (UC) twin probands (52 monozygotic) who had 137 non-twin siblings, and 129 Crohn's disease (CD) twin probands (48 monozygotic) who had 187 non-twin siblings. There were 52 concordant pairs (34 twin-twin, 18 twin-sib). In six cases the second affected member (3 twins, 3 non-twin siblings) had the opposite IBD phenotype e.g. UC rather than CD, or vice versa. In 10 cases the second affected member was of the opposite sex (4 twins, 6 non-twin siblings). The median time between diagnoses of the 34 concordant twin pairs was 5 years, range 0 - 21 years. IBD type
UC (pairs) CD (pairs)
PAIRWISE CONCORDANCE RATES Identical twins Non-identicaltwins Siblings adjusted adjusted adjusted 13.4% 16.5% 4.4% 5.3% 5.8% 6.8% 7/52 3/68 8/137 33.3% 42.2% 9.9% 12.0% 5.3% 6.0% 16/48 8/81 10/187
Conclusions: The concordance rate is significantly higher for identical twms compared with non-identical twins indicating a genetic component for both UC and CD. However there is evidence of environmental influences. The concordance rate in CD for non-identical twins is twice that for siblings, which may reflect the effects of shared early life-events. Three cases of identical twins manifesting different phenotypes of IBD (e.g. CD vs. UC) are described, indicating environmental modulators of disease expression. Both genes and environment are important in determining the risk and phenotype of IBD.
G4475 ItISTOLOGIC FEATURES IN THE PRESENCE OF PERITONITIS IN DIVERTICULAR DISEASE, C Subramony, S Bigler, RM Joseph, AA Mihas. University of Mississippi Medical Center, Jackson, MS. Back~,round: Recurrent diverticulitis resulting in peritonitis is a common complication that requires surgical intervention. The mucosal changes occuring in the diveriticula that lead to peritonitis are not well charecterized. The purpose of this study was to examine the histological changes in the diverticular mucosa in patients with peritonitis and compare them, to those seen in patients without peritonitis. Desien: Slides from 53 patients who had colon resections for diverticular disease were examined One to 5 diverticula were examined per patient. The presence of the following features were documented in each case: histologic evidence of peritonitis, mucosal ulcer, acute mucosal inflammation, lymphoid aggregates, granulomas and fecoliths. Results: Twenty patients (37%) showed evidence of peritonitis. The diverticular mucosa showed superficial ulceration in 10/20 patients (50%) with peritonitis and 7/33 (21%) patients without peritonitis. (Z2 =5.35, significant at p<0.05). Acute inflammation, characterized by the presence of neutrophils in the diverticular mucosa, was seen in 17/20 cases with peritonitis, but only in 11/33 cases without peritonitis (~2=13.2, p<0.001). Lymphoid aggregates in the mucosa were seen in 13/20 cases with peritonitis and 25/33 cases without peritonitis (Z2=0.67,NS). Fecaliths were seen in 2 cases, both with peritonitis, and granulomas were seen in 2 cases with peritonitis. Additionally, one case without peritonitis showed vascular necrosis with prominent mucosal and submucosal hemorrhage. Conclusions: Peritonitis in diverticular disease is often associated with superficial ulcers and acute inflammation of the diverticular mucosa.