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Short- and long-term efficacy of cyclosporin administration in patients with acute severe ulcerative colitis. Belgian IBD Group.

Cyclosporin (CsA) has been proposed in the management of patients with acute ulcerative colitis (UC) in whom standard therapy failed and who were candidates for colectomy. Seven academic hospitals contributed to this retrospective study that included 29 patients (median age: 33 y. (15-74 y.); 12 females and 17 males). The median duration of the disease was 4 y. (0.3 to 33 y.). Before initiating CsA, patients were unresponsive to treatment including i.v. corticosteroids (n = 29), 5-ASA or salazopyrine (n = 19), azathioprine (n = 3), antibiotics (n = 14). The i.v. mean dose was 4 mg/kg/day and was adapted to blood level. Concomitant treatment included corticosteroids (n = 27). The median duration of i.v. CsA administration was 10 days (4 to 41 days). At the end of CsA administration, a global improvement was described in 20 patients while a surgery had to be performed immediately in 8 patients because of exacerbation of symptoms (n = 7) or perforation (n = 1). One other patient (74 y.) died because of Pneumocystis carinii infection. For the responders, maintenance therapy included: tapering dose of steroids (n = 12), azathioprine (n = 12), 5-ASA or salazopyrine (n = 10), methotrexate (n = 1) or oral CsA (n = II). The median duration of follow-up was 12 months (4 to 48 months). Among the 20 responders, 7 were subsequently referred for colectomy either electively (n = 3) or because of recurrence of the disease (n = 4). Among the 12 patients treated by azathioprine as a maintenance therapy, only 3 had to be referred for surgery (25%). Among the 8 patients who did not receive azathioprine, 4 were subsequently referred for a colectomy (50%) (NS). In patients with acute refractory UC who received CsA, the short-term efficacy (avoidance of immediate colectomy) was obtained in 20 out of 29 patients (69%). However, after a median follow-up of 12 months, only 13 patients were colectomy free (45%).

Acute Disease↗

Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study.

BACKGROUND: Genetic factors may play a role in determining the development of extraintestinal manifestations (EIMs) and autoimmune diseases (AD) in patients with inflammatory bowel disease (IBD). We sought to determine the association between EIMs and AD in patients with first-degree familial IBD and sporadic IBD. METHODS: All patients evaluated in the IBD Clinic at the Mayo Clinic between January and September 1999 were offered enrollment. One clinic patient who was matched on age, gender, and geographic area of residence to each case served as controls. Information regarding EIMs and AD was obtained from a questionnaire completed by all IBD patients and controls. The adjusted odds ratios (95% CIs) for EIM as a function of first-degree familial IBD compared with sporadic IBD and AD as a function of first-degree familial IBD compared with sporadic IBD were estimated with a matched one-to-one conditional logistic regression model. RESULTS: Two hundred forty-three patients with IBD (47 first-degree familial IBD, 196 sporadic IBD) were enrolled. Forty percent of IBD patients had one or more EIMs compared with 14% matched controls [p < 0.001; OR = 3.1 (95% CI: 1.8 to 5.2)]. A total of 259 of the 1122 IBD patients and their first-degree family members indicated one or more EIM diagnoses (23%). The association between "familial versus sporadic" status and any EIM diagnosis was not significant [p = 0.59, the odds for an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.2 (95% CI: 0.8 to 1.7)]. Ten percent of IBD patients had one or more AD diagnoses compared with 19% matched controls [p = 0.04; OR = 0.4 (95% CI: 0.1 to 0.96)]. A total of 153 of the 1122 IBD patients and their first-degree family members indicated one or more AD diagnoses (14%). The association between disease status ("familial or sporadic") versus any AD diagnosis was not significant [p = 0.68, the odds for any AD in an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.4 (95% CI: 0.9 to 2.3)]. CONCLUSIONS: There was a positive association between IBD status (patient vs control) versus EIM, but not AD. A significant positive association between disease type (familial or sporadic) versus either EIM or AD was not detected.

Adolescent↗

The relationship between inflammatory bowel disease and socioeconomic variables.

OBJECTIVES: Inflammatory bowel diseases (IBD) are chronic diseases associated with considerable morbidity. This morbidity may have an impact on the ability of patients to remain employed, on their marital status, and on their ability to complete a course of higher education. It has long been held that IBD patients are of a higher socioeconomic status and more educated than the general population. Our aim was to determine the relationship between IBD and employment, income, disability, education, and marital status in two population-based data sets based in the province of Manitoba, Canada. METHODS: Two studies are reported here. In study A, we surveyed persons with IBD, using the population-based University of Manitoba IBD Database, created in 1995-1996. We compared these IBD patients to the general population with respect to employment, education, and marital status using data from the 1996 National Population Health Survey. IBD patients were queried as to their socioeconomic status as of the time of diagnosis and also at the time of the survey (1995-1996). In study B, we used a database that linked health care and census variables to determine differences in employment, income, occupation, and marital status among individuals who met the administrative definition of IBD (created in forming the University of Manitoba IBD Database, based on ICD-9-CM codes 555 for Crohn's disease and 556 for ulcerative colitis) compared with the rest of working-age population. RESULTS: In study A we found that, compared with the general population, patients with IBD were more likely to be unemployed. Crohn's disease appeared to affect employment more than ulcerative colitis. IBD patients, however, had a low rate of reporting themselves as disabled (1.3%). Among those married when diagnosed with IBD, approximately 10% of men and up to 20% of women were no longer married 5 yr later. More patients with IBD were married in 1995 compared with the general population; however, more were also divorced. Fewer patients with IBD achieved postsecondary education. In study B, we found that individuals with IBD were twice as likely to be out of the labor force as were controls. Sedentary occupations were twice as likely to be associated with IBD. The income, education level, and marital status of IBD patients were not significantly different from those of controls. CONCLUSIONS: Individuals with IBD at some time in the course of their illness are more likely not to be working than are those in the general population. Based on employment status and job classification, as well as income and education, IBD patients are not of a higher socioeconomic status as previously reported. IBD patients are at least as likely as the general population to be married.

Adolescent↗

Serum human cartilage glycoprotein 39 as a marker of arthritis associated with inflammatory bowel disease.

BACKGROUND: Common blood markers of arthritis are difficult to interpret in arthritis associated with inflammatory bowel disease (IBD) owing to the coexistence of two inflammatory events. No specific serological disease marker is available for IBD. OBJECTIVE: To determine a value of serum human cartilage glycoprotein 39 (HC gp39) as a marker of arthritis associated with IBD. METHODS: Serum levels of HC gp39 and ultrasensitive C reactive protein (CRP) were determined in 121 patients with IBD: 58 without arthritis (IBD-nonA) and 63 with arthritis (IBD-A), and in 20 healthy controls. IBD was classified as active (aIBD) and non-active (naIBD), and patients with IBD-A were classified as type I, II, and III arthritis by clinical activity indices. RESULTS: HC gp39 was higher in IBD-A than in IBD-nonA (p<0.001) and controls (p<0.01), while no difference was found between IBD-nonA and controls. CRP was increased in both IBD-A and IBD-nonA compared with the controls (p<0.01 and <0.05, respectively) and in aIBD-nonA v naIBD-nonA (p<0.05), but no difference in CRP was found between aIBD-A and naIBD-A. Finally, a correlation was found between the number of affected joints (NAJ) and HC gp39 (r = 0.6, p<0.001). DISCUSSION: Increased serum levels of HC gp39, which were higher in IBD-A than in IBD-nonA, suggest that this substance might be a marker of arthropathy in IBD. HC gp39, because of its relationship with NAJ in IBD-A, may also be proposed as a disease activity marker in arthritis associated with IBD.

Adipokines↗

Aberrant expression of maspin in idiopathic inflammatory bowel disease is associated with disease activity and neoplastic transformation.

BACKGROUND: Maspin is both overexpressed in tumors and inflammation, implicating a possible role in bridging inflammation and neoplasia. Idiopathic inflammatory bowel disease (IBD) and IBD-associated dysplasias and carcinomas represent a prototype for studying the relationship between chronic inflammatory states and neoplasia. AIM OF STUDY: To investigate expression of maspin in IBD and IBD-associated dysplasia and colorectal carcinoma. METHODS: Immunohistochemical labeling of maspin was examined using tissue microarrays constructed from archival biopsy and resection tissue from 90 patients with 125 histologically defined lesions including 30 with inactive chronic IBD, 51 with active chronic IBD, 4 IBD-associated foci with epithelial changes indefinite for dysplasia (IFD), 7 with IBD-associated low-grade epithelial dysplasia (LGD), 8 with IBD-associated high grade epithelial dysplasia (HGD), and 25 with IBD-associated invasive colorectal adenocarcinomas. RESULTS: Maspin was expressed in 47/51 (92%) active chronic IBD lesions, which was significantly higher than both inactive chronic IBD (13/30, 43%) and normal mucosa (1 of 9, 11%) (p < 0.01); in particular, the diffuse pattern of maspin expression was significantly higher in active IBD (41/51, 80%), compared with inactive IBD (5/30, 17%) and normal mucosa (0%) (p < 0.01). In the multistage progression model of colitis-associated neoplasia, aberrant labeling was observed at the earliest stages, with 3/4 (75%) IFD foci, 6/7 (86%) LGD, and 8/8 (100%) HGD specimens expressing maspin, virtually always in a diffuse pattern. Expectedly, 22/25 (88%) of invasive IBD-associated cancers overexpressed maspin, including 21 with diffuse labeling. CONCLUSIONS: Maspin is significantly overexpressed in both active IBD and colitis-associated dysplasia compared to either inactive IBD or normal colonic mucosa, suggesting a potential role in disease "flare" as well as neoplastic progression. Targeting maspin for control of disease activity and cancer prophylaxis may be a promising novel therapeutic strategy for IBD.

Adenocarcinoma↗

Risk factors of colorectal cancer in inflammatory bowel disease.

BACKGROUND: It is unknown whether colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) behaves differently from regular CRC in patients without IBD. A case-control study was conducted to compare CRC in patients with and without underlying IBD. METHODS: The Department of Veterans Affairs (VA) maintains a computerized file of all hospital discharges among U.S. military veterans since 1970. This file accrues the data of 1 million hospital discharges per year. All patients with IBD and all patients with CRC who had been discharged from a VA hospital between 1981 and 1993 were selected. The influence of various risk factors on the occurrence of CRC in IBD and its mortality in patients with and without IBD was tested by logistical regression analyses. RESULTS: Of the 11,446 subjects with IBD, 371 had colon cancer. CRC was diagnosed in 52,243 subjects without IBD. CRC patients with IBD were 7 yr younger than those without IBD, but in patients with Crohn's disease, more cancers were located in the proximal colon (chi 2 = 18.10, df = 5, p = 0.003). The occurrence of CRC in IBD was influenced by the following risk factors: age [odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.35-1.57], sclerosing cholangitis (OR) = 3.41, CI = 2.03-5.73), and history of a disease associated with consumption of nonsteroidal anti-inflammatory drugs (NSAID) (OR = 0.84, CI = 0.65-1.09). Sex, race, and type of IBD did not exert a significant influence on the development of cancer. Cancer-related mortality was influenced by the following risk factors: age (OR = 1.16, CI = 1.14-1.18), male gender (OR = 1.23, CI = 1.06-1.44), white race (OR) = 0.97, CI = 0.96-0.99), and history of NSAID consumption (OR = 0.68, CI = 0.65-0.72). Presence of IBD was not associated with a significant influence on CRC mortality (OR = 1.00, CI = 0.70-1.43). CONCLUSIONS: CRC affects IBD patients at a younger age and is characterized by a more proximal localization when compared with CRC of non-IBD patients. NSAID exert a protective influence against CRC in patients with IBD similarly as in patients without IBD. Sclerosing cholangitis is associated with a strong risk of developing colon cancer in patients with IBD.

Age Distribution↗

Infrequency of colonization with Oxalobacter formigenes in inflammatory bowel disease: possible role in renal stone formation.

BACKGROUND AND AIM: Calcium oxalate renal stones (RS) and hyperoxaluria are common in patients with inflammatory bowel disease (IBD). The absence of intestinal oxalate degrading bacteria, Oxalobacter formigenes, may cause hyperoxaluria in IBD. The aim of the present study was to examine: (i) the colonization of O. formigenes in patients with IBD and controls and to correlate its presence with urinary oxalate excretion; and (ii) urinary analytes contributing to RS in IBD. METHODS: Stool samples were studied for O. formigenes using polymerase chain reaction and Southern blotting in patients with IBD (n = 48: ulcerative colitis, 37; Crohn's disease, 11), RS (n = 87) and healthy subjects that were used as controls (n = 48). Levels of urinary oxalate, citrate, calcium, magnesium, creatinine and uric acid were estimated spectrophotometrically in each patient and in 13 controls for 24 h. RESULTS: Five of the 48 (10.4%) patients with IBD had RS. Five of the 48 (10.4%) patients with IBD, 25 of the 87 (29%) with RS and 27 of the 48 (56%) controls were colonized with O. formigenes (P < 0.001 for RS vs controls and P = 0.01 for RS vs IBD). Patients without O. formigenes had higher urinary oxalate than those with it (IBD, median 0.48 [range 0.11-2.09]vs 0.43 [range 0.16-1.10] mmol/24 h, P = NS; RS, median 0.59 mmol/24 h, range 0.14-1.90 vs 0.44 mmol/24 h, range 0.23-0.97; P = 0.008, Mann-Whitney U-test). Median excretion of oxalate was higher in IBD and RS than in controls (0.47 [0.11-2.09], 0.56 [0.14-1.9] and 0.41 [0.21-0.62] mmol/24 h; P < 0.01), respectively. Median calcium was also higher in IBD and RS than in controls (6.50 [1.38-21.00], 6.78 [1.55-20.30] and 4.99 [1.47-9.60] mmol/24 h; P < 0.05, Kruskal-Wallis H-test), respectively. Median urinary magnesium was higher in IBD than in RS and controls (4.57 [1.50-12.30], 3.60 [0.90-6.35] and 2.49 [0.74-4.80]; P < 0.001, Kruskal-Wallis H-test), respectively. Urinary citrate excretion was comparable in IBD, RS and controls. CONCLUSIONS: Patients with IBD and RS rarely have O. formigenes in their stools as compared with controls; this may contribute to hyperoxaluria in IBD. Hyperoxaluria and hypercalciuria may contribute to RS in patients with IBD. Hypermagnesuria in patients with IBD may protect them from RS.

Adolescent↗

Utilization of health care resources by individuals with inflammatory bowel disease in the United States: a profile of time since diagnosis.

BACKGROUND: There are no cost studies of inflammatory bowel disease (IBD) that describe its impact on resource utilization or treatment costs over long periods of time. Our aim was to determine if there are observable trends in health-care resource utilization by adults with IBD depending on disease duration. METHODS: The 1999 U.S. National Health Interview Survey (n = 30,801; N = 195,398,057) included 256 adult cases with IBD who indicated the number of years since the onset of disease. Cases were grouped according to the "number of years with IBD" to distinguish between recent diagnosis (0-5 yr with IBD), long-standing IBD (6-15 yr with IBD), and very long-standing IBD (16-62 yr). A group of non-IBD controls was established and age and gender were controlled for through logistic regression analysis. Odds ratios were computed for resource use including hospitalization, health provider contact, and prescription medication. Population estimates were computed, while accounting for the complex survey design. RESULTS: When compared with the general population, IBD patients were more likely to visit a specialist and to use prescription medication regardless of disease duration. GP visits were more likely until 15 yr with diagnosed IBD [0-5 yr with IBD: OR = 2.26; 95% CI = (1.21-4.21); 6-15 yr with IBD: OR = 2.73; 95% CI = (1.17-6.37)]. Home care was more likely in the IBD population with long-standing disease [OR = 3.21; 95% CI = (1.22-8.40)]. An emergency room visit [OR = 2.41; 95% CI = (1.49-3.88)] and hospitalization [OR = 2.34; 95% CI = (1.38-3.96)] were more likely in the first 5 yr since diagnosis as was hospitalization and surgical intervention [OR = 2.14; 95% CI = (1.09-4.19)]. CONCLUSION: Specialist physicians are visited by IBD patients, and prescription medications are provided to treat IBD patients throughout their lives. This is a statistically significant trend that is viewed from onset of the disease to up to 62 yr with IBD. Our results also suggest, at least tentatively, that patients within the first 5 yr after the onset of the disease have a stronger tendency than the general population to visit an emergency room, to be hospitalized, and to have been both hospitalized and to have had surgery. If these results were borne out by further studies, then this would indicate that we can measure the greatest proportion of treatment effects on these resources within a relatively short period.

Adolescent↗

Voluntary childlessness is increased in women with inflammatory bowel disease.

BACKGROUND: The women's health aspect of inflammatory bowel disease (IBD) is a newer area of study; childbearing issues have received little attention despite the fact that IBD affects women predominantly during their childbearing years. The aim of this study was to better understand patients' considerations about pregnancy-related issues and to examine trends in childbearing so that physicians are able to better tailor their advice to IBD-specific concerns. METHODS: Data were gathered from specific questions in 3147 surveys mailed anonymously to all members of the Crohn's and Colitis Foundation of America (CCFA) Illinois Carol Fisher chapter. The subjects were provided a pre-addressed, pre-stamped return envelope and were instructed to return their completed surveys with no identifying information. Subjects were from the Illinois community. Females IBD patients were 15-44 of age and were members of the CCFA Illinois Carol Fisher chapter. RESULTS: In this study, 169 females age 15-44 years with IBD, 110 with Crohn's disease (CD) and 59 with ulcerative colitis (UC), were identified. Most subjects were white. IBD patients had a higher rate of voluntary childlessness (CD 18%, UC 14%) than the 6.2% seen in the general population (P = 0.001 for CD, P = 0.08 for UC). Women with UC had a lower rate of temporary childlessness (CD 28%, UC 13.6%) than the general population (33%) (P = NS and P < 0.0001 for UC). The rates of nonvoluntary childlessness in IBD were similar to the general population. Women with IBD also had fewer children than their state and national counterparts. The state of the patients' IBD, including those who had gone through a previous pregnancy with IBD, did not alter their resolve to have children. The educational level of our subjects was higher than the nationwide and statewide levels; 76% of the subjects used contraception before diagnosis of IBD, and 82% used it after diagnosis. The most common choices were oral contraception, barrier methods, and abstinence. This study was unable to compare the lifetime rates of complications of pregnancy with population-based controls because such data were unavailable. Furthermore, their findings in this study may not be generalized to all ethnic groups because our population was mostly white. CONCLUSIONS: Women with IBD had a higher rate of voluntary childlessness and fewer children than the general population. These observations are likely attributable to a higher educational achievement and to racial background of the patients rather than to IBD-related reasons. Although contraception use in patients with IBD was lower that in the general population, use was higher after the diagnosis of IBD than before the diagnosis. Contraceptive choices and adoption rates were similar to the general population. Women with CD were more affected by miscarriages after diagnosis with IBD than those with UC.

Adolescent↗

Hyperhomocysteinaemia, coagulation pathway activation and thrombophilia in patients with inflammatory bowel disease.

BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism encoding the thermolabile variant is, when present as homozygote type (TT variant), a known genetic cause of mild hyperhomocysteinaemia (HHCY). This polymorphism has been observed in increased numbers in patients with inflammatory bowel disease (IBD). Coagulation and fibrinolysis are activated in patients with active IBD, but it is not known whether raised plasma homocysteine (HCY) found in patients with IBD significantly contributes to this activation. The aim of this study was to investigate if HHCY or presence of the TT variant significantly induces a hypercoagulable state in IBD patients receiving anti-inflammatory therapy during active disease, and to study if genetic determinants for thromboembolic disease are more frequent in these patients. METHODS: The study was designed as a cross-sectional study in an outpatient clinic comprising 106 IBD patients receiving anti-inflammatory therapy. Markers of coagulation were measured in order to elucidate whether patients with HHCY or the MTHFR TT variant were hypercoagulant compared with patients with no impairment of HCY metabolism. In addition, markers of inflammation and acute-phase reactants were measured in order to compare activity during active disease and during remission. Genetic determinants of thromboembolic disease in patients with IBD and in relevant controls were investigated in the expectation of a more frequent occurrence of these markers of thrombophilia if hypercoagulability could be a primary or contributory factor in IBD. RESULTS: No significant difference could be found in coagulation activity, acute-phase reactants or inflammatory markers in IBD patients with the TT variant of the 677C-->4T polymorphism or high (>15 micromol/L) plasma HCY levels, compared with IBD patients with no impairment of HCY metabolism. In patients with IBD, the coagulation activity was significantly increased during active disease compared with a state of remission. As expected, a significant difference regarding interleukin 6, C-reactive protein and erythrocyte sedimentation rate was present in IBD, comparing active disease with a state of remission. No significant complement activation was present in either of the groups or during active disease. Neither of the allele frequencies of genetic determinants for thrombophilia (coagulation factor V 1691G-->A (factor V Leiden) and factor II 20210G-->A polymorphisms) in the background population differed significantly from that in IBD patients. CONCLUSIONS: This study found no correlation between the MTHFR TT variant or HHCY and a hypercoagulable state in IBD patients receiving anti-inflammatory treatment. This coagulation activity is high during exacerbations of disease, but a considerable reduction is seen in patients on anti-inflammatory therapy compared with non-treated patients. Coagulation activation in IBD is probably a consequence of the inflammatory nature of the disease. That thrombophilia could be a contributory or primary factor in the development of IBD is not supported by the present study, as the frequencies for the genetic determinants for thrombophilia are similar in IBD patients and controls.

Adolescent↗

Bronchial hyperreactivity and allergic status in inflammatory bowel disease.

BACKGROUND: Despite the known systemic manifestations of inflammatory bowel disease (IBD) and a large number of reports associating lung disease and IBD, the frequency of atopy and bronchial hyperreactivity (BHR) in IBD remains obscure. OBJECTIVES: The aim of this study was to investigate the prevalence of abnormal pulmonary function tests, BHR and the atopic status in patients with IBD. METHODS: Thirty patients with IBD (19 with ulcerative colitis and 11 with Crohn's disease; 19 male, 11 female) and 16 controls without any gastrointestinal disease (9 female, 7 male) were included. Patients were questioned with respect to pulmonary and allergic symptoms; subsequently, lung function tests, BHR, skin prick test positivity, peripheral eosinophilia and serum IgE levels were evaluated and compared with those of control subjects. RESULTS: The mean duration of IBD was 5.3 +/- 4.8 years. IBD patients had significantly more often respiratory symptoms in comparison with controls (odds ratio, OR: 9.0, p < 0.04). A previous diagnosis of asthma and antiasthmatic drug treatment were noted in 3/30 (10%) IBD patients. Allergic symptoms were more prevalent in IBD patients in comparison with the controls (OR: 13, p < 0.007), particularly in patients with ulcerative colitis (OR: 16, p < 0.004). The mean FEV(1 )was 3.1 +/- 0.9 liters (96 +/- 18% predicted), mean methacholine PD(20): 14.7 +/- 3.6 mg/ml, mean IgE: 190.5 +/- 305.6 IU/ml (normal value <94 IU/ml) and the percentage of peripheral eosinophils was 3.1 +/- 3.3% in the IBD patients. These values did not result in statistically significant differences in comparison with controls. Furthermore, abnormal lung function and BHR were observed in 8/30 (27%) and 5/30 (17%) IBD patients, respectively. Abnormal lung function tests were more prevalent in the IBD patients than in the controls (OR: 12, p < 0.04). Skin prick tests were positive in 15/30 (50%) IBD patients. The risk of a positive skin prick test increased in the IBD patients in comparison with the controls (OR: 7.0, p < 0.02). Duration and activity of IBD did not influence the prevalence of BHR, allergic and respiratory symptoms, abnormal lung function, high serum IgE levels and skin test positivity. CONCLUSIONS: Allergic symptoms, respiratory symptoms, abnormal lung function tests and skin prick test positivity were more common among the IBD patients in comparison with the controls.

Adult↗

Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis.

BACKGROUND: Inflammatory bowel disease (IBD)--and Crohn's disease (CD) and ulcerative colitis (UC) in particular--could be more reliably diagnosed by using biopsy criteria incorporating the colorectal distribution of specific histologic features. The aim of this study was to elucidate criteria distinguishing IBD from other forms of colitis (non-IBD), and CD from UC on the basis of multiple colorectal biopsies. METHODS: We examined multiple biopsy specimens (mean, 6.1) from 299 consecutive Japanese subjects with active colitis and performed multiple logistic regression analyses on 70 histologic features, from which 2 equations were constructed for the probabilities (P(IBD) and P(CD)) of a) IBD (versus non-IBD), and b) CD (versus UC), respectively, being present. On the basis of a receiver-operating characteristic curve, we determined four cut-off values for P(IBD) and constructed the criteria, consisting of the five categories 'definite IBD', 'probable IBD', 'unknown', 'probable non-IBD', and 'definite non-IBD'. The criteria for CD versus UC were constructed in a similar manner. Their validities were evaluated using 132 Canadian subjects. RESULTS: The statistically significant histologic features were as follows: for IBD, crypt architectural abnormalities, basal plasmacytosis with severe chronic inflammation, and distal Paneth cell metaplasia; for CD, segmental crypt architectural abnormalities and mucin depletion, mucin preservation at the active sites, and focal chronic inflammation without crypt atrophy. In the categories of probable IBD and probable non-IBD, both sensitivities and specificities exceeded 97%. Probable CD and probable UC showed high specificities of more than 97%, and their sensitivities were 94% and 89%, respectively. Kappa statistics showed these criteria to be sufficiently reproducible. CONCLUSIONS: Specific histological features together with their distribution can reliably diagnose IBD, distinguish CD from UC, and provide an estimate of the probability of the underlying disease being present.

Adult↗

Management consensus of inflammatory bowel disease for the Asia-Pacific region.

At the present there are no large-scale epidemiologic data on inflammatory bowel disease (IBD) in the Asia-Pacific region, but several studies have shown an increased incidence and prevalence of IBD in this region. Compared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative colitis (UC) is more prevalent than Crohn's disease (CD). In addition to geographic differences, ethnic differences have been observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have not been found in Asian CD patients. In general, the clinical course of IBD seems to be less severe in the Asia-Pacific region than in Western countries. Diagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infectious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. So far, Western diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non-IBD enterocolitis also must be introduced, and a definite diagnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary to obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. The management of IBD also poses some special problems in the Asia-Pacific Region. There is often a delay in using proper medications for IBD, and alternative local remedies are still widely used. With a combination of Western guidelines and regional experiences, similar principles can be used for induction and maintenance of remission. A stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensive and individualized approaches are suggested for different IBD patients. Deeper understanding of disease pathogenesis and the unique characteristics of IBD in the Asia-Pacific region, combined with reasonable and practical guidelines for drug management and the future use of biological agents would improve the therapeutic outlook of IBD in this region.

Anti-Inflammatory Agents↗

Controversies surrounding the comorbidity of depression and anxiety in inflammatory bowel disease patients: a literature review.

Psychological disorders are highly prevalent in patients with inflammatory bowel disease (IBD). Anxiety and depression are known to independently affect quality of life and may additionally impair quality of life in IBD over and above the IBD itself. Some researchers have further proposed that anxiety and depression may influence the clinical course of IBD. However, despite the potential for anxiety and depression to play an important role in the clinical picture of IBD, there is little prospective well-controlled research in this area. Probably because of this lack of clear data, researchers dispute the actual role of these psychological disorders in IBD, with a number of conflicting opinions expressed. This article reports on a review of the literature in this field. Herein we discuss the five main areas of controversy regarding IBD and the specific psychological comorbidities of depression and anxiety: 1) the relative rate of cooccurrence of these psychological disorders with IBD; 2) the cooccurrence of these psychological disorders with particular phase of IBD; 3) the cooccurrence of these psychological disorders with the specific type of IBD; 4) the rate of these psychological comorbidities compared both to healthy subjects and to other disease states; and 5) the timing of onset of psychological comorbidity with respect to onset of IBD. Methodological weaknesses of the reviewed studies make it impossible to resolve these controversies. However, the results clearly show that anxiety/depression and IBD frequently interact. Given the long-term illness burden patients with IBD face, further prospective, appropriately controlled studies are needed to adequately answer the question of the precise interplay between anxiety/depression and IBD.

Anxiety Disorders↗

Relationship of inflammatory bowel disease and primary sclerosing cholangitis.

There is a strong association between PSC and IBD. PSC is the most common hepatobiliary lesion seen in association with IBD. Whether there are two subsets of PSC, one associated with IBD and one unassociated, is controversial. A lower male to female ratio in patients without IBD supports this view. The demonstration of the haplotype DRw52a in 100% of patients with PSC, irrespective of the absence of IBD, speaks against this view. Patients with isolated PSC tend to present with jaundice, pruritus, and fatigue more frequently than those with combined PSC and IBD. There may also be a difference in bile duct involvement between patients with and without IBD combined with PSC. Apart from usually being a total colitis, either Crohn's colitis or UC, the IBD associated with PSC cannot be distinguished from IBD without PSC with respect to symptoms and clinical course. Patients with combined IBD and PSC may have somewhat worse prognosis than those with isolated PSC. The majority of patients developing BDC have concomitant IBD, suggesting that patients without IBD represent a different subgroup of PSC and run a different clinical course. Most studies have, however, found no differences in epidemiology, pathogenetic factors, clinical findings related to the hepatobiliary disease and prognosis between those who present with PSC alone and those who present with combined PSC and IBD. A major problem when discussing the relationship between IBD and PSC is that the bowel is inadequately examined in many of the studies relating to this question.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholangitis, Sclerosing↗