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PubMed1990

Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease.

In a study designed to determine which T-cell subsets are involved in the development of murine graft-versus-host disease (GVHD), a prospective histologic analysis of gastrointestinal involvement was performed. In C57BL/6JXDBA/2F1 (B6D2F1) recipients of DBA/2 donor spleen and bone marrow cells, the colonic histologic findings were found to be similar in many respects to the histologic findings reported in human colonic GVHD and were much more severe and diffuse than were the abnormalities of the small intestine. Host irradiation before transplantation was found to play an additive or synergistic role in the development of GVHD. Furthermore the histologic features noted in DBA/2----B6D2F1 murine colonic GVHD suggest that bone marrow and spleen cell transplantation in this strain combination may be a useful model for studying the immunologic mechanisms involved in human inflammatory bowel disease. Thus severe colonic disease noted during the course of DBA/2----B6D2F1 murine GVHD was found to have significant histopathologic similarities to both human GVHD enteropathy and other inflammatory diseases of the human colon.

Animals↗
PubMed1999

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↗
PubMed2005

Epidemiology of juvenile-onset inflammatory bowel disease in central Saudi Arabia.

There is limited information about inflammatory bowel disease in Arab children. Hence, the objective of this study was to report on the epidemiology of this condition in our community. Medical records were analysed for all children below 18 years of age diagnosed with inflammatory bowel disease (IBD) and followed up in our institution over a period of 10 years. From 1993 to 2002, 50 consecutive children were diagnosed to have IBD. This gives an estimated incidence of 0.5 cases/100 000/year and a prevalence of 5 cases/100 000 populations for the region of Riyadh, Saudi Arabia. Most of the children (90 per cent) were Saudi nationals and the female to male ratio was 1 : 0.6. The age range was between 5 and 18 years with 16 per cent of the cases diagnosed in children below 12 years of age. Chronic ulcerative colitis was the commonest form accounting for 48 per cent, followed by Crohn's disease and indeterminate colitis in 38 per cent and 16 per cent of the children, respectively. The best agreement between colonoscopic and histopathologic findings (89 per cent) was in children with ulcerative colitis followed by normal findings and Crohn's disease in 63 per cent and 35 per cent of the cases, respectively. It was concluded that the incidence and prevalence of IBD in this report are lower than in any other population. Nevertheless, comparison with older data suggests that the incidence is increasing.

Adolescent↗
PubMed2005

Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988-1999).

OBJECTIVE: To assess the incidence and location at diagnosis of inflammatory bowel disease in children and adolescents in northern France between 1988 and 1999. METHODS: A 12-year prospective population-based study was conducted by gastroenterologists and pediatric gastroenterologists of northern France (1,312,141 children <17 years of age). RESULTS: From 1988 to 1999, 509 cases of childhood inflammatory bowel disease were recorded (7.2% of all inflammatory bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative colitis and 20 indeterminate colitis. The mean standardized incidence was 3.1/10(5) for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8 for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease location at diagnosis was: small bowel and colon (71%), colon only (10%) and small bowel only (19%). Location of initial ulcerative colitis was: proctitis (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in 1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2). CONCLUSIONS: The incidence of Crohn disease in the children of northern France showed an increasing trend (20%; not significant) during the 12-year period while the incidence of ulcerative colitis remained stable. In the entire population(children and adults)the incidence of Crohn disease increased significantly (+23%; P < 0.001), while the incidence of ulcerative colitis decreased (-17%; P < 0.0001).

Adolescent↗
PubMed1996

Susceptibility locus for inflammatory bowel disease on chromosome 16 has a role in Crohn's disease, but not in ulcerative colitis.

In the Western world, chronic inflammatory bowel disease (IBD) presents as two major clinical forms, Crohn's disease (CD) and ulcerative colitis (UC) [Targan, S.R. and Shanahan, F. (1994). In Retford, D.C (ed.), Inflammatory Bowel Disease: From Bench to Bedside. Williams and Wilkins, Baltimore]. Genetic epidemiological studies, the occurrence of rare syndromes associated with IBD, and animal models suggest that inherited factors play significant roles in the susceptibility to both forms of IBD [Yang, H.-Y. and Rotter, J.I. (1995) In Kirsner, J.B. and Shorter, R.G. (eds). Genetic Aspects of Idiopathic Inflammatory Bowel Disease. Williams and Wilkins, Baltimore, pp.301-331]. Recently, a genome-wide search on European families with multiple affected members with CD identified a putative susceptibility locus in the centromeric region of chromosome 16 [Hugot, J.-P. et al. (1996) Nature, 379, 821-823]. We have now tested this region in an independent set of US families, confirmed that this region is likely to contain a gene predisposing to CD, and further refined the chromosomal location of this gene. Most importantly with respect to this locus, our data also seem to indicate that there is heterogeneity both within the CD group, and between the CD and UC groups with respect to this locus. The susceptibility locus appears to be involved only in non-Jewish CD sibpairs and not in our Ashkenazi Jewish CD sibpairs. Additionally, we have tested sibpairs having either only UC or both UC and CD for involvement of this locus, and have found no evidence that this region predisposes to IBD in these patients.

Chromosome Mapping↗
PubMed1996

Methotrexate for inflammatory bowel disease: pharmacology and preliminary results.

OBJECTIVE: To review the limited published experience with methotrexate treatment for inflammatory bowel disease, to examine the proposed anti-inflammatory and immune-modifying mechanism of action and pharmacologic properties of methotrexate, and to detail its limiting toxicities. DESIGN: A comprehensive synopsis of methotrexate is presented to aid physicians who treat patients with inflammatory bowel disease. RESULTS: Methotrexate and its polyglutamate metabolites are folic acid analogues with inhibitory activity against many enzymes in the metabolic pathway of folic acid. Long-term low-dose methotrexate therapy (25 mg or less once a week) inhibits production of thymidylate, purines, and methionine and leads to accumulation of adenosine, a potent anti-inflammatory substance. These actions inhibit cellular proliferation, decrease formation of antibodies, and decrease production of mediators of inflammation such as interleukins and eicosanoids. Three uncontrolled trials and two controlled trials have demonstrated efficacy of low-dose methotrexate therapy for induction of remission in Crohn's disease and have also suggested possible benefit for ulcerative colitis and for remission maintenance indications in both diseases. Although methotrexate is generally well tolerated for long-term use at a low dose, several serious toxicities potentially limit its use. CONCLUSION: Methotrexate is a promising new agent for the treatment of inflammatory bowel disease.

Anti-Inflammatory Agents↗
PubMed2004

Increased incidence of inflammatory bowel disease: the price of the decline of infectious burden?

PURPOSE OF REVIEW: It is now apparent that the increase in the incidence of autoimmune and allergic diseases in Western countries is explained by the decrease in infections. The question is posed to determine whether a similar explanation can be proposed for the increased incidence of inflammatory bowel disease. RECENT FINDINGS: Studies performed in murine experimental models of inflammatory bowel disease have shown that colitis onset can be prevented by bacteria, bacterial extracts, or helminths. Particular interest was given to probiotics (either live or killed), which protect from disease in a toll-like receptor 9 dependent fashion. This protective effect involves regulatory cytokines as indicated by in vitro studies on human inflamed colonic cells. At the clinical level, there is strong suggestion but still limited proof that probiotics improve inflammatory bowel disease through immunoregulatory mechanisms. SUMMARY: Converging clinical and experimental data strongly suggest the protective nonspecific role of infections on inflammatory bowel disease independently from the triggering role of some specific bacteria. The extension to inflammatory bowel disease of the hygiene hypothesis opens new therapeutic perspectives including the revisiting of probiotics and other forms of exposure to bacteria or parasite components.

Journal Article↗
PubMed1999

Plasma and rectal adenosine in inflammatory bowel disease: effect of methotrexate.

In animal models, the antiinflammatory mechanism of action of methotrexate has been attributed to elevation of the extracellular concentration of the endogenous autocoid, adenosine. Our goal was to determine if methotrexate elevates adenosine concentrations in plasma and at the site of disease in patients with inflammatory bowel disease. In 10 patients with Crohn's disease or ulcerative colitis, rectal adenosine and plasma adenosine concentrations were measured before and immediately after a subcutaneous injection of methotrexate, 15 or 25 mg. The mean predose rectal adenosine concentration of 2.4 mumol/l was not significantly different from the postdose concentration of 2.1 mumol/l, p = 0.17, (paired two-tailed t test). Rectal adenosine concentration tended to correlate with rectal endoscopic disease activity, r = 0.59, p = 0.067 (Spearman rank order correlation). After methotrexate injection, neither the mean daily plasma adenosine concentration, nor the plasma adenosine at any individual time point, were significantly different from preinjection values. In patients with inflammatory bowel disease, an injection of methotrexate in the clinically effective dose range does not raise rectal or plasma adenosine concentrations. A role for adenosine as the mediator of the antiinflammatory action of methotrexate is not supported.

Adenosine↗
PubMed2003

HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease.

HYPOTHESIS AND OBJECTIVES: the hypothesis of this study is that genes involved in the regulation of the immune system, expressed by HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA), could be determinants of disease susceptibility and behavior in inflammatory bowel disease (IBD). MATERIAL AND METHOD: seventy patients with a diagnosis of inflammatory bowel disease, 46 with ulcerative colitis and 24 with Crohn"s disease were included. HLA class I (A and B) and II (DR) antigens were studied by serological techniques. Detection of ANCA was carried out in all patients by an indirect immunofluorescence method. The relative frequencies of HLA antigens were compared with a control group made up of 156 blood donors. The control group for the ANCA study was made up of 100 individuals. RESULTS: we found a significant increased frequency of HLA-DR2 in patients with ulcerative colitis. No significant differences were found between patients with Crohn"s disease and controls regarding HLA typing. We detected a significant increase of HLA-DR3 in extensive forms of ulcerative colitis. Detection of ANCA was positive in 46% of the patients with ulcerative colitis and in 12% of the patients with Crohn"s disease (p <0.05). We observed an increased frequency of ANCA in patients with UC and HLA-DR2 (p = 0.15). CONCLUSIONS: the association found between HLA-DR3 and extensive forms of ulcerative colitis provides evidence of genetic heterogeneity. The relationship between ANCA and HLA phenotype (although not significant) supports this concept.

Adolescent↗
PubMed1997

Inflammatory bowel disease: a study of the association between anxiety and depression, physical morbidity, and nutritional status.

BACKGROUND: The etiology of inflammatory bowel disease is unclear, and the role played by anxiety and depression is highly controversial. Anxiety and depression in patients with inflammatory bowel disease could be secondary to disabling symptoms, but the interaction between physical morbidity and psychologic illness in these subjects has not been sufficiently investigated. Patients with inflammatory bowel disease are nevertheless frequently undernourished, but there are no studies on the association between anxiety and depression and malnutrition. This study was designed to characterize anxiety and depression in subjects affected by inflammatory bowel disease and to establish the influence of physical morbidity and/or nutritional status on psychologic disorders. METHODS: Seventy-nine consecutive patients, 43 with Crohn's disease (CD) and 36 with ulcerative colitis (UC), were enrolled in the study. An index of the disease activity and physical morbidity was obtained by the simplified Crohn's Disease Activity Index and Truelove-Witts criteria and using the Clinical Rating Scale. Thirty-six healthy volunteers were studied as controls. All the subjects were given the State and Trait Anxiety Inventory (STAI) test and the Zung self-rating Depression Scale. RESULTS: The percentage of subjects with state anxiety was significantly higher in the CD (P < 0.001) and UC (P < 0.001) groups than in control subjects. There was no significant difference in trait anxiety among groups. The percentage of subjects with depression was significantly higher in the CD (P < 0.05) and UC (P < 0.05) groups than in control subjects. State anxiety and depression were significantly associated with physical morbidity and correlated with malnutrition in CD and UC patients. CONCLUSION: Anxiety and depression in patients with inflammatory bowel disease could be reactive to the disabling symptoms and to malnutrition. As measured with the STAI, personality trait of anxiety does not seem to play an important role in inflammatory bowel disease.

Adult↗
PubMed2000

Biochemical markers and bone densitometry in inflammatory bowel disease.

AIMS: Bone mineral density is reduced in patients with inflammatory bowel disease. The possible causes of this situation are delayed puberty, malabsorption, and corticosteroid use, among others. No published data exist regarding the use of biochemical markers and bone densitometry to assess osteopenia in these patients in Spain. METHODS: We studied 54 patients (24 men and 30 women), 22 with Crohn's disease and 32 with ulcerative colitis. Age, type of disease and average daily dose of prednisone-equivalent corticosteroids were evaluated. Lumbar bone mineral density was assessed quantitative digital radiography densitometry. The bone resorption marker urine D-pyridinoline and the bone formation marker serum osteocalcin were also assessed. RESULTS: Mean age was 36.61 +/- 13.37 years. Daily corticosteroid dose was correlated with D-pyridinoline (r = 0.413; p < 0.01), and D-pyridinoline was inversely correlated with osteocalcin (r = -0.304; p < 0.01). There was a negative correlation between bone mineral density and corticosteroid dose. There was no relationship between biochemical markers and bone densitometry findings in these patients. There were no differences in terms of bone densitometry findings or biochemical markers between the two types of inflammatory bowel disease. CONCLUSIONS: D-pyridinoline correlated inversely with osteocalcin. Daily corticosteroid dose correlated directly with D-pyridinoline, and inversely with bone mineral density.

Adrenal Cortex Hormones↗
PubMed1984

Rectal biopsy helps to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease.

A retrospective blind evaluation of rectal biopsy specimens from 44 patients with acute self-limited colitis and 104 patients with idiopathic inflammatory bowel disease was done. Seven histologic features proved highly discriminant because they occurred often in idiopathic inflammatory bowel disease but rarely, if at all, in acute self-limited colitis. The features with a high predictive probability (87%-100%) of diagnosing idiopathic inflammatory bowel disease were distorted crypt architecture, increased numbers of both round cells and neutrophils in the lamina propria, a villous surface, epithelioid granuloma, crypt atrophy, basal lymphoid aggregates, and basally located isolated giant cells. One or more of these features was present in 79% of all idiopathic inflammatory bowel disease cases. They were seen in both acute and chronic idiopathic inflammatory bowel disease. The biopsy features favoring acute self-limited colitis were less useful. Biopsy diagnosis of acute self-limited colitis is thus primarily based on the absence of histologic criteria favoring idiopathic inflammatory bowel disease. This study provides objective validation of histologic criteria in rectal biopsy that help differentiate acute self-limited colitis from idiopathic inflammatory bowel disease.

Acute Disease↗
PubMed2006

Assessment of the Japanese Inflammatory Bowel Disease Questionnaire in patients after ileal pouch anal anastomosis for ulcerative colitis.

BACKGROUND: The Inflammatory Bowel Disease Questionnaire (IBDQ) is the most widely used disease-specific health-related quality of life questionnaire for patients with inflammatory bowel disease. However, little has been reported about the validation of IBDQ for patients with ulcerative colitis after surgery. The aim of this study was to assess the validity and reliability of the Japanese version of IBDQ in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis (IPAA). METHODS: The validity and reliability of the Japanese IBDQ were assessed in patients with ulcerative colitis who had received IPAA in our hospital. We mailed them the Japanese IBDQ and a supplemental questionnaire on bowel function, which was developed at our institution. Internal consistency, discriminative validity, and factor validity were assessed. RESULTS: Of the 121 patients to whom we sent the questionnaires, 64 patients (53%) participated in this study. The Japanese IBDQ scores correlated well with Cronbach's alpha value (0.800 to 0.923) and daily life satisfaction score (Pearson's r, 0.492 to 0.700). The total IBDQ score and two subscale scores of the IBDQ, "bowel symptoms" and "systemic symptoms," correlated well with daily bowel-movement frequency (Pearson's r, -0.256 to -0.329). Factor analysis revealed a four-factor structure, and all correlations among factors were moderately positive (0.337 to 0.465). Although the factor distribution was not clearly divided into the four IBDQ subscales, these four factors showed a marked tendency to represent the IBDQ subscales independently. CONCLUSIONS: The Japanese IBDQ is a valid and reliable instrument for the assessment of Japanese patients with ulcerative colitis after IPAA.

Adult↗
PubMed1990

Liver damage in juvenile inflammatory bowel disease.

During a 12-year period, 46 children and adolescents with inflammatory bowel disease were followed from the time of diagnosis with regular biochemical tests of liver function. Thirty-four patients had ulcerative colitis and 12 had Crohn's disease. Mean age at the time of diagnosis was 10.2 years (range 7 months-17 years) and the mean follow-up period was 5.2 years (range 1-11 years). Pathological liver function tests were found in 60% of the 34 patients with ulcerative colitis: 9 of these 20 patients demonstrated more severe disturbance, usually at the time of diagnosis. Liver damage was most frequent in patients with total colitis. Liver biopsy was performed in eight patients, demonstrating "pericholangitis", fibrosis and in one case cirrhosis. Morphometry of electron microscopical pictures revealed a significantly increased number of lysosomes and dilated cisternae of the rough endoplasmic reticulum. ERCP was performed in two patients, verifying primary sclerosing cholangitis in one. Four of the 12 patients with Crohn's disease had mildly pathological liver function tests. No correlation was found to the extent, duration or treatment of bowel disease. In our series of juvenile inflammatory bowel disease, liver damage occurred frequently, especially in ulcerative colitis. The more severe changes tended to coincide with the onset of bowel disease.

Biopsy↗
PubMed1998

Preillness non dietary factors and habits in inflammatory bowel disease.

AIM: Environmental as well as genetic factors play a role in the pathogenesis of inflammatory bowel diseases. The effects of smoking and diet have been demonstrated. Other factors have not been extensively investigated. PATIENTS: Preillness non dietary habits and factors were studied in 88 patients with recent onset of inflammatory bowel diseases (55 with ulcerative colitis and 33 with Crohn's disease) and in matched 76 population and 68 clinic controls. RESULTS: No significant differences were found in relation to education, housing, birth weight, breast feeding in infancy and current weight. The current body mass index was significantly lower in patients as compared to clinic controls (p < 0.05). More patients had low levels of physical activity during the preillness period as compared to controls (p < 0.001 vs clinic controls), while more controls engaged in moderate (p < 0.05) or high levels of physical activity in the corresponding periods. Patients spent fewer hours in strenuous physical activity as compared to controls (NS). Patients slept fewer hours per day (p < 0.05 vs clinic controls). More patients than controls experienced stressful life events during the year prior to onset of symptoms (p < 0.05 for patients with Crohn's disease against both controls and all patients vs population controls). CONCLUSIONS: Other environmental factors besides smoking and diet may affect the pathogenesis of inflammatory bowel disease.

Adolescent↗
PubMed1998

The role of complementary medicine in European and Asian patients with inflammatory bowel disease.

Three hundred and eighty-two patients with known inflammatory bowel disease (IBD) (190 European and 192 Asians) and 190 with coeliac disease were sent a previously validated questionnaire to investigate patients' use of alternative medicine and their views on its effectiveness. Details sought included whether they have ever consulted an alternative practitioner, whether they had followed a course of treatment and its clinical effects. Information about where patients had heard about such alternative practitioners and whether they were told to discontinue their current allopathic medication was sought. Results were analysed after three consecutive mailings, including one in Gujurati to Asian patients. A randomly selected group was re-interviewed four months later. To validate the study alternative medicine practitioners were also interviewed to investigate what percentage of their attendees have IBD and how many of those clients were Asians. One hundred and fifty-eight questionnaires were returned from European patients with IBD (response rate = 83%), 145 from patients with coeliac disease (response rate = 76%) but only 81 Asian patients with IBD (response rate = 42%). Forty-seven European and Asian patients with inflammatory bowel disease sought advice or treatment from an alternative practitioner, compared with only 11 with coeliac disease (chi(2) = 11.64, df = 12, P < 0.003). There was no significant difference in consultation rates between Asian and European patients with IBD (Yates corrected chi(2) = 0.78, ns). The most common practitioners consulted by all groups were homeopaths (n = 23) and herbalists (n = 27) but 20 patients consulted more than one practitioner at a time. Patients with coeliac disease and European patients with IBD had consulted osteopaths (n = 6) and reflexologists (n = 7). Ten patients with IBD had also attended a spiritualist and five Asian patients a hakim. Common sources of information about alternative remedies included friends and relatives (n = 13), the media (n = 11), word of mouth (n = 11) and family practitioners (n = 6). Most patients were advised to continue their current medications, although two had been told to stop and 10 advised to reduce the dose of their allopathic medications. Twenty alternative medicine practitioners stated that overall between 2-5% of their attendees have IBD with 10% of those clients being Asian. Asians preferred to consult Asian practitioners rather than European practitioners. There was no clear consensus as to whether complementary therapies were felt beneficial, although many patients with IBD believed them to be helpful.

Asia↗