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Metabolic bone disease in inflammatory bowel disease.

Osteoporosis is associated with a high morbidity rate and is a risk factor for fractures. Patients with inflammatory bowel disease are at increased risk of developing osteopenia and osteoporosis. Corticosteroid use, malnutrition, and proinflammatory cytokines are unique risk factors for bone loss in ulcerative colitis and Crohn disease. Bone mineral density is assessed by dual-energy X-ray absorptiometry and reported as a T score or number of standard deviations away from the mean. A T score < 1 SD below the mean is normal, 1 to 2.5 SD below the mean is consistent with osteopenia, and greater than 2.5 SD below the mean is defined as osteoporosis. Treatment includes a combination of basic preventative measures, for example, weight-bearing exercise, calcium, vitamin D, and pharmacologic agents, (e.g., bisphosphonates).

Bone Density↗

Inflammatory Bowel Disease.

Inflammatory disease comprises at least two forms of chronic intestinal inflammation: Crohn's disease and ulcerative colitis. This article reviews the epidemiology, cause and pathogenesis, clinical presentation and course, potential complications, and treatment of both Crohn's disease and ulcerative colitis.

Journal Article↗

The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study.

OBJECTIVE: The aim of this study was to determine the prevalence of the major extraintestinal manifestations of inflammatory bowel disease (IBD) and their relation to disease diagnosis and gender. METHODS: We used the population-based University of Manitoba IBD Database, which includes longitudinal files on all subjects of all health system contacts identified by International Classification of Diseases, 9th Revision, Clinical Modification codes for visit diagnosis. We extracted a cohort from our database, which included subjects with a known diagnosis of IBD for at least 10 yr. We then determined how many contacts each subject had for each of the following extraintestinal IBD-associated immune diseases: primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, and erythema nodosum. We calculated the prevalence of the extraintestinal diseases using an administrative definition of having at least five health system contacts for the diagnosis in question. This administrative definition has previously been validated in Crohn's disease and ulcerative colitis (UC). RESULTS: A total of 6.2% of patients with IBD had one of six major extraintestinal diseases studied in this report. Only 0.3% of patients had multiple extraintestinal diseases. Iritis/uveitis was the most common extraintestinal disease of all assessed (2.2% of women and 1.1% of men). Iritis/uveitis was more common among women, particularly those with UC (3.8%). Primary sclerosing cholangitis was most common among men with UC (3%). Ankylosing spondylitis was more common among men, and the highest rate was seen among men with Crohn's disease (2.7%). Pyoderma gangrenosum was more common in Crohn's (1.2%) with no gender predilection. Erythema nodosum was similarly present in Crohn's and UC but was more common among women (1.9%). CONCLUSIONS: The associations of immune mediated diseases in extraintestinal sites may help us to further our understanding of IBD pathogenesis, and it may help us in developing a paradigm of disease subsets.

Adult↗

Endoscopic ultrasonography in inflammatory bowel disease, paracolorectal inflammatory pathology, and extramural abnormalities.

Endoscopic ultrasound (EUS) is easy to perform, noninvasive, and well tolerated in individuals with inflammatory bowel disease. In the anorectal region, the examination takes minimal preparation and has become a routine procedure in the diagnosis and therapeutic follow-up of malignant and nonmalignant disorders. Topics discussed in this article include techniques, abscesses, and fistulas.

Abscess↗

[Joint disease in inflammatory bowel disease].

The joint disorders taxonomically included in the group of seronegative spondyloarthropathies under the generic name of enteropathic arthropathy represent the most frequent extra-intestinal manifestation of inflammatory bowel disease (IBD), affecting 33% of patients. Their frequency is similar to that of ulcerative colitis and Crohn's disease. Enteropathic arthropathy consists of two main joint alterations, peripheral and axial arthritis, as well as a variable group of other peri-articular disorders. Type 1, or pauciarticular, peripheral arthritis generally coincides with IBD exacerbations, while type 2, or polyarticular, peripheral arthritis follows an independent course from IBD. Axial involvement precedes and follows an independent course from IBD and can behave as ankylosing spondylitis or asymptomatic sacroiliitis. The treatment of these rheumatologic disorders is based on the application of general measures and the use of nonsteroidal anti-inflammatory agents; intraarticular corticosteroid administration may eventually become necessary. Sulphasalazine and/or infliximab, which are indicated when the previously mentioned measures fail, can be used to treat both the articular and intestinal diseases simultaneously.

Arthritis↗

[Quality of life in patients with inflammatory bowel diseases: translation to Portuguese language and validation of the "Inflammatory Bowel Disease Questionnaire" (IBDQ)].

BACKGROUND: Crohn's disease comprises, together with ulcerative colitis, the inflammatory bowel diseases, which because their morbidity and chronic evolution have a considerable impact on the patient's quality of life. The measurement of quality of life requires the determination of the degree of subjective well-being attributed to the lack of symptoms, to psychological state and daily activity, and is useful as an instrument of evaluation, both in clinical trials and health programs. Inflammatory Bowel Disease Questionnaire is an instrument developed by North-American investigators of McMaster University which reproducibility and validity has been determined in several countries studies, and has shown its use in the measurement of the quality of life of patients with inflammatory bowel diseases. AIMS: Our purpose was to translate that instrument into Portuguese language, its adaptation to Brazilian culture and verify its psychometric properties (validity and reproducibility). METHODS: It was applied to a population of 50 inflammatory bowel diseases patients (24 with Crohn's disease, 26 with ulcerative colitis). To test the criteria and construction validity of the instrument's, it was compared with SF-36, a general questionnaire for establishing quality of life, and the Crohn's Disease Activity Index and Lichtiger's Index. RESULTS: The correlations obtained were mostly moderate. About the intestinal diseases activity index, Lichtiger's index showed better correlations than Crohn's Disease Activity Index. To evaluate its reproducibility, the instrument was applied on three occasions, twice by the same observer (12 days average between applications) and once by a second observer, resulting in a high degree of intra- and interobserver correlation. CONCLUSIONS: Portuguese version of Inflammatory Bowel Disease Questionnaire is a valid and reproducible instrument which can be used to evaluate the quality of life of Brazilian inflammatory bowel diseases patients.

Adult↗

Influence of SRBC/lymphocyte ratio on T-cell rosettes in alcoholic liver disease and inflammatory bowel disease.

Thymus-derived (T) rosette-forming cells were enumerated in patients with alcoholic liver disease and in patients with inflammatory bowel disease using variable sheep red blood cell (SRBC)/lymphocyte ratios. SRBC/lymphocyte ratios of 60:1 and 32:1 did not reveal significant differences from controls in Crohn's disease. The percentage, but not absolute count, of T cells was significantly reduced in alcoholic hepatitis at the 60:1 ratio. Both the percentage and absolute count of T cells were reduced in alcoholic hepatitis and Crohn's disease with the 8:1 ratio. No significant reduction in T cells was seen at any ratio in patients with compensated alcoholic cirrhosis or ulcerative colitis. Use of a SRBC/lymphocyte ratio of 8:1 indentifies T cells which demonstrate an avidity for SRBC. This avidity may be related to the density of SRBC receptors on the surface of T cells and/or the affinity of these receptor sites for SRBC. Use of the 8:1 ratio may provide a more sensitive means by which to monitor changes in T-cell rosettes in patients suspected of having an altered cellular immune state.

Colitis, Ulcerative↗

HLA disparity determines disease activity through pregnancy in women with inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD) activity during pregnancy is variable and factors influencing the course unknown. We studied the relationship between maternal-fetal HLA disparity and IBD course. METHODS: Women with IBD and childbirth were recruited and medical records were reviewed for five time periods. Twenty milliliters of blood was obtained from mother and child for genotyping. Each mother/child pair was assigned an HLA disparity status (+/-) for HLA A, B, C, DRB1, and DQ loci. Odds ratios were calculated comparing HLA disparity in women whose IBD improved versus those whose disease worsened or remained active. RESULTS: Fifty pregnancies in 38 women were studied. Forty-two of 50 pregnancies (84%) were disparate at the DRB1 locus; 34 (68%) were mismatched at the DQ locus. There was no difference in average disease score or overall activity score based on DRB1 or DQ disparity (p > 0.05 for all comparisons). There were 31 pregnancies disparate at both DRB1 and DQ loci; a significant difference was found in average disease scores and overall activity scores between women mismatched at both loci versus only one or neither locus (OR 8.4 [1.5-14, p = 0.01). Logistic regression identified prepartum disease activity and disparity at both DRB1 and DQ as significant predictors of overall disease activity during pregnancy. CONCLUSION: Improvement of IBD symptoms during pregnancy is associated with disparity in HLA class II antigens between mother and fetus. This suggests that the maternal immune response to paternal HLA antigens plays a role in pregnancy-induced remission. What is accepted and what this research adds are as follows: . The course of IBD during pregnancy is variable. . The factors involved with disease course are unknown. . The data presented here provides a scientific mechanism for disease course during pregnancy. . This is a novel work and it corroborates what has been seen in other autoimmune conditions.

Colitis, Ulcerative↗

Intestinal gamma/delta receptor-bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease.

We studied the numbers of T-cell receptor alpha/beta- and gamma/delta-bearing lymphocytes in 27 jejunal specimens from 19 celiac patients, 27 rectal and colonic specimens from 14 ulcerative colitis patients and four patients with Crohn's disease, and 24 control specimens. MAb and a three-layer peroxidase staining method were used. Only low numbers of gamma/delta + cells were seen in normal jejunum and rectum of controls, as well as in the specimens of patients with inflammatory bowel diseases. In the lamina propria of celiac patients, the mean number of gamma/delta + cells was significantly higher than in the controls before treatment, during gluten-free diet, and after the gluten challenge. Within the jejunal epithelium, the number of gamma/delta + cells was elevated before and during gluten elimination and after the challenge test. The absolute number of intraepithelial gamma/delta + cells remained constant during gluten elimination and provocation. We infer that the constantly elevated population of gamma/delta + T cells in the epithelium of celiac patients may play an important role in the pathogenesis of celiac disease.

Celiac Disease↗

Does primary sclerosing cholangitis occurring in association with inflammatory bowel disease differ from that occurring in the absence of inflammatory bowel disease? A study of sixty-six subjects.

Primary sclerosing cholangitis often occurs in association with inflammatory bowel disease, particularly ulcerative colitis but also Crohn's disease of the colon either with or without terminal ileal disease. Little data exist as to the effect of inflammatory bowel disease on the presenting symptoms, radiological features, response to liver transplantation, and potential risk of bile duct carcinoma in individuals with primary sclerosing cholangitis. In an effort to answer these questions, 66 patients with primary sclerosing cholangitis were studied. The definitive diagnosis of primary sclerosing cholangitis in each was accomplished using cholangiography, which in each case demonstrated characteristic beading, ectasia and stricturing of the intrahepatic and extrahepatic bile ducts. Inflammatory bowel disease was present in 47 (71.2%) patients. Thirty nine (59.1%) had ulcerative colitis; their mean age was 42.5 +/- 11.6 yr (mean +/- SD), and the male/female ratio was 2.9:1. In addition, eight patients (12.1%) had Crohn's colitis; their mean age was 40.5 +/- 6.5 yr, and the male/female ratio of this group was 1:1. Nineteen patients (28.8%) had primary sclerosing cholangitis without any inflammatory bowel disease; their mean age was 42.0 +/- 12.1 yr, and the male/female ratio in this group was 0.72:1. Seventy-two percent of the patients without inflammatory bowel disease had either jaundice, pruritus or fatigue at presentation compared with 41% of the patients with inflammatory bowel disease (p less than 0.05). In contrast, abnormal liver function tests were more common as the first manifestation of liver disease in the latter group (38% vs. 11%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Side effects of sulphasalazine in patients with rheumatic diseases or inflammatory bowel disease.

We compared sulphasalazine (SSZ) toxicity in 140 patients (196 treatment periods) of two patient groups, those with rheumatoid disease (RD) (rheumatoid arthritis, RA, ankylosing spondylitis, AS), and those with inflammatory bowel disease (IBD). Adverse events occurred in 64% of all patients (highest 85% in AS and lowest 50% in ulcerative colitis, CU). There were more recorded adverse events in patients with RD than in patients with IBD. Hepatic side effects were more frequent in patients with IBD than in patients with RD. Adverse events were the most common reason for discontinuing the treatment (in 34.8% of AS patients, in 46.2% of RA patients, in 21.7% of the Crohn's disease patients and in 32.6% of CU patients). There were no lethal or permanent adverse events. Age, sex, rheumatoid factor and HLA-B27 antigen positivity did not influence on the appearance of adverse events.

Adult↗

Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

Adult↗

Expression of cyclooxygenase-2 mRNA in active inflammatory bowel disease.

OBJECTIVES: In inflammatory bowel disease (IBD), increased amounts of prostaglandins correlate to disease activity. Prostaglandins are produced via the cyclooxygenase (COX) pathway and exhibit both pro- and anti-inflammatory effects. Whereas COX-1 is a constitutive enzyme present at all times and is thought to produce the cytoprotective prostaglandins, COX-2 represents the inducible form of cyclooxygenase leading to production of proinflammatory prostaglandins. In inflammatory bowel disease it is yet unclear whether COX-2 plays a role in the inflammatory response. The purpose of this study was to evaluate the role of COX-2 in inflammatory bowel disease. METHODS: Of the 44 individuals included in the study, 22 had ulcerative colitis, 11 had Crohn's disease, and 11 were healthy controls. Standard rigid rectoscopy was performed. The degree of inflammation was assessed using a semiquantitative scale. A biopsy was taken from the most affected area. mRNAs for COX-1 and COX-2 were detected using reverse transcription-polymerase chain reaction. RESULTS: The fraction of patients demonstrating COX-2 mRNA significantly increased with increasing disease activity (p < 0.005), whereas the fraction of patients demonstrating COX-1 mRNA remained unchanged (p > 0.05). CONCLUSIONS: This study demonstrates a clear relationship between endoscopic activity and relative presence of mRNA for COX-2. In contrast mRNA for COX-1 is detected equally often. This indicates that COX-2 is involved in the acute inflammatory response of chronic inflammatory bowel disease.

Acute Disease↗

Complications of inflammatory bowel disease.

Complications in inflammatory bowel disease determine the severity of disease as well as the complexities of medical or surgical treatment opportunities. Therefore, in known inflammatory bowel disease, the prevention, the early detection and the adequate therapeutic response to certain complications are important goals in the follow-up of inflammatory bowel disease patients. Disease complications are separated into intestinal and extraintestinal complications. Intestinal complications are somewhat disease specific, which means that they occur exclusively in either Crohn's disease or ulcerative colitis (e.g., enteric fistulas are particularly found in Crohn's disease and toxic megacolon in ulcerative colitis). Most extraintestinal complications occur in both forms of inflammatory bowel disease (e.g., anemia, thromboembolic events or osteoporosis). The current knowledge on pathogenesis, diagnostic tools, prevention and treatment of certain intestinal and extraintestinal complications is reviewed.

Anemia↗

The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region: no association with inflammatory bowel disease.

Genetic predisposition has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have identified a Crohn's disease susceptibility locus on chromosome 14 (14q11-12; IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5 and IL-13. The IL-25 gene is located within this susceptibility region at 14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine response, we hypothesized that genetic alterations within the IL-25 gene might contribute to IBD. First, direct sequencing of the coding regions of the IL-25 gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this polymorphism was further investigated in 151 patients with Crohn's disease, 111 patients with ulcerative colitis, and 119 healthy controls to determine its clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any significant differences between patients with Crohn's disease or ulcerative colitis and controls. Genoytype-phenotype relations in patients with Crohn's disease showed a comparable distribution of the c424C/A polymorphism in all subgroups of the Vienna classification. In summary, our data indicate that genetic alterations in the coding regions of the IL-25 gene are unlikely to play a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be investigated for a potential association with other chronic inflammatory and inherited disorders such as autoimmune diseases.

Adolescent↗

Advances in the assessment of disease activity in inflammatory bowel disease.

Knowledge of the severity and extent of the inflammation in inflammatory bowel diseases provides a means of determining rational therapeutic strategies in affected patients. During the past 3 decades, several clinical, laboratory, and combined indices have been proposed for the assessment of inflammatory bowel disease; refinements in radiologic methods and the availability of endoscopy and biopsy have facilitated the accurate assessment of the extent and severity of the disease. In relapsing conditions such as inflammatory bowel disease, however, the use of such procedures is limited by the radiation exposure or the relatively invasive nature of the technique. In this article, we review the proposed methods and recent advances in assessment of patients with inflammatory bowel disease; we also discuss possible strategies at the time of diagnosis, during recurrence, and in evaluation of the efficacy of drug or dietic therapy.

Colitis, Ulcerative↗

The changing epidemiology of inflammatory bowel diseases.

Epidemiological studies of inflammatory bowel disease are important in order to find possible clues to the still unknown etiology, as well as for the planning of the health service. In supplement to short-term studies, reporting the actual state of the disease, long-term studies are requisited to follow up the development of inflammatory bowel disease. Inflammatory bowel disease has become more frequent during the past decades, with an approximate prevalence of 0.5% in the northern part of the world. A changed disease panorama can be noted with increasing median age at diagnosis, a growing entity of patients with colorectal Crohn's disease and a shift towards more distal ulcerative colitis. The increased age at diagnosis is attributed to a postponement of the age-specific incidence peak. While the difference between gender has levelled off, difference still exists in young adults in Crohn's disease and in elderly in ulcerative colitis. Colorectal cancer has become a matter also in Crohn's disease.

Adolescent↗