Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease.

BACKGROUND: Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]. METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins. RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10-23] and oncostatin-M [OSM; p = 3.7 × 10-16]. Nine of these proteins are associated with cis-germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224-756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43-6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn's disease respectively. CONCLUSION: We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.

Faecal microbiota signatures of IBD and their relation to diagnosis, disease phenotype, inflammation, treatment escalation and anti-TNF response in a European Multicentre Study (IBD-Character).

METHOD: We examined faecal samples, using the GA-map™ Dysbiosis Test, to associate gut microbiota composition with Crohn's disease (CD) and ulcerative colitis (UC) and to identify markers for future biomarker identification. We conducted a prospective case-control study (EU-ref. no. 305676) in an inception cohort of 324 individuals (64 CD, 84 UC, 116 symptomatic non-IBD controls and 44 healthy controls) across five European centres and examined 54 predetermined bacterial markers. We categorized patients according to the Montreal Classification and calculated the dysbiosis index (DI). Non-parametric tests were used to compare groups and the Bonferroni correction to adjust for multiple comparisons. RESULTS: The fluorescent signals (FSSs) for Firmicutes and Eubacterium hallii were lower in inflammatory bowel disease (IBD) vs. symptomatic controls (p<.05). FSS for Firmicutes, Lachnospiraceae, Eubacterium hallii and Ruminococcus albus/bromii were lower, whereas the signal for Bacteroides Fragilis was higher in UC vs. symptomatic controls (p<.05). FSS was higher for Bifidobacterium spp., Eubacterium hallii, Actinobacteria and Firmicutes among patients with ulcerative proctitis, compared to extensive colitis (p<.05). In CD, we observed no association with disease location. The DI correlated with faecal-calprotectin in both CD and in UC (p<.001). In terms of treatment escalation and anti-TNF response, differences were observed for some bacterial markers, but none of these associations were statistically significant. CONCLUSION: Our data reveal that the GA-map™ Dysbiosis Test holds the potential to characterize the faecal microbiota composition and to assess the degree of dysbiosis in new-onset IBD. On the other hand, our results cannot demonstrate any proven diagnostic or predictive value of this method to support clinical decision making.

Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.

BACKGROUND: MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. METHODS: In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. RESULTS: In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20-3.27; logrank p = 1.80 × 10-3), in particular CD [HR 2.81; IQR: 1.11-3.53, p = 6.50 × 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. INTERPRETATION: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa.

Lymphocyte recruitment to peripheral tissues is fundamental for immune surveillance and homeostasis, but the chemokines and chemokine receptors responsible for tissue-specific homing of T cells to the upper airway mucosa have not been determined. To address this, we analyzed the chemokines expressed in the normal human nasal mucosa and found that CCL28 is preferentially expressed at a high level on the lumenal face of vascular endothelial cells in the mucosa. Analysis of the cognate chemokine receptors revealed that close to 50% of the CD4(+) T cells in the human nasal mucosa expressed the CCL28 receptor CCR3, whereas CCR3 was hardly detectable on T cells in the small intestine and skin. In the circulation, CCR3(+) T cells comprised a small subset that did not express homing receptors to the intestine or skin. Moreover, depletion of CCR3(+)CD4(+) T cells abrogated the proliferative response of human blood CD4(+) T cells against the opportunistic nasopharyngeal pathogen Haemophilus influenzae, indicating that the CCR3(+)CD4(+) T-cell subset in the circulation contains antigen specificities relevant for the upper airways. Together, these findings indicate that CCL28-CCR3 interactions are involved in the homeostatic trafficking of CD4(+) T cells to the upper airways.

Plasmacytoid dendritic cells are scarcely represented in the human gut mucosa and are not recruited to the celiac lesion.

Celiac disease (CD) is a chronic small intestinal inflammation precipitated by gluten ingestion. According to case reports, interferon (IFN)-α administration may induce development of overt CD. Plasmacytoid dendritic cells (PDCs) were thought to be the source of IFN-α and promote a T helper type 1 response leading to lesion formation. Surprisingly and contradicting to earlier findings, PDCs were described as the main antigen-presenting cells (APCs) in human duodenal mucosa and particularly in CD. Here we show that when assessed by flow cytometry and in situ staining, PDCs represent < 1% of APCs in both normal duodenal mucosa and the celiac lesion. Low levels of IFN-α were detected in the celiac lesion assessed by western blot, reverse transcriptase (RT)-PCR, and immunohistochemistry. In four cell populations sorted from the celiac lesion (based on their expression of HLA-DR and CD45), we found that equally low levels of mRNA for IFN-α were distributed among these cell populations. Together, these results suggest that relatively small amount of IFN-α, produced by a variety of cell types, is present in the celiac mucosa. IFN-λ, a type III IFN important in intestinal antiviral defense, was produced mainly by APCs, but its expression was not increased in the celiac lesion.

Density of CD163+ CD11c+ dendritic cells increases and CD103+ dendritic cells decreases in the coeliac lesion.

Coeliac disease is a chronic inflammation of the intestinal mucosa controlled by gluten-specific T cells restricted by disease-associated HLA-DQ molecules. We have previously reported that mucosal CD11c(+) dendritic cells (DCs) are responsible for activation of gluten-reactive T cells within the coeliac lesion. In mice, intestinal CD11c(+) DCs comprise several functionally distinct subsets. Here, we report that HLA-DQ(+) antigen-presenting cells (APCs) in normal human duodenal mucosa can be divided into four subsets with striking similarities to those described in mice: CD163(+) CD11c(-) macrophages (74%), and CD11c(+) cells expressing either CD163 (7%), CD103 (11%) or CD1c (13%). CD103(+) and CD1c(+) DCs belonged to partly overlapping populations, whereas CD163(+) CD11c(+) APCs appeared to be a distinct population. In the coeliac lesion, we found increased density of CD163(+) CD11c(+) APCs, whereas the density of CD103(+) and CD1c(+) DCs was decreased, suggesting that distinct subpopulations of APCs in coeliac disease may exert different functions in the pathogenesis.

C-reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study.

BACKGROUND AND AIMS: C-reactive protein (CRP) levels are often used in the follow-up of patients with inflammatory bowel disease (IBD). The aims of this study were to establish the relationship of CRP levels to disease extent in patients with ulcerative colitis and to phenotype in patients with Crohn's disease, and to investigate the predictive value of CRP levels for disease outcome. METHODS: CRP was measured at diagnosis and after 1 and 5 years in patients diagnosed with IBD in south-eastern Norway. After 5 years, 454 patients with ulcerative colitis and 200 with Crohn's disease were alive and provided sufficient data for analysis. RESULTS: Patients with Crohn's disease had a stronger CRP response than did those with ulcerative colitis. In patients with ulcerative colitis, CRP levels at diagnosis increased with increasing extent of disease. No differences in CRP levels at diagnosis were found between subgroups of patients with Crohn's disease as defined according to the Vienna classification. In patients with ulcerative colitis with extensive colitis, CRP levels above 23 mg/l at diagnosis predicted an increased risk of surgery (odds ratio (OR) 4.8, 95% confidence interval (CI) 1.5 to 15.1, p = 0.02). In patients with ulcerative colitis, CRP levels above 10 mg/l after 1 year predicted an increased risk of surgery during the subsequent 4 years (OR 3.0, 95% CI 1.1 to 7.8, p = 0.02). A significant association between CRP levels at diagnosis and risk of surgery was found in patients with Crohn's disease and terminal ileitis (L1), and the risk increased when CRP levels were above 53 mg/l in this subgroup (OR 6.0, 95% CI 1.1 to 31.9, p = 0.03). CONCLUSIONS: CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis. Phenotype had no influence on CRP levels in patients with Crohn's disease. CRP is a predictor of surgery in subgroups of patients with either ulcerative colitis or Crohn's disease.

Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study.

BACKGROUND: CDP870 is a PEGylated Fab' fragment of a humanized monoclonal antibody that neutralizes tumour necrosis factor-alpha. AIM: To evaluate the safety and efficacy of a single intravenous dose of CDP870 or placebo over a 12-week period in patients with moderate-to-severe Crohn's disease. METHODS: Ninety-two adult patients with Crohn's disease (Crohn's Disease Activity Index: 220-450 points) were randomized to receive CDP870 [1.25 (n = 2), 5 (n =26), 10 (n = 17) or 20 mg/kg (n = 23)] or placebo (n = 24). Crohn's Disease Activity Index scores were determined at weeks 0, 2, 4, 8 and 12. The primary end-point was the percentage of patients achieving clinical response [i.e. a decrease in Crohn's Disease Activity Index score > or = 100 points or remission (Crohn's Disease Activity Index score: < or =150 points)] at week 4 in the intent-to-treat population. RESULTS: The percentage of patients achieving the primary end-point was comparable across all treatment groups (56.0%, 60.0%, 58.8% and 47.8% for placebo, CDP870 5, 10 and 20 mg/kg, respectively). The remission rate at week 2 was 47.1% with CDP870 10 mg/kg vs. 16.0% for placebo (P = 0.041). All treatments were well-tolerated: adverse events, reported by 43 patients treated with CDP870 and 15 patients treated with placebo, were mainly mild-to-moderate in intensity. There were no infusion reactions. CONCLUSIONS: A single intravenous dose of CDP870 was well-tolerated by patients with Crohn's disease. While no statistically significant difference in clinical response rates between CDP870 and placebo was observed, clinical benefit in terms of remission was demonstrated.

Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow-up study of 100 Norwegian patients admitted to one unit.

BACKGROUND: Most follow-up studies in patients with alcoholic liver cirrhosis have been for a 5-year period or less. The aim of this study was to assess the long-term mortality and causes of death among patients with alcoholic liver cirrhosis and to identify predictors of mortality. METHODS: One hundred patients with alcoholic liver cirrhosis, consecutively admitted to one medical department, were included in the study from May 1984 until December 1988. All patients had a history of alcohol abuse of at least 100 g ethanol daily for several years. The study comprised 65 men and 35 women with a median age of 58 years (range 34-82). Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty-seven had ascites at admission and 34% had bleeding oesophageal varices. All patients were followed prospectively until death or until October 2000. RESULTS: During the follow-up period 90% of the patients died, 68 of whom (76 %) had been autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was 18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and 90%, respectively. None of the patients underwent liver transplantation during the study. The causes of death were bleeding, liver failure or a combination of these two conditions in 52 of 90 patients (58%), while 9 (11%) died of hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the Cox regression analysis, age, alcohol abuse and alkaline phosphatase were independent and significant predictors of mortality, but Child-Pugh class was not. CONCLUSIONS: The mortality in a group of patients with advanced alcoholic cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%, respectively. Independent predictors of a poor prognosis were high age, continuous alcohol consumption of more than 10 g ethanol per day and high levels of alkaline phosphatase.

Health-related quality of life in patients with inflammatory bowel disease five years after the initial diagnosis.

BACKGROUND: Health-related quality of life (HRQOL) has become an important tool in evaluating patient satisfaction in inflammatory bowel disease (IBD). So far, few prospective follow-up studies have been done to identify variables that influence HRQOL. We aimed to identify demographic and clinical variables that influence HRQOL 5 years after diagnosis in patients with ulcerative colitis (UC) or Crohn disease (CD) included in a prospective follow-up study from 1990 to 1994 (the IBSEN study). METHODS: All patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire translated into Norwegian and validated. We present data from 497 patients (328 UC patients and 169 CD patients, mean age 43.3 years, 48% female). The impact of age, gender, smoking, symptom severity, disease distribution, rheumatic symptoms and surgery on IBD patients' HRQOL was analysed. RESULTS: Women had a reduction in IBDQ total score of 10 points compared to men, CD patients had a reduction of 7.5 compared to UC patients. The patients with moderate/severe symptoms had a 50 points lower score than the patients without symptoms. The patients with rheumatic symptoms had a 10 points lower total score than the patients without these symptoms. All differences were statistically significant. The multiple regression analysis showed that symptom severity, rheumatic symptoms and female gender were the strongest predictors of reduction in HRQOL for both diagnosis groups. CONCLUSION: IBD symptoms, rheumatic symptoms and female gender have a significant influence on patients' HRQOL as measured by IBDQ. This was confirmed by the regression analysis.

Bone mineral density in patients with inflammatory bowel disease: a population-based prospective two-year follow-up study.

BACKGROUND: Bone loss and osteoporosis are commonly reported in inflammatory bowel disease (IBD), especially Crohn disease (CD). The aims of the present study were to evaluate changes in bone mineral density (BMD) in IBD patients during a 2-year follow-up period, and to investigate the role played by possible contributing factors in bone loss. METHODS: Sixty patients with CD and 60 with ulcerative colitis (UC) were studied initially. Fifty-five CD and 43 UC patients were re-examined after 1 year, and 50 CD and 44 UC patients after 2 years. Lumbar spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry (DXA), and Z scores were obtained by comparison with age-matched and sex-matched healthy subjects. Biochemical variables were assessed at inclusion and at the 1-year follow-up visit. RESULTS: Mean BMD values were unchanged in both CD and UC patients. In patients with repeated measurements, significant differences in Z scores (delta Z score) were found for femoral neck and total body in CD and for total body in UC. Significant bone loss occurred in 11 CD (22%) and 12 UC (27%) patients. A significant increase in BMD was found in 21 CD (42%) and 20 UC (46%) patients. In CD patients the initial BMD values for lumbar spine and femoral neck were inversely correlated to BMD changes at the same sites and the change in body mass index (BMI) was positively correlated to change in the total body BMD. C-reactive protein was significantly higher in CD patients with bone loss. Biochemical markers of bone metabolism could not be used to predict BMD changes. Although it was not significant, there was a relationship between corticosteroid therapy and bone loss in CD. CONCLUSIONS: Only minor changes in BMD were observed in both CD and UC patients during a 2-year period. The multifactorial pathogenesis of bone loss in IBD makes it difficult to assess the importance of each single contributing factor. However, our results indicate that disease activity and corticosteriod therapy are involved in bone loss in CD patients.

Interferon-gamma-secreting T cells localize to the epithelium in coeliac disease.

Increased levels of interferon-gamma (IFN-gamma) transcripts have previously been found in duodenal biopsy specimens from patients with untreated coeliac disease (CD). Such samples and duodenal control mucosa were therefore studied to locate and phenotype cells spontaneously secreting IFN-gamma. Specimens were collected from consecutively recruited patients with untreated (seven), treated (four) or refractory (three) CD and from five histologically normal controls. Morphological and immunohistochemical examinations were performed, and epithelial and lamina propria cell suspensions were prepared from parallel samples. Unstimulated viable cells secreting IFN-gamma were identified and phenotyped with a new fluorescence-activated cell sorter-based assay, and IFN-gamma messenger RNA (mRNA) was analysed in snap-frozen aliquots of the same suspensions. Untreated CD cases had the highest fraction of IFN-gamma+ cells in the epithelial compartment (median 2.6%, range 1.6-6.2%) and, less strikingly, in the lamina propria compartment (1.6%, range 0.3-3.6%), followed by refractory (1.4%, 1.0-1.9%; and 0.3%, 0.0-1.2%) and treated (0.8%, 0.5-0.9%; and 0.7%, 0.2-1.1%) disease and finally the controls (0.5%, 0.3-0.9%; and 0.2%, 0.1-0.7%). IFN-gamma mRNA data supported these findings. IFN-gamma+ intraepithelial lymphocytes were mostly CD3+ and CD8+, whereas many positive lamina propria cells were CD8-. We conclude that isolated T cells spontaneously secreting IFN-gamma localize preferentially in the epithelium of patients with classical and refractory CD.

Heterogeneity of intraepithelial lymphocytes in refractory sprue: potential implications of CD30 expression.

BACKGROUND: Refractory sprue is defined as primary or secondary failure to respond to a gluten free diet in patients with coeliac disease-like enteropathy and may signify cryptic or overt enteropathy associated T cell lymphoma. AIMS: To study in detail jejunal morphology and immunophenotypes in patients with refractory sprue in the search for features that might be useful to predict prognosis. PATIENTS: Seven patients are described, representing all such cases identified in our hospital over a 13 year period. METHODS: Biopsy and/or surgical resection specimens were examined by morphology, immunohistochemistry, including enzymatic and immunofluorescent detection, and molecular biology. RESULTS: All patients had phenotypically abnormal intraepithelial lymphocytes (IELs) that lacked CD8, T cell receptor alpha beta (or gamma delta), and/or expressed CD30 in addition to variable expression of the natural killer cell receptor CD94. A monoclonal T cell population was present in six cases, data from the seventh being inconclusive. Three patients had overt lymphoma with CD30+ tumour tissue intervening between intact mucosa that contained neoplastic IELs. Intriguingly, CD30+ IELs were observed both a long way away from, and in direct continuity with, the tumours in these patients. Such CD30+ cells were hardly detected in patients without tumours, two of which are in good health several years after the initial diagnosis. CONCLUSIONS: Our data suggest that abnormal IELs in patients with refractory sprue are phenotypically heterogeneous. CD30 expression by these cells may indicate a worse prognosis, including the occurrence of overt lymphoma.

Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease.

BACKGROUND: Although the pathogenesis of osteoporosis in inflammatory bowel disease (IBD) is not established, vitamin D deficiency and disturbances in calcium metabolism are thought to be of importance, especially in Crohn disease (CD). Vitamin D status is assessed and the relation between indices of calcium metabolism, including 25-hydroxyvitamin D and parathyroid hormone concentrations. and bone mineral density (BMD) in CD and ulcerative colitis (UC) are examined. Sixty patients with CD and 60 with UC were investigated. Each group comprised 24 men and 36 women. METHODS: Vitamin D metabolites, parathyroid hormone and biochemical markers of bone metabolism were measured in blood and urine. Lumbar spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry (DXA) and Z-scores were obtained by comparison with age- and sex-matched normal values. RESULTS: Vitamin D deficiency (25-hydroxyvitamin D3 <30 nmol/l) was present in 27% of patients with CD and in 15% with UC. Furthermore, CD patients had a significantly lower mean concentration of 25-hydroxyvitamin D3 compared with UC patients. Vitamin D status was not related to BMD at any of the skeletal sites measured. Secondary hyperparathyroidism was found in 10 out of 27 patients with CD after small-bowel resections. No differences were found in serum osteocalcin and urine pyridinoline between patients with CD and those with UC. CONCLUSIONS: Hypovitaminosis D is common in CD patients. Patients with CD and small-bowel resections are at risk of developing secondary hyperparathyroidism and low BMD.

The prevalence and incidence of peripheral arthritis in patients with inflammatory bowel disease, a prospective population-based study (the IBSEN study).

OBJECTIVES: To estimate the occurrence of peripheral arthritis (PA) 6 yr after diagnosis of inflammatory bowel disease (IBD). METHODS: In a population-based cohort of 654 patients with a definite diagnosis of IBD, 521 patients (80%) were clinically examined by a rheumatologist 6 yr after IBD diagnosis. RESULTS: PA related to IBD (PAIBD) was detected at examination in four patients (point prevalence 0.8%). If the patients' own reports of PA were accepted, 12% of the cases had developed such manifestations. The striking difference may be explained by the nature of PAIBD exhibiting a short-lasting, self-limiting, non-destructive course and by possible differences in the validity of both methods of ascertainment. CONCLUSION: Our results indicate that PAIBD occurs in a considerable number of IBD patients during the first years after diagnosis, but the point prevalence of PAIBD is low.

Fibromyalgia and chronic widespread pain in patients with inflammatory bowel disease: a cross sectional population survey.

OBJECTIVE: To assess the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in a population based cohort of patients with inflammatory bowel disease (IBD). METHODS: Patients in a prospective survey on newly diagnosed IBD were, 5 years after study entry, invited to a clinical examination including the investigation of musculoskeletal manifestations. A total of 521 patients were examined, corresponding to 80% of surviving cases with definite diagnoses of ulcerative colitis (UC) and Crohn's disease (CD). The diagnoses of FM and CWP strictly followed the American College of Rheumatology classification criteria of 1990. RESULTS: At clinical examination, FM was diagnosed in 18 patients (3.5%), 3.7% with UC and 3.0% with CD. The prevalence was 6.4% in females and 0.4% in males. Thirty-eight patients (7.3%) had CWP (8.5% with UC; 4.8% with CD). The female:male ratio was 27:3 in the UC group and 8:0 in CD. In 19 patients (50%), CWP occurred after onset of IBD. No correlation with the extent of intestinal inflammation and the occurrence of FM and CWP was found. CONCLUSION: The prevalences of FM and CWP in patients with IBD were similar to those of the general population. There were no differences in prevalence of FM and CWP between UC and CD. Chronic idiopathic inflammation of the intestine does not appear to predispose to chronic widespread pain.