S. Bollani

Altered bone metabolism in inflammatory bowel disease : there is a difference between Crohn's disease and ulcerative colitis

Abstract. Ardizzone S, Bollani S, Bettica P, Bevilacqua M, Molteni P, Bianchi Porro G (‘L. Sacco’ University‐Hospital, Milan, Italy). Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn’s disease and ulcerative colitis. J Intern Med 2000; 247: 63–70.

Bowel ultrasound in assessment of Crohn's disease and detection of related small bowel strictures: a prospective comparative study versus x ray and intraoperative findings

Background and aim: Despite the fact that bowel ultrasound (US) has recently been proved to be useful in the assessment of bowel diseases, uncertainty persists as to its diagnostic role in patients with complicated Crohns disease (CD). Therefore, we have prospectively investigated the accuracy of US compared with x ray procedures and intraoperative findings in detecting small bowel strictures complicating CD as well as its reliability in assessing disease extent and location within the bowel. Methods: A series of 296 consecutive patients with proven CD admitted to L Sacco University Hospital between 1997 and 1999, having undergone complete radiographic evaluation (including small bowel x ray, colonoscopy, or double contrast barium enema), were enrolled in the study. Bowel US was performed in each patient by two experienced operators unaware of the results of other diagnostic procedures. The accuracy of US in detecting strictures compared with x ray studies was determined separately in two different groups of patients: 211 patients treated conservatively (non-operative CD) and 85 patients who were candidates for surgery for CD complications or unresponsiveness to medical therapy (operative CD). Results: Overall sensitivity and specificity of US in assessing the anatomical distribution of CD were 93% and 97%, respectively. The extent of ileal disease measured at US correlated well with that determined by x ray (r=0.52, p<0.001) in medically treated patients as well as with that measured intraoperatively in surgical patients (r=0.64, p<0.001). One or more stenoses were detected in 75 patients (35.5%) at small bowel enteroclysis in the non-operative CD group compared with 70 (82%) in the operative CD series. Sensitivity, specificity, and positive predictive values of bowel US in the detection of strictures were 79%, 98%, and 95% in non-operative CD patients and 90%, 100%, and 100% in operative CD cases, respectively. Conclusions: In experienced hands, bowel US is an accurate technique for assessing CD extent and location and is very helpful in detecting small bowel strictures, especially in very severe cases that are candidates for surgery. The use of bowel US is therefore justified as a primary investigation in CD patients in whom complications are suspected.

Ultrasonographic detection of intestinal complications in Crohn's disease

The aim of this study was to evaluate the sensitivity and specificity of ultrasound (US) in assessing the main abdominal complications of Crohns disease (CD), such as strictures, fistulas and abscesses. A series of 98 consecutive inpatients with complicated and uncomplicated Crohns disease, having undergone a complete endoscopic and radiographic evaluation of the intestinal tract, entered the study. In particular, in these patients the presence of strictures, fistulas, and abscesses, detected by means of colonoscopy, small bowel x-ray, double-contrast barium enema, and computed tomography, was also assessed by means of transabdominal US. US sensitivity and specificity in the assessment of stenosis of Crohns disease were 74.4% and 93.1%, respectively. When ileal and colonic stenosis were considered separately, transabdominal US correctly assessed 84.6% of ileal stenosis and 58.8% of colonic stenosis. Eight of 12 fistulas were detected, but only 50% of enteroenteric fistulas were diagnosed. The presence of abscesses was correctly detected in 83.3% of cases by means of US. Our data suggest that US is a suitable complementary method for the detection of abdominal complications of Crohns disease, such as strictures and abscesses; however, its usefulness in assessing enteroenteric fistulas seems to be fairly limited.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn’s disease

BACKGROUND & AIMS Osteoporosis frequently occurs in Crohns disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. METHODS In 34 international centers, 272 patients with Crohns disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. RESULTS Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. CONCLUSIONS Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohns disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Comparison between methotrexate and azathioprine in the treatment of chronic active Crohn’s disease: a randomised, investigator-blind study

BACKGROUND AND AIMS The efficacy of azathioprine in the treatment of chronic active Crohns disease is well established. However, this drug has a long onset of action. Methotrexate has also been shown to be effective in chronic active Crohns disease. The aim of this study was to evaluate the efficacy and safety of methotrexate in comparison with azathioprine, and to establish whether methotrexate has a shorter onset of action in this setting. METHODS Patients with chronic active Crohns disease were admitted to this investigator-blind study. Chronicity was defined as the need for steroid therapy of > or = 10 mg/day for at least 4 months during the preceding 12 months, with at least one attempt to discontinue treatment. The disease had to be clinically active at entry, with a Crohns Disease Activity Index of > or = 200. Six patients treated with azathioprine and methotrexate, respectively, were found to have enterocutaneous and perianal fistulas. At entry, all patients received prednisolone (40 mg once a day) which was tapered over a period of 12 weeks unless their clinical condition deteriorated. All patients were randomised to receive i.v. methotrexate 25 mg/week, or oral azathioprine 2 mg/kg per day, for a 6-month follow-up period. After the first 3 months, methotrexate was switched to oral administration maintaining the same dose. The primary efficacy outcome considered was the proportion of patients entering first remission after 3 and 6 months of therapy. Clinical remission was defined as the lack of need for steroid treatment and a Crohns Disease Activity Index score of < or = 150 points at each scheduled visit. RESULTS In the 54 patients (26 F, 28 M, mean age 34 years, range 18-60) randomly assigned to methotrexate (n=27) or azathioprine (n=27), no statistically significant difference was found between the two treatment regimens with respect to remission rate after 3 (methotrexate 44%, azathioprine 33%, p=0.28, (95% CI, 0.369-0.147), and 6 months (methotrexate 56%, azathioprine 63%, p=0.39, 95% CI, 0.187-0.335), respectively. Six patients withdrew from therapy due to adverse events: 3/27 (11%) in methotrexate and 3/27 (11%) in azathioprine. Drug-related adverse events (asthenia, nausea and vomiting) that did not require withdrawal from therapy were more frequent in the methotrexate group (azathioprine: 2/27 (7%); methotrexate: 12/27 (44%), p=0.00009). The frequency of these adverse events was comparable during the intravenous or oral administration of the drug. CONCLUSIONS This study confirms that methotrexate is effective in inducing remission in patients with chronic active Crohns disease, therapeutic efficacy being comparable, but not faster, than that of azathioprine.

Perianal Fistulae Following Infliximab Treatment Clinical and Endosonographic Outcome

BackgroundManagement of perianal and rectovaginal fistulae complicating Crohn’s disease (CD) is unsatisfactory. Infliximab is effective in the treatment of fistulating CD. However, reopening of fistulae is frequent, suggesting the persistence of deep fistula tracts despite superficial healing. In this study, the clinical and endosonographic behavior of perianal fistulae were evaluated following infliximab infusions, as well as the role of anal endosonography (AE) in predicting their outcome. MethodsThirty CD patients presenting with perianal and/or rectovaginal fistulae received an infusion of infliximab at a dose of 5 mg/kg at weeks 0 (entry into the study), 2, and 6. Laboratory and clinical assessments were repeated at same intervals and at week 10. AE was performed at entry and at week 10. Thereafter, the perianal region was re-examined every 6 months, and patients were investigated regarding draining of the fistula in the previous months. ResultsFifteen patients (53.6%) showed closure of the fistulae at week 10, but only 5 patients had the fistula tracts disappeared at AE. Clinical and AE closure of rectovaginal fistulae was less prevalent than that of perianal fistulae [14.3% versus 63.6% at week 6 (p = 0.035); 28.6% versus 59.1% at week 10 (p = 0.21); 14.3% versus 22.7% at AE (p = 1.00)]. The behavior of fistulae was not affected by their number and AE classification, presence of rectal disease, or setons. Twenty patients with perianal fistulae were followed for a median of 15.5 months. Patients with closed perianal fistulae at week 10 and disappearance of fistulae tract at AE showed a lower relapse rate than those with endosonographic persistence of fistula tract. ConclusionsInfliximab can heal perianal and rectovaginal fistulae in approximately 60% and 30% of patients, respectively. Despite closure, most fistula tracts are still detectable at AE. Persistence of the internal tract is a condition at higher risk of fistula recurrence.

Focal gastric inflammatory infiltrates in inflammatory bowel diseases : Prevalence, immunohistochemical characteristics, and diagnostic role

OBJECTIVES:To date, few studies have evaluated gastric histology in patients with inflammatory bowel disease (IBD). The aim of this prospective controlled study was to establish the frequency of focal gastritis in Crohns disease (CD) and ulcerative colitis (UC) patients, as well as to evaluate its immunohistochemical characteristics and clinicoanatomical determinants.METHODS:We evaluated 141 consecutive patients with known CD of the large and/or small bowel, 79 patients with UC, and 141 CD- and UC-free controls; all underwent upper gastrointestinal (GI) endoscopy and 13C urea-breath test. Biopsy specimens taken from the antrum, angulus, and gastric body were evaluated by histology and immunohistochemistry. A series of variables, including CD activity index, duration, extent and location of disease, intestinal resection, number of recurrences, and previous and current medical therapy, as well as the presence of dyspeptic symptoms and mucosal lesions at endoscopy, were determined in all CD patients and correlated with the presence or absence of focal gastritis.RESULTS:Helicobacter pylori-associated gastritis was found in 47 patients with CD (33%), in 37 patients with UC (47%), and in 60% of CD-/UC-free controls (p < 0.01). In H. pylori-negative CD patients focal gastritis was found in 43% of cases (40/94), compared with 12% (5/42) of UC patients and 19% (11/57) of controls (p < 0.05). Specificity and positive predictive value of focal gastritis in CD were 84% and 71%, respectively. It was characterized by a focal perifoveolar or periglandular lymphomonocytic infiltrate, with CD8+/CD4+ cells predominant both in CD and UC patients. There were no significant correlations between the occurrence of focal gastritis and any clinicoanatomical CD features.CONCLUSIONS:Focal gastritis is relatively common in CD patients although it is not exclusive to this condition. Its recognition could be useful in the diagnostic workup of any patient with suspected or indeterminate inflammatory bowel disease, as it makes a diagnosis of CD more likely.

Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease.

Background : A high prevalence of osteoporosis has been noted in Crohns disease, but data about fractures are scarce.

Epidemiological aspects of irritable bowel syndrome in Europe and North America.

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription.

Long-term results and multivariate analysis of prognostic factors in 138 consecutive patients operated on for Crohn’s disease using “bowel-sparing” techniques

BACKGROUND Conservative surgery has become accepted as a useful option for the surgical treatment of complicated Crohns disease (CD). METHODS One hundred thirty-eight consecutive patients treated with strictureplasty or miniresections for complicated CD have been observed prospectively. The possible influence of a number of variables on the risk of recurrence was investigated using the Cox proportional hazard model, and a time-to-event analysis was made using the Kaplan-Meier function. RESULTS There was no perioperative mortality; the morbidity rate was 5.7%. A close correlation was found between the risk of recurrence and the time between diagnosis and first surgery. The overall 5-year recurrence rate was 24%, being 36% in the patients requiring surgery within 1 year of diagnosis and 14% in those operated on more than 1 year after diagnosis. CONCLUSIONS Risk factor analysis highlighted a group of patients at high risk of surgical recurrence. Given that our results are similar to those reported in other series, we consider strictureplasty and miniresections safe and effective procedures for the treatment of complicated CD.