A. Cozzolino

Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn's disease

Background : Small bowel bacterial overgrowth is common in Crohns disease but its treatment is not clearly defined. Metronidazole and ciprofloxacin are effective antibiotics in active Crohns disease.

Orocecal transit time and bacterial overgrowth in patients with Crohn's disease.

Bacterial overgrowth is frequent in patients with Crohns disease (CD) and can contribute to symptoms. Motility abnormalities can predispose to bacterial overgrowth. The hydrogen (H2) and methane (CH4) breath test is a sensitive and simple tool for the diagnosis of bacterial overgrowth and for the evaluation of orocecal transit time (OCTT). In this study, we investigated the prevalence of OCTT modifications and bacterial overgrowth in a series of consecutive adult patients with CD. In 43 healthy subjects and 67 patients with CD. we performed the lactulose breath test using a gas analyzer that offers the opportunity of measuring both H2 and CH4. Of the patients, 24 had undergone an ileocolic resection before the test with ablation of the ileocecal valve. At the time of the test 15 patients had active disease, whereas in 52 subjects the disease was quiescent. Fifty-seven patients and forty controls were evaluable for OCTT and bacterial overgrowth. In 10 patients and in 3 controls, no H2 or CH4 peak was recorded during the 8-hour test. Out of 57 patients, 13 (23%) were affected by bacterial overgrowth. The prevalence of bacterial overgrowth was higher in patients with previous surgery (30%) than in nonoperated patients (18%). In all patients with bacterial overgrowth, an antibiotic treatment induced a normalization of the test and an improvement of the symptoms. We observed a longer OCTT in the patients compared to controls, although this difference was not statistically significant (154 +/- 45 vs. 136 +/- 45 minutes). OCTT was significantly longer compared to controls in the 14 CD patients with previous ileocolic resection ( 180 +/- 53 vs. 136 + 45 minutes; p < 0.004). In conclusion, we found that a significant proportion of unselected patients with CD has bacterial overgrowth and prolongation of OCTT. We suggest that the modifications in OCTT in patients with CD can predispose to bacterial overgrowth. The lactulose breath test is a simple method that can be more widely used in patients with CD.

Infliximab in the treatment of extra‐intestinal manifestations of Crohn's disease

Background: Crohns disease (CD) is frequently associated with extra‐intestinal manifestations (EIMs) and infliximab has been recently proposed for the treatment of CD with EIMs. Our aim was to evaluate the short‐term efficacy of infliximab in this treatment. Patients and methods: Thirty CD patients were treated with infliximab. Fifteen patients (50%) showed EIMs before starting therapy. Ten patients presented an arthritis (five sacroiliitis, five spondylitis), with six also reporting peripheral arthralgias. Four patients presented cutaneous EIMs while three patients had an ocular EIM. Results: At week 10, all patients reported an improvement in EIMs. Regarding arthritis, ASAS20 and ASAS40 improvement was observed in 80% and 60% of patients, respectively. In the four patients with cutaneous EIMs and in the three with ocular EIMs, complete healing was observed. Recurrence was observed in 10 out of 15 patients (66%) and a second course of treatment with infliximab was required. This proved to be effective in all cases except for one patient who stopped treatment because of a severe adverse reaction. Conclusions: Infliximab is an effective drug in the short‐term treatment of EIMs complicating CD. Although relapse of EIMs occurs frequently, retreatment ensures effective control of the symptoms.

Bowel Wall Thickness at Abdominal Ultrasound and the One-Year-Risk of Surgery in Patients with Crohn's Disease

OBJECTIVES:Abdominal ultrasound can assess the extent and localization of Crohns disease, and an increased bowel wall thickness is the most common finding. Our aim was to correlate bowel wall thickness at ultrasound, with the risk of short-term surgical outcome in patients with Crohns disease.MATERIALS AND METHODS:From 1997 to 2000 we performed ultrasound in 174 consecutive patients with Crohns disease. Surgical operations were recorded over a 1-yr follow-up. Logistic regression analysis was performed to identify clinical and ultrasound risk factors for surgery.RESULTS:Fifty-two patients underwent surgery within 1 yr. Indication for surgery was strictures in most of the cases. Median bowel wall thickness was higher in patients with surgery (8 mm) than those without surgery (6 mm) (p < 0.0001). A receiver operating characteristic (ROC) curve was constructed taking into account bowel wall thickness for selecting patients with a high risk of surgery. The optimized cut-off for equally important sensitivity and specificity was calculated at 7.008 mm. The binary regression analysis showed that CDAI > 150, absence of previous surgery, stricturing–penetrating pattern, the presence of intestinal complications, and intestinal wall thickness >7 mm were associated with an increased risk of surgery. Patients with intestinal wall thickness >7 mm at ultrasound had the highest risk (OR: 19.521, 95% CI: 5.362–71.065).CONCLUSIONS:Data suggest that bowel wall thickness >7 mm at ultrasound is a risk factor for intestinal resection over a short period of time. Routine use of abdominal ultrasound during evaluation of patients with Crohns disease may identify a subgroup that is at high risk for surgery.

Noninvasive diagnosis of small bowel Crohn's disease: Combined use of bowel sonography and Tc-99m-hmpao leukocyte scintigraphy

Background: Crohns disease (CD) is frequently localized in the small bowel, with the diagnosis of disease and the assessment of its extension made by ileo‐colonoscopy (IC) and small bowel enteroclysis (SBE). Transabdominal bowel sonography (BS) and Tc‐99m‐HMPAO leukocyte scintigraphy (LS) are increasingly used for the diagnosis of CD because of their minimal invasiveness, reproducibility, and acceptable costs. Methods: From March 2000 to July 2003, we performed IC, SBE, BS, and LS in 84 patients with either suspected or known small bowel CD. Results: Small bowel CD was present in 50 patients, whereas the other 34 patients received a different diagnosis. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were, respectively, 98%, 97%, 98%, 97%, and 0.97 for SBE; 92%, 97%, 98%, 88%, and 0.94 for BS; and 90%, 93%, 96%, 85%, and 0.92 for LS. In addition, the combined use of BS and LS led to overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 100%, 93%, 96%, 100%, and 0.97, respectively. BS showed a fair concordance with SBE in terms of location (k = 0.71) and a correlation with the extension of the disease (r = 0.67, P < 0.001). LS showed a concordance with SBE with regard to location in about one‐half the population (k = 0.54), whereas it was less effective than SBE in defining disease extension. Conclusions: BS and LS are 2 accurate techniques for the diagnosis of small bowel CD, and their combined use can be recommended as an early diagnostic approach to patients in which the disease is suspected. SBE remains the best procedure for the definition of the location and extension of the disease.

Hepatitis related to cytomegalovirus infection in two patients with Crohn's disease treated with azathioprine

Azathioprine-related side-effects occur in about 15% of treated patients. Liver toxicity is a rare complication of this drug, but is considered, in most cases, a contraindication to the continuation of treatment. However, abnormal liver tests may occur in patients under azathioprine treatment also due to infections. The distinction between toxic and infective causes of abnormal liver tests is important in order to identify patients that can be rechallenged with the drug. Cytomegalovirus infection is common in immunosuppressed transplant recipients, while the incidence is lower in patients with inflammatory bowel disease treated with immunosuppressive drugs. To our knowledge, only 2 cases of cytomegalovirus hepatitis occurring during azathioprine treatment for Crohns disease had been reported so far. Here, we describe two patients who experienced mild hepatitis associated with the onset of cytomegalovirus infection during azathioprine treatment. The infection was documented by the appearance of IgM anti cytomegalovirus. Both cases were self-limiting. In one of the 2 patients, azathioprine was given again after resolution of the hepatitis with good control of Crohns disease and without other complications. We also retrospectively evaluated the incidence of liver abnormalities assessed by blood tests in 58 consecutive patients with Crohns disease treated with azathioprine at our institution. Abnormal results were obtained in 8 out of these 58 patients, requiring discontinuation of the drug in 3 patients, two of whom were the cytomegalovirus cases described above.

The occurrence of lower limb enthesopathy in coeliac disease patients without clinical signs of articular involvement

OBJECTIVE Coeliac disease (CD) is a systemic autoimmune condition induced by gluten consumption in genetically predisposed people, affecting ∼1% of the general population. In the literature, there are many studies that report the association between CD and different kinds of arthritis. The aim of this study was to investigate the presence of entheseal abnormalities by US in patients with CD without clinical signs of articular involvement as compared with healthy control subjects. METHODS Sixty patients with CD attending the gastroenterology outpatient clinic of the University Federico II of Naples and 60 healthy control subjects matched for age and sex were enrolled in this study. Coeliac patients and healthy controls underwent clinical and US examination. RESULTS Among 60 CD patients, 24 (40%) presented at least one entheseal alteration as compared with 6 (10%) control subjects (P < 0.01). In CD patients, the entheseal site more frequently involved was patellar (distal and proximal), while in the healthy controls the enthesopathies were all localized at the Achilles tendon. CONCLUSION In conclusion, the results of this study underline the ability of US to detect signs of subclinical enthesopathy and indicate the presence of a higher prevalence of subclinical enthesopathies in asymptomatic CD patients.

Crohn disease: susceptibility and disease heterogeneity revealed by HLA genotyping

Predisposition to Crohn disease (CD) seems to be genetically determined but, though several reports on the matter, the association between HLA antigens and the disease is still controversial. PCR-SSP high resolution typing in 107 CD patients, and in subgroups selected according to clinical features, showed a positive association with the rare haplotype DRB1*07, DQB1*0303 both in the overall patients (p = 0.002; pc = ns) and in the subgroup of nonfistulized patients (p = 0.0008; pc = 0.032). Moreover, the protective role of the haplotype DRB1*03, DQB1*0201 (p = 0.029) was confirmed also in Italian patients, whereas no strong association with HLA class I alleles has been found. In addition, variability of the HLA alleles frequency in CD subgroups was observed, supporting the hypothesis of a genetic heterogeneity of the disease and suggesting that HLA alleles distribution in selected groups may allow to identify patients with probably different prognosis or associated complications.

Bowel sonography in occlusive Crohn's disease

Dear Editor, A 28-year-old woman with an history of recurrent abdominal pain was urgently admitted to our Hospital because of intestinal occlusive symptoms. A plain film of the abdomen was performed and multiple air-fluid levels in the small bowel were evident. On admission, the patient underwent bowel sonography examination; this showed the presence of a stricturing terminal ileitis (bowel wall thickness of 8 mm) with severe concurrent dilation of the pelvic and proximal ileum …