Impaired contractile response of mesenteric arteries in Crohn's disease

BACKGROUND: Crohn's disease is associated with vascular injury and dysregulation of the intestinal immune system which together can provide disturbance of mesenteric circulation functional properties. AIM: To evaluate the vascular reactivity of mesenteric arteries from patients with Crohn's disease. METHODS: Phenylephrine-induced contractions were assessed from 10 patients with Crohn's disease and 8 control organ donors. NG-nitro-L-arginine-methyl-ester (L-NAME) was used to test the presence of inducible NO synthase. Endothelium dependent and independent relaxation was assessed using acetylcholine, bradykinin, calcium ionophore A23187 and sodium nitroprusside. RESULTS: The contractile response to phenylephrine was significantly decreased in arteries without endothelium from patients with Crohn's disease. Exposure to the NO synthase inhibitor L-NAME restored the contractile response to phenylephrine. Relaxation remained unaltered in both groups. CONCLUSION: These data provide direct evidence for fading of contraction caused by phenylephrine in Crohn's disease. The restored mesenteric artery tone by a specific NO synthase inhibitor suggests that an increased production for NO in vascular smooth muscle might be responsible of this altered vascular reactivity.     

Early vascular changes in Crohn's disease: an endoscopic fluorescence study

BACKGROUND AND STUDY AIMS: Early recurrent lesions occurring after surgery in Crohn's disease may be the result of localized vasculitis. The aim of this study was use fluorescence endoscopy to evaluate the mucosal microcirculation of the neoterminal ileum in relation to endoscopic recurrence in patients who had undergone ileocolonic resection for Crohn's disease. PATIENTS AND METHODS: Ten patients were prospectively enrolled in an endoscopic follow-up study one year after surgery. Recurrence was assessed using routine and fluorescence endoscopy. Biopsies were taken from fluorescent and nonfluorescent sites to look for inflammation and mucosal vascular lesions using standard histological and immunohistochemical methods. RESULTS: Endoscopic recurrence was found in eight patients. At fluorescence endoscopy, the mucosa displayed a heterogeneous pattern, with fluorescent areas corresponding to aphthoid ulcerations; fluorescent rims surrounding dark zones, corresponding to stellar deep ulcers; and small bright spots distributed singly in the mucosa, which appeared normal on routine endoscopy. Histology revealed inflammatory changes with evidence of vascular involvement in 79% of the biopsies taken from the fluorescent spots. CONCLUSIONS: Endoscopic recurrence in Crohn's disease is associated with fluorescent aspects that may reflect vasodilation associated with inflammation, or genuine microvascular lesions. Correlation with the histological findings suggests that these early vascular lesions were secondary to the inflammatory process.     

Adalimumab sustains steroid-free remission after 3 years of therapy for Crohn's disease

Aliment Pharmacol Ther 2011; 34: 306–317

Summary

Background Treatments that achieve sustainable steroid‐free clinical remission in Crohn’s disease are needed; however, long‐term steroid‐sparing efficacy data are limited. Aim To evaluate steroid‐sparing efficacy and the impact of steroid discontinuation on adverse events during treatment of Crohn's disease with adalimumab in the phase III randomised, double‐blind 1‐year CHARM trial and for an additional 2 years in its open‐label extension ADHERE. Methods Steroid‐free remission and response and steroid‐sparing (≥50% steroid dose reduction) remission rates were evaluated over 3 years in patients who were taking corticosteroids at CHARM baseline. Results Of 778 patients randomised in CHARM (including those who did not achieve clinical response to open‐label induction therapy), 313 patients (40%) were on corticosteroids at baseline. In the 206 patients randomised to adalimumab, rates of steroid‐free remission at 1 year and 3 years were 26% and 23% respectively; corresponding rates were 29% and 25% for steroid‐sparing remission and 32% and 28% for steroid‐free response. Although the incidence of serious infections with adalimumab treatment during CHARM was higher in patients taking steroids at baseline than those who were not, the rates of overall adverse events, serious infections and opportunistic infections were lower in patients who were able to discontinue corticosteroids than those who remained on steroids. Conclusion Adalimumab therapy resulted in modest but clinically meaningful rates of steroid‐free remission, sustained over 3 years of treatment, in a heavily pretreated population of patients with Crohn's disease receiving steroids at the start of therapy ( http://www.clinicaltrials.gov number: NCT00077779).     

Value of wireless capsule endoscopy in patients with indeterminate colitis (inflammatory bowel disease type unclassified)

BACKGROUND: Wireless capsule endoscopy (WCE) can identify small bowel mucosal lesions not seen with other imaging modalities. This technique can therefore play an important diagnostic role in the evaluation of patients with inflammatory bowel disease type unclassified (IBDU). We report on a multicentric study whose objective was to evaluate the value of WCE to increase diagnostic accuracy in categorizing IBDU. METHODS: Thirty patients with IBDU and negative serology were included. WCE was performed with a standard Pillcam capsule. Outcome measures were classified as suggestive of Crohn's disease (CD) when -3 ulcerations were present. RESULTS: WCE displayed endoscopic features suggestive for CD in 5 patients. In 6 other patients, WCE was negative, but repeated ileocolonoscopy with biopsies performed during follow-up evaluation revealed CD in 5 and ulcerative colitis (UC) in 1 patient. UC was found in a seventh case at colectomy performed just after WCE. Eighteen patients remained with a diagnosis of IBDU 16 months on average after WCE. CONCLUSIONS: WCE is a potentially clinically useful technique for categorizing a subgroup of patients with IBDU, although negative WCE does not exclude further diagnosis of CD. Patients with negative WCE who remain IBDU at follow-up evaluation may belong to an original subgroup of IBD.     

A controlled trial comparing ciprofloxacin with mesalazine for the treatment of active Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID)

OBJECTIVE: The aim of this randomized controlled study was to investigate the efficacy of ciprofloxacin compared with mesalazine in treating active Crohn's disease. METHODS: Patients with a mild to moderate flare-up of Crohn's disease (mean Crohn's Disease Activity Index [CDAI]; 217; range, 160-305) were randomized to receive ciprofloxacin 1 g/day or Pentasa 4 g/day for 6 wk. Complete remission was defined at wk 6 as a CDAI < or = 150 associated with a decrease (delta) in CDAI > 75. Partial remission was defined as a CDAI < or = 150 with 50 < delta CDAI < 75 or a CDAI > 150 with delta CDAI > 50 at wk 6. Group sequential procedure with triangular continuation regions was used to monitor the trial through the difference in complete remission rates, every 20 patients included. RESULTS: Inclusion of patients was stopped at the second step, i.e., after 40 inclusions, with the conclusion of no difference in complete remission rates between ciprofloxacin- and Pentasa-treated groups. Among the 18 patients taking ciprofloxacin, two decided to stop treatment during the trial and three were considered as treatment failures because of deterioration at wk 3. Among the 22 patients taking mesalazine, one patient was lost to follow-up and eight patients were considered as treatment failures. Complete remission was observed in 10 patients (56%) treated with ciprofloxacin and 12 patients (55%) treated with mesalazine and partial remission was observed in three and one patient, respectively. CONCLUSIONS: This study suggests that ciprofloxacin 1 g/day is as effective as mesalazine 4 g/day in treating mild to moderate flare-up of Crohn's disease.     

Familial Crohn's disease in Belgium: pedigrees, temporal relationships among cases, and family histories

BACKGROUND: Recently we published an analysis of environmental factors in familial Crohn's disease (CD) in Belgium. The aim of the current study was to assess pedigrees and sibships, temporal relationships among cases, and family circumstances relevant to the frequency or onset of CD. STUDY: Twenty-one families with 3 or more affected first-degree relatives were studied. Seventy-four patients with CD and 84 unaffected family members were interviewed together at the parental home, with the aid of a 176 item questionnaire. Pedigrees were constructed establishing which family members had the disease and their relationships within sibships. Dates of onset of disease, validation of first symptoms and circumstances potentially relevant to the onset and distribution of disease within families were among the data documented during the interviews. Sequence of disease within families, consecutive versus nonconsecutive sequence of disease within sibships, and temporal relationships among cases were tabulated. RESULTS: In 12 of the 21 families CD occurred in a parent before CD in any children. Five affected fathers preceded 9 affected children; 7 affected mothers preceded 10 affected children. First borns were affected more frequently. Within sibships there were 21 instances (36%) when an affected sibling was consecutive in birth order with an affected sibling. When a parent had CD before the birth of the first child the "exposure interval" to CD in the children was longer (mean 22.4 y) than when the parent developed CD after the child was born (mean 11.8 y). CONCLUSIONS: The clusterings of CD within sibships and in time suggest that there is a contagious element in the etiology of CD.