Vincenza Di Leo

Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease

Background and aimsCalprotectin and lactoferrin are specific neutrophil-derived proteins, which can be measured in the feces because they are released by cells in inflammatory conditions. We evaluated the efficacy of calprotectin and lactoferrin in detecting organic disease as assessed by colonoscopy.MethodsThe study comprised 144 patients undergoing colonoscopy for lower gastrointestinal symptoms (abdominal pain, altered bowel habits, and bloody stools) (67), or inflammatory bowel disease activity, or surveillance for dysplasia (77). A single stool sample was assayed for calprotectin and lactoferrin. The proportion of patients correctly diagnosed with each test and the relationship with endoscopic and histological findings were measured.ResultsFecal excretion of calprotectin significantly correlated with the finding of colonic inflammation at endoscopy, both in ulcerative colitis and in Crohn’s disease (p<0,001 and p<0,008, respectively), while lactoferrin excretion significantly correlated with histological inflammation (p=0.001 and p=0.009 respectively). Recommended cut-off values need to be adjusted in the inflammatory bowel disease group. Overall sensitivity, specificity, positive predictive value, and diagnostic efficacy were 78, 83, 86, and 80% for calprotectin and 80, 85, 87, and 81% for lactoferrin, respectively.ConclusionsFecal calprotectin and lactoferrin appear to be equally recommendable as inflammatory disease markers in patients with lower gastrointestinal symptoms. Both tests are needed to accurately discriminate activity in inflammatory bowel disease patients.

Can calprotectin predict relapse risk in inflammatory bowel disease

OBJECTIVE:Assessing the clinical course of inflammatory bowel disease (IBD) patients consists of periodical clinical evaluations and laboratory tests. We aimed to assess the role of calprotectin tests in predicting clinical relapse in IBD patients.METHODS:Ninety-seven patients with ulcerative colitis (UC) and 65 with Crohns disease (CD) in clinical remission were prospectively included in the study. A 10-g stool sample was collected for calprotectin assay. The cutoff level was set at 130 mg/kg of feces. Patients were followed up for 1 yr after the test or until relapse. The cumulative proportion of relapses was estimated by the Kaplan-Meier analysis. Statistics for equality of survival distribution were tested using the log-rank test.RESULTS:The calprotectin test was positive in 44 UC patients and 26 of them relapsed within a year, while 11 of 53 UC patients with a negative calprotectin test relapsed within the same time frame. Thirty CD patients had a positive calprotectin test and 13 of them relapsed within a year, as did 7 of the 35 with a negative test result. A significant correlation emerged between a positive calprotectin test and the probability of relapse in UC patients (P= 0.000). In CD patients, only cases of colonic CD showed a significant correlation between a positive calprotectin test and the probability of relapse, i.e., 6 colonic CD patients were positive for the calprotectin test and 4 relapsed (P= 0.02).CONCLUSIONS:Measuring calprotectin may help to identify UC and colonic CD patients at higher risk of clinical relapse.

Discrepancies Between Reported Food Intolerance and Sensitization Test Findings in Irritable Bowel Syndrome Patients

OBJECTIVES:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with clinical signs typical of “intestinal” food allergies or intolerance. The aim of this study was to characterize the clinical features of IBS patients suspected of suffering from adverse reactions to food.METHODS:The study involved 128 consecutive IBS patients divided into four groups according to their main symptom on presentation at our outpatient clinic. A detailed medical history was recorded, paying particular attention to any allergies and reported intolerance to food. Each patient was screened for allergies; intestinal permeability tests was performed in randomly selected patients from different groups. Findings were analyzed using the χ2 test.RESULTS:Adverse reactions to one or more foods were reported by 80 patients (62.5%); skin prick tests (SPT) were positive in 67 patients (52.3%) with no significant differences between patients complaining of different symptoms. Patients who reported a food intolerance had more positive SPTs than those who did not (47 of 80 [58.7%] vs 20 of 48 [41.7%]); this difference was not statistically significant, although it suggests a trend (p < 0.0610). There was little consistency between the specific foods reported to cause intolerance and those resulting from the tests (11 of 80 patients, 13.7%). The intestinal permeability test was normal in 29 of 33 patients (87.9%).CONCLUSIONS:More than 50% of IBS patients were found sensitized to some food or inhalant without any typical clinical signs. Patients were unable to identify potentially offending foods. The lack of a correlation between SPT results and reported food allergies needs further investigation to clarify the pathophysiology and improve the diagnosis of intestinal food allergies.

Zinc supplementation tightens "leaky gut" in Crohn's disease.

ObjectivesSmall intestinal permeability is often increased in patients with Crohn’s disease and may be pathogenic for clinical relapses. No effective prophylactic treatment is available for these patients. The aim of this study was to ascertain whether zinc supplementation may improve intestinal permeability. MethodsWe studied 12 patients with quiescent Crohn’s disease who had been in remission for at least 3 months and had increased intestinal permeability on two separate occasions within the last 2 months. Patients received oral zinc sulfate supplements (110 mg three times a day) for 8 weeks and were followed-up for 12 months thereafter to monitor relapses. ResultsWe found that the lactulose/mannitol ratio was significantly higher before supplementation than after (0.041 ± 0.003 versus 0.026 ± 0.005). During follow-up, 10 patients had normal intestinal permeability and did not relapse; of the remaining two who had increased intestinal permeability, one relapsed. ConclusionsOur findings show that zinc supplementation can resolve permeability alterations in patients with Crohn’s disease in remission. Improving intestinal barrier function may contribute to reduce the risk of relapse in Crohn’s disease.

Influence of Disease Site and Activity on Peripheral Neutrophil Function in Inflammatory Bowel Disease

Reactive oxygen species, released by phagocytes, are involved in tissue injury in inflammatory bowel diseases. The aim of our study was to evaluate peripheral neutrophil function in patients with ulcerative colitis (N = 66) and Crohns disease (N = 62) with respect to disease activity and extent, using chemiluminometry after three stimuli. Twenty-seven healthy subjects were enrolled as controls. Neutrophils from ulcerative colitis and Crohns disease patients had a significantly higher response than those from controls following phorbol myristate acetate (86.6 ± 6.5, 173.8 ± 11.9, 167.5 ± 12.2 mV, P < 0.0001), formyl-methionyl-leucyl-phenylalanine (39.5 ± 3.4, 41.3 ± 2.7, 58.6 ± 4.7 mV, P < 0.001), and zymosan (142.6 ± 10.4, 223.7 ± 8.9, 231.2 ± 9.5 mV, P < 0.0001) administration. The increased response was observed during both active disease and remission. The highest chemiluminescence values were found in patients with active ulcerative pancolitis and ileal Crohns disease. The activation of circulating neutrophils may indicate persistent intestinal inflammation or may be triggered by luminal factors even in the absence of symptoms.

Effect of penicillamine and zinc on iron metabolism in Wilson's disease

Objective. The physiology of iron metabolism in Wilsons disease is largely unknown, and there is a paucity of data on the real presence and progression of iron accumulation. The purpose of this study was to assess the iron metabolism parameters, including hepatic iron concentration, in follow-up liver biopsies and serum, and urinary pro-hepcidin. Material and methods. Twenty-three Wilsons disease patients undergoing long-term treatment were enrolled in the study. Results. Hepatic iron content was significantly increased in penicillamine-treated patients compared with zinc-treated patients. Serum and urinary pro-hepcidin concentrations were significantly higher in Wilsons disease patients than in healthy volunteers, despite a normal biochemical pattern of iron metabolism. Conclusions. Long-term penicillamine treatment seems to be responsible for a more marked iron accumulation in the liver. This observation may justify a revision of long-term Wilsons disease treatment modalities with penicillamine. The finding that serum and urinary pro-hepcidin is significantly increased in Wilsons disease patients compared with healthy volunteers suggests a role for hepcidin in iron metabolism in Wilsons disease, but this needs to be confirmed by a study of hepatic hepcidin expression in these patients.

Lactulose/mannitol test has high efficacy for excluding organic causes of chronic diarrhea

Abstract Objectives Diagnosis in chronic diarrhea in the absence of a distinctive clinical pattern is often challenging, as biochemical tests prescribed at the first evaluation do not show enough sensitivity and specificity to tailor further investigation. Intestinal permeability to sugars is an accurate test for detecting intestinal damage. The aim of this study was to evaluate the diagnostic value of the lactulose/mannitol (L/M) test in patients with chronic diarrhea. Methods We conducted a prospective cohort study to evaluate the diagnostic value of the L/M test in chronic diarrhea. The test was administered to 261 consecutive patients presenting with three or more bowel movements daily for at least 3 wk. Biochemical tests including complete blood cell count, acute phase reactive proteins, serum albumin and iron, and stool cultures for bacteria, ova, and parasites were assessed at the same time. Additional diagnostic investigations were directed by clinical features as well as first-line test results. Results Over 3 yr, 120 (46%) of our patients were found to have an organic cause for chronic diarrhea, whereas in 141 (54%) a functional condition was diagnosed. Multivariate logistic regression analysis revealed that the L/M test and C-reactive protein were independent predictors for the final diagnosis of organic cause of chronic diarrhea, with odds ratios of 1.5 (95% CI = 1.29–1.78) and 5.2 (95% CI = 1.90–14.12), respectively. The area under the receiver operating characteristic (ROC) curve of the adjusted model was 0.82, with positive predictive value of 80.4% and negative predictive value of 77.7%. Conclusions The L/M test is a powerful tool for workup in patients with chronic diarrhea. Introducing the L/M test as first-level test effectively improves the selection of patients who need further evaluation.

Clinical relevance of small-bowel findings detected by wireless capsule endoscopy

Objective. Capsule endoscopy is becoming known as a valid tool for identifying sources of obscure gastrointestinal (GI) bleeding. Fewer data are available about its clinical value for other indications. Material and methods. Sixty patients (31 F, mean age 47 years, range 14–80 years) with no signs of overt GI bleeding were investigated by Given M2A video capsule for suspected small-bowel disease. The main clinical features were: iron deficient anemia (20), abdominal pain (12), chronic diarrhea (9), malabsorption and weight loss (7), Crohns disease (CD) (5), and familial adenomatous polyposis (3). Three patients underwent wireless endoscopy for suspected GI neoplasm and one for portal thrombosis. Results. Complete vision of the small bowel was achieved in 55 patients. No small-bowel lesions were identified in 17 patients, but 5 of them had gastric abnormalities. Small-bowel abnormality was found in 38 patients. Lesions compatible with CD were found in 14 patients, diffuse or patchy enteropathy in 7 and polyps in 6. Actively bleeding lesions were detected in 6 patients and potential bleeding sources in 5. Capsule endoscopy had an overall diagnostic yield of 62%. In particular, three small-bowel malignancies were detected and 9 patients received a better definition of their already-known pathology. However, further endoscopies were needed in 10 patients to obtain a diagnosis. One patient, diagnosed with ileal CD, underwent surgery, as the capsule remained trapped in a stricture. Conclusions. Wireless endoscopy effectively visualizes small-bowel abnormalities even though more accurate selection of the patients is needed in order to optimize its diagnostic efficacy.