Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies

BACKGROUND: Symptoms of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can overlap. We aimed to determine the accuracy of fecal markers, C-reactive protein (CRP), blood leukocytes, and antibody panels for discriminating IBD from IBS and to define a "best test." METHODS: We prospectively included 64 patients with IBD (36 Crohn's disease [CD], 28 ulcerative colitis [UC]), 30 with IBS, and 42 healthy controls. Besides CRP and blood leukocytes, blinded fecal samples were measured for calprotectin (PhiCal Test, enzyme-linked immunosorbent assay [ELISA]), lactoferrin (IBD-SCAN, ELISA), Hexagon-OBTI (immunochromatographic test for detection of human hemoglobin), and LEUKO-TEST (lactoferrin latex-agglutination test). Blinded serum samples were measured for the antibodies ASCA (ELISA) and pANCA (immunofluorescence). RESULTS: Overall accuracy of tests for discriminating IBD from IBS: IBD-SCAN 90%, PhiCal Test 89%, LEUKO-TEST 78%, Hexagon-OBTI 74%, CRP 73%, blood leukocytes 63%, CD antibodies (ASCA+/pANCA- or ASCA+/pANCA+) 55%, UC antibodies (pANCA+/ASCA-) 49%. ASCA and pANCA had an accuracy of 78% for detecting CD and 75% for detecting UC, respectively. The overall accuracy of IBD-SCAN and PhiCal Test combined with ASCA/pANCA for discriminating IBD from IBS was 92% and 91%, respectively. CONCLUSIONS: The PhiCal Test and IBD-SCAN are highly accurate for discriminating IBD from IBS. There is only marginal additional diagnostic accuracy when the PhiCal Test and IBD-SCAN are combined with ASCA and pANCA. ASCA and pANCA have a high specificity for IBD.     

The Status of Diagnostic Markers for Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), which includes ulcerative colitis, Crohn’s disease, and indeterminate colitis, is characterized by chronic inflammation of the digestive tract and has a significant impact on quality of life. Coupled with clinical history, physicians rely on invasive tests (e.g. endoscopy and radiologic examinations) to diagnose IBD. Patients with other gastrointestinal illnesses (e.g. irritable bowel syndrome and celiac disease) may present with symptoms similar to those of an IBD patient. Therefore, a need exists for rapid and noninvasive measures to indicate the presence of IBD. The identification of potential biomarkers associated with IBD has expanded rapidly in the past decade. This article reviews the role of recently studied serologic and fecal markers in the diagnosis of IBD, and differentiation between subtypes of IBD.     

Fecal Lactoferrin and Calprotectin After Ileocolonic Resection for Crohn’s Disease

Purpose This study was designed to assess the role of fecal lactoferrin and calprotectin as markers of intestinal inflammation in patients with Crohn’s disease who have undergone ileocolonic resection. Methods Sixty-three patients who had undergone ileocolonic resection for Crohn’s disease with a median follow-up of 40.5 (range, 5–102) months were enrolled. Clinical examination and blood test were performed, and fecal lactoferrin and calprotectin levels were dosed. The predictors for fecal lactoferrin and calprotectin levels that resulted to be significant at the univariate analyses were included in two multiple regression analysis models. Results The mean lactoferrin level was 21 ± 3.9 μg/g and the mean calprotectin fecal level was 247 ± 22.7 ng/ml. C-reactive protein levels (P < 0.01), calprotectin levels (P < 0.01), and the presence of clinical recurrence (P = 0.04) resulted to be independent predictors of lactoferrin levels. Only lactoferrin levels resulted to be an independent predictor for calprotectin fecal levels (P < 0.01). Conclusions Crohn’s disease patients maintain high fecal levels of lactoferrin and calprotectin at long-term follow-up after resection of the diseased bowel even in case of clinical remission. The significant correlation between the two fecal markers may be the expression of the ongoing intestinal inflammation. Only lactoferrin significantly correlated with C-reactive protein and showed a reliable threshold value for systemic inflammation. Lactoferrin fecal levels may be a reliable indicator for intestinal inflammation influencing the systemic inflammatory status. The third predictor of lactoferrin fecal level was the presence of episodes of clinical recurrence during the postoperative follow-up. Supported in part by the MIUR grant ex 60%.     

Diagnostic advances in inflammatory bowel disease (imaging and laboratory)

Autoimmune and antimicrobial antibodies currently play only an adjunctive role in the diagnosis of inflammatory bowel disease (IBD). Their sensitivity and specificity are not high enough to be relied upon alone to secure a diagnosis; however, their most promising role seems to be in identifying Crohn’s disease patients at a higher risk of progression to intestinal complications. Serum C-reactive protein (CRP) correlates well with other measures of biologic activity but not as well with clinical activity. CRP can help predict IBD relapses, and in patients with severely active ulcerative colitis may indicate which patients are most likely to progress to colectomy. Similarly, fecal lactoferrin and calprotectin are reasonably accurate and noninvasive measures of disease activity, can predict relapse, and identify a high-risk group among acute severe colitis patients. Capsule endoscopy is a highly sensitive tool that can be used in patients with suspected Crohn’s disease with a negative traditional workup, but lower specificity and the risk of capsule retention preclude first-line use. CT enterography can delineate the extent and severity of bowel inflammation and detect extraluminal findings. Magnetic resonance enterography is a radiation-free cross-sectional imaging alternative that is comparable to CT enterography in diagnostic accuracy.     

Clinical Features and Quality of Life in Patients with Different Phenotypes of Crohn’s Disease of the Ileal Pouch

Purpose Crohn’s disease of the pouch can occur in patients with colectomy and ileal pouch-anal anastomosis performed for ulcerative colitis. The clinical features of inflammatory, fibrostenotic, and fistulizing Crohn’s disease have not been characterized. Methods A total of 73 eligible patients with Crohn’s disease of the pouch, who were seen in the Pouchitis Clinic, were enrolled: 25 with inflammatory Crohn’s disease, 17 with fibrostenotic Crohn’s disease, and 31 with fistulizing Crohn’s disease. The clinical phenotypes of Crohn’s disease were based on a combined assessment of clinical, endoscopic, radiographic, and histologic features. Clinical symptoms, endoscopic and histologic features, and health-related quality-of-life scores were assessed. Results Demographic and clinical features, including preoperative and postoperative parameters, were similar between the three phenotypes of Crohn’s disease of the pouch. The use of nonsteroidal anti-inflammatory drugs, neuropsychiatric drugs, antidiarrheal agents, and Crohn’s disease medicines was not different between the three groups. Predominant symptoms, as expected, were significantly different between the three phenotypes: diarrhea and/or pain in 92 percent of patients with inflammatory Crohn’s disease, obstructive symptoms in 64.7 percent of patients with fibrostenotic Crohn’s disease, and fistular drainage in 51.6 percent of those with fistulizing Crohn’s disease (P < 0.0001). There was no statistical difference in quality-of-life scores between the three phenotypes, adjusted for disease activity. There was no significant correlation between quality-of-life and symptom scores in any of the three groups. Although not statistically significant, patients with fistulizing Crohn’s disease (16.1 percent) tended to have an increased risk for pouch failure compared with inflammatory (8 percent) or fibrostenotic (5.9 percent) Crohn’s disease. Conclusions Predominant symptoms were different in clinical phenotypes of Crohn’s disease. Each of the three phenotypes of Crohn’s disease similarly affected quality-of-life. Fistulizing Crohn’s disease may be associated with a higher risk for pouch failure. Supported by NIH R03 DK 067275 and an American College of Gastroenterology Clinical Research Award. Reprints are not available.     

Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation

OBJECTIVE: Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls. METHODS: Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined. RESULTS: One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS. CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.     

Family History and Serology Predict Crohn’s Disease after Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

Purpose Approximately 5 to 10 percent of patients undergoing ileal pouch-anal anastomosis with a diagnosis of ulcerative colitis are subsequently diagnosed with Crohn’s disease. Preoperative predictors for Crohn’s disease post-ileal pouch-anal anastomosis have not been prospectively defined. Methods A total of 238 consecutive patients with ulcerative colitis or indeterminate colitis undergoing ileal pouch-anal anastomosis were prospectively enrolled into a longitudinal database. Clinical factors were assessed perioperatively. Serum drawn preoperatively was assayed for anti-Saccharomyces cerevisiae, antiouter membrane porin-C, anti-CBir1, and perinuclear antineutrophil cytoplasmic antibody using enzyme-linked immunosorbent assay. Crohn’s disease was defined by small bowel inflammation proximal to the ileal pouch or a perianal fistula identified at least three months after ileostomy closure. Predictors were assessed in a multivariate Cox proportional hazards model to predict the rate of Crohn’s disease after ileostomy closure. Results Sixteen patients (7 percent) were diagnosed with Crohn’s disease; median time to Crohn’s disease was 19 (range, 1–41) months. Significant factors for postoperative Crohn’s disease after ileal pouch-anal anastomosis included family history of Crohn’s disease (hazard ratio, 8.4; 95 percent confidence interval, 2.96–24.1; P < 0.0001) and anti-Saccharomyces cerevisiae immunoglobulin-A seropositivity (hazard ratio, 3.14; 95 percent confidence interval, 1.1–9.81; P = 0.04). Crohn’s disease developed in only 8 of 198 patients (4 percent) without these predictors vs. 8 of 40 patients (20 percent) in those with at least one of these factors (P = 0.002). The cumulative risk of Crohn’s disease among patients with two risk factors (67 percent) was higher than in patients with either risk factor (18 percent) or neither risk factor (4 percent, P < 0.001). Conclusions Patients with ulcerative colitis and indeterminate colitis with a family history of Crohn’s disease or preoperative anti-Saccharomyces cerevisiae immunoglobulin-A seropositivity are more likely to be diagnosed with Crohn’s disease after ileal pouch-anal anastomosis. Poster presentation of distinction at Digestive Disease Week, Washington, D.C., May 19 to 24, 2007, and Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 7, 2007. Financial disclosures: Prometheus Laboratories Speakers’ Bureau (Eric A. Vasiliauskas, Konstantinos A. Papadakis, Marla Dubinsky, Andrew Ippoliti), shareholder (Carol Landers, Stephan R. Targan), and cofounder (Stephan R. Targan).     

The Role of Tacrolimus in Inflammatory Bowel Disease: A Systematic Review

Therapeutic management of inflammatory bowel disease remains beyond the limits of conventional therapy in many cases. Novel therapies used include tacrolimus, a new powerful immunosuppressive drug, employed in some case reports and a few studies that have tried to evaluate its effectiveness in Crohn’s disease and ulcerative colitis with promising results, but its role in the management of inflammatory bowel disease remains controversial. We performed a systematic review that analyzed a total of 23 reported experiences in 286 patients with inflammatory bowel disease treated with tacrolimus. Although most of the published studies are uncontrolled, short, and heterogeneous, promising results have been obtained in fistulizing disease, unresponsive cases of both ulcerative colitis and Crohn’s disease, and even extraintestinal manifestations. The overall outcome was good enough to consider tacrolimus as a rationale therapeutic option. However, comparative studies with standard therapeutic options like infliximab are needed to assess the correct role that tacrolimus may play in these patients.     

Expression of p53, VEGF, Microvessel Density, and Cyclin-D1 in Noncancerous Tissue of Inflammatory Bowel Disease

We aimed to evaluate the carcinogenesis risk in inflammatory bowel disease via p53 mutation and its relation with hyperproliferation (cyclin-D1) and angiogenesis (with vascular endothelial growth factor [VEGF] and microvessel density) and whether these events play important roles in pathogenesis of inflammatory bowel disease. Colonic tissue samples of 26 ulcerative colitis, 6 Crohn’s disease, and 8 amoebic colitis patients as well as samples of 10 healthy controls were stained with p53, cyclin-D1, CD34, and VEGF monoclonal antibodies by immunohistochemistry and evaluated semiquantitatively. Expression of p53 was higher in ulcerative colitis than in the healthy control and amoebic colitis groups (4.15 ± 2.07, 1.4 ± 1.5, 1.3 ± 1.5; P < 0.001). The Crohn’s disease group had the highest p53 expression (4.6 ± 1.6). The Crohn’s disease, ulcerative colitis, and amoebic colitis groups all had higher VEGF expression than did the healthy controls (respectively, 4.3 ± 1.2, 2.92 ± 2.0, 2.3 ± 1.5, 0.6 ± 0.97; P < 0.001). Also, microvessel density was statistically higher in all three colitis groups than in healthy controls. Cyclin-D1 expression in all four groups was similar. The study showed that p53 mutation was present in nonneoplastic mucosa of inflammatory bowel disease patients. Detecting strong p53 overexpression with VEGF overexpression may help in differentiating inflammatory bowel disease from other colitis.     

Differences in Yeast Intolerance Between Patients with Crohn’s Disease and Ulcerative Colitis

Purpose Alimentary factors, especially those modifying the intestinal flora, may influence the course of inflammatory bowel disease. It is known that T and B cells of patients with Crohn’s disease can be stimulated with the yeast antigen, mannan. We evaluated the impact of eating habits with special respect to food containing yeast on the course of inflammatory bowel disease. Methods Questionnaires were sent to 180 German-speaking patients of the Inflammatory Bowel Disease Outpatient Clinic at the University Hospital Bern, Switzerland. The following information was obtained by the questionnaires: (1) course of disease, (2) eating habits, (3) environmental data, and (4) inflammatory bowel disease questionnaire. The survey was anonymous. Results A total of 145 patients (80.5 percent 95 with Crohn’s disease, and 50 with ulcerative colitis) responded. Food items containing yeast were better tolerated by patients with ulcerative colitis than by patients with Crohn’s disease. A significant difference between the two groups was observed concerning food containing raw yeast (dough, P = 0.04; and pastry, P = 0.001). Conclusions Food items containing raw yeast led to more frequent problems for patients with Crohn’s disease than for patients with ulcerative colitis. This observation supports our previous data, which showed the stimulatory effect of the yeast antigen, mannan, on B and T cells of patients with Crohn’s disease but not of controls. Poster presentation at Digestive Disease Week (DDW), organized by the American Gastrointestinal Association, Chicago, Illinois, May 14 to 19, 2005.     

1007fs, G908R, R702W Mutations and P268S, IVS8+158 Polymorphisms of the CARD15 Gene in Turkish Inflammatory Bowel Disease Patients and Their Relationship with Disease-Related Surgery

Introduction CARD15 gene mutations may present different frequencies in populations and sometimes surgical interventions may become a necessary therapy for inflammatory bowel disease patients. Mutations of 1007fs, G908R, R702W and polymorphisms of P268S, IVS8⁺¹⁵⁸ of the CARD15 gene and their relation with disease-related surgery were investigated in Turkish inflammatory bowel disease patients in this study. Material and Method 1007fs, G908R, R702W mutations and P268S, IVS8⁺¹⁵⁸ polymorphisms of CARD15 gene were analyzed in 130 inflammatory bowel disease patients (67 Crohn’s disease, 63 ulcerative colitis) and 87 healthy controls. After obtaining DNA samples, genotyping was performed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) analysis. Results were evaluated by statistical analysis and accepted as significant if P < 0.05. Results R702W gene mutation was significantly lower in the inflammatory bowel disease group (1.5%) than the controls (4.8%) (P < 0.05). The overall allele frequency of mutations in the inflammatory bowel disease group (2.7%) was lower than in controls (6.6%) (P < 0.05). Disease-related surgery history was present in 20 Crohn’s and 25 ulcerative colitis patients; familial history was present in four Crohn’s and five ulcerative colitis patients. Statistically, no relationship was detected between disease-related surgeries and the investigated genetic tests. Conclusion In Turkish patients, no important relationship was detected between the investigated allele frequencies of the CARD15 gene and inflammatory bowel disease nor between disease-related surgeries and inflammatory bowel disease. Dedicated to the memory of the Turkish scientist Turgut Tukel MD. Thanks for his contributions and supports.     

Optical Coherence Tomography in Inflammatory Bowel Disease: Prospective Evaluation of 35 Patients

Purpose  Optical coherence tomography is a technique using infrared light in tissues of the gastrointestinal tract and human colon affected by inflammatory diseases. We evaluated whether there are specific patterns of optical coherence tomography for inflammatory bowel disease and compared the technique performance to the histology. Methods  Optical coherence tomography was performed in 35 patients (18 men; 31 ulcerative colitis, 4 Crohn’s disease). The images were obtained from affected and normal colon at endoscopy. Two biopsies of the sites visualized were taken. Two endoscopists scored the images, and two pathologists, blind to the endoscopy and optical coherence tomography, performed the histologic evaluation. Results  Three optical coherence tomography patterns were identified: 1) mucosal backscattering alteration, 2) delimited dark areas, and 3) layered colonic wall. Compared with the histology, mucosal backscattering alteration was the most effective in recognizing the disease in patients (P = 0.007 in colon segments affected, and P < 0.001 in normal segments). The sensitivity and specificity have been 100 and 78 percent, respectively. Conclusions  The in vivo optical coherence tomography correctly detected inflammatory bowel disease features in affected and apparently normal colon, and allowed to discriminate patterns for active ulcerative colitis and Crohn’s disease.     

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

Background and aims Calprotectin 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. Methods The 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. Results Fecal 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. Conclusions Fecal 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.     

Age and Indication for Referral to Capsule Endoscopy Significantly Affect Small Bowel Transit Times: The Given Database

The purpose of this study was to examine the effect of age and selected indications for capsule endoscopy on small bowel transit times. Data on 67 clinical studies (790 subjects with different gastrointestinal pathologies [49.5% males; mean age, 51.9 ± 18.33 years; range, 18–91 years] and 87 healthy volunteers) were retrieved from the company (Given Imaging, Ltd.)-sponsored database. All subjects swallowed the PillCam SB Capsule after a 12-hr fast. The capsule reached the cecum in all 877 participants. Indications for referral for capsule endoscopy were as follows: 372 obscure gastrointestinal bleeding, 96 suspected Crohn’s disease, 65 celiac disease, 54 irritable bowel syndrome, and 116 familial adenomatous polyposis, intestinal lymphoma, or ulcerative colitis. One group consisted of patients <40 years old (n = 235), and the other patients 40 years old (n = 555). The younger group, volunteers, and Crohn’s disease patients had significantly shorter small bowel transit times than the others (P < 0.001). Gastric emptying indirectly influenced capsule transit time.     

Is Indeterminate Colitis Determinable?

About 10% of patients with colitis due to inflammatory bowel disease have indeterminate colitis. Despite newer diagnostic tools, the frequency has not diminished over the past 33 years. The current preferred term among academicians is colonic inflammatory bowel disease unclassified (IBDU), although indeterminate colitis is the term endorsed for inclusion in the ICD-10 coding system. Indeterminate colitis is more frequent among children. The anti-Saccharomyces cerevisiae (ASCA) and perinuclear anti-cytoplasmic antibody (pANCA) are useful in distinguishing IBDU from ulcerative colitis and Crohn’s disease. However, current serologic and genetic studies, as well as endoscopic and imaging studies lack sufficient positive predictive values to make a definite diagnosis of Crohn’s colitis or ulcerative colitis. Patients with IBDU who undergo proctocolectomy with ileal pouch-anal anastomosis have more complications than patients with ulcerative colitis. Although some patients with indeterminate colitis eventually develop characteristic ulcerative colitis or Crohn’s disease, a subgroup are durably indeterminate.     

Irritable Bowel Syndrome on Inflammatory Bowel Disease in Deep Remission: No Relation with Remission Deepening and Inflammation

Background: The aim of the study was to establish the frequency of irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in clinical, endoscopic, and histologic remission and in relation to both the depth of remission and inflammation markers. Methods: Patients with ulcerative colitis (UC) and with Crohn’s disease (CD) in clinical remission for at least 6 months were enrolled in the study. All of the patients underwent colonoscopy, and biopsy specimens were taken to evaluate endoscopic and histopathologic remission. Patients were evaluated according to Rome III criteria for IBS. Fecal calprotectin level and blood samples for C-reactive protein (CRP), sedimentation rate, and fibrinogen levels were studied.Results: IBS frequency was 20.9% in UC cases and 28.9% in CD cases in clinical remission. Rates with and without endoscopic remission in UC (20.5% vs. 22.2%, P = .727) and CD (25% vs. 33.3%, P = .837, respectively) were not different. Similarly, rates with and without histopathologic remission in UC (15.7% vs. 26.6%, P = .723), and CD (21.4% vs. 33.3%, P = .999) were not statistically different. Also, it was not related to inflammation markers.Conclusion: IBS frequency among IBD patients with remission was in a substantial rate; these rates kept up with the process of deep remission and even complete mucosal healing and were irrelevant to inflammation.     

Utility of a Rapid Fecal Latex Agglutination Test Detecting the Neutrophil Protein, Lactoferrin, for Diagnosing Inflammatory Causes of Chronic Diarrhea

Objective: The utility of tests for fecal neutrophils in the setting of chronic diarrhea has not been established. The purpose of this study was to determine the causes of chronic diarrhea associated with fecal neutrophils.
Methods: One fecal specimen from each of 10 normal subjects, 26 patients with known microscopic colitis, 13 with celiac sprue, eight with Crohn's disease, four with ulcerative colitis, and 103 with chronic diarrhea of unknown origin, as well as 10 fecal specimens from a patient with chronic nongranulomatous enterocolitis were analyzed blindly for the presence of a neutrophil granule protein called lactoferrin using a commercial latex agglutination kit. Diagnostic evaluation of the 103 patients with chronic diarrhea was carried out to determine the diagnostic accuracy of this test for chronic inflammatory bowel disease.
Results: None of the normal control subjects, three of 39 patients with microscopic colitis or celiac sprue, all 10 specimens from the patient with enterocolitis, and all 12 control patients with ulcerative colitis or Crohn's disease had a positive fecal lactoferrin test. Eleven of 103 patients with chronic diarrhea presenting without a diagnosis had a positive test, and all were diagnosed with an inflammatory condition of the colon (five-, ulcerative colitis; four-, Crohn's disease; one-, ischemic colitis; and one-, microscopic colitis). Only one patient with inflammatory bowel disease had a negative lactoferrin test. The sensitivity, specificity, and positive and negative predictive values of the fecal lactoferrin test for ulcerative or Crohn's colitis were 90%, 98%, 82%, and 99%, respectively.
Conclusion: The major cause of fecal neutrophils in patients with chronic diarrhea is chronic inflammatory bowel disease of the colon. The latex agglutination test for fecal lactoferrin offers a highly sensitive, specific, and simple means for detection of fecal neutrophils in these patients.     

Current and future anti-TNF therapy for inflammatory bowel disease

Opinion statement Anti-tumor necrosis factor-α (anti-TNF) therapy has become a very important modality in the treatment of patients with inflammatory bowel disease. A number of anti-TNF medications have been investigated for this purpose, many via randomized controlled trials. Infliximab, the most studied of these agents, has shown impressive efficacy in the treatment of luminal and fistulizing Crohn’s disease, as well as ulcerative colitis. Adalimumab and certolizumab have shown similar efficacy in Crohn’s disease but have not yet been studied in ulcerative colitis. Less impressive results were seen in randomized controlled trials involving CDP-571, etanercept, or onercept for patients with Crohn’s disease. Thalidomide and CNI-1493 have been evaluated only preliminarily in small, open-label pilot studies in patients with Crohn’s disease. The future of anti-TNF therapy in inflammatory bowel disease is very bright, as exciting new developments continue to be made at a rapid pace.     

Relationship between fecal lactoferrin and inflammatory bowel disease

OBJECTIVE: Lactoferrin as a glucoprotein that can reflect the activity of neutrophil leukocytes is a specific and sensitive indicator in the evaluation of intestinal inflammation. The aim of this study was to evaluate the relationship between fecal lactoferrin and intestinal inflammation by quantitative analysis and the effect of fecal lactoferrin in measuring the activity of inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD). MATERIAL AND METHODS: A total of 177 fresh stool samples were collected from 42 active UC, 17 inactive UC, 13 active CD, 5 inactive CD, 41 infectious bowel disease, 25 irritable bowel syndrome (IBS) and 34 healthy volunteers. IBD-SCAN was used quantitatively to measure the level of fecal lactoferrin. A modified Harvey-Bradshaw Active Index was used to evaluate the activity of IBD. RESULTS: Fecal lactoferrin was 3.15+/-1.60 microg/g in healthy volunteers, 2.54+/-1.49 microg/g in IBS, 83.3+/-29.9 microg/g in infectious bowel disease, 1126.29+/-431.21 microg/g in active UC, 1035.25+/-456.59 microg/g in active CD, 96.58+/-82.46 microg/g in inactive UC and 133.52+/-88.89 microg/g in inactive CD. Fecal lactoferrin was significantly higher in active IBD than in inactive IBD, IBS and infectious bowel disease. The sensitivity and specificity of fecal lactoferrin were 92% and 88%, respectively, for UC, and 92% and 80%, respectively, for CD. CCONCLUSIONS: Fecal lactoferrin is a sensitive and specific marker in measuring the activity of IBD. It provides us with a valid method in discriminating between inflammatory and non-inflammatory bowel disease. In addition, an elevated fecal lactoferrin level can lead us to exclude IBS in clinical practice.     

CRP Correlates with Clinical Score in Ulcerative Colitis but Not in Crohn’s Disease

The aim of this study was to prospectively evaluate the correlation between clinical scoring systems and C-reactive protein (CRP) in inflammatory bowel disease. The modified Harvey-Bradshaw index was used in 40 patients (58 assessments) with Crohn’s disease, and the Lichtiger score in 29 patients (36 assessments) with ulcerative colitis. In ulcerative colitis, CRP was elevated in 14%, 42%, 64%, and 83%, respectively, of subjects with quiescent, mild, moderate, and severe disease. There was a linear correlation of log(CRP) with clinical score except for proctitis. In Crohn’s disease, CRP was elevated in 54%, 70%, 75%, and 100%, respectively, of subjects with quiescent, mild, moderate, and severe disease. We conclude that the clinical score has a good correlation with CRP in ulcerative colitis except for proctitis, whereas clinical score has a poor correlation with CRP in Crohn’s disease, particularly in those with clinically quiescent, fibrostenotic, and ileal disease.