Screening for celiac disease among the personnel in active service of an Italian Armed Force.

INTRODUCTION AND OBJECTIVE: Celiac disease (CD) affects the 1% of the general population worldwide. Because of its clinical variability, roughly the 70% of CD patients are not correctly diagnosed and not adequately treated. Active military personnel represent an interesting cohort for a CD screening. Upon the enrollment in the Armed Forces, a complete health check is carried out to exclude any diseases. Aim of the present work is to assess the CD prevalence among the personnel of Carabinieri Corps, an Italian armed force, through a serological screening. RESULTS AND DISCUSSION: Out of 291 militaries (281 M, 10 F age range: 18.2-61.5) enrolled, 2 resulted affected by CD (prevalence: 0.7%); 1 to have high serological anti-TG and EMA level without duodenal mucosal lesions and 1 to have high serological anti-TG, but not EMA. CONCLUSION: These results show that the CD prevalence among a cohort of Italian militaries is similar to that of the general population.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

BACKGROUND: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. METHODS: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. RESULTS: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. CONCLUSIONS: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Faecal calprotectin assay after induction with anti-Tumour Necrosis Factor α agents in inflammatory bowel disease: Prediction of clinical response and mucosal healing at one year.

BACKGROUND: Faecal calprotectin levels correlate with inflammation in inflammatory bowel disease. We evaluated the role of faecal calprotectin after anti-Tumour Necrosis Factor α induction in inflammatory bowel disease patients to predict therapeutic effect at one year. METHODS: Faecal calprotectin levels were measured in stools of 63 patients before and after induction of anti-Tumour Necrosis Factor α therapy. Clinical activity, measured by clinical indices, was assessed before and after biologic treatment. Clinical responders after induction were included in the study and colonoscopy was performed before and after one year of treatment to assess mucosal healing. RESULTS: 63 patients (44 Crohn's disease, 19 ulcerative colitis) were prospectively included (41.2% males, mean age at diagnosis 33 years). A sustained clinical response during the first year was observed in 57% of patients; median faecal calprotectin was 106 µg/g after induction versus 308 µg/g pre-induction (p<0.0001). Post-induction faecal calprotectin was significantly lower in responders versus non-responders (p=0.0002). Post-induction faecal calprotectin had 83% sensitivity and 74% specificity (cut-off ≤ 168 µg/g) for predicting a sustained clinical response at one year (p=0.0001); also, sensitivity was 79% and specificity 57% (cut-off ≤ 121 µg/g) for predicting mucosal healing (p=0.0001). CONCLUSIONS: In inflammatory bowel disease faecal calprotectin assay after anti-Tumour Necrosis Factor α induction can be used as a marker to predict sustained clinical response and mucosal healing at one year.

Long-term combination therapy with infliximab plus azathioprine predicts sustained steroid-free clinical benefit in steroid-dependent ulcerative colitis.

BACKGROUND: Infliximab (IFX) has demonstrated effectiveness for inducing 12-month steroid-free clinical remission in patients with steroid-dependent ulcerative colitis (UC), but long-term data are lacking. The aim of the study was to describe the long-term outcome of IFX treatment in steroid-dependent UC and investigate if predictors of sustained clinical response and colectomy could be identified. METHODS: Consecutive patients with steroid-dependent UC treated with IFX were studied. The coprimary prespecified outcomes were sustained clinical response in patients who achieved clinical remission or response after IFX induction and colectomy-free survival. Secondary analyses were addressed to look for predictors of sustained clinical response and colectomy. RESULTS: After induction, 76% (96/126) of patients achieved clinical benefit. The median duration of follow-up on IFX maintenance therapy was 41.5 months (interquartile range, 26-45). Sixty-four percent (46/96) of patients had sustained clinical response at median follow-up. Colectomy-free survival was 77% at median follow-up. Combination therapy of IFX with thiopurines was an independent predictor of sustained clinical response (P < 0.0001; hazard ratio [HR], 3.98; 95% confidence interval [CI], 1.73-9.14). Independent predictors of colectomy were Mayo endoscopic subscore of 3 at baseline (P = 0.04; HR, 2.77; 95% CI, 1.09-7.05) and high C-reactive protein after induction (P = 0.001; HR, 5.65; 95% CI, 2.03-15.7). Thiopurine naive status (P = 0.025; HR, 0.34; 95% CI, 0.13-0.87) was protective from colectomy. CONCLUSIONS: Long-term IFX treatment is effective in inducing sustained clinical response in patients with steroid-dependent UC. Combination therapy is predictive of sustained clinical response in the long-term. Patients with more severe endoscopic lesions at baseline and high C-reactive protein after induction are at higher risk of colectomy. Conversely, thiopurine naive status is protective from colectomy.

FOXP3⁺ T regulatory cell modifications in inflammatory bowel disease patients treated with anti-TNFα agents.

Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factor α (TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4⁺CD25⁺FOXP3⁺ (Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFα therapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3⁺ cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFα therapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn's disease (CD). No significant differences were found in LP FOXP3⁺ cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFα may affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.

Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn's disease: an open-label pilot study.

BACKGROUND AND AIMS: Patients with Crohn's disease (CD) often require surgery over their clinical course. However, endoscopic and clinical recurrence of disease appear respectively in up to 80% and 30% of patients after one year. Thus, a prophylactic treatment is needed to reduce the possibility of recurrence. Both azathioprine and infliximab have been demonstrated to be effective, but head to head studies have not been performed so far. Aim of this open-label prospective study was to analyse endoscopic, histological and clinical recurrence after one year of treatment with azathioprine or infliximab as postoperative therapies in CD patients with "high risk" of recurrence. METHODS: Consecutive CD patients who underwent curative ileocolonic resection were randomized (1:1) to receive infliximab (standard induction and maintenance schedule) or azathioprine (2.5 mg/kg/day) for 1 year. Co-primary endpoints were endoscopic, histological and clinical recurrence after 12 months of therapy. RESULTS: Twenty-two consecutive CD patients (15 male; median age 32 years, IQR 22-38) were enrolled after curative ileocolonic resection. Eleven patients were treated with infliximab and 11 received azathioprine. Among patients treated with azathioprine, 4/10 (40%) had endoscopic recurrence compared to 1/11 (9%) in the infliximab group (p=0.14). Eight out of 10 (80%) among those who received azathioprine had severe histological activity, whereas 2/11 (18%) in the infliximab group presented histological recurrence (p=0.008). No significant clinical differences were found between the two groups. CONCLUSIONS: Infliximab was more effective than azathioprine in reducing histological, but not endoscopic and clinical recurrence after curative ileocolonic resection in "high risk" CD patients.

Infliximab in steroid-dependent ulcerative colitis: effectiveness and predictors of clinical and endoscopic remission.

BACKGROUND: Up to 20% of patients with ulcerative colitis (UC) become steroid-dependent during their course. Thiopurines are recommended in steroid-dependent UC, but their efficacy is debated. Data exploring the use of infliximab in these patients are scarce. Aims of this study were to evaluate the effectiveness of infliximab in steroid-dependent UC and identify predictors of steroid-free remission, mucosal healing (MH), and colectomy. METHODS: Steroid-dependent UC patients were enrolled and intentionally treated with infliximab. The prospectively designed analyses evaluated (1) steroid-free clinical remission at 6 and 12 months, (2) steroid-free clinical remission and MH at 12 months, and (3) colectomy within 12 months. RESULTS: One hundred and twenty-six active steroid-dependent UC patients were studied. Of the 126 patients, 36 patients were retrospectively included and 90 patients prospectively enrolled. Steroid-free remission was 53% and 47% at 6 and 12 months, respectively. Predictors of steroid-free remission at 6 and 12 months were thiopurine-naive status (hazard ratio [HR], 2.5 and HR, 2.8, respectively) and combination therapy (HR, 2.1 and HR, 2.2, respectively). At 12 months, 32% were in steroid-free remission and MH. Thiopurine-naive status predicted steroid-free remission and MH (odds ratio, 3.6). C-reactive protein drop to normal after infliximab induction was predictive of steroid-free remission at 6 (HR, 5.9) and 12 months (HR, 4.6) and steroid-free remission and MH at 12 months (odds ratio, 6.0). Twelve patients underwent colectomy after a median of 4.7 months. Steroid sparing significantly reduced the risk of colectomy within 12 months (HR, 0.14). CONCLUSIONS: Infliximab seems effective in steroid-dependent UC. Thiopurine-naive status and combination therapy significantly increase the rate of steroid-free remission up to 12 months.

Comparison of Quantiferon-TB Gold versus tuberculin skin test for tuberculosis screening in inflammatory bowel disease patients.

BACKGROUND & AIM: Screening for latent tuberculosis (LTB) is recommended before starting anti-TNF-alpha therapy. We compared the performance of Quantiferon-TB Gold (QFT-G) with the tuberculin skin test (TST) for the screening of LTB in a population of inflammatory bowel disease (IBD) patients who were candidates for anti-TNF-α therapy. METHODS: Ninety-two IBD patients who were candidates for anti-TNF-α therapy were tested with QTF-G and TST. Concomitant therapy and laboratory parameters were recorded. RESULTS: One subject was vaccinated with Bacille Calmette Guèrin (BCG), 76% of patients were on immunosuppressive therapy (IST), and all patients had a negative TB history and negative chest X-ray. Agreement between the two tests was observed in 89.2% of patients (79.4% +/+, 9.8% -/-), QFT-G+/TST- was observed in 4.4% (4) patients, and QFT-G-/TST+ was observed in 5.5%, one of which was previously vaccinated. All disagreements were observed in patients on IST (14.3% in this group). The agreement analysis showed moderate strength among the patients (k=0.508), while the agreement was only fair in the subgroup of patients on IST (k=0.388). CONCLUSION: Given the high risk of LTB reactivation in patients subjected to anti-TNF-α therapy, our results suggest that in our population, with low TB rate and very low BCG vaccination rate, both tests could be employed.

Prevalence and natural history of hepatitis B and C infections in a large population of IBD patients treated with anti-tumor necrosis factor-α agents.

BACKGROUND: The prevalence rates of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients with inflammatory bowel disease (IBD) have been reported to be higher than rates of infection among the general population. Although several cases of HBV infection reactivation in IBD patients treated with anti-TNF-α agents have been described, no evidence exists that anti-TNF-α therapy exacerbates the course of HCV. The aims of this study were to assess the prevalence of HBV and HCV and the rate of HBV vaccination in a population of IBD patients; and to investigate the long-term effects of anti-TNF-α therapy in the subgroup with HBV or HCV infections. METHODS: 301 patients were studied. Prior to the initiation of anti-TNF-α therapy, serum samples were tested for HBsAg and anti-HBc, anti-HBs and anti-HCV antibodies. During the follow-up, HBsAg and anti-HBc positive patients underwent periodic blood testing for viral markers, HBV-DNA and liver function; anti-HCV positive patients were assessed for liver function and HCV-RNA. RESULTS: One patient was HBsAg positive (0.3%), and 22 (7.3%) tested positive for anti-HBc. Seventy-two patients (23.9%) had been vaccinated for HBV. Four patients tested positive for anti-HCV (1.3%). During anti-TNF-α therapy, none of the patients experienced HBV or HCV reactivation. CONCLUSIONS: HBV and HCV infection rates were similar to infection rates among the general population. Less than one quarter of the patients had been vaccinated against HBV. Anti-TNF-α agents appear to be safe for patients with HBV infection; more data are needed for patients with HCV infection.

Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity.

PURPOSE: To quantitatively assess microvascular activation in the thickened ileal walls of patients with Crohn disease (CD) by using contrast-enhanced ultrasonography (US) and evaluate its correlation with widely used indexes of CD activity. MATERIALS AND METHODS: This prospective study was approved by the ethics committee, and written informed consent was obtained from all patients. The authors examined 54 consecutively enrolled patients (mean age, 35.29 years; age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the terminal ileum. Ileal wall segments thicker than 3 mm were examined with low-mechanical-index contrast-enhanced US and a second-generation US contrast agent. The authors analyzed software-plotted time-enhancement intensity curves to determine the maximum peak intensity (MPI) and wash-in slope coefficient (ß) and evaluated their correlation with (a) the composite index of CD activity (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum. Statistical analysis was performed with the Mann-Whitney test, Spearman rank test, and receiver operating characteristic (ROC) analysis. RESULTS: MPI and ß coefficients were significantly increased in the 36 patients with a CICDA indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES-CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed accurate identification (compared with CICDA) of active CD with an MPI threshold of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a ß coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). CONCLUSION: Contrast-enhanced US of the ileal wall is a promising method for objective, reproducible assessment of disease activity in patients with ileal CD.

Use of infliximab in particular clinical settings: management based on current evidence.

With the increasingly widespread use of the anti-tumor necrosis factor-alpha agent infliximab for the treatment of Crohn's disease and ulcerative colitis, there have been some concerns raised about the potential consequences of such therapy in particular clinical settings. In this review, we report the current strategies for optimizing treatment outcomes and minimizing the risks of some of the most serious events attributable to infliximab therapy. In particular, an up-to-date overview is provided on how to treat patients with inflammatory bowel disease using infliximab therapy, with regard to the diagnosis and management of latent tuberculosis infection and the risk of reactivation of hepatitis B and C infections. Furthermore, based on the available evidence, we evaluate the possibility of using infliximab during pregnancy. Finally, we evaluate whether patients with malignancies or pre-neoplastic lesions could be candidates for infliximab therapy. Overall, this review will provide physicians who use infliximab for the treatment of inflammatory bowel disease with several practical recommendations for the management of some complex situations that may occur in daily clinical practice.

Enteroclysis CT and PEG-CT in patients with previous small-bowel surgical resection for Crohn's disease: CT findings and correlation with endoscopy.

The aim of this study was to evaluate the accuracy of multidetector CT in patients with Crohn's disease (CD) relapse after ileocolic resection compared with endoscopy. Thirty-four patients were studied by endoscopy and multidetector CT, after oral administration of polyethylene glycol solution (n = 21) or after administration of methylcellulose via nasojejunal tube (n = 13). In CT examinations we evaluated the presence of mural thickening, target sign, perienteric stranding, comb sign, fibrofatty proliferation and complications. Endoscopic results were classified in accordance with Rutgeerts score (from 0 to 4). The statistical evaluations were carried out by using Fisher's exact text and chi (2) testing (p < 0.05, statistically significant difference). Sensitivity, specificity and accuracy of the CT were 96.9%, 100% and 97%, respectively. We found a statistically significant correlation between an endoscopic score of 4 and the CT signs of target sign, perienteric stranding, comb sign and fibrofatty proliferation, and between scores 1 and 2 and mucosal hyperdensity without or with mural thickening, respectively (p < 0.05). Moreover, only CT identified the presence of jejunal and proximal ileum disease in two and three patients, respectively, and fistulas in three patients. CT is a reliable method in the diagnosis of CD relapse and shows agreement with the approved endoscopic Rutgeerts score.

Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study.

OBJECTIVES: Duodenal biopsy is the current gold standard for diagnosis of celiac disease. Videocapsule endoscopy examines the entire small bowel and allows visualization of mucosal villi. We evaluated the potential of videocapsule endoscopy in assessing the severity and extent of mucosal changes in patients with suspected celiac disease. METHODS: Consecutive patients with signs/symptoms suggesting celiac disease and positive anti-gliadin and/or anti-endomysial and/or anti-tissue transglutaminase antibodies underwent upper gastrointestinal endoscopy and videocapsule endoscopy. Duodenal biopsies were classified according to modified Marsh's criteria. Capsule findings were evaluated for the presence of lesions compatible with celiac disease (scalloping of duodenal folds, fissures, flat mucosa, and mosaic appearance). RESULTS: Forty-three patients were studied. Duodenal histology was normal in 11 and compatible with celiac disease in 32. Using duodenal histology as the gold standard, the performance characteristics of capsule endoscopy for the diagnosis of celiac disease were: sensitivity 87.5% (95% CI 76.1-98.9%), specificity 90.9% (95% CI 81.0-100%), positive predictive value 96.5% (95% CI 90.1-100%), negative predictive value 71.4% (95% CI 55.8-87%), positive and negative likelihood ratios 9.6 and 0.14, respectively. Eighteen patients had mucosal changes extending beyond the duodenum, involving the entire small bowel in three. These patients tended to have more severe symptoms, but the difference was not statistically significant. Interobserver agreement for the diagnosis of celiac disease by capsule endoscopy ranged between 79.2 and 94.4%; kappa values ranged between 0.56 and 0.87. CONCLUSIONS: Videocapsule endoscopy shows good sensitivity and excellent specificity for the detection of villous atrophy in patients with suspected celiac disease.

A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease.

BACKGROUND: Treatment of celiac disease (CD) is based on the avoidance of gluten-containing food. However, it is not known whether trace amounts of gluten are harmful to treated patients. OBJECTIVE: The objective was to establish the safety threshold of prolonged exposure to trace amounts of gluten (ie, contaminating gluten). DESIGN: This was a multicenter, double-blind, placebo-controlled, randomized trial in 49 adults with biopsy-proven CD who were being treated with a gluten-free diet (GFD) for > or =2 y. The background daily gluten intake was maintained at < 5 mg. After a baseline evaluation (t0), patients were assigned to ingest daily for 90 d a capsule containing 0, 10, or 50 mg gluten. Clinical, serologic, and histologic evaluations of the small intestine were performed at t0 and after the gluten microchallenge (t1). RESULTS: At t0, the median villous height/crypt depth (Vh/Cd) in the small-intestinal mucosa was significantly lower and the intraepithelial lymphocyte (IEL) count (x 100 enterocytes) significantly higher in the CD patients (Vh/Cd: 2.20; 95% CI: 2.11, 2.89; IEL: 27; 95% CI: 23, 34) than in 20 non-CD control subjects (Vh/Cd: 2.87; 95% CI: 2.50, 3.09; IEL: 22; 95% CI: 18, 24). One patient (challenged with 10 mg gluten) developed a clinical relapse. At t(1), the percentage change in Vh/Cd was 9% (95% CI: 3%, 15%) in the placebo group (n = 13), -1% (-18%, 68%) in the 10-mg group (n = 13), and -20% (-22%, -13%) in the 50-mg group (n = 13). No significant differences in the IEL count were found between the 3 groups. CONCLUSIONS: The ingestion of contaminating gluten should be kept lower than 50 mg/d in the treatment of CD.

Small bowel diseases.

The study of small bowel disease is hampered by the organ length and shape. Malabsorption syndromes, small bowel bleeding, intestinal obstruction are analyzed with reference to the clinical characteristics and present laboratory and instrumental tests used in diagnosis. The introduction of sophisticated diagnostic imaging procedures, both endoscopic and radiologic have contributed to a better understanding of the symptomatic patterns.