A randomized trial comparing 4.8 vs. 2.4 g/day of oral mesalazine for maintenance of remission in ulcerative colitis.

BACKGROUND: Mesalazine is used as maintenance therapy in ulcerative colitis but the optimal dosage is still controversial. AIM: To compare the remission-maintenance efficacy and tolerability of two daily doses of oral mesalazine (4.8 g and 2.4 g) in patients with ulcerative colitis with frequent relapses in a randomized controlled trial. METHODS: 112 ulcerative colitis patients in remission were enrolled and randomly allocated to treatment for 1 year with oral mesalazine at a daily dose of 4.8 g (n=56, Group A) or 2.4 g (n=56, Group B). RESULTS: At the end of the 12 months, intention to treat analysis revealed persistent remission in 42 (75%) in Group A and 36 (64.2%) in Group B (p=0.3). The higher daily dose (4.8 g) proved to be significantly more effective for maintaining remission in patients under 40 years of age (90.5% Group A vs. 50% Group B; Fisher's exact test, p=0.0095) and in those with extensive disease (90.9% Group A vs. 46.7% Group B; Fisher's exact test, p=0.0064). CONCLUSIONS: In ulcerative colitis patients younger than 40 years and/or with extensive disease, a daily dose of 4.8 g oral mesalazine results in increased rates and duration of remission compared to 2.4 g.

Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios.

INTRODUCTION: Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. AIM: We wanted to test the uniformity of application of Marsh-Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. METHODS: We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh-Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A. RESULTS: Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. DISCUSSION: Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh-Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.

Chronic granulomatous disease mimicking early-onset Crohn's disease with cutaneous manifestations.

BACKGROUND: Chronic granulomatous disease is a rare inherited disorder of the innate immune system. In patients with a clinical history of recurrent or persistent infections, especially infections caused by uncommon species, chronic granulomatous disease should be considered. CASE PRESENTATION: We report the case of a 5-year-old boy with a presumptive diagnosis of Crohn's disease with extraintestinal manifestations. Chronic granulomatous disease was suspected in this case after Serratia marcescens was isolated from a skin ulcer culture. Granulomas were confirmed on histology and chronic granulomatous disease was diagnosed. CONCLUSION: This case emphasizes the importance of high clinical suspicion of an alternative diagnosis of immune deficiency in patients with presumed inflammatory bowel disease and opportunistic infections, especially when disease occurs in early life.

Autoimmune enteropathy in a 13-year-old celiac girl successfully treated with infliximab.

Autoimmune enteropathy (AIE) is a rare cause of small bowel villous atrophy, characterized by malabsorption, unresponsiveness to dietary restriction, circulating autoantibodies to enterocytes, and an overall predisposition to autoimmunity. Albeit mainly regarded as a disease of early childhood, several adult-onset AIE cases have been identified. This report describes for the first time the life-threatening clinical presentation and the management of overlapping AIE in a compliant-to-diet young celiac girl. A 13-year-old celiac girl was admitted because of vomiting, weight loss, diarrhea, hypoproteinemia, and neurological disturbances such as head tremors, vertical nystagmus, and lower limb hyperesthesia. Before this, she had always been compliant on a strict gluten-free diet and her medical history was unremarkable. The diagnosis of AIE was established on histologic findings and on the presence of antienterocyte antibodies. She was initially treated with high-dose Methylprednisolone and Azathioprine. However, only Infliximab proved itself as a highly effective tool for achieving clinical remission and restoring small bowel villous architecture.

Mapping histologic patchiness of celiac disease by push enteroscopy.

BACKGROUND: Despite great improvements in serologic testing, duodenal biopsies are still required to diagnose the majority of celiac disease (CD) cases. Nevertheless, the histologic pattern of CD is often patchy, leading to the risk of missing the diagnosis. OBJECTIVE: To evaluate the patchiness of the CD histologic lesions along the small bowel (SB), push enteroscopy has been performed instead of conventional upper GI endoscopy. DESIGN: Prospective, single-center study. SETTING: Tertiary-care referral center. PATIENTS: A total of 41 pediatric patients with suspected CD. INTERVENTION: Prospective evaluation of bulb, duodenal, and jejunal biopsy specimens in the diagnosis of CD. MAIN OUTCOME MEASUREMENTS: Pattern of lesion distribution along the SB (from bulb up to 60 cm beyond the ligament of Treitz) and yield as well accuracy of pediatric CD diagnosis by using push enteroscopy. RESULTS: There was a homogeneous pattern of histologic damage in 17 patients (41.5%), whereas 24 patients (58.5%) had a lesion pattern of patchiness. The second and fourth duodenal regions were involved in 38 children (92.7%) and 37 children (90.2%), respectively; the bulb was involved in 37 patients (90.2%); both distal and proximal jejunal samples showed histologic lesions in 38 children (92.7%). In 1 patient, without lesions in the bulb and duodenum, CD was diagnosed according to proximal and distal jejunal biopsies only (3B and C, respectively). A significant correlation was found between the degree of villous atrophy and the serum anti-transglutaminase titer. LIMITATIONS: Small sample size; academic tertiary-care setting. CONCLUSION: CD histologic lesions often have a discontinuous distribution along the SB, occasionally with an exclusive jejunal involvement. A high degree of villous atrophy correlates with a high anti-transglutaminase titer. When the new ESPGHAN "biopsy-sparing" criteria are not applicable, in case of potential CD, push enteroscopy might be a valuable second-step tool to re-evaluate and identify false "potential" CD hiding exclusive jejunal lesions.

Usefulness of the organ culture system when villous height/crypt depth ratio, intraepithelial lymphocyte count, or serum antibody tests are not diagnostic for celiac disease.

The existence of mild forms of celiac disease (CD) can make the histology-based diagnosis difficult to reach. Since anti-endomysium (EMA) and anti-tissue transglutaminase (anti-tTG) are detectable in culture supernatants of duodenal biopsies from CD patients, our aim was to assess if this system can support the histology in the diagnostic work-up. A total of 559 suspected CD patients underwent serum EMA/anti-tTG detection, upper endoscopy with duodenal biopsy sampling, histologic analysis, and organ culture to detect EMA/anti-tTG in supernatants. A subgroup of 30 patients with organ culture positive results were put on a gluten-free diet (GFD). Their gluten-dependency was evaluated by the psychological general well-being and beck depression inventory indexes. Statistical analysis was performed by Cohen k inter-test, Friedman test, and Dunn multiple comparison. Two hundred forty-one out of 559 (43.1%) patients showed intestinal villous atrophy, whereas serum and organ culture EMA/anti-tTG were positive in 293/559 (52.4%) and 334/559 (59.7%) patients, respectively. The strength of agreement resulted good for serology vs histology (k = 0.730), good for organ culture vs histology (k = 0.662), and very good for serology vs organ culture (k = 0.852). After 12 months of GFD, psychological general well-being index significantly increased, and beck depression inventory index significantly decreased (P < 0.001 for each one). Data highlight the organ culture system as a useful tool to assist the histology in diagnosing CD, mainly in cases without villous atrophy or in seronegative patients. The marked improvement in quality of life after a GFD further supports the reliability of this system in diagnosing CD.

A pediatric non-protein losing Menetrier's disease successfully treated with octreotide long acting release.

Pediatric Menetrier's disease (MD) is an uncommon, acute, self-limited hypertrophic gastropathy characterized by enlarged gastric folds associated with epithelial hyperplasia and usually accompanied by protein losing gastropathy. Gastric cytomegalovirus infection is found in one third of MD children and its treatment is often associated with remission. Diagnosis often requires full-thickness biopsy due to inability to detect typical histological findings with conventional endoscopic biopsy. We report an uncommon case of non self-limited pediatric MD needing endoscopic mucosal resection for diagnosis which was then successfully treated with octreotide long-acting release (LAR). To the best of our knowledge, this is the first pediatric MD case successfully treated with octreotide LAR. Our experience suggests octreotide LAR as treatment for refractory MD before gastrectomy.

Laparoscopic-assisted resection of juvenile polyp of the jejunum in a 3-year-old girl.

Sporadic juvenile polyp of the jejunum is exceedingly rare, reported only once in the English literature. We describe a 3-year-old girl with a long-lasting history of chronic iron deficiency anemia and a delayed diagnosis of jejunal polyp. The lesion was eventually discovered by ultrasonography and successfully resected using a laparoscopic-assisted transumbilical approach.

Small intestine contrast ultrasonography (SICUS) for the detection of small bowel complications in crohn's disease: a prospective comparative study versus intraoperative findings.

BACKGROUND: In Crohn's disease (CD) patients, small intestine contrast ultrasonography (SICUS) accurately assesses small bowel lesions. Its diagnostic role is not known in the assessment of intraabdominal CD complications. The aim was to assess the value of SICUS to detect intestinal complications in patients with CD. METHODS: Forty-nine CD patients (21 female, mean age 37.7 years; range 12-78 years) underwent resective bowel surgery and were included in this study. The accuracy of SICUS to preoperatively detect number, site, and length of strictures, fistulas, and abscesses was compared with surgical and pathological findings by kappa statistics. RESULTS: SICUS identified at least one stricture in 39/40 and excluded it in 9/9 (97.5% sensitivity, 100% specificity, k = 0.93); two or more strictures in 9/12 (75% sensitivity, 100% specificity, k = 0.78). The agreement by k-statistics between SICUS and surgery in identifying proximal and distal small intestine site of stricture was 1 and 0.92, respectively. The extension of strictures was 6.8 ± 5.4 cm at surgery, 6.6 ± 5.4 cm at SICUS (NS). Fistulas were correctly identified in 27/28 patients and excluded in 19/21 patients (96% sensitivity, 90.5% specificity, k = 0.88). Intraabdominal abscesses were correctly detected in 10/10 patients and excluded in 37/39 patients (100% sensitivity, 95% specificity, k = 0.89). CONCLUSIONS: SICUS is an accurate method for the detection of small intestinal complications in CD. Noninvasive SICUS is valuable as a primary investigative method for evaluating and planning proper treatment in patients with severe CD of the small bowel.

Allergic proctocolitis refractory to maternal hypoallergenic diet in exclusively breast-fed infants: a clinical observation.

BACKGROUND: Allergic proctocolitis (APC) in exclusively breast-fed infants is caused by food proteins, deriving from maternal diet, transferred through lactation. In most cases a maternal cow milk-free diet leads to a prompt resolution of rectal bleeding, while in some patients a multiple food allergy can occur. The aim of this study was to assess whether the atopy patch test (APT) could be helpful to identify this subgroup of patients requiring to discontinue breast-feeding due to polisensitization. Additionally, we assessed the efficacy of an amino acid-based formula (AAF) when multiple food allergy is suspected. amino acid-based formula METHODS: We have prospectively enrolled 14 exclusively breast-fed infants with APC refractory to maternal allergen avoidance. The diagnosis was confirmed by endoscopy with biopsies. Skin prick tests and serum specific IgE for common foods, together with APTs for common foods plus breast milk, were performed. After a 1 month therapy of an AAF all patients underwent a follow-up rectosigmoidoscopy. RESULTS: Prick tests and serum specific IgE were negative. APTs were positive in 100% infants, with a multiple positivity in 50%. Sensitization was found for breast milk in 100%, cow's milk (50%), soy (28%), egg (21%), rice (14%), wheat (7%). Follow-up rectosigmoidoscopy confirmed the remission of APC in all infants. CONCLUSIONS: These data suggest that APT might become a useful tool to identify subgroups of infants with multiple gastrointestinal food allergy involving a delayed immunogenic mechanism, with the aim to avoid unnecessary maternal dietary restrictions before discontinuing breast-feeding.

Ultrasonographic detection and assessment of the severity of Crohn's disease recurrence after ileal resection.

BACKGROUND: Recurrence and severity of Crohn's disease mucosal lesions after "curative" ileal resection is assessed at endoscopy. Intramural lesions can be detected as increased wall thickness at Small Intestine Contrast Ultrasonography (SICUS). AIMS: To assess after ileal resection whether: 1) SICUS detects recurrence of Crohn's disease lesions, 2) the intestinal wall thickness measured at the level of ileo-colonic anastomosis predicts the severity of endoscopic lesions, 3) the extension of intramural lesions of the neo-terminal ileum is useful for grading severity of the recurrence, 4) the combined measures of wall thickness of the ileo-colonic anastomosis and of the extension of intramural lesions at level of the neo-terminal ileum may predict the endoscopic Rutgeerts score METHODS: Fifty eight Crohn's disease patients (M 37, age range 19-75 yrs) were prospectively submitted at 6-12 months intervals after surgery to endoscopy and SICUS for a total of 111 observations. RESULTS: Six months or more after surgery wall thickness of ileo-colonic anastomosis > 3.5 mm identified 100% of patients with endoscopic lesions (p < 0.0001). ROC curve analysis, combining wall thickness of ileo-colonic anastomosis and the extension of intramural lesions of neo-terminal ileum, discriminated (0.95) patients with, from those without, endoscopic lesions. Performing two multiple logistic regression analyses only wall thickness of ileo-colonic anastomosis and extension of neo-terminal ileum intramural lesions were significantly associated with absence or presence of endoscopic lesions. An ordinal polychotomus logistic model, considering all investigated variables, confirmed that only SICUS variables were associated with endoscopic grading of severity. CONCLUSIONS: In patients submitted to ileal resection for Crohn's disease non-invasive Small Intestine Contrast Ultrasonography 1) by assessing thickness of ileo-colonic anastomosis accurately detects initial, minimal Crohn's disease recurrence, and 2) by assessing both thickness of ileo-colonic anastomosis and extension of intramural lesions of neo-terminal ileum grades the severity of the post-surgical recurrence.

Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-TNFalpha therapy.

BACKGROUND: Cytomegalovirus infection and disease is associated with poor prognosis and steroid refractoriness in inflammatory bowel disease patients. The unfavourable effect of steroids and immunosuppressive therapy on CMV infection is well known but few data are available concerning anti-TNFalpha therapy (Infliximab). Aim of the study was to evaluate the presence and severity of CMV infection and disease in Infliximab-treated IBD patients. PATIENTS AND METHODS: The severity of active CMV infection and disease was assessed in 11 consecutive patients with ileocolonic/colonic disease and 4 patients with ulcerative colitis before and after a standard 3-infusion course of Infliximab. Active CMV infection was evaluated by serology and diagnosed by means of pp65-antigenemia (pp65 AG), and quantification of CMV DNA isolated from biopsy specimens of colonic tissue. CMV disease was assessed on haematoxylin/eosin-stained colonic biopsies and immunohistochemical stains. RESULTS: Of the 11 patients, nine were CMV seropositive. As far as concerns CMV infection, only one patient had positive pp65 AG, before and after Infliximab. CMV DNA was detected in the colonic biopsies of three patients. In 2, CMV DNA persisted also after therapy with 410 and 1300 copies/microg of DNA, respectively, albeit with no evidence of worsening of the colonic disease. In the remaining patient, CMV DNA load became undetectable. Conventional histology and immunohistochemical stains were negative for CMV in all the patients, without evidence of CMV disease. CONCLUSIONS: Active CMV infection did not progress to disease following Infliximab therapy. Although these preliminary observations require confirmation, the response to Infliximab therapy does not appear to be influenced by, or influence the course of, CMV infection/disease.

Mesenteric adenitis caused by Yersinia pseudotubercolosis in a patient subsequently diagnosed with Crohn's disease of the terminal ileum.

Although the association between inflammatory bowel disease and gastrointestinal infections has been suggested, the mechanisms involved in the pathogenesis of Crohn's disease (CD) are still undetermined. We report the case of a man, who presented with mesenteric adenitis initially due to a Yersinia pseudotubercolosis infection, who was later diagnosed with Crohn's disease. This case is in keeping with recent evidence in the literature which suggests that CD is a disease linked to abnormal immune responses to enteric bacteria in genetically susceptible individuals.

Is Cronkhite-Canada Syndrome necessarily a late-onset disease?

Cronkhite-Canada Syndrome is a non-inherited, non-congenital disease characterized by juvenile hamartomatous gastrointestinal polyps with a typically late onset. In the case described herein the disease was diagnosed in a 17-year-old male with type I diabetes and thalassaemia minor, in coincidence with severe symptomatic intestinal candidiasis. Following the disappearance of the mycosis and correction of the protein and electrolyte imbalance, the ectodermal abnormalities returned to normal and the patient remained asymptomatic during a 7-year follow-up period, despite proteinuria resulting from membranous glomerulopathy. The concept that Cronkhite-Canada Syndrome is a late-onset disease should probably be reconsidered as it may remain asymptomatic, and thus not diagnosed, for a long a time.

Small intestine contrast ultrasonography: an alternative to radiology in the assessment of small bowel disease.

BACKGROUND: Radiology and transabdominal ultrasonography (TUS) are used in the evaluation of the small bowel; however, the former technique is limited by radiation exposure, and the latter by its inability to visualize the entire small bowel. AIM: To evaluate the diagnostic accuracy of small intestine contrast ultrasonography (SICUS) to assess the presence, number, site, and extension of small bowel lesions. SUBJECTS AND METHODS: TUS, SICUS, and small bowel follow-through (SBFT) were performed in 148 consecutive patients (78 women; age range, 12 to 89 yr), 91 with undiagnosed conditions, and 57 with previously diagnosed Crohn's disease (CD). RESULTS: In the undiagnosed patients, the sensitivity and specificity of TUS and SICUS were 57% and 100%, and 94.3% and 98%, respectively. In the CD patients, the sensitivity of TUS and SICUS was 87.3% and 98%, respectively. In comparison with SBFT, the extension of lesions was correctly assessed with SICUS and greatly underestimated with TUS. The concordance index between SBFT and SICUS for the number and site of lesions was 1 and 1 (P < 0.001), respectively, in undiagnosed patients, and 0.81 and 0.83 (P < 0.001), respectively, in CD patients. Between SBFT and TUS, the concordance index was 0.28 and 0.27 (not significant), respectively, in undiagnosed patients, and 0.28 and 0.31 (not significant), respectively, in CD patients. CONCLUSIONS: The diagnostic accuracy of SICUS is comparable to that of a radiologic examination, and is superior to that of TUS in detecting the presence, number, extension, and sites of small bowel lesions. These findings support the use of noninvasive SICUS for an initial investigation when small bowel disease is suspected and in the follow-up of CD patients.

Oral mesalazine (5-ASA) treatment may protect against proximal extension of mucosal inflammation in ulcerative proctitis.

OBJECTIVES: Studies aimed at establishing which characteristics of patients with ulcerative proctitis could be predictive of the extension of inflammation have failed to provide conclusive results. The aim of the study was to evaluate the prognostic role of clinical and therapeutic parameters in patients with proctitis. PATIENTS AND METHODS: Case records of 138 patients with ulcerative proctitis were retrospectively evaluated. The following parameters were considered: gender; age at onset of disease; smoking habits; histologic severity of disease at onset; mean number of clinical relapses of disease per year; mean duration of oral and topical mesalazine treatment; and number of topical corticosteroid treatments per year. RESULTS: Twenty-eight patients were excluded from the analysis for different reasons. During follow-up, inflammation spread proximally in 33 of 110 patients (30%). Patients with extended proctitis showed a significantly higher number of relapses and a shorter duration of oral mesalazine treatment than patients with nonprogressive proctitis (p < 0.001 for both). The multivariate analysis also found that the mean duration of topical mesalazine treatment was longer in patients with extended proctitis. CONCLUSIONS: Ulcerative proctitis patients with more frequent relapses who need a longer duration of topical therapy are at higher risk of extension of the disease, while a more prolonged oral mesalazine treatment period protects against the proximal spread of rectal inflammation.

Oxidative damage of the gastric mucosa in Helicobacter pylori positive chronic atrophic and nonatrophic gastritis, before and after eradication.

BACKGROUND: Helicobacter pylori is the main cause of gastritis and a primary carcinogen. The aim of this study was to assess oxidative damage in mucosal compartments of gastric mucosa in H. pylori positive and negative atrophic and nonatrophic gastritis. MATERIALS AND METHODS: Five groups of 10 patients each were identified according to H. pylori positive or negative chronic atrophic (Hp-CAG and CAG, respectively) and nonatrophic gastritis (Hp-CG and CG, respectively), and H. pylori negative normal mucosa (controls). Oxidative damage was evaluated by nitrotyrosine immunohistochemistry in the whole mucosa and in each compartment at baseline and at 2 and 12 months after eradication. Types of intestinal metaplasia were classified by histochemistry. RESULTS: Total nitrotyrosine levels appeared significantly higher in H. pylori positive than in negative patients, and in Hp-CAG than in Hp-CG (p <.001); no differences were found between H. pylori negative gastritis and normal mucosa. Nitrotyrosine were found in foveolae and intestinal metaplasia only in Hp-CAG. At 12 months after H. pylori eradication, total nitrotyrosine levels showed a trend toward a decrease in Hp-CG and decreased significantly in Hp-CAG (p =.002), disappearing from the foveolae (p =.002), but remaining unchanged in intestinal metaplasia. Type I and II of intestinal metaplasia were present with the same prevalence in Hp-CAG and CAG, and did not change after H. pylori eradication. CONCLUSIONS: Oxidative damage of the gastric mucosa increases from Hp-CG to Hp-CAG, involving the foveolae and intestinal metaplasia. H. pylori eradication induces a complete healing of foveolae but not of intestinal metaplasia, reducing the overall oxidative damage in the mucosa.