Patient with chest pain refractory to proton pump inhibitor: report of a case of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is the most common form of gastrointestinal disorders associated with eosinophilia. Typically, an inappropriate accumulation of eosinophils is found in the esophageal mucosa. EoE can be well managed and treated with several options that include an elimination diet, drug therapy (oral and topical steroids) and esophageal dilatations. We herein, report a case of a 49-year-old male affected by EoE associated to chest pain, treated with proton pump inhibitor without clinical response. The patient suffered from long lasting postprandial fullness and gastroesophageal reflux disease-like symptoms. He had a history of episodic asthmatic attacks and allergic rhinitis but had not dysphagia or food impaction. The patient recovered completely after an adequate treatment.

Azathioprine treatment in inflammatory bowel disease patients: type and time of onset of side effects.

BACKGROUND: Azathioprine (AZA) and 6-mercaptopurine (6-MP), purine analogues, are the immunosuppressant drugs most frequently used for inducing and maintaining remission in inflammatory bowel disease (IBD). The occurrence of adverse effects is a major drawback in the use of these drugs, and short- and long-term toxicity represent a major limitation to their use. AIM: The present study investigated the prevalence, type and time of onset of AZA-related adverse events, in a cohort of IBD patients in a single referral Centre. PATIENTS AND METHODS: The records of consecutive IBD outpatients, referred to our Institution between 1987-2009, were retrospectively evaluated. RESULTS: We reviewed 2014 patients, in whom AZA was prescribed in 302 of them, 139 (46%) with ulcerative colitis (UC) and 163 (54%) with Crohn's disease (CD). Side-effects were complained by 98 (32.4%) out of 302 patients, 50 UC and 48 CD, (36% UC vs 29.4% CD, p = 0.26). In 20 (20.4%) patients, 11 UC and 9 CD, side-effects recovered after dosage reduction whilst in 78 (79.6%), 39 UC and 39 CD, the treatment was discontinued (dose-dependent side-effects in 42 patients and dose-independent in 36). Overall, side-effects were observed after a mean period of 14.5 ± 7.8 months (range 0.5-123) of AZA treatment. The majority (76%) of the dose-dependent adverse events were reported between 12-18 months after the beginning of treatment. CONCLUSIONS: The prevalence of side effects leading to withdrawal of AZA treatment, in our series of Italian patients, was higher respect to data reported in the literature (25.8%).

Hydrogen breath test--diet and basal H2 excretion: a technical note.

BACKGROUND: Hydrogen breath tests are widely used in clinical practice. For a correct evaluation of data, low basal H2 excretion is required, thus, 12-hour fasting is usually prescribed. An additional reduction in the intake of complex carbohydrates in the preceding 24 h is suggested in some centers. The issue, however, has never been directly investigated. AIM: The aim of the present study was to analyze the effect of the pretest diet on the basal H2 excretion and the number of subjects excluded from the test due to high basal H2 excretion. METHODS: Two cohorts of 500 consecutive patients undergoing a lactose tolerance test in the years 1997-1998 (when 12-hour fasting was required) and in 2007-2008 (when a low-carbohydrate diet in the preceding 24 h was also prescribed) were retrospectively reviewed. RESULTS: The mean basal H2 excretion was significantly lower (p < 0.0001) in the low-carbohydrate diet group (2.46 +/- 6.8 vs. 4.73 +/- 3.3 ppm). In 1997-1998, 46/500 patients (9.2%) were excluded from the test due to basal H2 values as compared to 7/500 (1.4%) in the period 2007-2008. DISCUSSION: To the best of our knowledge, ours is the first study to provide objective data on the advantage offered by reducing the intake of complex carbohydrates before H2 breath tests.

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Effect of predominant methanogenic flora on the outcome of lactose breath test in irritable bowel syndrome patients.

BACKGROUND: The relationship between hydrogen and methane production is a possible confounding factor in the interpretation of H(2) breath tests (HBT), but is usually disregarded for the interpretation of HBT and, in most instances, only H(2) excretion is measured. The present study was designed to evaluate the effect of predominant fasting methane CH(4) or H(2) production on the outcome of lactose HBT, in a large, homogeneous series of adult patients with irritable bowel syndrome (IBS). PATIENTS AND METHODS: A lactose HBT was performed in 237 IBS patients with predominant fasting methane production (CH(4)>H(2)), recording the outcome of the test, amount of gas excreted and occurrence of clinical symptoms. Data were compared to those of 237 age- and sex-matched IBS patients with low fasting CH(4) excretion. RESULTS: The test was positive in 124 predominant CH(4) producers (52.3%) (PMP), as compared to 201 (84.8%) low methane producers (LMP) (P<0.0001). Peak hydrogen concentration and area under the curve of H(2) were significantly (P<0.001) lower, and the occurrence of symptoms during the test less frequent, in PMP vs LMP patients. During the test, CH(4) excretion doubled in 57/113 (50.4%) patients with negative HBT, and in 49/124 (39.5%) with positive HBT. CONCLUSIONS: Patients with predominant fasting methane production excrete less H(2) than LMP, after an oral load of lactose. The lower prevalence of severe lactose intolerance in PMP, as well as lower incidence of symptoms during the test, is, indeed, related to lower and slower H(2) excretion. The assumption that H(2) excretion is an effective means of quantifying the amount of malabsorbed carbohydrates is questionable in PMP. Methane-producing patients likely have a higher 'false negative' rate as compared to LMP after an oral load of lactose. Nonetheless, as symptoms are related to the amount of gas produced in the colon, HBT identifies patients with 'lactose intolerance', irrespective of the presence of lactose malabsorption, and helps in predicting the effect of lactose-restricted diet.

Infliximab in refractory pouchitis complicated by fistulae following ileo-anal pouch for ulcerative colitis.

AIM: To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis. METHODS: This open study included seven patients (four females, three males) with chronic refractory pouchitis complicated by fistulae. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. The sites of the fistulae were as follows: pouch-bladder in one, vaginal in three, perianal in two, and both vaginal and perianal in one. Extra-intestinal manifestations (erythema nodosum, arthralgia) were present in four patients. Crohn's disease was carefully excluded in all patients after re-evaluation of the history, re-examination of the original proctocolectomy specimen and examination of the proximal small bowel. All patients had been treated with antibiotics and three with steroids. Patients received infliximab, 5 mg/kg, at 0, 2 and 6 weeks. Azathioprine (2.5 mg/kg) was also started for all patients as bridge therapy. Clinical response was classified as complete, partial or no response. Fistulae closure was classified as complete (cessation of fistulae drainage and total closure of all fistulae), partial (a reduction in the number, size, drainage or discomfort associated with fistulae) or no closure. The pouchitis disease activity index and quality of life were also used as outcome measures. RESULTS: Clinically, all patients improved. At the 10-week follow-up, six of the seven patients had a complete clinical response, and five had complete fistulae closure. At the 10-week follow-up, the median pouchitis disease activity index decreased from 12 (baseline) (range, 10-15) to 5 (range, 3-8); the median quality of life decreased from 37 points (range, 33-40) to 14 (range, 9-18). Erythema nodosum and arthralgia showed complete remission soon after the first infusion of infliximab. CONCLUSIONS: These preliminary results indicate that infliximab may be recommended for the treatment of refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis.

Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial.

BACKGROUND: The treatment of distal ulcerative colitis, refractory to conventional 5-ASA/steroid treatment, is still a matter of debate. The present study aimed at confirming, with adequate statistical power, previous data indicating the usefulness of topical butyrate and 5-ASA in the treatment of this condition. DESIGN: Double-blind, placebo-controlled, multicentre study. A total of 51 patients with distal (< 65 cm) ulcerative colitis, refractory to topical 5-ASA/cortisone, were randomly allocated to receive topical 5-ASA 2 g and 80 mM L-1 sodium-butyrate bid (Group A; 24 patients) or 5-ASA 2 g and 80 mL saline bid (Group B; 27 patients) for 6 weeks. Sigmoidoscopy with biopsies, as well as clinical and laboratory evaluations, were carried out at enrollment and at the end of the trial. Primary endpoints: remission or marked improvement in endoscopic, histologic and clinical findings. RESULTS: Most parameters showed a significant improvement vs. baseline in both groups. Remission in six patients and improvement in 12 patients in Group A vs. one remission and 13 with improvement in Group B (P < 0.05). A significant difference in favour of Group A was recorded regarding the number of bowel movements (P < 0.01), urgency (P < 0.05) and the patients' self evaluation (P < 0.01). DISCUSSION: The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.

Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance.

BACKGROUND: The relationship between lactose malabsorption, irritable bowel syndrome and development of intestinal symptoms is unclear, especially when the ingested dose of milk is small. Thus, the role of hydrogen breath testing in the diagnostic work-up of patients with nonspecific intestinal symptoms is still debated. AIMS: To establish the relationship between lactose malabsorption, severe self-reported milk intolerance, irritable bowel syndrome and related symptoms. METHODS: The prevalence of lactose malabsorption was prospectively assessed by means of a hydrogen breath test in 839 patients (503 with irritable bowel syndrome, based on the Rome criteria, regularly consuming milk, and 336 subjects who identified themself as milk intolerant, after an oral load of 25 g lactose). The test was considered "positive" when a hydrogen peak exceeding 20 ppm over baseline values was observed in two or more samples. Attempts were also made to establish whether the predominant presenting symptom (diarrhoea, constipation, alternating diarrhoea and constipation, pain and gaseousness) might be helpful in predicting the outcome of the breath test. RESULTS: The prevalence of a positive breath test was comparable in the two groups (337 patients with irritable bowel syndrome (66.9%) vs 240 patients with milk intolerance (71.4%)). The same holds true for the first peak of hydrogen excretion, total hydrogen output and prevalence of symptoms during, and in the four hours after, the test. The predominant presenting symptom was not useful for predicting outcome of the test either in regular milk users or in milk intolerant subjects. CONCLUSIONS: The almost identical results of the lactose breath test of patients with irritable bowel syndrome and subjects with self-reported milk intolerance suggests that the two conditions overlap to such an extent that the clinical approach should be the same. A lactose breath test should always be included in the diagnostic work-up for irritable bowel syndrome, as fermentation of malabsorbed lactose is likely responsible for triggering symptoms. Conversely, lactase deficiency is probably irrelevant in most subjects not affected by irritable bowel syndrome, within a moderate milk consumption.

Topical butyrate for acute radiation proctitis: randomised, crossover trial.

BACKGROUND: No available therapy has, as yet, proven effective to treat acute radiation proctitis (ARP) following radiation therapy for malignant pelvic disease. We assessed whether sodium butyrate enemas, at a dose of 80 mmol/L (80 mL/24 h), might offer effective treatment for this condition. METHODS: 20 patients presenting with ARP after completing a cycle of 35-52 Gy external-beam radiation therapy for pelvic malignant disease, were treated for 3 weeks with topical sodium butyrate and saline enemas according to a randomised, double-blind, crossover protocol. Clinical, endoscopic, and histological findings were assessed at enrollment, at week 3, and then at the end of the study. Data were analysed by two-tailed t test for paired data (continuous variables) and a logistic-regression model with variable multiple response for ordered categorical data. FINDINGS: Topical butyrate, but not saline, led to remission of symptoms (clinical score from 8.2 [SE 1.6] to 1.5 [0.7] vs 7.9 [1.8] to 8.1 [3.4]). When the treatment regimen was switched, eight out of nine of the previously placebo-treated patients went into remission, whereas three patients relapsed when switched to saline. The advantage of butyrate over placebo, expressed as CI, odds ratio, and p value was significant for almost all the clinical, endoscopic and histological factors taken into consideration. INTERPRETATION: Topical sodium butyrate, unlike other therapeutic regimens used so far, proved effective in the treatment of ARP.

Multiple organ dysfunction in ulcerative colitis.

OBJECTIVE: The mortality rate in severe ulcerative colitis (UC) is commonly attributed to major colonic complications or surgical procedures. Early recognition of the severity of the colitis, intensive medical treatment, and prompt surgery have all contributed to improving its outcome over the past 40 yr. Recently, we have observed some fatal cases of severe UC in which death was related to multiple organ dysfunction syndrome (MODS). This complication, associated with a very high mortality rate, may occur in several acute critical diseases, both infectious and noninfectious, but has so far not been reported in UC. The aim of this study was to evaluate the prevalence and outcome of MODS in severe UC. METHODS: The records of 180 consecutive patients admitted to the Gastrointestinal Unit, University of Rome for an acute severe attack of UC during the period 1976-1998 were retrospectively analyzed. Severity of UC was defined according to the criteria of Truelove and Witts. MODS was defined according to the original criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992. All patients were on a standard intensive regimen consisting of total parenteral nutrition and hydrocortisone 100 mg q.i.d. Colectomy was performed according to the timing of the Oxford intensive regimen. RESULTS: Of these 180 severe UC patients, 11 (6.1%) experienced clinical and laboratory features of MODS. The lung was involved in five patients, the kidney in three, the liver in seven, the central nervous system in three, the hematological system in three, and the pancreas in one. MODS was preceded by toxic megacolon in five patients and by so-called "impending megacolon" in four, whereas in two patients no previous complications of UC were observed. MODS developed during the first attack of colitis in seven patients and during relapse in four. The overall mortality rate was 12/180 (6.6%). Of the 12 patients who died, eight (72.7%) had MODS. CONCLUSIONS: These data indicate that UC must be included among the causes of MODS. In our referral center for inflammatory bowel diseases, MODS was responsible for the majority of UC cases with a fatal outcome. The timely identification of signs of MODS should prompt admission to an intensive care unit and emergency surgery.

Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: randomized, double-blind, placebo-controlled pilot study.

Butyrate represents the main source of energy for colonic epithelial cells; however, its availability/utilization is impaired in ulcerative colitis (UC). In the present randomized, double-blind, placebo-controlled pilot study, the safety and efficacy of colonic targeted oral sodium butyrate tablets, coated with a pH-dependent soluble polymer, have been evaluated in ulcerative colitis. Thirty patients with mild to moderate colitis underwent a six-week course of oral sodium butyrate (4 g/day) plus oral mesalazine (2.4 g/day), (Group A) or of oral mesalazine plus placebo (Group B). Clinical, endoscopic, and histologic data were collected at the beginning and the end of the study. Twenty-five patients completed the study (12 in group A, 13 in group B). No untoward side effects were reported. In group A, seven patients underwent remission and four improved; in Group B the numbers were 5 and 5, respectively. After treatment, all clinical parameters had significantly improved in both treatment arms compared to pretreatment findings. The UC disease activity index (UCDAI) score decreased from 7.27 +/- 2.02 to 2.58 +/- 2.19 (P < 0.05) in the combined treatment group and from 6.07 +/-1.60 to 3.46 +/- 1.98 (P < 0.05) in group B. The endoscopic and histologic scores also significantly improved after treatment in both groups (P < 0.05). The difference between the two treatment arms was not significant, but a significantly better improvement vs baseline values (P < 0.05) was observed in the combined treatment group vs the mesalazine group, when considering both the clinical index (delta9.58 +/- 4.19 vs 5.92 +/- 3.48) and the UCDAI score (delta4.67 +/- 2.19 vs 2.54 +/- 2.18). A more favorable trend, although not significant, was observed for all individual parameters in group A. In conclusion, results of the present pilot study indicate that oral butyrate is safe and well tolerated. These data also suggest that oral butyrate may improve the efficacy of oral mesalazine in active ulcerative colitis and prompt the need of a large scale investigation to confirm the present findings.

Effect of rifaximin on intestinal bacterial overgrowth in Crohn's disease as assessed by the H2-Glucose Breath Test.

UNLABELLED: The occurrence of intestinal bacterial overgrowth in patients with Crohn's Disease (CD) has been described and antimicrobial treatment has been shown to be effective in reversing this condition. However, the mechanisms underlying the efficacy of antimicrobial therapy are still only partially known. The aim of the present study was to evaluate the effect of a non-absorbable antibiotic (rifaximin) in comparison to placebo on bacterial overgrowth in patients with CD. METHODS: Fourteen patients with inactive CD of the ileum and bacterial overgrowth, as assessed by the hydrogen breath test, were blindly allocated to receive rifaximin (1200 mg/day) or placebo t.i.d. for one week. A hydrogen breath test, and clinical and biochemical parameters were further performed 14 days and 30 days after starting treatment. RESULTS: After 14 days, the hydrogen breath test proved to be negative in seven out of seven patients treated with rifaximin (p < 0.05), and in two out of seven in the placebo group (p = ns). After 30 days, the hydrogen breath test was positive in all patients of the rifaximin and placebo group, respectively. No changes in the CDAI score were documented in any patients. CONCLUSIONS: Short-term administration of rifaximin is effective in the therapy of bacterial overgrowth in patients with inactive CD of the ileum, thus suggesting that the control of luminal bacterial growth could be useful in the management of these patients. However, since we observed a decline with time in this positive effect, further studies are needed to identify the most appropriate therapeutic strategies.

Circulating soluble factor-inhibiting natural killer (NK) activity of fresh peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease (IBD) patients.

This study was performed in order to assess the cytotoxic activity, both natural (NK) and antibody-dependent (ADCC), of PBMC from 38 IBD patients and correlate it with their clinical features. Cytotoxicity assays were performed using sensitive target cells for NK and ADCC activities. In some experiments, highly purified NK cells, obtained both by Percoll density gradient and by co-culturing non-adherent PBMC with RPMI 8866 feeder cells, were used as effector cells. Furthermore, we evaluated NK cell parameters such as number, surface expression of adhesion molecules (CD11a/CD18, CD49d and CD54) and response to different stimuli. We observed a decreased NK cytotoxicity of PBMC from IBD patients, both in ulcerative colitis (UC) and Crohn's disease (CD), independently of the clinical activity of disease. In contrast, the ADCC lytic activity was within normal range. The lower NK cytotoxic activity observed in our IBD patients cannot be related to a decreased number of NK cells, surface expression of adhesion molecules, defective response to IL-2 and maturative defect. Decreased NK activity was induced in PBMC of controls when serum of patients was added and this was unrelated to monocyte-derived modulating factor(s). Our data show a decreased natural killing by fresh PBMC from IBD patients. This lower activity seems to be unrelated to a primary NK cell defect, since purified NK cells exhibited normal levels of killing. It might be hypothesized that serum factors, possibly derived from lymphocytes, with inhibitory properties on NK activity, might be functionally active in the blood of IBD patients, thus modulating NK activity.