Case report: Dupilumab treatment improved type 2 disorders in a patient with IPEX syndrome diagnosis.

We described a case of IPEX syndrome successfully controlled with dupilumab, an anti-IL4 receptor alpha subunit inhibitor. IPEX syndrome is a rare and generally fatal genetic disorder characterized by immune dysregulation, polyendocrinopathy and enteropathy, mostly diagnosed in early childhood. Nonetheless, cases reported in the last 20 years demonstrated that IPEX clinical spectrum encompasses more than the classical triad of early-onset intractable diarrhea, type 1 diabetes and eczema. Atypical cases of IPEX include patients with late-onset of symptoms, single-organ involvement, mild disease phenotypes or rare clinical features. A 21-year-old caucasian man presented with immune dysregulation (hypereosinophilia and elevated IgE), protein-losing enteropathy, polyendocrinopathy (thyroiditis, osteoporosis, delayed puberty), weight loss, eczema manifestations and celiac disease. IPEX syndrome was diagnosed because of the presence of a hemizygous mutation in FOXP3 gene (c.543C>T (p.S181S) in the exon 5). During the course of the disease, the patient developed erosive proctitis, pyoderma gangrenosum, and erythema nodosum. Symptoms improved only after enteral and parenteral corticosteroid therapy and the patient soon developed steroid-dependence. Notwithstanding various therapies including azathioprine, sirolimus, tacrolimus, adalimumab, vedolizumab, the patient failed to achieve a good control of symptoms without steroids. Almost exclusive enteral nutrition with a hypoallergenic, milk-protein free, amino acid-based food for special medical purposes. He continued to lose weight (BMI 14.5 kg/m2) with a consequent high limitation of physical activity and a progressive worsening of the quality of life. In consideration of the poor response to conventional immunosuppressants and the presence of type 2 inflammatory manifestations, treatment with dupilumab at an initial dose of 600 mg, followed by a maintenance dose of 300 mg every other week, according to atopic dermatitis labeled dose, was started and combined to oral budesonide 6 mg/day and 6-mercaptopurine 75 mg/day. The patient experienced a rapid improvement in bowel and skin symptoms, leading to a progressive tapering of steroids. By our knowledge, this is the first report of IPEX syndrome successfully treated by antiIL-4/IL-13 therapy. In this case dupilumab demonstrated to be an effective, safe and steroid-sparing option.

Efficacy and Mechanisms of Action of Fecal Microbiota Transplantation in Ulcerative Colitis: Pitfalls and Promises From a First Meta-Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is the results of a chronic inflammatory process deriving from disequilibrium between self-microbiota composition and immune response. METHODS: New evidence, coming from Clostridium difficile infection, clearly showed that active and powerful modulation of microbiota composition by fecal microbiota composition (FMT) is safe, easy to perform, and efficacious, opening new frontiers in gastrointestinal and extra-intestinal diseases. FMT has been proposed also for IBD as well as other non-gastrointestinal conditions related to intestinal microbiota dysfunctions, with good preliminary data. RESULTS: In this setting, ulcerative colitis (UC) represents one of the most robust potential indications for FMT after C difficile colitis. CONCLUSIONS: In the present review, we focus on FMT and its application on ulcerative colitis, clarifying mechanisms of actions and efficacy data, trough completion of a meta-analysis on available randomized, controlled trial data in UC. Because microbiota is so crucially involved in this topic, a short review of microbial alterations in UC will also be performed.

Onset of ulcerative colitis after thyrotoxicosis: a case report and review of the literature.

OBJECTIVE: Ulcerative colitis is a chronic disease that could be triggered by acute stressful events, such as gastrointestinal infections or emotional stress. PATIENTS AND METHODS: We reported the case of the onset of an ulcerative colitis after a thyrotoxicosis crisis and reviewed the literature about the relationships between thyroid dysfunctions and ulcerative colitis. RESULTS: A 38-year-old woman was diagnosed with ulcerative colitis after her third thyrotoxicosis crisis, two years after the diagnosis of Graves' disease. In this case, thyrotoxicosis acted as a trigger for ulcerative colitis onset. CONCLUSIONS: Hyperthyroidism could be a trigger able to elicit ulcerative colitis in susceptible patients.

Intestinal gas production and gastrointestinal symptoms: from pathogenesis to clinical implication.

Intestinal gases are the expression of metabolic activity of gut microbiota in the gut, particularly carbohydrates in the case of H2, CH4. Alterations in composition of gases and air handling, directly or upon challenge with food are relevant for GI and extra-GI diseases. Assessing gas composition in breath can be a very useful tool for clinic, but technical issues are crucial (breath sampling, storing and analyzing). Aim of the present review is to summarize the understanding of the importance of intestinal gases in gastro-intestinal physiology and patho-physiology. Practical considerations on how to collect samples and instruments available for the clinic have also been provided.

13C-octanoic acid breath test to study gastric emptying time.

Digestion is a complex process regulated by several factors. Among these, one of the most important is the time of gastric emptying. A delayed gastric emptying time can be caused by several factors and can generate considerable discomfort in humans. It ranges from mild to real debilitating disorders. Until now, different tests are suggested to study the gastric emptying time. The present review presents the mayor cause and the main symptoms linked to delayed gastric emptying and will focus on the (13)C-octanoid acid breath test, as a good candidate for studying solid gastric emptying time.

Pancreatic function assessment.

Several non invasive tests are available to assess pancreatic function, but no one is routinely used in clinical practice to diagnose chronic pancreatitis, due to their poor sensitivity in diagnosing mild pancreatic insufficiency. (13)C breath tests share the same limits of the other non invasive functional tests, but the mixed triglyceride breath test seems to be useful in finding the correct dosage of enzyme substitutive therapy to prevent malnutrition in patients with known pancreatic insufficiency.

Tricks for interpreting and making a good report on hydrogen and 13C breath tests.

Breath tests (BT) represent a valid and non-invasive diagnostic tool in many gastroenterological disorders. Their wide diffusion is due to the low cost, simplicity and reproducibility and their common indications include diagnosis of carbohydrate malabsorption, Helicobacter pylori infection, small bowel bacterial overgrowth, gastric emptying time and orocaecal transit time. The review deals with key points on methodology, which would influence the correct interpretation of the test and on a correct report. While a clear guideline is available for lactose and glucose breath tests, no gold standard is available for Sorbitol, Fructose or other H2 BTs. Orocaecal transit time (OCTT) defined as time between assumption of 10 g lactulose and a peak > 10 ppm over the baseline value, is a well-defined breath test. The possible value of lactulose as a diagnostic test for the diagnosis of small bowel bacterial overgrowth is still under debate. Among (13)C breath test, the best and well characterized is represented by the urea breath test. Well-defined protocols are available also for other (13)C tests, although a reimbursement for these tests is still not available. Critical points in breath testing include the patient preparation for test, type of substrate utilized, reading machines, time between when the test is performed and when the test is processed. Another crucial point involves clinical conclusions coming from each test. For example, even if lactulose could be utilized for diagnosing small bowel bacterial overgrowth, this indication should be only secondary to orocaecal transit time, and added into notes, as clinical guidelines are still uncertain.

Randomised clinical trial: preventive treatment with topical rectal beclomethasone dipropionate reduces post-radiation risk of bleeding in patients irradiated for prostate cancer.

BACKGROUND: Radiotherapy is an established treatment modality for prostate cancer; however, up to a third of patients develops a radiation-induced proctopathy. AIM: To assess the effect of topical beclomethasone dipropionate (BDP) in the prevention of radiation-induced proctopathy in patients undergoing radiotherapy for prostate cancer through a double-blind, placebo-controlled, randomised trial. METHODS: Patients were randomised either to BDP or to placebo (PL). Patients received daily a 3mg BDP enema or identical-looking PL during radiotherapy and, subsequently, two 3mg BDP suppositories or PL for 4 more weeks. Clinical and endoscopic evaluations before, 3 and 12months after the end of radiotherapy were assessed with the RTOG/EORTC toxicity scales, the modified Simple Clinical Colitis Activity Index (SCCAI), the modified Inflammatory Bowel disease Quality of Life Index (IBDQ) and the Vienna Rectoscopy Score (VRS). RESULTS: From June 2007 to October 2008, 120 patients were randomised to the BDP (n=60) and PL (n=60) arms and were followed up for 12months. The overall assessment of rectal side effects did not show significant differences between the two groups of treatment. However, when only rectal bleeding was considered, a significantly reduced risk was observed in patients on BDP (OR 0.38; 95% CI 0.17-0.86; P=0.02; NNT=5). Patients on BDP had also significantly lower VRS scores (P=0.028) and significantly higher IBDQ scores (P=0.034). CONCLUSIONS: Preventive treatment with topical rectal BDP during radiotherapy for prostate cancer significantly reduces the risk of rectal bleeding and radiation-induced mucosal changes and improves patient's quality of life, but does not influence other radiation-induced symptoms.

Can early precut implementation reduce endoscopic retrograde cholangiopancreatography-related complication risk? Meta-analysis of randomized controlled trials.

BACKGROUND AND STUDY AIMS: Precut papillotomy is considered a risk factor for endoscopic retrograde cholangiopancreatography (ERCP)-related complications; however whether the complication risk is due to precut itself or to the prior prolonged attempts is still debated; therefore, early precut implementation has been suggested to reduce the complication rate. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing cannulation and complication rates of early precut implementation with persistent attempts by the standard approach. METHODS: RCTs that compared cannulation and complication rates of the early precut implementation and of persistent attempts by the standard approach were included. Summary effect sizes were estimated by odds ratio (OR) with a random-effects model and by Peto OR. RESULTS: Six RCTs with a total of 966 subjects met the inclusion criteria. Overall cannulation rates were 90 % in both randomization groups (OR 1.20; 95 % confidence interval [CI] 0.54 - 2.69). Post-ERCP pancreatitis developed in 2.5 % of patients randomized to the early precut groups and in 5.3 % of patients from the persistent attempts groups (OR 0.47; 95 %CI 0.24 - 0.91). The overall complication rates, considering pancreatitis, bleeding, cholangitis, and perforation rates, were 5.0 % in the early precut groups and 6.3 % in the persistent attempts groups (OR 0.78; 95 %CI 0.44 - 1.37). CONCLUSIONS: RCTs that investigated the issue of timing of the precut procedure were limited. Current evidence suggests that in experienced hands the early implementation of precut and persistent cannulation attempts have similar overall cannulation rates; early precut implementation reduces post-ERCP pancreatitis risk but not the overall complication rate. Further studies are needed to confirm these findings.

Endoscopic argon plasma coagulation for the treatment of gastric antral vascular ectasia-related bleeding in patients with liver cirrhosis.

BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) is a cause of bleeding in patients with liver cirrhosis. Argon plasma coagulation (APC) is the most used endoscopic treatment for GAVE-related bleeding. Treatment failures have been described in patients with haemorrhagic diathesis; post-procedure complications include haemorrhages and septicaemia. The aim of the study was to evaluate efficacy and safety of APC treatment of GAVE-related bleeding in patients with liver cirrhosis. METHODS: Patients included were suffering from GAVE-related bleeding and liver cirrhosis. APC treatment was performed until eradication. Resolution of transfusion-dependent anaemia and evaluation of complications were the primary outcomes. RESULTS: 20 patients (16 Child C and 4 Child B) were enrolled and prospectively followed for a mean period of 28 months. GAVE eradication was achieved in all patients after a median of 3 sessions (range 1-10). Resolution of anaemia was achieved in 18 patients. Six patients had relapse of GAVE after a mean of 7.7 months, successfully retreated by APC. Hyperplastic polyps developed in 3 patients causing active bleeding in 2 cases. Five patients had liver transplants and 1 had a relapse of GAVE after transplantation. CONCLUSION: APC is an effective and safe endoscopic treatment for GAVE in patients with liver cirrhosis.