Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal

Irritable bowel syndrome is a group of functional gastrointestinal disorders with not yet fully clarified etiology. Recent evidence suggesting that mast cells may play a central role in the pathogenesis of irritable bowel syndrome paves the way for agents targeting histamine receptors as a potential therapeutic option in clinical treatment. In this review, the role of histamine and histamine receptors is debated. Moreover, the clinical evidence of anti-histamine therapeutics in irritable bowel syndrome is discussed.

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

There is an unmet need for effective pharmacological therapies for constipation, a symptom that significantly deteriorates patients' quality of life and impacts health care. Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor and has been shown to exert prokinetic effects on gastrointestinal (GI) motility via the vagus and pelvic nerves. The pharmacological potential of ghrelin is hampered by its short half-life. Ghrelin receptor (GRLN-R) agonists with enhanced pharmacokinetics were thus developed. Centrally penetrant GRLN-R agonists stimulate defecation and improve impaired lower GI transit in animals and humans. This review summarizes the current knowledge on relamorelin, a potent ghrelin mimetic, and other GRLN-R analogs which are in preclinical or clinical stages of development for the management of disorders with underlying GI hypomotility, like constipation.

Probiotic Therapy of the Irritable Bowel Syndrome: Why Is the Evidence Still Poor and What Can Be Done About It?

BACKGROUND/AIMS: Despite numerous randomized clinical trials and meta-analyses, there is no increased evidence for the efficacy of probiotics in the treatment of irritable bowel syndrome (IBS). We review this evidence, identify and analyse the reasons for this lack of evidence and propose methodological improvements for future studies. METHODS: Based on a literature search, we identified 56 papers that matched the purpose of our analyses. Twenty-seven studies used multi-species bacterial preparations and 29 used single-strain probiotics. They were analysed regarding patients included, treatment duration, probiotic dosage, and outcome measures. RESULTS: Trials in both groups suffered from heterogeneity with respect to probiotic concentration, duration of treatment, and other methodological issues (crossover design and underpowered studies). This heterogeneity did not allow the application of a meta-analytic approach and a systematic review was therefore performed instead. Multi-strain preparations combined 2 to 8 different bacterial subspecies, mostly lactobacilli or bifidobacteria, and used variable lengths of treatments. Overall, more than 50% of trials presented negative outcomes. The majority of the single-strain probiotic trials employing lactobacilli or Saccharomyces were negative, whereas trials employing bifidobacteria showed positive results. CONCLUSIONS: The heterogeneity of the studies of probiotics in IBS questions the value of meta-analyses. The use of different bacterial strains and different mixtures of these strains, as well as different dosages, are the main contributors to this heterogeneity. Current data provides limited evidence for the efficacy of a small number of single-strain probiotics in IBS (mostly bifidobacteria) and sound studies following strict trial guidelines (Food and Drug Administration and European Medicines Agency guidelines for clinical trials) are needed. We summarised and proposed some methodological issues for future studies in the field.

Lichen Planus Is an Uncommon Cause of Nonspecific Proximal Esophageal Inflammation

BACKGROUND/AIMS: Esophageal lichen planus (LP) has been described as a cause of nonspecific esophagitis that may cause dysphagia, but its incidence is unknown. We aimed to estimate the incidence of esophageal LP in a defined geographic region and describe the clinical characteristics of affected patients. METHODS: A histopathology database for a population of 1 million people was searched for all esophageal mucosal biopsy results over an 8-year period. Cases showing inflammation or abnormalities without a diagnosis after three or more biopsies were reviewed for findings of LP. RESULTS: Of 13,589 esophageal biopsies, only one received a diagnosis of LP. Seven patients (four male; mean age, 59 years; range, 39 to 76 years) were identified as having chronic dysphagia and nonspecific proximal esophagitis for which no diagnosis could be made. All patients had proximal inflammation, and six of seven had full-thickness lymphocytic infiltration. Elongation of the lamina propria papillae was noted in all patients, whereas six patients had parakeratosis and ballooning. Only one patient had findings potentially consistent with, but not sufficient for, a diagnosis of esophageal LP. CONCLUSIONS: Esophageal LP appears to be extremely uncommon in this North American population, and esophageal biopsy alone is likely not sufficient to establish a diagnosis of LP.