Lawrence R. Schiller M.D.

Schiller, L. R. (2019). “Network meta-analysis in chronic constipation: what have we learned?” Lancet Gastroenterol Hepatol Aug 29. [Epub ahead of print].

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Schiller, L. R. (2019). “Chronic Diarrhea Evaluation in the Elderly: IBS or Something Else?” Curr Gastroenterol Rep 21(9): 45.

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PURPOSE OF REVIEW: Chronic diarrhea is a common problem in all age groups but is a particularly challenging diagnostic problem in the elderly, since many different conditions need to be considered. The purpose of this review is to discuss the evaluation of chronic diarrhea in older individuals. It highlights those conditions that seem to occur with increased frequency in the elderly, discusses the diagnostic tests that are of greatest value in sorting out these problems, and presents an approach to evaluation that is both practical and affordable. RECENT FINDINGS: There appears to be little value in distinguishing irritable bowel syndrome with diarrhea (IBS-D) from functional diarrhea in most patients, including older individuals. Both conditions need a thoughtful analysis of potential causes that may lead to more focused treatment. Older individuals may be more at risk of having certain structural disorders, and these need to be considered when constructing a differential diagnosis. In addition, elderly patients may have atypical presentations of specific disorders that require an increased index of suspicion. Diagnostic tests generally seem to perform well in older patients but have not been validated in this cohort of patients. Although the pretest probabilities of certain diseases are different in the elderly, the conventional algorithm for assessment of chronic diarrhea should lead to a diagnosis in most cases. Better studies are needed to adequately quantitate the likelihood of different diagnoses and the operating characteristics of diagnostic tests in older patients with chronic diarrhea. Lacking that information, physicians can still do a good job of making a diagnosis in these patients by adopting a stepwise approach.

Schiller, L. R. (2018). “Response to: The Significance of Mast Cell Activation in The Era of Precision Medicine.” Am J Gastroenterol Oct 17. [Epub ahead of print].

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To the Editor: I thank Drs. Weinstock, Rezaie and Afrin for their thoughtful letter commenting on my paper about the evaluation of patients with chronic diarrhea and irritable bowel syndrome with diarrhea (IBS-D) [1]. Mast cell activation syndrome (MCAS) should be considered in patients with multi-system symptoms, including those with IBS-D. The role of mast cells in more ordinary cases of IBS-D is still unresolved. Like Rodney Dangerfield, intestinal mucosal mast cells “don’t get no respect,” probably related to their poor uptake of commonly used histological stains, such as hematoxylin and eosin, which lets them blend in with other cells during routine histological analysis. With the use of appropriate stains, it is apparent that the intestine has plenty of mast cells, with up to 55 per high-power field in healthy subjects one study. While earlier studies claimed that IBS-D patients had greater numbers of mast cells than healthy subjects, there is substantial overlap between these two groups and attention has been focused on hyperresponsiveness of mast cells in IBS-D patients. Current studies indicate that this can happen and that therapy aimed at mast cells or their mediators with drugs such as disodium cromoglycate or antihistamines may modify symptoms in some IBS-D patients. What is not known is how often this happens and what role mast cells might play with other etiologies of IBS-D, such as food intolerances or post-infectious IBS. Future studies should clear this up. Until they do, as suggested by Drs. Weinstock, Rezaie and Afrin, clinicians should keep this mechanism in mind when dealing with patients with chronic diarrhea or IBS-D. (Text of Author’s reply to the comment of Weinstock et al. on Schiller LR. Evaluation of chronic diarrhea and irritable bowel syndrome with diarrhea in adults in the era of precision medicine. Am J Gastroenterol. 2018;113:660–9.)

Schiller, L. R. (2018). “Evaluation of chronic diarrhea and irritable bowel syndrome with diarrhea in adults in the era of precision medicine.” Am J Gastroenterol. May 1. [Epub ahead of print].

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Chronic diarrhea is a common clinical problem, affecting roughly 5% of the population in any given year. Evaluation and management of these patients can be difficult due to the extensive differential diagnosis of this symptom. Many patients with chronic diarrhea have structural problems, such as inflammatory bowel disease or celiac disease, that can be readily identified. Others do not, and often are given a diagnosis of irritable bowel syndrome with diarrhea (IBS-D). When based on generally accepted clinical criteria, a diagnosis of IBS-D identifies a group of patients who are unlikely to have disorders producing anatomical changes in the gut. It is less clear that a diagnosis of IBS-D identifies a specific pathophysiology or leads to better management of symptoms. Disorders such as small intestinal bacterial overgrowth, bile acid malabsorption, food intolerance, and motility disorders may account for symptoms in patients with IBS-D. More effective tests are being developed to identify the clinical problems underlying IBS-D and may lead to more specific diagnoses that may improve the results of therapy. Application of the principles of precision medicine (identifying a specific mechanism for disease and applying treatments that work on that mechanism) should lead to more expeditious diagnosis and treatment for patients with chronic diarrhea including IBS-D, but currently is limited by the availability of sufficiently sensitive and specific tests for underlying mechanisms that can predict response to treatment.

Schiller, L. R. (2017). “Antidiarrheal drug therapy.” Curr Gastroenterol Rep 19(5): 18.

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INTRODUCTION: Acute diarrhea often runs a self-limited course and little by way of treatment is needed except for oral rehydration therapy. Chronic diarrhea poses a longer-term problem. If not treatable with specific therapy aimed at the underlying pathophysiology, chronic diarrhea often needs long-term symptomatic therapy. PURPOSE OF REVIEW: This paper aims to examine the options for symptomatic, nonspecific treatment of diarrhea. RECENT FINDINGS: The most frequently used therapies are opiate antidiarrheal drugs. These drugs are effective for a wide variety of diarrheal conditions and generally can be used safely if monitored closely. They work by slowing motility and allowing more time for absorption. They vary in potency and in addictive liability. In recent years, a variety of other drugs have been developed, which provide more targeted therapy that can mitigate diarrhea in specific situations. These drugs work on other regulatory pathways in the gut or on mucosal absorptive mechanisms. There is evidence for efficacy for both traditional and newer agents used for the symptomatic management of diarrhea. Opiates are used most often for this indication. Other agents may benefit individuals, but further research is needed to establish indications and best practices.