Tag Archives: irritable bowel syndrome

Chronic Diarrhea Recommendations

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Recent guidelines for adults with chronic diarrhea (>4 weeks):

Full text link: LR Schiller, DS Pardi, JH Sellin. Clin Gastroenterol Hepatol 2017; 15: 182-193.

A few key points:

  • The authors advocate treatment, not testing, for adults who meet Rome criteria for irritable bowel syndrome (IBS) without alarm symptoms.
  • Dietary history is essential.
  • “True food allergies are rare causes of chronic diarrhea in adults”
One of my colleagues questioned whether this product could be part of an effective cleanout

One of my colleagues questioned whether this product could be part of an effective cleanout

 

Blind Men and The Elephant: Lasting Consequences of Enteric Infections

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Recently, Ben Gold handed me a supplement which alluded to the case of “the blind men and the elephant.”  So, of course, I wanted to know more about this.

According to Wikipedia:

In various versions of the tale, a group of blind men (or men in the dark) touch an elephant to learn what it is like. Each one feels a different part, but only one part, such as the side or the tusk. They then compare notes and learn that they are in complete disagreement. The stories differ primarily in how the elephant’s body parts are described, how violent the conflict becomes and how (or if) the conflict among the men and their perspectives is resolved.  In some versions, they stop talking, start listening and collaborate to “see” the full elephant. When a sighted man walks by and sees the entire elephant all at once, the blind men also learn they are all blind. While one’s subjective experience is true, it may not be the totality of truth. If the sighted man were deaf, he would not hear the elephant bellow.

It has been used to illustrate a range of truths and fallacies; broadly, the parable implies that one’s subjective experience can be true, but that such experience is inherently limited by its failure to account for other truths or a totality of truth. At various times the parable has provided insight into the relativism, opaqueness or inexpressible nature of truth, the behavior of experts in fields where there is a deficit or inaccessibility of information, the need for communication, and respect for different perspectives.

The rest of the supplement regarding chronic health consequences following acute enteric infections was less interesting but probably more important than learning a new anecdote.

The introduction notes that nearly 600,000 children under 5 years die from dehydrating diarrhea each year.  Many more suffer from consequences of disease-associated malnutrition with both physical and cognitive deficits.

Articles in supplement:

  • Am J Gastroenterol Suppl 2016; 3: 4-11. –details diarrhea-associated years lived with disability 51 per 100,000 in developed regions compared with 685 in developing regions.
  • Am J Gastroenterol Suppl 2016; 3: 12-23. –details the likelihood of consequences following enteric infections, including functional GI disorders, inflammatory bowel disease, celiac disease (data limited), Guillain-Barré syndrome, hemolytic uremic syndrome, chronic fatigue, and neurologic sequelae.
  • Other articles in the supplement describe changes in the microbiome, the micorbiome-gut-brain axis, and the relationship between autoimmunity and irritable bowel.

 

Yoga Therapy for Abdominal Pain

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A recent study (JJ Korterink et al. JPGN 2016; 63: 481-7) showed that yoga treatment may be helpful with children (8-18 years) with functional abdominal pain.  The authors studied 69 subjects who received either standard medical care or standard care with yoga therapy.  Pain intensity was followed with a pain dairy as was quality of life with KIDSCREEN-27. Key finding: At 1 year follow-up, 58% of the yoga group had a treatment response compared to 29% in the control group.  Yoga therapy was associated with reduction in school absences as well as reduced abdominal pain.

While yoga is considered helpful in stress management and has been suggested as treatment for adults with irritable bowel, an associated editorial by Yvan Vanderplas (pg 451) notes that the scientific basis for yoga therapy remains weak. He notes that yoga trials are biased due to selection bias and the results are tainted due to lack of blinding with regard to the intervention.

My take: If families are interested in yoga therapy, this should be encouraged.  Yoga therapy is safer and at least as effective as many other therapies offered for abdominal pain.

screen-shot-2016-12-12-at-8-44-13-pm

 

Learned Fear of Gastrointestinal Sensations Plus Two

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Briefly noted: The authors of a recent study (E Ceunen et al. Clin Gastroenterol Hepatol 2016; 14: 1552-58) set out to study whether it is likely that healthy adults could learn to fear “innocuous visceral sensations.”  Fifty-two healthy subjects received  2 types of esophageal balloon distentions –one that was perceptible and non-painful and one that was painful.  Not surprisingly, when the researchers paired these two interventions in the experimental group, the experimental group learned to fear the innocuous stimulation as well as the painful distention.  This study provides theoretical support for one mechanism that could trigger ongoing functional gastrointestinal symptoms and a potential rationale for therapies, like cognitive behavioral therapy, which attempt to extinguish these symptoms.

In a retrospective study (AM Moon et al. Clin Gastroenterol 2016; 14: 1629-37) with 6451 patients with cirrhosis (mean age 60.6 yrs), the authors note that use of antibiotics during upper gastrointestinal bleeding (which is currently recommended) is associated with reduced mortality by ~30% at 30 days.  Despite its benefit, this intervention is often overlooked.  In the current study, only 48.6% of admissions received timely antibiotics; however, during the course of the study, the rate of antibiotic use improved from 30.6% in 2005 to 58.1% in 2013.

A recent retrospective study (N Goossens et al. Clin Gastroenterol 2016; 14: 1619-28) with 492 subjects showed that histologic NASH (in 12% of cohort) was associated with increased risk of death in patients who underwent bariatric surgery compared to patients without NASH.  Overall, bariatric surgery reduced the risk of death during the study period with HR of 0.54; the median follow-up was 10.2 years, with surgery taking place 1997-2004.  However, in patients with NASH the HR 0.90 which indicated that there was not a significant reduction in the risk of death.

Bar Harbor, ME (low tide)

Bar Harbor, ME (low tide)

Is there a link between the microbes in your colon and depression?

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A recent study (Y Liu et al. Clin Gastroenterol Hepatol 2016; 14: 1602-11) showed that fecal microbiota signatures were similar between patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and in patients with depression.

The authors analyzed stool samples from 100 Chinese subjects.  In addition to analyzed stool microbiota, the authors evaluated visceral hypersensitivity with a barostat and assessed for mucosal disease with immunohistochemical analyses of sigmoid biopsies.

In both IBS-D patients and patients with depression, the stool diversity was much less than controls and had similar abundance of many alterations, including higher proportions of Bacteroides and Prevotella (see below).

My take: It is interesting to speculate on whether changes in our microbiome could trigger/be related to the pathogenesis of not only IBS-D but other non-GI disorders like depression.

In the screenshot below, the term “COMO” refers to the 25 subjects who had both IBS and depression.

screen-shot-2016-11-14-at-12-10-03-pm

Psychological Therapies for Irritable Bowel Syndrome

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A recent meta-analysis (KT Laird et al. Clin Gastroenterol Hepatol 2016; 14: 937-47) of 41 randomized, controlled trials shows that psychological therapies improved symptoms of irritable bowel in adults.

Key finding:

  • “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition…This effect remained significant” for at least 6-12 months.

A summary of this study from GIHepNews.com:  Psychological Therapies for Irritable Bowel Syndrome

Excerpt of commentary by Dr. Christopher Almario:

While these findings are impressive and continue to support the use of psychotherapy in IBS, important issues remain. First, these results are based on data gathered in the highly controlled environment of randomized controlled trials (RCTs), and it is unclear whether they will translate to the “real world.” RCT participants may be more willing to complete psychotherapy because they know they are being observed by research staff (referred to as the Hawthorne, or observer, effect). However, in real clinical practice, patients with IBS not subject to the Hawthorne effect may be less compliant with such therapies.

Other issues relate to the current limited adoption of psychotherapy in clinical practice. Factors contributing to the low uptake include variable third-party reimbursement and poor patient and provider acceptance (JAMA. 2015 Mar;313:949-58). Another factor is limited access to qualified psychotherapists.

My take: I often refer patients to a “pain psychologist” who works in our office.  With the right psychologist, this can be very helpful.  In addition, I feel that families are more willing to see a psychologist than in the past.

Related blog posts:

JulyClinGastroCover

 

Gluten-Free for IBS-D?

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A recent study (I Aziz et al. Clin Gastroenterol Hepatol 2016; 14: 696-703) shows that a 6 week gluten-free diet reduced IBS-D symptoms in 29 of 41 (71%) patients.

  • The authors performed a prospective study with all patients receiving a gluten-free diet.  At 6 weeks, 21 of 29 who had responded to GFD continued GFD through 18 months followup.
  • One difference with this study compared to prior studies –these patients were irritable bowel syndrome with diarrhea and fulfilled Rome III criteria.  Celiac disease had been excluded with serology and histology; thus, these patients did not have “potential” celiac disease.
  • In addition to GI symptoms like abdominal pain, distention, and stooling problems, patients experienced improvement in mood, fatigue and quality of life.
  • The authors note that the response rate of 71% is much higher than they would have expected if the response was related solely to a placebo effect.

My take: This small study shows that a gluten free diet may be effective in improving the symptoms in many patients with IBS-D.  Other studies have shown that several other diets are effective as well.

Related blog posts:

IBS diagram

 

Don’t Skip this Article -Rome IV Summary

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When I visited MIT, one of the slogans I heard was “Getting an Education from MIT is like taking a drink from a Fire Hose.” While this is a ridiculous notion, it is also true that the amount of information to consume, not just at MIT, but in so many areas is tremendous in quantity.  As such, one has to figure out what to read and what to toss.  For GI physicians, a recent summary (DA Drossman. Gastroenterol 2016; 1262-80) is worth a read due to the ubiquitous nature of the problems discussed.

Here were some key points:

  • “The possibility that passions or emotions could lead to the development of medical disease was first proposed by the Greek physician Claudius Galen.”
  • “Rome IV is a compendium of knowledge accumulated since Rome III” –10 years ago.

Some of the Changes:

  • New diagnoses:  Narcotic bowel syndrome, opioid-induced constipation, cannabinoid hyperemesis syndrome
  • Removal of functional terminology when possible…functional abdominal pain syndrome has been changed to centrally mediated abdominal pain syndrome
  • Threshold changes for diagnostic criteria
  • Addition of reflux hypersensitivity diagnosis.
  • Revision of Sphincter of Oddi  dysfunction disorder…  “driven by evidence that debunks the value of sphincterotomy for type III SOD.”
  • Emphasis that functional disorders exist on a spectrum with linked pathogenesis, particularly with regard to irritable bowel syndrome (IBS) subtypes.
  • Removal of the term discomfort for IBS criteria and using pain as the key criterion.

Approach to Patients with Functional GI Disorders:

  • The author discusses ways to engage patient to create partner-like interaction.
  • “Determine the immediate reason for the patient’s visit (eg. What led you to see me at this time?)”  Potential reasons: exacerbating factors, concern for serious disease, stressors, emotional comorbidity, impairment in daily functioning or hidden agenda (eg. disability, narcotics, litigation)
  • “Determine what the patient understands of the illness…What do you think is causing your symptoms?”
  • Provide a thorough explanation of the disorder.  “For example: ‘I understand you believe you have an infection that has been missed; as we understand it, the infection is gone but your nerves have even affected by the infection to make you feel like it is still there, similar to phantom limb.”
  • “Identify and respond realistically to the patient’s expectations for improvement (e.g. How do you feel I can be helpful to you?)”
  • Explain ways that stress can be associated.  “I understand you do not see stress as causing your pain, but you have mentioned how severe and disabling your  pain is.  How much do you think that is causing you emotional distress?”
  • “Set consistent limits..narcotic medication is not indicated because it can be harmful.”
  • “Involve patient in treatment plan (e.g. Let me suggest some treatments for you to consider).”
  • With regard to use of TCAs, the author explains that antidepressants can be used “to turn down the pain, and pain benefit occurs in doses lower than that used for depression.”  “Tricyclic antidepressants or the serotonin-norepinephrine reuptake inhibitors help control pain via central analgesia as well as provide relief of associated depressive symptoms.  The selective serotonin reuptake inhibitors are less effective for pain but can help reduce anxiety and associated depression.”
  • Establish an ongoing relationship.  “Whatever the result of this treatment, I am prepared to consider other options, and I will continue to work with you through this.”

My take: This summary provides a succinct update on a 6-year effort of 117 investigators/clinicians from 23 countries.  After reading this article, you will probably want to glance at the other articles in the same issue.

Vik Muniz Collage

Vik Muniz Collage

A closer look at the front wheel

A closer look at the front wheel

Clinically Useful Biomarkers for Irritable Bowel Syndrome?

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A selected summary (Gastroenterol 2016; 150: 277-79) provides good insight into the subject of irritable bowel syndrome (IBS) biomarkers.  This summary focuses on a study by Pimental M et al (PLoS One 2015; 10: e0126438).

“In this study, the authors validated 2 serum biomarkers, antibodies (Abs) to cytolethal distending toxin (CdtB) and vinculin, primarily focused on differentiating diarrhea-predominant IBS (IBS-D) from IBD. CdtB is a bacterial toxin commonly produced by Campylobacter jejuni, as well as Escherichia coli, Salmonella, and Shigella…presence of Cdtb seems to be positively associated with the likelihood of developing a postinfectious IBS phenotype…Vinculin is a host cell adhesion protein, with which anti-CdtB Abs are known to cross-react.”

The study recruited 2681 participants (18-65 years) from 180 centers; most (n=2375) had Rome III IBS-D.

Key findings:

  • Anti-CdtB levels were higher in IBS-D 2.53 (± 0.69) compared with Crohn’s disease 1.72 (± 0.81), ulcerative colitis 1.54 (± 0.68), celiac disease 2.23 (± 0.70), and healthy subjects 1.81 (± 0.73)
  • Anti-vinculin Abs were higher in IBS-D as well: 1.34 (± 0.85) compared with Crohn’s disease 1.05 (± 0.91),ulcerative colitis 0.96 (± 0.77), celiac disease 1.07 (± 0.98), and healthy subjects 0.81 (± 0.59)

“Using a cutoff point of >2.80 for anti-CdtB Abs, the sensitivity was 43.7%, specificity was 91.6%.”  The positive likelihood ratio (LR) was 5.2 with this cutoff.  For vinculin, a cutoff of >1.68, resulted in a sensitivity of 32.6%, specificity of 83.8%, and a positive LR of 2.0.

For comparison, the commentary notes that the Rome III criteria in one study had a sensitivity of 68.8%, specificity of 79.5%, and positive LR of 3.35.

“The current study is important for 2 reasons.  First, that these 2 Abs were able to differentiate IBS-D from IBD and healthy controls, with a reasonable degree of accuracy, suggests that a substantial proportion of individuals with IBS may have an overt or subclinical postinfectious trigger, resulting in intestinal microbial disturbances…Second, the ability of these tests, if positive, to rule in IBS-D and rule out IBD is encouraging.”

But…

  • This study may not be representative of a typical primary care population with IBS
  • And,”as a rule of thumb, positive LRs of >10 are very useful in ruling in a disease…the complex, and likely multifactorial etiology of IBS may mean that a single biomarker that can diagnose IBS with the accuracy required for a test to be clinically useful is not possible.”

My take: I would like to see pediatric studies, perhaps this would help determine if a postinfectious mechanism is more common in children and adolescents.

Related blog posts:

Plantains

Plantains

Eluxadoline for Irritable Bowel Syndrome with Diarrhea

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A recent study (AJ Lembo et al. NEJM 2016; 374: 242-53) found that eluxadoline, an oral agent with mixed opioid effects was helpful in some with irritable bowel syndrome with diarrhea (IBS-D).

Study methods: 2427 adults with IBS-D received either 75 mg, 100 mg of study medication or placebo twice daily for 26 weeks.  The primary endpoint was a composite response of decreased abdominal pain and stool consistency.

Eluxadoline in IBS

Eluxadoline in IBS.  Primary efficacy end point was defined as the proportion of patients who recorded a reduction of 30% or more from baseline in the daily average score for their worst abdominal pain for at least 50% of days assessed and, on the same days, a daily stool consistency score of less than 5.  Panel A: weeks 1-12.  Panel B for weeks 1-26.

While the absolute difference in response compared to placebo appears modest (see Figure above), the authors note that the treatment effects “were similar to those reported with alosetron and rifaximin.” Adverse effects included nausea (7.5% in 100 mg group compared with 5.1% in placebo), constipation (8.6%% in 100 mg group compared with 2.5% in placebo), and abdominal pain (7.2% in 100 mg group compared with 4.1% in placebo).  Pancreatitis developed in 5 patients in the treatment group (0.3%).

My take: While Eluxadoline helped some with IBS-D, better, more effective treatments are needed.

Related blog post: