Tag Archives: irritable bowel syndrome

Headlines and Shorts for IBD and IBS

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“Higher Levels of Knowledge Reduce Health Care Costs in Patients with Inflammatory Bowel Disease.” Inflamm Bowel Dis 2015; 21: 615-22.  This retrospective observational cohort study asked 91 patients to complete a questionnaire about their knowledge on the disease after 1 year of follow-up. The authors noted an association between higher levels of knowledge and lower health care costs. While their are many limitations to this study, it is hard to argue with the conclusion that better education is worthwhile; it may also improve outcome and costs.

“Surgery and Postoperative Recurrence in Children with Crohn Disease.” Hansen LF et al. JPGN 2015; 60: 347-51. In a retrospective study dating back to 1978, the authors noted a high recurrence of surgery in children (n=115) with Crohn disease (CD).  More than 1 bowel resection was needed in 39%. The use of biologics occurred late in the study and its potential effect on lowering recurrent resection is unclear in this study. Related post:  More Lessons in TNF Therapy (Part 1) | gutsandgrowth

“Risk of Drug-Induced Liver Injury from Tumor Necrosis Factor Antagonists.” Bjornsson ES, et al. Clin Gastroenterol Hepatol 2015; 13: 602-08.  9 cases of DILI associated with infliximab (1 in 120 patients), 1 case (of 270) with adalimumab, and 1 case (of 430) associated with etanercept. 8 of 11 patients who were tested for ANA were positive. DILI was treated with steroids in 5 patients. 8 patients went on to receive a different anti-TNF without recurrent liver dysfunction. Related blog posts:

“The Prevalence of Intestinal Parasites is Not Greater Among Individuals with Irritable Bowel Syndrome: A Population-based Case-control Study” Clin Gastroenterol Hepatol 2015; 13: 507-13. Related post: Does it make sense to look for parasites in RAP …

Will I Have This Stomach Pain Forever? (Part 2)

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The article reviewed earlier today on this blog (Clinical Gastroenterology and Hepatology 2014; 12: 2026-32) has been reviewed on the AGA blog as well (some of this information is redundant from earlier post):

Here’s a link to a summary of the article: AGA blog on RAP and here’s an excerpt: Sara Horst et al investigated whether pediatric functional abdominal pain leads to functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS) in adulthood. They performed a longitudinal analysis of 392 children (8−16 years old) initially seen at a subspecialty clinic for recurrent abdominal pain. Horst et al assessed the contribution of gastrointestinal symptoms, extra-intestinal somatic symptoms, and depressive symptoms to FGIDs 5−15 years later. They found that on average 9 years later, 41% met symptom criteria for FGID—mostly irritable bowel syndrome and functional dyspepsia. Levels of depressive symptoms in childhood correlated a greater likelihood of FGID later in life (see figure).   The probability of FGID in adolescence or young adulthood increases with each increase in Children's Depression Inventory (CDI) score up to a score of 13—the cut-off point used in screening children for depression. At CDI scores higher than 13, the probability of FGID remained fairly constant.

Amplified Pain Syndromes in Children

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A recent review (Curr Opin Rheumatol 2014; 23: 1-12 -thanks to our pain team for sending reference) makes a number of important points regarding the pathogenesis and management of amplified pain syndromes (APS).

Table 1 lists the diagnosis and pain presentations.  These include complex regional pain syndromes, juvenile fibromyalgia, diffuse idiopathic pain, concomitant conditions (including irritable bowel syndrome, chronic fatigue syndrome, interstitial cystitis, chronic headache, functional abdominal pain, and conversion symptoms/disorder).

Key points:

  • Pediatric APS are widespread and under-recognized
  • Pathophysiology is complex with numerous contributors “including central sensitization, abnormal cytokine production, sympathetic-sensory disorders, autoimmune responses, altered blood flow, genetic predisposition, and psychosocial factors.”
  • “The clinical effectiveness of medication management in pediatric APS remains unclear and controversial.”  It is noted that preoperative gabapentin and pregabalin may reduce the incidence of chronic post surgical pain (in adults); this has not been documented in a pediatric population.
  • “Exercise-based and cognitive-based treatments remain the cornerstone of therapy.” Intensive multidisciplinary pain rehabilitation “restores functioning rapidly, reduces pain in the long run, improves comorbid psychological distress, and reduces medical utilization.”
  • Potential elements of treatment noted in Table 2 (geared more towards rheumatology), including exercise, desensitization, self-regulation (eg. diaphragmatic breathing, guided imagery), and stress management/counseling.

Bottomline: For children with severe pain symptoms, multidisciplinary pain teams can be very helpful.  However, there is not a simple pill that will fix everything.

Related blog posts:

 

Looking More Closely at a Persistent Question

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Virtually everyday, families that I care for are trying to ascertain the link between their GI symptoms and the foods in their diet.  Many authoritative recommendations on irritable bowel have concluded that “food allergies (symptoms caused by an immune response) are rarely the culprit in IBS patients. Most IBS patients with food-related symptoms have food sensitivities or intolerances, which are not caused by an immune response.” (From Univ Virginia Irritable Bowel Diet PDF)

Whether the process is a sensitivity or an immune-reaction, many patients are quite sensitive to certain foods and many have had improvement with a low FODMAPs diet.

A much closer look at this problem with confocal laser endomicroscopy (CLE), in a pilot study (Gastroenterol 2014; 147: 1012-20), has shown measurable changes within five minutes of a food challenge that takes place during an endoscopy.  In this study, the researchers examined 36 patients with IBS who had suspected food intolerance and 10 control patients with Barrett’s esophagus.  Then during an endoscopy, the researchers used provoking solutions of cow’s milk, wheat, yeast, or soy.  The subjects had CLE before and after the challenges. To enhance visualization of changes, subjects had fluorescein dye injected intravenously prior to examination of the duodenum.

Results

  • In 22 of 36 patients, the challenges were considered positive.  These patients had mucosal changes including increase in intraepithelial lymphocytes, followed by disruption of the villi tips/shedding of cells, then fluorescein leakage into the lumen.
  • None of the control patients exhibited these changes.
  • 19 of 22 patients with positive challenges had a >50% reduction, after 4-weeks, in symptom score with individualized diet based on inciting antigen.

Bottomline:

This provocative study indicates that subtle mucosal changes can occur in a number of IBS patients in a quick and direct response to food challenges.  Perhaps when we look closer with technologies like CLE we will find more answers as to why certain foods provoke symptoms in adults and children with IBS.

Related blog posts:

Also noted –web-based information on gastroparesis:

AGA Guidelines on Medicines for Irritable Bowel

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New guidelines on the use of medicines for irritable bowel syndrome from Atlanta Gastroenterology Association (AGA) have been published (Gastroenterol 2014; 1146-48, technical review: 1149-72).

Here’s the link: AGA IBS Guidelines.

In brief:

For IBS-C

  • Linaclotide: AGA recommends as better than no drug treatment in adult. This is the only “strong” recommendation with high-quality evidence.
  • Lubiprostone: AGA suggests over no drug treatment.
  • PEG Laxatives: AGA suggests over no drug treatment.

For IBS-D:

  • Rifaximin: AGA suggests over no drug treatment.
  • Alosetron: AGA suggests over no drug treatment.
  • Loperamide: AGA suggests over no drug treatment.

For IBS:

  • Tricyclic antidepressants: AGA suggests over no drug treatment.
  • Selective Serotonin Reuptake Inhibitors: AGA suggests against using for IBS.
  • Antispasmotics: AGA suggests over no drug treatment.

 

Also noted:

Am J Gastroenterol 2014; 109: 1547-61. (Thanks to Ben Gold for this reference.) Meta-analysis of prebiotics/probiotics for IBS.  43 RCTs were eligible for inclusion.  Key finding: IBS symptoms, including pain, bloating and flatulence were improved with RR of 0.79 compared with placebo.  “Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear.”

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NASPGHAN Postgraduate Course 2014 -Nutriton Module

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Thanks to those who attended yesterday’s talk (10/24/14) at the clinical practice session and to those who provided helpful feedback.

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  If you make it to the bottom of this post, you will find some useful patient resources along with previous related blog entries.

Diet and the Microbiome –Robert Baldassano (CHOP) pg 140 in Syllabus

This was a very effective lecture; it brought together a lot of useful information.

Trying to sort out balance between health and disease and role of dysbiosis (altered microbiome)

  • Things that we ingest such as food (diet), antibiotics, and xenobiotics shape the composition of the gut microbiota and serve as substrates for the gut microbiota to produce metabolites
  • We are not the only organism consuming what we eat

Specific studies:

  • Wu G, et al. Science. 2011 Oct 7;334(6052):105-8  The Bacteroides enterotype was highly associated with animal protein and saturated fats, which equates to frequent meat consumption as in a Western diet. The Prevotella enterotype high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet more typical of agrarian societies.
  • De Filippo C, et al. PNAS 2010: 14691-96: African children (compared with European) with more bacterial diversity & richness along with higher levels of short-chain fatty acids
  • Holmes et al. Cell Met 2012; 16: 559. Diet serves as a substrate for the microbiota to produce certain metabolites.

IBD and diet (Hou JK et al. American Journal of Gastro 2011;106:563-73)

  • High dietary intakes of total fats, PUFAs, omega-6 and meat were associated with an increased risk of CD and UC
  • High fiber and fruit intakes were associated with decreased CD risk
  • High vegetable intake was associated with decreased UC risk.
  • Consumption of meat, particularly red and processed meat increased the likelihood of relapse (Jowett et al Gut 2004)
  • Enteral diet for IBD can improve stool calprotectin within 1-2 weeks.

Take-home messages: Don’t tell your patients with non-stricturing IBD to eat a low fiber diet.  Reduced red meat and reduced oral iron may be helpful.  Vegetarian diet and Mediterranean diets may be helpful.

Related blog posts:

FODMAP: Navigating this Novel Diet –Bruno Chumpitazi, MD, MPH (Texas Children’s Hospital) -page 152 in Syllabus

  • Fermentable Oligosaccharides Disaccharides and Polyols (FODMAPs): Poorly absorbed, osmotically active, rapidly fermented (produce gas)
  • Higher FODMAPs increase breath hydrogen (Murray K et al. Am J Gastroenterol 2014;109:110-9)
  • Higher FODMAPs increase stool/ileostomy output (Barret JS et al. Aliment Pharmacol Ther 2010;31:874-882,Halmos EP J Gastroenterol Hepatol 2013;28(Suppl4):25-28)

Evidence for use of low FODMAPs diet is best in adult irritable bowel syndrome.

  • Shepherd SJ et al. Clin Gastroenterol Hepatol 2008;6:765-71
  • Staudacher HM et al J Nutr 2012;142:1510-18
  • Ong DK et al. J Gastroenterol Hepatol 2010;25:1366-1373
  • Halmos EP et al. Gastroenterology 2014;146:67-75

Limited studies in children.

  • Chumpitazi BP et al. NASPGHAN 2014 abstract n=33 pediatric IBS.  Favorable response noted to low FODMAP diet.

Dietary recommendations were reviewed along with the caveat that obtaining the assistance of a dietician/nutritionist is recommended.

Resources:

Related blog posts:

Nutrition in the Child with Neurological Disabilities –Kathleen Motil (Baylor College of Medicine) pg 162 in Syllabus

  • Nutritional disorders are highly prevalent in children with neurological disabilities: 29-46% are underweight; 8-14% are overweight.
  • Improved nutrition improves behavior, activity level, improves growth, and reduces infections.
  • Cause of nutritional disorders mostly related to inappropriate dietary intake but other factors can play a role
  • Growth/anthropometric measures are key determinant of nutritional assessment
  • Key questions: Is child taking all day to eat? Is child choking with feedings?
  • Critical BMI <12 kg/m-squared
  • Goal for BMI ~25%

Reasons for gastrostomy:

  • Flat growth >6 months/weight below curve
  • Parental request
  • Medication administration
  • Aspiration

Resource:

www.feedingtubeawareness.com  This site contains a terrific PDF download which explains enteral tubes in an easy to understand style along with good graphics. “What You Need to Know Now, A Parent’s Introduction to Tube Feeding is the guide book that every parent wished they had when they were first introduced to feeding tubes.”

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Brave New World: Psychotropic Manipulation & Pediatric Functional GI Disorders

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A recent review (JPGN 2014; 59: 280-87) provides helpful advice for the use of psychotropic medications in pediatric functional GI disorders.  That being said, a couple key caveats need to be stated first and foremost:

  • “A minority of psychotropic drugs has been studied in children and safety data remain inadequate.  Psychotropic drugs used for gastrointestinal symptoms in pediatric patients will be off-label for the foreseeable future.”
  • “Descriptions of individual drugs in the present review are too brief to provide accurate guidance to someone who is not already familiar with them.”

Given the limited data, the authors, in my opinion, bravely state recommendations regarding these medications.  Despite their common usage, providing explicit recommendations is quite uncommon.  The title of the blog references Aldous Huxley’s book which discusses psychological manipulation.  This book in turn is titled after a line from Shakespeare’s The Tempest, Act V, Scene I (from Wikipedia):

“O wonder!
How many goodly creatures are there here!
How beauteous mankind is! O brave new world,
That has such people in’s.”

Back to the review of psychotropic medications, the authors provide a rationale/pathophysiologic mechanism for the use of these drugs mainly for recurrent abdominal pain and chronic nausea/dyspepsia.  Table 1 lists the authors’ specific suggestions regarding first to fourth choices:

  • For abdominal pain, first choice was amitriptyline, followed by gabapentin, clonidine patch, and SSRI.
  • For nausea/dyspepsia,  first choice was amitriptyline, followed by mirtazapine, buspirone, and clonazepam.
  • For d-IBS,  first choice was amitriptyline, followed by alosetron [not a psychotropic], clonidine patch, and SSRI.
  • For c-IBS (along with polyethylene glycol),  first choice was imipramine, followed by lubiprostone [not a psychotropic], gabapentin, and SSRI.

Table 2 provides dosing suggestions, and common adverse effects.  For example, with amitriptyline, suggested dose is 10-50 mg qhs and “best to begin low dose…titrate up by response.” Other suggestions:

  • SSRIs: “should begin with low dose; titrate up by response.  With SSRIs, benefit is usually apparent after 4 to 6 wk.  Most GI adverse effects disappear in 1 to 2 wk.”
  • Mirtazapine: 7.5 mg dosing for sleep, 15-30 mg qAM for nausea/dyspepsia (higher dose is usually not sedating.  “Few drug interactions; safer than TCAs.” Weight gain is common.
  • Buspirone: 10-60 mg/day, divided twice daily; “may start with half dose in the morning.” Avoid grapefruit juice. Can “used alone or in combination with SSRIs or TCAs.”
  • Gabapentin (100 mg BID to 800 mg TID). “Rare adverse effects include drowsiness and blurred vision…Safe but only effective in about one-third of patients.”
  • Recommends that second-generation antipsychotics (quetiapine, risperidone, and olanzapine) be used only in collaboration with child psychiatry (Figure 2)

Additional pointers:

TCAs:“In RCTs, among children with functional abdominal pain, both amitriptyline and placebo were associated with an excellent therapeutic response.”  It is interesting to note the authors lack of critical comments regarding this statement.  “The usual dose of amitriptyline for chronic functional pain is 1 mg/kg/day up to a maximum of 50 mg/day.”

TCAs and EKGs: “at doses <1 mg/kg/day used to treat chronic pain and nausea, there have been no reports of death or cardiac arrhythmias in >60 years.  An EKG before starting a TCA is unnecessary in otherwise healthy children and adolescents, but may be advisable in those with a personal or family history of corrected QT interval prolongation or heart disease, or in children requiring a dose >50 mg/day.”

TCAs: some tricyclics may be less sedating and constipating including imipramine, doxepin, and nortriptyline.  The later two also come in liquid formulations.

SSRIs: “may be used in combination with TCAs in teens and adolescents…using them simultaneously may increase serum concentrations of both.” “In children there was a single RCT showing citalopram superior to placebo in IBS. Some clinicians obtain an EKG assessing corrected QT interval before initiating citalopram doses >20 mg daily.”

Clonidine has “improved diarrhea-predominant IBS…Common adverse effects include dry mouth, drowsiness, dizziness, and tiredness…checking blood pressure at each clinic visit [is recommended].” It is available as a patch (0.1-0.3 mg/wk).

Melatonin: dosed 3- to 10-mg at bedtime can promote sleep.

Take-home message: This article provides practical advice for the use of these agents.  Discussion with patients and parents regarding the role of these medications in targeting CNS arousal which perpetuates disabling chronic symptoms is crucial as well.  More studies are needed to determine conclusively their effectiveness.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

IBS Subtypes in Pediatrics

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A recent study (Clin Gastroenterol Hepatol 2014; 12: 1468-73) examined irritable bowel syndrome (IBS) subtypes among 129 subjects ages 7 to 18 who met Pediatric Rome III IBS criteria.  These children were part of larger studies of functional gastrointestinal disorders and recruited from primary and tertiary care centers.  Participants completed pain and stool diaries.

Key finding:

  • IBS with constipation (IBS-C) was the most common subtype (58.1%); in the other categories IBS unsubtyped (IBS-U) was next at 34.1%, then IBS with diarrhea (IBS-D) at 5.4%, and least common was mixed IBS (IBS-M) at 2.3%

The authors note that in adults with IBS studies tend to yield a more even distribution among the subtypes IBS-C, IBS-D, and IBS-U along with smaller numbers in IBS-M.

Take-home message: IBS with constipation is common in pediatrics.  Among patients who have been labelled as having isolated constipation, many in fact have IBS-C and may have persistent gastrointestinal symptoms despite the use of laxatives.

Related blog post:

Mechanisms of irritable bowel syndrome | gutsandgrowth

Ondansetron for Irritable Bowel with Diarrhea?

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Briefly noted: A selected summary (Gastroenterol 2014; 147: 527-28) reviews the potential utility of ondansetron (median dose in adult participants was 4 mg) for irritable bowel syndrome with diarrhea (IBS-D) based on a recent study (Link to full online journal article: Randomized Trial of Ondansetron for IBS-D in Gut).

Several limitations are discussed including patient dropout, crossover study design, and short term study (in chronic disease).  As such, even though this study provides some evidence that ondansetron may be helpful for IBS-D, this probably needs “to be replicated in large-scale, parallel group, randomized, placebo-controlled trials…with longer duration of therapy..before the true place of ondansetron in the management of IBS-D is known.”

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Mechanism for FODMAPs diet

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According to a recent study (Gut doi:10.1136/gutjnl-2014-307264 -thanks to KT Park for reference), a low FODMAPs diet changes the microbiome which in turn may relate to improvements in patients with irritable bowel syndrome.

Abstract

Objective A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial.

Design Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed.

Results Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs 9.83 (9.72 to 9.93) log10 copies/g; p<0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa (median ratio 6.62; p<0.001) and mucus-associated Akkermansia muciniphila (19.3; p<0.001), and reduced Ruminococcus torques.

Conclusions Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation.

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