AGA Recommendations for Management of Functional Symptoms in Patients with Inflammatory Bowel Disease

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Full text: AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review (JF Columbel et al. Clin Gastroenterol Hepatol 2019; 17: 380-90).

My take: Overall, this article presents a concise review of a tricky problem and appropiriate management.  The algorithm, tables and figures are useful.

Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging).

In the report, the authors note that endoscopy and cross-sectional imaging are not needed in all patients; mainly in patients with a suspected flare based on presentation, calprotectin, and blood work.

Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management.

Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation.

Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns.

Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy.

Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms.

Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation.

Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD.

Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided.

Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD.

Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder.

Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD.

Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms.

Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD.

Monticello

Origins of Hygiene Hypothesis

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A recent NY Times article explains the background of the ‘hygiene hypothesis’ and how it has held up remarkably well as a likely factor in the rising number of allergic and immune-mediated diseases.

Link: Your Environment is Cleaner. Your Immune System Has Never Been So Unprepared

An excerpt:

The British Journal of Homeopathy, volume 29, published in 1872, included a startlingly prescient observation: “Hay fever is said to be an aristocratic disease, and there can be no doubt that, if it is not almost wholly confined to the upper classes of society, it is rarely, if ever, met with but among the educated.”..

In November 1989, another highly influential paper was published on the subject of hay fever. The paper was short, less than two pages, in BMJ, titled “Hay Fever, Hygiene, and Household Size.”

The author looked at the prevalence of hay fever among 17,414 children born in March 1958. Of 16 variables the scientist explored, he described as “most striking” an association between the likelihood that a child would get hay fever allergy and the number of his or her siblings.

It was an inverse relationship, meaning the more siblings the child had, the less likely it was that he or she would get the allergy…The paper hypothesized that “allergic diseases were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings, or acquired prenatally from a mother infected by contact with her older children…

[To avoid disease] we started washing our hands and took care to avoid certain foods that experience showed could be dangerous or deadly…Particularly in the wealthier areas of the world, we purified our water, and developed plumbing and waste treatment plants; we isolated and killed bacteria and other germs…

What does the immune system do when it’s not properly trained?

It can overreact. It becomes aggrieved by things like dust mites or pollen. It develops what we called allergies, chronic immune system attacks — inflammation — in a way that is counterproductive, irritating, even dangerous.

The percentage of children in the United States with a food allergy rose 50 percent between 1997–1999 and 2009–2011, according to the Centers for Disease Control and Prevention…

There are related trends in inflammatory bowel disease, lupus, rheumatic conditions and, in particular, celiac disease. The last results from the immune’s system overreacting to gluten..

And even doctors have been wrong….They have vastly overprescribed antibiotics. These may be a huge boon to an immune system faced with an otherwise deadly infection. But when used without good reason, the drugs can wipe out healthy microbes in our gut.

My take: With the increasing frequency of many diseases, there has to be environmental influences since our population genetic makeup does not change rapidly. Thus factors like infections, microbiome and exposure to antibiotics are likely important in the changing epidemiology.

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Mortality After Feeding Tube Placement in Children with Neurologic Impairment

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A population-based study (KE Nelson et al. Pediatrics 2019; 143: e20182863) used an administrative data based from Ontario, Canada to examine the mortality rates among children with a diagnosis of neurologic impairment who underwent either gastrostomy placement or gastrojejunal placement between 1993-2015.

Key findings:

  • Two-year survival after feeding tube placement was 87.4% and 5-year survival was 75.8%
  • Unplanned hospital days, emergency room visits and outpatient visits were not significantly different after tube placement compared to pre-tube placement.

The authors interpret their findings as showing a high mortality which is likely due to medical fragility as there was “stability of health care use before and after the procedure.”

In the associated commentary (by KJ Lee and TE Corden, e20183623) the authors note the placement of a Gtube often took place after an increase in health care in the weeks prior.  They recommended engaging in shared-decision making regarding Gtube placement prior to crisis.

My take: There have been a number of studies, particularly in adults, that have shown that Gtubes may not prolong survival in many conditions.  However, they have been shown to improve nutritional status, simplify care, and improve quality of life.

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Pediatric Livers Bypassing Needy Children

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A recent study (J Ge, EK Hsu, J Bucuvalas, JC Lai. Hepatology 2019; 69: 1231-41) provides data showing that current liver allocation policy allow pediatric donor organs to bypass desperately ill children in favor of adult liver transplant recipients. The authors utilized national registry data over a 5-year period to follow the allocation of pediatric liver donor organs.

Key points:

  • About 60 children (~12% of waitlist candidates) die awaiting liver transplantation each year
  • From 2010-2014, 3318 pediatric donor livers were transplanted; 45% of these organs went to adults.
  • 390 of the 1569 adult recipients received a pediatric organ that was NEVER offered to a child
  • In this group of 390, 71% of these adults were lower acuity with MELD <35 and non-status 1A.

These data identify a deviation from the policy goal that pediatric organs are offered first to pediatric recipients.

My take: this study adds more data showing that children <12 years of age are disadvantaged with current allocation policies.  This is despite the fact that children have lower posttransplant mortality, indicating that organ transplantation is more likely to be truly life-saving in children.

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Can We Ignore Laryngeal Penetration?

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A recent retrospective study (DR Duncan et al. JPGN 2019; 68: 218-24) makes it clear that laryngeal penetration is an important finding when identified on a swallow study. The authors reviewed charts from 137 subjects (mean age 9 months) who had laryngeal penetration but not aspiration with a video swallow study (VSS).

Key findings:

  • 40% of patients with laryngeal penetration receiving thickening of feeds as treatment, 15% had a change in flow rate.  60% were maintained on thin liquids.
  • Thickening feeds was significantly associated with improvement in symptoms with OR 41.8.  91% of subjects with thickening had symptom improvement compared to 19% among group with no feeding intervention.
  • Subjects receiving a feeding intervention (thickening or change in flow rate) had decreased total  and pulmonary hospitalizations.  In contrast, in patients who did not have a feeding intervention, no significant decrease in hospitalization was noted. These data are tabulated in Table 3.  It is worth noting that those who had feeding intervention had higher risk of admission prior to feeding intervention, 0.69 compared to 0.53 for non-intervention group. Afterwards, the feeding intervention group  risk was  0.40 compared to 0.45 for the non-intervention group.
  • On followup VSS, 26% had evidence of aspiration.

One key point is that those with deep penetration were much more likely to have their feeds thickened/adjusted.

My take: This study makes it clear that all symptomatic children with laryngeal penetration should have adjustment in their feedings, most often thickening of their feeds.   These interventions appear to lower hospitalizations and are needed because in many cases the swallow dysfunction does not resolve or worsens.

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How Progressive Familial Intrahepatic Cholestasis (PFIC) Recurs After Liver Transplantation

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A recent case-report study (D Krebs-Schmitt et al. JPGN 2019; 68: 169-74) describes how progressive familial intrahepatic cholestasis (PFIC) due to bile salt export pump (BSEP) deficiency can recur after liver transplantation.

BSEP deficiency due to mutations in ABCB11 gene causes the development of PFIC type 2.  In this case report, the authors describe recurrence of BSEP-deficiency following liver transplantaion in 3 patients.

Key points:

  • Following liver transplantation, patients with PFIC 2 can develop antibodies to BSEP as this antigen was not present in the pretransplant period.  Since initial reports, more than 20 patients have been described. “In most of these cases, intensifying the immunosuppression led to normalization of graft function.”
  • In this case report, the 3 patients ultimately required retransplantation due to recurrent disease and one patient died (following retransplantation). One patient also received stem cell transplantation after a complicated course.

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Clostridium difficile and Cannabis

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Briefly noted:

W El-Matary et al. J Pediatr 2019; 206: 20-5.  This study from Manitoba using electronic database found that the incidence rate of C difficile was stable from 2005-2015, with an overall rate of 7.8 per 100,000 person-years.  Children with Hirschsprung’s and inflammatory bowel disease had increased prevalence rates.

JL O’Loughlin et al. J Pediatr 2019; 206: 142-7. Using data from two longitudinal studies in Montreal (Cannabis is legal for adults in Canada since 2018), the authors examined the rate of cannabis initiation starting in 6th grade through 11th grade. Key finding was that cannabis use was 1.8 time more likely among children whose parents used cannabis.  Overall, cannabis use increased from 3.1% in grade 6 to 25.7% in grade 11.

What is erythromelagia?  This term was noted in the title of a recent report (J Pediatr 2019; 206: 217-24) and refers to bilateral episodic pain and redness that occurs in feet, hands and occasionally the ears.  In some case, symptoms progress proximally to involve the legs, arms, and rarely the face.

 

Are Liver Tests Needed in Pediatric Patients Receiving Statin Therapy?

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A recent study (NK Desai et al. JPGN 2019; 68: 175-81) showed excellent safety of statins with regard to hepatotoxicity. This study utilized prospectively collected ALT values from the Preventive Cardiology Program at Boston Children’s and their lipid program from 2010 until 2014.  They included 943 patients (mean age 14 years) with 111 always on statin, 97 started on statin, and 735 never on a statin.

Key findings:

  • In this cohort with dyslipidemia, there was no higher burden of ALT elevations among pediatric patients receiving statin therapy compared to those who did not receive statin therapy.
  • Patients with ALT values ≥5 times ULN were not increased among patients receiving statins (n=3) compared to those who did not receiving statins (n=13)
  • Mean ALT was actually greater in the non-statin cohort by 2 U/L but likely related to the increased frequency of obesity in the non-statin group.

My take: Due to the high prevalence of nonalcoholic fatty liver disease (NAFLD), it is likely that most patients who need statin therapy would get liver biochemistries; however, this study suggests that additional monitoring is not required in asymptomatic patients who receive statins for dyslipidemia.

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