AGA Guidelines for Evaluation of Functional Diarrhea and IBS-D

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W Smalley et al. Gastroenterol 2019; 157: 851-54. Full Text Link: AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D)

Clinical support tool on pg 855, Patient Summary 856-57, and Technical Review 859-80.

These guidelines/recommendations (listed below) do NOT apply to patients with any of the following:

  • Alarm features such as gross blood, weight loss, anemia, and hypoalbuminemia
  • Family history of of IBD, colon cancer, or celiac disease
  • Travel to areas with high prevalence of infectious diarrhea
  • Immune suppression
  • Ingestion of medications or substances known to cause diarrhea

 

Table 3  Summary of Recommendations of the American Gastroenterological Association on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults
Statement Strength of recommendation Quality of evidence
Recommendation 1: In patients presenting with chronic diarrhea, the AGA suggests the use of either fecal calprotectin or fecal lactoferrin to screen for IBD. Conditional Low
Recommendation 2: In patients presenting with chronic diarrhea, the AGA suggests against the use of ESR or CRP to screen for IBD. Conditional Low
Recommendation 3: In patients presenting with chronic diarrhea, the AGA recommends testing for Giardia. Strong High
Recommendation 4: In patients presenting with chronic diarrhea with no travel history to or recent immigration from high-risk areas, the AGA suggests against testing stools for ova and parasites (other than Giardia). Conditional Low
Recommendation 5: In patients presenting with chronic diarrhea, the AGA recommends testing for celiac disease with IgA-tTG and a second test to detect celiac disease in the setting of IgA deficiency Strong Moderate
Recommendation 6: In patients presenting with chronic diarrhea, the AGA suggests testing for bile acid diarrhea. Conditional Low
Recommendation 7. In patients presenting with chronic diarrhea, the AGA makes no recommendation for the use of currently available serologic tests for diagnosis of IBS None Knowledge gap

For recommendation #6, the authors note that tests for bile acid mediated diarrhea in the U.S. include total bile acid in a 48-hour stool collection and serum fibroblalt growth factor 19.

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IBD Shorts: September 2019

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S Olivia et al (including Stanley Cohen from GI Care for Kids) Clin Gastroenterol Hepatol 2019; 17: 2060-7. “A Treat to Target Strategy Using Panenteric Capsule Endoscopy in Pediatric Patients with Crohn’s Disease”  In this prospective study with 48 children with Crohn’s disease, pan-enteric capsule endoscopy (PCE) detected inflammation in 34 (71%) at baseline, 22 (46%) at week 24, and 18 (39%) at week 52.  PCE results were used to manage treatment and resulted in change in therapy in 71% at baseline and 23% at week 24.  Furthermore, PCE increased the proportions of patients in deep remission, up to 58% at week 52.

M Wright, et al. J Pediatr 2019; 210: 220-5. This case report of a 4 year-old boy with a perianal abscess and granulomatous colitis identified a NCF4 mutation causing severe neutrophil dysfunction.  He developed osteomyelitis with anti-TNF therapy and did not respond to vedolizumab. He had an excellent outcome following a hematopoietic stem cell transplantation. This study reinforces the potential benefit of investigating VEO-IBD which could allow more targeted therapy. Related blog post:

P Zapater et al. Inflamm Bowel Dis 2019; 25: 1357-66. This study with 112 patients with Crohn’s disease showed that serum interleukin-10 levels were directly related to infliximab and adalimumab levels.  This suggests that serum anti-TNF levels are significantly influenced by immunological activation.

JE Axelrad et al. Clin Gastroenterol Hepatol 2019; 17: 1311-22.  This study, using the Swedish National Patient Register, showed that gastrointestinal infection increased the odds of developing IBD in a nationwide case-control study.  “Of the patients with IBD, 3105 (7%) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR 1.64), bacterial gastrointestinal infection (aOR 2.02) and viral gastrointestinal infection (aOR 1.55)…a previous episode of gastroenteriitis remained associated with odds for IBD more than 10 years later (aOR 1.26).”  The authors note that they cannot formally exclude misclassification bias, but it appears that enteric infections contribute to the development of IBD in susceptible individuals.

Polyposis in Pediatric Patients -Review

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A recent review article (SP MacFarland et al. JPGN 2019; 69: 273-80) provides clearcut guidelines on polyposis syndromes in pediatric patients.

Table 1 lists the syndrome, the mutated gene (s), and recommended screening (onset & interval). The article and table provide more nuance/guidance but the basic recommendations are noted as follows:

  • For Familial Adenomatous Polyposis (FAP), the authors recommend onset of colonoscopy at 10 years and with 1 year intervals.  “Colectomy recommended by 20 to 25 years.”  EGD is recommended at 18 to 20 years. Thyroid ultrasound is recommended at 18 years.  Alpha-fetoprotein levels to check for hepatoblastoma are recommneded every 3-6 months in infancy up to 5 years of age.
  • For Juvenile Polyposis Syndrome, EGD and Colonoscopy are recommended at 15 years with interval evaluations at 1-3 years.
  • For Peutz-Jeghers syndrome, EGD and Colonoscopy are recommended at 8 to 10 years (along with small bowel evaluation with either MRE or video capsule).  Interval followup is recommended every 2-3 years.

Table 2 provides suggestions for familial screening in pediatric polyposis syndromes.

Related blog posts:

Pittock Mansion, Portland OR

 

Preliminary Recommendations from NASPGHAN on Zantac/Ranitidine Warnings

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Recently, there have been concerns about zantac (ranitidine).  NASPGHAN has made the following preliminary recommendations:

NASPGHAN has been in conversation with the FDA and would like to offer the following language for you/your office/your division and your patients/parents.

The U.S. Food and Drug Administration has learned that some ranitidine medicines, including some products commonly known as the brand-name drug Zantac, contain a nitrosamine impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables.
The FDA has been investigating NDMA and other nitrosamine impurities in blood pressure and heart failure medicines called Angiotensin II Receptor Blockers (ARBs) since last year, and when it discovered unacceptable levels of nitrosamines the ARBs have been recalled.

The FDA is evaluating whether the low levels of NDMA in ranitidine pose a risk to patients and will post that information when it is available.

It is important to note that although NDMA may cause harm in large amounts, the levels the FDA is finding in ranitidine from preliminary tests barely exceed amounts you might expect to find in common foods.

The agency is working with international regulators and industry partners to determine the source of this impurity in ranitidine. The agency is examining levels of NDMA in ranitidine and evaluating any possible risk to patients. The agency will provide more information as it becomes available.

The FDA is not calling for individuals to stop taking ranitidine at this time; however, patients taking prescription ranitidine who wish to discontinue use should talk to their health care professional about other treatment options. People taking OTC ranitidine could consider using other OTC medicines approved for their condition. There are multiple drugs on the market that are approved for the same or similar uses as ranitidine.

Are There Any Babies with a Normal GI Tract?

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A recent study (S Salvatore et al. J Pediatr 2019; 212: 44-51) examines the role of neonatal antibiotics and prematurity on the development of functional gastrointestinal disorders in the first year of life.

What is most striking, though, in this study is how many of these infants have a GI disorder.

Background: Prospective cohort multicenter study with 934 infants who completed study; n=302 premature, n=320 antibiotic recipients

Key findings:

  • 718 (77%) had at least one functional GI disorder (FGID) based on Rome III criteria, including 47% with colic, 40% with regurgitation, 32% with dyschezia, 27% with constipation, and 4% with functional diarrhea
  • Preterm infants had FGID rate of 86% compared with 73% of full term infants (P=.0001)
  • Use of antibiotics was associated with FGIDs as well, with aRR of 1.16 (P=.001)
  • The prevalence of FGIDs was highest in the first three months of life and then improved markedly by 6 months of age; by 12 months of age, each of the FGIDs was well below 10%.

Limitation: This study relied on parental reports which could overestimate infant’s symptoms.

My take: More than 75% of infants had at least one FGID.

Related blog posts:

Good Food and Bad Food for Crohn’s Disease -No Agreement

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As noted in a previous blog (IBD Briefs August 2019), there have been numerous diets proposed to help with Crohn’s disease.   The chart below illustrates the lack of any consensus.

Related blog posts:

Breifly Noted: Duodenal and Rectal Eosinophilia in Nonceliac Gluten Sensitivity

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A Carroccio et al. Clin Gastroenterol Hepatol 2019; 17: 682-90. This prospective study examined 78 patients with a diagnosis of non-celiac gluten sensitivity (NCGS) based on double-blind wheat challenge.  The authors identified markers of inflammation including eosinophils in the duodenum and rectum of patients with NCGS:  –the mean eosinophil infiltration was more than 2.5-fold the upper limit of normal in rectum and almost 2-fold in duodenum.

Rectal eosinophilia (>9 eos in the rectal lamina propria) had a sensitivity of 94%, specificity of 70%, positive predictive value of 81% and negative predictive value of 89% for NCGS.

My take: (from the editorial,pg 613-4) “In many cases, NCGS is likely a mislabeled functional GI disorder (IBS or FD) induced by wheat proteins or FODMAPs…tissue eosinophilia [is a] potential biomarker..although this observation needs further confirmation.”

Yummy! Though, probably the wrong place for those trying to be gluten-free

Liver Briefs -September 2019

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P Rosenthal et al. Hepatology 2019; 69: 2326-37.  This study examined the efficacy and safety of combined entecavir and Peginterferon for immune-tolerant chronic hepatitis B-infected children (n=60). 48 weeks after completing treatment (week 96), 2 children (3%) achieved the primary outcome of undetectable HBeAg with HBV DNA levels <1000 IU/mL.  These two children were also HBsAg negative/anti-HBs positive. In the other children (55 completed study), the ALT and HBV DNA levels were similar to baseline.  37 children experienced adverse events.  My take: Entecavir/peginterferon is not very effective in immune-tolerant children infected with chronic HBV.

DL Thomas. NEJM 2019; 380: 2041-50. This article reviews the pathway to the global elimination of chronic hepatitis.  Currently, it is estimated that hepatitis C virus (HCV) and hepatitis B virus (HBV) kill more than 1 million persons each year. “In fact, by 2040, deaths from chronic hepatitis are projected to exceed the combined mortality associated with HIV infection, tuberculosis, and malaria.”

JR Dillman et al. J Pediatr 2019; 212: 60-5. This study with 41 patients and 13 patients with biliary atresia prospectively assessed ultrasound shear wave elastography (SWE). The authors found that SWE with a cut-off value of >1.84 m/s had 92% sensitivity and 79% specificity.  Also, in their cohort, GGT >320 had a sensitivity of 100% and specificity of 78%.

Z Younossi et al. Hepatology 2019; 69: 2672-82.  This review provides a global perspective of NAFLD.  25% of the world’s population is currently thought to have NAFLD with highest prevalence in South America at 30.45% and lowest in Africa at 13.5%. This article usggest North America to have 24.1% prevalence rate.

Briefly Noted: Alpha-Fetoprotein Norms for Beckwith-Wiedeman Spectrum

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Alpha-fetoprotein (AFP) levels are increased in >95% of patients with hepatoblastoma.  These levels have to be interpreted carefully in infants as these levels typically are elevated in the first 6-12 months of life.

For patients with Beckwith-Wiedeman Spectrum (BWS), the relative risk of hepatoblastoma has been estimated to be 2280 times greater than the general population.  In addition, in patients with BWS, AFP levels are known to be elevated compared to the general population in the absence of hepatoblastoma as well.

A recent study (KA Duffy et al. J Pediatr 2019; 212: 195-200) obtained 1372 AFP levels from 147 patients to establish normative values.

Table 2 -will be a useful reference. The authors found that AFP values were significantly higher in premature infants with BWS compared to full term and gradually approached normal levels around 12 months of life.

Some example AFP (95% CI) values from the entire cohort:

  • 1 week 5364 (3554-8095)
  • 4 weeks 3134 (2136-4597)
  • 12 weeks 849 (613-1176)
  • 6 months 134 (102-177)
  • 12 months 13.8 (11.1-17.3)

My take: This article will be very useful when monitoring for the risk of hepatoblastoma in patients with BWS