Category Archives: Pediatric Gastroenterology Intestinal Disorder

Clever Study to Assess Utility of TTG IgA For Monitoring Response to a Gluten-Free Diet

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K Payne et al. JPGN Reports: 2021; August 2021 – Volume 2 – Issue 3 – p e097. Open Access Repeat Biopsy to Assess Duodenal Healing in Children With Celiac Disease and Eosinophilic Gastrointestinal Disorders

Background: “Current standard of care in the management of uncomplicated CD is not to undergo multiple esophagogastroduodenoscopies (EGDs)…  In this study, patients with both CD and eosinophilic gastrointestinal disorders (EGID) …) were identified to explore [the mucosal response to a gluten-free diet], as it is standard for patients with EGID to undergo repeat EGDs for disease surveillance.”

Key findings in this retrospective study from CHOP:

  • At second biopsy, 44% (17/39) of patients showed no histologic evidence of active CD and 36% (14/39) of patients had negative tTG-IgA values
  • 9/15 (60%) of patients with no evidence of CD on biopsy had abnormal tTG-IgA levels
  • 8/14 (57%) of patients with normal tTG-IgA levels had evidence of active disease on biopsy
  • Among the 18 who had been on a GFD for at least 2 years, 94% (17/18) had normal duodenal biopsies after 2 years, and 83% (15/18) had normal tTG-IgA values after 2 years
  • Of the patients with elevated tTG-IgA and normal duodenal biopsies, 66% (6/9) had inflammation elsewhere in the upper gastrointestinal tract, including 4 patients with active EOE and 2 patients with gastritis

My take: This study confirms that tTG-IgA levels are not optimal for monitoring. Current guidelines recognize this and recommend repeat biopsy in patients with persistent or relapsing symptoms even with negative serology

Related blog posts:

Biologic Treatment Effectiveness for Esophageal Crohn’s Disease

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J Lui et al. Inflamm Bowel Dis 2021; 27: 1544-1547. The Use of Biologics for the Treatment of Esophageal Crohn Disease

In this retrospective review (1998-2018), the authors identified 39 patients with esophageal Crohn disease (ECD) who met inclusion criteria.

Key findings:

  • 35 (92%) had a clinical response to treatment and 21 (55%) went into clinical remission
  • ECD seems to be associated with more disabling intestinal CD phenotypes. Of the 39 patients, 10 (26%) had stricturing phenotype and 21 (54%) had penetrating phenotype; 19 (49%) had perianal disease
  • “Initial treatment after diagnosis with anti-TNFalpha agents compared to other biologics was associated with greater improvement in clinical (97% vs 71%; P=0.02) and endoscopic response (95% vs. 40%; P<0.01) and in clinical remission (64.5% vs. 14.2%; P=0.01).”
  • Initial treatment with an anti-TNFalpha agent was initial treatment in 18 patients with ECD; 14 had an inflammatory, 3 had a stricturing, and 1 had a fistulizing phenotype.

While this study showed better response to anti-TNFalpha agents compared to other biologics (eg. anti-IL-12/IL-23 agents), this may be due to a selection bias as other biologics are often used as a second-line treatment and are selected more often in refractory disease.

My take: Esophageal Crohn’s disease is a rare diagnosis and appears associated with more severe disease.

Chesapeake and Ohio Canal National Historic Park (near Washington D.C.)

Accolades: Bess Schoen

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I want to recognize Dr. Bess Schoen. Bess is a colleague at Emory. I met her when I was a 4th year medical student. Since we work at different hospitals, I do not see her often but greatly respect her and her work.

From one of my colleagues, Tanya Hofmekler:

This month, we are celebrating Dr. Bess Schoen’s retirement and her long career in academic medicine.  She will be greatly missed.  Dr. Schoen has always modeled the best characteristics of a well-rounded academic physician. On top of those, she is smart, an excellent teacher and is an overall wonderful person.  She has trained and impacted many residents and fellows that have passed through Emory.  Her trainees walk away with practical medical knowledge and an example of compassionate care.  As one of her trainees, I find myself from time to time asking: “What would Dr. Schoen do?”

Dr. Schoen has also dedicated herself to improve the care of pediatric patients with Inflammatory Bowel Disease through her leadership of Improve Care Now at Emory.  This year, she will be honored by the Crohn’s and Colitis Foundation of America for her commitment and passion.

Disparity in the Care of Black Inflammatory Bowel Disease Patients

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J Liu. Inflamm Bowel Dis 2021; 27: 1548-1549. Disparity in the Care of Black Inflammatory Bowel Disease Patients

This first-hand account of the challenges of IBD care for black patients comes from the first IBD specialist recruited to Grady Hospital (Atlanta) which has a predominantly Black patient population.

Key points:

  • “The clinical, endoscopic, and histologic end points…on treatment in this patient population are all largely unknown…Black people account for 13% of the U.S. population but only 1% of the patients in nearly 200 outcome-based IBD studies [and] less than 5% of the patients participating in clinical trials of IBD therapeutics.” This is important as “we just do not know how they work for Black people.” Treatment response could be much worse (author notes that prior treatments for Hepatitis C were much less effective in Black patients).
  • Yet, “the most severe forms of Crohn’s –peri-anal and fistulizing disease– are more common in Black patients.”
  • Review of emergency visits of IBD children “showed that Black children received less medication and had more repeat emergency room visits than white children.” (Inflamm Bowel Dis 2019; 25: 194-203)
  • Because IBD is not perceived to occur frequently in Black patients, the author states that some patients are not accommodated by their employers and patients are less comfortable with support groups.
  • “However, the incidence of Crohn’s disease …in Black people has risen sharply over the past 3 decades…now approaches that of non-Hispanic whites.”

My take: Inflammatory bowel disease is definitely a disease that affects Black people; it is often more severe and requires careful treatment.

Billy Goat Trail, Chesapeake and Ohio Canal National Historic Park
(outside Washington D.C.). Yes, we made it to the top!

Enteral Naloxone for Opioid-Induced Constipation

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At a recent pharmacy committee meeting, we discussed the potential use of enteral naloxone for ICU patients with opioid-induced constipation.

Background:

  • Opioids bind to mu receptors within the gastrointestinal tract. Activation of the bowel opioid receptors slow gastric transit time, decreases gastric secretions, and reduces intestinal muscle tone leading to enhanced fluid absorption and subsequently dry and hard stools.
  • Naloxone (Narcan®) solution for oral/enteral use
    • Mechanism of action:
      • Pure opioid antagonist that competes and displaces opioid at opioid receptor sites
    • FDA-approved indication: Antidote; opioid antagonist
    • Mechanism of action:
      • As an antidote – pure opioid antagonist that competes and displaces opioids at opioid receptor sites
      • As an oral agent – Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability (if dosed properly) due to marked hepatic first-pass metabolism. As a result, oral naloxone only binds strong enough for a pharmacologic response at opioid receptors in the gastrointestinal tract without reducing the central effect of the opioid and precipitating systemic withdrawal.

Potential alternatives:

  • Methylnaltrexone (Relistor®) SQ 12mg/0.6mL (much more expensive)
  • Rectal treatments: Bisacodyl (Dulcolax®), Enema
  • Oral constipation medications:
    • Polyethylene glycol (Miralax®)
    • Bisacodyl (Dulcolax®)
    • Senna (Senokot®)

Administration:

  • Dose recommendations: 10 – 20 mcg/kg dose PO q8h (max dose: 400mcg) for 5 – 7 days, then re-evaluate therapy
  • Oral/enteral dose should be not administered intravenously to prevent systemic effect and withdrawal in patients

My take: Enteral naloxone (IV solution) may be helpful for opioid-induced constipation but caution is needed to assure it is administered enterally and at proper dose.

Some of the research studies:

  1. Tofil N, Benner K, Faro S, Winkler M. The Use of Enteral Naloxone to Treat Opioid-Induced Constipation in a Pediatric Intensive Care Unit. Pediatr Crit Care Med. 2006;7(3):254-272.
  2. Akkawi R, Eksborg S, Andersson A, et al. Effect of Oral Naloxone Hydrochloride on Gastrointestinal Transit in Premature Infants Treated with Morphine. Acta Paediatrica.2008;98:442-447
  3. Liu M, Wittbrodt E. Low-Dose Oral Naloxone Reverses Opioid-Induced Constipation and Analgesia. J Pain Symptom Manage. 2002;23(1):48-53
  4. Friedman J, Dello Buono F. Opioid antagonist in the Treatment of Opioid-Induced Constipation and Pruritus. Ann Pharmcother. 2001;35:85-91
  5. Meissner W, Schmidt U, Hartmann M, et al. Oral Naloxone Reverses Opioid-Associated Constipation. Pain. 2000;84:105-109

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Smoking, Alcohol and Obesity Increase Risk of Malignancies + Staff Morale (Humor)

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S-M Wang et al. The American Journal of Gastroenterology: September 2021 – Volume 116 – Issue 9 – p 1844-1852. Open Access: Population Attributable Risks of Subtypes of Esophageal and Gastric Cancers in the United States

This study examined population risks for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA).

“We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011.”

Key findings:

My take: Tobacco, Obesity and Alcohol are associated with increased risk for a large proportion of esophageal and gastric cancers in the United States

Related article: VK Rustgi et al. Gastroenterol 2021; 161: 171-184. Open Access: Bariatric Surgery Reduces Cancer Risk in Adults With Nonalcoholic Fatty Liver Disease and Severe Obesity

Key findings:

  • The IPTW (inverse probability of treatment weighting)-adjusted risk of any cancer and obesity-related cancer was reduced by 18% (hazard ratio, 0.82; 95% CI, 0.76–0.89) and 25% (hazard ratio, 0.65; 95% CI, 0.56–0.75), respectively, in patients with versus without bariatric surgery.
  • In cancer-specific models, bariatric surgery was associated with significant risk reductions for colorectal, pancreatic, endometrial, thyroid cancers, hepatocellular carcinoma, and multiple myeloma.

Link: Improving Morale (53 seconds)

What To Do with Perianastomotic Ulcerations

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C Madre et al. JPGN 2021; 73: 333-337. A European Survey on Digestive Perianastomotic Ulcerations, a Rare Crohn-like Disorder Occurring in Children and Young Adults

This survey study with 51 children described the etiology and treatment of perianastomic ulcerations (PAU).

Key findings:

  • Most common initial etiologies: necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11)
  • Median onset of symptoms: 39 [22–106] months after surgery
  • Clinical features: Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common
  • Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%)
  • Treatments:  treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%). The authors note that despite similarity to Crohn’s disease, there was a lack of response to immunosuppressors and anti-TNF therapies
From JPGN twitter feed. Figure 2 in article showing examples of ileocolonic ulcerations

Related article: H Barraclough et al. JPGN 2021; 73: 329-332. Anastomotic Ulcers: A Tertiary Centre Experience of Endoscopic Management Techniques This study summarized a tertiary care center experience with 9 patients (2 with IBD). Frequent treatment included aminosalicylates, and endoscopic treatments (APC, endoclips).

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Not The Onion: Cow Potty Training

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AP: No bull: Scientists potty train cows to use ‘MooLoo’

An excerpt:

Turns out cows can be potty trained as easily as toddlers… 11 out of 16 cows learned to use the “MooLoo” when they had to go…And it took only 15 days to train the young calves.

[Results were] published Monday in the journal Current Biology...Massive amounts of urine waste is a serious environmental issue,…A single cow can produce about 8 gallons (30 liters) of urine a day… toilet training animals makes it easier to manage waste products and reduce greenhouse gas emissions

The researchers mimicked a toddler’s training, putting the cows in the special pen, waiting until they urinated and then giving them a reward: a sweet liquid of mostly molasses… If the cows urinated outside the MooLoo after the initial training, they got a squirt of cold water…

The biggest environmental problem for livestock, though, is the heat-trapping gas methane they emit in belches and flatulence, a significant source of global warming. The cows can’t be trained not to belch or fart, Matthews said: “They would blow up.”

And below from The Onion:

From The Onion

Celiac Disease and Lack of Response to Hepatitis B Immunization

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A Aneja et al. JPGN Reports February 2021 – Volume 2 – Issue 1 – p e046: Open Access: Clinical Characteristics of Children With Celiac Disease Not Responding to Hepatitis B Vaccination in India

Methods: The study population from consisted of 3 groups—50 newly diagnosed CD children (group 1), 50 previously diagnosed CD children who were on gluten free diet (GFD) >3 months (group 2), and 100 age and gender matched healthy controls (group 3).

Key findings:

  • Positive anti-HBs response was found in 46% in newly diagnosed CD children, 60% in CD children on GFD, and 83% in healthy controls (P < 0.001)
  • Ongoing gluten intake has significant impact on protective immune response to Hepatitis B vaccine
  • 44 out of 45 (97.77%) nonresponders from CD group seroconverted after a single booster dose

My take: Check Hep B immune response in patients with celiac disease.

Related blog post: Improving Care Process in Celiac Disease

AGA Clinical Practice: Colorectal Dysplasia in Inflammatory Bowel Diseases

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SK Murthy et al. Gastroenterol 2021: DOI:https://doi.org/10.1053/j.gastro.2021.05.063. Full Text: AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review

Some of the recommendations:

Best Practice Advice 1: Precancerous colorectal lesions in inflammatory bowel disease should be described as either polypoid (≥2.5 mm tall), nonpolypoid (<2.5 mm), or invisible (detected on nontargeted biopsy), using a modified Paris Classification. The older terms dysplasia-associated lesion or mass, adenoma-like mass, and flat dysplasia (when referring to dysplasia detected in nontargeted biopsies) should be abandoned.

Best Practice Advice 3: Initial colonoscopy screening for dysplasia should be performed at 8–10 years after disease diagnosis in all people with colonic inflammatory bowel disease, and immediately on diagnosis of primary sclerosing cholangitis. Staging biopsies should be taken from multiple colonic segments to assess histologic disease activity and extent and to help guide future surveillance intervals.

Best Practice Advice 8: Extensive nontargeted biopsies (roughly 4 adequately spaced biopsies every 10 cm) should be taken from flat colorectal mucosa in areas previously affected by colitis when white light endoscopy is used without dye spray chromoendoscopy or virtual chromoendoscopy. Additional biopsies should be taken from areas of prior dysplasia or poor mucosal visibility. Nontargeted biopsies are not routinely required if dye spray chromoendoscopy or virtual chromoendoscopy is performed using a high-defintion endoscope, but should be considered if there is a history of dysplasia or primary sclerosing cholangitis.