Category Archives: Pediatric Gastroenterology Intestinal Disorder

How To Achieve Helicobacter Pylori Cure Rates of >95%

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Related to yesterday’s blog, here is an SNL commercial for the “Koohl” toilet (also with Benedict Cumberbatch) in 2016: SNL Koohl Toilet

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DY Graham, SF Moss. Am J Gastroenterol 2022. 117: 524-528. Antimicrobial Susceptibility Testing for Helicobacter pylori Is Now Widely Available: When, How, Why

Key points:

  • Susceptibility testing for H pylori is widely available in the U.S. and should help optimize treatments to get success rates >95%. Testing is now available for the most common treatment antibiotics: amoxicillin, metronidazole, tetracycline, levofloxacin, clarithromycin, and rifabutin.
  • Handling/shipping specimens properly is important with susceptibility testing
  • The authors recommend a PPI which is minimally-affected by CYP2C19 metabolism, namely rabeprazole or esomeprazole.
  • Provide careful instructions to patient/family regarding treatment

Susceptibility Testing Labs (see Table 1):

  • Quest: Our Quest representative indicated code: 36994 (H. pylori culture with reflex to susceptibility). Preferred Specimen: 3 mm Gastric/Antral or Duodenal biopsy collected in Brucella broth or Trypticase Soy Broth (TSB) with 10-20% glycerol
  • LabCorp: Helicobacter pylori Culture Test Code Test Code 180885
  • ARUP: Helicobacter pylori Culture Test Code 2006686
  • Culture (Catalog HELIS) or Stool PCR testing (Catalog HPFRP) can be done by Mayo Clinic
  • Reflex stool testing as well as PCR gastric testing from formalin is available through by American Molecular laboratories

A treatment algorithm is listed:

  • In the absence of highly effective empiric treatment or after treatment failure, the authors recommend susceptibility testing.
  • If clarithromycin susceptible, then a 14-day clarithromycin triple therapy course is recommended
  • If clarithromycin resistant but metronidazole susceptible, then 14-day metronidazole triple therapy
  • If resistant to both clarithromycin and metronidazole, then either a 14-day bismuth quadruple therapy, or a rifabutin triple therapy are preferred. However, if H pylori organisms are levofloxacin susceptible, then 14-day levofloxacin triple therapy may be a good option.
  • The authors recommend quinolone therapy only in the setting of susceptibility testing due to the FDA warnings about long-term adverse effects.

My take: Perhaps H pylori susceptibility testing availability needs to be a quality metric for hospitals and endoscopy centers.


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AAP Guidelines for Down Syndrome & Screening for Celiac Disease Plus One (How to Fix Diarrhea)

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The AAP has updated recommendations for Down syndrome: MJ Bull et al. Pediatrics (2022) 149 (5): e2022057010. Open Access: Health Supervision for Children and Adolescents With Down Syndrome

For gastroenterologists, one area of concern is screening for celiac disease in this population due to a mildly increased risk.

Here is what is recommended in children after 1 year of age:

“For children on a diet that contains gluten, review for symptoms potentially related to celiac disease at each health supervision visit because children with Down syndrome are at increased risk. These symptoms include diarrhea or protracted constipation, slow growth, unexplained failure to thrive, anemia, abdominal pain or bloating, or refractory developmental or behavioral problems.97–99  For those with symptoms, obtain a tissue transglutaminase immunoglobulin A (TTG IgA) concentration and simultaneous quantitative IgA. The quantitative IgA is important, because an IgA deficiency renders the TTG IgA unreliable. Refer patients with abnormal laboratory values for specialty assessment. Do not institute a gluten-free diet before confirmation of the diagnosis, because lack of gluten can make interpretation of endoscopic results difficult. There is no evidence that routine screening of asymptomatic individuals would be beneficial. There are neither data nor consensus that would indicate whether patients with persistent symptoms who had normal laboratory values on initial evaluation should have further laboratory tests.”

In addition to celiac disease, the AAP article has a ton of useful resources regarding Down syndrome for clinicians and families.

My take: Celiac disease is difficult to diagnose and is much more common in children with Down syndrome. It is worth noting that other Down syndrome groups, NICE and NASPGHAN have recommended screening for celiac in all children with Down syndrome. (Ref: M Pavlovic et al. World J Clin Cases. 2017 Jul 16; 5(7): 264–269. Open Access: Screening of celiac disease in Down syndrome – Old and new dilemmas)

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White Sands National Park, New Mexico

Also, a keen observation from Carlo Di Lorenzo’s twitter feed:

The corollary of this is how miraculous it is when a child who has not stooled for 3 weeks straight has no residual markers after swallowing a Sitz capsule.

@MondayNightIBD and Acute Severe Ulcerative Colitis Algorithm

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A summary of the discussion and more detailed information on this topic from Gastroenterology and Endoscopy News (4/20/22): Open Access: ASUC: A Medical and Surgical Emergency Requiring Comprehensive, Timely Multidisciplinary Care

Lab workup per article:

For infliximab salvage therapy, the article recommends re-dosing at 3-5 days after initial dose.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

IBD Shorts: Pediatric Colonic CD, UC Colectomy Risk Factors, Ustekimumab for 5 years

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TD Berger et al. JPGN 2022; 74: 258-266. Clinical Features and Outcomes of Paediatric Patients With Isolated Colonic Crohn Disease

This study focused on 94 with isolated colonic Crohn’s disease (L2). Key findings: Response to enteral nutrition (78.3%) was comparable to those with L1 disease (82.4%) (n=104). Skp lesions and granulomas, identified in 65% and 36% in those with L2 disease was similar to those with L1 disease.

JS Hyams et al. Inflamm Bowel Dis 2022; 28: 151-160. Open Access: Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis

Key findings:

  • 25/428 (6%) children with recently diagnosed UC underwent colectomy at ≤1 year, 33 (9%) at ≤2 years, and 35 (13%) at ≤3 years. 
  • An initial PUCAI ≥ 65 was highly associated with colectomy (P = 0.0001)
  • A  pretreatment rectal gene expression panel showed that patients who had colectomy had significantly higher values for this genetic signature in comparison with those who did not require colectomy

WJ Sandborn et al. Clin Gastroenterol Hepatol 2022; 20: 578-590. Open Access: Five-Year Efficacy and Safety of Ustekinumab Treatment in Crohn’s Disease: The IM-UNITI Trial

Key findings:

  • Using an intent-to-treat analysis of all patients randomized to ustekinumab at maintenance baseline, 34.4% of patients in the every-8-weeks group and 28.7% in the every-12-weeks group were in clinical remission at week 252. In the 8 week group in the long-term extension portion of the study the rate was 54.9%
  • Adverse effect profile (per 100 patient-years): generally were similar in the placebo and combined ustekinumab groups for all adverse events (440.3 vs 327.6), serious adverse events (19.3 vs 17.5), infections (99.8 vs 93.8), and serious infections (3.9 vs 3.4).
White Sands (actually gypsum) at White Sands National Park, NM

“For Hospitalized Patients With ASUC, 5-ASA Adds No Value to Steroids”

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From Gastroenterology and Endoscopy News (4/25/22): Open Access: For Hospitalized Patients With ASUC, 5-ASA Adds No Value to Steroids

In the first prospective randomized study, presented at the 2022 Crohn’s & Colitis Congress and published in Inflammatory Bowel Dis (S Ben-Horin et al 2022;28 [suppl 1]:S14 CORTICOSTEROIDS AND 5ASA VERSUS CORTICOSTEROIDS ALONE FOR ACUTE SEVERE ULCERATIVE COLITIS: A RANDOMIZED CONTROLLED TRIAL), investigators at 10 centers in six countries randomly assigned 149 patients hospitalized for ASUC to receive daily doses of 300 mg of hydrocortisone (or equivalent methylprednisolone) alone or in combination with 4 g of mesalamine.

Key findings:

  • 72.6% of patients receiving combination corticosteroids with 5-ASA responded to treatment at one week compared with 76.3% of responders in the group receiving corticosteroids alone
  • “There were no differences in hospital length of stay between groups (median, 10 vs. nine days for the combination and monotherapy groups, respectively), the proportion of patients whose C-reactive protein level normalized (34.2% vs. 34.3%, respectively), or the proportion requiring colectomy within 90 days (4.9% vs. 4.5%, respectively).”
  • While 5-ASAs did not alter the trajectory of acute colitis, one other finding was a lower rate of biologic use (27% vs 47%, P=.07) at 90 days in those who continued to receive 5-ASA therapy at 90 days.

My take: 5-ASAs do not appear to be helpful during hospitalization for ASUC but may be beneficial as a maintenance therapy in some patients.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

Esophageal Squamous Papilloma in the Pediatric Population

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N Malhotra et al JPGN Reports 2022; doi: 10.1097/PG9.0000000000000178. Open Access: Esophageal Squamous Papilloma in the Pediatric Population

  • This is a case report of 4 cases of esophageal squamous papilloma (ESP); Three out of the 4 cases of ESP identified at our institution were positive for HPV in situ hybridization.
  • “Chronic mucosal irritation due to GERD or HPV is thought to be the most common cause of ESP…a recent study failed to identify a relationship between the prevalence of HPV and the occurrence of ESP in pediatric patients”
  • “Small esophageal lesions can be managed by excisional biopsy; however, conservative management is advised when the disease is extensive to avoid mucosal scarring and stenosis…Acid suppression may decrease ongoing inflammation.”
  • “Vaccinating children with active HPV infection could theoretically increase the immune response and potentially aid in clearance of lesions caused by the disease.”

Related blog post: Esophageal Squamous Papilloma in Children Are Rare

Interesting Case of Superior Mesenteric Artery Syndrome

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D Hsu et al. JPGN Reports; 2022; doi: 10.1097/PG9.0000000000000194. Open Access: Superior Mesenteric Artery Syndrome in an Adolescent With Anorexia and Suspected Pancreatitis

“A 17-year-old … presented with cachexia, nonbilious, nonbloody emesis, lower abdominal discomfort, and decreased oral intake for four days and 40 lb weight loss for 1 year”…Lipase was 4544 U/L, and abdominal ultrasound was reported as normal. Due to “persistent emesis, despite being on bowel rest… CT abdomen and pelvis was performed, which showed a massively dilated stomach and duodenum with cutoff at the third portion of the duodenum..due to the severity of the obstruction, duodenojejunal anastomosis, and gastrostomy tube placement were performed.”

FLUTE Study: Fluticasone ODT for EoE -Phase 2b Study Shows Efficacy

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ES Dellon et al. Clin Gastroenterol Hepatol 2022; https://doi.org/10.1016/j.cgh.2022.02.013 (Ahead of print) Open Access: Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial

Methods: In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011  (fluticasone propionate oral disintegrating tablet) doses or placebo for a 12-week induction period and 40 weeks of maintenance. 

Key findings:

  • Histologic response (≤6 eosinophils per high-power field at Week 12) rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). 
  • There was also improvement in treatment group in dysphagia and EoE Endoscopic Reference Score (EREFS); the EREFS improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. See Figure 2 for 52 week trend in EREFS.
  • Candidiasis: For the 3-mg BID group, oral and esophageal candidiasis was 40% in Part 1 and 32% in Part 2, 18% and 16% for 1.5 mg BID, and 5% and 7% for 3 mg HS (same subject)
  • Low morning cortisol noted 3 times in part 1 and 5 times in part 2. “All cortisol test abnormalities resolved upon retesting, with no dose adjustment or interruption of treatment.” Adrenal suppression is expected to be low because “FP undergoes extensive first-pass metabolism to inactive metabolites, with bioavailability demonstrated as <1%”

My take: A fluticasone ODT would represent a big improvement compared to current situation of asking families to either spray a pulmonary inhaler down their throat or to create a budesonide slurry using either honey or splenda. How much would this cost?

Histologic responders at Weeks 12. Interestingly, the 1.5 mg BID had a modestly higher response rate at 12 weeks, 26 weeks, and 52 weeks than the the 3 mg BID and the 3 mg qhs dosing groups.

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How Esophageal Dilatation Affects Symptoms and Inflammation in Eosinophilic Esophagitis

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E Safroneeva et al. Clin Gastroenterol Hepatol 2022; 20: 766-775. Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis

100 adults enrolled in a multisite prospective observational study in which 55 underwent dilatation. Key findings:

  • In nondilated patients, the association between eos/hpf and symptoms was moderate (ρ = 0.49; P < .001) based on the symptom-based EoE activity index (EEsAI); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P = .002)
  • In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (ρ = -0.38; P = .157 for ≤1 y and ρ = 0.02; P = .883 >1 y)

Limitations: sample size (only 25% subset of total cohort due to missing data), cross-sectional study design

My take: This finding is a double-edge sword. The good part is that dilatation improves dysphagia despite ongoing inflammation which may be refractory to current medical treatments. The bad part is this dissociation in symptoms makes it less likely for patients to be adherent to therapy.

Pic from relative -Artic Circle

Good Study, Bad Practice: Placebo for IBS and Functional Abdominal Pain

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Have a great day (Mt Yonah, Cleveland GA)

S Nurko et al. JAMA Pediatr. 2022;176(4):349-356. doi:10.1001/jamapediatrics.2021.5750. Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome

Design: Patients completed 1 week of observation prior to randomization to 1 of 2 counterbalanced groups: OLP for 3 weeks followed by a 3-week control period or control period for 3 weeks followed by OLP for 3 weeks. During the OLP period, participants took 1.5 mL of an inert liquid placebo twice a day.

Key findings:

  • The mean (SD) pain scores were significantly lower during open label placebo (OLP) treatment compared with the control period (39.9 [18.9] vs 45.0 [14.7]; difference, 5.2; 95% CI, 0.2-10.1; P = .03)
  • Patients took nearly twice as many hyoscyamine pills during the control period compared with during the OLP period (mean [SD] number, 3.8 [5.1] pills vs 2.0 [3.0] pills; difference, 1.8 pills; 95% CI, 0.5-3.1 pills)

My take: It is a mistake to consider placebo as a treatment for functional abdominal pain. In many children, pain fluctuates and may improve with reassurance, distraction, healthier diets, and physical activity. However, we also need more effective therapies including pain psychology, dietary approaches and medications. The idea that placebo helps is misleading and undermines the fact that patients with functional disorders need effective treatment.

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