Category Archives: Pediatric Gastroenterology Intestinal Disorder

Low Adherence Rate with Polyethylene Glycol

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The sentiment of wanting to get their kid off laxatives/stool softeners is frequently expressed at GI visits.  I certainly understand this.  Though, if a child is not stooling adequately when these medicines are withheld, this is usually detrimental for the child.

Given the frequency of this sentiment, it is not surprising that a recent study (IJN Koppen et al. J Pediatr 2018; 199: 132-9) reports low adherence with polyethylene glycol treatment in children with functional constipation.

In this cross-sectional survey using the Medication Adherence Report Scale (MARS-5), with scores of ≥23 indicating better adherence, the authors found that only 43 of 115 (37%) children were adherent.  The authors note that one of the determinants of adherence was treatment convenience.

The MARS-5 does not objectively measure the exact intake of medication; thus, the exact rate of adherence is unclear.  In addition, there is likely to wide variation in adherence among different populations.

My take: this study shows, at least in some populations, a low adherence with constipation therapy.  Sticking with treatment, for constipation and every other condition, usually results in better outcomes.

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If someone is not taking their medication, perhaps this cereal would help. (I am not officially endorsing this product, but think the name is funny.)

Transmural Disease, Biomarkers, and Correlation between MRI and Endoscopy

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A recent study (I Weinstein-Nakar et al. Clin Gastroenterol Hepatol 2018; 16: 1089-97, editorial 1037-39)) provide data from 151 children who underwent multiple modalities to assess their Crohn’s disease (CD) (ImageKids Study group).

Key findings:

  • MRE and ileocolonoscopy had concordance in 69% of cases.  55% had neither transmural nor mucosal healing, 14% had both transmural and mucosal healing.
  • MRE did not show features of active disease in 25% that was identified on ileocolonoscopy.  This is an expected finding given the ability of endoscopy (& capsule endoscopy) to identify milder mucosal lesions more precisely.
  • MRE did show evidence of disease in 6% who had unremarkable ileocolonoscopy (mucosal healing)
  • Calprotectin at a cut-off of 100 mcg/mL had 71% sensitivity and 92% specificity for diagnosing mucosal and transmural healing whereas a level of 300 mcg/mL had a sensitivity of 80% and specificity of 81%.

My take: This study confirms the complementary nature of cross-sectional imaging with endoscopy to determine healing.  In addition, in children with CD, calprotectin levels of more than 100 mcg/mL could indicate the need for further assessment (if this would affect management).

This is in agreement with another recent post: IBD Reviews: Antibiotics and Biomarkers:  “a calprotectin has a high level of excluding active inflammation/IBD. In populations with IBD, levels more than 250 mcg/g indicate a high likelihood of active inflammation whereas levels between 100-250 are indeterminate.”

Related blog posts:

Sunshine Meadows, Banff Nat’l Parke

DGAT1 Deficiency

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Briefly noted: JM van Rijn et al. Gastroenterol 2018; 155: 130-43.  This study of 10 patients from 6 families (5 had consanguinity) was the largest cohort to date describing the clinical features in this disorder and used patient-derived fibroblasts and organoids to understand the pathophysiology.

Key clinical features:

  • Early-onset vomiting and/or diarrhea
  • Protein-losing enteropathy/hypoalbuminemia

Key finding in study:

  • These patients had altered lipid metabolism and were susceptible to lipid induced cell death.  Thus DGAT1 mutations cause congenital diarrhea and this is linked to fat intolerance.

Related blog posts:

Sunshine Meadows, Banff Natl Park

Active Colitis More Likely in Children in Clinical Remission Who Have PSC and IBD

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A recent study (A Ricciuto et al. Clin Gastroenterol Hepatol 2018; 16: 1098-1105) provides more data regarding the lack of symptom correlation and inflammatory bowel disease (IBD) activity in children with primary sclerosing cholangitis (PSC).

In a prospective study of children with colonic IBD with and without PSC, the authors followed clinical features (eg. PUCAI), fecal calprotectin and endoscopy severity.

Key findings:

  • Patients with PSC-IBD (n=37) in clinical remission had higher endoscopic scores and greater odd of active endoscopic disease than IBD-only controls (n=50) (odds ratio 5.9, with CI 1.6-21.5)
  • Fecal calprotectin level <93 mcg/g were identified mucosal healing with 100% sensitivity and 92% specificity when compared with UC Endoscopic Index of Severity (UCEIS)

Overall, this study is in agreement with a prior adult study showing higher levels of active disease in those with PSC-IBD compared to those with IBD alone, despite clinical remission (Why does PSC increase the risk of colorectal cancer in UC?).

My take: Particularly in individuals with the combination of IBD-PSC, objective biomarkers (eg. Calprotectin) are needed to identify the accuracy of clinical remission; though, even in patients with IBD without PSC, objective biomarkers are needed as well due to the limitations of clinical symptom indices.

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Moraine Lake, Banff

Management of Pediatric Ulcerative Colitis -ESGHAN/ECCO Recommendations

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Two complementary articles provide extensive guidance on the management of ulcerative colitis and acute severe colitis:

  • D Turner et al. JPGN 2018; 67: 257-91
  • D Turner et al. JPGN 2018; 67: 292-310

Between the two articles there are more than 60 practice recommendations, more than 120 practice points, and more than 700 references.  As such, these articles are probably better for a journal review meeting rather than a brief blog post.

Figure 1 (2nd article, page 299) provides a handy algorithm for management of acute severe colitis:

  • On day 1-2, the algorithm recommends stool studies, starting methylprednisolone, and withholding 5-ASA.
  • On day 3, if PUCAI <45, suggests continuing steroid and transitioning to oral therapy when PUCAI <35.  On day 3, if PUCAI ≥45, the authors suggest screening for second line therapy, involve surgery (to discuss colectomy if there is nonresponse to medical treatment), and looking for CMV infection (eg. sigmoidoscopy).
  • On day 5, if PUCAI >65, recommendation is to start 2nd line Rx (eg. infliximab, tacrolimus, or cyclosporine). If PUCAI 35-65, continue corticosteroids for additional 2-5 days. The authors note that infliximab is preferred 2nd line Rx unless planning to transition to vedolizumab.
  • The authors recommend weaning corticosteroids when 2nd line Rx is started
  • The authors recommend addition of an immunomodulator for at least 6 months in responders to infliximab in effort to lower the risk of colectomy.
  • The authors state “urgent colectomy is recommended following failure of 1 second-line therapy.”

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

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Marijuana Use in Adolescents/Young Adults with Inflammatory Bowel Disease

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A recent study (EJ Hoffenberg et al. J Pediatr 2018; 199: 99-105) examined the use of marijuana in 13-23 year age group with inflammatory bowel disease (IBD) at the Children’s Hospital for Colorado.

This relatively small study (n=99 — 62 with Crohn’s, 27 with ulcerative colitis, 10 with indeterminate colitis) found the following:

  • Marijuana use was endorsed by 32 (32%) and that 9 used daily or almost-daily.
  • Users were 10.7 times more likely to perceive low risk of harm (P<.001)
  • 17 of 30 stated a medical reason for use (16 with physical pain)
  • The most common route of use was smoking (83%)

Limitations:

  • 80% of participants had inactive or mild disease
  • There was no control (non-IBD) group to compare frequency of marijuana use
  • Study performed in state with legalized recreational marijuana

My take: We know very little about how marijuana impacts IBD course and whether it is safe.  This study indicates frequent use of marijuana in the 13-23 year age group.  Thus, it is an issue that needs to be examined further.

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Three Sisters, Peaks near Canmore, Alberta

Parasitology in 2018: Should we still be ordering O&P times three?

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A terrific review article (S Mohapatra et al. Am J Gastroenterol 2018; 113: 805-18) provides a great deal of information about gastrointestinal parasites. Thanks to Ben Gold for this reference (& don’t forget to vote for NASPGHAN president).

Generally, the authors dispute the usefulness of testing for ova and parasites (O&P) with three separate specimens.  While classic training has noted the intermittent shedding of parasites and the suboptimal sensitivity of O&P, the authors note that a recent study showed a detection of 91% of parasites in the first stool sample.  In addition, newer PCR based assays are more appropriate in many clinical situations due to their improved sensitivity.

The authors first review the protozoa, which are single-celled, motile, free-living organisms, in depth & summarized in Table 1; these include the following:

  • Amoeba: Entamoeba histolytica (E histolytica),
  • Dientamoeba fragilis
  • Blastocystis hominis
  • Coccidia: Cryptosporidium, Cystiospora, Cyclospora
  • Ciliates: Balantidium coli
  • Flagellates: Giardia lamblia
  • Microsporidiosis
  • Trypanosoma cruzi

Next, they review the helminths in depth and in Table 2, which are large, multicellular organisms that can be seen with the naked eye and include the following:

  • Ascariasis: A lumbridcoides
  • Capillariasis
  • Diphyllobothriasis
  • Enterobiasis: E vermicularis
  • Hookworm disease: A dudenale, N amercanus
  • Hymenolepiasis
  • Strongyloides: S stercoralis
  • Schistosomiasis
  • Taeniasis
  • Trichinellosis
  • Trichuriasis
  • Groups of helminths: trematodes (eg. Schistosomes), cestodes (tapeworms eg. Taenia), and nematodes (roundworms eg. Ascariasis, hookworm, pinworms, and whipworms).

Key points:

  • For E histolytica, ELISA fecal antigen test is superior to O&P as is the PCR assay.  If the diagnosis of E histolytica is being considered in the setting of ulcerative colitis, the authors note that this infection must be excluded before the initiation of corticosteroid therapy since steroids can lead to hyperinfection and could be fatal.  Also, the so-called “flask shaped” ulcers seen with this infection refers to the microscopic appearance of the ulcer into the submucosa. Most infections (>90%) remain asymptomatic.
  • Blastocystis “is the most common parasite identified in stool samples in the US” though the pathogenicity remains controversial and is often self-limited.
  • D fragilis “as a pathogen is controversial…[but] recent studies on patients infected only with D fragilis have found an association with diarrhea, abdominal pain, nausea, weight loss, anorexia, and flatus which resolve after eradication.”
  • Giardiasis is “the most common intestinal parasitic disease affecting humans in the US.” PCR/molecular methods are highly sensitive (>90%) and specific (nearly 100%)
  • Enterobius vermicularis (pinworms). The “CDC does not recommend stool examination for O&P since the yield is low.” The diagnostic test is the “Scotch test” in which tape is left overnight in the perianal region and then examined for captured eggs.

Author Recommendations:

  • “Restrict stool examination [for parasites] to patients with persistent diarrheal illness with a duration greater than 7 days.”  Do not check O&P in hospitalized patients more than 3 days into their hospitalization.
  • The most  common parasitic infections, Giardia and Cryptosporidium, are best diagnosed with a stool immunoassay (EIA) rather than O&P.  For E histolytica EIA is recommended over O&P.
  • In those who are persistently symptomatic and with travel history with likely parasite exposure, stool O&P with wet mount/AFB stain/special stains for detection of rare parasites still is worthwhile.  In those without exposure history and with persistent diarrhea (after exclusion of Giardia and Cryptosporidium), consider non-infectious causes of diarrhea.
  • We discourage repeating the O&P due to the “very low incremental yield of second and third samples”

My take: This article makes a strong argument that “O&P times three” represents an outdated approach in the diagnosis of parasitic diseases in the US.

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Near the top of Old Rag Mountain, Shenandoah Natl Park

 

 

 

Chronic Fatigue and Irritable Bowel Syndrome -10 years after Giardia Infection!

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A recent study (S Litleskare et al. Clin Gastroenterol Hepatol 2018; 16: 1064-72) involved prospective follow-up of 1252 laboratory-confirmed cases of giardiasis from a 2004 outbreak in Norway.

Key findings:

  • Prevalence of irritable bowel syndrome (IBS) was 43% 10 years after the outbreak among 576 exposed individuals compared with 14% among 685 controls. Thus, the odds ration of developing IBS was 4.74 following Giardia exposure.
  • Chronic fatigue at 10 years was higher as well, reported in 26% in the exposed group compared with 11% in the control group.
  • The authors note that the change in IBS between 6 years and 10 years following the infection was 40% and 43% respectively and the change in chronic fatigue was 31% at 6 years and 26% at 10 years.

My take: Don’t get Giardia!! It may cause chronic fatigue and IBS 10 years after acquisition of an infection.  This study reinforces other studies which have shown that numerous enteric pathogens can increase the risk of IBS.  These other studies reported lower rates of IBS following infections, between 7-36%.

Moraine Lake, Banff

Reslizumab (recombinant anti-IL-5) for Eosinophilic Esophagitis

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Reslizumab, a monoclonal recombinant antibody to interleukin-5 did not receive FDA approval for eosinophilic esophagitis.  However, a recent report (J Markowitz et al. Journal of Pediatric Gastroenterology and Nutrition: June 2018 – Volume 66 – Issue 6 – p 893–897)  describes the outcomes of patients who entered the randomized control trial and continued to receive subsequently via open label extension (OLE, n=6) or through compassionate use (CU, n=4. This study provides data over 9 years of treatment.

Key findings:

  • Median eosinophil count dropped from 35 to 3
  • No serious adverse events were noted
  • Clinical features improved.  For example, dysphagia dropped from 42% to 0% and vomiting dropped from 67% to 17%

My take: Though this is a small study, it shows that in selected patients disruption of the inflammatory pathways can result in significant clinical improvement.

Pics from Ameila Island and thereabouts -Not sure whose dog  (not ours)

Is it really necessary to check for Cytomegalovirus in Children with Inflammatory Bowel Disease?

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A recent retrospective study (W El-Matary et al. JPGN 2018; 67: 221-24) examined the practice of looking for Cytomegalovirus (CMV) in children with a flareup of their inflammatory bowel disease (IBD) which is currently recommended by expert consensus (JPGN 2018; 67: 292-310 –recommendation #3).

Key findings:

  • “Four of 61 patients encounters (6.6%) with UC/IBD-U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC.  They responded to escalated medical therapy, without needing anti-viral therapy.”
  • All children who had colectomy during the study did not have CMV detected in colonic mucosa.

The authors note that the rationale for looking for CMV is derived mainly from adult populations.  Since age is a known risk factor for CMV reactivation, the risk of CMV causing refractory IBD in children is less.

My take (borrowed in part from authors): “The low frequency of CMV in our study challenges current guidelines that recommend assessment for CMV in all pediatric patients with acute severe UC refractory to corticosteroids.”  This issue would be another that would benefit by collecting the experience of a large cohort (eg. ICN).

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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.