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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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Patient T-shirt

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.

Impedance Measurements with Eosinophilic Esophagitis

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Briefly noted: MA Lowry et al. JPGN 2018; 67: 198-203.  This study showed that active eosinophilic esophagitis (EoE) was associated with much lower impedance values that inactive EoE, NERD, and controls.  At 2, 5 and 10 cm above the squamo-columnar junction, median values of impedance with active EoE were 1069, 1368, and 1707 respectively.  In comparison, inactive EoE had median values were 3663, 3657, and 4494, respectively.  My take: Since impedance was also performed during endoscopy with sedation, this does not represent a significant advance in current management.

Sunrise at Amelia Island

Long-term Use of Proton Pump Inhibitors for Eosinophilic Esophagitis

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A prospective pediatric eosinophilic esophagitis (EoE) study (C Gutierrez-Junquera et al. JPGN 2018; 67: 210-6) examines the use of proton pump inhibitors (PPIs) for long-term management for this disorder.

After diagnosis of EoE, children received esomeproazole (1 mg/kg/dose BID).  For those with a response (<15 eos/hpf), they were maintained on 1 mg/kg/day for one year.

Key findings:

  • Of the initial cohort of 109, 72 (66%) had response to esomeprazole.
  • 57 of these responders were subsequently followed in this study.  At the lower daily esomeprazole dose, 70.1% (n=40) continued with <15 eos/hpf and 29.9% (n=17) had relapse.
  • Maintaining response was more common among those who achieved an initial response (with BID esomeprazole) of <5 eos/hpf compared to those who had achieved an initial response of 6-14 eos/hpf.  At 1 year, in those with who had a more complete response, 81% maintained eosinophil count <15/hpf compared with only 50% in those with a lesser initial response.
  • Adverse events with prolonged treatment were uncommon and included self-resolving diarrhea in three, headache in one and urticaria in one; the latter two adverse effects responded to change to lansoprazole

My takes: 

  1. PPI treatment is effective in probably 40-50% of individuals with EoE (though higher response in this study)
  2. Some individuals need higher doses of PPIs
  3. Due to the high response rate, this underscores the need to diagnose EoE prior to using PPIs or after they have been discontinued.

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Clostridium difficile and Inflammatory Bowel Disease

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My view is that Clostridium difficile infection (CDI) in children with inflammatory bowel disease is often overdiagnosed due to detection of a carrier state in many when tested by PCR assays and the overlapping clinical features.  This is particularly important when considering fecal microbiota transplantation (FMT) due to the potential risks of this treatment.

Recently, I had a letter to the editor (J Pediatr 2018; 199: 283) on this topic that was accepted:

The author’s reply suggested that their approach followed IDSA guidelines by checking CDI with PCR in those who were clinically-symptomatic.  Yet, the IDSA guidelines (link here: IDSA C diff guidelines) do not focus on the issue of IBD flare-ups which cause identical symptoms.  Expert IBD specialists have recommended the following for identifying CDI in patients with IBD:

“Start with enzyme immunoassay-based tests with a reflex to PCR test for discordant enzyme immunoassay results.”  Rationale: “PCR is quite sensitive for the presence of toxigenic C difficile, it may increase the detection of asymptomatic colonization and shedding.” (K Rao, PDR Higgins. Inflamm Bowel Dis 2016; 22: 1744-54.)

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Long-term Bone Health of Children with Celiac Disease

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In a recent study (C Canova et al. J Pediatr 2018; 198: 117-20) from Padua, Italy compared 1233 individuals with celiac disease to a comparison group of 6167 (from a population-based cohort of >200,000 individuals).  In this longitudinal study with a maximum followup of up to 23 years, the authors found no increase risk of fractures in youths diagnosed with celiac disease (HR of 0.87).

Findings:

  • 22 individuals had fractures compared to 128 in the reference population
  • Median age of celiac diagnosis was 6 years

Significance:

  • While celiac disease is linked to osteoporosis, “the vast majority of individuals with childhood celiac disease are likely to heal shortly after the introduction of a gluten-free diet.”

My take: Institution of a gluten-free diet for children with celiac disease likely removes the risk of osteoporosis.

Related blog posts:

  • Good News for Celiac Disease  –Gastroenterology 2010; 139: 763. Mortality NOT worsened in undiagnosed celiac disease (identified by review of serology) in Olmstead County, though bone density decreased. n=129 of 16,847. (?milder cases undiagnosed)
  • Common to be ‘D-ficient

Amelia Island -Restaurant Greeting

Cumberland Island 2018

IBD Reviews: Role of Antibiotics and Data on Biomarkers

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A clinical review, “Antibiotics in IBD: Still a Role in the Biological Era?” (O Ledder, D Turner, Inflamm Bowel Dis 2018; 24: 1676-88).  While this article provides a detailed review of the use of antibiotics for Crohn’s (including perianal disease), Ulcerative colitis and the effects on the microbiome, the potential use for very early onset (VEO) IBD caught my attention:

“We have recently begun considering oral vancomycin and gentamicin as sole firstline therapy in the rare form of infantile (ie <2 years of age) mild to moderate IBD, with promising success…this is merely investigational” at this time.  (Ref: Lev-Tzion R et al. Digestion 2017; 95: 310-13).

My take: Antibiotics can be a helpful adjunct therapy in both Crohn’s disease and Ulcerative colitis. It is unclear what role antibiotics will have for VEO-IBD.

A recent commentary (R Khanna et al, Inflamm Bowel Dis 2018; 24: 1619-23) examines the role of biomarkers.  While much of this topic has been reviewed extensively, I found the part about calprotectin helpful.  One of the topics with discrepant data has been the negative predictive value of calprotectin for detecting inflammatory bowel disease.  The data in this review:

  • From a meta-analysis in patients with symptomatic ulcerative colitis, calprotectin had a sensitivity of 0.88 and specificity of 0.79 compared to endoscopic inflammation.  For Crohn’s disease, the respective values were 0.87 and 0.67.
  • For histologic remission in ulcerative colitis, a study found that with a threshold of 155 mcg/g, calprotectin had a sensitivity of 78% and specificity of 71%.
  • Another study suggested that values <100 mcg/g indicate quiescent disease, values 100-250 suggest possible active inflammation, and values >250 mcg/g suggest active inflammation.
  • A cross-sectional study indicated that calprotectin ≥57  mcg/g had a sensitivity of 91% and specificity of 90% to identify endoscopically-active disease (Gastroenterol 2016; 150: 96-102)

My take: Sensitivity/specificity vary greatly based on the likelihood of disease; in populations at lower risk for IBD, 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.

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