Long-term Use of Proton Pump Inhibitors for Eosinophilic Esophagitis

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

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

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, 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

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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Delayed Pouch Closure in the Surgical Management of Ulcerative Colitis

B Kochar et al. Inflamm Bowel Dis 2018; 24: 1833-9.  This study reviewed prospectively collected data from 2011-2015 involving 2390 Ileal Pouch Anal Anastomosis (IPAA) surgeries for ulcerative colitis in those ≥18 years of age.  Two approaches were compared:

  1. ‘Traditional’ 2- stage IPAA where the pouch is created with the colectomy
  2. Or a 3-stage surgery where the pouch is created in a second surgery after the colectomy (delayed pouch creation)

Key findings:

  • Delayed pouch creation were significantly less likely to have an unplanned reoperation (RR =0.42, CI 0.24-0.75) and less likely to have major adverse events (RR=0.72, CI 0.52-0.99)
  • Those in the delayed pouch creation group were much less likely to be receiving chronic immunosuppression at the time of surgery –15% compared to 51% in 2-stage group

My take: Particularly for sicker patients, delayed pouch creation (3-stage procedure) is likely to be best approach.

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Reflux Management in Preterm Infants

A recent review (EC Eichenwald, AAP  COMMITTEE ON FETUS AND NEWBORN. Pediatrics. June 2018) on reflux in pretern infants reinforces several important issues:

  1. Reflux medicines have not been shown to be effective and can cause harm
  2. Feeding regimen manipulation is not effective

Diagnosis/Testing:

  • The report asserts that pH monitoring is not reliable “to diagnose GER in preterm infants19 because their stomach pH is rarely <4 owing to frequent milk feedings and a higher baseline pH. In addition, abnormal esophageal pH does not correlate well with symptom severity…Currently, the most accurate method for detecting GER is MII monitoring, which is frequently combined with simultaneous measurement of pH.2 ”  There are problems with impedance testing as well, including sparse normative data.

Apnea, Bradycardia and Desaturations:

  • “Researchers examining the timing of reflux episodes in relation to apneic events have found that they are rarely temporally related14,27 and that GER does not prolong or worsen apnea… there is no evidence that pharmacologic treatment of GER with agents that decrease gastric acidity or promote gastrointestinal motility decrease the risk of recurrent apnea or bradycardia in preterm infants.30,31

Feeding problems:

  • “Feeding-associated arching or irritability and oral feeding aversion, are not temporally associated with MII or lower pH documented reflux events and, thus, are not reliable markers of clinically significant reflux.”20,24

Lung disease/BPD:

  • “Data regarding the possible association between worsening lung disease attributable to GER and microaspiration in mechanically ventilated preterm infants are sparse.”

Full Text: Diagnosis and Management of Gastroesophageal Reflux in Preterm Infants

Abstract: Gastroesophageal reflux (GER), generally defined as the passage of gastric contents into the esophagus, is an almost universal phenomenon in preterm infants. It is a common diagnosis in the NICU; however, there is large variation in its treatment across NICU sites. In this clinical report, the physiology, diagnosis, and symptomatology in preterm infants as well as currently used treatment strategies in the NICU are examined. Conservative measures to control reflux, such as left lateral body position, head elevation, and feeding regimen manipulation, have not been shown to reduce clinically assessed signs of GER in the preterm infant. In addition, preterm infants with clinically diagnosed GER are often treated with pharmacologic agents; however, a lack of evidence of efficacy together with emerging evidence of significant harm (particularly with gastric acid blockade) strongly suggest that these agents should be used sparingly, if at all, in preterm infants.

My take: The information and recommendations in this review will not come with any surprises for most pediatric gastroenterologists.  Nevertheless, I think it may influence the care of neonatologists (and others) to use acid blockers less often in this population.

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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.