“When is Celiac Disease Celiac Disease?”

Posted on by

A recent study (R Auricchio et al. Gastroenterol 2019; 157: 413-20, and editorial PR Green S Guandalini, pg 293-4) provides insight into the topic of “potential celiac disease.”

It is difficult trying to explain the concept of potential celiac disease (CD) to families.  Potential CD refers to the situation of having positive celiac serology but normal duodenal mucosa. In this study, the authors prospectively followed 280 children (age 2-18 yrs) with 2 consecutive abnormal serological tests (anit-TG2, EMA) along with normal duodenal architecture who continued a diet containing gluten.

Key findings:

  • 42 (15%) developed villous atrophy at median followup of 60 months
  • 89 (32%) became serologically-negative for CD
  • Cumulative incidence of progression to villous atrophy was 43% at 12 years.
  • The strongest predictive factor for villous atrophy was age: 7% of children less than 3 years developed flat mucosa, compared with 51% for age 3-10 and 55% for those older than 10 years

Advice on potential CD from editorial –titled “When is Celiac Disease Celiac Disease?”

  • Review the biopsies: were there adequate biopsy specimens? ≥4 from descending duodenum and ≥1 from duodenal bulb
  • Have a second specialist pathologist review specimens
  • If a patient with potential CD is symptomatic, institute a gluten-free diet and then follow for clinical and serologic response
  • If asymptomatic, “a wait and see approach is appropriate with interval biopsies every 2 years, if the elevated antibodies persist”

The editorial also note that none of the patients in this cohort would have been mislabeled with a diagnosis of CD using the non-biopsy approach as none of them had tTG antibodies >10 times the upper level of normal.

My take: This useful study should help with counseling parents about the likelihood of developing celiac disease in those with the “potential” label.  Younger children (<3 yrs), compared to older children, are less likely to convert from potential celiac disease to actual celiac disease..

Related blog posts:

Crater Lake, OR

How Long Should Be PPIs Be Used in Patients with Esophageal Atresia?

Posted on by

A recent study (FR Grunder et al. JPGN 2019; 69: 45-51) examines the use of proton pump inhibitor use after surgical repair of esophageal atresia; this involved a longitudinal cohort (n=73) with prospectively collected data over 11 years.

Background: While PPIs have been used for long-term treatment due to the high frequency of reflux and concerns regarding anastomotic strictures, the authors note that data on long-term outcomes/natural history and benefits/risks of this approach are lacking.

Key findings:

  • 48% of patients had PPIs discontinued at followup.
  • Among the 43 with PPI discontinuation, 40 had endoscopy results available.  Histologic abnormalities were noted in 8 (19%) which was lower than in the group receiving ongoing PPI use (n=19, 63%).. These 8 patients had PPI restarted.
  • Among patients unable to discontinue PPI therapy, there was a higher rate of prior anti-reflux surgical procedure, 27% compared to 5% who had anti-reflux procedure among group who were able to discontinue PPI therapy.
  • Patients more likely to remain on PPIs more frequently had a prior anastomotic leak and/or moderate to severe tracheomalacia.
  • The authors state that among patients receiving PPIs, there was more frequent recurrent pneumonia as well as more frequent use of inhaled beta-adrenergic agonists and steroids. However, this was not shown to be a causal association.  It is unclear whether these patients had more severe esophageal dysfunction or whether PPI use contributed to this outcome.

In their discussion, the authors note that PPIs have not been shown to reduce the rate of anastomotic strictures.  They argue that “PPI could be used more selectively in the following: in children with long-gap EA or anastomotic tension or anastomotic leak; after a first dilatation for anastomotic stricture rather than systematically, given the lack of preventive effect of PPI; and in children whose esophagoscopy demonstrates peptic esophagitis, eosinophilic esophagitis, or gastric metaplasia.”

My take: The authors are probably right that a large fraction of EA patients may not need long-term PPI use.  Selecting which patients will benefit will remain a challenge. Published guidelines recommend monitoring for GERD complications in EA, especially after stopping PPIs.

Related blog posts:

University of Virginia

 

Sunshine and Inflammatory Bowel Disease

Posted on by

A recent provocative study (EA Holmes et al. JPGN 2019; 69: 182-88) describes an inverse association between sunshine exposure and the development of pediatric inflammatory bowel disease (IBD).  Among a cohort of 99 children with IBD and 396 controls, the authors used questionnaires to estimate past sun exposure along with other variables.

Key finding:

  • “For each 10 min increment in leisure-time sun exposure in summer or winter there was a linear 6% reduction in the odds of having IBD (P=0.002)”

There was no corresponding data with regard to vitamin D status.

My take:  Being active and going outside are likely good for one’s health and there have been other studies suggesting more sun exposure could reduce the rate of Crohn’s disease. Does Sun Exposure Lower the Risk of Crohn Disease? | gutsandgrowth  Despite this, in my view, this study’s findings have limited value.

  1. There may be many confounders that separate children with more sun exposure from those with less exposure, including diets, exercise, camping, exposure to animals and soil, and many other variables. In addition, there may have been problems with recall bias.
  2. The role of vitamin D was not studied. In previous studies, the importance of vitamin D in its effect on the IBD/immune system have yielded inconsistent results.
  3. In those with IBD, suggesting that more sun exposure may have prevented IBD would not be helpful; this is due to the flimsy evidence and this information could be interpreted  as blaming the family.
  4. Correlation does not prove causation.  For example, a far-fetched association of correlation that is not likely to have a causal association: Rates of Drowning by Falling in Pools and Nicholas Cage Films (National Geographic: Nicholas Cage Movies vs. Drownings)

Related blog posts:

View from Wahkeenah Falls Trail, OR

 

 

Non-Adherence Leads to Treatment Escalation and More on Early Infliximab Trough Levels

Posted on by

Briefly noted: JK Carmody et al. AP&T 2019; first published 02 August 2019: https://doi.org/10.1111/apt.15445 Full text link: Longitudinal non‐adherence predicts treatment escalation in paediatric ulcerative colitis

In this cohort of 268 pediatric patients with ulcerative colitis in the prospective PROTECT study, non-adherence to mesalamine was associated with need for treatment escalation.

Key finding:

  • Declining adherence over time strongly predicted treatment escalation (β = −.037, P = .001). By month 6, adherence rate ≤85.7% was associated with treatment escalation.

As noted in a previous blog (Briefly noted: Induction Inflixmab Levels), a recent study (K Clarkston et al. JPGN 2019; 69: 68-74) identified target early infliximab trough levels for infliximab as≥ 29 for week 2 (infusion 2) and ≥18 for week 6 (infusion 3). Below is an associated figure:

Image courtesy of Michael Rosen twitter feed

IBD Briefs August 2019

Posted on by

A Levine et al. Gastroenterol 2019; 157: 440-50.  This study found that a Crohn’s Disease Exclusion Diet plus partial enteral nutrition induced sustained remission in a 12-week prospective randomized controlled trial with 74 children.  At week 12, “76% of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given” EEN followed by PEN.  The associated editorial on pages 295-6 provides a useful diagram of various dietary therapy components for a large number of diets that have been given for IBD.  The editorial recommends:

“For now, simple dietetic recommendations such as consuming a well-balanced diet prepared largely from fresh ingredients and thereby avoidance of emulsifiers and additives and processed foods are appropriate for all patients.  In select patients,…a trial of dietary therapy alone with a diet such as CDED could be attempted for a short period of time, with close follow-up, and with agreement with the patient that failure to fully respond is an indication to escalate therapy.”  More dietary trials are ongoing.

Related blog posts:

NJ Samadder et al Clin Gastroenterol Hepatol 2019; 17: 1807-13. In this cohort from Utah 1996-2011 with 9505 individuals with IBD, 101 developed colorectal cancer.  Standardized incidence ratio (SIR) for CRC in patients with Crohn’s disease was 3.4, in ulcerative colitis 5.2, in patients with primary sclerosing cholangitis 14.8.  A family history of CRC increased the risk of CRC in patients with IBD to 7.9 compared to general population.  Family hx/o CRC increased the SIR by about double the CRC risk in IBD patients without a family hx/o CRC.

CR Ballengee et al. Clin Gastroenterol Hepatol 2019; 17: 1799-1806. In this study with 161 subjects from the RISK cohort, the authors found that elevated CLO3A1 levels in subjects with CD was associated with the development of stricturing disease but was not elevated in those with strictures at presentation and in those who did not develop  strictures.

AL Lightner et al IBD 2019; 25: 1152-68.  Short- and Long-term Outcomes After Ileal Pouch Anal Anastomosis in Pediatric Patients: A Systematic Review.  This review included 42 papers.

  • Rates of superficial surgical site infection, pelvic sepsis, and small bowel obstruction at <30 days were 10%, 11%, and 14% respectively.
  • Rates of pouchitis, stricture, chronic fistula, incontinence and pouch failure were 30%, 17%, 12%, 20% and 8% respectively with followup between 37-109 months.
  • Mean 24-hour stool frequency was 5.

MC Choy et al IBD 2019; 25: 1169-86.  Systematic review and meta-analysis: Optimal salvage therapy in acute severe ulcerative colitis.  Among 41 cohorts (n=2158 cases) with infliximab salvage, overall colectomy-free survival was 69.8% at 12 months.  The authors could not identify an advantage of dose-intensification in outcomes, though this was used more often in patients with increased disease severity, “which may have confounded the results.”

Hood River, OR

“We Have Ruined Childhood” and Possible Link to Depression, Anxiety and Suicide

Posted on by

A recent NY Times commentary (We Have Ruined Childhood) details the rising rates of depression, anxiety, and suicide and suggests a link between these mental health issues and a lack of childhood free play.

An excerpt:

No longer able to rely on communal structures for child care or allow children time alone, parents who need to work are forced to warehouse their youngsters for long stretches of time. School days are longer and more regimented…

The role of school stress in mental distress is backed up by data on the timing of child suicide. “The suicide rate for children is twice what it is for children during months when school is in session than when it’s not in session,..

For many children, when the school day is over, it hardly matters; the hours outside school are more like school than ever…

The areas where children once congregated for unstructured, unsupervised play are now often off limits. And so those who can afford it drive their children from one structured activity to another. Those who can’t keep them inside. Free play and childhood independence have become relics, insurance risks, at times criminal offenses…

Many parents and pediatricians speculate about the role that screen time and social media might play in this social deficit. But it’s important to acknowledge that simply taking away or limiting screens is not enough. Children turn to screens because opportunities for real-life human interaction have vanished.

Related blog posts:

Jejunal Tube Feeding –ESPGHAN Position Paper

Posted on by

A recent position paper (IJ Borekaert et al. JPGN 2019; 69: 239-58) makes 33 recommendations on the use of jejunal tube feedings.

Full Text Link: The Use of Jejunal Tube Feeding in Children: A Position Paper by the Gastroenterology and Nutrition Committees of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition 2019.

Here are a few of the recommendations:

  • #1 Jejunal feeding is route of choice for enteral nutrition with failure of oral and intragastric feeds or gastric outlet obstruction
  • #5 Expert group recommends the use of jejunal feeding in children with acute pancreatitis only in cases in which oral or gastric feeding is not tolerated
  • #6 Recommends trial of continuous gastric feeds or a hydrolyzed or elemental formula prior to jejunal feedings
  • #8 & 9 Expert group recommends to consider UGI/SBFT and an upper GI endoscopy in all patients before jejunal tube placement
  • #12 Recommends NOT to use jejunal tube feedings in preterm infants (<37 weeks gestation).  This is based on systemic reviews including Cochrane review which concluded “that there is no evidence of any benefit for transpyloric feeding in preterm infants compared to gastric feeding”
  • #21 Recommends monitoring for nutrient deficiencies –checking copper, zinc, selenium, and iron every 6-12 months (Low level of evidence).  The authors note that some studies have shown reductions in these nutrients; this may be related in part to be due to bypassing the duodenum
  • #24 Avoiding using jejunal tube for medication unless absolutely essential or delivery into the stomach is not possible

Hood River Bridge (crossing Columbia River). Hood River, OR

 

Sad Truth: Job Security in Hepatology

Posted on by

A recent study (ND Parikh et al. Hepatology 2019; 70: 487-95, and associated editorial JA Marrero. 459-61) provide a forecast of increasing liver disease and liver disease severity, driven mainly by fatty liver disease and obesity.

Key findings:

  • Nonalcoholic fatty liver disease (NAFLD) related additions to the liver transplant waitlist expanded from 391 in 2000 to 1605 in 2014.  This corresponded to an overall increase in obesity of 44.1% during that time period.
  • NAFLD-related wait-list additions were predicted by the prevalence of obesity 9 years prior.
  • The authors anticipate that obesity population will increase to over 92 million adults by 2025.
  • The authors project that NAFLD-related wait-list additions will increase to 2104 by 2030, a 55% increase

Because the decrease in complications related to new treatments for Hepatitis C is not expected “until well into the next decade,” the burden of chronic liver disease will continue to rise.

The editorial notes that overall graft survival rates for obese patients with BMI less than 40 do not appear different than those of lean individuals.  Those with BMI >40 had reduced 5-year graft and survival rates.  Also, obese patients have higher morbidities, even in those without reduced survival.

My take: This study identifies a marked increase in end-stage liver disease in the growing population of obese patients.

Related blog posts:

Blaming Reflux for BRUEs -Not Changing Despite Guideline Recommendations

Posted on by

Briefly noted: DR Duncan et al. J Pediatr 2019; 211: 112-9.

In this retrospective cohort study of infants with brief resolved unexplained events (BRUEs) at Boston Children’s Hospital, the authors examined guideline implementation among 359 subjects in the year before and the year after AAP guidelines.

Key findings:

  • There were no significant changes in practice after guideline publication
  • Only 13% had videofluoroscopic swallow study performed; 72% of these showed aspiration/penetration
  • No subject had reflux testing, “yet reflux was implicated as the cause” for BRUE in 40%. Children continued to be “discharged on acid suppression despite lack of efficacy”

My take: The pendulum is (slowly) starting to swing back from blaming everything (including BRUEs) on reflux but this change is not evident in this study.

Related blog posts:

Ensuring Safe Infant Formula Use -More Complicated Than You Think

Posted on by

A recent commentary (SA Abrams, SR Daniels. J Pediatr 2019; 211: 201-6) highlight some important issues regarding infant formula use/misuse.

The authors indicate that their commentary is not intended to undermine the use of breastmilk in infants.  However, they note that only about 25% of infants are exclusively breastfed until 6 months of age; thus, utilizing formula appropriately is crucial.

Annual Costs per article estimates (based on powder formula):

  • $1109 generic store-brand formula
  • $2021 name-brand routine formula
  • $222 Typical out-of-pocket for WIC clients –store brands (this assumes about 20% of formula is not covered by WIC)
  • $404 Typical out-of-pocket for WIC clients –name brands (this assumes about 20% of formula is not covered by WIC)
  • $215 Whole cow milk (not recommended)

Key points:

  • The authors discuss the role of the WIC program which is a supplemental program –does not provide 100% of an infant’s needs.
  • They describe deceptive formula marketing practices and the difficulty of ascertaining the best value of formulas.  In addition, “marketing of more expensive formula choices as having unique health benefits can easily lead families to spend more money than might be necessary” based on “meaningless” claims of being ‘closest to mother’s milk.’
  • Additives such as oligosaccharides and formulas marketed as organic or free of genetically modified organisms can be used to increase the cost of formula.
  • Use of WIC has decreased by 15% from 2010 to 2017; some may be related to fears related to immigration status of some WIC recipients.
  • Families faced with increased costs may dilute formula or use inadequate substitutes (eg. juice, cow’s milk, prepare home-made alternative)
  • Recent government shutdown placed many infants at risk.

Mistrust Concerns:

  • Many families, abetted by social media, have become distrustful of standard formulas as well as government and even pediatrician advice.
  • There has been an increase in importation of foreign formulas, especially from Europe.  THESE FORMULAS ARE NOT FDA MONITORED OR APPROVED. These illegally imported formulas have no proven advantages and their safety has not been ensured.  They do not undergo routine testing for 30 nutrients which are required by FDA monitored formulas.
  • Raw cow’s milk and raw goat milk have been promoted to ‘improve immune or gastrointestinal function.’ These products have no scientific proof of any advantage and place infants at risk as they are unpasteurized and nutrient deficient.

Author Recommendations:

  • Provide educational programs focused on formula feeding for medical providers and families
  • Increase information and regulation from government and industry about contamination issues
  • Protect the WIC program from consequences of potential government shutdown
  • Mandate improved price clarity
  • Fund research into all aspects of formula feeding, including behavioral interventions to limit inappropriate formula use
  • Monitor social media and provide correct information

Related blog posts:

Outside Portland, OR