Celiac Disease Epidemic?

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A recent prospective study (E Liu et al. Gastroenterol 2017; 152: 1329-36) reports a very high rate of celiac disease in Denver.

The authors collected data on HAL-DR, DQ genotypes in 31,766 infants.  Among the various genotypes, a total of 1339 were followed .for 20 years (starting in 1993). The key outcomes were development of celiac disease autoimmunity (CDA) indicated by persistence of anti-TTG IgA antibody for at least 3 months or development of celiac disease (CD) with biopsies showing at least Marsh 2 histologic lesions.  The authors weighted the genotypes based on their frequency in the population to develop estimates for the entire Denver population.

Key findings:

  • 66 (of 1339) developed both CD and CDA. Another 46 developed only CDA. In this group of 46, seropositivity reverted to normal in 21 (46%).
  • Cumulative incidence for CDA at 5, 10 and 15 yrs of age: 2.4%, 4.3%, and 5.1% respectively
  • Cumulative incidence for CD at 5, 10 and 15 yrs of age: 1.6%, 2.8%, and 3.1% respectively

In their discussion, the authors note that “the 3.1% cumulative incidence of CD in Denver by age 15 is the highest to date in North America and is consistent with the 3% prevalence reported in Sweden for 12 year olds born during an ‘epidemic’ thought to be the result of early introduction…of gluten.” This theory about the epidemic is has been discounted: “timing of gluten introduction is not likely a factor” though the quantity could be a factor.

My take: These rates of CD and CDA are very high; ongoing data to determine the frequency in other parts of the country are needed.  This high rate of CD is clearly bad news for a lot of people, excepting those with commercial interests in gluten free products.

 

For 1-3 year old, AAP recommendation for maximum of 4 oz./day of 100% juice, and for 4-6 year olds a maximum of 6 oz/day.  For 7 years and older, AAP recommends a maximum of 8 oz/day

Liver Briefs May 2017

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Briefly noted:

O Jeanniard-Malet et al. JPGN 2017; 64: 524-7. This survey of 28 centers in France assessed clinical practice with regard to primary prophylaxis in portal hypertension. More than 75% use endoscopy to screen for varices in patients with chronic liver conditions. “In cases of grade 2 varices with red marks and grade 3 varices >90% of centres perform sclerotherapy or endoscopic variceal ligation.”

Y-D Ren et al. Hepatology 2017; 65: 1765-8. FMT for chronic HBV? This small study with 5 patients who received fecal microbiota transplantation in an effort to clear HBeAg.  There were 13 controls.  Patients in both group received either ongoing entecavir or tenofovir antiviral therapy (& had received for at least 3 years). FMT was given every 4 weeks (1 to 7 treatments). HBeAg declined gradually after each round.  Three patients in the FMT arm cleared HBeAg compared with none in the control arm.  Two of the three cleared HBeAg after on FMT and the third after two rounds of FMT.

Y Sun et al. Hepatology 2017; 65: 1438-50.  In this report, the authors propose to augment the liver biopsy classification in patients with Hepatitis B.  Their goal is to provide more information about dynamic changes regarding fibrosis using three terms:

  • Predominantly progressive: thick/broad/loose/pale septa with inflammation
  • Predominantly regressive: delicate/thin/dense/splitting septa
  • Indeteminate

Using this new designation, they characterized 71 paired liver biopsies before and after entecavir for 78 weeks.  Before treatment: 58%, 29%, and 13% for progressive, regressive and indeterminate; after treatment: 11%, 11%, and 78% respectively.

Rodin Museum, Gates of Hell

 

Brain-Gut Axis in 2017

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“Brain–gut interactions and maintenance factors in pediatric gastroenterological disorders. Recommendations for clinical care.” B Reed-Knight et al. Clinical Practice in Pediatric Psychology, 2017; 5: 93-105.

A summary of this review article by Sharon Berry, PhD, ABPP, Past President, Society of Pediatric Psychology:

This review article describes the brain–gut axis as a means to increase understanding of how biological mechanisms implicated in a range of pediatric GI disorders interact with psychological and contextual factors to maintain GI symptoms and (b) provide practical ways for pediatricians and other healthcare providers to  incorporate a discussion of the brain–gut axis into patient education for pediatric GI disorders.

Biological mechanisms of the brain–gut axis including alterations in pain processing, the stress response system, and gut microbiome activity are reviewed. Psychosocial factors that contribute to or maintain disturbances in the brain–gut axis are discussed with implications for clinical assessment and intervention. The authors assert that a mutual understanding by patients, families, and providers alike of the relevant brain–gut interactions and the biopsychosocial model, in general, will serve as a foundation for successful delivery of and adherence to medical and psychological interventions. Important clinical conclusions include:

  • Early discussion of the brain-gut axis may reduce resistance to integrated behavioral or psychological treatment for pediatric gastroenterological disorders.
  • Sample visual aids and descriptive scripts are available within this review to guide discussions of the brain-gut axis with patients and families for a range of pediatric GI disorders.

My take: This article serves is a useful resource for pediatric psychologists to better understand the ideas of visceral hypersensitivity, stress response, and biological triggers (eg. gut microbiome, infections) for gastrointestinal disorders. Its discussion of biopsychosocial assessment and psychological interventions are helpful for pediatric gastroenterologists to understand the psychological approaches toward treatment.

Related blog posts:

NPR: Banana Diet for Celiac Disease

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A recent report from NPR highlights a previous diet for celiac disease -the banana diet. While celiac disease had been discovered in the 1890s by Dr. Samuel Gee, the role of gluten was not understood until WWII.

NPR: Doctors Once Thought Bananas Cured Celiac Disease

Here’s an excerpt:

a high-calorie, banana-based diet [was] invented by Dr. Sidney Haas in 1924. The diet forbade starches but included numerous daily bananas, along with milk, cottage cheese, meat and vegetables…

Haas arrived at his banana diet through an honest error — one that, unfortunately, had serious repercussions for people with celiac disease. In his 1924 paper, he wrote of a town in Puerto Rico where “dwellers who eat much bread suffer from [celiac] sprue while the farmers who live largely on bananas never.”

Haas skipped over the role of wheat and focused instead on the exotic bananas, which he thought held curative powers…

But Haas’ honest error led to serious consequences. As the children recovered, wheat was reintroduced.

It was a Dutch pediatrician, Willem Karel Dicke, who first realized that wheat might be linked to celiac disease. He noticed that in the last few years of World War II, when bread was unavailable in the Netherlands, the mortality rate from celiac disease dropped to zero. In 1952, Dicke and his colleagues identified gluten as the trigger for celiac disease, and the gluten-free diet was born.

 

Vaccine for Celiac Disease

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A recent study (KM Kemppainen et al. Clin Gastroenterol Hepatol 2017; 15: 694-702, editorial 703-5) showed that gastrointestinal infections can trigger celiac disease (CD) and that immunization with the rotavirus vaccine was protective against developing CD.

This study is part of the TEDDY study: The Environmental Determinants of Diabetes in the Young.  The TEDDY cohort involves more than 8000 children who are part of an international prospective cohort who carry genes (HLA-DR-DQ genotypes) with increased risk for diabetes and CD. In this particular group, the authors identified 6327 children who were 4 yrs old by March 2015.

Key Definition: CD autoimmunity (CDA) -children who tested positive for tTG IgA at their annual visit and remained persistently positive 3 months later

Key Findings:

  • Gastointestinal infections (n=13,881) but not respiratory infections (n=79,816) were associated with an increased risk of CDA.  CDA risk was increased within the 3 months of the GI infection.
  • 732 of 6327 (11.6%) developed CDA.  In this cohort, 318 underwent duodenal biopsy and 283 (90%) had biopsy indicative of CD (Marsh score >1). Thus, in their cohort, there is variability in the onset of CD from the onset of CDA.
  • Risk of CDA was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR =0.57).
  • The exact risk depending on interaction with multiple factors including breastfeeding, HLA genotype, seasonality of birth, and timing of gluten introduction. Timing of infection plays a role as well, as earlier exposure to GI infections earlier in life was associated with a decreased risk of celiac disease.

This reference should be kept handy for vaccine advocates.  Not only can vaccines prevent infections, but they have now been shown to prevent an autoimmune disease (CD).  In addition, previous studies have shown that vaccines can prevent cancers, including hepatocellular carcinoma and cervical cancer.

My take (modified from editorial): This study “demonstrates the power of rigorously conducted prospective studies to reveal complex interactions among genetic and environmental factors.” In addition, this study shows that preventing rotavirus infection with vaccination lowers the risk of celiac disease.

Related blog posts:

SuperPoopers CCFA Team 2017

IBD Resources for Clinicians/IBD Tweets

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Another website with a few useful resources:

  • Steroid taper calendar -helps develop a calendar (can use to print out or take a picture)
  • Imaging risk calculator -this is not that great.  In essence if you have a patient present to ER with a CRP of 1 mg/dL and ESR of 20, it states that risk of a complication like a perforation is “NOT LOW” and to consider imaging
  • IBD School Video collection -links to UM website

Note -therapeutic drug monitoring may be more useful in children due to their changing size.

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.

Tofacitinib Induction and Maintenance for Ulcerative Colitis

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W Sandborn et al. N Engl J Med 2017; 376:1723-1736 May 4, 2017DOI: 10.1056/NEJMoa1606910

Abstract from NEJM:

BACKGROUND

Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy.

 

METHODS

We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks.

 

RESULTS

In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.

 

CONCLUSIONS

In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo.

Heroin Epidemic Causing Surge in Hepatitis C Infections

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From NPR: Heroin Epidemic is Driving a Spike in Hepatitis C Cases

An excerpt:

The number of new Hepatitis C cases leaped nearly 300 percent from 2010 to 2015, according to a report released Thursday by the Centers for Disease Control and Prevention. And the CDC points to the likely culprit behind the spike in cases of the infectious disease: the use of heroin and other injection drugs.

And despite the existence of therapies that can cure more than 90 percent of infections, the organization says the disease remains a deadly threat. In 2013, for instance, the CDC says some 19,000 people died of their infections.

From CNN: New Hepatitis C Infections Triple due to Opioid Epidemic

The number of new nationally reported infections with the virus swelled from 850 in 2010 to 2,436 cases in 2015, with the highest rates among young people, mainly 20- to 29-year-olds, who inject drugs, according to a new report released Thursday by the Centers for Disease Control and Prevention.

NPR: Safety Problems in 1/3rd of New Medications

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From NPR: Safety Problems in 1/3rd of New Medications After FDA Approval

From 2001-2010:

Seventy-one of the 222 drugs approved in the first decade of the millennium were withdrawn, required a “black box” warning on side effects or warranted a safety announcement about new risks to the public, Dr. Joseph Ross, an associate professor of medicine at Yale School of Medicine and colleagues reported in JAMA on Tuesday. The study included safety actions through Feb. 28…

It took a median of 4.2 years after the drugs were approved for these safety concerns to come to light, the study found, and issues were more common among psychiatric drugs, biologic drugs, drugs that were granted “accelerated approval” and drugs that were approved near the regulatory deadline for approval…

“In the 21st Century Cures Act, there’s a push to have the FDA move to further support the use of surrogate markers … [but] they’re more likely to have concerns in the post-market setting.”…

The study included market withdrawals of three drugs: The anti-inflammatory drug Bextra; a drug called Zelnorm that was used to treat irritable bowel syndrome; and the psoriasis drug Raptiva. Bextra and Zelnorm were withdrawn over cardiovascular risk, and Raptiva was withdrawn because of increased risk of a rare and fatal infection that causes brain damage.

My take: FDA approval does not guarantee safety.  All medications have potential risks along with their benefits.