Tag Archives: celiac disease

Gluten-free diet “has legs”

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From NY Times: http://t.co/5cQijw7do9

An excerpt:

The Girl Scouts recently introduced a gluten-free chocolate chip shortbread cookie to their annually anticipated line of sweet treats…And Trader Joe’s recently joked in an advertising flier promoting gluten-free foods that it was selling “Gluten Free Greeting Cards 99 Cents Each! Every Day!” — even though it then went on to say the cards were not edible.

Makers of products that have always been gluten-free, including popcorn, potato chips, nuts and rice crackers, are busy hawking that quality in ads and on their packaging.

And consumers are responding with gusto. The portion of households reporting purchases of gluten-free food products to Nielsen hit 11 percent last year, rising from 5 percent in 2010.

In dollars and cents, sales of gluten-free products were expected to total $10.5 billion last year, according to Mintel, a market research company, which estimates the category will produce more than $15 billion in annual sales in 2016…

“About 30 percent of the public says it would like to cut back on the amount of gluten it’s eating, and if you find 30 percent of the public doing anything, you’ll find a lot of marketers right there, too.”

Never mind that a Mayo Clinic survey in 2012 concluded that only 1.8 million Americans have celiac disease, an autoimmune disorder that causes the body to attack the small intestine when gluten is ingested and can lead to other debilitating medical problems if not diagnosed.

An additional 18 million people, or about 6 percent of the population, is believed to have gluten sensitivity, a less severe problem with the protein in wheat, barley and rye and their relatives that gives elasticity to dough and stability to the shape of baked goods.

“There are truly people out there who need gluten-free foods for health reasons, but they are not the majority of consumers who are driving this market,” said Virginia Morris, vice president for consumer strategy and insights at Daymon Worldwide, a private brand and consumer interactions company…

“The reason I do believe this has legs is that it ties into this whole naked and ‘free from’ trend,” she said. “I think we as a country and as a globe will continue to be concerned about what’s going into our food supply.”

Rebecca Thompson, a marketing manager at General Mills, said ..“When you think about the dynamics in a household, where there are likely to be three other people eating at the same time as one person with celiac or gluten sensitivity, it’s much easier to prepare one meal for everyone.”…

General Mills, whose brands include Bisquick, Pillsbury and Betty Crocker, might seem like the least likely company to embrace gluten-free. But in the mid-2000s, more and more customers began seeking alternatives to its traditional products.

So in 2008, it began reformulating its Chex cereals, underscoring the first change, to Rice Chex, with a major marketing effort. It was relatively easy to tweak Chex by switching a few minor ingredients. But the next year, Betty Crocker introduced gluten-free brownies, cookies and cakes in a far more complicated process…

Gluten-free customers are valuable, ringing up roughly $100 in sales with their average grocery basket compared with $33 for the overall average basket, according to Catalina Marketing…

Last August, the Food and Drug Administration, which oversees food labeling, ruled that products labeled gluten free were permitted to contain no more than 20 parts of gluten per million, which made it more difficult for large food companies to get into the business. “You really need to have a captive facility because wheat floats,” Mr. Hughes said.

Sales of Udi’s and Glutino were up 50 percent last year, and Boulder Brands is finding more demand from regional food service businesses and institutions. Udi’s hot dog buns are available now in most major baseball parks, and Dunkin’ Donuts and others are turning to the company for individually wrapped gluten-free bagels and muffins…

Mr. Hughes said. “We think this is a trend with long legs because there is some insulation from the big players — it’s hard to produce gluten-free — and because so much of the category is represented by $10- and $15-million mom-and-pop businesses.”

Interest in gluten-free products also has been a boon for fruits and vegetables and other foods that are inherently gluten-free. Popcorn Indiana, for example, has labeled its ready-to-eat popcorn gluten-free since before the fad began, in part because the chief executive, Hitesh Hajarnavis, has children who have food allergies. “I had become an avid reader of labels, and so when I came over to Popcorn Indiana, I knew the value of having a clear gluten-free label for what was then a very small number of people with gluten allergies,” Mr. Hajarnavis said… “But there is a growing population of people who have somehow heard that gluten-free is healthier or think of it as fashionable, and when they remove gluten from their diet, they’re inadvertently taking out a lot of processed foods and are really feeling the benefits of eating healthier foods.”

Celiac Update: Quinoa –probably OK for gluten-free diet based on small study.  Here’s the link: nature.com/ajg/journal/vaop/ncurrent/full/ajg2013431a.html … (from KT Park twitter feed)

Related blog posts:

Timing of Solid-Food Introduction

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The “DAISY” (diabetes autoimmunity  study in the young) study indicates that the timing of solid-food introduction can influence the likelihood of developing type 1 diabetes (T1DM) (JAMA Pediatr 2013; 167: 808-15).

The participants were 1853 children at increased genetic risk for T1DM who were enrolled in a longitudinal observational cohort study in Denver. Early solid-food exposure was considered <4 months of age and late >6 months of age.

Results:

  • “Both early and late first exposure to any solid food predicted development of T1DM.”  For early exposure, the Hazard Ratio was 1.91 and for late HR was 3.02.
  • Breastfeeding at the time of introduction to wheat/barley conferred protection (HR 0.47)

The study has several limitations, particularly the relatively low numbers of children who developed T1DM (n=53).

A second study (Pediatrics 2013 [doi: 10.1542/peds2012-3692]) –thanks to Ben Gold for this reference –showed that “solid foods were introduced significantly earlier among the infants with allergies, with 35% of them receiving their first solids before and including 16 weeks, compared with 14% of control infants (P=.011).”   (Solid foods before 17 weeks linked to food allergy)

Bottomline: As with celiac disease (“Gluten–Related Disorders” (Part 1) | gutsandgrowth), current science suggests the introduction of solid foods between 4-6 months of age may diminish the risk of developing T1DM as well as food allergies.

 

“Gluten-Related Disorders” (Part 2)

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Non-celiac Gluten Sensitivity NCGS -Focused discussion in Section III
  • No biologically measurable response has been found – these are people with normal celiac serology (neg ttg/ema) and normal biopsies.
  • Specific discussions regarding autism and schizophrenia.  On page 44, authors note that a 2008 Cochrane review concluded the evidence for a gluten-free diet for autism was poor.  In 2012, a two-stage RCT (Whiteley et al) of gluten-free casein-free diet reported significant group improvements after 8 and 12 months on diet. Thus, diet may be helpful.
  • Other chapters allude to NCGS as well.  Page 124: “There are no epidemiologic studies assessing the prevalence of NCGS. Bizzaro et al estimated that for every one person with CD, there are at least six to seven with gluten sensitivity.”
Wheat Allergy -Section IV
  • Forms include oral food allergy, “wheat-dependent, exercise-induced anaphylaxis,” and Baker’s asthma (aerosolized exposure).
  • Skin prick tests or RAST’s are notorious for providing a high rate of false-positive results.  Low rate of false negative results, though, are noted.

Treatment -Section VI:

  • This section provides a number of tables to assist with diet and hidden sources of gluten.
  • GFD may lead to specific nutrient deficiencies: fiber, iron, folate, niacin, zinc, vitamins B12, A, D, E, and K; also, GFD may be higher in fat.

Psychological Aspects -Section VII:

 “The family has to buy gluten-free foods and all members have to learn how to avoid contaminating gluten-free foods, dishes, toasters, and so on.” Parents have to read all food labels and prepare special meals while attending social events.
A nice sample letter is included on page 129 –should make a good EPIC smartphrase.
Difficult Cases -Section VIII:
  • Labs to check in sick CD patient (Table 2 -page 133).
  • Causes of Nonresponse to GFD: poor compliance, accidental ingestions, nonceliac disease causing symptoms.
  • While some of the authors state that true refractory disease is “rare in adults,extremely rare in children,” in other parts of the book it is noted that complete histologic response is not seen in all patients (some with apparently good adherence).

IgA deficiency (page 139).

  • 85-90% of IgA deficient patients have no clinical symptoms.  Occurs in about 1 in 300.  For those with symptoms, manifestations could include sinopulmonary disease, allergy/atopy, autoimmune diseases, giardiasis/infections, and transfusion reactions (against IgA) (see Table 8 on page 143).
  • Transiently low IgA is common in children <4 years.
  • For IgA deficient patients, risk of CD is 10-20 times general population.
  • In true deficiency, level is typically <7 mg/dL.  More often, there is a partial deficiency which is ‘almost always asymptomatic.’  In partial IgA deficiency, IgA assays identify about 90% of CD cases.
Also, in the difficult cases section an algorithm for follow-up of newly diagnosed CD is presented and discussed (page 154).  Recommendations include nutritional counseling, resource identification, family screening, and celiac education.  Consider checking iron status, vitamin D, folate, zinc, copper and DEXA.  Recommends followup serology 6 months following diagnosis and if normal, then on a yearly basis.
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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

“Gluten-Related Disorders” (Part 1)

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On the way back from our National Meeting (NASPGHAN), I had the opportunity to read “Gluten-Related Disorders” ed. by Alessio Fasano.  The book is a very good summary about the science of celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity (NCGS); at the same time, there is some redundancy due to multiple authors (particularly evident in later chapters). One of the book’s features is clinical vignettes to drive home multiple teaching points.  For example, the ‘refractory’ CD patient who in fact has Crohn’s disease. The book also provides a code to obtain the information online, so it is fully searchable.  In the introduction, there is an in-depth explanation of why gluten can be so difficult for the GI tract.  The discovery that a gluten-free diet can be helpful was a byproduct of wheat shortages during WWII.  Here are some useful insights that were noteworthy:

Definitions (page 9):  reviews the terms “silent CD,” “potential CD,” and “latent CD.”

  • Silent =asymptomatic but with all other features: +antibodies, +HLA type, +abnl histology
  • Potential =+antibodies but lack of histology evidence  (antibodies often precede development of clinical disease)
  • Latent =previous evidence of CD but currently tolerating gluten in diet with normal histology

Epidemiology:

  • While increase in CD is partly due to awareness, there has been a “true increase in prevalence, with rates doubling every 20 years or so.”
  • Early vaccinations are not risk factors for the development of CD
  • Breastfeeding can reduce risk of CD by about 50% though gluten should be introduced between 4-6 months.

Presentation:

  • Table of the main extraintestinal manifestations on page 24.  Most common: anemia (especially iron deficiency), short stature, and pubertal delay.
  • Associated diseases (Table 3, page 29): Down syndrome, Turner syndrome, Type I Diabetes, Williams syndrome, IgA deficiency, and Autoimmune thyroid disease.
  • Eosinophilic esophagitis has been identified in a small number of patients with celiac disease.  The book notes a study with 7 pediatric patients; only one of them improved their esophageal eosinophilia with a GFD.

Tips on diagnosing celiac

  • Bulb abnormalities with a normal 2nd portion of duodenum biopsy can be seen in 10% or more of patients with celiac.  The authors recommend obtaining 4 biopsies from 2nd and 3rd portion and 2 biopsies from bulb (separate containers) (page 144-145).
  • Most celiac experts say there is no celiac without DQ2 or DQ8.  There are several situations in which a negative HLA type could be helpful (page 78)
  1. -negative serology but abnormal histology
  2. -gluten-free diet (GFD) started before diagnosis confirmed
  3. -failure to respond to GFD
  4. -asymptomatic high-risk individuals to help determine if periodic serology is worthwhile
  • In most individuals, obtaining TTG IgA along with serum IgA is recommended for diagnosis (and avoiding older gliadin antibody tests).  If clinical suspicion is high, endoscopy is warranted regardless of result.
  • Under the age of 2, deamidated anti-gliadin antibodies appear months earlier than the TTG in prospective studies, so order the dAGA IgG and dAGA IgA in kids under 2. (Available with both quest and labcorp).  The deamindated anti-gliadin antibodies may be more helpful/sensitive in monitoring dietary adherence than TTG.
  • Infants who have a first degree family member with celiac should be introduced to “small” amounts of gluten between 4 and 6 mos of age – not before and not delayed.  It appears to promote tolerance though it’s not clear if it just delays inevitable onset.  Small amounts can be a serving a day of a mixed, barley baby cereal.
  • Section V is devoted to diagnosis.  Table 1 (page 72) lists the sensitivity/specificity of the available serologies.
  • Screening asymptomatic persons.  The controversy regarding this practice is alluded to on page 75.  Currently NASPGHAN recommends screening at risk groups whereas AGA does not.
  • Endoscopy/Biopsy discussed (pages 78-82).  States a biopsy is not needed in the case of dermatitis herpetiformis due to characteristic deposits of IgA in the dermal papilla.  The authors recommend biopsy in all cases, but review ESPGHAN guidelines which state that biopsy can be omitted if TTG IgA >10 time ULN –if verified by positive EMA, HLA typing, and followed for symptomatic improvement.
  • Antibody tests “become negative in 15% after 1 month on GFD and in 57% after 3 months…diagnosis of CD cannot be made while on GFD.”  Algorithm for diagnosis of CD with a child on GFD presented on page 148.
Related blog links:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

What is Gluten-Free?

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An excerpt from the National Foundation for Celiac Awareness Press Release:

NFCA Press Release about FDA Gluten-Free Labeling Rule

AMBLER, Pa. (August 2, 2013) – The National Foundation for Celiac Awareness (NFCA), a national non-profit organization dedicated to increasing diagnoses and improving quality of life for those with gluten-related disorders, is responding promptly to the U.S. Food & Drug Administration’s (FDA) final rule on gluten-free labeling by announcing new resources for gluten-free consumers to understand the federal regulations.

“For years, gluten-free labels have gone unregulated, putting our gluten-free community in danger,” said Alice Bast, President of NFCA. “We applaud the FDA for finally publishing a standard definition of gluten-free.”NFCA logo

The new regulations state that a food must contain less than 20 parts per million (ppm) of gluten in order to bear a “gluten-free” label. Researchers support less than 20 ppm as a safe threshold for a product to be consumed by individuals with celiac disease and other gluten-related disorders.

“Evidence-based research conclusively supports the 20 ppm level as a safety threshold for gluten-free products,” said Dr. Alessio Fasano, Director of the Center for Celiac Research at MassGeneral Hospital for Children in Boston. “We welcome the new FDA regulations, which will bring us in line with gluten-free labeling regulations for millions of people around the world.”

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Thanks to Kayla Lewis for forwarding the press release.

 

Elevated Celiac Serology Associated with Reduced Infant Birth Weights

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Using a population-based study of 7046 singleton pregnancies (from the Netherlands), the authors of a recent study have shown an inverse relationship between levels of anti-tissue transglutaminase IgA (TTG) antibodies and fetal growth (Gastroenterol 2013; 144: 726-35).

Results:

  • Newborns of positive TTG (>6 U/mL) weighed 159 g less at birth than newborns of mothers who tested negative for TTG.  In addition, newborns with mothers who had intermediate TTG levels ( 0.8 U/mL to 6 U/mL) had growth restriction of 53 g.
  • Among the intermediate TTG group, the results were more pronounced (2-fold greater) in those carrying the HLA risk molecules for celiac disease.
  • These birth weight changes were not associated with maternal nutritional status or deficiencies related to hemoglobin, iron, folate, or vitamin B12 deficiency.
  • Gestational age was not affected by TTG titers.

In the discussion, the authors note that other studies have shown that undiagnosed celiac disease increases the risk for intrauterine growth retardation; this risk can be eliminated by treating celiac disease.  The latter is a risk factor for lower neuropsychological performance.  This study was the first that took into effect the different TTG titers and correlated with additional nutritional parameters.

The authors speculate that celiac disease could have direct effects on the placenta.  In addition, other nutritional parameters could play a role such as vitamin D and calcium which were not included in this study.  Another important consideration is that celiac disease can result in increased miscarriages.  As a result, the “true” effect on newborn growth may be underestimated due to a “survivor bias.”

Related blog posts:

Celiac hepatopathies

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There has been a longstanding recognition that celiac disease can be associated with elevated liver enzymes.  Two articles provide further information about celiac hepatopathies.

  • JPGN 2013; 56: 663-70
  • JPGN 2013; 56: 671-74

The first study describes a review of nine studies identified in a MEDLINE search for celiac disease and hypertransamminasemia (HTS) or autoimmune hepatitis (AIH). In total 2046 patients were identified.

Key findings:

  • 12% of patients with mild persistent HTS had celiac disease.  Among individuals with HTS, the relative risk for celiac disease was 11.59 compared to general population.
  • 36% of newly diagnosed children with celiac disease, has elevated aminotransferases.  A gluten-free diet normalized transaminases in 77% within 4 to 8 months.
  • Among children with celiac disease, 1.4% had AIH.  Among children with AIH, 6.3% had celiac disease.

While this meta-analysis had many limitations, it is clear that celiac disease needs to be considered in patients presenting with elevated aminotransferases and in patients with AIH.  In addition, other liver conditions like primary biliary cirrhosis and sclerosing cholangitis, which are infrequent in the pediatric population, are more common in patients with celiac disease.

The second study involved both retrospective (1995-2000) and prospective evaluation (2000-2012) of patients followed at a single center.  The authors sought to determine the long-term response to immunosuppressive treatment in children with autoimmune hepatitis (AIH) and celiac disease.

In their cohort of 79 AIH patients, 15 (9%) had celiac disease.  There was a similar frequency of type 1, type 2 and seronegative AIH among the celiac patients (47%, 20%, and 33%) compared with the entire cohort (55%, 34%, and 11%).  All 15 patients responded to treatment with prednisone and azathioprine or cyclosporine, along with a gluten-free diet.  When immunosuppressive treatment was withdrawn in 9 patients, 4 relapsed and 5 were maintained off immunosuppression for a mean period of 89 months. A much lower rate of immunosuppression withdrawal was achieved in those AIH patients without celiac disease.  24 of 64 attempted to stop immunosuppression; 5 (8%) were successful.

Take-home point of second study: All AIH patients should be screened for celiac disease as a gluten-free diet may increase the likelihood of withdrawal of immunosuppression.

IBS Symptoms in Patients with Celiac Disease

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While a gluten-free diet (GFD) is the optimal treatment, adult patients with celiac disease still have a high prevalence of irritable bowel symptoms (IBS) (Clin Gastroenterol Hepatol 2013; 11: 359-65).

The authors examined the prevalence of IBS symptoms by reviewing cross-sectional and case-control studies in adults with celiac disease (≥16 years old).  Initially, the literature search identified 624 studies; the vast majority did not fit the study requirements.  Seven studies (n=3383 participants) reported the prevalence of IBS symptoms in celiac disease.  These studies took place between 2002 to 2011 in five different countries.  IBS was defined using either Rome I, II, or III criteria.  Only one of these studies assessed adherence to a GFD by using negative tissue transglutaminase antibodies on the 2 most recent outpatient visits.

Results: IBS symptoms were present in 38% of all patients with celiac disease.  The pooled odds ratio was higher for celiac disease than controls (OR 5.6, with 95% CI 3.23-9.7).  Nonadherence to a GFD increased the likelihood over those who were adherent by an odds ratio of 2.69

Take-home message: IBS symptoms are present in a high proportion of patients with celiac disease.  While a GFD may improve these symptoms, some individuals will have persistent symptoms.

Related blog entry:

Is functional pain more common in children with … – gutsandgrowth  Previous blog entry examines functional abdominal pain in children and celiac disease.

Additional references:

  • -JPGN 2011; 53: 216. Case report of refractory celiac treated with 6-MP.
  • -Clincal Gastroenterol & Hep 2011; 9: 13. Celaic with persistent symptoms: consider poor adherence**, SBBO*, pancreatic insufficiency*/subclinical pancreatitis, refractory celiac (rare), PLE, giardia, malignancy, lactose intolerance, functional d/o*, microscopic colitis, Crohn’s*, NSAIDs
  • -Gastroenterol 2009; 136: 81, 91, 99, 32. Refractory celiac can be divided into 2 types; 2nd type assoc c abnormal IEL and has poor prognosis. Risk of non-hodgkins lymphoma 3.8-5 .3 fold over gen population in larg Sweish study. n=37869 c NHL, 236,408 controls, 613,961 1st degree relatives. Relatives c 2 fold risk. Absolute NHL risk ~1 in 1421 person-yrs for celiac pt.
  • -Clin Gastroenterol & Hep 2007; 5: 445-450. Causes of nonresponsive celiac.
  • -NEJM 2007; 356: 2548. Nonresponsive due to inhaled gluten in farm setting.
  • -Clin Gastro & Hep 2007; 5: 445. Gluten exposure in 36%, IBS n 22%, lactose intol 8%, refractory CD 10%
  • -Gastroenterol 2011; 141: 1187.  Prevalence of celiac similar in IBS as general population though higher number (7%) with celiac antibodies (esp gliadin).

Gluten-related Disorders

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For those who missed a recent NASPGHAN Foundation webinar, I’ve attached two links (with permission from NASPGHAN foundation):

1. The PDF of the slides –these are very useful:

NASPGHAN GlutenWebinar 6_5_13 Final v34

2. Link to webinar, including CME:

http://limelightdc.com/clientarea/naspghan_gluten_webinar_06_13/landing_page.html

The experts provide a useful review of celiac, wheat allergy, and wheat intolerance.  For celiac screening, the webinar recommends avoiding a panel of serology tests in favor of isolated Tissue Transglutaminase IgA Antibody (possibly with serum IgA level.

Related blog links:

What really causes Celiac disease?

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A fascinating article in the NY Times delves into a number of environmental factors that are likely playing a role in the increasing incidence of celiac disease. Here’s the link (thanks to Kayla Lewis for this reference):

Some excerpts:
“Scientists are pursuing some intriguing possibilities. One is that breast-feeding may protect against the disease. Another is that we have neglected the teeming ecosystem of microbes in the gut — bacteria that may determine whether the immune system treats gluten as food or as a deadly invader.Celiac disease is generally considered an autoimmune disorder. The name celiac derives from the Greek word for “hollow,” as in bowels. Gluten proteins in wheat, barley and rye prompt the body to turn on itself and attack the small intestine. Complications range from diarrhea and anemia to osteoporosis and, in extreme cases, lymphoma. Some important exceptions notwithstanding, the prevalence of celiac disease is estimated to range between 0.6 and 1 percent of the world’s population….Yet the more scientists study celiac disease, the more some crucial component appears in need of identification. Roughly 30 percent of people with European ancestry carry predisposing genes, for example. Yet more than 95 percent of the carriers tolerate gluten just fine. So while these genes (plus gluten) are necessary to produce the disease, they’re evidently insufficient to cause it….

A recent study, which analyzed blood serum from more than 3,500 Americans who were followed since 1974, suggested that such a trigger could strike adults at any time. By 1989, the prevalence of celiac disease in this cohort had doubled.

“You’re talking about an autoimmune disease in which we thought we had all the dots connected,” says Alessio Fasano, head of the Center for Celiac Research and Treatment at the Massachusetts General Hospital for Children in Boston, and the senior author of the study. “Then we start to accumulate evidence that there was something else.”

Identifying that “something else” has gained some urgency. In the United States, improved diagnosis doesn’t seem to explain the rising prevalence. Scientists use the presence of certain self-directed antibodies to predict celiac disease. They have analyzed serum stored since the mid-20th century and compared it to serum from Americans today. Today’s serum is more than four times as likely to carry those antibodies…

your microbes change you, but your genes also shape your microbes — as do environment, breast milk, diet and antibiotics, among many other factors.

Such complexity both confounds notions of one-way causality and suggests different paths to the same disease. “You have the same endpoint,” Dr. Jabri says, “but how you get there may be variable.”…

In a far-flung corner of Europe, people develop celiac disease and other autoimmune diseases as infrequently as Americans and Finns did a half-century ago. The same genes exposed to the same quantity of gluten do not, in that environment, produce the same frequency of disease.

“We could probably prevent celiac disease if we just give the same environment to the Finnish children as they have in Karelia,” says Dr. Hyoty. “But there’s no way to do it now, except to move the babies there.”

Author of NY Times article:

Moises Velasquez-Manoff.  Also, he is the author of “An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases.”

Related blog links: