Tag Archives: celiac disease

Something You Probably Have Not Seen with Celiac Disease and Headaches

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An “image of the month” in the NEJM shows the association between celiac disease and occipital calcifications in a 24 year-old with a 10 year history of headaches, here’s the link: 

The course and explanation: Treatment with a gluten-free diet, folic acid supplementation, and carbamazepine was initiated, and the patient’s condition improved, with remission of all symptoms. The combination of celiac disease, epilepsy, and cerebral calcification is a rare condition known as the CEC syndrome. Folate malabsorption is a suggested mechanism

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Also, there is a useful patient celiac education page from JAMA Pediatrics & University of Chicago: http://dlvr.it/55h6Rd 

Why is Celiac Disease Becoming More Prevalent?

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A recent editorial helps provide some answers and even explains the term “protopathic bias.”  Ostensibly, the editorial’s task is to explain the potential interaction of maternal serum iron ingestion and the risk of celiac disease (see previous blog post: Is There a Link Between Maternal Iron Supplementation and …).  However, the editorial provides an explanation for the Swedish epidemic and the ongoing slower, wider epidemic.

Here’s the link, http://ow.ly/vQGQ7, and here’s an excerpt:

The Swedish epidemic of CD of 1985–1994 has been extensively documented, and resulted in the development of hypotheses regarding environmental risk factors for this disorder.7 This epidemic was restricted to children younger than 2 years; in that age group, the incidence of diagnosed CD rose from 65 cases per 100,000 person-years to 198 cases per 100,000 person-years. In contrast, incidence data for older children were relatively flat during this period. The epidemic abruptly ended in 1995, although children born during the period of the epidemic have an ongoing increased risk of developing CD. Subsequent investigation led to the hypothesis that infant feeding practices affect the risk of CD in young children. The epidemic occurred during a period of relatively low rates of breastfeeding at the age of 6 months and during the same period of time, the quantity of gluten in infant formula greatly increased. Although it is difficult to separate the relative importance of each feeding practice, it seemed that high quantity of initial gluten intake without overlapping with breastfeeding was responsible for this epidemic. Although a systematic review of the issue has concluded that breastfeeding has not been definitively proved to be associated with risk of CD,8 subsequent research has indicated that the timing of gluten introduction is important in determining risk.9PreventCD, a prospective randomized trial of infants with a family history of CD, is testing specifically whether the introduction of small quantities of gluten beginning at age 4 months of age will induce tolerance to gluten in this high-risk group.

The second epidemic is more diffusely spread over time and space. Studies from the United States and elsewhere have shown that the seroprevalence of CD (as defined by positive tissue transglutaminase and endomysial antibodies) has increased markedly in recent decades. An analysis of stored serum from military recruits at the Warren Air Force Base in the years spanning 1948–1954 found a CD seroprevalence of 0.2%, whereas 2 recent cohorts from Olmsted County (spanning the years 2006–2008) matched by year of birth and age at sampling found a seroprevalence of 0.9% and 0.8%, respectively.11 An analysis of another cohort in this country found a doubling in seroprevalence during adulthood from 1974 (0.21%) to 1989 (0.45%).12 The mode of presentation of CD has changed in the past generation, with rising numbers of patients presenting without diarrhea.13 Patients presenting with anemia may have more severe disease expression (as measured by the degree of villous atrophy and the presence of metabolic bone disease) than patients presenting with diarrhea.14 Because most individuals in the United States with CD are undiagnosed,15 this is largely a hidden epidemic, but there is no reason to believe that the prevalence has peaked. In Finland, which had a higher prevalence of CD than the United States to begin with, the seroprevalence of CD doubled between the years 1978 (1.05%) and 2000 (1.99%).16 It is not known whether this epidemic will subside or if the prevalence of CD will continue to rise to a new set-point. But given the morbidity associated with CD17 and the cost and difficulty of the gluten-free diet18, 19 these data have sparked interest in identifying the cause of this less visible epidemic.

Certain infections (eg, rotavirus among infants20 and Campylobacter among adults21) have recently been shown to be associated with a increased risk of CD, but rates of these infections have not increased markedly, and so are not likely to be driving this epidemic. In contrast, a lack of exposure to certain microbes is a hallmark of modern times, and the increase in CD disease is congruent with the hygiene hypothesis, which states that decreased exposure to microbes may be driving the rise in autoimmune and atopic conditions. This hypothesis is particularly compelling in light of a recent study that found a dramatically different seroprevalence of CD in Finland (1.4%) and the Russian Karelia (0.6%), geographically proximate areas with a similar prevalence of HLA DQ2 and DQ8 but with major differences in economic development.22

Further evidence implicating the modern relationship with microbes is now accumulating. Children who were born by elective cesarean section are at increased risk of developing CD, whereas those born by emergent cesarean section (and may have had contact with the birth canal) are not.23 In addition, there seems to be an inverse relationship between Helicobacter pylori colonization and CD.24 Drugs are another modern innovation that may be affecting the CD epidemic. Population-based studies from Sweden have shown that prescription of antibiotics25 and proton pump inhibitors26 are each associated with an increased risk of the subsequent development of CD.

The associations identified in these studies are not necessarily causal. Studies of drug exposure in particular may be prone to protopathic bias, wherein early symptoms of the outcome of interest (CD) may lead to the prescription of the exposure (eg, antibiotics or proton pump inhibitors).

From the NY Times: Gluten-free, veggie snacks, vegan desserts, spring salads. They’re all in our new recipe finder.

Is There a Link Between Maternal Iron Supplementation and Celiac Disease?

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According to a recent study, maternal iron supplementation may increase the risk of celiac disease in children (Clin Gastroenterol Hepatol 2014; 12: 624-31).

Using the Norwegian Mother and Child cohort study (1999-2008) which included data for 78,846 children, the authors analyzed the risk of developing celiac disease by examining prospectively collected questionnaires regarding iron supplements, diet, and anemia.  Questionnaires were obtained 3 times during pregnancy, then at age 18 months, 6 years, 7 years and 8 years.

Key Results:

  • 4.65 of 1000 children whose mothers took iron supplements while pregnant developed celiac disease compared to 3.15 of 1000 whose mothers did not.
  • After adjustment for multiple variables, the OR was 1.33 for children developing celiac disease if their mother took iron supplementation during pregnancy.
  • The authors note that maternal anemia was not associated with celiac disease in offspring nor was iron supplementation in childhood.

While these findings are intriguing, the associated editorial (pg 632-35) notes that unmeasured confounding variables could explain the findings.  For example, undiagnosed maternal celiac disease which could increase the likelihood of iron exposure could increase the risk of celiac disease in the offspring and account for the increased association with iron supplementation.

Take-home message (from the editorial): “it is premature to argue that iron supplementation during pregnancy should be avoided in individuals with celiac disease…the observed effect (an absolute risk increase of 0.15%) is modest in magnitude. This exposure is not driving the slow, ongoing epidemic of celiac disease.”

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Withdrawing Immunosuppression with Autoimmune Hepatitis

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A recent retrospective study indicates that withdrawal of immunosuppression in autoimmune hepatitis (AIH) can be successful in carefully selected children (J Pediatr 2014; 164: 714-19).

A cohort of 56 children with AIH were followed for a median of 5.6 years and with a median age of 11 years (62% female).  Demographics noted that cirrhosis was present in 14%, primary sclerosing cholangitis 21%, and AIH type II in 9%.

Key findings:

  • Biochemical remission with immunosuppression was achieved in 76% of all patients at a median of 1.2 years; 23% of these patients experienced a subsequent relapse.
  • Withdrawal of immunosuppression was successful in 14 of 16 of patients with type 1 AIH who had been treated for a median of 2.0 years after diagnosis.
  • When the authors excluded patients with inflammatory bowel disease, they noted that the probability of achieving a sustained immunosuppression-free remission was 42% at 5 years.  Sustained remission was defined as biochemical remission for >1 year, liver biopsy without inflammation, and no relapses.
  • Patients less likely to reach a biochemical remission with immunosuppression included patients with cirrhosis, elevated INR, positive ANCA titer, and patients with coexisting autoimmune disorder.

In their discussion, the authors note that treatment withdrawal is “generally considered more successful after at least 3 years of therapy,” though only 50% of their patients who had therapy withdrawn had been treated that long.  In addition, they state that while coexisting immune disorders often result in more frequent relapses, the one exception in the literature is celiac disease when patients adhere to a strict gluten-free diet.  They also urge all patients diagnosed with AIH to undergo testing for celiac disease and thyroid disease.

Limitations of the study include the following: small numbers of patients, single center (Utah), retrospective design, and cholangiography was not performed uniformly.

Take-home message: In patients doing well with AIH for 2-3 years & with normalized liver histology, it may be possible to withdraw immunosuppression.

Related blog posts:

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.

 

Camp Weekaneatit for Kids with Celiac

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From my colleague, Jeff Lewis:  “The camp is called Camp Weekaneatit, it is July 13 to July 18, overnight camp, strictly gluten-free so the kids can eat what they want without having to worry.  Its part of Camp Twin Lakes – an organization that hosts tons of medical camps.  We have kids from all over – as far away as California the last two years.  Scholarships are available.”

Anyone who tries to follow a strict gluten-free diet knows how difficult it can be to take a trip outside the home.  This camp lets kids enjoy camp without the worry about the next meal or snack.  Spread the word!

 

CampInformation 

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)

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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.
Related blog posts:
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.