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Meeting the Nutritional Needs of Adults with
Celiac Disease
Daniel Leffler, MD, MSClinical Research Director
Celiac CenterBeth Israel Deaconess
Medical Centerwww.bidmc.harvard.edu/
celiaccenter
HARVARD MEDICAL SCHOOL
Objectives
Define and review pathogensis of celiac disease
Identify currently accepted diagnostic testing methods for celiac disease
Identify the risk factors and extra-intestinal manifestations associated with celiac disease
Learn standard treatment approach Recognize key nutritional deficiencies and
standard supplementation recommendations Discuss causes of continued GI symptoms
despite a patient’s strict adherence to the GF diet
Patient: Jill Initial Visit: May 09
Jill, a 32 year old, has been experiencing fatigue, gas, bloating, and loose stools since a GI virus affected her whole family while on a cruise. All other members recovered while Jill did not. She experimented with the gluten free diet and noticed that her symptoms improved somewhat. Her PCP has sent her to GI for a work-up.
Ht: 5’7 Wt: 126#PMHx: anemia SHx: Nonsmoker, minimal alcohol Food allergies/intolerances: lactose
What important diseases/ disorders would you elicit in the patient’s family history?
Patient: Jill Initial Visit: May 09
Jill, a 32 year old, has been experiencing fatigue, gas, bloating, and loose stools since a GI virus affected her whole family while on a cruise. All other members recovered while Jill did not. Her PCP has sent her to GI for a work-up.
Ht: 5’7 Wt: 126# PMHx: anemia Meds: Allegra, Loestrin SHx: Nonsmoker, minimal alcohol Food allergies/intolerances: lactose
FHx: breast cancer, autoimmune thyroid disease, Type 1 diabetes, diverticulitis, IBS
What are possible causes of Jill’s symptoms?
Patient: Jill Differential
Ht: 5’7 Wt: 126#
Irritable Bowel SyndromeLactose intoleranceInflammatory Bowel DiseaseSmall intestinal bacterial overgrowthChronic infectionCeliac Disease
What makes you suspect celiac disease in Jill?
Diseases Associated with Celiac Disease
Chronic Diarrhea: 25%First degree relative with celiac: 7-10% Iron deficiency anemia: 10%Type 1 diabetes: 5%Autoimmune thyroid disease: 4%Osteoporosis: 2.5-4%Sjogrens Syndrome: 10%Downs Syndrome: 5% IBS: 4-5%Family history of autoimmune disease
What is Celiac Disease?
Celiac Disease: A heightened immune responsiveness to gluten (wheat, rye, barley proteins) leading to an autoimmune enteropathy often with systemic manifestations.
PathophysiologyStep 1: Gluten Entry into the Submucosa
*Green, Cellier NEJM 2007
Step 2: Deamidation of Gluten by Tissue Transglutaminase (tTG)Step 3: Immune Activation Only HLA DQ2 and DQ8 are able to bind gluten!
Step 1
Step 2 Step
3
Serologic tests
Celiac Disease is Not Rare
* Talley et al, Am. J. Gastroenterol, 1994
Estimated Prevalence:• Previously: 1/1000 in Europe & 1/5000 in the U.S.*• Currently: ~1/150 in US, Europe stretching to North India ~ areas with high prevalence of HLA
DQ2/DQ8• Compare to Type 1 diabetes 1/500
However:• Number of known celiacs in the U.S.: ~40,000• Projected number of celiacs in the U.S.: well > 3 million• For each known celiac there are 53 undiagnosed individuals
Not a Pediatric Disorder
Until the 1980’s celiac disease was almost exclusively diagnosed in children between the ages of 2 and 8
Currently the average age of diagnosis in the United States is 50 years
2/3 of current diagnoses are femaleSerologic studies suggest slight female
predominance
Signs and Symptoms of Celiac Disease
Can Present at Any Age to Any SpecialtyNon- Classic Symptoms
AsymptomaticLFT elevationsConstipationAphthous ulcersNausea/VomitingHeartburn/GERDHypospleniaPancreatitisArthralgias/MyalgiasNeuropathy/AtaxiaAlopeciaHeadachesOsteopenia/OsteoporosisDental defectsFertility problemsCognitive impairment
Classic Symptoms
Diarrhea Iron deficiency anemiaAbdominal PainWeight Loss/Failure to thriveFatigue/LethargyBloating/GasDermatitis herpetiformis
Dermatitis Herpetiformis
The skin manifestation of celiac disease Intensely itchy 2-5 mm blistersExtensor surfaces: Elbows > buttocks > knees > trunk > faceOnset late childhood/early adult lifeAuto-antibodies formed in the intestine deposit at the dermal-epidermal junction Gluten responsive but often treated with Dapsone
Complications of Undiagnosed and/or Untreated Celiac Disease Malnutrition/malabsorption
Anemia Osteopenia/osteoporosis Lymphoma (all, but especially EATL) Carcinoma of the oropharynx, esophagus and
small bowel, ? Melanoma Reproductive complications Other autoimmune diseases Infectious complications including sepsis and TB* Decreased quality of life SMR 2-4 times greater than the general
population normalizing within 5 years of gluten withdrawal
*Influenza and Pneumococcal vaccines should be considered for newly diagnosed patients
Many Medical Specialties are Now Diagnosing Celiac Disease
OB/GYN: Infertility, recurrent miscarriage
Endocrine: Poorly controlled Type I diabetes, increasing thyroid medication need, early onset or severe osteopenia/ osteoporosis
Hematology: Unexplained anemiaNeurology: Ataxia, peripheral neuropathy, epilepsy
Dental: Enamel defects
If you suspect celiac disease, what do you recommend for testing?
Improved Diagnostic Tools Prior to 1982: Clinical Suspicion
and Biopsy (Endoscopic since 1976, before that Crosby Capsule)
1982: Anti-Gliadin Antibody ELISA Sensitivity/Specificity: 70-80%
1985: Endomysial Antibody Immunofluoresence Sensitivity/Specificity: 95%
1997: Anti-tTG ELISA Sensitivity/Specificity: 95% New ELISA for deamidated
anti-gliadin antibodies have similar accuracy to tTG
Celiac Disease: Diagnostic Criteria
Consistent small bowel histology Positive IgA tTG serology
Clinical response to GFD Histologic response to GFD Symptoms, tTG and biopsy relapse with
gluten challenge
•Major criteria:
•Other supportive criteria:
Please Note: ALL diagnostic tests normalize on a GFD so DO NOT start treatment before confirming the diagnosis!
Endoscopic Small Intestinal Biopsyfor Diagnosis of Celiac Disease
Scalloping, Mosaic Pattern, Nodularity
Villous Atrophy, Crypt Hyperplasia, Increased IELs
Villous Atrophy in Celiac Disease
What About Genetic Testing?
Celiac
General Population
DQ2 Positive 79% 30%
DQ8 positive 12% 7%
DQ2 & DQ8 + 9% 5%
DQ2 & DQ8 - <0.1% 62%
Sensitivity: 100%; Specificity: 31%NPV: 100%; PPV: 1.5%Excellent at excluding celiac disease but Terrible for diagnosing it
IBS: Abnormalities in movement of the intestines, sensitivity of the nerves of the intestines, or the way in which the brain controls these functions. no structural abnormalities are seen
Wheat Allergy: Adverse reactions involving IgE antibodies to one or more proteins found in wheat formal allergy testing.
Celiac Disease: A heightened immune responsiveness to gluten (wheat, rye, barley proteins) leading to an small intestinal damage often with systemic manifestations
Gluten Intolerance: ???
Not everyone who feels better on a GFD has Celiac Disease
Gluten Intolerance
Gluten intolerance is a “functional” disorder that may mimic celiac disease in terms of symptoms and response to gluten withdrawal
Unlike celiac disease, there is no (or minimal) autoimmune or inflammatory component to gluten intolerance, and long-term health is similar to those with irritable bowel syndrome
Antigliadin antibodies are commonly elevated in gluten intolerance while IgA tTG levels and duodenal biopsy are normal (unlike celiac disease where all three are usually abnormal)
If having celiac disease has been adequately ruled out, the only restriction on your intake of gluten is how much you can comfortably eat
Back to Jill
Ttg and biopsy confirmed celiac disease
What additional labs would you request?
Recommended Standard Labs CBC 25 OH Vitamin D B12 Folate Ferritin Lipids TSH +/- Zinc, calcium, albumin,
etc
• Average 10% incidence of iron deficiency anemia in patients with newly diagnosed CD in the U.S.
Patient: Jill
Labs: HBG: 11.0 LOW HCT: 33.7 LOW
Ferritin: 2.3 LOW Iron: 22 LOW 25 OHD:12 LOW Folate: 12
Normal B12: 670 Normal Zinc: 75 Normal
IgA-tTG: 82 units Normal (>20 HIGH)
Supplements: Iron Sulfate, multivitamin with Iron
Treatment of Celiac Disease Strict gluten free diet is the
only accepted treatment for celiac disease
Involves avoidance of all wheat, rye and barley products
Less than 1 mg of gluten (1/50th of a slice of bread) can cause significant, mucosal inflammation
Anatomy of Grain
Bran is the Outer Layer containing:• Fiber• B vitamins• Minerals• Protein
Endosperm is the Middle Layer containing:• Gluten: Protein needed for
germination• Carbohydrates
Germ is the Inner Layer containing:• Minerals• B Vitamins• Vitamin E
Impact
Cost - $$$
Label reading
Diet education and health
Social and professional life
Access to GF foods
Hidden gluten/cross contamination
Health
Gluten is Everwhere
“Wheat-free” does not necessarily mean “gluten-free.”Breading
Broth/BouillonCandy
Coating/Drink mixes Communion wafers
Croutons
DressingFlour or cereal products
GraviesImitation bacon Imitation seafood
Lipstick and lip balm
MarinadesPankoPastas
Play-DohProcessed luncheon meats
SaucesDry pet food
SeasoningsSelf-basting poultry
Soup bases Thickeners (Roux)
Toothpaste Dental pumiceMedications
RestaurantCross-
contamination
Ate Mislabeled
Food
Ate a Serving of Pasta
Thinking It Was “Gluten
Free”
Gluten Exposure
on a “Gluten-
Free” Diet
TimePersistent
Symptoms & Inflammation
Typical Gluten Threshold
A Month in the Life of a Celiac Patient: Attempting the Gluten-Free Diet
General Nutrition Review: Jill’s Initial Visit Review gluten free diet – safe/toxic ingredients Monitor and recommend adequate calcium and
vitamin D intake. Assess/recommend multivitamin
Check all medications, supplements and body care products for gluten
Review 3-day food record Recommend local/national support group,
resources Educate on safe dining out techniques and
cross contamination Request labs
Need: Low-fat, high fiber, nutrient-rich GF foods, and
free of some common food intolerances
Enrichment/Fortification: Most GF cereals, pasta and bread are NOT enriched and are low in:
B vitamins – thiamin, riboflavin, niacin, iron, folate
Weight Gain on GF Diet: Excessive reliance on protein-rich, high fat foods High carbohydrate, low fiber content of some gluten-free grains
Coexisting Food Intolerances: lactose, soy, fructose, etc. Lactose: Found in 30-60% in newly diagnosed
Caused by intestinal injury in untreated CDMay resolve on treatment w/ GF diet
Fructose: Increasingly common cause of GI symptomsDoes not typically resolve on a gluten-free diet
Dietary and Health Concerns
WomenFiber (46%)Grain foods
(21%)Iron (44%)Calcium (31%)
MenFiber (88%)Grain foods
(63%)Iron (100%)Calcium (63%)
Thompson T, Dennis M, Higgins LA, Lee AR, Sharrett MK. Gluten-free diet survey: are Americans with coeliac disease consuming recommended amounts of fibre, iron, calcium and grain foods? Journal of Human Nutrition and Dietetics. 2005;18(3):163-9.
Results of 2005 GF Diet Survey:Percentage of People with Celiac Disease Meeting Recommended
Amounts of Nutrients
Safe Grains, Starches & Flours
Arrowroot Amaranth Quinoa Rice bran Sago Buckwheat Flax Sorghum Millet Corn (maize) Seed flours (sesame) Soy (soya)
Teff (tef) Tapioca (also called
cassava or manioc) Legume flours (garbanzo/
chickpea, lentil, pea) Rice - brown, white, wild,
Basmati, etc Potato starch, potato
flour, sweet potato flour Montina® (Indian Rice
Grass) Nut flours (almond,
hazelnut, pecan) Bean flours (garfava,
romano)
© M. Dennis, S. Case, 2008
*As appeared in Practical Gastroenterology, April 2004.
0
2
4
6
8
10
12
14
Fiber per cup
GF Grains & Their Fiber Content
Iron & Routine Supplementation
~95% of patients w/ celiac disease will resolve their anemia after one year on the gf diet*
50% replete their iron stores in the same time period
A multivitamin/mineral is recommended for those with celiac disease based on age, gender, lab studies and diet history
Men do not need iron in a multivitamin unless they are anemic. Iron supplementation, when needed, should be discontinued when ferritin is normal
If anemia or other significant nutrient deficiencies persist after more than a year on the gluten free diet, assess for hidden gluten intake and refer to celiac-proficient MD
Efficacy of gfd alone on recovery from iron deficiency anemia in adult celiac patients, Am J Gastro, 2001.
Bone Disease At celiac disease diagnosis:
~10-30% have osteoporosis~40% have osteopenia
15% improvement over the first year of treatment (bisphosphonates ~5%)
Hazard ratio for fracture is 1.30 (1.16–1.46)
Vit D/Ca++ deficiency result in greater risk of bone loss, fractures, falls, and perhaps infections, autoimmune diseases and cancer
Meyer D, AJG 2001; McFarlane et al., Gut 1996; West et al., Gastroenterology 2003
Key Points: Celiac Disease & Bone Metabolism
Vitamin D and calcium deficiency are common across the United States – ½ of Americans have suboptimal levels
Vit D/Ca++ absorption may not completely normalize with GFD
Patients with celiac should have adequacy of the Vit D/Ca++ regimen checked after 6 months of GFD We are looking for:
Normal ca, alb, phos25 OHD >30 ng/ml (or 40)PTH <65 (maybe <46)
25(OH)D Is Essential for Calcium Absorption
Adapted from Heaney RP. Am J Clin Nutr. 2004;80(suppl):1706S–1709S. Reproduced with permission form The American Journal of Clinical Nutrition.
Calcium Absorption Plateaus at Serum 25(OH)D Levels 32
ng/mL
0 403224168 645648
Serum 25(OH)D, ng/mL
0.5
0.4
0.3
0.2
0.1
0.0
Calc
ium
Ab
sorp
tion
Fra
cti
on
Bischoff HA et al. J Bone Miner Res. 2003; 18: 343–351.
Heaney RP et al. J Am Coll Nutr. 2003; 22: 142–146.
Barger-Lux MJ et al. J Clin Endocrinol Metab. 2002; 87: 4952–4956.
Holick MF et al. J Clin Endocrinol Metab. 2005;90:3215–3224.
Vitamin D Levels of <30 ng/mL:Prevalent Across Latitudes in the United States
●
●
P = NS for Test of Trend.
N=198/362
(54.7%)
N=342/642
(53.3%)
N=259/532
(48.7%)
National Osteoporosis Foundation:
March 2007 RecommendationsRecommended Intake for Adults ≥50 Years
Calcium Calcium
(mg/day(mg/day))
Vitamin DVitamin D33
(IU/day)(IU/day)
Previous Previous (2003)(2003)11 12001200 400400–800–800
March March 2007 2007 updateupdate22
12001200 800–800–10001000Revised March 13, 2007, after careful
consideration and review of a growing body of evidence that individuals 50 years and older are not getting enough calcium and vitamin D3, both in the United States and
worldwide.21. National Osteoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. Available at: http://www.nof.org/physguide/index.asp. Accessed April 24, 2007.
2. National Osteoporosis Foundation. National Osteoporosis Foundation’s Updated Recommendations for Calcium and Vitamin D3 Intake. Available at: http://www.nof.org/prevention/calcium_and_VitmaminD.htm. Accessed April 24, 2007.
Jill’s Follow-up at 6 months
Weight stableBrother has celiac diseaseFollowing the gluten-free diet carefullyLabs:
Iron, B12 improved; 25 OHD: 37ng/mLtTG: 26 units
Still complaining of mild gas, bloating & loose stool
What do you suspect is the issue now?
Other included: • Peptic ulcer disease•Crohn’s disease• Duodenal cancer• Food allergy•Gastroparesis
“Non-Responsive” Celiac Disease:Persistent or recurrent signs/symptoms despite
confirmed & treated CD. It occurs in ~10% of patients.
Leffler et al. CGH 2006
Refractory Sprue
Persistent small intestinal villous atrophy not responding primarily or secondarily to a strict gluten-free diet.
Wide spectrum of disease•Weight loss is almost always a
presenting symptomOccurs in ~1% of patientsPredominantly treated symptomaticallyPotential for progression to Enteropathy
Associated T Cell Lymphoma (EATL)
Trier JS et al. 1978, 1991, 1998
Small Intestinal Bacterial Overgrowth• Abnormally high bacterial populations in the upper bowel
• May complicate nearly any GI or endocrine disorder including: – celiac disease, diabetes, Crohns, IBS, scleroderma, partially obstructing
lesions, small bowel diverticula, gastroparesis or any intestinal dysmotility syndrome, fistulas, chronic pancreatitis,etc.
• Can lead to carbohydrate, protein, fat malabsorption, inflammation, macrocytic anemia, & toxin production
Most frequent symptoms: •Gas & bloating •Cramps•Weight loss •Diarrhea
Diagnosis: Clinical evaluation and diagnostic testingMost common tool: Breath test Treatment: Antibiotics
www.uptodateonline.com Accessed 10/07
Key Elements in the Management of Celiac Disease
• Consultation with a skilled dietitian• Education about the disease• Lifelong adherence to a gluten-free diet• Identification and treatment of nutritional deficiencies• Access to an advocacy group• Continuous long-term follow-up by a multidisciplinary team
NIH Consensus Development Conference on Celiac Disease, 2004
Celiac Disease Resources
Internet Sites:
• Gluten Intolerance Group of North America; www.gluten.net
• Celiac Disease Foundation; www.celiac.org• NIH:
http//:digestive.niddk.nih.gov/ddiseases/pubs/celiac• www.HealthyVilli.org• www.celiac.com• Celiac Sprue Association of the USA, Inc.;
www.csaceliacs.org• Canadian Celiac Association/L’association
Canadienne de la Maladie Coeliaque; www.celiac.ca• ADA: Celiac Disease; www.nutritioncaremanual.org
and the Evidence Analysis Library
Do’s & Don’ts of Celiac DiseaseDo:
• Think of it (unexplained GI symptoms, anemia, suspicious low BMD, fertility issues, autoimmune diseases)
• Test for it by IgA tTG serology and total IgA• Recommend a biopsy (before starting a GFD!)• Refer to a skilled celiac dietitian• Suggest a local support group• Assess for related conditions such as bone density &
thyroid• Follow up on tTG and symptoms• Treat nutritional deficiencies
Don’t:• Order anti-gliadin antibody serology• Recommend a GFD without a verified diagnosis• Neglect the follow up
CELIAC DISEASE…
it’s a GUT REACTION.
www.bidmc.harvard.edu/celiaccenter