Transcript nesgna 2009 s pics

Meeting the Nutritional
Needs of Adults with
Celiac Disease
Daniel Leffler, MD, MS
Clinical Research Director
Celiac Center
Beth Israel Deaconess
Medical Center
www.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 Syndrome
Lactose intolerance
Inflammatory Bowel Disease
Small intestinal bacterial overgrowth
Chronic infection
Celiac 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.
Pathophysiology
Step 1:
Gluten Entry into
the Submucosa
Step 2:
Deamidation of
Gluten by Tissue
Transglutaminase
(tTG)
Step 3:
Immune
Activation
Only HLA DQ2
and DQ8 are able
to bind gluten!
*Green, Cellier NEJM 2007
Step 1
Step 2
Step 3
Serologic tests
Celiac Disease is Not Rare
 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
* Talley et al, Am. J. Gastroenterol, 1994
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 female
 Serologic studies suggest slight female
predominance
Signs and Symptoms of Celiac Disease
Can Present at Any Age to Any Specialty
Classic Symptoms
Diarrhea
Iron deficiency anemia
Abdominal Pain
Weight Loss/Failure to
thrive
Fatigue/Lethargy
Bloating/Gas
Dermatitis herpetiformis
Non- Classic Symptoms
Asymptomatic
LFT elevations
Constipation
Aphthous ulcers
Nausea/Vomiting
Heartburn/GERD
Hyposplenia
Pancreatitis
Arthralgias/Myalgias
Neuropathy/Ataxia
Alopecia
Headaches
Osteopenia/Osteoporosis
Dental defects
Fertility problems
Cognitive impairment
Dermatitis Herpetiformis
The skin manifestation of celiac disease
Intensely itchy 2-5 mm blisters
Extensor surfaces: Elbows > buttocks > knees > trunk >
face
Onset late childhood/early adult life
Auto-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 anemia
Neurology: 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 antigliadin antibodies have similar
accuracy to tTG
Celiac Disease: Diagnostic Criteria
•Major criteria:

Consistent small bowel histology

Positive IgA tTG serology
•Other supportive criteria:
 Clinical response to GFD
Histologic response to GFD
 Symptoms, tTG and biopsy relapse with gluten
challenge

Please Note: ALL diagnostic tests normalize on a GFD so DO NOT
start treatment before confirming the diagnosis!
Endoscopic Small Intestinal Biopsy
for 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
Not everyone who feels better on a
GFD has Celiac Disease
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: ???
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
Ferritin: 2.3 LOW
25 OHD:12 LOW
B12: 670
Normal
IgA-tTG: 82 units Normal
HCT: 33.7 LOW
Iron: 22 LOW
Folate: 12 Normal
Zinc: 75 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
Hidden
gluten/cross
contamination
Social and
professional
life
Diet
education
and health
Health
Impact
Cost $$$
Label
reading
Access to GF
foods
Gluten is Everwhere
“Wheat-free” does not necessarily mean “gluten-free.”
Breading
Broth/Bouillon
Candy
Coating/Drink mixes
Communion wafers
Croutons
Marinades
Panko
Pastas
Play-Doh
Processed luncheon meats
Sauces
Dry pet food
Dressing
Flour or cereal products
Gravies
Imitation bacon
Imitation seafood
Lipstick and lip balm
Seasonings
Self-basting poultry
Soup bases
Thickeners (Roux)
Toothpaste
Dental pumice
Medications
A Month in the Life of a Celiac Patient:
Attempting the Gluten-Free Diet
Gluten
Exposure on
a
“GlutenFree” Diet
Restaurant
Crosscontamination
Ate Mislabeled
Food
Ate a Serving of
Pasta Thinking
It Was “Gluten
Free”
Typical
Gluten
Threshold
Time
Persistent
Symptoms &
Inflammation
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
Dietary and Health Concerns
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 CD
 May resolve on treatment w/ GF diet
 Fructose: Increasingly common cause of GI symptoms
 Does not typically resolve on a gluten-free diet
Need:
Low-fat, high fiber, nutrient-rich GF foods, and
free of some common food intolerances
Results of 2005 GF Diet Survey:
Percentage of People with Celiac Disease
Meeting Recommended
Amounts of Nutrients
Women
Fiber (46%)
Grain foods (21%)
Iron (44%)
Calcium (31%)
Men
Fiber (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.
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.
GF Grains & Their Fiber Content
14
12
10
8
6
Fiber per cup
4
2
0
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at
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 celiacproficient 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, phos
25 OHD >30 ng/ml (or 40)
PTH <65 (maybe <46)
Calcium Absorption Fraction
25(OH)D Is Essential for Calcium Absorption
Calcium Absorption Plateaus at
Serum 25(OH)D Levels 32 ng/mL
0.5
0.4
0.3
0.2
Bischoff HA et al. J Bone Miner Res. 2003; 18: 343–351.
Heaney RP et al. J Am Coll Nutr. 2003; 22: 142–146.
0.1
Barger-Lux MJ et al. J Clin Endocrinol Metab. 2002; 87:
4952–4956.
0.0
0
8
16
24
32
40
48
56
64
Serum 25(OH)D, ng/mL
Adapted from Heaney RP. Am J Clin Nutr. 2004;80(suppl):1706S–1709S. Reproduced with permission form The American Journal of Clinical Nutrition.
Vitamin D Levels of <30 ng/mL:
Prevalent Across Latitudes in the United States
N=259/532
(48.7%)
●
N=342/642
(53.3%)
●
N=198/362
(54.7%)
P = NS for Test of Trend.
Holick MF et al. J Clin Endocrinol Metab. 2005;90:3215–3224.
National Osteoporosis Foundation:
March 2007 Recommendations
Recommended Intake for Adults ≥50 Years
Calcium Vitamin D3
(mg/day)
(IU/day)
Previous
(2003)1
March 2007
update2
1200
400–800
1200
800–1000
Revised 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.2
1. 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 D 3 Intake. Available at:
http://www.nof.org/prevention/calcium_and_VitmaminD.htm. Accessed April 24, 2007.
Jill’s Follow-up at 6 months
 Weight stable
 Brother has celiac disease
 Following the gluten-free diet carefully
 Labs:
Iron, B12 improved; 25 OHD: 37ng/mL
tTG: 26 units
Still complaining of mild gas, bloating &
loose stool
What do you suspect is
the issue now?
“Non-Responsive” Celiac Disease:
Persistent or recurrent signs/symptoms despite confirmed &
treated CD. It occurs in ~10% of patients.
Other included:
• Peptic ulcer disease
•Crohn’s disease
• Duodenal cancer
• Food allergy
•Gastroparesis
Other
8%
IBS
18%
Refractory
Sprue
Eating
11% Small
Intestinal Disorder
Bacterial
6%
Overgrowth
6%
Gluten
Exposure
36%
Microscopic
Disaccharidase
Colitis
Deficiency
7%
9%
Leffler et al. CGH 2006
Refractory Sprue
Persistent small intestinal villous atrophy not
responding primarily or secondarily to a strict glutenfree diet.
Wide spectrum of disease
• Weight loss is almost always a presenting
symptom
Occurs in ~1% of patients
Predominantly treated symptomatically
Potential 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 testing
 Most 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 Disease
 Do:
• 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