CELIAC DISEASE/FOOD ALLERGY
| CELIAC DISEASE UPDATE —Maria Oliva-Hemker, MD, Interim Chief, Division of Pediatric Gastroenterology and Nutrition,
Associate Professor of Pediatrics, and Stermer Family Professor of Pediatric Inflammatory Bowel Disease, Johns
Hopkins University School of Medicine, Baltimore, MD
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| Definition of “celiac disease”: immune-mediated enteropathy caused by sensitivity to gluten in genetically susceptible
individuals; not food allergy (not IgE-mediated); classic finding—normally upright long villi of small intestine flattened
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| Prevalence in United States (Fasano et al, 2003): study screened >13,000 individuals; at-risk group had symptoms
consistent with celiac disease or first- or second-degree relatives with celiac disease; prevalence in general population as
high as 1% (ie, 3 million people); prevalence higher for at-risk groups
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Diagnosis
 | Classic: pot-bellied infant with decreased submucosal fat and sagging buttocks; thin irritable child; history of recent exposure
to gluten products for 6 to 12 mo
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| Gastrointestinal (GI) presentation: typically occurs after exposure to gluten (as early as 6 mo of age); signs and symptoms
of malabsorption—chronic diarrhea; abdominal distention from increased gas production; failure to thrive; poor
weight gain; abdominal pain; irritability; vomiting; constipation
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| Non-GI manifestations: most common age of presentation older childhood to adulthood; dermatitis herpetiformis; dental
enamel hypoplasia; osteopenia or osteoporosis without other explanation; short stature; delayed puberty; iron-deficiency
anemia that does not respond to iron therapy (iron absorbed in duodenum; if mucosa flat, absorption impaired);
elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT); joint symptoms; seizures with occipital
calcifications; psychiatric or behavioral presentations; dermatitis herpetiformis—itchy rash on extensor surfaces
of limbs (sometimes on trunk); many patients do not complain of GI symptoms; villous atrophy seen on biopsy; IgA
antibodies between upper layers of skin almost pathognomonic for celiac disease; patients respond to gluten-free diet
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| Asymptomatic presentation
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| Silent: symptoms minimal or absent, but serology positive; damaged mucosa seen on endoscopy; risk factors—first-degree
relative with celiac disease; Down, Turner’s, or Williams syndromes; type 1 diabetes
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| Latent: possible positive serology, normal mucosa, no symptoms; patients may develop mucosal changes in future; triggers
include GI surgery, pregnancy, or GI illness; diagnosis and timing of intervention controversial
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| Complications: weight loss, malnutrition, growth failure; short stature; vitamin and mineral deficiencies (fat-soluble vitamins,
iron, folate, and calcium); osteopenia or osteoporosis; fertility problems; behavioral and psychiatric diagnoses;
neurologic disturbances; GI tract—collagenous gastroenteritis; refractory celiac disease; intestinal lymphoma or adenocarcinoma
of small intestine
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| Pathogenesis: genetic predisposition combined with environmental triggers yields damaged intestinal lining
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| Genetic factors: celiac disease strongly associated with HLA antigens; 95% of patients with celiac disease positive for
genetic markers DQ2 and DQ8, but 40% of healthy population carries same markers; negative finding more reliable than
positive finding; if negative, certain patients not at risk for celiac disease
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| Dietary factors: glutens in wheat; gluten-like proteins in rye, barley, and other grains; rice and oats not necessarily factors
in celiac disease; gluten—components gliadin and glutenin; rich in proline and glutamine residues
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| Tissue transglutaminase (TTG): normal gut enzyme released during injury; plays role in tissue repair by cross-linking
proteins in granulation tissue and stabilizing them; TTG forms bonds between glutamine and other amino acids; TTG
modifies gluten peptides, increasing their affinity with HLA DQ2 and DQ8 epitopes; T-cell- and immune-cell-mediated
process (not IgE-mediated); autoantibodies against TTG correlate with celiac disease
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| Confirm diagnosis before instituting treatment: other problems can cause flattened mucosa; diagnosis mandates
strict gluten-free diet for life; failure to treat has potential for long-term adverse consequences; diagnosis requires small-
bowel biopsy (characteristic small-intestine histology resolves on gluten-free diet)
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| Serologic tests useful to: identify symptomatic individual (biopsy also indicated); screen asymptomatic at-risk individuals;
support diagnosis; monitor dietary compliance
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| Antigliadin antibodies (AGA): fairly inexpensive, but less sensitive and specific than other tests
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| Antiendomysial antibodies (AEMA): IgA-based antibody against connective tissue; preferred over AGA; advantages—
high sensitivity and specificity; disadvantages—operator-dependent; expensive and time-consuming; false-negative
results in individuals with IgA deficiency
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| Anti-TTG antibodies: IgA-based antibody against TTG; advantages—high sensitivity and specificity; enzyme-linked
immunosorbent assay (ELISA) and radioimmunoassay (RIA) less operator-dependent; relatively inexpensive;
disadvantages—false negatives in those with IgA deficiencies; for all antibody tests, sensitivity and specificity decreased
in young children
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| Combination of EMA and TTG: probably best for screening; if AGA performed, EMA and TTG still indicated
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| Serum IgA deficiency may cause false-negative serology: individuals with celiac disease have higher prevalence
of IgA deficiency; AEMA and anti-TTG test alone may be falsely negative (speaker also checks serum IgA
level); if laboratory able to test for IgG antibodies, serum IgA measurement not necessary
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| Endoscopic biopsy: need tissue to confirm diagnosis; scalloping or clear-cut nodularity; normal mucosa (long villi, finger-like
projections); abnormal mucosa (partially atrophied mucosa with blunted villi or total atrophy); increased lymphocytes
(especially in epithelial layer); conglomerate of findings, with serologies, gives diagnosis
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| HLA testing: genetic test; not needed routinely; helpful when diagnosis elusive; some parents refuse to take patient off
gluten-free diet for food challenge; high negative predictive value (can help put family’s at ease)
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| National Institutes of Health consensus guidelines for serologic testing: best tests IgA, TTG, and EMA;
AGA testing not recommended routinely; serologic testing of young children less reliable; age limit unknown, but if
patient <5 yr of age and serologic tests negative, and if index of suspicion high, perform additional testing (eg, endoscopy
with small-bowel biopsy)
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| Indications for screening: GI symptoms; refractory iron-deficiency anemia; growth failure; delayed puberty; type 1
diabetes; Down syndrome; irritable bowel syndrome; autoimmune disease; family history of celiac disease
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| Treatment: strict lifelong gluten-free diet
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| Sources of gluten: avoid gluten-containing grains used in breads, bagels, and other baked goods; other potential
foods—candy; communion wafers; drink mixes; gravy; turkey; soy sauce; ingredients—caramel colors; extracts and
flavorings; other items—lipstick; wheat-based modeling clay; envelopes; some vitamin, herbal, and mineral preparations
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| Gluten-free foods: pure oats not associated with celiac disease; however, oats routinely processed by same machinery
as other grains (cross-contamination high); fruits, vegetables, rice, meat, poultry, fish, nuts, milk, oils, and butter; single
herbs and spices; avoid processed foods
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| Keys to management: 1) consultation with skilled dietitian; 2) education about disease; 3) lifelong adherence to gluten-
free diet; 4) identification and treatment of nutritional deficiencies; 5) access to advocacy group; 6) continuous long-term
follow-up by multidisciplinary team
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| FOOD ALLERGY UPDATE —Hary T. Katz, MD, Staff Physician, Division of Pulmonology/Allergy and Immunology,
Nemours Children’s Clinic, University of Florida, College of Medicine, Jacksonville
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| Definitions: food allergy—adverse immunologic reaction that might be due to IgE- or non–IgE-mediated immune
mechanisms; food intolerance—adverse responses caused by physiologic characteristics of host (eg, lactase deficiency);
not due to immune mechanisms; toxic reaction—may mimic food hypersensitivity; exposure to toxic contaminants
(eg, histamine in scombroid fish poisoning); pharmacologic substances in food (eg, tyramine in aged cheeses)
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| IgE-mediated food allergies: symptoms usually appear within 1 hr of ingestion (rarely after 3 hr); food allergies often
first manifestation of atopic march (eczema, allergic rhinitis, and asthma); approximately one-third of children ≤3
yr of age with moderate to severe eczema have IgE-mediated food allergies
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| Epidemiology: in United States, food allergy leading cause of anaphylaxis treated in emergency department; 30,000 anaphylactic
reactions per year; ≈2000 hospitalizations per year; ≥200 deaths per year; peanuts and tree nuts account for majority
of fatal and near-fatal reactions; prevalence—≈6% of infants <3 yr of age have IgE-mediated food allergy; ≈80%
of children outgrow allergies to milk, eggs, wheat, and soy by 5 yr of age; however, sensitivity to peanuts, tree nuts, and
seafood typically persists throughout adulthood
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Diagnosis
| History: almost 90% of children with history of food allergy develop urticaria and/or angioedema within 2 hr of ingestion;
GI symptoms—occur in ≈50% of those patients (usually vomiting, but patients also can have abdominal pain or diarrhea
[diarrhea typically occurs 4-6 hr later]); respiratory symptoms—occur in ≈25% of patients with IgE-mediated
food allergy; 25% of patients have oral symptoms (eg, lip or oral/palatal itching); eczema—can occur within 48 hr of ingestion
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| Description: commercially available allergen extracts containing purified food protein lightly scratched into skin; if allergen-specific
IgE in skin mast cells, wheal and flare reaction occurs; if extract not available or test negative, fresh food
sometimes used
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| Benefits: test less invasive and less expensive than radioallergosorbent test (RAST); results same day (RAST may take
2 wk)
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| Systemic reactions: risk small, but can occur in patients with history of severe anaphylaxis
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| Positive predictive value: 30% to 50%; use skin testing to confirm clinical suspicion (routine use frustrating, especially in
patients with eczema); select suspicious foods; negative predictive value—>95%; patients must discontinue antihistamines
3 to 5 days before testing; avoid testing eczematous skin sites; size of wheal correlates with risk of having adverse
reaction; performed in children as young as 2 mo of age (patients must be able to sit still for 15 min); response to
inhalant allergens (eg, cats, dogs, dust mites, molds, pollens) typically negative in early infancy
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| More about RAST: fluorescent enzyme immunoassay; measures specific level of allergen-specific IgE per concentration
of blood (range <0.35 to >100 kU/L; classification system of 1-6 not very useful); positive predictive value
30% to 50%; be selective when testing for food allergy (test causes parental anxiety); less sensitive than skin testing,
so negative predictive value not as high; specific levels (kU/L) for milk, eggs, peanuts, and tree nuts help predict risk
of reaction (not severity); specific IgE levels and risk for clinical reaction—well-characterized for milk, eggs, and
peanuts (less for soy and wheat); if RAST response to milk 15 kU/L, child has >95% risk for clinical reaction (speaker
would not offer office challenge); speaker uses RAST to help decide whether to offer open challenge in clinic
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| Food challenge: double-blind placebo-controlled food challenge—gold standard, but not practical clinically (used in
research); open supervised challenge—graded dosing over 2 hr at 15- to 20-min intervals; once reaction occurs or challenge
completed, observe for 2 hr; start with tiny dose and increase gradually(for milk, start with one-quarter teaspoon);
goal cumulative dose of 8 to 10 g protein
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Treatment
| Overview: avoidance number one management strategy; education about food labels essential; dietitian helpful to make
sure patient getting adequate nutrition (especially patients with milk allergy or multiple food allergies); Food Allergy and
Anaphylaxis Network excellent resource (www.foodallergy.org); self-injectable epinephrine and proper instruction in
use essential for all patients with suspected food allergies; consider Medic Alert bracelets for children in preschool or at
school away from parents
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| Epinephrine: treatment of choice for all forms of anaphylaxis; prescribed for all patients with suspected or confirmed
IgE-mediated food allergies; patients with asthma at risk for more severe reactions; if child with asthma has accidental ingestion
and develops symptoms, administer epinephrine; if child has only cutaneous reaction and no history of asthma,
oral antihistamines fine; if >1 system (especially respiratory) or hemodynamic manifestations involved, eg, child pale,
has look of impending doom, and parents frightened, give epinephrine; types of injectors—Epi-Pen and Twinject; 2
dosages available, 0.15 mg and 0.3 mg, based on patient’s weight; preferred route for quickest absorption, vastus lateralis
muscle (upper outer thigh); 2 doses should be carried on-person at all times (Twinject contains 2 doses in single injector);
chance second dose needed probably <20% (in some studies, 35%)
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| Measles, mumps, and rubella (MMR) vaccine: not contraindicated in patients with egg allergy; landmark study (James
et al, 1995)—54 patients with confirmed egg allergy safely received MMR vaccine
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| Influenza vaccine: currently contraindicated in patients with egg allergy
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| Yellow fever vaccine: also contraindicated
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| Peanut allergy: prevalence in young children has doubled in past decade (affects ≈1% of US population); one-third of
patients with peanut allergy also allergic to tree nuts; ≈20% of children outgrow peanut allergy (typically patients have
peanut-specific IgE level <5 kU/L); even if child outgrows it, skin or RAST testing remains positive (patient sensitized
but not clinically allergic); small group of patients redevelops clinical reactivity after passing challenge (consider daily
teaspoon of peanut butter); hot-pressed peanut oil usually does not contain peanut protein (cold-pressed peanut oil does);
casual contact (Sicherer et al, 2003)—33 patients with peanut-specific IgE levels >100 kU/L; no systemic reactions
after exposure to smell of peanut butter (chemical odor differs from aerosolized particles, ie, residue of cracked shells)
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| Eczema and food allergy: many patients with eczema have high IgE levels (>5000 kU/L not uncommon); RAST or
skin testing positive to “everything” (often, falsely positive); if reaction to RAST class 3 or greater, consider 10- to 14-
day elimination of suspected foods, then rechallenge
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| Conclusion: IgE-mediated food allergies increasing (reason unknown); allergen-specific IgE levels help guide decision
whether to offer supervised food challenges; epinephrine treatment of choice for all forms of anaphylaxis and should be
prescribed to all patients with suspected food allergies
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Suggested Reading
[No authors listed]: National Institutes of Health Consensus Development Conference Statement on Celiac Disease,
June 28-30, 2004. Gastroenterology 128:S1, 2005; Farrell RJ, Kelly CP: Diagnosis of celiac sprue. Am J Gastroenterol
96:3237, 2001; Fasano et al: Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a
large multicenter study. Arch Intern Med 163:286, 2003; Gadewar S, Fasano A: Celiac disease: is the atypical really
typical? Summary of the recent National Institutes of Health Consensus Conference and latest advances. Curr Gastroenterol
Rep 7:455, 2005; James JM et al: Safe administration of the measles vaccine to children allergic to eggs. N Engl
J Med 332:1262, 1995; Maki M et al: Normal small bowel biopsy followed by coeliac disease. Arch Dis Child 65:1137,
1990; Perry TT et al: The relationship of allergen-specific IgE levels and oral food challenge outcome. J Allergy Clin
Immunol 114:144, 2004; Reunala T, Collin P: Diseases associated with dermatitis herpetiformis. Br J Dermatol
136:315, 1997; Sampson HA: Clinical practice. Peanut allergy. N Engl J Med 346:1294, 2002; Sampson HA: Utility
of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 107, 891, 2001;
Sicherer SH et al: Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit
dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol 112, 1203, 2003. Simonte SJ et al: Relevance
of casual contact with peanut butter in children with peanut allergy. J Allergy Clin Immunol 112:180, 2003.
Educational Objectives
| The goal of this program is to improve primary care management of celiac disease and food allergy. After hearing and assimilating
this program, the clinician will be better able to:
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| 1. Describe the clinical presentation of celiac disease.
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| 2. Review serologic tests for celiac disease.
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| 3. Discuss management of celiac disease.
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| 4. Diagnose various IgE-mediated food allergies.
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| 5. Choose appropriate therapy for managing food allergy.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of
interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and
not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Katz has participated
in the Speakers’ Bureaus of AstraZeneca and GlaxoSmithKline. The planning committee reported nothing to disclose.
Acknowledgments
Dr. Oliva-Hemker was recorded at Pediatrics for the Practitioner, presented September 27-28, 2007, in Baltimore, MD, by
Johns Hopkins University School of Medicine, Division of General Pediatric and Adolescent Medicine, and Johns Hopkins
Children’s Center, Baltimore, MD, and jointly sponsored by the Maryland Chapter, American Academy of Pediatrics. Dr.
Katz was recorded at Pediatrics for the Primary Care Physician, presented June 29 to July 1, 2007, in Amelia Island, FL,
by Nemours. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this
program.
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