Residency · Residency · Pediatrics

Celiac Disease and Food Allergy

Overview

Celiac disease and food allergy are distinct immune-mediated conditions triggered by dietary proteins. Celiac disease is an autoimmune enteropathy triggered by gluten in genetically susceptible individuals, with a prevalence of approximately 1% worldwide. IgE-mediated food allergy is an immediate hypersensitivity reaction occurring within minutes to 2 hours, affecting roughly 5-8% of children. Non-IgE-mediated food allergy includes conditions such as FPIES, food protein-induced allergic proctocolitis, and eosinophilic esophagitis. Accurate diagnosis is critical to avoid unnecessary dietary restrictions and ensure appropriate management.

Celiac Disease

Pathophysiology

Gluten (specifically gliadin) from wheat, barley, and rye triggers an immune response in genetically predisposed individuals. HLA-DQ2 is present in 90-95% of celiac patients, with HLA-DQ8 accounting for the remaining 5-10%. These HLA types are necessary but not sufficient for disease development. Tissue transglutaminase (tTG) deamidates gliadin, creating immunogenic peptides that drive a Th1-mediated inflammatory response. This results in villous atrophy and crypt hyperplasia in the small intestine.

Clinical Presentation

The classic presentation includes chronic diarrhea, abdominal distension, and failure to thrive, typically appearing at 6-24 months after gluten introduction. Non-classic presentations include constipation, iron deficiency anemia resistant to oral iron, short stature, delayed puberty, dental enamel defects, recurrent aphthous ulcers, and elevated transaminases. Some patients are identified through screening and are silent or asymptomatic, with positive serology and biopsy findings. Dermatitis herpetiformis is an intensely pruritic papulovesicular rash on extensor surfaces and is pathognomonic for celiac disease.

At-Risk Groups (Screen)

Screening should be performed in first-degree relatives of celiac patients (approximately 10% prevalence), patients with type 1 diabetes (5-10% prevalence), Down syndrome, Turner syndrome, Williams syndrome, autoimmune thyroid disease, and selective IgA deficiency.

Diagnosis

Initial screening uses tissue transglutaminase IgA (TTG-IgA) along with total serum IgA. TTG-IgA has a sensitivity and specificity exceeding 95%. Total IgA must be checked because 2-3% of celiac patients are IgA deficient and will produce false-negative TTG-IgA results. For IgA-deficient patients, TTG-IgG or deamidated gliadin peptide (DGP) IgG should be used instead.

Confirmatory biopsy requires EGD with duodenal biopsies (at least 4 biopsies from the second part of the duodenum and at least 1 from the bulb). The Marsh classification ranges from Marsh 0 (normal) to Marsh 3c (total villous atrophy). The patient must be on a gluten-containing diet at the time of biopsy.

The ESPGHAN biopsy-sparing pathway, available for children only, allows diagnosis without endoscopy when TTG-IgA is at least 10 times the upper limit of normal, endomysial antibody (EMA) is positive on a separate blood draw, HLA-DQ2/DQ8 is positive, and symptoms are compatible. This pathway avoids endoscopy in approximately 50% of symptomatic children.

HLA typing has a high negative predictive value: negative HLA-DQ2/DQ8 essentially excludes celiac disease and is useful when the diagnosis is uncertain.

Treatment

Treatment is a strict lifelong gluten-free diet with complete elimination of wheat, barley, and rye. Oats are generally safe if uncontaminated, but cross-contamination is common. Referral to an experienced dietitian for education and identification of hidden gluten sources is important. TTG-IgA should normalize within 6-12 months on a gluten-free diet and serves as an adherence marker. Repeat biopsy is not routinely needed if the serologic response is adequate. Nutritional deficiencies in iron, folate, vitamin D, calcium, zinc, and B12 should be assessed. Non-responsive celiac disease warrants reassessment of adherence (the most common cause); refractory celiac disease is rare in children.

<image>Celiac disease diagnostic pathway showing initial TTG-IgA screening with total IgA, branching into standard biopsy confirmation versus ESPGHAN biopsy-sparing pathway (TTG >= 10x ULN, positive EMA, compatible symptoms, HLA-DQ2/DQ8), and management with gluten-free diet and serologic monitoring</image>

IgE-Mediated Food Allergy

Epidemiology and Common Allergens

IgE-mediated food allergy has a prevalence of approximately 5-8% in children under 5 years and about 4% in older children and adults. The top 9 allergens (per the FASTER Act) are milk, egg, peanut, tree nuts, wheat, soy, fish, shellfish, and sesame. Milk, egg, wheat, and soy allergies are often outgrown (60-80% by school age), while peanut, tree nut, fish, and shellfish allergies tend to persist, with only about 20% outgrowing them.

Clinical Presentation

Symptoms onset within minutes to 2 hours of exposure. Cutaneous manifestations (urticaria, angioedema, flushing, pruritus) are the most common. GI symptoms include nausea, vomiting, abdominal pain, and diarrhea. Respiratory symptoms include rhinitis, wheezing, stridor, and cough. Cardiovascular involvement (hypotension, tachycardia, syncope) indicates anaphylaxis, a life-threatening multisystem reaction.

Diagnosis

Clinical history is the most important diagnostic tool, identifying the food, timing, symptoms, and reproducibility. Skin prick testing (SPT) is positive when the wheal is 3 mm or more above the negative control. SPT has high sensitivity but moderate specificity, and a positive result does not prove clinical allergy. It cannot be performed while the patient is on antihistamines. Serum specific IgE (sIgE) is a quantitative measurement, with higher levels correlating with likelihood of clinical reactivity. Decision points vary by allergen (for example, peanut sIgE of 14 kU/L or greater indicates more than 95% probability of clinical reaction).

Component-resolved diagnostics (CRD) measures IgE to specific allergenic proteins. For peanut, Ara h 2 is the dominant predictor of clinical allergy, while Ara h 8 (a PR-10 protein) is associated with oral allergy syndrome only. CRD helps distinguish true allergy from cross-reactivity, potentially reducing unnecessary dietary avoidance.

The oral food challenge (OFC) is the gold standard for diagnosis. It involves graded, supervised exposure in a clinical setting and is used to confirm or rule out allergy when history and testing are inconclusive, as well as to document resolution of allergy.

Management

Management centers on strict allergen avoidance with careful label reading and education about cross-contamination. A written emergency action plan should be provided for schools and caregivers. An epinephrine auto-injector must be prescribed for all patients with IgE-mediated food allergy (0.15 mg for children under 25 kg; 0.3 mg for those 25 kg and above), injected into the anterolateral thigh with a repeat dose in 5-15 minutes if symptoms persist. Periodic reassessment with SPT or sIgE helps determine if the allergy has been outgrown. FDA-approved peanut oral immunotherapy (Palforzia) is available for ages 4-17 and desensitizes patients but requires ongoing daily dosing, does not cure the allergy, and carries a risk of anaphylaxis during treatment.

<image>Diagnostic approach to IgE-mediated food allergy showing clinical history assessment, skin prick testing and serum specific IgE interpretation (with decision points for common allergens), component-resolved diagnostics for peanut (Ara h 2 as key component), and oral food challenge as the gold standard confirmatory test</image>

Early Allergen Introduction (LEAP Trial and Beyond)

Key Evidence

The LEAP trial demonstrated that early peanut introduction (4-11 months) in high-risk infants (those with severe eczema and/or egg allergy) reduced peanut allergy by approximately 80% compared to avoidance. The EAT trial explored early introduction of 6 allergenic foods from 3 months; the intention-to-treat analysis was not significant, but per-protocol analysis showed benefit for peanut and egg. The PETIT trial showed that early egg introduction reduced egg allergy in infants with eczema.

Current Guidelines (AAP/NIAID)

For high-risk infants (severe eczema and/or egg allergy), peanut should be introduced at 4-6 months, with consideration of peanut-specific IgE or SPT beforehand. Moderate-risk infants (mild-to-moderate eczema) should have peanut introduced around 6 months. Low-risk infants (no eczema or food allergy) can have peanut introduced freely with other complementary foods. Early introduction of other allergens (egg, milk, tree nuts, fish, wheat, soy, sesame) is also recommended. The key paradigm shift, supported by strong evidence, is that allergenic food introduction should not be delayed.

Implementation Barriers

Barriers include parental anxiety about introducing allergens, confusion about guidelines among primary care providers, limited access to allergists for pre-screening high-risk infants, and cultural and practical barriers to early peanut introduction.

Non-IgE-Mediated Food Allergy

Food Protein-Induced Enterocolitis Syndrome (FPIES)

Acute FPIES presents with profuse, repetitive vomiting 2-4 hours after ingestion of a trigger food, potentially progressing to lethargy, pallor, hypotension, and a shock-like state. Common triggers include milk, soy, rice, and oat. Laboratory findings may show thrombocytosis, methemoglobinemia, and metabolic acidosis. Treatment involves IV fluid resuscitation and ondansetron (0.15 mg/kg IV) for acute episodes; epinephrine is not indicated unless anaphylaxis is suspected. Chronic FPIES presents with intermittent vomiting, chronic diarrhea, and failure to thrive with ongoing exposure. SPT and sIgE are typically negative because this is a non-IgE-mediated process. Diagnosis relies on clinical history and is confirmed by supervised oral food challenge. Most children outgrow FPIES by age 3-5 years.

Food Protein-Induced Allergic Proctocolitis (FPIAP)

FPIAP presents in early infancy (1-4 weeks of age) with blood-streaked stools in an otherwise well-appearing infant. It is most commonly triggered by cow's milk protein through breast milk or formula. Diagnosis is clinical, and stool may show eosinophils. Treatment involves maternal dairy elimination if breastfed, or extensively hydrolyzed or amino acid formula if formula-fed. The condition self-resolves by 12-24 months and is benign.

Eosinophilic Esophagitis (EoE)

Eosinophilic esophagitis is a chronic, immune-mediated esophageal disease characterized by eosinophilic infiltration of 15 or more eosinophils per high-power field. Older children and adolescents present with dysphagia and food impaction, while younger children present with feeding refusal and vomiting. Diagnosis requires EGD with esophageal biopsies (at least 5 biopsies from proximal and distal esophagus). Treatment options include PPI (which may be sufficient), topical swallowed corticosteroids (budesonide, fluticasone), dietary elimination (empiric or directed), and dupilumab (FDA-approved for EoE in patients aged 12 years and older).

<image>Overview of non-IgE-mediated food allergy syndromes comparing FPIES (acute vomiting 2-4 hours post-ingestion, potential shock, IV fluids and ondansetron treatment), FPIAP (bloody stools in well infant, maternal diet elimination), and eosinophilic esophagitis (dysphagia, food impaction, esophageal eosinophilia >= 15/HPF, treated with PPI or topical steroids)</image>

Clinical Pearls

A positive skin prick test or specific IgE does not equal clinical food allergy; always correlate with history, since unnecessary dietary restrictions impair quality of life and nutrition. Component-resolved diagnostics (especially Ara h 2 for peanut) can significantly reduce unnecessary avoidance by distinguishing true sensitization from cross-reactivity. Early peanut introduction in high-risk infants is one of the most impactful preventive strategies in pediatric allergy, and allergenic food introduction should not be delayed. FPIES can mimic sepsis in infants, so this diagnosis should be considered in any infant with profuse vomiting and lethargy 2-4 hours after feeding a new food. Total IgA should always be checked when screening for celiac disease because IgA deficiency causes false-negative TTG-IgA results. Celiac disease and type 1 diabetes frequently co-occur, and T1DM patients should be screened for celiac disease at diagnosis and periodically thereafter.

Key Controversy: Early Peanut Introduction Implementation Barriers

Despite overwhelming evidence from the LEAP trial, implementation of early peanut introduction remains suboptimal. Barriers include parental fear, provider unfamiliarity with guidelines, inconsistent pre-screening recommendations, and lack of allergist access. Some guidelines recommend screening (SPT or sIgE) before introduction in high-risk infants, while others advocate direct introduction at home. Component-resolved diagnostics may help reduce unnecessary avoidance by refining risk assessment. Cost and access to allergists for supervised introduction or food challenges remain challenges. Equity concerns are also important, as guidelines may not account for cultural dietary practices or food availability in diverse populations.

References

• Du Toit G, et al. Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy (LEAP). N Engl J Med. 2015;372(9):803-813.
• Togias A, et al. Addendum Guidelines for the Prevention of Peanut Allergy in the United States (NIAID-Sponsored Expert Panel). J Allergy Clin Immunol. 2017;139(1):29-44.
• Husby S, et al. ESPGHAN Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2020;70(1):141-156.
• Nowak-Wegrzyn A, et al. International Consensus Guidelines for the Diagnosis and Management of FPIES. J Allergy Clin Immunol. 2017;139(4):1111-1126.
• Sampson HA, et al. Food Allergy: A Practice Parameter Update — 2014 (AAAAI/ACAAI/JCAAI). J Allergy Clin Immunol. 2014;134(5):1016-1025.
• Vickery BP, et al. AR101 Oral Immunotherapy for Peanut Allergy (PALISADE). N Engl J Med. 2018;379(21):1991-2001.

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