7.2 Food Allergy, FPIES & Eosinophilic Esophagitis

Immunology Primer and the Big 9

Food adverse reactions divide by mechanism, and the mechanism dictates the testing, the treatment, and the natural history. IgE-mediated food allergy produces symptoms within minutes to 2 hours — hives, angioedema, wheeze, vomiting, and potentially anaphylaxis — because allergen cross-links IgE on mast cells and basophils. Non-IgE-mediated disorders are delayed (hours to days), involve T-cell and other pathways, and present with GI-predominant disease: food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy. Mixed disorders involve both mechanisms — eosinophilic esophagitis (EoE) and atopic dermatitis flares are the examples. The big 9 allergens — milk, egg, peanut, tree nuts, soy, wheat, fish, shellfish, and sesame — account for roughly 90% of food allergy in the United States. Sesame was added by the FASTER Act, with mandatory labeling required since January 1, 2023; the original FALCPA law of 2004 governs plain-language labeling of the other eight on packaged foods.

Diagnosing IgE-Mediated Food Allergy

Diagnosis starts with history: what food, what symptoms, how soon, reproducibility. Serum specific IgE and skin-prick testing demonstrate sensitization, not clinical allergy — positive tests without a compatible history reflect sensitization alone, and indiscriminate large-panel testing leads to over-diagnosis and dangerous over-restriction. Component-resolved diagnostics refine risk (for peanut, Ara h 2 positivity correlates with persistent systemic allergy, while Ara h 8 positivity suggests milder pollen-related reactions). The oral food challenge remains the gold standard, used both to confirm allergy and to document resolution. Epinephrine is the only first-line treatment for anaphylaxis, given intramuscularly into the anterolateral thigh without delay; antihistamines and steroids are adjuncts that do not treat airway or cardiovascular compromise. Every allergic child needs autoinjector training, two available devices, and a written emergency action plan.

Natural History and Prevention

Natural history is allergen-specific: roughly half of children outgrow milk allergy by age 5-10 and the large majority by adolescence; egg follows a similar course; peanut and tree nut allergies persist in about 80-90%, with only around 20% resolving. Prevention flipped from avoidance to early introduction after the LEAP trial, which showed that regular peanut consumption from infancy (4-11 months) in high-risk infants cut peanut allergy development by about 80% — current guidance introduces peanut around 4-6 months in high-risk infants (severe eczema, egg allergy) after evaluation, alongside early introduction of egg and other allergens once solids begin.

Cow's Milk Allergy Management, Baked Milk, and the Formula Ladder

Cow's milk protein allergy (CMPA) is the most common food allergy of infancy, affecting roughly 2-3% of infants, and its management is a formula-selection ladder matched to severity:

1. Extensively hydrolyzed formula (EHF) is first-line for most formula-fed infants with CMPA; the proteins are broken into peptides small enough that about 90% of allergic infants tolerate them. Breastfed infants continue breastfeeding with maternal elimination of milk (and calcium/vitamin D supplementation for the mother).
2. Amino acid-based formula (AAF) is reserved for the roughly 10% who fail EHF, for severe disease (anaphylaxis, EoE, severe FPIES, faltering growth), and when symptoms persist despite maternal elimination in a breastfed infant.
3. Soy formula is an alternative only in infants over 6 months without soy co-allergy; it is not recommended under 6 months for CMPA. Rice-based hydrolyzed formulas are used in some countries.
4. Goat's and sheep's milk are not alternatives — high cross-reactivity with cow's milk protein — and plant milks are nutritionally inadequate as a main drink under 12 months.

The baked milk and baked egg ladder concept recognizes that about 70-75% of milk- and egg-allergic children tolerate the allergen extensively heated in a wheat matrix (a muffin, for example), because heating alters conformational epitopes and the matrix slows absorption. Supervised introduction of baked forms — often via a structured ladder progressing from trace baked amounts to less-heated forms — is associated with accelerated development of tolerance to the unheated food, and regular ingestion appears to shift the immune response. Baked-milk tolerance must be confirmed by challenge under specialist supervision before home introduction, and children who react to baked forms continue strict avoidance.

FPIES — Food Protein-Induced Enterocolitis Syndrome

FPIES is a non-IgE-mediated disorder with two forms. Acute FPIES causes profuse, repetitive vomiting 1-4 hours after ingesting the trigger, often with pallor, lethargy, and later diarrhea; severe episodes progress to dehydration and hypotension, and the picture mimics sepsis — misdiagnosis rates are high because IgE testing is negative and the timing is delayed. Chronic FPIES occurs in young infants fed a trigger daily (milk or soy formula), producing intermittent vomiting, watery diarrhea, and poor growth/faltering weight until the trigger is removed. The most common triggers are milk and soy, and among solid foods notably rice and oats — grains are a classic FPIES trap because they are assumed hypoallergenic. Management is avoidance of the trigger: exclusively breastfed infants rarely have FPIES; formula-fed infants with milk/soy FPIES need an extensively hydrolyzed formula, and about 10-20% with severe or refractory disease require an amino acid-based formula. Acute reactions are treated with IV fluids (and ondansetron in some protocols), not epinephrine, since the mechanism is not IgE-mediated. Most children outgrow FPIES by age 3-5, and resolution is documented with a supervised oral food challenge.

FPIAP — Allergic Proctocolitis

FPIAP is the mildest non-IgE disorder: blood-streaked, mucousy stools in an otherwise thriving, well-appearing infant, typically in the first months of life and classically in the breastfed infant reacting to maternally ingested cow's milk. Management is maternal elimination of milk (with calcium and vitamin D supplementation), expecting stool improvement over 1-2 weeks; soy elimination is added if milk elimination fails, and extensively hydrolyzed formula is used for formula-fed infants. The course is benign — growth is unaffected, anemia is rare — and most infants tolerate reintroduction of milk around 12 months of age (some clinicians trial home reintroduction at 6-12 months given the mild phenotype). Overly broad or prolonged maternal elimination is the main dietitian-facing hazard, not the disease itself.

Eosinophilic Esophagitis, Oral Allergy Syndrome, and Enteropathy

Eosinophilic Esophagitis (EoE)

EoE is a chronic, immune-mediated (mixed IgE/non-IgE) esophageal disease driven largely by food antigens. Symptoms vary by age: infants and young children present with feeding dysfunction — food refusal, slow eating, gagging, poor growth; school-age children report abdominal pain, vomiting, and heartburn; adolescents present with dysphagia and food impaction, sometimes as an emergency. Diagnosis requires symptoms of esophageal dysfunction plus endoscopy with biopsy showing at least 15 eosinophils per high-power field, after other causes (especially GERD) are addressed — PPI-responsive disease is now handled within updated diagnostic frameworks. Endoscopic signs include rings, furrows, white exudates, and strictures.

Treatment has three pillars, often combined:

• Proton pump inhibitors — first-line pharmacotherapy; a substantial minority of patients achieve histologic remission on PPI alone.
• Topical (swallowed) corticosteroids — fluticasone from a multidose inhaler sprayed into the mouth and swallowed, or budesonide mixed into a slurry; effective but disease recurs when stopped.
• Dietary elimination — options range from elemental formula (amino acid-based; most effective, near-complete remission, but difficult) to the six-food elimination diet (milk, wheat, egg, soy, nuts, fish/shellfish), the four-food version (milk, wheat, egg, soy), and two-food (milk and wheat) or milk-only elimination, each followed by endoscopic reassessment and stepwise reintroduction to identify triggers. Milk is the single most common trigger, followed by wheat, egg, and soy. The step-up vs step-down debate concerns whether to start with the broad six-food elimination and relax (step-down) or begin with milk-only/two-food elimination and expand only if needed (step-up); current practice increasingly favors step-up to minimize unnecessary restriction, endoscopies, and nutritional risk.

Oral Allergy Syndrome and Enteropathy

Oral allergy syndrome (pollen-food allergy syndrome) is a mixed/IgE-mediated phenomenon: pollen-sensitized patients (classically birch) experience itching and tingling of the mouth and throat with certain raw fruits and vegetables (apple, carrot, stone fruits) because of cross-reactive proteins - chiefly the PR-10 (Bet v 1 homologue) family, with profilins as a second, separate cross-reactive family. Symptoms stay local because these labile proteins are destroyed by digestion and heat — cooked forms are tolerated — and systemic reactions are uncommon. Food protein-induced enteropathy is a rare non-IgE disorder of chronic diarrhea, malabsorption, and poor growth with mild mucosal injury, usually triggered by milk or soy in infants; it resolves with elimination and is largely outgrown.

Nutritional Adequacy, Labels, and the Team

Elimination diets create predictable gaps that the pediatric dietitian owns. On a milk-free diet, monitor calcium and vitamin D closely — cow's milk is the dominant source for US children — plus protein, riboflavin, B12, and iodine; fortified soy beverage is the usual substitute (not under 12 months), while most other plant beverages are poor protein sources. Wheat elimination risks fiber and B vitamins; multiple-food elimination (as in EoE therapy) demands formal growth monitoring and often supplementation. Growth monitoring at every visit is non-negotiable on any elimination diet, and diets should be challenged and liberalized as soon as tolerance allows — elimination without a re-evaluation plan is a common error. Label reading follows FALCPA plain-language rules (major allergens declared in the ingredient list or a Contains statement), with sesame added under the FASTER Act since 2023; precautionary labels like may contain are voluntary and unregulated, so families need explicit guidance on their interpretation. Management is a collaboration with allergists: the allergist owns testing, challenges, and epinephrine prescriptions, while the dietitian owns avoidance education, substitute foods, label skills, baked-ladder implementation, and nutrition surveillance.