Introduction & Epidemiology

• Definition: Adverse health effect arising from specific immune response occurring reproducibly on exposure to given food.
• Prevalence: Approximately 7.6% to 8% of children in United States.
• Severity: 42.3% of food-allergic children experience severe reactions; 39.9% have multiple food allergies.
• Atopic Comorbidities: High association with asthma, atopic dermatitis (eczema), and allergic rhinitis.

Classification & Immunopathogenesis

Pathophysiological Subtypes of Food Allergy

Allergen Profiles & Natural History

• Major Food Allergens (Top 9): Cow's milk, egg, peanut, tree nuts, soy, wheat, sesame, fish, crustacean shellfish.
• Resolution Rates: Sensitivity to milk and egg resolves in ~85% of children. Sensitivity to peanuts (~20% resolution), tree nuts (~10%), and seafood usually persists into adulthood.

Food Protein-Induced Enterocolitis Syndrome (FPIES)

Pathophysiology & Triggers

• Mechanism: Non-IgE, T-cell-mediated gastrointestinal allergy. Local inflammation characterized by increased TNF-\(\alpha\), elevated circulating mononuclear cells, and decreased intestinal mucosal TGF-\(\beta\) receptor expression.
• Common Triggers:
  • Formula-fed infants: Cow's milk, soy (onset usually 1–4 weeks after introduction).
  • Solid foods: Rice, oats, barley, chicken, turkey, egg white, green peas, peanuts, sweet potatoes, white potatoes, fruits, fish, mollusks.
  • Solid-food FPIES typically presents during weaning at 4–7 months of age.
  • 65% of children with solid-food FPIES have prior milk/soy FPIES; 80% react to multiple foods.

Clinical Subtypes

Acute FPIES

• Latency: 1–3 hours after ingestion of causative food.
• Features: Profuse, repetitive vomiting, marked pallor, extreme lethargy, hypothermia, dehydration.
• Cardiovascular: Hypotension or shock manifests in 15% of acute presentations.
• Delayed phase: Diarrhea (frequently containing blood and mucus) begins 5–10 hours post-ingestion.

Chronic FPIES

• Trigger: Continued daily exposure to offending allergen (e.g., milk or soy formula).
• Features: Intermittent progressive vomiting, chronic diarrhea (sometimes bloody), failure to thrive (FTT), severe weight loss, metabolic acidosis, dehydration.

Diagnostic Criteria (Nowak-Węgrzyn et al.)

• Major Criterion: Repetitive vomiting in the 1–4 hour period after ingestion of suspect food AND absence of classic IgE-mediated cutaneous or respiratory symptoms.
• Minor Criteria (Minimum of 3 required for diagnosis):
  • \(\ge 2\) episodes of repetitive vomiting after eating the same suspect food.
  • Repetitive vomiting 1–4 hours after eating a different food.
  • Extreme lethargy.
  • Marked pallor.
  • Emergency department visit required.
  • Intravenous fluid support required.
  • Diarrhea within 24 hours (usually 5–10 hours).
  • Hypotension.
  • Hypothermia.
• Diagnostic Nuance: Symptoms must completely resolve within hours of eliminating the suspect food. A supervised oral food challenge is highly recommended to confirm diagnosis if only a single episode has occurred (differentiates from common viral gastroenteritis).

Laboratory & Radiologic Evaluation

• Complete Blood Count: Leukocytosis with left shift, thrombocytosis, anemia, eosinophilia.
• Biochemistry: Hypoalbuminemia, metabolic acidosis.
• Co-oximetry: Transient methemoglobinemia.
• Abdominal Radiographs: Intramural gas (mimics necrotizing enterocolitis).

Management of FPIES

Acute Episode Management

• Mild Episode: Attempt oral rehydration (clear fluids/breastfeeding). Consider IM ondansetron (0.15 mg/kg, max 16 mg) for infants \(\ge 6\) months of age.
• Moderate Episode: Administer IM ondansetron. Establish peripheral IV line; deliver normal saline bolus (20 mL/kg), repeat as needed. Monitor vital signs and clinical status.
• Severe Episode (Hypotension/Shock): Rapid IV access; administer rapid normal saline bolus (20 mL/kg), repeat to correct hypotension. Administer IV corticosteroids (methylprednisolone). Methylene blue for methemoglobinemia. Urgent PICU or ED transfer.

Maintenance Management

• Strict elimination of identified food triggers.
• Transition formula-fed infants to casein hydrolysate or amino acid-based formula; chronic symptoms typically resolve in 3–10 days.
• Resolution: Majority resolve by age 3. Supervised oral food challenges evaluate for resolution in a monitored medical facility with resuscitation equipment.

Food-Dependent Exercise-Induced Anaphylaxis (FDEIA)

Pathophysiology & Mechanisms

• Pathogenesis: IgE-mediated hypersensitivity reaction.
• Synergistic trigger: Occurs exclusively when vigorous physical exercise is performed within a few hours of consuming a specific food allergen.
• Clinical Nuance: Ingestion of the food alone or exercise alone does not precipitate any allergic symptoms.

Etiology & Prevention

• Triggers: Wheat (most common), other grains, celery, seafood, or nuts. In some patients, any food ingested prior to exercise can trigger the reaction.
• Prevention: Complete avoidance of the trigger food prior to any physical exertion. Carry self-injectable epinephrine at all times.

Other Pediatric Cell-Mediated Enteropathies

General Diagnostic Evaluation & Management of Pediatric Food Allergies

Standard Diagnostic Modalities

• Clinical History: Pretest probability determination. IgE-mediated symptoms occur rapidly (<2 hours post-ingestion); cell-mediated symptoms are delayed.
• Skin Prick Testing (SPT): Wheal and flare response. High sensitivity (~90%), low specificity (~50%). Larger wheal size correlates with likelihood of clinical allergy, not severity of future reactions.
• In Vitro IgE Testing (FEIA): Phadia ImmunoCAP system. 95%+ PPVs established for 5-year-olds: Egg (\(\ge 7\) kUA/L), Milk (\(\ge 15\) kUA/L), Peanut (\(\ge 14\) kUA/L), Fish (\(\ge 20\) kUA/L). Component-resolved diagnostics (e.g., Ara h 2 stable storage protein vs Ara h 8 labile protein) distinguish true risk of systemic reactions from pollen cross-reactivity.
• Oral Food Challenge (OFC): Gold standard of food allergy diagnosis. Confirms resolution or establishes diagnosis when clinical history and serology are discordant. Perform under strict specialist supervision.
• Unproven Tests (Not Recommended): Food-specific IgG/IgG4, applied kinesiology, lymphocyte activation tests, sublingual or intradermal provocation, cytotoxic tests.

Management Principles

• Dietary Avoidance: Complete allergen elimination. Reading food labels. Avoid cross-contact in food preparation.
• Anaphylaxis Management: Prompt administration of intramuscular epinephrine is the first-line therapy. Repeat doses may be needed.
• Immunotherapy: Oral immunotherapy (OIT), sublingual immunotherapy (SLIT), epicutaneous immunotherapy (EPIT) are emerging to raise threshold tolerance. Standardized peanut OIT is the only FDA-approved option.
• Nutritional Support: Consult with a pediatric dietitian to prevent macronutrient/micronutrient deficiencies and ensure appropriate growth.