Food Protein-Induced Enterocolitis Syndrome (FPIES)
FPIES is a non-IgE-mediated food allergy diagnosed primarily by clinical history showing repetitive vomiting 1-4 hours after food ingestion, with resolution upon food elimination, and confirmed by oral food challenge when the diagnosis is unclear. 1
Recognition and Diagnosis
Acute FPIES Diagnostic Criteria
Major criterion (required):
- Vomiting within 1-4 hours after ingesting suspect food
- Absence of classic IgE-mediated symptoms (no urticaria, wheezing, or immediate reactions) 1
Minor criteria (need ≥3):
- Second episode of repetitive vomiting after eating the same food
- Repetitive vomiting 1-4 hours after eating a different food
- Extreme lethargy with any suspected reaction
- Marked pallor
- Need for emergency department visit
- Need for intravenous fluid support
- Diarrhea within 24 hours (usually 5-10 hours)
- Hypotension
- Hypothermia 1
Critical distinction: If only a single episode has occurred, perform an oral food challenge to confirm diagnosis, as viral gastroenteritis is common in this age group. FPIES reactions completely resolve within hours, unlike gastroenteritis which lasts several days. 1
Chronic FPIES (Infants <4 months)
Occurs with daily ingestion of cow's milk or soy formula, presenting with:
- Intermittent vomiting and watery diarrhea
- Poor weight gain or failure to thrive
- Hypoalbuminemia (predictive finding) 1
Key diagnostic feature: Symptoms resolve within 3-10 days after switching to hypoallergenic formula, but acute symptoms recur 1-4 hours after reintroduction. This acute-on-chronic pattern distinguishes FPIES from enteropathy, eosinophilic gastroenteritis, or celiac disease. 1
Common Triggers by Age
Infants (<6 months):
- Cow's milk and soy (most common, 20-40% cross-reactivity in US) 1
Older infants (6-12 months):
- Rice and oat (most common solid food triggers)
- Combined rice/oat reactions occur in ~30% of rice-FPIES cases 1
Geographic variation: Fish/shellfish common in Italy/Spain; soy less common outside US 1
Acute Management Algorithm
At Home Assessment
Mild (1-2 episodes vomiting, no/mild lethargy):
- Attempt oral rehydration at home (breastfeeding or clear fluids) 1
Moderate-to-severe (≥3 episodes vomiting with moderate-to-severe lethargy):
- Call 911 or go to emergency department immediately 1
Exception: Any child with history of severe FPIES who ingests trigger food should go to emergency department even without symptoms or with any symptoms regardless of severity. 1
Emergency Department/Hospital Management
Immediate interventions (in order):
Establish IV access and fluid resuscitation: Normal saline 20 mL/kg bolus rapidly; repeat as needed for hypotension 1
Antiemetic (if age ≥6 months):
- IV ondansetron 0.15 mg/kg/dose (maximum 16 mg)
- If IV access delayed: IM ondansetron 0.15 mg/kg/dose (maximum 16 mg) 1
Consider corticosteroids: IV methylprednisolone 1 mg/kg (maximum 60-80 mg/dose) 1
Monitor and correct:
- Acid-base abnormalities
- Electrolyte disturbances
- Methemoglobinemia (if present)
- Vital signs continuously 1
Discharge criteria: After 4-6 hours from reaction onset when patient returns to baseline and tolerates oral fluids 1
Transfer to ICU if: Persistent/severe hypotension, shock, extreme lethargy, or respiratory distress 1
Dietary Management
Formula Selection for Cow's Milk/Soy FPIES
First-line: Extensively hydrolyzed casein-based formula. Continue breastfeeding when possible. 1
If inadequate response (10-20% of cases): Amino acid-based formula 1
Avoid:
- Goat and sheep milk (high protein homology with cow's milk)
- Cross-introduction of soy in cow's milk FPIES without physician supervision (20-40% cross-reactivity in US) 1
May consider: Donkey or camel milk (often tolerated in IgE-mediated cow's milk allergy) 1
Breastfeeding Mothers
Do not recommend routine maternal dietary elimination if infant is thriving and asymptomatic. 1
Maternal elimination required only if:
- Reactions occur after breastfeeding
- Infant has failure to thrive
- Seek immediate allergy specialist consultation and nutritional consultation 1
Oral Food Challenge Protocol
Challenge Setting
Hospital/monitored setting with IV access immediately available:
- All patients with history of severe FPIES (mandatory) 1
Physician office (with caution):
- Only patients with no history of severe reactions
- Recognize that future reaction severity cannot be predicted 1
Challenge Dosing
Initial dose: Maximum 3 g protein or 10 g total food (100 mL liquid) 1
Observation: 4-6 hours after ingestion 1
Modified approach for high-risk patients:
- Lower starting doses
- Longer observation between doses
- Gradual administration if food-specific IgE detectable 1
Positive Challenge Criteria
Major criterion (required):
- Vomiting 1-4 hours after ingestion without IgE-mediated symptoms 1
Minor criteria (need ≥2):
- Lethargy
- Pallor
- Diarrhea 5-10 hours post-ingestion
- Hypotension
- Hypothermia
- Neutrophil count increase ≥1,500 above baseline 1
Important caveat: Rapid ondansetron use may prevent minor criteria (repetitive vomiting, pallor, lethargy), so treating physician may diagnose FPIES even if only major criterion met. For research purposes, adhere to stringent criteria. 1
Common Pitfalls
Misdiagnosis as viral gastroenteritis or sepsis: FPIES resolves within 24 hours versus several days for gastroenteritis. Laboratory findings (leukocytosis with left shift, thrombocytosis) often trigger sepsis workup. 1, 2
Assuming single trigger: Patients can have multiple triggers; 30% with rice-FPIES also react to oat. 1
Premature challenge: Reintroduce trigger foods only under physician supervision, not at home. 1
Overlooking nutritional risk: Children with ≥3 FPIES triggers are at increased risk for poor weight gain and food aversion. 3
Prognosis
Favorable natural history: Most cases resolve by age 3-5 years. 4
Exception: Fish-FPIES has lower resolution rates and may persist into adulthood. 5, 4
No fatalities reported despite potential severity of reactions. 4