Overview
Definition:
Non-IgE mediated food allergies involve immune responses not primarily driven by IgE antibodies, leading to delayed and diverse clinical manifestations
Food Protein-Induced Enterocolitis Syndrome (FPIES) is a classic example, characterized by gastrointestinal distress, while Eosinophilic Esophagitis (EoE) is a chronic immune-mediated esophageal disease triggered by food antigens, leading to eosinophilic infiltration and esophageal dysfunction
Both are distinct from IgE-mediated reactions like urticaria or anaphylaxis.
Epidemiology:
FPIES is more common in infants and young children, affecting approximately 0.3% to 0.7% of infants
Prevalence is higher with introduction of solid foods
EoE prevalence is increasing, with estimates ranging from 1 in 1,000 to 1 in 10,000 children, and it is a leading cause of food-responsive dysphagia in children and adults.
Clinical Significance:
Distinguishing between FPIES and EoE is crucial for accurate diagnosis and management
Misdiagnosis can lead to prolonged suffering, malnutrition (FPIES), or esophageal strictures and fibrosis (EoE)
Understanding these non-IgE mechanisms is vital for pediatric residents preparing for DNB and NEET SS examinations, as these conditions are frequently tested due to their diagnostic challenges and management complexities.
Clinical Presentation
Symptoms:
FPIES (Acute): Profuse vomiting, pallor, lethargy, diarrhea (often bloody) occurring 1-3 hours after ingestion
FPIES (Chronic): Poor weight gain, recurrent vomiting, diarrhea, abdominal distension, constipation
EoE: Dysphagia, vomiting, abdominal pain, food impaction, failure to thrive, reflux symptoms refractory to PPIs
In infants, symptoms can mimic FPIES (vomiting, poor feeding).
Signs:
FPIES (Acute): Dehydration, shock, hypothermia, pallor, lethargy
FPIES (Chronic): Growth faltering, distended abdomen
EoE: Esophageal rings or exudates on endoscopy, often normal or subtle physical exam findings
Signs of atopy (eczema, asthma, allergic rhinitis) may be present in both conditions but are more consistently associated with EoE.
Diagnostic Criteria:
FPIES (Adapted Consensus): A history of symptoms occurring after ingestion of a specific food trigger
Positive food challenge (reproduction of symptoms)
Exclusion of other causes
EoE (Consensus Guidelines): Chronic esophageal dysfunction (dysphagia, vomiting, abdominal pain)
Histologic evidence of eosinophilic inflammation (≥15 eosinophils per high-power field in esophageal biopsies)
Exclusion of other causes of esophageal eosinophilia (e.g., GERD, EoE treated with PPIs).
Diagnostic Approach
History Taking:
Detailed dietary history including timing of food introduction, specific food triggers, and symptom onset relative to ingestion
Quantify vomiting, stool frequency, and presence of blood
For EoE, inquire about dysphagia, food impaction, and reflux symptoms
Assess for atopic history (eczema, asthma, allergic rhinitis)
Ask about failure to thrive or poor weight gain.
Physical Examination:
Assess hydration status, vital signs, and growth parameters (weight, height, head circumference)
Examine for signs of malnutrition
Assess for atopic stigmata (eczema, wheezing)
Palpate abdomen for distension or tenderness
A thorough oral examination for signs of candidiasis or other lesions is important.
Investigations:
FPIES: No specific diagnostic tests
diagnosis is clinical and confirmed by oral food challenge
Allergy testing (skin prick tests, specific IgE) is typically negative for FPIES triggers
EoE: Upper endoscopy with biopsies is the gold standard
Biopsies from proximal and distal esophagus are mandatory for histologic evaluation
Standard allergy testing (skin prick tests, specific IgE) can identify comorbid IgE-mediated allergies but is not diagnostic for EoE
PPI trial can help differentiate from GERD but does not exclude EoE if symptoms persist
Total IgE and eosinophil counts may be elevated but are non-specific.
Differential Diagnosis:
FPIES: IgE-mediated food allergy, gastroenteritis, sepsis, surgical emergencies (intussusception, volvulus), cow's milk protein intolerance (non-IgE), lactose intolerance
EoE: Gastroesophageal reflux disease (GERD), infectious esophagitis, achalasia, eosinophilic gastroenteritis, other causes of dysphagia.
Management
Initial Management:
FPIES (Acute): Aggressive fluid resuscitation to correct dehydration and shock
Antiemetics may be used cautiously
If severe, hospitalization is necessary
FPIES (Chronic): Avoidance of trigger foods
Nutritional support to correct malnutrition
Gradual reintroduction of trigger foods under medical supervision
EoE: Dietary elimination therapy is the cornerstone
Removal of trigger foods based on clinical suspicion or allergy testing
Proton Pump Inhibitors (PPIs) can reduce esophageal eosinophilia and improve symptoms in a subset of patients
Esophageal dilation may be required for strictures.
Medical Management:
FPIES: Avoidance of the offending food is the primary treatment
For chronic FPIES, gradual reintroduction is guided by a physician
EoE: Topical corticosteroids (e.g., fluticasone, budesonide) swallowed and not inhaled are effective for reducing eosinophilic inflammation
Doses vary based on formulation and patient age
PPIs can be used as first-line or adjunctive therapy
Antihistamines are not effective for EoE.
Surgical Management:
Generally not indicated for FPIES or EoE
Esophageal dilation is a procedural intervention, not surgical, and is used for significant strictures in EoE that do not respond to medical therapy.
Supportive Care:
FPIES: Close monitoring of hydration and nutritional status
Parental education on trigger identification and management
EoE: Nutritional counseling for dietary restrictions
Education on medication administration (swallowed steroids)
Management of comorbidities like asthma and eczema
Long-term follow-up to monitor disease activity and progression.
Complications
Early Complications:
FPIES (Acute): Severe dehydration, hypovolemic shock, electrolyte imbalances, metabolic acidosis, failure to thrive, intestinal obstruction (rare)
EoE: Food impaction, esophageal strictures, esophageal dysmotility.
Late Complications:
FPIES (Chronic): Persistent failure to thrive, significant growth deficits, developmental delays
EoE: Progressive esophageal remodeling with fibrosis, stricture formation, potentially leading to achalasia-like symptoms, increased risk of dysphagia and aspiration.
Prevention Strategies:
FPIES: Careful introduction of solid foods, particularly common triggers like grains and dairy
Prompt recognition and management of acute episodes
EoE: Early diagnosis and adherence to dietary management and medical therapy can prevent progressive esophageal damage
Identifying and managing comorbid atopic conditions may also play a role.
Prognosis
Factors Affecting Prognosis:
FPIES: Age at onset, severity of symptoms, type of trigger food, adherence to avoidance
Many children outgrow FPIES by school age
EoE: Duration of untreated disease, adherence to therapy, extent of esophageal remodeling, presence of comorbidities
EoE is often a lifelong condition.
Outcomes:
FPIES: Generally excellent, with most children outgrowing the condition
Chronic FPIES can be managed effectively with avoidance and nutritional support
EoE: Variable
With appropriate management, symptoms can be controlled and disease progression slowed
However, complete remission is rare, and lifelong monitoring and therapy are often necessary.
Follow Up:
FPIES: Regular growth monitoring
Re-evaluation of trigger foods as per physician's guidance, often with gradual reintroduction in later childhood
EoE: Regular follow-up with pediatric allergist/gastroenterologist
Endoscopic surveillance may be required to assess treatment response and disease activity
Monitoring for complications such as strictures and malnutrition.
Key Points
Exam Focus:
Differentiate between IgE-mediated and Non-IgE mediated food reactions
Key features of FPIES (delayed, GI symptoms, negative allergy tests) and EoE (dysphagia, eosinophilic infiltration, food trigger)
Understanding the diagnostic workup and management strategies for both
Recognizing EoE on histology (≥15 eos/HPF) and FPIES on clinical presentation/food challenge
Importance of dietary elimination and swallowed corticosteroids in EoE management.
Clinical Pearls:
Always consider FPIES in an infant with recurrent vomiting and diarrhea, especially after trying new foods
Remember that allergy tests are typically negative in FPIES
In EoE, symptoms can mimic reflux, but are often refractory to PPIs and associated with dysphagia
Esophageal biopsies are crucial for EoE diagnosis
Swallowed fluticasone is a key treatment for EoE
FPIES is often outgrown
EoE is typically chronic.
Common Mistakes:
Attributing FPIES symptoms solely to viral gastroenteritis or IgE-mediated allergy
Over-reliance on IgE testing for FPIES diagnosis
Failing to biopsy the esophagus in suspected EoE cases
Prescribing inhaled steroids instead of swallowed steroids for EoE
Not considering EoE in children with persistent dysphagia or food refusal
Underestimating the impact of chronic inflammation in EoE on esophageal structure.