How can I tell if my infant has a cow's milk protein allergy?

How to Diagnose Cow's Milk Protein Allergy in Infants

The diagnosis of cow's milk protein allergy (CMPA) in infants is primarily clinical, based on symptom pattern recognition followed by a diagnostic elimination diet and subsequent rechallenge to confirm the diagnosis. 1, 2

Clinical Presentation: What Symptoms to Look For

CMPA manifests through three distinct immunologic patterns, each with characteristic symptoms:

IgE-Mediated (Immediate) Reactions

• Acute symptoms appearing within minutes to 2 hours after milk exposure 3
• Skin manifestations: urticaria, angioedema, acute flare of atopic dermatitis 4
• Gastrointestinal symptoms: immediate vomiting, diarrhea 5
• Respiratory symptoms: wheezing, stridor, cough 4
• Anaphylaxis in severe cases (rare but life-threatening) 3

Non-IgE-Mediated (Delayed) Reactions

• Delayed symptoms appearing hours to days after exposure 3
• Gastrointestinal manifestations: chronic diarrhea, blood in stools, vomiting, poor weight gain, irritability 5
• Severe presentations: food protein-induced enterocolitis syndrome (FPIES) with profuse vomiting and lethargy 3
• Hematemesis (unusual but documented presentation) 6
• Dermatological: chronic eczema 4

Mixed IgE and Non-IgE-Mediated

• Eosinophilic esophagitis with feeding difficulties and failure to thrive 3

Diagnostic Approach: The Gold Standard

Step 1: Comprehensive History

• Age of symptom onset: CMPA typically occurs before age 3 years, often in first year of life 6, 5
• Timing of symptoms relative to milk exposure (immediate vs. delayed) 4
• Feeding history: exclusively breastfed (0.5% incidence), formula-fed, or mixed feeding 7
• Family history of atopy increases risk 3
• Pattern of symptoms: persistent vs. intermittent 4

Step 2: Physical Examination Findings

• Growth parameters: assess for failure to thrive or poor weight gain 1, 5
• Skin examination: look for eczema, urticaria, or signs of atopic dermatitis 4
• Abdominal examination: assess for distension or tenderness 4
• Signs of dehydration in severe cases 5

Step 3: Diagnostic Elimination Diet (The Definitive Test)

For breastfed infants:

• Mother eliminates all cow's milk and dairy products (milk, cheese, yogurt, butter, hidden sources in processed foods) from her diet 1, 2
• Expected timeframe for improvement: 72-96 hours to 2 weeks 2
• Continue breastfeeding throughout the elimination period 1, 8

For formula-fed infants:

• Switch to extensively hydrolyzed formula (eHF) as first-line 2
• Use amino acid-based formula (AAF) if symptoms are severe, life-threatening, or if no improvement after 2-4 weeks on eHF 2
• Expected improvement: within 2-4 weeks 2

Step 4: Confirmation by Rechallenge

• After 1-2 weeks of symptom resolution, perform a rechallenge to confirm diagnosis before implementing longer-term dietary restrictions 1, 2
• Reintroduce cow's milk protein under medical supervision 1
• If symptoms recur, diagnosis is confirmed 4, 5
• Do not rechallenge if initial presentation was anaphylaxis or severe life-threatening reaction 1

Role of Laboratory Testing

Laboratory tests are supportive but NOT diagnostic on their own:

Tests That May Support Diagnosis

• Skin prick tests: only indicative, not confirmatory 5
• Serum-specific IgE (RAST/ImmunoCAP): helpful for IgE-mediated reactions but does not rule out CMPA if negative 6, 5
• Patch tests: may help identify delayed reactions 5
• Stool occult blood: can indicate gastrointestinal involvement 6

Important Limitations

• Negative IgE testing does not exclude non-IgE-mediated CMPA 5
• Positive testing alone without clinical correlation is insufficient for diagnosis 5
• The double-blind placebo-controlled food challenge remains the gold standard, though elimination and open rechallenge is the practical clinical standard 4, 5

Critical Pitfalls to Avoid

• Do not diagnose CMPA based solely on laboratory tests without clinical correlation and elimination/rechallenge 5
• Do not skip the rechallenge step before committing to long-term dietary restrictions, as this leads to unnecessary elimination diets 1, 2
• Do not assume all gastrointestinal symptoms are CMPA—exclude other conditions like gastroesophageal reflux, lactose intolerance, or infectious causes 4
• Do not use partially hydrolyzed formulas for treatment of confirmed CMPA—they are inadequate 2
• Do not recommend goat's milk, sheep's milk, or regular soy formula as alternatives due to cross-reactivity 1, 8, 2
• Do not implement overly restrictive maternal elimination diets beyond confirmed allergens, as this compromises maternal nutrition 8, 2

When to Refer to a Specialist

• Severe symptoms or life-threatening reactions requiring immediate specialist input 4
• Symptoms persist despite strict elimination for 2 weeks 8, 2
• Failure to thrive despite appropriate dietary management 1
• Multiple food allergies suspected 2
• Uncertainty about diagnosis or management 4