What is the diagnostic approach for suspected milk or lactose allergy, including the role of serum testing for Immunoglobulin E (IgE) antibodies?

Serum Testing for Milk or Lactose Allergy

Serum specific IgE (sIgE) testing is recommended for diagnosing milk allergy, but it cannot diagnose lactose intolerance, which is a non-immunologic condition requiring different testing. 1

Critical Distinction: Milk Allergy vs. Lactose Intolerance

Milk allergy and lactose intolerance are completely different conditions that require different diagnostic approaches. 2

• Milk allergy is an immune-mediated reaction to milk proteins (casein, whey proteins like alpha-lactalbumin and beta-lactoglobulin) that can be diagnosed with serum IgE testing 1, 3
• Lactose intolerance is a non-allergic condition caused by lactase enzyme deficiency and cannot be diagnosed with IgE testing—it requires hydrogen breath testing or lactose tolerance testing 2
• Children with confirmed milk protein allergy are clinically tolerant to lactose itself and can safely consume lactose-containing products 2

When to Order Serum IgE Testing for Milk Allergy

Order milk-specific IgE testing when the patient has symptoms occurring within minutes to hours after milk ingestion, especially if reproducible on multiple occasions. 1, 4

Specific scenarios where serum testing is particularly useful: 1

• Extensive dermatitis or dermatographism preventing skin prick testing
• Inability to discontinue antihistamines for skin testing
• Very young children where skin testing is challenging

Which Serum Test to Order

Order milk-specific IgE using modern fluorescence-labeled antibody assays (such as ImmunoCAP), not the outdated RAST test. 1, 4

• Test for cow's milk-specific IgE as the primary screening test 4
• Component-resolved diagnostics (testing IgE to specific milk proteins like casein, alpha-lactalbumin, beta-lactoglobulin) may provide additional information but are not routinely necessary 1, 3
• Do NOT order total serum IgE—it has insufficient sensitivity and specificity for diagnosing food allergy 1

Interpreting Serum IgE Results

A positive milk-specific IgE indicates sensitization only, not necessarily clinical allergy, and must be correlated with clinical history. 1, 4

Negative Results (< 0.35 kUA/L):

• High negative predictive value (>95%) effectively ruling out IgE-mediated milk allergy 4
• However, undetectable sIgE occasionally occurs in patients with true IgE-mediated food allergy, so if history is highly suggestive, proceed to oral food challenge 1

Positive Results:

• Higher sIgE levels correlate with increased probability of clinical reactivity, though predictive values vary between studies 1, 4
• Milk-specific IgE > 3 kUA/L in the first year of life predicts persistent milk allergy at age 3 years with 82.6% positive predictive value 5
• Critical caveat: 50-90% of presumed food allergies based on history and positive testing alone are not actual allergies when formally challenged 1, 4

Laboratory Variability Warning:

Different laboratory assay systems (ImmunoCAP, Turbo-MP, Immulite) provide significantly different measurements for the same serum samples. 1

• Predictive values established for one system cannot be applied to another system 1, 4
• Always use the same laboratory system for serial monitoring

Diagnostic Algorithm for Suspected Milk Allergy

1. Obtain detailed history: Focus on timing of symptoms (within minutes to hours), reproducibility with repeated exposures, and specific symptoms (urticaria, angioedema, gastrointestinal symptoms, respiratory symptoms, anaphylaxis) 1

2. Order milk-specific IgE using fluorescence-labeled assay (ImmunoCAP preferred) 1, 4

3. Interpret results in clinical context: 1, 4

   • Negative sIgE + negative history = milk allergy ruled out
   • Positive sIgE + convincing history = likely milk allergy, but confirmation needed
   • Positive sIgE + unclear history = proceed to oral food challenge

4. Confirm diagnosis with oral food challenge when diagnosis remains uncertain—this is the gold standard 1

   • Double-blind placebo-controlled food challenge is preferred 1
   • Single-blind or open challenge acceptable if negative or if positive with objective symptoms correlating with history 1

Tests NOT to Order

Do not order the following tests for milk allergy diagnosis: 1

• Intradermal testing (higher risk of systemic reactions without improved sensitivity) 1
• Total serum IgE (insufficient sensitivity and specificity) 1
• Atopy patch testing (insufficient evidence for routine use in non-contact food allergy) 1

Common Pitfalls to Avoid

• Do not confuse milk allergy with lactose intolerance—they require completely different diagnostic approaches 2
• Do not diagnose milk allergy based solely on positive serum IgE without clinical correlation—sensitization does not equal clinical allergy 1, 4
• Do not use outdated RAST terminology or testing—modern fluorescence assays have replaced this 1
• Do not assume lactose must be avoided in milk-allergic children—lactose itself is safe even in milk protein allergy 2
• Do not compare results between different laboratory systems—they are not interchangeable 1, 4