What laboratory tests are recommended for diagnosing a cow's milk allergy?

Laboratory Testing for Cow's Milk Allergy

Order cow's milk-specific IgE (sIgE) testing as the primary laboratory test for diagnosing IgE-mediated cow's milk allergy, but recognize that this test alone cannot diagnose clinical allergy and must be interpreted alongside clinical history. 1

Primary Laboratory Test

• Cow's milk-specific IgE (sIgE) is the recommended blood test for identifying IgE-mediated sensitization to cow's milk proteins 1
• Use modern fluorescence-labeled antibody assays (such as ImmunoCAP) rather than the outdated RAST test 1
• This test is particularly valuable when skin prick testing cannot be performed due to extensive dermatitis, dermatographism, or inability to discontinue antihistamines 1

Interpreting Cow's Milk-Specific IgE Results

• **Negative result (<0.35 kU/L)**: Effectively rules out IgE-mediated cow's milk allergy with >95% negative predictive value 2
• Positive result (≥0.35 kU/L): Indicates sensitization only, not necessarily clinical allergy—must correlate with clinical history 1
• ≥2.5 kU/L: 90% positive predictive value for clinical allergy in infants 3
• ≥5 kU/L: 95% positive predictive value for clinical allergy in infants—oral food challenge may not be necessary at this level 3

Critical Caveat About Test Interpretation

Different laboratory assay systems (ImmunoCAP, Turbo-MP, Immulite 2000) provide significantly different measurements for identical serum samples, so predictive values established for one system cannot be applied to another 1, 2

Component-Resolved Diagnostics (Optional Advanced Testing)

• Casein-specific IgE can help predict tolerance to baked milk products—children with high casein IgE levels are less likely to tolerate extensively heated milk in baked goods 4
• Individual milk protein testing (α-lactalbumin, β-lactoglobulin, caseins) may help predict persistence versus transient allergy, but this is not routinely necessary for initial diagnosis 4, 5, 6
• Specific IgE-binding patterns to casein and β-lactoglobulin peptides may predict natural resolution and identify patients more likely to have persistent allergy 4, 6

Tests NOT to Order

• Total serum IgE: Do not order routinely—insufficient sensitivity and specificity for diagnosing food allergy 1
• IgG or IgA antibodies to milk proteins: These cannot distinguish patients with non-IgE-mediated cow's milk protein intolerance from those without intolerance 7
• Atopy patch testing: Should not be used in routine evaluation of food allergy due to lack of standardization and variable sensitivity/specificity 1

Diagnostic Algorithm

1. Start with detailed clinical history: Look for symptoms occurring within minutes to 2 hours after milk ingestion, especially if reproducible on multiple occasions 1, 2

2. Order cow's milk-specific IgE testing using a validated fluorescence-labeled assay system 1

3. Interpret results in clinical context:

   • If sIgE <0.35 kU/L: IgE-mediated allergy effectively ruled out 2
   • If sIgE ≥5 kU/L in infants: Clinical allergy highly likely (95% PPV), may proceed with avoidance without oral challenge 3
   • If sIgE 0.35-5 kU/L: Sensitization present but clinical significance uncertain—consider oral food challenge 1, 3

4. Consider physician-supervised oral food challenge when diagnosis remains uncertain despite testing, as this remains the gold standard 1, 2

Special Considerations for Non-IgE-Mediated Allergy

• Approximately 23.6% of children with cow's milk allergy have non-IgE-mediated disease, defined as positive oral challenge with sIgE <0.35 kU/L and negative skin prick test 1
• For suspected non-IgE-mediated cow's milk protein intolerance (delayed gastrointestinal symptoms), do not order IgG or IgA antibody testing—these cannot diagnose this condition 7
• Diagnosis of non-IgE-mediated allergy relies on clinical history, elimination diet, and supervised reintroduction rather than laboratory testing 1, 7

Common Pitfalls to Avoid

• Do not diagnose allergy based solely on positive sIgE—sensitization does not equal clinical allergy, and correlation with clinical history is mandatory 1
• Do not assume undetectable sIgE excludes allergy if clinical history is highly suggestive—oral food challenge may still be necessary 1
• Do not compare results across different laboratory platforms—predictive values are platform-specific 1, 2
• Do not order IgG testing for milk allergy—this is not validated for diagnosis and cannot distinguish allergic from non-allergic individuals 7