What are the differences between testing for cow's milk allergy and lactose intolerance?

Cow's Milk Allergy vs. Lactose Intolerance Testing

Cow's milk allergy and lactose intolerance require fundamentally different diagnostic approaches: cow's milk allergy is diagnosed through IgE testing (skin prick test or serum-specific IgE) combined with clinical history and oral food challenge, while lactose intolerance is diagnosed through hydrogen breath testing or lactose elimination trials without any immunologic testing. 1, 2

Key Distinction Between the Two Conditions

Cow's milk allergy is an immune-mediated response to milk proteins, whereas lactose intolerance is a non-immunologic metabolic condition caused by lactase enzyme deficiency. 1 This fundamental difference drives completely separate testing strategies:

• Cow's milk allergy triggers immune responses (IgE-mediated or non-IgE-mediated) to milk proteins, causing symptoms like hives, angioedema, wheezing, vomiting, anaphylaxis (IgE-mediated) or chronic diarrhea, blood-streaked stools, and enteropathy (non-IgE-mediated). 1, 2

• Lactose intolerance results from inability to digest lactose sugar, causing bloating, flatulence, abdominal pain, and diarrhea without any immune system involvement. 1, 2

Diagnostic Testing for Cow's Milk Allergy

IgE-Mediated Cow's Milk Allergy Testing

For suspected IgE-mediated reactions (occurring within minutes to 2 hours), begin with skin prick testing (SPT) or serum-specific IgE (sIgE) measurement. 2, 3

• Positive SPT or sIgE indicates sensitization but does NOT confirm clinical allergy—it only demonstrates the presence of IgE antibodies. 2, 4

• Negative tests have high negative predictive value and effectively rule out IgE-mediated allergy. 2

• Definitive diagnosis requires oral food challenge (OFC) when testing results are equivocal or when confirming the diagnosis before implementing strict avoidance. 2, 3, 4

Non-IgE-Mediated Cow's Milk Allergy Testing

For suspected non-IgE-mediated reactions (chronic gastrointestinal symptoms), SPT and sIgE testing are NOT useful. 2, 4

• Diagnosis relies on clinical history, diagnostic elimination diet (1-4 weeks), and supervised oral challenge to confirm symptom recurrence. 2, 3, 5

• Patch testing may detect non-IgE-mediated cow's milk allergy when prick tests are negative—one study found patch testing positive in 44% of challenge-proven cases versus only 14% for prick testing. 4

• Specific presentations like allergic proctocolitis and food protein-induced enteropathy are diagnosed based on clinical symptoms, resolution with elimination, and recurrence following oral challenge. 2

When to Test Children with Atopic Dermatitis

Test children under 5 years with moderate-to-severe atopic dermatitis for cow's milk allergy ONLY if eczema persists despite optimized topical therapy and skin care management, or if there is a reliable history of immediate reaction after milk ingestion. 2 Up to 37% of these children have IgE-mediated food allergy, but skin care optimization must come first. 2

Diagnostic Testing for Lactose Intolerance

Lactose intolerance testing uses completely different methods that assess digestive function rather than immune response:

• Hydrogen breath testing measures hydrogen production after lactose ingestion (elevated hydrogen indicates malabsorption)
• Lactose elimination trial followed by reintroduction to assess symptom resolution and recurrence
• Lactose tolerance test measures blood glucose response after lactose ingestion

No immunologic testing (SPT, sIgE, patch testing) is relevant for lactose intolerance. 1

Critical Pitfalls to Avoid

Never use lactose as a placebo in oral food challenges for patients with suspected milk allergy or lactose intolerance—this can confound results. 1

Do not diagnose cow's milk allergy based solely on positive SPT or sIgE without clinical correlation—sensitization alone does not equal clinical allergy. 1, 2

Do not assume a child with gastrointestinal symptoms after milk has lactose intolerance—in infants and young children, cow's milk allergy (particularly non-IgE-mediated) is far more common than primary lactose intolerance. 1, 2, 5

Recognize that patients can have both conditions simultaneously, though this is uncommon. 1

Practical Testing Algorithm

For Immediate Reactions (Within 2 Hours of Milk Ingestion):

1. Obtain detailed history of reproducible symptoms 2
2. Perform SPT or measure serum-specific IgE 2
3. If positive with convincing history: diagnose IgE-mediated cow's milk allergy 2
4. If negative: cow's milk allergy is ruled out; consider lactose intolerance or other diagnoses 2
5. If equivocal: proceed to supervised oral food challenge 2, 3

For Chronic Gastrointestinal Symptoms:

1. Obtain detailed history focusing on symptom pattern 2, 5
2. Implement diagnostic elimination diet for 1-4 weeks 2, 5
3. If symptoms resolve: perform supervised oral challenge 2, 5
4. If symptoms recur with challenge: diagnose non-IgE-mediated cow's milk allergy 2, 5
5. If symptoms persist despite elimination: cow's milk allergy is unlikely; consider lactose intolerance testing or other diagnoses 5

For Suspected Lactose Intolerance (Older Children/Adults):

1. Implement lactose elimination trial
2. Assess symptom resolution
3. Perform hydrogen breath testing if diagnosis remains uncertain
4. No immunologic testing is indicated 1