How to Determine Milk Allergy
Milk allergy diagnosis requires a detailed clinical history of reproducible symptoms following milk exposure, combined with either skin prick testing (SPT) or specific IgE (sIgE) testing to demonstrate sensitization, followed by confirmation with an oral food challenge when the diagnosis remains uncertain. 1
Diagnostic Approach
Step 1: Clinical History Assessment
Document the following specific details:
- Timing of symptoms: IgE-mediated reactions occur within minutes to 2 hours after milk ingestion 1
- Type of symptoms:
- Reproducibility: symptoms must occur consistently with milk exposure 1
- Age of onset: typically presents in the first year of life 1
Critical distinction: Milk allergy is immune-mediated and differs from lactose intolerance, which causes bloating, flatulence, and diarrhea due to lactase deficiency without immune involvement 1
Step 2: Allergy Testing
For IgE-mediated milk allergy:
- Skin prick testing (SPT) or serum-specific IgE (sIgE) should be performed 1
- A positive test indicates sensitization but does NOT confirm clinical allergy 1
- Negative tests have high negative predictive value and can help rule out IgE-mediated allergy 1
- Different laboratory systems (ImmunoCAP, Turbo-MP, Immulite) provide different measurements; predictive values from one system cannot be applied to others 1
Important caveat: In Danish cohorts, 54% of confirmed milk allergy was IgE-mediated while 46% was non-IgE-mediated 1. For non-IgE-mediated reactions, SPT and sIgE are typically negative 1.
Atopy patch testing (APT) is NOT recommended for routine evaluation of milk allergy due to lack of standardization and variable sensitivity/specificity 1
Step 3: Elimination Diet
Step 4: Oral Food Challenge (Confirmation)
Gold standard: Double-blind, placebo-controlled food challenge (DBPCFC) 2, 4, 5, 6
In clinical practice:
- Open challenges under medical supervision are commonly used except when symptoms are severe (e.g., anaphylaxis) 3, 5
- Open challenges can overestimate milk allergy and should be used to reject rather than confirm diagnosis 4
- For definitive diagnosis, DBPCFC is mandatory 4
Challenge protocol considerations:
- Perform in a medically supervised setting with emergency equipment available 5
- Contraindicated if recent severe anaphylaxis 3
- For non-IgE-mediated allergic proctocolitis with classic history and symptom resolution on elimination, many experts believe oral challenge is not required 1
Special Diagnostic Considerations
Non-IgE-Mediated Presentations
Allergic proctocolitis:
- Diagnosis based on: medical history, resolution with elimination, and recurrence following oral challenge 1
- Presents as mucoid, blood-streaked stools in otherwise healthy infants 1
- Colonoscopy/biopsy not generally necessary but shows mucosal edema with eosinophil infiltration if performed 1
Food protein-induced enteropathy:
- Presents with chronic diarrhea, steatorrhea (80% of cases), weight loss, and growth failure 1
- Diagnosis based on clinical symptoms, resolution with elimination, and recurrence following oral challenge 1
Treatment
Primary management: Strict elimination of cow's milk protein from the diet 2, 3, 4
Formula substitutes for infants:
- Extensively hydrolyzed whey or casein formulas are first-line 2, 4, 5
- Amino acid-based formulas rarely indicated 4
- Soy-based formulas may be used in resource-limited settings 3
Emergency preparedness for IgE-mediated allergy:
- Prescribe epinephrine autoinjector for severe reactions 1
- Prescribe antihistamines for mild reactions 1
Natural History and Re-challenge
- Most children develop tolerance by 2-3 years of age for non-IgE-mediated disease 1
- Majority regain tolerance within first 5 years for IgE-mediated disease 1, 4
- Re-challenge timing: Attempt reintroduction every 6 months after initial year of elimination 3
- Use graded milk ladder approach for reintroduction at home or supervised in hospital depending on severity 5