What is the recommended initial evaluation and laboratory workup for a patient suspected of Immunoglobulin E‑mediated allergy?

Laboratory Workup for Suspected IgE-Mediated Allergy

Primary Recommendation

Order allergen-specific serum IgE testing as your primary laboratory test, directed by clinical history, using modern fluorescence-labeled antibody assays such as ImmunoCAP for optimal accuracy. 1, 2

Initial Clinical Assessment

Before ordering any laboratory tests, obtain a detailed medical history focusing on:

• Timing of symptoms: Reactions occurring within minutes to 2 hours after allergen exposure are characteristic of IgE-mediated allergy 1, 3
• Reproducibility: Symptoms that occur consistently with repeated exposures to the same allergen strengthen the diagnosis 1, 3
• Symptom pattern: Look for urticaria, angioedema, respiratory symptoms (wheezing, rhinorrhea), gastrointestinal symptoms (nausea, vomiting), or anaphylaxis 4

Laboratory Testing Algorithm

Step 1: Allergen-Specific Serum IgE Testing

• This is your first-line laboratory test for confirming IgE-mediated sensitization 1, 2
• Select specific allergens to test based on clinical history—do not order broad panels indiscriminately 4, 1
• A negative result (<0.35 kUA/L) effectively rules out IgE-mediated allergy with high negative predictive value 1, 3
• Higher allergen-specific IgE levels correlate with increased probability of clinical reactivity, though thresholds vary by allergen 1, 2

Step 2: Skin Prick Testing (Alternative or Complementary)

• Skin prick testing can be performed as the initial technique or alongside serum IgE testing 4, 1, 5
• Advantages: Results available in 15-20 minutes, tests multiple allergens simultaneously, less expensive than serum testing 6, 5
• A positive test is defined as a wheal ≥3 mm greater than negative control with accompanying flare 4, 7
• Skin prick tests have high sensitivity (70-75%) and high negative predictive value but lower specificity 4

Tests You Should NOT Order

Total Serum IgE

• Do not order total serum IgE for allergy diagnosis—it lacks specificity for individual allergens and does not help diagnose clinical allergy 4, 1

Intradermal Testing

• Do not use intradermal testing for food allergy diagnosis—it carries higher risk of systemic reactions without providing additional diagnostic benefit for protein-induced allergies 4, 1
• Limited utility exists only for certain respiratory allergens, not for routine food allergy evaluation 4, 1

Atopy Patch Testing

• Do not order atopy patch testing for routine evaluation of non-contact allergies—it is not recommended for standard allergy workup 1, 2

Critical Interpretation Principles

Never Diagnose on Laboratory Tests Alone

• Laboratory tests confirm sensitization, not clinical allergy—you must correlate positive results with clinical symptoms 1, 3, 2
• Approximately 50-90% of presumed food allergies are not true allergies when properly evaluated 3
• Many patients have positive tests without clinical symptoms—sensitization does not equal clinical allergy 1, 2

When Results Are Equivocal or Contradictory

• Consider oral food challenge (for food allergies) as the gold standard for definitive diagnosis when history and laboratory tests are inconclusive 3, 8
• In specialized centers, component-resolved diagnostics can be used to measure IgE to specific allergen components (e.g., Ara h 2 for peanut, Ana o 3 for cashew) 1, 3

Common Pitfalls to Avoid

• Do not switch between different laboratory assay systems—they provide significantly different measurements for the same samples, and predictive values cannot be transferred between systems 1, 2
• Do not test patients currently taking antihistamines if planning skin prick testing—these medications must be discontinued based on their half-life (typically 3-10 days before testing) 7
• Do not perform skin testing within the first week after anaphylaxis—there may be a refractory period affecting test accuracy 7
• Do not test for allergens unrelated to clinical history—this leads to false positive results and unnecessary dietary restrictions or avoidance measures 4, 1

Special Considerations for Specific Allergen Categories

For Food Allergies

• Start with allergen-specific IgE or skin prick testing to common food allergens suggested by history 4, 3
• Fresh food testing may be more sensitive for oral allergy syndrome or when commercial extracts don't correlate with history 4

For Inhalant Allergies (Indoor/Outdoor)

• Test for dust mites, animal dander, cockroach, molds (indoor) based on perennial symptoms 2
• Test for tree, grass, weed pollens, outdoor molds based on seasonal symptom patterns 2

For Drug Allergies

• Penicillin skin testing is indicated for patients with history of anaphylaxis or recent suspected IgE-mediated reactions 4
• Serum-specific IgE has lower sensitivity (19.3%) compared to skin testing (30.7%) for drug allergy evaluation 4