What are the indications and modalities for allergy testing?

Allergy Testing: Indications and Modalities

When to Order Allergy Testing

Perform specific IgE allergy testing (skin or blood) only when patients with clinically suspected allergic disease fail empiric treatment, when the diagnosis is uncertain, or when identifying the specific allergen will change management decisions. 1

Specific Clinical Indications

• Failure of empiric therapy: Patients with persistent symptoms despite 2-4 weeks of adequate treatment with antihistamines and moderate-dose intranasal steroids 1
• Uncertain diagnosis: When history and physical examination findings are equivocal or inconsistent with allergic disease 1
• Treatment planning: When identification of specific allergens would guide immunotherapy decisions, allergen avoidance strategies, or medication titration 1
• Severe reactions: Patients with anaphylactic reactions to insect stings require immediate testing 2
• Drug allergies: Penicillin skin testing has high negative predictive value when penicillin administration is indicated with limited alternatives 2

When NOT to Test

• Do not test patients with negative clinical history or symptoms inconsistent with allergic triggers 1
• Do not test without a specific clinical suspicion, as this leads to false-positive results and misleading diagnoses 1, 3
• Do not use IgG antibody testing or total IgE measurement—these provide no useful diagnostic information for allergic rhinitis or food allergy 1

Testing Modalities: Algorithmic Approach

First-Line: Skin Prick Testing

Skin prick/puncture testing is the preferred initial diagnostic test due to superior sensitivity (>80%), immediate results, lower cost, and direct visualization of allergic response. 4, 1

Technical Specifications

• Mechanism: Allergen introduced into epidermis activates cutaneous mast cells, causing histamine release and wheal-flare reaction within 15-20 minutes 1
• Positive result: Mean wheal diameter ≥3 mm greater than negative control 4, 1
• Reading time: Measure at 15-20 minutes after allergen placement 1, 4
• Sensitivity/specificity: Both typically exceed 80% 1, 4

Key Advantages

• Direct observation of body's allergic reaction 1
• More sensitive than blood testing 1, 4
• Less expensive than serum IgE testing 1
• Immediate results allow same-visit counseling 4

Critical Contraindications and Pitfalls

• Discontinue antihistamines before testing—they suppress skin responses and invalidate results 1, 4
• Avoid in patients with widespread eczema, severe dermatographism, or inability to stop antihistamines 4
• Do not use in patients on β-blockers due to increased anaphylaxis risk 1, 4
• Document all medications taken within past week 1, 4
• Always use positive (histamine) and negative controls to validate test 4

Second-Line: Intradermal Testing

Use intradermal testing only when skin prick testing is negative but clinical suspicion remains high, or when increased sensitivity is required. 1, 4

Safety Considerations

• Positive result: Mean wheal diameter ≥5 mm at 15-20 minutes 4
• Never proceed directly to intradermal testing—always perform prick testing first 4
• Six historical fatalities reported from intradermal inhalant testing, five in asthmatics who skipped prick testing 1, 4
• Higher risk of systemic reactions including anaphylaxis 1

Alternative: Blood Testing (Serum-Specific IgE)

Order blood-based allergen-specific IgE testing when skin testing is contraindicated or impractical. 4

Specific Indications for Blood Testing

• Widespread eczema or severe dermatographism preventing accurate skin testing 1, 4
• Inability to discontinue antihistamines 1, 4
• Patients on β-blockers 1, 4
• History suggesting unusually high anaphylaxis risk 4
• Very young children where cooperation is difficult 4

Technical Characteristics

• Mechanism: Enzyme-labeled anti-IgE antibodies detect specific IgE in serum 4
• Sensitivity: Average 70-75% compared to skin prick tests 4
• Advantages: No anaphylaxis risk, not affected by medications, can be used with β-blockers 1, 4
• Disadvantages: Requires reliable laboratory, potential for errors, generally less sensitive than skin testing 1, 4

Advanced Testing: Component-Resolved Diagnostics (CRD)

Order CRD only as second-line testing when initial skin prick or whole allergen serum IgE results are equivocal—not as first-line testing. 4

• CRD identifies specific allergenic proteins within foods, distinguishing genuine sensitization from cross-reactivity 4
• Positive CRD to storage proteins indicates high likelihood of clinical allergy and potential for severe reactions 4
• Can reduce need for oral food challenges by nearly two-thirds 4

Gold Standard: Oral Food Challenge

When diagnosis remains uncertain after testing, oral food challenge is the definitive diagnostic test, though it carries risk and requires specialist supervision. 1, 4

Critical Interpretation Principles

Understanding Test Results

A positive allergy test (skin or blood) indicates only sensitization—the presence of allergen-specific IgE—not necessarily clinical allergy. 3, 5

• Negative predictive value: >95% (highly reliable for ruling out allergy) 1, 4
• Positive predictive value: 40-60% (many false positives) 4, 3
• Clinical correlation is mandatory: Test results must align with patient's symptom history and exposure patterns 1, 6, 3

Common Pitfalls to Avoid

• Testing without clinical suspicion generates false positives and unnecessary dietary restrictions 1, 3
• Measuring only erythema rather than wheal diameter leads to misinterpretation 4
• Ignoring medication interference: Antihistamines, tricyclic antidepressants suppress responses 1, 4
• Using unvalidated tests: IgG testing, total IgE, cytotoxic testing have no role 1
• Ordering broad panels without clinical direction wastes resources and creates confusion 1

Special Populations

Food Allergy in Children

• Initial approach: Eliminate suspected food from diet based on history 1
• If elimination fails: Proceed to IgE-specific antibody or skin testing 1
• Confirm diagnosis: Oral food challenge when testing is equivocal 1
• Do not use: Atopy patch testing, intradermal food testing, or IgG4 testing 1

Atopic Dermatitis

• Food elimination diets may be useful diagnostically, especially for identifying non-IgE-mediated reactions 1
• Atopy patch testing remains investigational with no standardized methodology 1