Algorithm for Ordering Component-Resolved Diagnostics in Allergy
Component-resolved diagnostics (CRD) should be ordered as a second-step test when initial skin prick testing (SPT) or specific IgE (sIgE) results fall in the equivocal range, specifically when SPT wheal diameter is 3-8 mm or whole allergen sIgE is 0.35-15 kUA/L, to reduce unnecessary oral food challenges and improve diagnostic precision. 1
Step 1: Initial Diagnostic Approach
- Begin with detailed clinical history focusing on timing of symptoms (within minutes to hours after exposure), reproducibility of reactions, quantity of food consumed, and whether the food was cooked or raw 1
- Perform SPT or measure whole allergen sIgE first as the initial diagnostic test, directed by clinical history rather than ordering broad panels 1
- Recognize that SPT and sIgE alone detect sensitization, not clinical allergy—they have high sensitivity and negative predictive value but low positive predictive value 1
Step 2: When to Order Component-Resolved Diagnostics
Order CRD in the following specific scenarios:
- When initial tests are equivocal: SPT wheal 3-8 mm or sIgE 0.35-15 kUA/L for the whole allergen 1
- In polysensitized patients to distinguish genuine sensitization from cross-reactive sensitization 2, 3
- When predicting severity of reactions, particularly risk of anaphylaxis versus mild local reactions 2, 3
- Before considering specific immunotherapy to identify the triggering allergen components 4
Step 3: Specific Component-Resolved Diagnostic Panels by Allergen
For peanut allergy:
- Order Ara h 2-specific IgE as the primary component—this is the most predictive marker for clinical peanut allergy and severe reactions 1, 5
- Consider adding Ara h 9 in combination with Ara h 2, which together provide sensitivity of 84% and specificity of 90% 5
- Calculate the ratio of Ara h 2 sIgE to whole peanut sIgE—a ratio ≥0.6 predicts patients at risk for severe reactions/anaphylaxis 5
- Using Ara h 2 in a two-step algorithm (after initial SPT or whole peanut sIgE) reduces the need for oral food challenges by almost two-thirds 1
For other common allergens:
Step 4: Interpreting Component-Resolved Diagnostic Results
Positive CRD to storage proteins or specific risk markers:
- Indicates genuine sensitization and high likelihood of clinical allergy with potential for severe reactions 2, 5
- Proceed with strict avoidance and consider oral food challenge only in controlled settings if diagnosis confirmation is essential 1
Positive whole allergen sIgE but negative CRD to major components:
- Suggests cross-reactive sensitization rather than genuine allergy 2, 3
- Consider oral food challenge to confirm tolerance, as 90% of peanut-tolerant patients have negative Ara h 2 and Ara h 9 despite positive whole peanut tests 5
Positive CRD to cross-reactive carbohydrate determinants (CCD) only:
- Strongly suggests clinical tolerance despite positive conventional tests—CCD sensitization is found exclusively in tolerant patients 5
Critical Pitfalls to Avoid
- Never order CRD as a first-line test—it should follow initial SPT or sIgE testing guided by clinical history 1
- Do not order broad CRD panels without clinical justification—select components based on the suspected allergen from history 1, 6
- Recognize that CRD availability is limited to specialized centers in many countries and may not be accessible in resource-limited settings 1
- Understand that different laboratory assay systems provide significantly different measurements—predictive values from one system cannot be applied to another 7, 6
- Remember that 50-90% of presumed food allergies are not confirmed when formally tested, so avoid over-diagnosis based on testing alone 1, 7