What is the role of component resolved diagnostics (CRD) in managing aeroallergy?

Component-Resolved Diagnostics in Aeroallergy

Component-resolved diagnostics (CRD) should be used selectively in aeroallergy management—specifically when initial skin prick testing or whole allergen-specific IgE results are equivocal, when polysensitization complicates the clinical picture, or when you need to distinguish true sensitization from cross-reactivity to guide immunotherapy decisions. 1, 2

When to Order CRD in Aeroallergy

Initial Diagnostic Approach

• Always begin with skin prick testing (SPT) or serum-specific IgE to whole allergen extracts as your first-line test, guided by clinical history noting timing of symptoms, environmental exposures, and regional aerobiology 1, 2
• SPT remains highly sensitive and specific for aeroallergens and should be the preferred initial method 1
• Never order CRD as a first-line test—this is a critical pitfall that leads to unnecessary costs and diagnostic confusion 2

Specific Indications for CRD in Aeroallergy

• Order CRD when you have polysensitization on initial testing and need to identify which allergens are clinically relevant versus cross-reactive 1, 3, 4
• Use CRD to distinguish genuine sensitization from cross-reactivity to panallergens (such as profilins or Bet v 1 homologues), which may cause positive tests without clinical significance 1, 5, 4
• CRD is particularly valuable when selecting allergens for immunotherapy—it helps identify the primary sensitizing allergen and avoids including clinically irrelevant allergens that could cause new sensitization rather than tolerance 1, 3
• Consider CRD in vernal keratoconjunctivitis when you need to map IgE-mediated hypersensitivity at the molecular level, though note that less than 50% of vernal conjunctivitis cases show specific IgE sensitization 1

How CRD Changes Clinical Management

Impact on Diagnosis

• CRD modifies the conventional diagnosis in approximately 30% of pollen allergy cases—either by detecting new relevant sensitizations (particularly to Olea/olive) or by ruling out clinically irrelevant sensitizations caused by panallergens 5
• In complex polysensitization cases, CRD helps identify the primary allergen causing symptoms versus secondary cross-reactive allergens 1, 3
• CRD provides important risk stratification—sensitization to major allergens like Fel d 1 (cat) and Can f 1 (dog) are associated with higher risk of developing asthma and allergic rhinitis 3

Impact on Immunotherapy Selection

• CRD significantly influences the choice of specific immunotherapy and reduces overprescription by ensuring only clinically relevant allergens are included in the treatment extract 1, 3
• Including allergens without demonstrable specific IgE (non-relevant allergens) may result in new sensitization rather than tolerance induction 1
• Only 32% of patients currently receiving immunotherapy have been studied with CRD beforehand, representing a gap in optimal practice 6

Practical Implementation

The "U-Shaped" Diagnostic Approach

• Follow the European Academy of Allergy and Clinical Immunology's U-shaped approach: start with conventional diagnostics (history, SPT, whole allergen sIgE), add CRD for complex cases, then return to clinical correlation 3
• This prevents overuse of molecular diagnostics while capturing the cases where CRD provides actionable information 3

Interpreting CRD Results

• Positive CRD to storage proteins or major allergens indicates genuine sensitization with higher likelihood of clinical symptoms 2, 4
• Positive results to panallergens (profilins, polcalcins, lipid transfer proteins) often represent cross-reactivity without clinical relevance to that specific allergen 1, 4
• Always correlate CRD results with clinical history—sensitization does not equal clinical allergy 1, 3

Common Pitfalls to Avoid

• Do not order broad CRD panels without clinical justification—select specific components based on suspected allergens from history and initial testing 2
• Avoid using CRD when initial SPT or whole allergen sIgE is clearly negative (effectively rules out IgE-mediated allergy) or clearly positive with strong clinical correlation 2
• Do not assume all CRD platforms are equivalent—different methods (singleplex vs. multiplex microarray) may have varying sensitivities for specific allergens (e.g., ISAC-CRD-89 has deficiencies detecting Salsola and Plantago) 5
• Remember that CRD availability is limited in many hospitals, which restricts practical implementation for many allergists 6

Role in Specific Aeroallergy Conditions

Allergic Rhinitis and Asthma

• CRD helps identify sensitization patterns that predict asthma development, particularly polysensitization to inhalant allergens 3
• Molecular diagnostics can uncover cross-reactivity patterns in patients with idiopathic reactions or complex polysensitization 3

Allergic Conjunctivitis

• In vernal keratoconjunctivitis specifically, CRD in tears and serum may be helpful for mapping IgE-mediated hypersensitivity at the molecular level 1
• However, the association with specific IgE sensitization occurs in less than 50% of vernal conjunctivitis cases, limiting CRD utility 1

Atopic Dermatitis with Aeroallergen Triggers

• When aeroallergens are suspected triggers (seasonal flares, exacerbation after animal contact, dermatitis on exposed surfaces), use SPT or specific IgE first 1
• Atopic patch testing may have higher specificity than SPT for aeroallergens in atopic dermatitis, though standardization remains problematic 1