Blood Testing After Negative Skin Tests in Cough Variant Asthma
The likelihood of blood IgE testing detecting clinically relevant allergies missed by skin testing in cough variant asthma is low, but blood testing should still be performed when clinical suspicion remains high despite negative skin tests. 1
Understanding the Discordance Between Tests
Comparative Sensitivity and Specificity
- Skin prick testing is generally more sensitive than blood IgE testing for detecting allergic sensitization, with sensitivity and specificity both typically exceeding 80% 1
- Blood-specific IgE measurements demonstrate sensitivity of 0.58-0.90 but notably lower specificity of 0.56-0.65 compared to skin testing 1
- When skin prick tests are negative but clinical suspicion remains high, intradermal testing is more sensitive than standard skin prick tests and should be considered before proceeding to blood testing 1
When Blood Tests May Detect Missed Allergens
A small proportion of patients demonstrate discrepant results between blood and skin testing, which justifies blood testing in select circumstances 1:
- Patients taking antihistamines or tricyclic antidepressants that suppress skin test responses 1
- Patients with extensive eczema, dermographism, or urticaria that interfere with skin test interpretation 1
- Patients on beta-blockers or with comorbid conditions precluding skin testing 1
- When standardized allergen extracts used in skin testing have poor sensitivity for specific allergens (particularly certain fungal allergens) 1
Clinical Context for Cough Variant Asthma
Atopic Features and Their Relevance
- Patients with cough variant asthma generally demonstrate less atopy than those with classic asthma, including lower total IgE levels, fewer sensitized allergens, and lower rates of sensitization to common aeroallergens 2
- However, increased allergen sensitization correlates with progression from cough variant asthma to classic asthma with wheezing 2
- Specifically, sensitization to house dust mites and dog dander predicts wheezing development in cough variant asthma patients 2
Diagnostic Limitations of Allergy Testing
Both skin and blood allergy tests have limited diagnostic value for asthma itself and should not be used as primary diagnostic tools 1:
- The low specificity of allergy testing leads to over-diagnosis of allergic asthma, particularly in children with other atopic diseases 1
- A positive allergy test indicates only sensitization, not necessarily clinical allergy (i.e., symptoms with exposure) 3
- Non-allergic cough variant asthma will be under-diagnosed if physicians rely solely on allergy testing 1
Practical Approach
When to Pursue Blood Testing
Order blood-specific IgE testing when:
- Skin testing is negative but clinical history strongly suggests allergic triggers for cough 1
- Patient cannot discontinue interfering medications (antihistamines, certain antidepressants) 1
- Skin conditions prevent reliable skin test interpretation 1
- Specific allergens suspected from history have poor skin test extract quality 1
Interpretation Caveats
- Blood testing offers the advantage of not requiring medication discontinuation and provides more standardized laboratory quality control 1
- Consider testing for total IgE in addition to specific IgE, as the combination may improve sensitivity for detecting allergic disease 1
- Remember that bronchial hyperresponsiveness, not allergen sensitization, is the most important predictor of progression from cough variant asthma to classic asthma 4
Management Implications
- Early inhaled corticosteroid treatment prevents progression to classic asthma regardless of allergy test results 5
- Allergy testing is more useful for phenotyping and planning allergen avoidance strategies after diagnosis than for establishing the diagnosis itself 1
- The presence of sputum eosinophilia (≥3% non-squamous cells) is more diagnostically relevant than allergy testing for confirming eosinophilic airway inflammation in cough variant asthma 1