When to Perform Environmental Allergy Testing After Stopping Antihistamines in Children
Skin prick testing for environmental allergens should be performed at least 3 days after discontinuing second-generation antihistamines in children, as all patients who stopped these medications 3 days before testing demonstrated positive histamine controls. 1
Medication Withdrawal Timeline
Second-Generation Antihistamines (Most Common)
- Discontinue for a minimum of 3 days before skin prick testing 1
- All patients in a retrospective study who stopped second-generation H1-antihistamines 3 days prior had adequate positive histamine controls, indicating reliable test interpretation 1
- These medications (cetirizine, loratadine, fexofenadine, levocetirizine, desloratadine) are the most commonly prescribed antihistamines in children 2
First-Generation Antihistamines
- Discontinue for 3-7 days before testing, as these have more variable suppression of skin test responses 1
- Examples include diphenhydramine, hydroxyzine, and chlorpheniramine 2
- These medications have longer-lasting effects on histamine skin responses compared to second-generation agents 1
H2-Receptor Antagonists
- Discontinue for at least 3 days if clinically feasible 1
- H2-blockers (ranitidine, famotidine) showed odds ratio of 2.91 for negative histamine tests, though this was not statistically significant 1
- These medications showed minimal but measurable interference with skin testing 1
Critical Considerations for Test Interpretation
Antihistamines That Interfere Most
The following medications significantly suppress skin test responses and require discontinuation 1:
- Tricyclic antidepressants: Odds ratio 6.33 for negative histamine test—highest interference 1
- H1-antihistamines: Odds ratio 4.95 for negative histamine test 1
- Benzodiazepines: Odds ratio 5.01 for negative histamine test 1
- Atypical antidepressants (quetiapine, mirtazapine): Odds ratio 3.11 for negative histamine test 1
Medications That Do NOT Require Discontinuation
- SSRIs, SNRIs, and proton pump inhibitors showed no significant interference with skin testing and do not need to be stopped 1
- These medications had 97-100% positive histamine control rates regardless of timing 1
Alternative Testing When Antihistamines Cannot Be Stopped
Serum-Specific IgE Testing
- Use blood testing when antihistamines cannot be discontinued for medical reasons 3
- Serum-specific IgE measurements are not affected by antihistamine use 3
- Blood testing has sensitivity of 0.58-0.90 but lower specificity (0.56-0.65) compared to skin prick testing 3
- The European Respiratory Society notes that skin prick testing is not practical in patients taking antihistamines or other medications that interfere with test interpretation 3
Important Limitation
- Both skin and blood allergy tests should NOT be used as primary diagnostic tools for asthma in children aged 5-16 years 3
- The European Respiratory Society strongly recommends against using skin-prick tests or serum IgE as diagnostic tests for asthma due to low specificity (0.23-0.40 for skin tests) 3
- However, after diagnosis, allergy tests are useful for phenotyping and planning allergen avoidance strategies 3
Common Pitfalls to Avoid
Testing Too Soon After Discontinuation
- Testing before 3 days may yield false-negative results due to persistent antihistamine suppression of histamine wheal response 1
- Even topical antihistamines (5% doxepin cream) suppress histamine skin responses for up to 270 minutes (4.5 hours) 4
Overlooking Interfering Medications
- Always review the complete medication list, not just obvious antihistamines 1
- Psychiatric medications (TCAs, benzodiazepines, quetiapine, mirtazapine) have significant interference and must be discontinued if clinically safe 1
- Document all medications with exact timing relative to testing 5
Misinterpreting Positive Results
- A positive allergy test indicates sensitization, not necessarily clinical allergy 6
- Testing without clinical suspicion of symptom-provoking episodes leads to false positives and over-diagnosis 6
- Correlation with clinical history is essential—positive tests alone do not establish diagnosis 6
Testing in Inappropriate Clinical Contexts
- Skin prick testing is not practical in children with extensive eczema, dermographism, or urticaria 3
- In these situations, proceed directly to serum-specific IgE testing rather than attempting skin testing 3
Practical Algorithm
- Review all medications including antihistamines, psychiatric drugs, and H2-blockers 1
- If second-generation antihistamines only: Stop for 3 days minimum before skin testing 1
- If first-generation antihistamines or interfering psychiatric medications: Stop for 3-7 days if medically safe 1
- If medications cannot be stopped: Proceed with serum-specific IgE blood testing instead 3
- Verify positive histamine control at time of testing to ensure adequate skin reactivity 1
- Correlate all positive results with clinical history before making treatment decisions 6