What blood work is necessary to diagnose an allergic reaction in the emergency department?

Blood Work for Diagnosing Allergic Reactions in the Emergency Department

The primary blood test for diagnosing an allergic reaction in the ED is serum mast cell tryptase, which should be drawn as soon as feasible during resuscitation (ideally within the first 1-2 hours), followed by a second sample at 1-2 hours after symptom onset, and a third baseline sample at 24 hours or during convalescence. 1

Timing of Tryptase Sampling

The timing of blood draws is critical for diagnostic accuracy:

• First sample: Draw as soon as feasible after resuscitation has started—do not delay resuscitation to obtain the sample 1
• Second sample: Obtain at 1-2 hours after the start of symptoms 1
• Third sample: Collect at 24 hours or during convalescence to establish baseline tryptase levels, as some individuals have naturally elevated baseline levels 1
• All samples should be labeled with exact time and date 1

Interpretation of Tryptase Results

Understanding tryptase levels requires knowledge of diagnostic thresholds and limitations:

• Elevated tryptase is defined as >12-15 ng/mL (varies by laboratory) 2, 3
• Tryptase elevation occurs in only 20-40% of anaphylaxis cases, making it specific (85-97%) but not sensitive (40-55%) 4, 3
• Two diagnostic strategies exist: Strategy 1 uses a threshold of reaction tryptase >2 ng/mL + 1.2×(baseline tryptase), while Strategy 2 uses a ratio of reaction/baseline tryptase >1.685 4
• Strategy 1 demonstrates slightly better diagnostic accuracy (AUC 0.69 vs 0.64), though both have low sensitivity 4

Additional Blood Tests

Beyond tryptase, consider these supplementary tests:

• Plasma histamine (>10 nmol/L is elevated) is more sensitive than tryptase and correlates better with clinical signs, particularly urticaria, extensive erythema, wheezing, and abnormal abdominal findings 2
• Histamine must be drawn during the acute reaction or soon afterward, as levels normalize rapidly 2
• Allergen-specific IgE testing can be drawn during the acute reaction or shortly afterward, but should be repeated 4-6 weeks later if initially negative, as IgE antibodies may be temporarily consumed during the acute reaction 5

Critical Pitfalls to Avoid

Several common errors can lead to misdiagnosis:

• Never rely solely on tryptase to rule out anaphylaxis—approximately 50-60% of true anaphylaxis cases will have normal tryptase levels 4, 3
• Fatal anaphylaxis cases show mucocutaneous signs less frequently than milder cases, so absence of skin findings does not exclude the diagnosis 6
• Some patients with systemic mediator release lack classical features like hypotension or tachycardia but still have elevated histamine or tryptase 2
• The lack of tryptase elevation in many patients with elevated histamine suggests basophil involvement rather than mast cell degranulation 2
• Approximately 23.6% of allergic reactions are non-IgE-mediated and will have negative blood tests despite true clinical allergy 5

When Tryptase is Most Useful

Tryptase measurement provides the greatest clinical value in specific scenarios:

• Atypical presentations where the diagnosis of anaphylaxis is uncertain based on history and physical examination alone 3, 6
• Cases where documentation of systemic mediator release is needed for medicolegal purposes or future risk stratification 1
• Patients with higher baseline tryptase levels (>5-6 ng/mL) may be at increased risk of more severe anaphylaxis 7
• Detectable beta-tryptase (≥1 ng/mL) may provide additional diagnostic information even when total tryptase is not elevated 2

Clinical Correlation is Mandatory

Laboratory results must always be interpreted in clinical context:

• Never diagnose allergy based solely on positive specific IgE or tryptase without correlating with clinical history—this is the most common diagnostic error 5
• The presence of drug-specific IgE indicates sensitization but is not proof that the drug caused the reaction 5
• Higher specific IgE levels correlate with increased probability of clinical reactivity, but the relationship varies by allergen, patient age, and clinical context 5
• Sensitization does not equal clinical allergy, as many patients with positive IgE tests tolerate the allergen without symptoms 5