What is tryptase and its clinical significance in patients with a history of allergic reactions or suspected mast cell disorders?

What is Tryptase

Tryptase is a protease enzyme stored in and released by mast cells that serves as the primary biomarker for mast cell activation and systemic mastocytosis in clinical practice. 1

Basic Biochemistry and Types

Tryptase exists in two main forms with distinct clinical significance 1:

• β-tryptase (mature tryptase) is stored in mast cell granules and released acutely during mast cell degranulation via calcium-dependent mechanisms, making it the key marker for anaphylaxis 1
• α-tryptase is secreted constitutively by mast cells and represents the baseline level found in healthy individuals 1
• Pro-β-tryptase is also constitutively secreted and contributes to baseline measurements 1

The enzyme functions through protease-activated receptors (PARs) distributed throughout the body, mediating effects on smooth muscle relaxation in blood vessels and bronchi, modulating calcium and chloride ion transport, and stimulating pro-inflammatory interleukin release during inflammation 1

Clinical Significance in Anaphylaxis

The change in tryptase concentration from baseline is more diagnostically valuable than absolute values alone, with a rise of at least 20% + 2 μg/L being the diagnostic criterion for mast cell activation. 2, 3

Critical Timing Considerations

Understanding tryptase kinetics is essential for proper interpretation 1, 3:

• Tryptase peaks approximately 1 hour after symptom onset
• Half-life is approximately 2 hours in circulation
• Levels fall rapidly, returning to baseline within 5-6 hours
• Optimal sampling window is 1-2 hours after symptom onset, but no longer than 6 hours 2, 3
• A baseline measurement must be obtained >24 hours after any acute event to establish true baseline 2

Important Limitations

A normal tryptase level does NOT exclude anaphylaxis—this is a critical pitfall to avoid 1, 4:

• Anaphylaxis can occur through basophil or complement activation pathways that do not release mast cell tryptase 1
• The current assay has high specificity but relatively low sensitivity, missing some cases 1
• Intravenous fluid resuscitation during treatment dilutes blood and artificially lowers measured concentrations 1
• The rise in tryptase may be less marked in non-allergic anaphylaxis 1

Clinical Significance in Mast Cell Disorders

Baseline Tryptase Interpretation

Normal range is 0-11.4 μg/L, with values <15 ng/mL generally considered normal 2, 5:

• Persistently elevated baseline >20 μg/L (when asymptomatic) is a minor diagnostic criterion for systemic mastocytosis and mandates bone marrow evaluation 2, 4, 5
• Elevated α-tryptase in resting state reflects increased mast cell numbers in systemic mastocytosis 1
• Tryptase >200 ng/mL indicates high mast cell burden requiring urgent hematology referral 2, 4

Diagnostic Workup Algorithm

When baseline tryptase is >20 μg/L 4:

1. Examine skin for urticaria pigmentosa or mastocytosis lesions
2. Document symptoms of mast cell mediator release (flushing, pruritus, abdominal cramping, diarrhea)
3. Review for severe anaphylaxis to insect stings, unexplained osteoporosis, hepatosplenomegaly
4. Proceed to bone marrow aspiration and biopsy with immunohistochemistry for CD117, CD25, CD2 expression
5. Test for KIT D816V mutation
6. Evaluate for associated hematologic neoplasms (present in up to 71% of advanced cases)

Other Conditions Causing Elevated Tryptase

Beyond anaphylaxis and systemic mastocytosis, tryptase can be elevated in 6:

• Acute myelocytic leukemia
• Various myelodysplastic syndromes
• Hypereosinophilic syndrome with FLP1L1-PDGFRA mutation
• End-stage renal failure
• Post-mortem samples (though with lower predictive value than antemortem samples) 1
• Trauma or myocardial infarction (β-tryptase specifically) 1

Laboratory Measurement

The most widely used assay is the ImmunoCAP fluorescence enzyme immunoassay (FEIA), which measures the sum of α and β-tryptase concentrations 1. This means acute elevations reflect β-tryptase release, while chronically elevated baseline typically reflects α-tryptase from increased mast cell numbers 1.

Clinical Management Implications

All patients with documented elevated baseline tryptase or mast cell activation syndrome require 4:

• Two epinephrine auto-injectors carried at all times
• Medic Alert identification documenting elevated tryptase and anaphylaxis risk
• Education on avoiding mast cell degranulation triggers (extreme temperatures, physical trauma, alcohol, NSAIDs, opioids, certain antibiotics, contrast media, stress, vigorous exercise)
• Serial tryptase monitoring every 3-6 months once diagnosis established 2

For surgical procedures, anesthesia teams must be notified, baseline coagulation studies obtained, and specific precautions taken including using fentanyl or sufentanil rather than morphine, avoiding ketorolac, and having emergency anaphylaxis protocols ready 4.