Symptoms of Elevated Tryptase
Elevated tryptase itself causes no symptoms—symptoms arise only when mast cells actively degranulate and release mediators, which can manifest as episodic flushing, urticaria, pruritus, gastrointestinal distress, cardiovascular instability, or anaphylaxis affecting at least two organ systems concurrently. 1
Understanding the Critical Distinction
The key clinical concept is differentiating between baseline elevated tryptase (which is asymptomatic) and acute mast cell activation (which produces symptoms):
- Baseline elevated tryptase (>8-20 ng/mL) occurs in hereditary alpha-tryptasemia (4-6% of the general population), cutaneous mastocytosis in children, chronic kidney disease, obesity, and hematological neoplasms—none of these conditions produce symptoms from the elevated tryptase alone 2, 3
- Symptomatic mast cell activation requires documented acute tryptase elevation of >20% + 2 μg/L above baseline during symptomatic episodes 1, 4
Organ System-Specific Manifestations When Mast Cells Degranulate
Cutaneous Symptoms
- Urticaria, pruritus, flushing, and angioedema are the most common manifestations 1
- Positive Darier's sign (wheal formation with stroking of skin lesions) occurs in 89-94% of patients with cutaneous mastocytosis 5
- Bullae formation can occur, particularly in mastocytoma cases 5
Gastrointestinal Symptoms
- Diarrhea, abdominal cramping, nausea, vomiting, and bloating 5, 6
- These symptoms respond to H2 antihistamines and cromolyn sodium 1
Cardiovascular Symptoms
- Hypotension, tachycardia, syncope, or near-syncope indicate systemic anaphylaxis when occurring with at least one other organ system 1
- Palpitations and vasomotor instability 5
Neurologic Symptoms
- Lightheadedness and altered mental status during acute episodes 6
- These symptoms respond to cromolyn sodium 1
Respiratory Symptoms
- Wheezing, bronchospasm, and sensation of throat tightness 6
Common Symptom Triggers
Temperature changes, hot water, alcohol, certain drugs, stress, exercise, hormonal fluctuations, infection, and physical stimuli such as pressure or friction are the most frequently identified triggers 5, 1
Critical Clinical Pitfalls
The Asymptomatic Elevated Baseline
- Persistently elevated baseline tryptase >20 ng/mL serves as a minor diagnostic criterion for systemic mastocytosis but does not cause symptoms by itself 2, 4
- In children with cutaneous mastocytosis, elevated tryptase >20 μg/L indicates increased mast cell burden but typically does not progress to systemic disease and may be asymptomatic 2
The Protracted Anaphylaxis Pattern
- Mast cell degranulation can continue for 96-120 hours, producing prolonged symptoms with persistently elevated tryptase levels throughout this period 6
- This is often missed because clinicians expect anaphylaxis to resolve within hours 6
The Correlation Fallacy
- Neither the extent nor density of cutaneous mastocytosis predicts systemic involvement or symptom severity 5
- Serum tryptase is significantly elevated only in children with systemic disease, not in isolated cutaneous disease 5
When Symptoms Indicate High-Risk Disease
Tryptase >200 ng/mL indicates high mast cell burden requiring urgent hematology referral and possible hospitalization 2, 7, with symptoms typically including:
- Severe recurrent anaphylaxis
- Multi-organ system involvement
- Bone pain (indicating bone marrow infiltration) 5
Diagnostic Approach to Symptomatic Patients
- Obtain serum tryptase during acute episodes: initial sample as soon as feasible, second at 1-2 hours after symptom onset, and third at 24 hours or in convalescence 1
- Acute elevation >20% + 2 μg/L above baseline on at least 2 separate occasions is diagnostic of mast cell activation syndrome 1
- Symptoms must affect at least 2 organ systems concurrently to meet diagnostic criteria 1