Tryptase Triggers and Mast Cell Activation
Common triggers that elevate tryptase and activate mast cells include hot water, alcohol, certain drugs (especially NSAIDs, aspirin, radiocontrast agents, and specific anesthetic agents), stress, exercise, hormonal fluctuations, infection, and physical stimuli such as pressure, friction, temperature extremes, and insect venoms. 1, 2
Primary Trigger Categories
Environmental and Physical Triggers
- Temperature extremes (both hot and cold) can provoke mast cell degranulation, with hot water being particularly problematic 1
- Mechanical stimulation including pressure, friction, and vibration can trigger activation 1
- Insect venoms (particularly wasp and bee stings) are well-documented triggers that can cause significant tryptase elevation 2, 3
Pharmacologic Triggers
- NSAIDs and aspirin are common culprits, particularly in patients with aspirin-exacerbated respiratory disease (AERD), where acute systemic anaphylaxis can occur 1, 2
- Radiocontrast agents used in imaging procedures 2
- Specific anesthetic agents including certain muscle relaxants (atracurium, mivacurium, succinylcholine) and some opioids (morphine, codeine, meperidine) 1, 2, 4
- Ketorolac has been associated with lethal reactions and should be avoided 1
Physiologic and Lifestyle Triggers
- Alcohol consumption is a frequently reported trigger 1, 2
- Exercise can provoke mast cell activation in susceptible individuals 1
- Emotional stress serves as a potentiating factor 1
- Hormonal fluctuations (particularly in women) can trigger episodes 1
- Infections and febrile illnesses 1
Immunologic Triggers
- IgE-mediated allergen exposure through FcεRI receptor engagement (foods, medications, environmental allergens) 1
- IgG-mediated activation through FcγRI/IIa receptors 1
- Complement anaphylatoxins acting on G protein-coupled receptors 1
Important Clinical Considerations
Trigger Identification Strategy
The connection between specific triggers and mast cell activation is generally inconclusive except in patients with rare monogenic disorders, making it essential to document biomarker elevation (tryptase >baseline × 1.2 + 2 ng/mL) when symptoms occur after suspected triggers. 1
Common Pitfalls
- Not all patients will identify clear triggers; idiopathic MCAS exists where no trigger, mutation, or genetic trait has been identified 1
- Pain itself can trigger mast cell activation, creating a vicious cycle where inadequate pain control worsens MCAS symptoms 4
- Skin testing to anesthetic drugs or opioids prior to procedures is not reliably predictive, as some drugs can directly degranulate mast cells in vivo without true allergy 1
Trigger Avoidance Recommendations
Patients with documented MCAS and history of systemic anaphylaxis should receive lifelong venom immunotherapy if insect venom sensitivity is confirmed, and must carry epinephrine autoinjectors. 2
Temperature control within reasonable ranges (avoiding extreme hot baths, showers, swimming pools) can decrease symptom frequency 1
Identifying and documenting specific personal triggers through symptom diaries correlated with tryptase measurements during acute episodes helps guide individualized avoidance strategies 1, 2, 5