Tryptase: An important tool in the assessment of severe allergic disease

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Tryptase: An important tool in the assessment of severe allergic disease

31 January 2024

By Anthea Anantharajah

Wednesday 31 January 2024, 12:30 AM

4 minutes to Read

The patient’s serum tryptase level was elevated immediately following a bee sting and remained elevated one week later [Image: Aaron Burden on Unsplash]

Measurement of mast cell tryptase is a vital yet underused tool in the assessment of severe allergic and mast cell disorders. This article summarises the causes of elevated serum tryptase, indications for testing and interpretation of results

Key points

Tryptase measurement is an important tool in the diagnosis of anaphylaxis and mast cell disorders.
Tryptase levels can help determine the severity of an allergic reaction, particularly when not obvious on clinical assessment.
It is important to measure a baseline serum tryptase level at least 24 hours after an anaphylactic reaction to exclude an underlying mast cell disorder.
Hereditary alpha tryptasemia is the most common cause of an elevated BST level, and most carriers are asymptomatic.
Individuals with an elevated BST level should be referred to an immunologist/allergist for further investigation.

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A 46-year-old woman attends for review after an emergency department presentation with anaphylaxis following a bee sting. She was treated with intramuscular adrenaline in the ED but subsequently required an adrenaline infusion for ongoing hypotension. A serum tryptase measured three hours after the reaction was 63μg/L (reference range: ≤11.4μg/L). A second tryptase measurement taken one week after the reaction was 21.3μg/L.

What does this result mean and what are the next steps in investigation?

What are tryptases?

During activation of mast cells (eg, in anaphylaxis), mature tryptases are released

Tryptases are preformed chemical mediators that are stored within the secretory granules of mast cells. They are released continuously into the circulation in an inactive, precursor form, and this release is not associated with any biological effects.

However, during activation and degranulation of mast cells (eg, in anaphylaxis), mature tryptases are released. Release of mature tryptases and other mast cell mediators results in a range of symptoms and signs, including urticaria, angioedema, flushing, diarrhoea, vomiting and hypotension.

There are two major measurable forms of tryptase in humans: alpha and beta. Laboratory tryptase assays measure all forms (both precursor and mature forms) of alpha and beta tryptases in combination, although only mature beta tryptase exerts biological effects.

When should serum tryptase be measured and how should the results be interpreted?

The most common indication to measure serum tryptase is in the diagnosis of anaphylaxis. Levels peak within one to two hours of a reaction, but measurements within four hours can still be clinically useful. Tryptase levels correlate with the severity of anaphylaxis and are more likely to be elevated if the reaction was associated with hypotension or due to a venom allergy.¹

Although serum tryptase is not always elevated in cases of clinically confirmed anaphylaxis, it can be a useful tool in the assessment of less clear-cut allergic presentations. This includes unexplained hypotension without other obvious features of allergy.

A baseline serum tryptase (BST) measurement should always be performed after an elevated serum tryptase is detected during an acute reaction, to ensure this has normalised. A persistently elevated BST level can be due to a number of causes (see table),^2,3 but the most important conditions to consider are clonal mast cell disorders such as systemic mastocytosis. Patients with mastocytosis are at higher risk of venom anaphylaxis, and this may be the presenting symptom of this disease.

Causes of elevated baseline serum tryptase levels [Click to enlarge]

Another reason to perform a BST measurement in the assessment of suspected anaphylaxis is that even when the acute serum tryptase level is not elevated above the reference range, it may still reflect systemic mast cell degranulation if it is significantly different from the BST level. The most widely used formula to calculate what constitutes a significant difference between acute and baseline levels is shown in the panel below.

Is the tryptase change significant?

Significant acute tryptase level ≥ (1.2 × BST) + 2μg/L

Another important reason to measure tryptase is for the diagnosis of non-clonal disorders of mast cell activation. Mast cell activation syndrome is characterised by episodic symptoms caused by mast cell mediator release. As the symptoms can be non-specific (flushing, diarrhoea, palpitations, fatigue, poor concentration), to avoid inappropriate diagnosis of this condition, diagnostic criteria require the detection of elevated or significantly fluctuating (see panel) mast cell mediators.⁴ The most reliable and best validated mediator in this context is tryptase; currently, it is the only mast cell mediator widely tested in New Zealand.

The case revisited

The patient is referred to an immunology specialist clinic for management of bee venom anaphylaxis and for further investigation of the elevated BST level.

A bone marrow biopsy is performed, showing increased bone marrow mast cells, and molecular testing reveals the c-kit D816V mutation.

A diagnosis of indolent systemic mastocytosis is made. This diagnosis may have been missed if a BST measurement had not been performed.

Details have been changed to protect patient confidentiality

Anthea Anantharajah is a clinical immunologist, allergist and immunopathologist working at Awanui Labs, Wellington

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Investigations

Immunology

References

1. Sala-Cunill A, Cardona V, Labrador-Horrillo M, et al. Usefulness and limitations of sequential serum tryptase for the diagnosis of anaphylaxis in 102 patients. Int Arch Allergy Immunol 2013;160(2):192–99.

2. Chollet MB, Akin C. Hereditary alpha tryptasemia is not associated with specific clinical phenotypes. J Allergy Clin Immunol 2022;149(2):728–35.e2.

3. Lee AYS. Elevated serum tryptase in non-anaphylaxis cases: A concise review. Int Arch Allergy Immunol 2020;181(5):357–64.

4. Gulen T, Akin C, Bonadonna P, et al. Selecting the right criteria and proper classification to diagnose mast cell activation syndromes: A critical review. J Allergy Clin Immunol Pract 2021;9(11):3918–28.

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