Tests
1st tests to order
serum tryptase
Test
Measure serum tryptase level within 1 to 4 hours of onset of a suspected acute MCAS episode.[2][3][5][18][41] The tryptase level usually peaks around 1 hour after symptom onset.[18] Arrange for an additional sample to be taken at least 24 hours after all symptoms have resolved to determine the baseline tryptase level.
Elevation of a validated mast cell marker during an acute episode is essential for confirmation of an MCAS diagnosis and serum tryptase is the standard test.[2][3][5][18]
Result
Elevation of acute tryptase level of at least 20% above baseline +2 ng/ml (1.2 x baseline +2). Tryptase must return to the patient’s baseline level once symptoms resolve.
urinary metabolites of histamine and/or prostaglandin D2 and/ or leukotriene C4 (LTC4)
Test
These are alternative or additional markers of mast cell activation that are less specific and less sensitive than serum tryptase measurement. Testing urine for their metabolites may be helpful to support a diagnosis of MCAS, particularly if tryptase levels are inconclusive or if no blood (but only urine) could be collected during the acute event.[2][3][5][18][43][44][45][46][47]
If these tests are available in your center, order them during a symptomatic episode and then obtain a baseline value at least 24 hours after full resolution of symptoms. 24-hour urine or spot urine can be used.[2][5][18]
Substantially elevated levels during an acute episode signify mast cell activation but a precise diagnostic threshold for MCAS has yet to be determined for adults and normal ranges have not been established for children.
Result
Elevated. Specific cut-off levels have not been established.
12-lead ECG
Test
Essential if the patient presents with cardiovascular symptoms. Arrhythmias and/or potential ST changes may be a sign of myocardial ischemia. Note when interpreting findings that transient ST changes may occur after administration of epinephrine (adrenaline), particularly if intravenous.
Result
May indicate arrhythmias and/or potential ST changes
Tests to consider
allergy workup
Test
After making a diagnosis of MCAS, it is important to determine the subtype as this will inform the long-term management plan.[5][18]
Consider requesting a workup for IgE- and non-IgE mediated triggers, based on the patient’s history. IgE-dependent allergy is the commonest underlying cause of MCAS.[5]
However, do not request a battery of nonspecific IgE tests or unproven diagnostic tests, such as IgG testing, in the evaluation of allergy. Such testing could lead to inappropriate diagnosis and treatment.[48]
Result
Positive result may suggest secondary MCAS
peripheral blood KIT D816V mutation analysis
Test
This test is important to determine the subtype of MCAS, as this will inform the long-term management plan.[5][18]
Highly sensitive peripheral blood detection of KIT D816V mutation (such as allele-specific PCR or ddPCR with an allelic limit of detection of at least <0.1%) is used, where available, to look for evidence of clonal mast cell disease (mastocytosis).[5][49][50] Mastocytosis is the most common underlying cause of primary MCAS.
This investigation is indicated if there are any pointers toward primary MCAS (e.g., elevated baseline tryptase, hypotensive syncope during acute episodes, or signs of urticaria pigmentosa).[5]
Result
Detection of KIT D816V mutation in the case of mastocytosis (primary MCAS)
bone marrow biopsy
Test
In an adult patient presenting with skin signs of mastocytosis, if KIT D816V mutation is detected in peripheral blood then a bone marrow biopsy is recommended for confirmation of systemic mastocytosis according to the World Health Organization diagnostic criteria.[18][50][52]
Result
In systemic mastocytosis, detection of multifocal, dense infiltrates of ≥15 mast cells with abnormal morphology including spindle shape forms
trial of mast cell mediator blocking agent/mast cell stabilizer
Test
An MCAS diagnosis can only be formally confirmed after a successful trial of treatment with a mast cell mediator blocking agent (e.g., antihistamine, H2 antagonist, leukotriene receptor antagonist) or mast cell stabilizer (e.g., cromolyn, ketotifen).[2][3][5][18][28]
Result
Significant and sustained relief of symptoms and decreased frequency and severity of acute episodes
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