From the Guidelines
The recommended lab workup for suspected mast cell activation includes serum tryptase, 24-hour urine collection for N-methylhistamine, prostaglandin D2 or its metabolite 11β-prostaglandin F2α, and leukotriene E4, as well as a complete blood count with differential, comprehensive metabolic panel, and serum total IgE 1. When evaluating a patient with suspected mast cell activation, it is essential to consider the timing of sample collection, as mediator levels often normalize between reactions.
Key Laboratory Tests
- Serum tryptase level, ideally collected within 4 hours of a reaction
- 24-hour urine collection for N-methylhistamine, prostaglandin D2 or its metabolite 11β-prostaglandin F2α, and leukotriene E4
- Complete blood count with differential
- Comprehensive metabolic panel
- Serum total IgE Additional testing, such as plasma histamine levels, may be considered, although these are less reliable due to rapid degradation.
Specialized Testing
Bone marrow biopsy may be necessary if systemic mastocytosis is suspected, particularly with persistently elevated tryptase levels above 20 ng/mL 1. Genetic testing for KIT D816V mutation can help diagnose systemic mastocytosis, as recommended by the NCCN clinical practice guidelines in oncology 1. It is crucial to collect samples during symptomatic episodes when mediator levels are highest, and multiple collections may be necessary due to the episodic nature of mast cell activation. These tests help document the abnormal release of mast cell mediators, which is essential for diagnosis according to consensus criteria. Patients should be instructed to seek medical attention promptly during reactions to capture elevated mediator levels. In terms of specific laboratory tests, the 2018 NCCN guidelines recommend a comprehensive metabolic panel with uric acid, lactate dehydrogenase (LDH), and liver function tests (LFTs), as well as a CBC with differential and examination of blood smear 1. Molecular testing for KIT D816V by allele-specific PCR or alternative high-sensitivity method is also recommended, along with myeloid mutation panel and FISH as needed for associated hematologic neoplasm (AHN)-related abnormalities 1.
From the Research
Lab Workup for Mast Cell Activation
The lab workup for a patient with suspected mast cell activation includes:
- Serum tryptase levels: An increase in serum tryptase from baseline during a mast cell activation episode is currently the most accepted biomarker measurement of mast cell release 2, 3, 4
- Urine mast cell mediators: Such as histamine, cysteinyl leukotrienes, and prostaglandins, which can be collected at home and are non-invasive tests 3
- 24-hour urine 11β-prostaglandin-F₂α: This test can help identify elevation of mast cell mediators in patients with MCAS 5
- Urinary N-methylhistamine: This test can be used to indicate bone marrow involvement in mastocytosis, with a threshold indicator of 297 micro mol/mol creatinine or higher 6
Interpretation of Lab Results
- An increase in serum tryptase of 20% + 2 from baseline is a required criterion in the diagnosis of mast cell activation syndrome 2
- A tryptase level > 20 ng/mL serves as a minor criterion to diagnose systemic mastocytosis 2
- Elevated urinary N-methylhistamine levels can indicate mast cell accumulation in the bone marrow 6
- Elevated 24-hour urine 11β-prostaglandin-F₂α levels can indicate mast cell activation in patients with MCAS 5
Additional Considerations
- Genetic traits, such as hereditary alpha tryptasemia, can affect baseline tryptase levels 2
- Chronic kidney disease, obesity, and hematological neoplasms can also cause elevated tryptase levels 2
- Aspirin therapy may be recommended for patients with MCAS and elevated 24-hour urine 11β-prostaglandin-F₂α levels 5