Clinical Approach to MCAS Diagnosis and Cutaneous Mastocytosis
Table 3. Biochemical tests for MCAS
(ideally documented ≥ 2 separate episodes, [10]) [1, 2, 8- 11, 13, 18-23]
During an acute event (within 2-4 hours of onset of symptoms) | Notes |
Serum tryptase | Drawn within 4 hours of onset of symptoms (ideally between 30 minutes and 2 hours) |
N-methylhistamine | 24-hour or spot urine > 200% baseline [9] |
9α-11β-prostaglandin F2 (11β PGF2α) | 24-hour or spot urine > 200% baseline [9] |
Leukotriene E4 (LTE4) | 24-hour or spot urine > 200% baseline [9] |
Baseline labs (when asymptomatic) | |
Serum basal tryptase (sBT) | sBT × 1.2 + 2 ng/mL to calculate whether tryptase level when symptomatic is significant [2] *Others have proposed an increase of 1.685 (sAT ≥ 1.685 x sBT) to improve specific amongst individuals with hereditary alpha tryptasemia (HaT) and indolent systemic mastocytosis (ISM) [15, 16] |
Genetic testing | |
D816V mutation analysis | Whole blood or bone marrow in lavender (EDTA) preferred. Also acceptable: Green (sodium heparin) |
HαT | Buccal swab to GeneByGene.com is the only commercial test for HαT |
When to consider bone marrow biopsy | |
Adults | D816V mutation identified in peripheral blood, regardless of tryptase level or HαT [24] |
Children | -CM with hepatosplenomegaly, lymphadenopathy or severe systemic symptoms -Abnormal blood counts (cytopenias, immature forms), organ dysfunction (abnormal liver/kidney function) -Tryptase *no absolute threshold identified, as even those with extremely high sBT typically have normal bone marrow findings [25-27] *some sources recommend biopsy with sBT > 20 [24] or > 100 ng/mL [28] or significant increase sBT continues to be above the upper limit of normal (without HαT) in adolescence [27] -D816V mutation identified -Failure of lesions to regress [27] |
Tests to consider, based on clinical history, ROS, and PE | |
Cortisol | Adrenal disease |
BUN/creatinine | Renal insufficiency |
Thyroid stimulating hormone (TSH) | Thyroid disease |
Calcitonin | Medullary thyroid tumor (globus, hoarseness) |
Gastrin | Zollinger-Ellison Syndrome (GERD/heartburn, diarrhea, tarry stool) |
Vasoactive intestinal protein (VIP) | VIPoma (diarrhea, flushing) |
5-hydroxy indoleacetic acid (urine, serum) | Carcinoid (diarrhea, flushing, tachycardia) |
Metanephrines, catecholamines | Pheochromocytoma (episodic headache, palpitations, tachycardia, sweating) |