A new study has determined that increases in mast cell (MC) mediator metabolites in serum tryptase can help confirm a diagnosis of mast cell activation syndrome (MCAS), which can accompany systemic mastocytosis (SM).

The study, published in The Journal of Allergy in Clinical Practice, found that acute/baseline ratio increases of about 1.3 in the mediators measured, while accompanying a tryptase increase of 20% plus 2 ng/mL, could corroborate the MCAS diagnosis.

“There is no consensus of what constitutes excretion of a substantial increase in metabolites from prostaglandin D2, histamine, or leukotriene E4 in MCAS,” the authors wrote. “Here, we present the findings of a survey of the acute/baseline urinary excretion of the metabolites of histamine, PGD2, and LTC4 detected during symptomatic MC activation episodes.”

Currently, the diagnosis of MCAS is based on a serum tryptase level increased by 20% above baseline plus 2 ng/mL, with accompanying symptoms of MC degranulation that have affected multiple organ systems. Given that there have been reports of urinary MC mediator metabolite increases during MC activation episodes, the authors suspected that noninvasive sampling of urine could provide a useful additional indication of MCAS.

Read more about SM diagnosis

The authors conducted a database search of Mayo Clinic patients with SM with or without MCAS who had measurements taken of serum tryptase as well as acute/baseline levels of urinary MC mediator metabolites, including prostaglandin D2, histamine, and leukotriene E4.

They found that, along with serum tryptase increases of 20% plus 2 ng/mL, leukotriene E4 was the most increased, with an average acute/baseline ratio of 35.98. Prostaglandin D2 followed at a ratio of 7.28, and the histamine level ratio was 3.2. The lowest ratio observed was about 1.3.

The authors note that this convenient, noninvasive measurement method could assist busy emergency room clinicians who might not have time to obtain a venous sample from patients with symptoms of MCAS.


Butterfield JH. Increased excretion of mast cell mediator metabolites during mast cell activation syndrome. J Allergy Clin Prac. Published online February 28, 2023. doi:10.1016/j.jaip.2023.02.017