Patients with systemic mastocytosis (SM) tend to have elevated urinary levels of mast cell metabolites and their symptoms mitigate with mastocyte control drugs, according to a new study published in the Journal of Allergy and Clinical Immunology. In contrast, patients with hereditary alpha-tryptasemia, despite showing mast cell activation symptoms, do not have mast cell metabolites in the urine, suggesting that these metabolites do not play a role in the development of symptoms.

Both SM and hereditary alpha-tryptasemia can present with symptoms of mast cell activation, but determining what played a role in each disease process was the objective of the study conducted by Giannetti and colleagues.

The authors conducted a retrospective analysis of 63 patients with hereditary alpha-tryptasemia with mast cell activation symptoms, 20 patients with SM, and 23 healthy controls. The patients were mostly female (85%) with an average age of 53 years.

Read more about SM etiology

Mastocyte activation involves the discharge of preformed granules and the active synthesis of membrane products. Usually, 11β-prostaglandin F2α and n-methylhistamine are urinary metabolites that increase chronically or during acute flares of mast cell activation, and they are the targets of drug interventions.

Moreover, the authors found an average baseline serum tryptase level that was 3 times higher and statistically significant in patients with SM compared to those with hereditary alpha-tryptasemia. Likewise, in comparison to patients with hereditary alpha-tryptasemia, those with SM exhibited statistically significant levels of n-methylhistamine and 11β-prostaglandin F2α in the urine.

“The data indicates that patients with [hereditary alpha-tryptasemia] and symptoms of [mast cell] activation do not overproduce histamine, prostaglandin and leukotriene mediators at baseline,” the authors said. They explained that nearly 3 out of 4 patients with hereditary alpha-tryptasemia had daily mast cell activation symptoms that did not respond to antimediator medications.

Conversely, all patients with SM with elevated urinary metabolites could control their symptoms with antimediator medications, which suggests the underlying pathophysiology responsible for the symptoms.

“Symptomatic [hereditary alpha-tryptasemia] patients do not have elevations of mast cell urinary metabolites suggesting that granule and membrane derived mediators may not drive symptoms in [hereditary alpha-tryptasemia],” the authors concluded.


Giannetti MP, Godwin G, Weller E, Butterfield JH, Castells M. Differential mast cell mediators in systemic mastocytosis and hereditary alpha-tryptasemiaJ Allergy Clin Immunol. Published online May 8, 2022. doi:10.1016/j.jaci.2022.04.025