Table 3.

Current provisional criteria to define mast cell activation syndrome (MCAS; modified from Afrin and Molderings 2014)

Major criterion
	Constellation of clinical complaints attributable to pathologically increased mast cell activity (mast cell mediator release syndrome)
Minor criteria
1.	Focal or disseminated increased number of mast cells in marrow and/or extracutaneous organ(s) (e.g., gastrointestinal tract biopsies; CD117-, tryptase-, and CD25-stained)
2.	Abnormal spindle-shaped morphology in >25 % of mast cells in marrow or other extracutaneous organ(s)
3.	Abnormal mast cell expression of CD2 and/or CD25 (i.e., co-expression of CD117/CD25 or CD117/CD2)
4.	Detection of genetic changes in mast cells from the blood, bone marrow, or extracutaneous organs for which an impact on the state of activity of affected mast cells in terms of an increased activity has been proven
5.	Evidence (typically from body fluids such as whole blood, serum, plasma, or urine) of above-normal levels of mast cell mediators including:
	•	Tryptase in the blood
	•	Histamine or its metabolites (e.g., N-methylhistamine) in the urine
	•	Heparin in the blood
	•	Chromogranin A in the blood (potential confounders of cardiac or renal failure, neuroendocrine tumors, or recent proton pump inhibitor use were excluded)
	•	Other relatively mast cell-specific mediators (e.g., eicosanoids including prostaglandin PGD2, its metabolite 11-β-PGF2α, or leukotriene E4)
6.	Symptomatic response to inhibitors of mast cell activation or mast cell mediator production or action (e.g., histamine H1 and/or H2 receptor antagonists, cromolyn)

Diagnosis of MCAS made by either (1) the major criterion plus any one of the minor criteria or (2) any three minor criteria