What the clinician should know when ordering a mast cell tryptase test: A review article for the North American practicing clinician.

Tryptase is currently the most specific mast cell biomarker available in clinical laboratories. Tryptase levels in peripheral blood contribute to the diagnostic, prognostic and therapeutic evaluation of three clinical categories: (1) immediate hypersensitivity reactions including the life-threatening systemic form known as anaphylaxis, (2) clonal mast cell diseases and other myeloid malignancies, including as a biomarker for efficacy of chemotherapeutic agents targeting mast cell survival, and (3) hereditary α-tryptasemia (HαT), a genetic trait found in 4 - 8% of general population associated to increased risk of severe immediate hypersensitivity reactions. Rapidly evolving pathophysiology knowledge and management guidelines impact tryptase use in clinical practice, explaining the need for frequent updates. Such updates often lack context on the pathophysiology and methods regarding mast cells and tryptase, thus hampering the practicing clinician's ability to get the full picture from tryptase test results. Here, we provide the practicing physician with the 2025 state-of-the-art recommendations on tryptase use and interpretation in clinical practice, also exposing their basic, clinical and technical foundations. Successive additions to mast cells and tryptase research are summarized and revisited in the light of today's knowledge. The review sections are titled to reflect matter-of-fact questions arising in clinical practice. Currently unmet needs of tryptase use and selected lines of ongoing research expected to influence clinical practice in the near future are also presented.