Fig. 1.

Step-wise approach and application of diagnostic criteria in patients with suspected mast cell activation syndrome (MCAS). In patients with clinical signs and symptoms of anaphylaxis (severe hypotension, collapse, acute urticaria, allergic asthma, red skin rash, edema, abdominal pain plus vomiting and diarrhea, others), it is a reasonable diagnostic approach to ask for an event-related increase in tryptase. To define the increase in tryptase, serum samples have to be collected during or shortly after the anaphylactic event and in a symptom-free interval. A diagnostic increase in the event-related tryptase > 120% + 2 ng/mL confirms the involvement of the mast cell (MC) lineage and serves as diagnostic criterion of MCAS. In these cases, the symptoms will respond to drugs stabilizing MC and/or drugs targeting MC mediator effects. In patients without clinical symptoms of MC activation or anaphylaxis, the tryptase level may also be increased to 120% + 2 ng/mL compared to previous examinations (right panel). In these cases, the etiology of the (further) increase in tryptase (for example: progression of mastocytosis) should be explored. If no such etiology is detectable, the increase may be due to a recent anaphylactic event (then the final diagnosis may be MCAS), or may be due to fluctuations in the basal serum tryptase: in these patients, the increase to > 120% + 2 ng/mL (over baseline) does not count as criterion of MCAS