What to ask your doctor for

The core panel

These are the tests both criteria sets are built on. If only one thing gets ordered, it is the tryptase pair.

• Serum tryptase — baseline Blood

  Also called sBT, Resting tryptase

  Shows

  The resting tryptase level this patient runs at, which the episode sample is measured against. A level below 8 ng/mL is generally considered normal.

  When

  Drawn at least 24 hours after complete recovery from a suspected episode. A sample taken too soon is not a baseline.

  Worth knowing

  A normal baseline does not rule MCAS out, and a raised baseline on its own is not a criterion for it. Raised baseline tryptase also occurs in hereditary alpha-tryptasemia, systemic mastocytosis, some blood disorders, end-stage kidney disease, and parasitic infection.

• Serum tryptase — during an episode Blood

  Also called Acute tryptase, Event-related tryptase

  Shows

  Whether tryptase actually rose during the episode. Both criteria sets look for a rise above the patient's own baseline multiplied by 1.2, plus 2 ng/mL.

  When

  This is the part most often got wrong. Tryptase peaks in serum about an hour after symptoms start, then falls with a half-life of roughly two hours — so it may still be raised at three hours, sometimes at five, and not much beyond. A sample drawn the next day, or at a routine appointment weeks later, cannot meet this criterion no matter how severe the episode was.

  Worth knowing

  Because the window is short, the practical problem is access: someone has to be able to order it while the episode is happening or shortly after. This is worth planning before an episode rather than during one.

• Urinary leukotriene E4 Urine

  Also called LTE4

  Shows

  A cysteinyl leukotriene metabolite. Leukotrienes are made by mast cells on activation rather than stored ready-made, so they report a different part of the response than tryptase does.

  When

  Collected during the onset of an episode and for several hours after.

  Worth knowing

  Like the prostaglandin metabolite, the assay is available in relatively few laboratories.

• Urinary 1-methyl-4-imidazole acetic acid Urine

  Also called MIAA

  Shows

  The other commonly measured histamine metabolite, used alongside or instead of N-methylhistamine.

  When

  As for N-methylhistamine — collected across the episode and the hours following.

  Worth knowing

  Less specific to mast cells than tryptase.

• Urinary N-methylhistamine Urine

  Also called N-methyl histamine

  Shows

  A histamine breakdown product. Reported to track both mast cell burden and mast cell activation.

  When

  A 24-hour collection is the usual advice, though shorter collections and spot samples are also discussed. Most informative when the collection covers the episode and the hours after it.

  Worth knowing

  Less specific to mast cells than tryptase.

• Urinary prostaglandin D2 metabolite Urine

  Also called 9α,11β-PGF2, PGD2 metabolite

  Shows

  A breakdown product of prostaglandin D2, which mast cells make on activation. Found raised during anaphylaxis and in systemic mastocytosis compared with healthy controls.

  When

  Collected during the onset of an episode and for several hours after.

  Worth knowing

  The assay is technically difficult and offered by only a few laboratories, so it may need to be sent out. Rises over an individual's own baseline have not been reported in most studies, which limits how it can be interpreted.

Tests that change the answer

Not markers of activation, but tests that explain a result or point somewhere else entirely. Both are ordinary send-outs.

• KIT D816V testing Blood or bone marrow

  Also called KIT mutation analysis, Clonality testing

  Shows

  The mutation that drives clonal mast cell disease. Its presence points towards mastocytosis or monoclonal mast cell activation syndrome rather than non-clonal MCAS.

  When

  Any time. Blood assays are screening tests; bone marrow examination is the definitive one and is a specialist referral.

  Worth knowing

  This distinguishes between conditions with different treatments, so it changes what follows rather than merely confirming a label. Sensitive blood assays exist but a negative result does not exclude clonal disease.

• TPSAB1 copy number Blood

  Also called Hereditary alpha-tryptasemia genotyping, HαT testing

  Shows

  Extra germline copies of the alpha-tryptase gene. This causes hereditary alpha-tryptasemia, in which baseline tryptase is raised for genetic reasons and rises further with each additional gene copy.

  When

  Any time; it is a genetic test, not an episode-dependent one.

  Worth knowing

  Worth knowing about because it is a common benign explanation for a raised baseline tryptase. Without it, a high resting tryptase can be read as evidence of mast cell disease when it is inherited and unrelated.

Ordered under the broader criteria

Where the two criteria sets visibly disagree. Worth knowing which side of that disagreement a given clinician is on.

• Heparin, chromogranin A, platelet-activating factor and serotonin Blood or urine

  Also called Extended mediator panel

  Shows

  Additional mediators sometimes ordered when working to the broader criteria, on the reasoning that tryptase misses patients whose activation shows up in other mediators.

  When

  Varies by marker and laboratory.

  Worth knowing

  This is where the two criteria sets visibly diverge. Clinicians working to the stricter criteria regard the clinical utility of these markers as unproven on current data. That is a real disagreement in the literature rather than an oversight, and a clinician declining to order them is not necessarily dismissing the question.

Commonly asked for, but not recommended

Included because patients often arrive asking for it, and a clinician declining is following the literature rather than dismissing the question.

• Plasma histamine Blood

  Also called Blood histamine

  Shows

  Circulating histamine.

  When

  —

  Worth knowing

  Not generally recommended as a marker of mast cell activation. At baseline much of it comes from basophils rather than mast cells, and the result is affected by how the sample is drawn and stored, by diet, and by bacterial flora of the urinary tract. Frequently requested and hard to interpret.

The drug classes the criteria refer to

1. Step 1 · H1 antihistamines

   described as the initial treatment, with second-generation agents prioritised over first

   Cetirizine Hydroxyzine

2. Step 2 · H2 antihistamines

   described as add-on therapy where episodes involve gastrointestinal symptoms

   Famotidine

3. Step 3 · Leukotriene receptor antagonists

   the next class described; in Canada montelukast is the only available option

   Montelukast

4. Step 4 · Cromolyn

   described for persistent gastrointestinal symptoms despite H1 and H2 blockade

   Cromolyn sodium

5. Step 5 · Ketotifen

   described for patients not controlled on high-dose second-generation H1 antihistamines

   Ketotifen

6. Step 6 · Aspirin

   described as limited evidence, for persistent episodes despite H1 blockade

   Aspirin

7. Step 7 · Oral corticosteroids

   described for frequent episodes, with use limited by adverse effects

   Systemic corticosteroids (prednisone representative)

8. Step 8 · Omalizumab

   described for severe recurrent reactions despite the preceding treatments

   Omalizumab

The criteria also name aspirin and other non-steroidal anti-inflammatory drugs among the mediator-targeting agents. This site does not yet have an entry for them, so they are noted here rather than linked.

Finding a clinician

• European Competence Network on Mastocytosis (ECNM)

  Network of European reference centres for mast cell disease. Useful for locating specialist centres and for following the research consortium's output.

• Mast Cell Action

  UK charity focused on MCAS specifically. Publishes patient-facing resources and materials intended to be taken to appointments.

• Mastocytosis Society Canada

  Canadian patient organization for mast cell disease, with region-specific care and emergency information.

• The Mast Cell Disease Society (TMS)

  US non-profit for mastocytosis and mast cell activation disorders. Maintains physician referral lists, emergency-protocol documents, and patient education material.

Worth establishing early