Tryptase

If patient did not experience symptoms of mast cell activation during the hours before collection, in ng/mL (eg if this is the patient's “baseline” level) Note that it may take up to two weeks after a reaction for a patient's tryptase to return to baseline.):

Under 11.5: in reference range, most typical of MCAS, seen in some cases of ISM

Between 11.5 and 20: slight elevation, common with MCAS and some cases of ISM. These levels do not meet any criteria for (any)SM diagnosis.

Between 20 and 30: Some practitioners perform a bone marrow biopsy to screen for SM (usually ISM), for which this satisfies one minor criterion. Others monitor levels with regular testing. Testing for HATS and possible screening for other conditions is also warranted.

30-500+: A bone marrow biopsy is typically (but not always in this lower range) recommended to screen for SM, for which this satisfies one minor criterion. Additionally, baseline tryptase over 200 satisfies one possible minor criterion for SSM after general SM diagnostic criteria have been met. Testing for HATS and basic screening for other conditions is also warranted.

When tryptase indicates the need for further screening for systemic mastocytosis, mutation in the KIT D816V gene may also be diagnostically relevant. The patient's KIT status may also be relevant in the selection of certain drugs listed under fourth line therapies. This may be tested in peripheral blood or bone marrow. See diagnostic criteria.

Some frequently asked questions about tryptase and related concerns:

Is tryptase correlated with disease severity?

No, not at all. There are many severe cases of MCAS patients with a tryptase of 2, for example, and some patients with a tryptase of 300+ with very little impact on their daily lives. Tryptase is most relevant diagnostically as regards systemic mastocytosis typing by indicating the likely presence of SSM or ASM, particularly in the absence of HATS.

How prevalent are these disorders?

MCAS was most recently estimated to affect 17% of the population (1 in 5 or 6). All forms of systemic mastocytosis are estimated to affect 1 in 10,000, of which roughly 90%, and quite possibly more, are classed as Indolent Systemic Mastocytosis. Aggressive Systemic Mastocytosis is estimated to affect 1-2 in a million/year.

Is it possible to have normal trypase with ASM (Aggressive Systemic Mastocytosis)?

A fraction of the cases of Indolent Systemic Mastocytosis present with normal or only slightly elevated tryptase, but a tryptase under 200 (200, not 20) is rare to find with SSM (Smoldering Systemic Mastocytosis), which is a stage before ASM. See this criterion, which is one of three for which two are required for SSM diagnosis, after the patient meets the general requirements for SM diagnosis.

I had an old gastrointestinal biopsy re-stained, and my patient meets the first criteria for SM diagnosis with dense infiltrates of mast cells in this tissue. Why is this this particular biopsy not preferred for the major criterion for SM diagnosis?

Use this information at your discretion (and note that this is also common in MCAS patients and is sometimes cited as laboratory evidence of MCAS), but infiltrates of mast cells in the gastrointestinal tract are extremely common due to a number of other conditions and are in no way specific to either inappropriate mast cell activation or systemic mastocytosis (consider, as an inexhaustive list, allergies, injuries, inflammation, foods or supplements which irritate the gastrointestinal tract for other reasons, irritable bowel syndrome, Crohn's, diverticulitis...). Some patients with either MCAS or SM also present with perfectly normal gastrointestinal biopsies, even with significant GI symptoms (perhaps the infiltrates are in one of the many areas of the tract you have not biopsied.)

My patient has a biopsy positive for Cutaneous Mastocytosis. How will I know whether I need to refer/order a bone marrow biopsy and whether the disorder is systemic and requires treatment?

Most base bone marrow biopsy decisions on results of the patient's baseline tryptase level. Also see systemic symptom checklist and treat accordingly. While diagnoses of CM are common among babies and toddlers and precautions are often taken in this population, patients diagnosed with CM as adults are more likely to have systemic symptoms.

Who should monitor my patient with confirmed systemic mastocytosis, or to whom should I refer my patient with significantly elevated tryptase?

A qualified hematologist/oncologist with experience with this disorder.

Notes on some other results/relevant investigations:

If calcium is higher than 10 mg/dL in adult patient

PTH (parathyroid)

if normal, followed by, in 24 hour urine, 5-HIAA, calcium, and other testing

If total IgE is elevated

in the hundreds, a complete autoimmune panel (blood), and perhaps a more comprehensive IgE blood testing

particularly in the thousands, an investigation into chronic infections or possible implant rejection (both are also common triggers for mast cell dysfunction)

If specific IgE is elevated, this is a confirmed allergen which should be avoided. If symptoms remain after cutting the allergen or there remain other reasons to suspect the presence of a mast cell disorder, the patient must continue to refuse any kind of skin or injectable testing or allergen treatments (shots, various low dose therapies, challenges, and so on).

Thyroid, hormone, clotting, or endocrine issues may result from conditions which commonly trigger or worsen a mast cell disorder, may mimic a mast cell disorder but be unrelated, or may arise as a result of a mast cell disorder (also see this incomplete list). These warrant individual investigation if they fail to resolve with appropriate mast cell treatment or indicate the presence of an unrelated condition.