What is being tested?
his test measures the amount of tryptase in the blood. Tryptase is an enzyme that is released, along with histamine and other chemicals, from mast cells when they are activated, often as part of an allergic immune response.
Mast cells are large tissue cells found throughout the body, but in highest amounts in the skin, in the lining of the intestine and air passages, and also in the bone marrow. Mast cells are part of the body's normal response to injury as well as allergic (hypersensitivity) responses. They contain granules that store a number of chemicals, including tryptase and histamine, that are released when mast cells become activated. In the body, mast cells recognise and bind IgE, a special type of antibody that is often increased in people with allergies and parasitic infections. When IgE that is bound to the surface of mast cells attaches to its target (antigen), mast cells become activated and release their contents. The chemicals released from mast cells (especially histamine) are responsible for many of the symptoms in persons with allergies.
Mast cells contain different forms of the enzyme tryptase, termed alpha and beta tryptase, in both inactive (protryptase) and active forms. In the body, beta tryptase is typically the predominant form of mature tryptase. Testing can be performed to measure total tryptase, which is all of the forms together, or mature tryptase, which measures the mature forms of alpha and beta tryptase. Comparison of the results of these two tests in a total-to-mature ratio may be useful in some instances though is not available at present in Australia.
Normally concentrations of tryptase in the blood are very low. When mast cells are activated, levels increase rapidly, rising within 15 to 30 minutes, peaking at 1 to 2 hours, and returning to normal after several hours to a couple of days. In persons with severe allergies, activation of many mast cells can cause a severe form of allergic reaction termed anaphylaxis, which can cause low blood pressure, hives (blisters on the skin), severe narrowing of the air passages, and even death. Tryptase levels will be very high in persons with anaphylaxis only if they have had low blood pressure with the reaction. In many food associated reactions, tryptase may not be elevated.
In some cases, tryptase levels will be high in persons with mast cell activation disorders, in which mast cells become activated without apparent allergies or other reasons.
Tryptase levels can also be significantly and persistently increased with mastocytosis, a rare group of disorders associated with the neoplastic proliferation of mast cells and their infiltration and accumulation in the skin (cutaneous mastocytosis) and/or in organs throughout the body (systemic mastocytosis). Systemic mastocytosis may progress slowly and be relatively slowly progressive or may be aggressive, causing organ dysfunction and, in rare cases, is a form of leukaemia. It may also be associated with some forms of lymphoma.
How is it used?
The tryptase test is a useful indicator of mast cell activation. It may be ordered to confirm a diagnosis of anaphylaxis and to help diagnose mastocytosis.
Anaphylaxis is primarily diagnosed clinically, but a total tryptase may be ordered, to help confirm anaphylaxis as the cause of someone's acute symptoms. This is especially true if the person has recurrent episodes and/or if the diagnosis is uncertain.
A tryptase test may be ordered to help diagnose mastocytosis or mast cell activation disorder. While cutaneous mastocytosis typically only causes skin problems (particularly hives), people with systemic mastocytosis or mast cell activation disorder may experience anaphylaxis and its associated symptoms. Persons with systemic mastocytosis may also have persistent symptoms related to the organs affected by mast cell infiltration. If systemic mastocytosis is suspected, an abnormal tryptase test is typically followed by a bone marrow aspiration and biopsy to determine if systemic mastocytosis is present. (Typically there are increased numbers of mast cells in the bone marrow in this disease).
Other testing may be ordered to evaluate a person's health status and to help rule out other conditions that can cause similar symptoms. These may include specific allergy tests to help determine the cause of an allergic reaction, tests such as a FBC (Full Blood Count) to evaluate red and white blood cells, Urea, electrolytes and LFT’s to evaluate organ function, and/or a 5-HIAA (5-hydroxyindoleacetic acid) urine test to rule out a carcinoid tumor that may cause similar symptoms, such as flushing, diarrhoea, and/or wheezing. If stomach or intestinal ulcers are also present, a gastrin test may be done to determine if high gastrin may be the cause.
Occasionally, a tryptase test may be performed post-mortem to help determine if anaphylaxis was the cause of a person's death though this is challenging to interpret.
When is it requested?
Tryptase is not a frequently ordered test. Anaphylaxis is often diagnosed without testing for tryptase, and mastocytosis is rare. A tryptase test is sometimes ordered when a person has symptoms that suggest anaphylaxis, especially when the diagnosis is not clear and/or the symptoms are recurrent. Symptoms of anaphylaxis may include:
Many of these symptoms are also seen with other conditions.
It may also be ordered when a doctor suspects that a person may have cutaneous or systemic mastocytosis or mast cell activation disorder. Persons with such conditions may have many of the same symptoms and signs as persons with severe allergies but often without any specific trigger, such as exposure to a specific food (such as peanuts) or a bee sting, for example. Persons with systemic mastocytosis may have symptoms that indicate organ involvement such as peptic ulcers, chronic diarrhoea, and joint pain. There may be enlargement of organs such as the liver and spleen or enlargement of lymph nodes. There may be skin involvement with rashes or characteristic red blistering lesions that may be present singly or by the hundreds.
A tryptase test may sometimes be ordered after a person's death to help determine if anaphylaxis was the cause of death.
What does the result mean?
Normal tryptase results may indicate that a person's symptoms are due to another cause or may be a matter of sample timing. With anaphylaxis, tryptase levels typically peak about 1 to 2 hours after symptoms begin. If a sample is drawn too early or late, results may be normal. If a histamine test is also performed, it can be compared to the tryptase levels. Histamine concentrations peak within several minutes of the onset of anaphylaxis and fall within about an hour. If the timing of sample collection was appropriate and neither the histamine or tryptase concentrations are elevated, it is less likely that a person had anaphylaxis, but it cannot be ruled out.
Acutely elevated tryptase levels in a person with symptoms of anaphylaxis indicate it as the likely diagnosis.
Acute or persistently elevated "baseline" tryptase levels in a person with symptoms that may be due to mastocytosis make it likely that the person has this condition, but the diagnosis must be confirmed with other testing. Tryptase levels are thought to correlate with mast cell "burden" in those with systemic mastocytosis.
Is there anything else I should know?
Tryptase can also be elevated with asthma, myelodysplastic syndrome (a type of bone marrow disorder), acute myelocytic leukemia, and with any condition that activates the mast cells.
The release of tryptase from mast cells may be triggered by a wide variety of substances, but reaction to a food is thought to be the most common cause of anaphylaxis.
Anyone can have mastocytosis, but children are more frequently affected with cutaneous mastocytosis. In children, mastocytosis is more likely to be self-limited and may be transient.
Studies have linked genetic mutations with some cases of systemic mastocytosis. One of the common mutations identified is a codon-816 C-KIT mutation. Testing for this mutation is not routine but can be performed in Australia at reference centres.
Basophils also produce small amounts of tryptase.
Common questions
No, tryptase is a specialised test that is not offered in every laboratory and must usually be sent to a reference laboratory for testing.
Your doctor may order specific allergy tests to help determine the substances you are allergic to, but a tryptase test would usually be done only if severe allergic symptoms (such as those in anaphylaxis) are present. Most people with allergies will never need to have a tryptase test performed.
Anaphylaxis can be rapidly fatal and requires immediate medical treatment with injections of epinephrine and other medications. This is followed by careful monitoring as it is not uncommon for anaphylaxis to recur within a couple of days of the initial episode. Those who are known to have severe allergic reactions are encouraged to carry a kit that contains an emergency injection of epinephrine with them at all times.
Not necessarily. Tryptase is just one of the criteria that your doctor will consider before making a diagnosis of mastocytosis, which is a rare disorder.
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