Tryptase Test

Tryptase

How is it used?

The tryptase test is a useful indicator of mast cell activation. Mast cells are large tissue cells present in highest amounts in the skin, the lining of the intestine and air passages, and the bone marrow. They release tryptase and other substances as part of the body's normal response to injury but also may release them as part of an allergic response. The tryptase test may be used:

• To confirm a diagnosis of anaphylaxis. Anaphylaxis is primarily diagnosed clinically, but a total tryptase may be ordered, along with a histamine test, 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.
• To help diagnose mastocytosis (too many mast cells) or a mast cell activation disorder. Mastocytosis is a rare group of disorders associated with an abnormal increase in the number of mast cells, which may accumulate in the skin (cutaneous mastocytosis) or in organs throughout the body (systemic mastocytosis).

Other tests may be used to evaluate a person's health status and to help rule out other conditions that can cause similar symptoms. These may include:

• Allergen-specific IgE blood tests to help determine the cause of an allergic reaction
• Complete Blood Count (CBC) to evaluate red and white blood cells
• Comprehensive Metabolic Panel (CMP) to evaluate organ function
• 5-hydroxyindoleacetic acid (5-HIAA) urine test to rule out a carcinoid tumor that may cause similar symptoms, such as flushing, diarrhea, and/or wheezing
• Gastrin test to look for increased secretion of this hormone, which may cause stomach or intestinal ulcers

Occasionally, a tryptase test may be performed postmortem to help determine if anaphylaxis was the cause of a person's death.

When is it ordered?

Tryptase is not a frequently ordered test. Anaphylaxis is usually 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:

• Flushing
• Swelling of the throat, face, tongue, and/or eyes
• Low blood pressure
• Nausea, vomiting, diarrhea, abdominal pain
• Cardiac arrhythmias
• Light-headedness or dizziness
• Difficulty breathing, wheezing
• Itching, often with visible hives
• Confusion and/or loss of consciousness

Many of these symptoms are also seen with other conditions.

This test may also be ordered when a health practitioner suspects that a person may have cutaneous or systemic mastocytosis or a mast cell activation disorder. People with such conditions may have many of the same symptoms and signsas people with severe allergies but often without any specific trigger, such as exposure to a specific food (such as peanuts) or a bee sting. People with systemic mastocytosis may have symptoms that indicate organ involvement, such as peptic ulcers, chronic diarrhea, and joint pain. There may be enlargement of organs such as the liver, spleen, or lymph nodes. There may be skin involvement with rashes or characteristic red, blistering lesions.

A tryptase test may be ordered after a person's death to help determine if anaphylaxis was the cause of death.

What does the test result mean?

Normal tryptase results may indicate that a person's symptoms are not due to mast cell activation, or there could be a problem with 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 unlikely 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.

Persistently elevated tryptase levels in a person with symptoms of mast cell activation suggest that the person has mastocytosis. Additional testing is required to confirm this diagnosis. Tryptase levels are thought to correlate with mast cell "burden" (quantity) in those with systemic mastocytosis.

Is there anything else I should know?

Mast cells contain different forms of the enzyme tryptase, called alpha (α) and beta (β) tryptase, in both inactive and active (mature) forms. Laboratory testing can be performed to measure total tryptase, which is all of the forms together, or mature tryptase. In most cases, a total tryptase is ordered, but sometimes both a total and mature tryptase may be ordered and the ratio of the two compared. As the predominant mature tryptase in the blood is usually beta tryptase, this is essentially a comparison between total tryptase and beta tryptase. Total-to-mature tryptase ratios that are less than 10 are suggestive ofanaphylaxis, while ratios greater than 20 are suggestive of systemic mastocytosis.

If systemic mastocytosis is suspected, an elevated tryptase test may be 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.

Tryptase can also be elevated with asthma, myelodysplastic syndrome (a type of bone marrow disorder), acute myelocytic leukemia, and with any condition that activates 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 may occasionally be performed.

Common Questions

1. Can tryptase testing be done in my doctor's office?
2. If I think I have an allergy, should I have a tryptase test done?
3. How is anaphylaxis treated?
4. If I have an elevated tryptase, does this mean I have mastocytosis?

1.  Can tryptase testing be done in my doctor's office?

No, the tryptase test is a specialized test that is not offered in every laboratory and the sample must usually be sent to areference laboratory for testing.

2.  If I think I have an allergy, should I have a tryptase test done?

Your health practitioner 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 are present. Most people with allergies will never need to have a tryptase test performed.

3.  How is anaphylaxis treated?

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.

4.  If I have an elevated tryptase, does this mean I have mastocytosis?

Not necessarily. Tryptase is just one of the criteria that your healthcare provider will consider before making a diagnosis of mastocytosis, which is a rare disorder.

Histamine Test

Histamine Test

Why Get Tested?

To help confirm a diagnosis of anaphylaxis, mastocytosis, or mast cell activation

When to Get Tested?

When you have symptoms such as flushing, nausea, throat swelling or low blood pressure that may be due to a life-threatening allergic reaction; sometimes when your doctor suspects that you have mastocytosis or mast cell activation

Sample Required?

A blood sample drawn from a vein in your arm or a 24-hour urine collection

Test Preparation Needed?

None for anaphylaxis, but timing of the sample very soon after the beginning of symptoms is important. If testing is done for other conditions, you may be instructed to refrain from taking antihistamine and other medications. This should be discussed with your doctor.

The Test Sample

What is being tested?

Histamine is a substance that is released from specialized cells called mast cells when they are activated, often as part of an allergic immune response. This test measures the amount of histamine in the blood or urine.

Mast cells are large tissue cells found throughout the body. They are present mainly in the skin, the lining of the intestine and air passages, and 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 histamine and tryptase, which are released when mast cells become activated. Histamine is responsible for many of the symptoms in persons with allergies.

Concentrations of histamine in the blood and urine are normally very low. Significant increases can be seen in people with a severe allergic reaction and in those with a disorder in which the number of mast cells increase (proliferate) and/or activate without apparent allergies.

The activation of many mast cells is associated with a severe form of acute allergic reaction termed anaphylaxis, which can cause hives (blisters on the skin), reddening of the skin (flushing), low blood pressure, severe narrowing of the air passages, and even death. With anaphylaxis, histamine concentrations in the blood increase rapidly, rising within 10 minutes of the start of symptoms and returning to normal within about 30 to 60 minutes. This increased production is also reflected a short time later in the urine as histamine and its primary metabolite, N-methylhistamine, are excreted.

Histamine and tryptase levels may be persistently increased in people with mastocytosis. This rare condition is associated with abnormal proliferation of mast cells and their infiltration and accumulation in the skin (cutaneous mastocytosis) and/or in organs throughout the body (systemic mastocytosis).

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm. For a 24-hour urine collection, all of the urine should be saved for a 24-hour period. It is best to keep the sample in a cool, dark place such as a refrigerator.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

If anaphylaxis is suspected, it is important to collect the sample very soon after the beginning of symptoms. If testing is done for other conditions, you may be instructed to refrain from taking antihistamine and other medications. This should be discussed with your doctor.

The Test

1. How is it used?
2. When is it ordered?
3. What does the test result mean?
4. Is there anything else I should know?

How is it used?

The histamine test is a useful indicator of mast cell activation. The test may be used to help confirm that a person has had ananaphylactic reaction, or it may be used to help diagnose mastocytosis, a rare group of disorders characterized by abnormal proliferation of mast cells.

Anaphylaxis is usually diagnosed clinically, but a histamine test may be used along with a tryptase test 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 blood histamine test must be collected rapidly, as soon as symptoms develop.

Instead of a blood test, a histamine test performed on urine collected over a 24-hour period may be ordered instead to evaluate histamine production over a longer time frame. In some cases, the metabolite N-methylhistamine may be measured in urine instead of histamine.

Histamine testing may sometimes be ordered along with a tryptase test to help diagnose mastocytosis or mast cell activation disorder. 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.

When is it ordered?

Histamine is not a frequently ordered test. Anaphylaxis is usually diagnosed without testing for histamine or tryptase, and mastocytosis is rare. Histamine and tryptase tests are 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 include:

• Difficulty breathing, wheezing
• Flushing
• Itching, often with visible hives
• Light-headedness or dizziness
• Low blood pressure
• Swelling of the throat, face, tongue, and/or eyes

Many of these symptoms are also seen with other conditions.

Testing may also be ordered when a doctor suspects that a person may have mastocytosis or a mast cell activation disorder. People with these disorders have many of the same symptoms and signs as persons with severe allergies, but without any specific trigger, such as exposure to certain foods (e.g., peanuts) or a bee sting. Persons with systemic mastocytosis may have signs and symptoms such as peptic ulcers, chronic diarrhea, joint pain, enlarged liver, spleen or lymph nodes, rashes or characteristic red, blistering lesions that may be present singly or by the hundreds.

What does the test result mean?

Acutely elevated histamine and/or tryptase levels in a person with symptoms ofanaphylaxis are strong evidence for that diagnosis.

Normal histamine results may indicate that a person's symptoms are due to another cause, or that the sample was not collected at the right time. With anaphylaxis, blood histamine levels rise rapidly and can fall back to normal within about 30-60 minutes. If a sample is drawn too late, results may be normal. If a tryptase test is also performed, its value can be compared to the histamine levels. Tryptase levels rise and fall more slowly than histamine levels, peaking within 1 to 2 hours of symptom development.

If the timing of sample collection was appropriate and neither the blood histamine or tryptase concentration is elevated, it is less likely that a person had anaphylaxis. However, a person can have anaphylaxis or mastocytosis without elevated histamine levels, so the diagnosis cannot be ruled out just because the test is negative.

Increased levels of histamine and/or N-methylhistamine in a 24-hour urine sample indicate an event associated with mast cellactivation. Persistently elevated histamine and/or tryptase levels in a person with mastocytosis symptoms make it likely that the person has this condition. The diagnosis must still be confirmed with other testing.

Is there anything else I should know?

Histamine may be elevated with any condition that activates mast cells, and the release of histamine may be triggered by a wide variety of substances.

An allergic reaction to a food is thought to be the most common cause of anaphylaxis.

In some people, histamine-related symptoms, such as flushing, headache, diarrhea, itching, etc., may develop after eating histamine-rich foods. Histamine can be found in a variety of foods, especially those that are "aged" such as cheese, wine, and sauerkraut. Symptoms may also be caused by ingesting alcohol, or by drugs that either stimulate the release of histamine or block its metabolism.

Rarely, histamine poisoning can occur by eating fish that has spoiled (e.g., tuna, mackerel) and has high quantities of bacteria-produced histamine. Called scombroid fish poisoning, this condition can cause flushing, sweating, vomiting, headache, and diarrhea.

Some gastrointestinal carcinoid tumors produce excess histamine.

Common Questions

1. Does histamine do anything besides cause allergic reaction symptoms?
2. If I think I have an allergy, should I have a histamine test done?
3. How is anaphylaxis treated?
4. Can histamine testing be done in my doctor's office?

1.  Does histamine do anything besides cause allergic reaction symptoms?

Yes. In addition to allergic reactions, histamine plays a role in inflammatory processes, stimulates gastric acid secretion, acts as a neurotransmitter, dilates blood vessels, increases vascular permeability (allows fluids to move through blood vessel walls), affects smooth muscle contraction in the intestines and lungs, and affects heart rate and contraction. Medications have been developed to block some of the actions of histamine, including antihistamines and drugs that reduce stomach acid secretion.

2.  If I think I have an allergy, should I have a histamine test done?

Your doctor may order specific allergy tests to help determine the substances you are allergic to, but a histamine 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 histamine test performed.

3.  How is anaphylaxis treated?

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.

4.  Can histamine testing be done in my doctor's office?

No. Though your sample may be collected at your doctor's office, it will be sent to a laboratory for testing. Histamine is a specialized test that is only performed in large or specialized laboratories.