At a Glance

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 healthcare practitioner 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 health care practitioner.

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.

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 health care practitioner.

Common Questions

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 an anaphylactic 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 health care practitioner 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?

Significantly elevated histamine and/or tryptase levels in a person with symptoms of anaphylaxis 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 cell activation. 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 carcinoid tumors located within the digestive tract produce excess histamine.

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 (chemical substance that transmits messages between nerve cells), 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.

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

Your healthcare practitioner 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.

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.

Can histamine testing be done in my healthcare practitioner's office?

No. Though your sample may be collected at your health care practitioner’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.


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