Histamine

At a Glance

Why get tested?

To help confirm a diagnosis of anaphylaxis or symptomatic mastocytosis. However, due to the need for blood samples to be processed extremely quickly after the blood is taken, this test is rarely performed.

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.

Sample required?

A blood sample drawn from a vein in your arm or a 24-hour urine collection. The blood sample must be spun and frozen within 5 minutes of 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 healthcare professional.

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you may be able to access your results online. Your GP practice will be able to provide specific details.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, sex, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

What is being tested?

Histamine is a substance that is released from specialised cells called mast cells when they are activated, often as part of an allergic immune response. This test measures the amount of histamine or its breakdown products 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. Please follow any instructions you are given.

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 healthcare professional.

Common Questions

How is it used?

The histamine test is an 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 characterised by abnormal proliferation of mast cells. It is more common to use mast cell tryptase in this setting, on very rare occasions clinicians may want to confirm the significance of an unexpected tryptase result.

Anaphylaxis is usually diagnosed clinically, but a histamine test may be used along with a tryptase test result 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 sample for analysis of histamine must be collected rapidly, as soon as symptoms develop and prepared and frozen almost immediately.

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

Histamine testing may sometimes be requested 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 may experience anaphylaxis and its associated symptoms.
When is it requested?
Histamine measurement is is only available in specialist centres, and is not a frequently requested test, due to the sample collection and processing requirements. Anaphylaxis is usually diagnosed without testing for histamine, and mastocytosis is rare. Histamine and tryptase tests are sometimes requested when a person has symptoms that suggest anaphylaxis, especially when the diagnosis is not clear and/or the symptoms are recurrent or there are concerns that the tryptase result is incorrect.

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 requested when a specialist practitioner suspects that a person may have mastocytosis. People with this disorder 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 diarrhoea, 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 supporting 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, or that it wasn’t processed rapidly enough. 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.

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.