Histamine

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.

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.

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.

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.

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.