Tryptase

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 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.

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 signs as 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.

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.

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 of anaphylaxis, 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.

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