Tryptase: Diagnosis for Mast Cell Activation

by | Mar 6, 2023 | Blog

I regularly talk about histamine on this blog. Today, I want to discuss another mast cell mediator, tryptase. Though tryptase is rarely talked about on the internet, it is an important enzyme found in your mast cells. 

When your mast cells get activated, they not only release histamine but tryptase and other chemicals too as a natural immune response. Measuring tryptase levels can be used as a biomarker for mast cell activation and to see if there is a severe immune reaction in your body. 

What Are Mast Cells?

Your mast cells play a critical role in your immune and overall health. They are a type of white blood cells in connective tissues, including your digestive tract, skin, respiratory tract, urinary tract, reproductive organs, surrounding your nerves, and near your blood vessels and lymph vessels. Your mast cells are in charge of storing histamine and other inflammatory mast cell mediators. When your body encounters an allergen or is exposed to a foreign pathogen or chemical, it can release these inflammatory mediators to fight invaders and protect your body.

Your mast cells are clearly critical for your overall health. However, overactive mast cells can cause issues. They may lead to mast cell activation syndrome (MCAS) or other mast cell disorders.

MCAS is a complex health condition that can cause chronic inflammation and widespread symptoms, including skin issues, headaches, migraines, fatigue, brain fog, weakness, dizziness, gastrointestinal troubles, anxiety, rhinitis, and more (1, 2, 3, 4).

Triggers of Mast Cell Activation

Mast cell activation may be triggered by a variety of factors, including:

  • Mold
  • Allergens, including insect bites, gluten, other foods, and preservatives
  • Infections, including viruses and fungi
  • Chemicals and other toxins, including conventional cleaning and personal hygiene products
  • Heavy metals, including mercury from dental work
  • Smells, including perfumes and other conventional beauty or body products
  • Medications, including antibiotics, ibuprofen, and opiate pain relievers
  • Physical or psychological stress from anxiety, exercise, lack of sleep, pain, rapid temperature changes, or other factors
  • Hormonal changes, including hormonal fluctuations during the menstrual cycle
  • Mast cell hyperplasia, a rare health condition related to certain chronic infections or cancers

What Is Tryptase

Tryptase is an enzyme found in your mast cells. When your mast cells get activated, they release tryptase along with histamine and other chemicals as part of your natural immune response to allergens or other triggers. Measuring tryptase levels can be used as a biomarker for mast cell activation and to see if there is a severe immune reaction in your body. Measuring tryptase levels may also help to detect various blood disorders that affect mast cell functions (7, 8, 9). 

Using tryptase as a measure for mast cell disorders is not a new idea. A 1987 study published in the New England Journal of Medicine had discussed that tryptase levels may indicate mast cell activation, anaphylaxis, mastocytosis, and other mast cell-related events (10). According to a 2004 review published in Anesthesia, the release of tryptase is a characteristic of mast cell degradation. Tryptase levels may increase in mast cell disorders and hematological conditions (11).

A 2010 study published in the Journal of Allergy and Clinical Immunology has discussed tryptase as a diagnostic criteria option for mast cell issues (12). According to a 2017 review published in the Journal of Allergy and Clinical Immunology, increased levels of tryptase may be linked to mastocytosis, mast cell hyperplasia, mast cell issues, hypertryptasemia, chronic kidney disease, and myeloid neoplasms (13). According to a 2020 review published in the Polish Archives of Internal Medicine, tryptase may be important for the diagnosis of MCAS, especially in those with anaphylaxis, osteoporosis, and those requiring an epinephrine emergency kit or needing insect venom immunotherapy (14).

What Does the Tryptase Test Measure?

Tryptase is an enzyme that is stored in your mast cells throughout your body. When these mast cells are activated, they release tryptase, histamine, and other chemicals. This will lead to symptoms of allergies, including itching, redness, flushing, or difficulty breathing. If you have a severe allergic reaction, your tryptase levels will likely be elevated for about 12 to 24 hours before returning to normal. The tryptase test measures your blood tryptase levels to check markers for severe allergic reactions and mast cell activation.

Purpose of the Tryptase Test

Checking your tryptase levels may be helpful for

  • Diagnosing mast cell disorders
  • Monitoring patients with mast cell activation problems and see if their disease is progressing, stabilizing, or improving 
  • Checking if you’ve had a recent severe allergic reaction or anaphylaxis

Symptoms Attributed to Tryptase

Symptoms associated with elevated tryptase levels may include:

  • Itching
  • Hives
  • Skin flushing
  • Swollen skin
  • Dizziness
  • Difficulty breathing
  • Anaphylaxis 
  • Mucus buildup
  • Wheezing
  • Difficulty maintaining a normal pulse or blood pressure
  • Chronic joint pain, head pain, or back pain
  • Headache or migraine
  • Digestive issues, such as vomiting, nausea, and diarrhea
  • Confusion or unconsciousness

When and How to Measure Tryptase

Measuring tryptase levels may be important if you have symptoms of flushing, throat swelling, low blood pressure, nausea, or other serious allergic reactions. It may also be beneficial if you have symptoms of mast cell activation or mastocytosis (17).

Tryptase testing is simple. There is no test preparation necessary. The test can be done as soon as symptoms appear or whenever your doctor orders it. It only requires a blood sample drawn from the vein in your arm (17).

Criteria for Mast Cell Diagnosis

According to a 2014 review published in Expert Review in Hematology, the average normal tryptase level is around 5 ng/ml, with a range of <1 to 30 ng/ml (15). In 99 percent of healthy individuals, tryptase levels are equal to or under 15 ng/mL. Many providers consider under 11.4 or even under 10 ng/ml normal. According to a 2020 review published in Experimental and Therapeutic Medicine and a 2021 consensus proposal paper published in HemaSphere, “greater than 20 ng/ml tryptase is a minor diagnostic criterion for systemic mastocytosis” (18, 19). Seeing higher levels than 20 ng/ml may suggest systemic mastocytosis or mast cell activation syndrome

There is some suggestion that the tryptase test is under-utilized in primary care. For anaphylactic reactions, the level will be higher in the 1-2 hours after the reaction than at any other time. The measurement is best done within 2 hours, but not after 4 hours according to specific published guidelines. (20) Also important is checking a baseline level in suspected mast cell patients i.e. not during a flare, and then re-testing the tryptase when symptoms do flare at a later date in order to compare results, checking for elevation. This helps with diagnosis.

Your doctor may also order a histamine test to compare results. For further diagnosis and to rule out other conditions, your doctor may order other tests as well, including a complete blood count (CBC), comprehensive metabolic panel (CMP), allergy testing, 5-hydroxyindoleacetic acid (5-HIAA) urine test, or gastrin test (17).

Next Steps

Are you interested in tryptase testing? Are you experiencing symptoms of mast cell disorders or histamine intolerance? Working with a healthcare practitioner knowledgeable about histamine intolerance and MCAS is the best way to get to the root cause of your symptoms and create an individualized treatment. I welcome you to start a personalized functional medicine consultation with me for further guidance to improve your health. You may book your consultation here.

Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.

Learn more about working with Dr. Gannage