Symptoms and Triggers of Mast Cell Activation


Mast Cell Activation and Triggers

Mast cells can be activated to release mediators by multiple triggers. Possible triggers of mediator release are shown below in Figure 1. Please note that any patient with a mast cell disease can potentially react to any trigger, and triggers can change over the course of the disease. In addition, patients may experience reactions to virtually any medications, including medications that they have tolerated previously. Common medication reactions in mast cell disease patients include, but are not limited to: opioids, antibiotics, NSAIDs, alcohol-containing medicines and intravenous vancomycin. Use with caution. More information related to drug hypersensitivity in mast cell diseases is available in a position paper by European specialists.1

Figure 1. Some Potential Mast Cell Triggers2-5

  • Heat, cold or sudden temperature changes
  • Stress: emotional, physical, including pain, or environmental (i.e., weather changes, pollution, pollen, pet dander, etc.)
  • Exercise
  • Fatigue
  • Food or beverages, including alcohol
  • Drugs (opioids, NSAIDs, antibiotics and some local anesthetics) and contrast dyes
  • Natural odors, chemical odors, perfumes and scents
  • Venoms (bee, wasp, mixed vespids, spiders, fire ants, jelly fish, snakes, biting insects, such as flies, mosquitos and fleas, etc.)
  • Infections (viral, bacterial or fungal)
  • Mechanical irritation, friction, vibration
  • Sun/sunlight

Mast Cell Mediator Symptoms

The myriad symptoms patients with mast cell diseases experience during mast cell activation can wreak havoc on patients on a daily basis, and multiple organ systems, including pulmonary, cardiovascular, dermatologic, gastrointestinal, musculoskeletal, and neurologic can be involved. Table 1 lists some potential effects linked to specific mediators.5-13 Symptoms (Table 2) may include, but are not limited to: flushing of the face, neck, and chest; headache; tachycardia and chest pain; abdominal pain, bloating, gastroesophageal reflux disease (GERD), diarrhea, vomiting; uterine cramps or bleeding; rashes, including maculopapular cutaneous mastocytosis (MPCM)/urticaria pigmentosa (UP), telangiectatic lesions; bone/muscle pain, osteosclerosis, osteopenia, osteoporosis; itching, +/- rash; blood pressure instability; brain fog, cognitive dysfunction; anxiety/depression; lightheadedness, syncope; and anaphylaxis. These symptoms may appear as acute (as in anaphylaxis, see Table 3) or as chronic conditions. It should be noted that the manifestation of anaphylaxis or similar symptoms among infants and preschoolers may be more difficult to identify.

Table 1. Possible Effects of Some Mast Cell Mediators13, 14




Flushing, itching, diarrhea, hypotension


Shortness of breath


Flushing, bone pain, brain fog, cramping


Osteoporosis, skin lesions


Fatigue, weight loss, enlarged lymph nodes


Osteoporosis, problems with clotting/bleeding

Tumor Necrosis Factor-α

Fatigue, headaches, body aches

This list is by no means complete and serves as an example. Mast cells secrete many mediators responsible for numerous symptoms within different organ systems.

Table 2. Mast Cell Mediator Symptoms12, 13



Flushing of the face, neck, and chest

Itching, +/- rash

Hives, skin rashes

Angioedema (swelling)

Nasal itching and congestion

Wheezing and shortness of breath

Throat itching and swelling

Headache and/or brain fog, cognitive dysfunction, anxiety, depression

Diarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux disease (GERD)

Bone/muscle pain, osteosclerosis, osteopenia, osteoporosis

Light-headedness, syncope/fainting

Rapid heart rate, chest pain

Low blood pressure, high blood pressure at the start of a reaction, blood pressure instability

Uterine cramps or bleeding

When does this Become Anaphylaxis?

 Anaphylaxis is an acute life-threatening systemic reaction that results from the sudden, rapid, systemic release of mediators. Please refer to Allergy and Anaphylaxis Australia for signs and symptoms and more information about anaphylaxis.


  1. Bonadonna P, Pagani M, Aberer W, Bilo MB, Brockow K, Oude Elberink H, et al. Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper. Allergy. 2015 Jul;70(7):755-63.
  2. Silva I, Carvalho S, Pinto PL, Machado S, Rosado Pinto J. Mastocytosis: a rare case of anaphylaxis in paediatric age and literature review. Allergol Immunopathol (Madr). 2008 May-Jun;36(3):154-63.
  3. Jennings S, Russell N, Jennings B, Slee V, Sterling L, Castells M, et al. The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions. J Allergy Clin Immunol Pract. 2014 Jan-Feb;2(1):70-6.
  4. Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, et al. Vibratory Urticaria Associated with a Missense Variant in ADGRE2. N Engl J Med. 2016 Feb 18;374(7):656-63.
  5. Akin C, Metcalfe DD. Mastocytosis and mast cell activation syndromes presenting as anaphylaxis.In: Castells MC, editor. Anaphylaxis and hypersensitivity reactions. New York: Humana Press; 2011. p. 245-56.
  6. Escribano L, Akin C, Castells M, Orfao A, Metcalfe DD. Mastocytosis: current concepts in diagnosis and treatment. Ann Hematol. 2002 Dec;81(12):677-90.
  7. Castells M, Austen KF. Mastocytosis: mediator-related signs and symptoms. Int Arch Allergy Immunol. 2002 Feb;127(2):147-52.
  8. Castells M. Mast cell mediators in allergic inflammation and mastocytosis. Immunol Allergy Clin North Am. 2006 Aug;26(3):465-85.
  9. Butterfield JH, Weiler CR. Prevention of mast cell activation disorder-associated clinical sequelae of excessive prostaglandin D(2) production. Int Arch Allergy Immunol. 2008;147(4):338-43.
  10. Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol. 2010 Dec;126(6):1099-104 e4.
  11. Afrin LB. Presentation, diagnosis and management of mast cell activation syndrome.In: Murray DB, editor. Mast cells: phenotypic features, biological functions and role in immunity. Hauppauge: Nova Science Publishers, Inc.; 2013. p. 155-232.
  12. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-25.
  13. Theoharides TC, Valent P, Akin C. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med. 2015 Jul 9;373(2):163-72.
  14. Carter MC, Metcalfe DD, Komarow HD. Mastocytosis. Immunol Allergy Clin North Am. 2014 Feb;34(1):181-96.
  15. Lieberman P, American College of Allergy, Asthma and Immunology and American Academy of Allergy, Asthma and Immunology. Anaphylaxis Guidelines Pocketcard. Baltimore, MD: International Guidelines Center; 2011.


TAMS wish to acknowledge The Mast Cell Diseases Society (TMS) as the original authors of the above information. Reproduced with permission. View original source on the TMS website.

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