Symptoms and Triggers of Mast Cell ActivationMast Cell Activation and TriggersMast 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.1Figure 1. Some Potential Mast Cell Triggers2-5Heat, cold or sudden temperature changesStress: emotional, physical, including pain, or environmental (i.e., weather changes, pollution, pollen, pet dander, etc.)ExerciseFatigueFood or beverages, including alcoholDrugs (opioids, NSAIDs, antibiotics and some local anesthetics) and contrast dyesNatural odors, chemical odors, perfumes and scentsVenoms (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, vibrationSun/sunlightMast Cell Mediator SymptomsThe 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, 14MEDIATORPOSSIBLE EFFECTSHistamineFlushing, itching, diarrhea, hypotensionLeukotrienesShortness of breathProstaglandinsFlushing, bone pain, brain fog, crampingTryptaseOsteoporosis, skin lesionsInterleukinsFatigue, weight loss, enlarged lymph nodesHeparinOsteoporosis, problems with clotting/bleedingTumor Necrosis Factor-αFatigue, headaches, body achesThis 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, 13MAST CELL MEDIATOR SYMPTOMSAnaphylaxisFlushing of the face, neck, and chestItching, +/- rashHives, skin rashesAngioedema (swelling)Nasal itching and congestionWheezing and shortness of breathThroat itching and swellingHeadache and/or brain fog, cognitive dysfunction, anxiety, depressionDiarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux disease (GERD)Bone/muscle pain, osteosclerosis, osteopenia, osteoporosisLight-headedness, syncope/faintingRapid heart rate, chest painLow blood pressure, high blood pressure at the start of a reaction, blood pressure instabilityUterine cramps or bleedingTable 3. When Does this Become Anaphylaxis?(Taken from the American Academy of Allergy, Asthma and Immunology (AAAAI) Anaphylaxis Emergency Action Plan15 and the Anaphylaxis Guidelines Pocketcard16)Anaphylaxis is an acute life-threatening systemic reaction that results from the sudden, rapid, systemic release of mediators.MOUTHItching, swelling of lips and/or tongueTHROAT*Itching, tightness/closure, hoarsenessSKINItching, hives, redness, swellingGUTVomiting, diarrhea, crampsLUNG*Shortness of breath, cough, wheezeHEART*Weak pulse, dizziness, passing outOnly a few symptoms may be present. Severity of symptoms can change quickly. *Some symptoms can be life-threatening. ACT FAST! Use your anaphylaxis action plan! An AAAAI Anaphylaxis Card in English and Spanish is also available. View all References 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. 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