# Mast cell activation syndrome | Symptoms, Causes, Tests and Treatment | OSANG > MCAS causes repetitive and unpredictable symptoms in various organs, including the skin (urticaria, angioedema), digestive system (abdominal pain, diarrhea), cardiovascu… - Official page: https://osns.co.kr/en/encyclopedia/mast-cell-activation - Organization: OSANG Neurosurgery ## Page content Neurological Conditions ## Mast cell activation syndrome Mast Cell Activation Syndrome · D89.40 Mast cell activation syndrome (MCAS) is a disease in which mast cells are inappropriately activated and secrete excessive mediators such as histamine, causing multi-organ symptoms. ## At a glance MCAS causes repetitive and unpredictable symptoms in various organs, including the skin (urticaria, angioedema), digestive system (abdominal pain, diarrhea), cardiovascular (hypotension, tachycardia), and nervous system (headache, cognitive impairment, dizziness). Triple comorbidity with EDS and POTS is frequent, and this combination has recently received clinical attention. Elevations of tryptase, N-methylhistamine, and prostaglandin D2 in blood or urine are used for diagnosis. - 01Definition and Overview - 02pathophysiology - 03clinical symptoms - 04diagnosis - 05EDS-POTS-MCAS triple companion - 06treatment - 07prognosis ## Definition and Overview Mast cell activation syndrome (MCAS) is a disease that causes multi-organ symptoms by excessively secreting mediators such as histamine, tryptase, prostaglandins, leukotrienes, and cytokines when mast cells are activated without normal stimulation or are excessively activated. Mast cells are immune cells involved in immune surveillance, allergic reactions, and tissue repair, and are distributed around the connective tissue and blood vessels of almost all organs. Therefore, inappropriate activation of mast cells can cause a wide range of symptoms including skin, digestive, cardiovascular, respiratory, and nervous systems. ## pathophysiology ### Mast cell mediator Activated mast cells secrete the following mediators: - Histamine: dilates blood vessels, increases permeability, promotes gastric acid secretion, itching, bronchoconstriction - Tryptase: Decomposes connective tissue, increases vascular permeability - Prostaglandin D2: Vasodilation, bronchoconstriction, pain sensitization. - Leukotrienes C4/D4/E4: Bronchoconstriction, mucus secretion - Cytokines (TNF-α, IL-6): systemic inflammation, fatigue ### Activation mechanism The exact mechanisms of mast cell activation in MCAS vary. IgE-independent pathways (complement, neuropeptide, physical stimulation, stress), hypersensitivity of mast cell surface receptors, and abnormalities in signaling pathways within mast cells are suggested. ## clinical symptoms ### skin - Urticaria, angioedema - facial flushing - Pruritus (itching) - dermatographism ### Digestive system - Abdominal pain, bloating, nausea - Diarrhea or constipation (alternating) - Gastroesophageal reflux - Irritable Bowel Syndrome Patterns ### cardiovascular - hypotension, tachycardia - presyncope, fainting - heart pounding ### nervous system - Headache (including migraine features) - dizzy - Cognitive impairment (brain fog: poor concentration, memory loss) - anxiety, irritability ### respiratory system - Nasal congestion, runny nose - wheezing - shortness of breath ### systemic symptoms - Anaphylaxis (in severe cases) - chronic fatigue - temperature intolerance ## diagnosis ### Diagnostic criteria The diagnostic criteria proposed by Akin et al. in 2010 and refined in a subsequent consensus statement must meet all three of the following: 1. Recurrent (episodic) symptoms of multi-organ mast cell activation (involvement of two or more organs among the skin, digestive system, cardiovascular system, respiratory system, and nervous system) 2. Elevation of mast cell mediators when symptoms appear - Blood tryptase: increase of 20% + 2 ng/mL or more compared to baseline - Increased 24-hour urinary N-methylhistamine, prostaglandin D2, and leukotriene E4 3. Clinical response to antihistamines, mast cell stabilizers, or other drugs targeting mast cell mediators ### Differential diagnosis Mastocytosis, systemic anaphylaxis, carcinoid syndrome, pheochromocytoma, and food allergy must be differentiated. A bone marrow examination may be performed to rule out mastocytosis. ## EDS-POTS-MCAS triple companion The triple comorbidity of EDS (particularly hEDS), POTS, and MCAS has been actively recognized clinically over the past decade. There are several hypotheses about the common mechanism of the three diseases. - Connective tissue abnormalities → decreased mast cell degranulation threshold - Mast cell mediator → vasodilation → worsening of POTS - Autonomic nervous system dysfunction → failure to control mast cell activation This triple disease is more effective when treated in an integrated manner rather than treating each disease individually. ## treatment ### medication A phased approach is recommended. - Step 1: H1 receptor antagonists (cetirizine, loratadine) + H2 receptor antagonists (famotidine, ranitidine) - Step 2: Mast cell stabilizers (cromolyn sodium, ketotifen) - Step 3: Leukotriene receptor antagonist (montelukast) - Step 4: Aspirin (administer with caution in case of prostaglandin excess) - Step 5: Omalizumab (anti-IgE), immunomodulator (in case of refractory disease) ### Avoidance of triggers - Physical stimulation: extreme temperature changes, friction, vibration - Food: Foods high in histamine content (fermented foods, aged cheese, alcohol), individual trigger foods - Drugs: Opioids, NSAIDs (some), contrast media - emotional stress, lack of sleep ### emergency preparedness Patients at risk of anaphylaxis should always carry an epinephrine auto-injector (EpiPen) and know how to use it. It is also recommended to wear a medical alert bracelet to notify medical staff of an MCAS diagnosis. ## prognosis MCAS has a chronic course, but symptoms can be controlled in most patients with appropriate mediator blocking treatment. Long-term symptom management rather than complete remission is a realistic goal, and response to treatment varies greatly from person to person. Identifying and avoiding triggering factors, and optimizing treatment medications step by step are key to improving long-term quality of life. ## Frequently asked questions ### Q01Is MCAS the same disease as allergies? It's different. Allergy is an IgE-mediated immune response to a specific allergen, but MCAS is a condition in which mast cells are inappropriately activated and secrete mediators even in the absence of a specific allergen. Symptoms may be similar to allergies (hives, angioedema, anaphylaxis), but routine allergy tests are often negative. ### Q02What are the symptoms of MCAS? Multi-organ symptoms appear repeatedly, including skin (hives, flushing, angioedema), digestive (abdominal pain, diarrhea, nausea, abdominal distension), cardiovascular (hypotension, tachycardia, syncope), respiratory (wheezing, nasal congestion), and nervous system (headache, dizziness, brain fog, anxiety). Diagnosis is difficult because the type and intensity of symptoms vary each time. ### Q03How is MCAS diagnosed? All three criteria must be met. (1) Recurrent multi-organ mast cell activation symptoms, (2) When symptoms appear, mast cell mediators (blood tryptase, urinary N-methylhistamine, prostaglandin D2) increase, (3) Treatment response to antihistamines or mast cell stabilizers. ### Q04Why do they appear together with EDS and POTS? The exact mechanism has not been fully elucidated. A vicious cycle is assumed in which connective tissue abnormalities (EDS) impede the stability of mast cells, and mast cell mediators promote vasodilation and autonomic dysfunction (POTS). This triple companionship has been actively studied in recent clinical research. ### Q05What is the treatment for MCAS? Combination use of antihistamines (H1 receptor: cetirizine, H2 receptor: famotidine) is the first-line treatment. Mast cell stabilizer (cromolyn sodium) and leukotriene receptor antagonist (montelukast) are added. Avoiding triggers (stress, temperature changes, certain foods) is important, and having an epinephrine auto-injector is essential to prepare for anaphylaxis. ## Related articles - delirium - Cervical radiculopathy - Cervical disc herniation - dystonia This article provides general medical information and does not replace an individual diagnosis or treatment plan. Please seek a medical assessment if symptoms persist. ## Important notice This Markdown alternative helps search and AI tools understand the public page accurately. It provides general health information and does not replace an individual diagnosis or treatment.