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.