What are the signs and symptoms of Mast Cell Activation Syndrome (MCAS)?

Signs and Symptoms of Mast Cell Activation Syndrome (MCAS)

MCAS presents with recurrent, episodic symptoms affecting at least 2 organ systems simultaneously—not chronic or persistent symptoms—with the four primary systems being cardiovascular, dermatologic, respiratory, and gastrointestinal. 1

Key Diagnostic Feature: Episodic Nature

The defining characteristic is episodic attacks, not continuous symptoms—persistent or chronic symptoms should redirect you toward alternative diagnoses like chronic urticaria or poorly controlled asthma. 1, 2

Cardiovascular Manifestations

• Hypotension 1, 2
• Tachycardia 1, 2
• Syncope or near-syncope (often described as lightheadedness or presyncope) 1, 3, 2
• Anaphylaxis represents the most severe, life-threatening presentation requiring immediate epinephrine 3, 2

Dermatologic Manifestations

• Flushing of face, neck, and chest 1, 3, 2
• Urticaria (hives) 1, 2
• Pruritus (itching) with or without visible rash 1, 3, 2
• Angioedema, particularly affecting eyelids, lips, and tongue 1, 2
• Dermatographism 2

Respiratory Manifestations

• Wheezing 1, 2
• Shortness of breath 1, 2
• Inspiratory stridor 1, 2

Gastrointestinal Manifestations

• Crampy abdominal pain 1, 2
• Diarrhea 1, 3, 2
• Nausea 1, 2
• Vomiting 1, 2
• Abdominal cramping 3, 2

Neurologic/Neuropsychiatric Symptoms

• Neuropsychiatric symptoms are frequently reported but less well-characterized in the formal diagnostic criteria 3, 4, 5
• Conjunctival injection 4, 5
• Nasal stuffiness 4, 5

Critical Clinical Pitfalls

Avoid misdiagnosing MCAS when symptoms are isolated to a single organ system (such as abdominal pain and diarrhea alone, or flushing alone) or when symptoms are chronic rather than episodic—these patterns suggest alternative diagnoses. 1

Do not diagnose MCAS based on symptoms alone—the diagnosis requires all three components: (1) episodic symptoms affecting ≥2 organ systems concurrently, (2) documented acute increases in mast cell mediators during symptomatic episodes on at least 2 occasions, and (3) clinical response to mast cell-targeted therapies. 1, 2, 6

Common Triggers That Precipitate Episodes

• Hot water exposure 2
• Alcohol 2
• Certain medications (particularly opioids, though they should not be categorically avoided) 2, 6
• Physical/emotional stress 2
• Exercise 2
• Infection 2
• Temperature extremes 2
• Mechanical irritation or trauma 2, 6
• Hormonal fluctuations 2

Laboratory Correlation Required

Symptoms must correlate with acute increases in mast cell mediators including serum tryptase (≥20% above baseline PLUS ≥2 ng/mL absolute increase), urinary N-methylhistamine, urinary leukotriene E4, or urinary 11β-prostaglandin F2α measured during symptomatic episodes. 1, 6