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

Symptoms of Mast Cell Activation Syndrome (MCAS)

Mast Cell Activation Syndrome (MCAS) is characterized by recurrent episodes affecting at least two organ systems, including cardiovascular, respiratory, dermatologic, and gastrointestinal systems, with symptoms such as hypotension, tachycardia, syncope, wheezing, flushing, urticaria, and abdominal pain. 1

Multi-System Manifestations

Cardiovascular Symptoms

• Hypotension
• Tachycardia
• Syncope (fainting)
• Flushing

Respiratory Symptoms

• Wheezing
• Shortness of breath
• Nasal congestion/stuffiness

Dermatologic Symptoms

• Urticaria (hives)
• Pruritus (itching)
• Angioedema
• Flushing

Gastrointestinal Symptoms

• Abdominal pain/cramping
• Nausea
• Vomiting
• Diarrhea
• Bloating
• Symptoms resembling irritable bowel syndrome or dyspepsia 2

Neurologic Symptoms

• Headache
• Brain fog
• Cognitive difficulties
• Anxiety
• Neuropsychiatric manifestations 1

Common Triggers for Mast Cell Activation

MCAS symptoms are often triggered by specific factors, including:

• Foods (particularly high-histamine or histamine-releasing foods)
• Temperature extremes (hot or cold)
• Mechanical irritation
• Alcohol and fermented beverages
• Certain medications
• Emotional stress
• Physical exertion 1

Diagnostic Considerations

For a diagnosis of MCAS, patients must demonstrate:

1. Recurrent episodes affecting at least 2 organ systems
2. Laboratory evidence of mast cell activation during symptomatic episodes
3. Documented improvement with antimediator therapy 1

Laboratory evidence typically includes:

• Serum tryptase increase of >20% + 2 ng/mL from baseline during symptomatic episodes
• Increased urinary levels of mast cell mediators during symptomatic periods:
  • N-methylhistamine
  • Prostaglandin D2 or 11β-PGF2α
  • Leukotriene E4 1

Clinical Variants of MCAS

MCAS can be classified into three main categories:

1. Primary MCAS: Associated with KIT-mutated, clonal mast cells 3
2. Secondary MCAS: Triggered by underlying inflammatory disease, often IgE-dependent allergy 3
3. Idiopathic MCAS: No identifiable underlying disease or KIT-mutated mast cells 3

Severity Spectrum

The severity of MCAS symptoms ranges from mild to severe to life-threatening, depending on:

• Genetic predisposition
• Number and releasability of mast cells
• Organs affected
• Type and consequences of comorbid conditions 3

Important Clinical Considerations

• MCAS is often misdiagnosed as a functional disorder, leading to significant delays in diagnosis 2
• Symptoms may be refractory to standard symptom-targeted medications 2
• Severe cases may present with life-threatening anaphylaxis, especially in patients with combined forms of MCAS 3
• Patients with MCAS should carry epinephrine autoinjectors for potential severe reactions 1

The recognition of MCAS symptoms is crucial for proper diagnosis and management, as appropriate treatment can dramatically improve quality of life for affected patients.