What are the symptoms and treatment options for Mast Cell Activation Syndrome (MCAS)?

Symptoms and Treatment of Mast Cell Activation Syndrome (MCAS)

Mast cell activation syndrome presents with recurrent episodes affecting multiple organ systems, particularly cardiovascular, dermatologic, respiratory, and gastrointestinal systems, and requires treatment with antihistamines, mast cell stabilizers, and other mediator-targeting medications for symptom management. 1

Clinical Presentation of MCAS

Key Symptoms by Organ System

Cardiovascular Symptoms

• Hypotension
• Tachycardia
• Syncope or near-syncope 1

Dermatologic Symptoms

• Urticaria (hives)
• Pruritus (itching)
• Flushing
• Angioedema, particularly of eyelids, lips, and tongue 1

Respiratory Symptoms

• Wheezing
• Shortness of breath
• Inspiratory stridor 1

Gastrointestinal Symptoms

• Crampy abdominal pain
• Diarrhea
• Nausea
• Vomiting 1
• Bloating 2

Important Clinical Features

• Episodes typically involve at least 2 organ systems simultaneously
• Symptoms are recurrent and episodic rather than persistent
• Symptoms correlate with increased mast cell mediator levels
• Anaphylaxis can be life-threatening and requires immediate attention 1

Common Triggers

• Hot water
• Alcohol
• Medications
• Stress
• Exercise
• Hormonal fluctuations
• Infections
• Physical stimuli (pressure, friction) 1

Diagnostic Approach

For proper diagnosis of MCAS, patients must meet these criteria:

1. Recurrent episodes with symptoms affecting multiple organ systems
2. Laboratory evidence of mast cell activation:
   • Elevated serum tryptase during episodes (>20% + 2 ng/mL above baseline)
   • Increased urinary histamine metabolites
   • Elevated prostaglandin D2 or its metabolites
   • Elevated leukotriene E4 1
3. Response to medications targeting mast cell mediators 1

Treatment Algorithm

First-Line Therapies

1. H1 Antihistamines:

   • Non-sedating options (preferred): fexofenadine, cetirizine
   • Can be increased to 2-4 times standard dosing
   • Target symptoms: flushing, pruritus, urticaria, tachycardia 1

2. H2 Antihistamines:

   • Options: famotidine, ranitidine
   • Target symptoms: gastrointestinal symptoms, cardiovascular symptoms 1

3. Mast Cell Stabilizers:

   • Oral cromolyn sodium
   • FDA-indicated for mastocytosis
   • Target symptoms: diarrhea, flushing, headaches, vomiting, abdominal pain 3
   • Begin with divided dosing and weekly upward titration 1

Second-Line Therapies

1. Leukotriene Modifiers:

   • Montelukast or zileuton
   • Particularly helpful for respiratory and gastrointestinal symptoms
   • Most effective when urinary LTE4 levels are elevated 1

2. Aspirin:

   • May reduce flushing and hypotension
   • Most effective when prostaglandin levels are elevated
   • Caution: Contraindicated in those with adverse reactions to NSAIDs
   • May require dosing up to 650 mg twice daily 1

3. Other Antihistamine Options:

   • Cyproheptadine: Helps with gastrointestinal symptoms
   • Ketotifen: Available as compounded medication in US 1

For Severe or Refractory Symptoms

1. Corticosteroids:

   • Short-term use for severe flares
   • Initial dosage: 0.5 mg/kg/day with slow taper over 1-3 months
   • Consider 50 mg prednisone 13 hours, 7 hours, and 1 hour before procedures when mast cell activation has been problematic 1

2. Omalizumab:

   • For prevention of anaphylactic episodes
   • Particularly useful when conventional therapies fail 1

Acute Management

1. Epinephrine autoinjector:

   • Essential for patients with history of anaphylaxis
   • Patients should be trained on proper usage 1

2. Positioning:

   • Supine position for hypotensive episodes 1

3. Bronchodilators:

   • Albuterol for bronchospasm 1

Important Considerations and Pitfalls

1. Medication Side Effects:

   • First-generation H1 antihistamines can cause sedation and cognitive decline, especially in elderly patients 1
   • Long-term steroid use has significant side effects 1

2. Diagnostic Challenges:

   • MCAS is often misdiagnosed as a functional gastrointestinal disorder 2
   • Symptoms must be episodic rather than chronic to support MCAS diagnosis 1

3. Treatment Approach:

   • Antihistamines work better as preventive rather than acute treatment 1
   • Combination therapy targeting multiple mediators is often more effective than monotherapy 1

4. Comorbidities:

   • Consider hereditary alpha-tryptasemia in patients with elevated baseline tryptase levels 1
   • Rule out secondary causes of mast cell activation (allergies, inflammatory disorders) 1

By following this systematic approach to diagnosis and treatment, patients with MCAS can experience significant improvement in symptoms and quality of life.