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

Mast Cell Activation Syndrome (MCAS): Symptoms and Treatment

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

Symptoms of MCAS

Key Clinical Manifestations by Organ System

1. Cardiovascular System:

   • Hypotension
   • Tachycardia
   • Syncope 1

2. Respiratory System:

   • Wheezing
   • Shortness of breath 1
   • Bronchospasm 1

3. Dermatologic System:

   • Flushing
   • Urticaria (hives)
   • Pruritus (itching)
   • Angioedema 1

4. Gastrointestinal System:

   • Diarrhea
   • Nausea
   • Vomiting
   • Abdominal cramping/pain 1, 2
   • Bloating 2

5. Neurologic/Cognitive Symptoms:

   • Headaches 3
   • Cognitive dysfunction 1
   • Neuropsychiatric manifestations 1

Diagnostic Criteria

For diagnosis of MCAS, patients must demonstrate:

• Recurrent episodes affecting at least 2 organ systems 4
• Laboratory evidence of mast cell activation during symptomatic episodes:
  • Serum tryptase increase of >20% + 2 ng/mL from baseline 1
  • Elevated urinary markers (N-methylhistamine, prostaglandin D2 or 11β-PGF2α, leukotriene E4) 1
• Documented improvement with antimediator therapy 1

Treatment Options for MCAS

First-Line Treatments

1. Antihistamines:

   • Combination of H1 and H2 antihistamines as initial therapy 1
   • Non-sedating H1 antihistamines preferred for dermatologic manifestations, tachycardia, and abdominal discomfort 1
   • H2 antihistamines for gastrointestinal symptoms 1

2. Mast Cell Stabilizers:

   • Cromolyn sodium: Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting) 1, 3
     • Start at lowest dose and gradually increase to 200 mg 4 times daily before meals and at bedtime 1
     • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 3

3. Leukotriene Modifiers:

   • Montelukast or other leukotriene receptor antagonists 1
   • Most effective for respiratory and dermatologic symptoms 1
   • Works best in conjunction with antihistamines 1

Second-Line and Advanced Therapies

1. Aspirin:

   • May reduce flushing and hypotension, particularly with increased urinary prostaglandin metabolites 1
   • Use with caution due to risk of triggering mast cell degranulation 1
   • Contraindicated in patients with allergic reactions to NSAIDs 1

2. Omalizumab:

   • Consider for MCAS resistant to mediator-targeted therapies 1
   • Reduces severity and frequency of allergic reactions 1
   • May prevent spontaneous episodes of anaphylaxis 1

3. Systemic Corticosteroids:

   • For refractory symptoms 1
   • Initial oral dosage of 0.5 mg/kg/day, followed by slow taper over 1-3 months 1
   • Not recommended for long-term use due to side effects 1

Emergency Management

• Epinephrine autoinjector: Essential for patients with history of systemic anaphylaxis or airway angioedema 1
• Patients should carry two autoinjectors 1
• Albuterol: For bronchospasm symptoms 1
• Supine positioning: For recurrent hypotensive episodes 1

Management Approach

Treatment Algorithm

1. Start with H1 and H2 antihistamines
2. Add cromolyn sodium for persistent gastrointestinal symptoms
3. Add leukotriene antagonists for respiratory/dermatologic symptoms
4. Consider aspirin for prostaglandin-mediated symptoms (with caution)
5. For refractory cases, consider omalizumab or short-term corticosteroids
6. Ensure emergency preparedness with epinephrine autoinjectors

Special Considerations

• Premedication protocol for procedures/surgery: anxiolytic agents, H1 and H2 blockers, and corticosteroids 1
• Bone health management: calcium and vitamin D supplementation for patients with osteopenia/osteoporosis 1
• Referral to specialized centers with expertise in mastocytosis/MCAS for complex cases 1

Treatment Monitoring

• Document symptom improvement with treatment
• Repeat mediator testing to assess biochemical response
• Consider alternative diagnoses if no response to appropriate therapy after 8-12 weeks 1

Common Pitfalls and Caveats

1. MCAS is often misdiagnosed as functional gastrointestinal disorders or irritable bowel syndrome 2
2. Patients experience significant delays in diagnosis 2
3. Persistent symptoms (chronic urticaria, poorly controlled asthma) should direct clinician to different underlying diagnoses 4
4. Chronic increases in mediator levels without episodic symptoms suggest alternative diagnoses 4
5. MCAS requires exclusion of other conditions with similar presentations 4

By following this structured approach to diagnosis and treatment, patients with MCAS can experience significant improvement in quality of life and reduction in symptom burden.