What is the treatment for Mast Cell Activation Syndrome (MCAS)?

Treatment of Mast Cell Activation Syndrome (MCAS)

The treatment of MCAS requires a stepwise approach targeting symptom control through avoidance of triggers and pharmacologic interventions with H1/H2 antihistamines, mast cell stabilizers like cromolyn sodium, and leukotriene modifiers as first-line therapies. 1

First-Line Treatment Approach

Trigger Avoidance

• Identify and avoid known triggers including:
  • Insect venoms
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Medications (aspirin, radiocontrast agents, certain anesthetics)

Pharmacologic Management

1. H1 Antihistamines

   • Nonsedating H1 antihistamines are preferred
   • Can be increased to 2-4 times standard dose if needed
   • Sedating antihistamines may cause drowsiness and cognitive impairment, especially in elderly 1

2. H2 Antihistamines

   • First-line for gastrointestinal symptoms
   • Help H1 antihistamines attenuate cardiovascular symptoms 1

3. Cromolyn Sodium (oral)

   • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain, bloating)
   • May also help with neuropsychiatric manifestations
   • Clinical improvement typically occurs within 2-6 weeks and persists 2-3 weeks after withdrawal
   • Recommended dosing: Start low and gradually increase to 200 mg four times daily before meals and at bedtime 1, 2

4. Leukotriene Receptor Antagonists

   • Montelukast or zafirlukast
   • Most effective for dermatologic symptoms when used with H1 antihistamines 1

Acute Management of Mast Cell Activation Attacks

For acute severe reactions (anaphylaxis):

• Intramuscular epinephrine for hypotension or laryngeal angioedema
• Supine positioning for hypotensive episodes
• Inhaled bronchodilators (albuterol) for bronchospasm
• Patients at risk should carry epinephrine autoinjector 1

Second-Line and Refractory Disease Management

For patients with inadequate response to first-line therapy:

1. Aspirin

   • For refractory flushing and hypotensive episodes associated with PGD2 secretion
   • Must be introduced in controlled clinical setting due to risk of triggering mast cell degranulation 1

2. Doxepin

   • Potent H1/H2 antihistamine with tricyclic antidepressant activity
   • May reduce central nervous system manifestations
   • Caution: may cause drowsiness, cognitive decline, and increase suicidal tendencies in young adults with depression 1

3. Glucocorticosteroids

   • For refractory symptoms
   • Should be tapered as quickly as possible to limit adverse effects 1

4. Omalizumab (Anti-IgE therapy)

   • Consider for MCAS resistant to mediator-targeted therapies
   • Can prevent spontaneous episodes of anaphylaxis
   • Reduces severity and frequency of allergic reactions
   • Expensive but may reduce emergency department visits 1

5. Cytoreductive Therapies

   • For clonal MCAS with symptoms refractory to antimediator therapy
   • Options include interferon-alpha and cladribine
   • Significant side effects: flu-like symptoms, depression, hypothyroidism for IFN-α; increased infection risk for cladribine 1

6. Signal Transduction Inhibitors

   • Midostaurin: multikinase inhibitor with activity against wild-type and D816V Kit
   • Masitinib: tyrosine kinase inhibitor with activity against wild-type Kit and Lyn tyrosine kinases
   • Consider for severe cases unresponsive to other interventions 1

Special Considerations

Surgery

• Higher risk of anaphylaxis during perioperative period
• Multidisciplinary management with surgical, anesthesia, and perioperative medical teams
• Pre-anesthetic treatment with anxiolytics, antihistamines, and possibly corticosteroids
• Safer anesthetic agents include propofol, sevoflurane, isoflurane, fentanyl, remifentanil
• Avoid muscle relaxants atracurium and mivacurium; use rocuronium and vecuronium with caution
• Avoid unnecessary trauma and temperature extremes during positioning 1

Pregnancy

• Multidisciplinary management with high-risk obstetrics, anesthesia, and allergy specialists
• Avoidance of triggers, prophylactic antihistamines, as-needed corticosteroids
• Interferon-alpha can be considered for severe refractory cases during pregnancy
• Avoid cladribine and tyrosine kinase inhibitors during pregnancy 1

Common Pitfalls and Caveats

1. Misdiagnosis is common - ensure proper diagnostic criteria are met before initiating treatment 3
2. Not all symptoms attributed to MCAS are actually due to mast cell activation; thorough evaluation for other conditions is essential 3
3. Cromolyn sodium requires at least 1 month trial before determining efficacy 1
4. Aspirin can trigger mast cell degranulation in some patients - introduce with caution 1
5. Medications with additives don't need to be compounded - additive allergies are rare 1
6. Gastrointestinal symptoms of MCAS are often misdiagnosed as functional GI disorders 4

By following this systematic approach to MCAS treatment, clinicians can significantly improve quality of life and reduce morbidity for patients suffering from this challenging condition.