What is the initial management approach for a patient with suspected Mast Cell Activation Syndrome (MCAS)?

Management of Mast Cell Activation Syndrome (MCAS): Testing and Treatment

For suspected Mast Cell Activation Syndrome (MCAS), initial management should focus on confirming the diagnosis through specific testing and implementing a stepwise treatment approach with antihistamines, mast cell stabilizers, and leukotriene modifiers as first-line therapies. 1

Diagnostic Testing for MCAS

• Collect blood samples for Mast Cell Tryptase at three time points:

  • Initial sample as soon as feasible after symptoms begin
  • Second sample at 1-2 hours after symptom onset
  • Third sample at 24 hours or during convalescence (baseline level) 2

• Diagnosis requires meeting three criteria:

  • Typical clinical signs/symptoms of recurrent, systemic mast cell activation
  • Documented increase in tryptase level >20% + 2 ng/mL within 1-4 hours after symptom onset
  • Response of symptoms to antimediator therapy 3

• Consider measuring other mediator levels to guide therapy:

  • Urinary histamine metabolites
  • Urinary leukotrienes (LTE4)
  • Prostaglandin D2 metabolites 1, 4

First-Line Treatment Approach

• H1 Antihistamines:

  • Use nonsedating options (fexofenadine, cetirizine) as first choice
  • Can increase to 2-4 times standard dose for symptom control
  • First-generation antihistamines may help but can cause sedation and cognitive impairment, especially in elderly patients 1, 5

• H2 Antihistamines:

  • Add famotidine or similar H2 blocker for gastrointestinal symptoms
  • Help attenuate cardiovascular symptoms when combined with H1 blockers 1, 2

• Mast Cell Stabilizers:

  • Oral cromolyn sodium is FDA-approved for mastocytosis
  • Start at lowest dose and gradually increase to 200 mg 4 times daily before meals and at bedtime
  • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting)
  • May take up to a month to show benefit 2, 6

Second-Line Treatment Options

• Leukotriene Modifiers:

  • Montelukast, zafirlukast, or zileuton
  • Most effective when combined with H1 antihistamines
  • Particularly helpful for dermatologic and respiratory symptoms
  • Consider if urinary LTE4 levels are elevated 2, 1

• Aspirin:

  • Can help with refractory flushing and hypotensive episodes associated with PGD2 secretion
  • Should be introduced in a controlled clinical setting due to risk of triggering mast cell degranulation
  • Consider if prostaglandin metabolite levels are elevated 2, 1

• Glucocorticosteroids:

  • May help some patients during acute episodes
  • Should be tapered as quickly as possible to limit adverse effects 2

Management of Acute Episodes

• Prescribe epinephrine autoinjector for patients with history of systemic anaphylaxis or airway angioedema

  • Provide proper training on use 1

• For anaphylaxis management:

  • Use ABC approach (Airway, Breathing, Circulation)
  • Remove all potential causative agents
  • Call for help and note the time
  • Administer oxygen 100%
  • Elevate legs if hypotension present
  • Administer epinephrine (initial dose 50 μg IV for adults)
  • Administer IV fluids (saline 0.9% or lactated Ringer's) 2

• Secondary management:

  • Chlorphenamine 10 mg IV (adult dose)
  • Hydrocortisone 200 mg IV (adult dose)
  • Consider alternative vasopressors if blood pressure doesn't recover
  • Treat persistent bronchospasm with salbutamol infusion 2

Advanced Therapies for Refractory Cases

• Omalizumab:

  • Consider for MCAS resistant to mediator-targeted therapies
  • Binds free IgE, preventing its binding to FcεRI
  • Can reduce severity and frequency of allergic reactions
  • May prevent spontaneous episodes of anaphylaxis 2

• Cytoreductive Therapies:

  • For patients with clonal MCAS in advanced systemic mastocytosis
  • Options include IFN-α and cladribine
  • Associated with significant adverse effects 2

• Signal Transduction Inhibitors:

  • Midostaurin - approved for advanced systemic mastocytosis
  • Masitinib - may help with mediator-related symptoms
  • Imatinib - not indicated if D816V mutation is present 2

Prevention Strategies

• Identify and avoid known triggers:

  • Insect venoms
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Certain medications (radiocontrast agents, specific anesthetics) 1

• For perioperative management:

  • Multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams
  • Pre-anesthetic treatment with anxiolytics, antihistamines, and possibly corticosteroids
  • Use safer anesthetic agents (propofol, sevoflurane, isoflurane, fentanyl)
  • Avoid certain muscle relaxants (atracurium, mivacurium, succinylcholine) 1, 7

Common Pitfalls to Avoid

• Sedating H1 antihistamines can cause cognitive decline, particularly in elderly patients 1
• Aspirin should be used with caution due to risk of triggering mast cell degranulation 2, 1
• Long-term steroid use should be avoided due to side effects 1
• Misdiagnosis is common - complete thorough evaluation before confirming MCAS 8
• Symptoms may be misinterpreted as MCAS when other clinically relevant conditions are present 8