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

Treatment for Mast Cell Activation Syndrome (MCAS)

The treatment of Mast Cell Activation Syndrome requires a stepwise approach with H1 and H2 antihistamines as first-line therapy, followed by mast cell stabilizers and other targeted medications based on symptom presentation and mediator levels. 1

First-Line Treatments

Antihistamines

• H1 receptor antihistamines:

  • Non-sedating H1 antihistamines (cetirizine, fexofenadine) are preferred and can be increased to 2-4 times the standard dose 1
  • Target symptoms: skin manifestations (flushing, pruritus), tachycardia, abdominal discomfort 1
  • Caution: First-generation (sedating) antihistamines like diphenhydramine can cause drowsiness, impair driving ability, and lead to cognitive decline, especially in elderly patients 1

• H2 receptor antihistamines:

  • Options include famotidine, ranitidine, cimetidine 1
  • First-line therapy for gastrointestinal symptoms 1
  • Help H1 antihistamines attenuate cardiovascular symptoms 1

Mast Cell Stabilizers

• Oral cromolyn sodium:
  • Reduces abdominal bloating, diarrhea, and cramps 1
  • May extend benefit to neuropsychiatric manifestations 1
  • Works by stabilizing mast cells and preventing mediator release 2
  • Administration tips: Use divided dosing with weekly upward titration to improve tolerance and adherence 1

Second-Line Treatments

Leukotriene Modifiers

• Montelukast (cysteinyl leukotriene inhibitor) or zileuton (5-lipoxygenase inhibitor):
  • May reduce bronchospasm or gastrointestinal symptoms 1
  • Most effective when urinary LTE4 levels are elevated 1

Anti-inflammatory Agents

• Aspirin:
  • May reduce flushing and hypotension, particularly in patients with elevated urinary 11β-PGF2α levels 1
  • Dosing may require increase up to 650 mg twice daily as tolerated 1
  • Contraindicated in those with allergic or adverse reactions to NSAIDs 1

Other Antihistamines with Additional Properties

• Doxepin: Potent H1 and H2 antihistamine with tricyclic antidepressant activity 1
• Cyproheptadine: Sedating H1 antihistamine with antiserotonergic activities that may help gastrointestinal symptoms 1
• Ketotifen: Sedating H1 antagonist available as compounded tablets in the US 1

Treatments for Severe or Refractory Symptoms

Corticosteroids

• Steroid taper/burst:
  • Useful for refractory symptoms at initial oral dosage of 0.5 mg/kg/day 1
  • Follow with slow taper over 1-3 months 1
  • Consider 50 mg prednisone 13 hours, 7 hours, and 1 hour before procedures when mast cell activation has been problematic 1
  • Long-term use limited by side effects 1

Biologics

• Omalizumab:
  • Can prevent anaphylactic episodes in some patients 1
  • Useful for patients who cannot tolerate needed insect venom immunotherapy 1

Acute Management of Mast Cell Activation

• Epinephrine autoinjector:

  • Essential for patients with history of systemic anaphylaxis or airway angioedema 1
  • Patients should be instructed on proper use 1

• Positioning:

  • Patients with recurrent hypotensive episodes should assume supine position as soon as possible 1

• Bronchodilators:

  • Albuterol can be used via nebulizer or metered-dose inhaler for bronchospasm 1

Trigger Avoidance

• Identify and avoid known triggers (foods, medications, environmental factors) 1
• Common triggers include:
  • Insect venoms
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Medications (aspirin, radiocontrast agents, certain anesthetics) 1

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams 1
• Pre-anesthetic treatment with anxiolytics (benzodiazepines), antihistamines (H1 and H2 blockers), and possibly corticosteroids 1
• Avoid muscle relaxants like atracurium, mivacurium, and succinylcholine 1
• Safer anesthetic agents include propofol, sevoflurane, isoflurane, fentanyl, and remifentanil 1

Skin Care

• Avoid skin dryness
• Use moisturizers
• Water-soluble sodium cromolyn cream for urticaria, pruritus (2-4 times daily) 1
• Topical corticosteroids as needed 1

Common Pitfalls and Caveats

1. Delayed diagnosis: MCAS is often misdiagnosed as a functional disorder, leading to significant delays in proper treatment 3

2. Overreliance on tryptase: While elevated tryptase can confirm mast cell activation, many MCAS patients have normal tryptase levels. Consider measuring other mediators like histamine metabolites, prostaglandins, or leukotrienes 1, 4

3. Inadequate dosing: Antihistamines often need to be used at higher-than-standard doses (2-4x) for effectiveness in MCAS 1

4. Focusing only on histamine: MCAS involves multiple mediators beyond histamine. Treatment targeting only histamine receptors may be insufficient 4

5. Medication interactions: Be aware of potential cognitive effects of anticholinergic antihistamines, especially in elderly patients 1

6. Prophylaxis vs. acute treatment: Antihistamines work better as prophylactic than acute treatment because once symptoms appear, it's too late to block mediator binding 1