When is Cromolyn (cromolyn sodium) indicated in Mast Cell Activation Syndrome (MCAS)?

Cromolyn Sodium in Mast Cell Activation Syndrome (MCAS)

Oral cromolyn sodium is primarily indicated for gastrointestinal symptoms in MCAS, and should be introduced at the lowest dose and gradually increased to 200 mg four times daily before meals and at bedtime. 1

Primary Indications for Cromolyn in MCAS

• Gastrointestinal symptoms: Cromolyn is most effective for managing:

  • Diarrhea 1, 2
  • Abdominal pain 1, 2
  • Nausea 1, 2
  • Vomiting 1, 2

• Cutaneous symptoms: Cromolyn can help with:

  • Pruritus (itching) - both oral and topical formulations 1
  • Urticaria 2
  • Flushing 2

• Neurologic symptoms: May improve:

  • Headaches 2
  • Cognitive dysfunction 1

Dosing and Administration

• Starting dose: Begin with the lowest possible dose 1
• Titration: Gradually increase to full therapeutic dose 1
• Target dose: 200 mg four times daily (before each meal and at bedtime) 1
• Duration of trial: Patients should be counseled that onset of action can be delayed and should take cromolyn for at least 1 month before deciding whether it is helping 1

Mechanism of Action

Cromolyn sodium inhibits the degranulation of sensitized mast cells, preventing the release of mediators including histamine and slow-reacting substance of anaphylaxis (SRS-A) 3. It has no intrinsic vasoconstrictor, antihistamine, or anti-inflammatory activity 3.

Treatment Algorithm for MCAS

1. First-line therapy: H1 and H2 antihistamines 1

   • For skin symptoms, gastrointestinal symptoms, neurologic symptoms

2. Second-line therapy: Add cromolyn sodium 1

   • Particularly when gastrointestinal symptoms predominate
   • When first-line therapy is insufficient

3. Third-line options (if symptoms persist):

   • Leukotriene receptor antagonists (for skin and GI symptoms) 1
   • Aspirin (for flushing and hypotensive episodes) - caution needed as it may trigger mast cell degranulation 1
   • Omalizumab (for refractory cases with anaphylaxis) 1

Limitations and Considerations

• Cromolyn has poor systemic absorption when taken orally 3
• It is a relatively weak inhibitor of histamine release from human mast cells compared to some natural flavonoids like luteolin 4
• Newer alternatives like quercetin may be more effective than cromolyn in blocking human mast cell cytokine release 5
• Cromolyn must be administered with the trigger or it rapidly loses its effect 5

Special Considerations

• Topical application: Cromolyn in the form of ointment or cream can be used to decrease flare-ups of cutaneous symptoms in response to triggers 1
• Preventative use: Can be effective for episodic symptoms when taken before anticipated trigger exposure 1
• Combination therapy: Often used alongside H1 and H2 antihistamines for better symptom control 1

Monitoring Response

• Evaluate response after at least 1 month of consistent use 1
• If beneficial, continue as maintenance therapy 1
• If ineffective after adequate trial, consider alternative or additional therapies 1

Cromolyn sodium remains an important medication in the management of MCAS, particularly for gastrointestinal symptoms, though its effectiveness varies between patients and symptom types.