What is the initial treatment for patients with mast cell disorders?

Initial Treatment for Mast Cell Disorders

All patients with mast cell disorders should be started on a combination of H1 and H2 receptor antihistamines, with the addition of oral cromolyn sodium as a mast cell stabilizer, and all patients must carry two epinephrine auto-injectors for emergency management of anaphylaxis. 1, 2

Emergency Preparedness (Critical First Step)

• Every patient with a mast cell disorder must carry two epinephrine auto-injectors to manage potential anaphylaxis, as this is a life-threatening complication that can occur unpredictably 1
• Adult dosing: 500 μg IM (0.5 ml of 1:1000 solution) for patients >12 years 1
• Patients should be educated on triggers that can induce mast cell activation and anaphylaxis, including surgery, endoscopy, invasive procedures, temperature extremes, and certain medications 1, 3

First-Line Anti-Mediator Therapy (Start Immediately)

H1 Receptor Antihistamines

• Begin with second-generation non-sedating H1 antihistamines such as cetirizine or fexofenadine at 2-4 times the FDA-approved doses to effectively reduce inflammation and symptoms 2, 4
• These agents control pruritus, flushing, urticaria, angioedema, gastrointestinal symptoms (diarrhea, abdominal cramping, nausea, vomiting), neurologic symptoms (headache, poor concentration, brain fog), cardiovascular symptoms (presyncope, syncope, tachycardia), and pulmonary symptoms (wheezing, throat swelling) 1
• Avoid first-generation H1 antihistamines (diphenhydramine, hydroxyzine) as primary therapy due to significant sedation and cognitive decline, particularly in elderly patients 2, 4

H2 Receptor Antagonists

• Add an H2 receptor antagonist (famotidine, ranitidine, or cimetidine) to specifically target abdominal symptoms and complement H1 blocker effects 1, 2
• The combination of H1 and H2 blockers is more effective than either agent alone for controlling mast cell mediator symptoms 1, 4

Cromolyn Sodium (Mast Cell Stabilizer)

• Add oral cromolyn sodium to prevent mast cell degranulation and mediator release, particularly effective for gastrointestinal and neurologic symptoms 1, 2, 5
• FDA-approved dosing: 200 mg four times daily 5
• Clinical improvement typically occurs within 2-6 weeks of treatment initiation and persists for 2-3 weeks after withdrawal 5
• Cromolyn sodium has demonstrated improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching 5
• Topical cromolyn sodium (ointment or cream) can be used to decrease flare-ups of cutaneous symptoms in response to triggers 1

Second-Line Therapy (Add if Symptoms Persist)

Leukotriene Pathway Inhibitors

• Add montelukast (leukotriene receptor antagonist) or zileuton (5-lipoxygenase inhibitor) if symptoms persist despite H1/H2 blockers and cromolyn sodium, particularly if urinary LTE4 levels are elevated 1, 2, 4
• These agents are particularly useful for skin and gastrointestinal symptoms refractory to antihistamines 1

Aspirin Therapy

• Consider aspirin for patients with elevated urinary prostaglandin levels, but use with extreme caution as aspirin can trigger mast cell activation in some patients 1, 4
• The risks and benefits must be carefully weighed on an individual basis 1

Cyproheptadine

• Consider cyproheptadine (sedating H1 blocker with serotonin receptor antagonist properties) for refractory diarrhea and nausea 2

Refractory Symptoms

Corticosteroids

• Short course of oral corticosteroids (prednisone 0.5 mg/kg/day with slow taper over 1-3 months) for refractory symptoms not responding to first-line therapy 2
• Hydrocortisone 200 mg IV for acute severe reactions in adults 1

Omalizumab

• Anti-IgE monoclonal antibody therapy can be used for mast cell activation symptoms insufficiently controlled by other measures 1

Systemic Mastocytosis Specific Considerations

• All patients with systemic mastocytosis require anti-mediator drug therapy as described above 1
• Cytoreductive therapy is recommended for advanced systemic mastocytosis (aggressive systemic mastocytosis, SM with associated hematologic neoplasm, and mast cell leukemia) due to organ damage and shortened survival 1
• Enrollment in clinical trials investigating selective KIT D816V inhibitors is encouraged for advanced disease 1

Critical Medication Precautions

Opioids

• Use morphine and codeine with caution as they can trigger mast cell activation, though they should not be withheld if needed since pain itself triggers mast cell degranulation 3, 4
• Fentanyl and remifentanil are safer opioid options compared to morphine or codeine 2, 3
• IV administration is preferred over oral administration to ensure reliable drug delivery 3

Premedication for Procedures

• Premedications are recommended for most procedures (surgery, endoscopy, invasive and radiologic procedures) as these can induce mast cell activation and anaphylaxis 1

Treatment Monitoring

• Treatment efficacy may take weeks to become apparent, particularly with cromolyn sodium 2, 5
• Monitor symptom improvement using validated tools; assessment at baseline and during treatment is recommended 1
• Have emergency medications (epinephrine, corticosteroids, additional antihistamines) readily available during treatment adjustments 3