What are the treatment options for mast cell disorders?

Treatment Options for Mast Cell Disorders

The first-line treatment for mast cell disorders includes a multimodal approach using mast cell stabilizers and non-sedating antihistamines, followed by carefully selected medications that avoid triggering mast cell degranulation. 1

First-Line Medications

Antihistamines

• H1 Antihistamines (Non-sedating)

  • Fexofenadine or cetirizine
  • Can be increased to 2-4 times standard dose for better control
  • Target symptoms: pruritus, flushing, urticaria, angioedema 1

• H2 Antihistamines

  • Famotidine, ranitidine, or cimetidine
  • Should be added concurrently with H1 antihistamines
  • Target symptoms: abdominal discomfort, vascular symptoms, gastrointestinal symptoms 1

Mast Cell Stabilizers

• Cromolyn Sodium
  • Starting dose with gradual increase to 200 mg 4 times daily (before meals and at bedtime)
  • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain, nausea)
  • May also benefit neuropsychiatric manifestations 1

Second-Line Medications

• Leukotriene Receptor Antagonists

  • Montelukast
  • Useful for skin and gastrointestinal symptoms refractory to other treatments 1

• Aspirin

  • Consider for patients with flushing and hypotension, particularly with increased urinary 11β-PGF2α levels
  • Contraindicated in those with allergic reactions to NSAIDs
  • May require dosing up to 650 mg twice daily (use with caution) 1

• Corticosteroids

  • For short-term management of severe symptoms
  • Initial oral dosage: 0.5 mg/kg/day with slow taper over 1-3 months
  • Not recommended for long-term use due to side effects 1

Advanced Therapies

• Omalizumab

  • Consider for antihistamine-resistant symptoms
  • Particularly effective for recurrent anaphylaxis and skin symptoms 1

• Interferon-alpha

  • FDA-approved for aggressive systemic mastocytosis (ASM) 2
  • Reserved for patients with advanced/aggressive systemic mastocytosis 3

• Imatinib

  • Can be considered in KIT-D816V-negative mast cell disorders
  • May improve quality of life in severe cases 4
  • FDA-approved for aggressive systemic mastocytosis (ASM) 2

• Continuous Diphenhydramine Infusion

  • For severe cases with frequent anaphylactic reactions
  • Consider in intensive care settings when patient is particularly prone to anaphylaxis 4

Emergency Management

• Epinephrine

  • All patients should carry two epinephrine auto-injectors
  • Administer intramuscularly immediately for anaphylaxis 1

• Emergency Action Plan

  • Create for all patients with history of severe reactions
  • Patients should learn supine positioning for hypotensive episodes 1

Treatment Algorithm

1. Initial Approach:

   • Start with H1 antihistamine (non-sedating) + H2 antihistamine
   • Add cromolyn sodium for gastrointestinal symptoms

2. If inadequate response:

   • Increase H1 antihistamine dose (up to 4x standard)
   • Add leukotriene receptor antagonist

3. For persistent symptoms:

   • Consider aspirin (if no NSAID allergy)
   • Short course of corticosteroids for severe flares

4. For refractory cases:

   • Consider omalizumab
   • For aggressive systemic mastocytosis: interferon-alpha or imatinib

Special Considerations

• Medication Adjustments:

  • Reduce doses of antihistamines in renal impairment
  • Use medications metabolized by the liver with caution in hepatic impairment 1

• Timing Optimization:

  • Adjust timing of medication to ensure highest drug levels when symptoms are anticipated
  • For nighttime symptoms, consider adding sedating antihistamine at night (e.g., hydroxyzine 10-25 mg) 1

• Avoid Triggers:

  • NSAIDs should be avoided unless specifically tolerated
  • Avoid opioids when possible due to risk of mast cell activation 1

Monitoring and Follow-up

• Regular assessment of symptom control and medication efficacy

• Periodic laboratory evaluation during symptomatic episodes

• Adjustment of treatment regimen based on response 1

• For patients with osteopenia/osteoporosis: consider calcium and vitamin D supplementation and bisphosphonates with continued antihistamine use 1

The treatment approach should be stepwise and based on symptom severity, with the goal of controlling symptoms caused by mast cell mediator release in most patients, while reserving cytoreductive therapies for those with advanced/aggressive systemic mastocytosis 3, 5.