What is the treatment for mastocytosis?

Treatment of Mastocytosis

The treatment of mastocytosis should focus on antimediator therapy as first-line management, with cytoreductive options reserved for severe systemic disease that is unresponsive to symptom control measures. 1

Classification and Initial Assessment

Mastocytosis treatment depends on disease classification:

• Cutaneous mastocytosis: Primarily affects skin, common in children
• Systemic mastocytosis: Involves multiple organs, more common in adults
• Mast cell sarcoma: Rare aggressive form

Diagnostic Workup

• Skin biopsy: Confirms diagnosis with aggregates of >20 mast cells
• Laboratory tests: CBC, differential, platelet count, biochemistries, baseline serum tryptase
• Further evaluation for systemic involvement:
  • Abdominal ultrasound if organomegaly suspected
  • Bone marrow biopsy for severe symptoms, organomegaly, lymphadenopathy, or persistent skin lesions after puberty 2

Treatment Approach

First-Line: Antimediator Therapy

1. H1 Antihistamines

   • Non-sedating options (fexofenadine, cetirizine)
   • May increase to 2-4 times standard dose for better control
   • For nighttime symptoms, consider adding sedating antihistamine (hydroxyzine 10-25 mg) 1

2. H2 Antihistamines

   • Famotidine, ranitidine, cimetidine
   • Particularly helpful for gastrointestinal and cardiovascular symptoms
   • Should be used concurrently with H1 antihistamines for enhanced effect 1

3. Mast Cell Stabilizers

   • Cromolyn sodium: FDA-approved for mastocytosis
   • Dosing: Start low and gradually increase to 200 mg 4 times daily before meals and at bedtime
   • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain, nausea)
   • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 1, 3

4. Leukotriene Antagonists

   • Montelukast useful for refractory skin and gastrointestinal symptoms 1

5. Aspirin

   • Consider for patients with flushing and hypotension
   • Contraindicated in those with allergic reactions to NSAIDs
   • May require dosing up to 650 mg twice daily (use with caution) 1

6. 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

Second-Line Therapies

1. Omalizumab

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

2. Cytoreductive Therapies (for systemic mastocytosis with inadequate response to antimediator therapy)

   • KIT inhibitors (midostaurin, avapritinib)
   • Cladribine
   • Imatinib
   • Interferon 1, 4

Emergency Management

• All patients should carry two epinephrine auto-injectors, especially those with history of anaphylaxis
• For anaphylaxis: administer intramuscular epinephrine immediately
• Follow ABC approach (Airway, Breathing, Circulation)
• Consider IV antihistamines (chlorphenamine 10 mg) and hydrocortisone (200 mg) 1

Special Considerations

Perioperative Management

• Multidisciplinary approach with surgical, anesthesia, and medical teams
• Premedication with benzodiazepines, antihistamines, and corticosteroids
• Caution with opioids (can trigger mast cell activation) 1

Pregnancy

• Multidisciplinary team including high-risk obstetrician
• Avoid known triggers
• Continue prophylactic anti-mediator drugs
• Consider interferon-alfa for severe symptoms
• Avoid cladribine, imatinib, and midostaurin during pregnancy 1

Prognosis and Follow-up

• Regular assessment of symptom control and medication efficacy
• Periodic laboratory evaluation during symptomatic episodes
• Patients with indolent systemic mastocytosis demonstrate normal life expectancy
• Bone health management should be considered for patients with osteopenia/osteoporosis 1

Treatment Pitfalls to Avoid

• Delaying epinephrine in anaphylaxis
• Using aggressive cytoreductive therapy in pediatric mastocytosis (most children show improvement over time) 2
• Failing to adjust medication timing to ensure highest drug levels when symptoms are anticipated
• Not considering medication adjustments for patients with renal or hepatic impairment 1