What is the treatment for mastocytosis?

Treatment of Mastocytosis

The primary treatment for mastocytosis involves a stepwise approach with H1 and H2 antihistamines as first-line therapy, followed by mast cell stabilizers for symptom control, while cytoreductive therapy is reserved only for advanced systemic mastocytosis. 1

Classification-Based Treatment Approach

Cutaneous Mastocytosis (CM)

• First-line treatment:

  • H1 antihistamines (diphenhydramine, hydroxyzine, cetirizine) to control pruritus, flushing, urticaria, and tachycardia 1
  • H2 antihistamines (ranitidine, famotidine) for gastrointestinal symptoms 1, 2
  • Avoidance of known triggers (temperature extremes, stress, anxiety) 1

• Second-line treatment:

  • Oral cromolyn sodium for gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting) 1
  • Short-term topical corticosteroids for severe skin manifestations 3
  • Phototherapy when antihistamines fail to provide adequate relief 3

Systemic Mastocytosis (SM)

1. Indolent Systemic Mastocytosis (ISM) and Smoldering Systemic Mastocytosis (SSM):

   • Anti-mediator therapy as in cutaneous mastocytosis 1
   • For osteopenia/osteoporosis:
     • Calcium and vitamin D supplementation
     • Bisphosphonates (continue antihistamines)
     • Anti-RANKL monoclonal antibody (denosumab) as second-line therapy 1

2. Advanced Systemic Mastocytosis (ASM, SM-AHN, MCL):

   • Cytoreductive therapy is recommended due to organ damage and shortened survival 1
   • Imatinib for patients with FIP1L1-PDGFRα fusion kinase (100-400 mg daily) 4
   • Midostaurin 100 mg twice daily with food for KIT D816V mutation 1
   • For patients with aggressive SM refractory to other therapies, clinical trials of novel KIT inhibitors should be considered 1

Management of Specific Symptoms

Anaphylaxis Prevention and Management

• All patients should carry two epinephrine auto-injectors 1
• For recurrent anaphylactic attacks, administer epinephrine intramuscularly in recumbent position 1

Gastrointestinal Symptoms

1. H2 antihistamines (ranitidine, famotidine) 1
2. If H2 antihistamines fail, add proton pump inhibitors 1
3. Oral cromolyn sodium for diarrhea, abdominal pain, nausea, and vomiting 1

Bone Pain and Osteoporosis

1. Calcium and vitamin D supplementation
2. Bisphosphonates (first-line)
3. Anti-RANKL antibody (denosumab) for refractory bone pain or patients with renal insufficiency
4. Vertebroplasty/kyphoplasty for refractory pain with vertebral compression fractures 1

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams
• Pre-anesthetic medications: anxiolytics (benzodiazepines), antihistamines (H1 and H2), and possibly corticosteroids
• Safer anesthetic agents: propofol, sevoflurane, isoflurane, fentanyl, remifentanil, lidocaine, bupivacaine
• Avoid: atracurium, mivacurium, succinylcholine; use caution with opiates 1

Pregnancy Management

• Multidisciplinary team including high-risk obstetrics, anesthesia, and allergy
• Continue antihistamines as needed
• Avoid triggers
• Use epinephrine for anaphylaxis
• For severe cases refractory to conventional therapy, interferon-alfa may be considered
• Avoid cladribine and tyrosine kinase inhibitors during pregnancy 1

Monitoring and Follow-up

• Baseline serum tryptase level before starting therapy
• Regular monitoring of symptoms using standardized assessment tools
• Follow-up every 6-12 months for cutaneous mastocytosis 1
• Imaging (CT/MRI) based on disease classification:
  • ISM: only if symptoms worsen
  • SSM: every 6-12 months
  • Advanced SM: more frequently based on treatment response 5

Common Pitfalls to Avoid

1. Using cytoreductive therapy in cutaneous mastocytosis (not recommended due to high rate of spontaneous regression) 1
2. Withholding analgesics during procedures (pain can trigger mast cell activation) 1
3. Failing to equip patients with epinephrine auto-injectors (especially adults and children with severe CM) 3
4. Overlooking the need for comprehensive baseline imaging in systemic mastocytosis 5
5. Using KIT inhibitors in patients with D816V c-Kit mutation who are not sensitive to imatinib 4