Mast Cell Disease

Mast Cell Disease

 

Systemic mastocytosis, the most common mast cell disease, is associated with mast cell hyperplasia and elevated histamine and tryptase levels.

Epidemiology

  • Incidence – rare disease
  • Age – except for cutaneous mastocytosis, the disease predominates in adults

Classification

  • WHO classification of mastocytosis
    • Cutaneous mastocytosis
    • Indolent systemic mastocytosis
    • Systemic mastocytosis associated with clonal cell lineage disease
    • Aggressive systemic mastocytosis
    • Mast cell leukemia
    • Mast cell sarcoma
    • Extracutaneous mastocytosis

Pathophysiology

  • Mutation in the kit tyrosine kinase domain D816 V gene is the main cause of the disease process
  • This gene, in combination with others, exerts proliferation, which enhances uncontrolled mast cell proliferation
  • Mast cells produce histamine and tryptase
    • Disease process is marked by increased levels of both histamine and tryptase
    • Increased histamine concentrations in plasma and urine may indicate:
      • Allergic response (anaphylaxis)
      • Carcinoid tumors, particularly of gastric origin
      • Chronic myeloproliferative disorders
      • Urticaria pigmentosa or systemic mastocytosis
    • Increased tryptase levels may be occur in:
      • Mastocytosis
      • Urticaria
      • Asthma
      • Anaphylaxis
    • Tryptase levels in mast cell diseases typically rise within 1 hour and remain elevated 4-6 hours
      • In contrast, histamine levels peak at 5 minutes and return to baseline by 30 minutes
      • Beta-tryptase is usually elevated in systemic anaphylaxis of sufficient severity to cause hypotension

Clinical Presentation

  • Recurrent episodic flushing
  • Anaphylaxis
  • Tachycardia
  • Nausea, emesis, diarrhea, hepatomegaly
  • Wheezing, hives and angioedema are very uncommon
  • Skin
    • Urticaria pigmentosa
      • Individual hyperpigmented and telangiectatic papules
  • Prognostic indicators for systemic mastocytosis
    • B – elevated tryptase >200 ng mL, dysmyelopoiesis and organomegaly
    • C – evidence of impaired organ function (hepatic, gastrointestinal, bone marrow)

Diagnosis

  • Laboratory testing
    • Screening
      • Serum, histamine and tryptase levels
        • Tryptase level correlates with total mast cell burden in systemic mastocytosis
        • Measure tryptase within 3 hours of anaphylactic event
          • Repeated measures may be more sensitive
          • Tryptase levels >20 µg/L and ratios of total tryptase to beta tryptase >20 µg/L suggest mastocytosis
    • Definitive
      • Skin or organ biopsy demonstrating mast cells

See Also