mastocytosis

see also:

• anaphylaxis

• a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (“mastocytes”) and CD34+ mast cell precursors
• usually present as recurrent anaphylaxis or urticaria or GIT symptoms
• some patients develop systemic pathologies
  • systemic mastocytosis (SM) involves the bone marrow in the majority of cases and in some cases other internal organs, usually in addition to involving the skin
    • five types
      • indolent systemic mastocytosis (ISM)
        • >90% of cases of SM
        • have a normal life expectancy
      • smouldering systemic mastocytosis (SSM)
      • systemic mastocytosis with associated hematological neoplasm (SM-AHN)
      • aggressive systemic mastocytosis (ASM)
      • mast cell leukemia (MCL)
        • may evolve from a more progressive form of SM
        • criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood
        • tends to cause fever, headache, flushing of face and trunk
        • in most cases, multi-organ failure including bone marrow failure develops over weeks to months
        • median survival after diagnosis is only about 6 months

• mutations of the gene coding for the c-kit receptor (mutation KIT(D816V)), leading to constitutive signalling through the receptor is found in >90% of patients with systemic mastocytosis

• may cause:
  • anaphylaxis
  • urticaria pigmentosa (cutaneous mastocytosis)
  • urticaria including dermatographic urticaria
  • fatigue
  • “Darier's Sign” of skin
  • GIT symptoms such as abdominal discomfort, nausea, vomiting, diarrhoea, peptic ulcers, malabsorption
  • ENT inflammation
  • episodes of pre-syncope due to transient low BP
  • bone pain
  • muscle pain
  • osteoporosis
  • osteosclerosis
  • headache
  • depression
  • hepatosplenomegaly
  • lymphadenopathy
  • aggressive disease can rapidly produce cirrhosis and portal hypertension

• cutaneous disease:
  • characteristic skin changes of urticaria pigmentosa (cutaneous mastocytosis) - fixed, dark brown - can be confirmed on biopsy
    • especially on the upper arms, legs, and trunk
  • telangiectasia macularis eruptiva perstans (TMEP) is a much rarer form of cutaneous mastocytosis that affects adults
  • homme orange appearance - generalised orange skin
  • cutaneous mastocytosis in children usually presents in the first year after birth and in most cases vanishes during adolescence
• systemic disease:
  • serum tryptase
    • if the base level of s-tryptase is elevated, this implies that the mastocytosis can be systemic
  • analysis of mutation in KIT(D816V) in peripheral blood using sensitive PCR
  • major criteria:
    • dense infiltrates of >15 mast cells in the bone marrow or an extracutaneous organ
  • minor criteria:
    • aberrant phenotype on the mast cells (pos. for CD2 and/or CD25)
    • aberrant mast cell morphology (spindle-shaped
    • mutation in KIT(D816V)
    • serum tryptase >20 ng/ml

• monoclonal mast cell activation
• mast cell activation syndrome
• mast cell sarcoma