Systemic mastocytosis

Mastocytosis is a heterogeneous disorder characterized by the abnormal growth and accumulation of morphologically and immunophenotypically abnormal mast cells (MCs) in one or more organs (1)

• mastocytosis is an uncommon disease resulting from a pathological increase in mast cells in different tissues including skin, bone marrow, liver, spleen, and lymph nodes (1)
• the clinical presentation of mastocytosis is diverse, and many patients do not fit the classical description - namely, a variably long history of urticaria pigmentosa (UP), followed by the insidious onset of flushing, cramping abdominal pain, diarrhea, bone pain, and hepatosplenomegaly (1)
  • clinical presentation of mastocytosis is heterogeneous, varying from sole skin presentation found in UP and mastocytoma, to different forms of systemic disease including indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis and mast cell leukemia (2, 3)
    • of the adult patients with systemic mastocytosis, the large majority (ca. 90%) have the indolent form of the disease
    • unlike paediatric cases, most adults with UP-like skin lesions have systemic disease (ie, systemic mastocytosis [SM]) at presentation, a condition generally confirmed by a bone marrow (BM) biopsy (1)
      • MCs are derived from CD34+/KIT+ pluripotent hematopoietic cells in the bone marrow; its neoplastic counterparts are morphologically atypical (spindled shape, hypogranular cytoplasm, nuclear atypia), and express abnormal cell surface markers (CD25 and/or CD2)
        • most, if not all, adult mastocytosis patients carry gain-of-function KIT receptor mutations, most commonly D816V in the tyrosine kinase domain (1)
          
          
  • symptoms of the disease result from skin involvement, mast cell mediator release and massive mast cell infiltration, as found in aggressive variants of the disease
    • symptoms of mast cell degranulation may vary from pruritus and flushing to anaphylaxis with profound hypotension and with occasionally even fatal outcome
    • cumulative prevalence of anaphylaxis in patients with mastocytosis has been reported to be as high as 50% (4)
      
      
• anaphylaxis is thought to be the most important burden for the majority of patients with mastocytosis
  • the most important eliciting factor of anaphylaxis in patients with mastocytosis is an insect sting (4). It is estimated that 30% of patients with mastocytosis suffer from insect venom anaphylaxis (4)
    
    
• the natural history of SM, ranging from indolent forms spanning years to more aggressive subtypes that rapidly progress to leukaemia, complicates decision making regarding the choice of therapeutic modalities and timing of intervention. In 2001, the World Health Organization (WHO) formalized this classification and further refined it by incorporating recent advances in SM, including identification of KITD816V, aberrant expression of cell surface markers on neoplastic MCs, and elevated tryptase level in serum

Reference:

• 1) Lim KH et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009 Jun 4;113(23):5727-36. Epub 2009 Apr 10
• 2) Valent P, Sperr W, Schwartz L, Horny H. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol 2004;114:3-11.
• 3) Akin C, Metcalfe D. The biology of Kit in disease and the application of pharmacogenetics. J Allergy Clin Immunol 2004;114:13-19.
• 4) Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy 2008;63:226-232.