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Systemic mastocytosis

Orpha number ORPHA2467
Synonym(s) Mast cell disease
Prevalence 1-9 / 100 000
Inheritance
  • Sporadic
Age of onset Variable
ICD-10
  • C96.2
OMIM -
UMLS
  • C0221013
MeSH
  • D034721
MedDRA
  • 10042949
SNOMED CT
  • 397016004

Summary

Systemic mastocytosis (SM) comprises a heterogeneous group of rare acquired and chronic hematological malignancies that are related to an abnormal proliferation of mast cells in tissue, including bone marrow, with or without skin involvement. The worldwide prevalence is estimated at between 1/20,000 and 1/40,000. SM preferentially affects Caucasians and there is no sex predominance. SM can be divided into indolent SM (ISM) and aggressive SM (ASM) (see these terms). SM is mainly observed in adults (average age at diagnosis is 60 years). The clinical manifestations result from the release of mast cell mediators and/or tumor syndrome. The release of mediators (histamine, leukotrienes, prostaglandins, heparin) causes recurrent syncope, headache, flushing and, in severe cases, anaphylactic shock. Mast cell proliferation in bone marrow can cause abnormalities in peripheral blood: anemia (the most common abnormality), cytopenias and pancytopenia. Mast cell infiltration may also affect the digestive system with esophageal, gastric, intestinal (malabsorption syndrome) and hepatic (ascites, portal hypertension, hepatomegaly which can evolve into portal fibrosis, and more rarely, cirrhosis) involvement, which results in abdominal pain and sometimes diarrhea, nausea and vomiting. Mast cell infiltration may also affect the skin (urticaria pigmentosa, which is sometimes itchy), the spleen (splenomegaly, which is generally asymptomatic), and the skeleton (bone pain, arthralgia, and osteolysis, osteosclerosis or osteoporosis on medical imaging). SM is usually sporadic but rare familial cases have been reported. Different somatic point mutations of the KIT gene have been described. The most frequent mutation (codon 816; D816V) results in uncontrolled activation of the receptor making the migration, survival and activation of the mast cells independent of stem cell factor. Diagnosis is based on histological and cytological study of bone marrow showing infiltration, which is often multifocal, by mast cells of frequently atypical morphology (elongated cells and sometimes hypergranulosis), which frequently abnormally express non-mast cell markers (CD25 and/or CD2). An elevated level of serum tryptase above 20 ng/mL or the presence of an activating mutation of KIT confirms the diagnosis. The extent of the proliferation of mast cells can be analyzed using medical imaging (radiography, ultrasound, CT scanning). Differential diagnoses include other forms of mastocytosis (mast cell leukemia, mastocytoma), endocrine disorders (adrenal tumors, vipoma, gastrinoma), some gastrointestinal pathologies, allergies, other myeloproliferative diseases that affect bone marrow, histiocytosis, hypereosinophilic syndrome and Waldenström macroglobulinemia (see these terms). Management depends on the type of SM. Treatment of ISM is often symptomatic (antihistamines, corticosteroids or disodium cromgylcate). For ASM treatment is symptomatic (antihistamines anti-H1 and H2) and antiproliferative (interferon alpha with or without corticosteroids, cladribine). Imatinib mesylate or Masitinib may be indicated for the few patients without the D816V KIT mutation. Molecules inhibiting the mutated D816V form are currently in clinical trials and other therapeutic approaches are proposed (rapamycin, bortezomib, thalidomide). Prognosis depends on the type of SM. For ISM, the evolution is slow and benign and life expectancy is normal. For ASM, average survival is 2 to 4 years.

Expert reviewer(s)

  • Pr Michel AROCK

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Detailed information

Summary information
Emergency guidelines
  • FR (2013,pdf)
Article for general public
  • FR (2013,pdf)
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