What is the pathophysiology of mastocytosis?

Updated: Sep 16, 2020
  • Author: Jacquiline Habashy, DO, MSc; Chief Editor: Dirk M Elston, MD  more...
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Mastocytosis is now classified with the myeloproliferative neoplasms. [11] Increased local concentrations of soluble mast cell growth factor in lesions of cutaneous mastocytosis are believed to stimulate mast cell proliferation, melanocyte proliferation, and melanin pigment production. The induction of melanocytes explains the hyperpigmentation that commonly is associated with cutaneous mast cell lesions. The stimulation of pruritus seen in mastocytosis is associated with the production of interleukin (IL)–31. [12] Impaired mast cell apoptosis has been postulated to be involved, as evidenced by up-regulation of the apoptosis-preventing protein BCL-2 demonstrated in patients with mastocytosis. [13] Activating mutations of the proto-oncogene c-kit have been identified but do not explain the initiation of the disease. [14] IL-6 levels have been shown to be elevated and correlated with disease severity, indicating interleukin 6 is involved in the pathophysiology of mastocytosis. [15]

Although pediatric mastocytosis can spontaneously regress, it is a clonal disease most commonly associated with D816V and other activating c-kit mutations. [16]

Research from 2016 has shown that there are varied gene expressions in patients with mastocytosis and associated allergies. Those with associated food allergies have an elevated expression of the TRAF4 gene. [17] In the same study, patients who had an allergy to insect venom had a decreased gene expression of B3GAT1.

Associated systemic manifestations are believed to reflect the release of mast cell–derived mediators, such as histamine, prostaglandins, heparin, neutral proteases, and acid hydrolases. Symptoms and signs induced by mediators may include headache, neuropsychiatric symptoms (cognitive disorganization), flushing, dizziness, tachycardia, hypotension, syncope, anorexia, nausea, vomiting, abdominal pain, and diarrhea. The skeletal, hematopoietic, gastrointestinal (GI), cardiopulmonary, and central nervous systems may be involved either directly, via mast cell infiltration, or indirectly, via mast cell mediator release.

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