Pharmacological treatment options for mast cell activation disease

Naunyn Schmiedebergs Arch Pharmacol. 2016 Jul;389(7):671-94. doi: 10.1007/s00210-016-1247-1. Epub 2016 Apr 30.


Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. In most cases, treatment of MCAD is directed primarily at controlling the symptoms associated with MC mediator release. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as kinase inhibitors may be provided. Targeted therapies aimed at blocking mutant protein variants and/or downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies. Since clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous disease, we seek to familiarize clinicians with MCAD and review current and future treatment approaches.

Keywords: Mast cell; Mast cell activation disease; Systemic mast cell activation syndrome; Systemic mastocytosis; Therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Cell Degranulation / drug effects
  • Cell Proliferation / drug effects*
  • Histamine Antagonists / adverse effects
  • Histamine Antagonists / therapeutic use*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Leukemia, Mast-Cell / drug therapy*
  • Leukemia, Mast-Cell / immunology
  • Leukemia, Mast-Cell / metabolism
  • Leukemia, Mast-Cell / pathology
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Mastocytosis, Systemic / drug therapy*
  • Mastocytosis, Systemic / immunology
  • Mastocytosis, Systemic / metabolism
  • Mastocytosis, Systemic / pathology
  • Molecular Targeted Therapy
  • Treatment Outcome


  • Antineoplastic Agents
  • Histamine Antagonists
  • Immunosuppressive Agents