title: Pharmacological treatment options for mast cell activation disease.
abstract: 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.
authors.affiliation: Institute of Human Genetics, University Hospital of Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany. molderings@uni-bonn.de.
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Molderings
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Haenisch
authors.affiliation: Department of Oncology, Hematology and Palliative Care, Kreiskrankenhaus Waldbröl, Waldbröl, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Brettner
authors.affiliation: Allgemeine Innere Medizin, Gastroenterologie und Diabetologie, Gemeinschaftskrankenhaus, Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Homann
authors.affiliation: Allgemeine Innere Medizin, Gastroenterologie und Diabetologie, Gemeinschaftskrankenhaus, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Menzen
authors.affiliation: Allgemeine Innere Medizin, Gastroenterologie und Diabetologie, Gemeinschaftskrankenhaus, Bonn, Germany.
authors.forename: Franz Ludwig
authors.initials: FL
authors.lastname: Dumoulin
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.affiliation: Program for the Study of Mast Cell and Eosinophil Disorders, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Butterfield
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Afrin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis; D015550:Cell Degranulation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006633:Histamine Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007946:Leukemia, Mast-Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006633:Histamine Antagonists; D007166:Immunosuppressive Agents
keywords: Mast cell; Mast cell activation disease; Systemic mast cell activation syndrome; Systemic mastocytosis; Therapy