title: Successful targeted treatment of mast cell activation syndrome with tofacitinib.
abstract: Mast cell (MC) activation syndrome (MCAS) is a collection of illnesses of inappropriate MC activation with little to no neoplastic MC proliferation, distinguishing it from mastocytosis. MCAS presents as chronic, generally inflammatory multisystem polymorbidity likely driven in most by heterogeneous patterns of constitutively activating mutations in MC regulatory elements, posing challenges for identifying optimal mutation-targeted treatment in individual patients. Targeting commonly affected downstream effectors may yield clinical benefit independent of upstream mutational profile. For example, both activated KIT and numerous cytokine receptors activate the Janus kinases (JAKs). Thus, JAK-inhibiting therapies may be useful against the downstream inflammatory effects of MCAS. The oral JAK1/JAK3 inhibitor, tofacitinib, is currently approved for rheumatoid arthritis and is in clinical trials for other chronic inflammatory disorders. Herein, we report two patients with MCAS who rapidly gained substantial symptomatic response to tofacitinib. Their improvement suggests need for further evaluation of this class of drugs in MCAS treatment.
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lawrence B
authors.identifier: http://orcid.org/0000-0003-3550-4244
authors.initials: LB
authors.lastname: Afrin
authors.affiliation: Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Fox
authors.affiliation: Suncoast Internal Medicine Consultants, Largo, FL, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Zito
authors.affiliation: Suncoast Internal Medicine Consultants, Largo, FL, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Choe
authors.affiliation: Inflammatory Bowel and Celiac Disease Program, University of Florida, Gainesville, FL, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Glover
mesh_terms: D000328:Adult; D015415:Biomarkers; D005260:Female; D006801:Humans; D008415:Mastocytosis / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D063189:Symptom Assessment; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: JAK inhibitors; KIT activation; dysautonomia; fibromyalgia; mast cell activation syndrome; mast cells; rheumatoid arthritis; tofacitinib