title: Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms.
abstract: BACKGROUND
  Systemic mast cell activation disorders (MCADs) are characterized by severe and systemic mast cell (MC) mediators-related symptoms frequently associated with increased serum baseline tryptase (sBt).
  
  
  OBJECTIVE
  To analyze the clinical, biological, and molecular characteristics of adult patients presenting with systemic MC activation symptoms/anaphylaxis in the absence of skin mastocytosis who showed clonal (c) versus nonclonal (nc) MCs and to provide indication criteria for bone marrow (BM) studies.
  
  
  METHODS
  Eighty-three patients were studied. Patients showing clonal BM MCs were grouped into indolent systemic mastocytosis without skin lesions (ISMs(-); n = 48) and other c-MCADs (n = 3)-both with CD25(++) BM MCs and either positive mast/stem cell growth factor receptor gene (KIT) mutation or clonal human androgen receptor assay (HUMARA) tests-and nc-MCAD (CD25-negative BM MCs in the absence of KIT mutation; n = 32) and compared for their clinical, biological, and molecular characteristics.
  
  
  RESULTS
  Most clonal patients (48/51; 94%) met the World Health Organization criteria for systemic mastocytosis and were classified as ISMs(-), whereas the other 3 c-MCAD and all nc-MCAD patients did not. In addition, although both patients with ISMs(-) and patients with nc-MCAD presented with idiopathic and allergen-induced anaphylaxis, the former showed a higher frequency of men, cardiovascular symptoms, and insect bite as a trigger, together with greater sBt. Based on a multivariate analysis, a highly efficient model to predict clonality before BM sampling was built that includes male sex (P = .01), presyncopal and/or syncopal episodes (P = .009) in the absence of urticaria and angioedema (P = .003), and sBt >25 microg/L (P = .006) as independent predictive factors.
  
  
  CONCLUSIONS
  Patients with c-MCAD and ISMs(-) display unique clinical and laboratory features different from nc-MCAD patients. A significant percentage of c-MCAD patients can be considered as true ISMs(-) diagnosed at early phases of the disease.
authors.affiliation: Centro de Estudios de Mastocitosis de Castilla La Mancha, Hospital Virgen del Valle, Toledo, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Alvarez-Twose
authors.forename: David
authors.initials: D
authors.lastname: González de Olano
authors.forename: Laura
authors.initials: L
authors.lastname: Sánchez-Muñoz
authors.forename: Almudena
authors.initials: A
authors.lastname: Matito
authors.forename: Maria I
authors.initials: MI
authors.lastname: Esteban-López
authors.forename: Arantza
authors.initials: A
authors.lastname: Vega
authors.forename: Maria Belén
authors.initials: MB
authors.lastname: Mateo
authors.forename: Maria D
authors.initials: MD
authors.lastname: Alonso Díaz de Durana
authors.forename: Belén
authors.initials: B
authors.lastname: de la Hoz
authors.forename: Maria D
authors.initials: MD
authors.lastname: Del Pozo Gil
authors.forename: Teresa
authors.initials: T
authors.lastname: Caballero
authors.forename: Ana
authors.initials: A
authors.lastname: Rosado
authors.forename: Isabel
authors.initials: I
authors.lastname: Sánchez Matas
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodósio
authors.forename: María
authors.initials: M
authors.lastname: Jara-Acevedo
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.forename: Andrés
authors.initials: A
authors.lastname: García-Montero
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Luis
authors.initials: L
authors.lastname: Escribano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D015550:Cell Degranulation; D002999:Clone Cells; D005260:Female; D006323:Heart Arrest; D006801:Humans; D007022:Hypotension; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism; D013575:Syncope; D053802:Tryptases / Q000097:blood
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D011944:Receptors, Androgen; D019009:Proto-Oncogene Proteins c-kit; D053802:Tryptases