Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms

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 μg/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.