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 mu g/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. (J Allergy Clin Immunol 2010;125:1269-78.)