D3.318 - Evaluation of Clinical Predictors and Serum Tryptase Levels in Systemic Mastocytosis

Several cut-off values for baseline serum tryptase have been proposed for the diagnosis of systemic mastocytosis (SM). However, some patients present with predominant mast cell–mediated symptoms and evidence of clonality but do not fully meet World Health Organization criteria for SM and are considered to fall within the pre-systemic mastocytosis (pre-SM) spectrum. No universally accepted baseline serum tryptase cut-off encompassing both pre-SM and systemic mastocytosis has yet been established.To identify clinical features predictive of systemic mastocytosis, including patients within the pre-SM spectrum, and to determine a baseline serum tryptase threshold associated with increased diagnostic likelihood.

Between January 2015 and 2025, 1,495 adults who underwent baseline serum tryptase measurement at a tertiary allergy and immunology center were retrospectively screened; 244 were included in the analysis. The dependent variable was the presence of clonal bone marrow findings compatible with pre-SM or SM. Anaphylaxis severity was classified according to the Brown grading system. Primary and secondary outcomes were the identification of clinical risk factors and determination of a cohort-based baseline serum tryptase cut-off, respectively.

Of the 244 patients, 146 (59.8%) were female; median age was 43.0 years (IQR: 31.0–53.0). Chronic urticaria, allergic rhinitis, and asthma were present in 35.7%, 25.2%, and 12.9% of patients, respectively. Anaphylaxis was reported in 183 patients (78.9%). Bone marrow biopsy was performed in 64 patients with high clinical suspicion, revealing clonal findings compatible with pre-SM/SM in 35 (14.3%). In univariate analyses, older age, male sex, and low total IgE were associated with pre-SM/SM; however, these associations were not retained after multivariable adjustment. Among patients with pre-SM/SM, 65.0% had a history of anaphylaxis. In multivariable analysis of patients with anaphylaxis, increasing anaphylaxis frequency (OR=1.8,p=0.018), neurological symptoms (OR=8.1, p=0.010), gastrointestinal symptoms (OR=7.6,p=0.035), and absence of cutaneous manifestations (OR=0.098,p=0.012,1/OR≈10,2) were independently associated with pre-SM/SM. In severe anaphylaxis, these associations were stronger. ROC analysis identified a baseline serum tryptase cut-off of 11.8 ng/mL (sensitivity 0.94, specificity 0.90, AUC 0.95; p<0.001).

Recurrent anaphylaxis, neurological and gastrointestinal involvement, and absence of cutaneous findings are strong predictors of pre-SM/SM. A baseline serum tryptase cut-off of 11.8 ng/mL may help identify high-risk patients who warrant bone marrow evaluation, suggesting a clinically useful threshold below the generally accepted ≥20 ng/mL.