Among individuals with indolent systemic mastocytosis (SM), the standardization of screening and the use of diagnostic testing are associated with improvements in diagnosing the disorder and detecting rates of KIT p.D816V, according to findings from a retrospective study recently published in Blood.
It is well recognized that the timely diagnosis of SM presents a challenge because of the heterogeneity of care received by patients. In more than 90% of patients with SM, the driving mutation present is recognized to be the somatic variant of KIT p.D816V.
In the current analysis, the researchers sought to apply a standardized strategy for the screening and diagnosis of SM that uses a novel health care system–wide international registry. Rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses both prior to and two years following standardization of care were evaluated.
The accuracy of individual as well as combined SM screening tests was evaluated. Moreover, basal serum tryptase (BST) levels of ≥11.5 ng/mL and ≥20.0 ng/mL, along with REMA scores of ≥2 (which are indicative of high-risk anaphylaxis), monomorphic maculopapular CM (MPCM), and elevated BST levels according to tryptase genotyping, were evaluated as well.
Read more about SM causes and risk factors
The study retrospectively compared two time points—July 1, 2021, and July 1, 2023—in a cohort of Tricare beneficiaries with a diagnosis of SM or those who were deemed to be at high risk for SM. All clinical assessments were performed in this 2-year time frame, based on clinical screening algorithms. After the fulfillment of certain exclusion criteria, a total of 82 individuals with SM or monomorphic MPCM were included in the study on July 1, 2021.
Also on July 1, 2021, a total of 357 persons who did not have a diagnosis of SM or adult-onset monomorphic MPCM, but had either a history of anaphylaxis with a REMA score of ≥2 or a BST level of ≥11.5 ng/mL, were evaluated as well. By July 1, 2023, among these 357 individuals, there were 20 who were identified with a BST concentration of <11.4 ng/mL and a REMA score of ≥2, along with 337 persons with a BST level of ≥11.5 ng/mL.
Results of the study demonstrated that tryptase genotyping and high-sensitivity KIT p.D816V increased considerably two years following the standardization of care. Further, SM diagnoses doubled, and researchers noted a smaller increase in KIT p.D816V molecular diagnoses as well.
The KIT p.D816V variant allele frequency values and the mean BST levels were both significantly lower among those patients who were diagnosed after standardization. Although the prevalence of hereditary-alpha tryptasemia increased in those with SM prior to the standardization of care, the prevalence reflected those of the general population two years later.
Elevated BST levels that are based on genotype and BST concentrations of ≥11.5 ng/mL had the highest sensitivities—that is, 84.2% and 88.3%, respectively. The presence of monomorphic MPCM, elevated BST concentrations based on tryptase genotype, and the combination of REMA score of ≥2 plus elevated BST levels based on tryptase genotypes all exhibited specificities that were greater than 90%.
“[W]e have shown that a unique clinical SM screening and care registry linked to [centers of excellence] can improve SM pathological and KIT p.D816V molecular diagnosis rates over regular referral pathways,” the authors stated.
