Timely diagnosis of systemic mastocytosis (SM) remains challenging because of care heterogeneity. We implemented a standardized approach for SM screening and diagnosis using a novel health care system–wide international screening registry. A retrospective analysis assessed rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses before and 2 years after care standardization. The accuracy of individual and combined SM screening tests, basal serum tryptase (BST) ≥11.5 and ≥20.0 ng/mL, REMA ≥2, monomorphic maculopapular CM (MPCM), and elevated BST based upon tryptase genotype, was analyzed. Tryptase genotyping and high-sensitivity p.D816V testing increased substantially 2 years after care standardization. SM diagnoses doubled from 47 to 94, and p.D816V molecular diagnoses increased from 24 to 79. Mean BST and p.D816V variant allele frequency values were significantly lower in patients diagnosed after standardization. Hereditary-alpha tryptasemia prevalence was increased in SM before care standardization (4/30 [13.3%]) but reflected the general population prevalence 2 years later at (5/76 [6.6%]). Elevated BST based upon genotype and BST ≥11.5 ng/mL had the highest sensitivities at 84.2% and 88.3%, respectively. The presence of monomorphic MPCM, elevated BST based upon tryptase genotype, and the combination of REMA ≥2 with elevated BST based upon tryptase genotype had specificities >90%. BST >20.0 ng/mL had low sensitivity and specificity and was not required to establish any indolent SM (ISM) diagnosis. Care standardization increased SM diagnosis rates, particularly in patients with low BSTs. Stratifying BST based upon genotype had the best overall sensitivity and specificity of any ISM screening test and improved the REMA score specificity.

中文翻译：

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整个医疗保健系统的标准化惰性系统性肥大细胞增多症评估：对筛查准确性的影响


由于护理的异质性，系统性肥大细胞增多症 (SM) 的及时诊断仍然具有挑战性。我们使用新型医疗保健系统范围的国际筛查登记处实施了标准化的 SM 筛查和诊断方法。一项回顾性分析评估了护理标准化之前和之后 2 年的 SM、皮肤肥大细胞增多症 (CM) 和分子诊断率。分析了单独和组合 SM 筛查试验、基础血清类胰蛋白酶 (BST) ≥11.5 和 ≥20.0 ng/mL、REMA ≥2、单形性斑丘疹 CM (MPCM) 以及基于类胰蛋白酶基因型的 BST 升高的准确性。护理标准化后两年，类胰蛋白酶基因分型和高灵敏度 p.D816V 测试大幅增加。 SM 诊断从 47 例翻倍至 94 例，p.D816V 分子诊断从 24 例增加至 79 例。标准化后诊断的患者的平均 BST 和 p.D816V 变异等位基因频率值显着降低。在护理标准化之前，SM 中遗传性 α 类胰蛋白酶血症的患病率有所增加 (4/30 [13.3%])，但反映了 2 年后一般人群的患病率 (5/76 [6.6%])。基于基因型的 BST 升高和 BST ≥11.5 ng/mL 的灵敏度最高，分别为 84.2% 和 88.3%。单态 MPCM 的存在、基于类胰蛋白酶基因型的升高的 BST 以及 REMA ≥2 与基于类胰蛋白酶基因型的升高的 BST 的组合具有 >90% 的特异性。 BST >20.0 ng/mL 的敏感性和特异性较低，不需要建立任何惰性 SM (ISM) 诊断。护理标准化提高了 SM 诊断率，特别是对于 BST 较低的患者。基于基因型的分层 BST 具有所有 ISM 筛查测试中最佳的总体敏感性和特异性，并提高了 REMA 评分的特异性。