Standardized indolent systemic mastocytosis evaluations across a health care system: implications for screening accuracy.

ABSTRACT: 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 KIT p.D816V testing increased substantially 2 years after care standardization. SM diagnoses doubled from 47 to 94, and KIT p.D816V molecular diagnoses increased from 24 to 79. Mean BST and KIT 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.

Elevated Basal Serum Tryptase: Disease Distribution and Variability in a Regional Health System.

BACKGROUND: Hereditary-alpha tryptasemia (HαT) is the most common etiology for elevated basal serum tryptase (BST). However, the utility of tryptase genotyping of individuals with elevated BST in general clinical practice remains undefined. Moreover, studies showing associations between elevated BST and chronic kidney disease (CKD), myelodysplastic syndrome (MDS), rheumatoid arthritis, or eosinophilic esophagitis did not include tryptase genotyping. OBJECTIVE: To determine the utility of tryptase genotyping among individuals with moderate elevations in BST at a regional health system. METHODS: Clinical and laboratory data from 109 subjects with basal tryptase values of 7.5 ng/mL or greater who were tested for HαT or had a disorder previously linked to elevated BST were collected retrospectively by chart review. RESULTS: Fifty-eight subjects had elevated BST defined as 11.5 ng/mL or greater. HαT was found in 63.8% (n = 37), 12.1% (n = 7) had CKD, and 20.7% (n = 12) had clonal myeloid disorders. A total of 6.9% (n = 4) with elevated BST had negative testing for HαT, CKD, and myeloid neoplasms. Two subjects with CKD, 1 subject with MDS, and 1 with myeloid hypereosinophilic syndrome had negative testing for HαT. Among subjects with elevated BST and more than 1 tryptase measurement, 41.5% (n = 22) had BST variability that exceeded the 20% plus 2 formula. Increased BST variability was found in subjects with HαT, all forms of mastocytosis, CKD, MDS, and those with no associated diagnosis. CONCLUSIONS: HαT, CKD, and clonal myeloid disorders or a combination of the 3 constitute approximately 90% of individuals with elevated BST in clinical practice. Myeloid neoplasms were over-represented in this cohort relative to population prevalence data suggesting tryptase measurement selection bias by clinicians or higher prevalence. Elevated BST is associated with increased tryptase variability, regardless of etiology.

Alternative Immunization Clinics to Improve Vaccination Access during the COVID-19 Pandemic.

The United States declared a national emergency on March 13, 2020, in response to the rapidly spreading COVID-19 pandemic after all 50 states reported laboratory-confirmed cases.1 The demand for ambulatory medical care in the US fell by almost 60% and immunization encounters at Walter Reed National Military Medical Center decreased by 76% as patients became concerned about the risk of coronavirus exposure within a clinic or hospital setting.2 Our vaccination initiatives aimed to increase our pediatric and adult immunization rates through offering two alternative immunization platforms aimed to reduce patient concerns about COVID exposure.

Hb Grifton [α87(F8)His→Pro; HBA1: C.263A > C (or HBA2)] Causes Abnormal Pulse Oximetry Measurements.

An asymptomatic toddler and his mother consistently demonstrated low transcutaneous pulse oximetry (SpO2) measurements, discordant with normal arterial blood gas analyses while breathing room air. Previous evaluations by medical teams were unable to identify an etiology of their perceived hypoxia. Further investigation revealed that the boy carried an abnormal variant, Hb Grifton or α87(F8)His→Pro; HBA1: c.263A > C (or HBA2), discovered on newborn screening, which was not suspected as the underlying cause of his abnormal pulse oximetry readings until an inpatient admission to our hospital for asymptomatic "hypoxia," where he was found to share these same characteristics with his mother. We showed that a difference in light absorption between the oxygenated Hb Grifton variant and oxygenated Hb A resulted in erroneous pulse oximetry values. This phenomenon has previously been reported in a handful of other variant Hbs. Astute clinical suspicion, in conjunction with laboratory testing leading to correct diagnoses of variant Hbs, may prevent expensive work-ups and unnecessary medical treatments for asymptomatic patients falsely presumed to be hypoxemic based on low pulse oximetry measurements.