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.

Ideal body position for epinephrine autoinjector administration.

Background: Epinephrine is the first-line therapy for patients with anaphylaxis, and intramuscular (IM) delivery is shown to be superior to subcutaneous (SC) delivery. There currently is no consensus on the ideal body position for epinephrine autoinjector (EAI) administration. Objective: We designed this study to investigate whether SC tissue depth (SCTD) is affected by body position (e.g., standing, sitting, supine), which can potentially impact delivery of EAI into the IM space. Methods: Volunteer adults (ages ≥ 18 years) from a military medical treatment facility in the United States were recruited to participate in this study. SCTD of the vastus lateralis was measured via ultrasound at standing, sitting, and supine body positions. Subjects' age, sex, and body mass index (BMI) were collected. Statistical analysis was performed to compare average SCTD between body positions, sex, and BMI. Results: An analysis of variance of 51 participants (33 men and 18 women) did not reveal statistically significant difference in SCTD among standing, sitting, and supine body positions. It did show a significantly greater SCTD in women than in men (2.72 ± 1.36 cm versus 1.10 ± 0.38 cm; p < 0.001). There was no significant association observed between BMI and SCTD in this study. Conclusion: Body position did not seem to significantly change the distance between skin and thigh muscle in adults. This would suggest that there might not be an ideal body position for EAI administration. Therefore, in case of anaphylaxis, prompt administration of epinephrine is recommended at any position.

Ideal body position for epinephrine autoinjector administration.

BACKGROUND: Epinephrine is the first-line therapy for patients with anaphylaxis, and intramuscular (IM) delivery is shownto be superior to subcutaneous (SC) delivery. There currently is no consensus on the ideal body position for epinephrine autoinjector (EAI) administration. OBJECTIVE: We designed this study to investigate whether SC tissue depth (SCTD) is affected by body position (e.g., standing, sitting, supine), which can potentially impact delivery of EAI into the IM space. METHODS: Volunteer adults (ages >/= 18 years) from a military medical treatment facility in the United States were recruitedto participate in this study. SCTD of the vastus lateralis was measured via ultrasound at standing, sitting, and supine bodypositions. Subjects' age, sex, and body mass index (BMI) were collected. Statistical analysis was performed to compare averageSCTD between body positions, sex, and BMI. RESULTS: An analysis of variance of 51 participants (33 men and 18 women) did not reveal statistically significant differencein SCTD among standing, sitting, and supine body positions. It did show a significantly greater SCTD in women than in men (2.72 +/- 1.36 cm versus 1.10 +/- 0.38 cm; p < 0.001). There was no significant association observed between BMI and SCTD in this study. CONCLUSION: Body position did not seem to significantly change the distance between skin and thigh muscle in adults. Thiswould suggest that there might not be an ideal body position for EAI administration. Therefore, in case of anaphylaxis, promptadministration of epinephrine is recommended at any position.

Treatment of idiopathic anaphylaxis with dupilumab: a case report.

BACKGROUND: Anaphylaxis is an acute, potentially life-threatening allergic reaction that typically occurs after exposure to a trigger, while idiopathic anaphylaxis (IA) occurs in the absence of a trigger. Acute management of both triggered anaphylaxis and IA relies on the use of epinephrine. In some patients with recurrent IA, glucocorticoid prophylaxis with prednisone can be effective. While there is currently no high quality evidence for the use of other prophylactic options to prevent recurrent IA, evolving data exists to support the consideration of biologics that target IgE or the Th2 pathway. CASE PRESENTATION: We present the case of a 28 year old female with no atopic or autoimmune history with recurrent episodes of IA since childhood occurring up to twice weekly. There was improvement in acute symptoms with administration of first or second generation antihistamines and/or intramuscular epinephrine. Without an identifiable trigger, she was diagnosed with IA and frequent idiopathic urticaria and omalizumab was added to her treatment regimen with improvement in symptom frequency. After being lost to follow up, she had recurrence of symptom frequency and severity without omalizumab therapy and subsequently presented to our institution. Her workup at this point was negative for food allergy, alpha gal syndrome, systemic mastocytosis, hereditary alpha tryptasemia, carcinoid syndrome, and pheochromocytoma, and she was trialed on dupilumab with near resolution of her symptom frequency over a six month time period. CONCLUSION: Recurrent IA is a diagnosis of exclusion that is associated with high morbidity. Prophylaxis remains an area of uncertainty, although prednisone has been effective in some cases. When prednisone is contraindicated or ineffective for the prevention of IA, biologic therapies that target IgE or the Th2 pathway may present a reasonable consideration. This case adds support to the suggestion that dupilumab may be a logical off-label consideration for prophylaxis of recurrent IA. The data for dupilumab in this clinical scenario is still very limited, and further research is required before any recommendation can be made.

Paradoxical Bronchoconstriction with Short-Acting Beta Agonist.

BACKGROUND Asthma is a common disease in the U.S. POPULATION: Initial therapy in the stepwise approach for asthma management is short-acting ß2-agonist (SABA) therapy as needed for symptom control. However, a significant adverse event that can occur with administration is bronchospasm. Here, we report a case of paradoxical bronchospasm with administration of SABAs during multiple pulmonary function tests (PFTs). CASE REPORT A 25-year-old, non-smoking, African American male with a history of moderate asthma and allergic rhinitis treated with fluticasone/salmeterol diskus, albuterol hydrofluoroalkane (HFA) inhaler, and montelukast presented to our clinic complaining of recurrent episodes of acute shortness of breath immediately following each administration of albuterol for 4 weeks. PFTs were performed with levalbuterol (Xopenex) and albuterol (ProAir), yielding significant decrease in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Nebulized albuterol and ipratropium bromide also improved FEV1 and FVC. He was successfully transitioned to an ipratropium rescue inhaler for asthma exacerbations. CONCLUSIONS Paradoxical bronchoconstriction is the unexpected constriction of smooth muscle walls of the bronchi that occurs in the setting of an expected bronchodilatory response. This phenomenon has been observed with ß2-agonist-containing inhaler formulations and is an under-recognized adverse event. Theories suggest that the formulation excipients can trigger airway hyperresponsiveness in patients with allergically inflamed airways. Removal of excipients or use of anticholinergic inhalers improved respiratory function. Clinicians should be aware of paradoxical bronchospasm as an adverse effect with common inhaler formulations containing ß2-agonists and counsel patients accordingly in the appropriate clinical setting.