Journal of Allergy and Clinical Immunology-In Practice最新文献

Background: Patients with mastocytosis are at increased risk of anaphylaxis. Idiopathic anaphylaxis and venom induced allergy are commonly reported in mastocytosis, however the incidence of other allergies has been less well studied.

Objective: We sought to characterize the true prevalence of allergic disease including food, venom, contrast, and drug allergy compared to the number of patients that simply avoid potential triggers. We also gathered demographic information.

Methods: We performed a retrospective study of 259 consecutive pediatric and adult patients with a confirmed diagnosis of either cutaneous or systemic mastocytosis who received care through the University of Michigan Health system from 1/1/2018 to 3/17/2021.

Results: Mastocytosis was more prevalent in non-Hispanic white population. As compared to the general population, patients had similar rates of atopy and allergies with a slight increase in reported asthma prevalence. Overall prevalence of anaphylaxis was 28% and the great majority occurred in SM, with most common trigger being hymenoptera venoms. Most patients reported drug allergies preemptively in order to avoid exposure, particularly to NSAIDs. We also saw an increase in contrast-induced anaphylaxis compared to prior literature, and a lower prevalence of venom allergy as compared to European cohorts.

Conclusion: Our study characterizes the rate of common atopic conditions as well as allergies in a large cohort of patients with mastocytosis in the US. Anaphylaxis in CM is rare. Hymenoptera venoms were the most common trigger for anaphylaxis while drug allergies were overreported preemptively in order to avoid potential exposures due to concern for having a reaction.

Background: Hypereosinophilic syndromes (HES) are defined as hypereosinophilia with eosinophil-related clinical manifestations, some of which overlap in presentation with asthma, atopic dermatitis, eosinophilic esophagitis, and/or chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count (AEC) and rare eosinophil-related complications.

Objective: To determine whether eosinophil-related complications of dupilumab are increased in HES.

Methods: Retrospective chart review of patients with HES treated with dupilumab enrolled on an IRB-approved research protocol at the National Institutes of Health (NCT00001406) or receiving care at Walter Reed National Military Medical Center. Clinical response and treatment-emergent adverse events were recorded. Serum mediators were assessed in a subset of patients before and after dupilumab using stored samples.

Results: Among the 28 patients (15 male, 13 female; median age 41.5), the most common prescribing indication for dupilumab was CRSwNP (n=11). Twenty-three patients (82%) showed significant clinical improvement on dupilumab. Hypereosinophilia (AEC >1.5x10⁹/L) recurred or worsened in 9/20 patients on dupilumab monotherapy. Moreover, 4/20 (20%) patients developed an eosinophil-related complication with dupilumab discontinuation and/or addition of eosinophil-lowering therapy. None of the 8 patients who received dupilumab while in hematologic remission on an eosinophil-lowering biologic developed hypereosinophilia or an eosinophil-related complication. Serum IgE and eotaxin levels decreased on dupilumab therapy.

Conclusion: These data suggest that dupilumab is effective in treating residual symptoms in HES patients but that the incidence of eosinophil-related complications is increased. Concomitant eosinophil-lowering therapy may reduce the risk of eosinophil-related complications during dupilumab therapy in patients with HES.

Background: Limited information is available regarding the physicochemical stability of penicillins-based preparations for skin testing purposes and no information is currently available for other classes of antibiotics.

Objective: To perform chemical and physical stability studies on 16 parenteral antibiotics for skin testing purposes, with an overall aim to provide practical recommendations to clinicians on suitable components, storage, and optimal shelf-life of such preparations.

Methods: Chemical stability was assessed via validated stability-indicating high performance liquid chromatography with ultraviolet detection assays, while absence of precipitations or haziness, significant pH shift and colour change were used to determine physical stability.

Results: Other than amoxicillin/clavulanic acid, all of the parenteral antibiotics were found to have adequate physicochemical stability between 2 to 7 days. Amoxicillin in Water for Injection BP retained >90% stability, while amoxicillin/clavulanic acid dropped to <80%. Ampicillin remained >90% stable for 2 days, and benzylpenicillin, flucloxacillin, and piperacillin/tazobactam were stable for ≥2 days at ∼95%. Cephalosporins were stable for 2 days, except ceftazidime, which increased to >110%. Aztreonam, ciprofloxacin, and vancomycin retained >95% stability for 7 days, while meropenem was stable for 2 days. Sulfamethoxazole/trimethoprim lost 15% but stabilized at ∼85% for 7 days. No precipitation occurred, but amoxicillin/clavulanic acid changed colour by day 7. pH decreases of ≤1.0 unit were observed in penicillins, while cefepime dropped below acceptable pH limits by day 7. Absorbance shifts >100 units were seen in several antibiotics by day 7.

Conclusions: This study has generated practical stability information for clinicians, allowing 15 parenteral antibiotics from 7 different classes to be aseptically prepared in advance for use in the testing of drug allergy reactions.

Background: Clinical remission (CR) is a new realistic management goal for patients with asthma, regardless of the disease severity.

Objective: To investigate the rate of achievement of CR in patients treated with inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) and nonbiologics and the characteristics of patients who achieved CR.

Methods: We performed a post hoc analysis from a multicenter, cross-sectional survey in Japan. 3-way CR was defined as the absence of exacerbation, no use of maintenance oral corticosteroids, and the absence of significant asthma symptoms (5-item Asthma Control Questionnaire < 1.5). We defined 4-way CR as 3-way CR plus having normalized lung function (forced expiratory volume in 1 second [%FEV₁] ≥ 80%). Deep remission was defined as 4-way CR plus suppressed type 2 airway inflammation (fraction of exhaled nitric oxide [FeNO] < 35 ppb).

Results: The criteria for 3-way CR, 4-way CR, and deep remission were met by 56.9%, 35.0%, and 24.7% of patients, respectively. Compared with patients who achieved the 3-way CR, unachieved patients have lower %FEV₁ (77.6% vs 85.4%; P < .0001) and higher FeNO levels (42 ppb vs 34 ppb; P = .0182), and there were more discordances in asthma control perception between patient and physicians (38.5% vs 9.3%; P < .0001). Physician-patient discordance was an independent factor that prevented the achievement of the 3-way CR in the logistic regression analysis, even when adjusted for %FEV₁ and FeNO (odds ratio 0.397; P < 0.0001).

Conclusions: Achieving CR in patients treated with ICS/LABA without biologics is challenging. Discrepancies between patient and physician perceptions on asthma control are significant barriers to achieving CR.

Background: Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), shows superior lung cancer treatment efficacy. However, osimertinib-induced severe hypersensitivity, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), is frequently observed in Asian populations and hinders cancer treatment.

Objective: We investigated the genetic HLA predisposition and immune pathomechanism of osimertinib-induced hypersensitivity.

Methods: We enrolled 17 patients with osimertinib-induced delayed hypersensitivity (7 with severe SJS/TEN and 10 with mild maculopapular exanthema [MPE]), 98 osimertinib-tolerant subjects, and 2123 general population controls. HLA genotyping, drug-induced lymphocyte activation test (LAT), and surface plasmon resonance (SPR) assay were performed.

Results: HLA-B*51:02 was present in 83.3% of osimertinib-induced SJS/TEN patients but only in 3.3% of the general population controls (P = 2.8×10^-7, Pc=6.9×10^-6, odds ratio [OR]=146), and 0% of osimertinib-tolerant controls (P = 6.5×10^-8, Pc=1.6×10^-6, OR=707). The association of HLA-B*51:01 and HLA-A*24:02 with osimertinib-induced MPE patients, rather than with osimertinib-tolerant subjects (P = 0.002, OR=15.7 for HLA-B*51:01; P = 0.003, OR=9.5 for HLA-A*24:02), was identified as a phenotype-specific association. Granulysin-the SJS/TEN-specific cytotoxic protein-was significantly higher in SJS/TEN patients' plasma (39.8±4.5 ng/ml, P<0.001) and in in vitro LAT (sensitivity=83.3%, P<0.01) compared to the tolerant controls. Patients with osimertinib-induced hypersensitivity appeared to tolerate alternative EGFR-TKIs. SPR results also confirmed that HLA-B*51:02 protein has a higher binding affinity for osimertinib and lower or no affinity for other EGFR-TKIs.

Conclusions: HLA-B*51:02 frequently occurs in Asian populations and is strongly associated with osimertinib-induced SJS/TEN. Our findings suggest HLA-B*51:02 screening as a preemptive test to reduce osimertinib-induced severe hypersensitivity.

Background: Venom-allergic patients are frequently double-sensitized to honeybee venom (BV) and Vespula venom (VV); genuine double allergy is uncommon.

Objectives: To assess if quantitative comparison of BV and VV-specific IgE levels permits to identify the culprit venom in double-sensitized patients; to evaluate whether independent sensitization to BV- and VV-specific components corresponds to an indication for double immunotherapy.

Methods: This single centre observational study evaluates 1069 consecutive patients; 490 non-allergic controls were available for statistical comparison. The diagnosis (BV allergy, VV allergy, double allergy) based on a comprehensive allergological work-up including patient history, IgE serology, intradermal skin test, and - if required - basophil activation testing. Quantitative allergen-specific IgE to BV, VV, rApi m 1, rVes v 5 was retrospectively compared with the final diagnosis; the ratio of BV/VV-specific IgE levels was considered in double-sensitized venom-allergic patients.

Results: Sensitization to whole venom preparations and components was frequent in patients and asymptomatic controls, with higher specific IgE levels in the patient group. An at least 5:1-dominance of the specific IgE to either BV or VV was documented in 239 (52.1 %) of 459 double-sensitized venom-allergic patients; 232 (97.1%) of these patients were diagnosed mono-allergic to only the venom they were dominantly sensitized to.

Conclusions: Five:1-dominant specific IgE indicates the culprit venom in double-sensitized allergic patients. Additional component-resolved diagnostic testing can be restricted to cases with double sensitization to whole venoms at a ratio less than 5:1. Double sensitization to rApi m 1 and rVes v 5 per se does not justify double venom immunotherapy.

Background: Pollen-food-allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable.

Objective: To develop consensus recommendation statements for managing patients with PFAS.

Methods: An international panel of allergists, researchers, and nutritionists with an interest in PFAS from 25 different institutions across 11 countries convened and a list of statements was written by 3 authors. The RAND/University of California Los Angeles methodology was adopted to establish consensus on the statements.

Results: After 2 Delphi rounds, a consensus was reached on 14 statements. The panel agreed that patients with PFAS would benefit from counseling on the nature and basis of PFAS and the rare chance of more severe systemic reactions and their recognition. The panel agreed on avoiding the raw food responsible for the index reaction, but not potentially cross-reactive fruits/vegetables based on the responsible food of the index reaction. Epinephrine autoinjectors should be recommended for patients with PFAS who experienced severe symptoms (beyond the oropharynx) or for patients considered at risk for severe reactions. The panel agreed that the benefit of allergen immunotherapy remains unclear and that PFAS should not be considered the primary indication for such intervention.

Conclusions: We developed consensus statements regarding counselling patients about the nature and severity of PFAS, potential risk factors, dietary avoidance, epinephrine autoinjector prescription, and allergen immunotherapy consideration for patients with PFAS.

The term "allergy" is inaccurate for the vast majority of the contents in the current allergy fields of electronic health records (EHRs). While EHRs have transformed access to health information and streamlined the delivery of care, their ability to reliably indicate medications, vaccines, or foods that mandate avoidance versus preferences or mild intolerances, is suboptimal. The current systems are reactive instead of being proactive and frequently fail to communicate the appropriate course of action. This Position Statement of the American Academy of Allergy, Asthma and Immunology (AAAAI) advocates for a change in terminology. The section of the EHR currently labeled "allergies" should be renamed "alerts." The term "alert" accurately captures the purpose of this section without incorrectly assigning an allergic mechanism, and prioritizes easily understood and actionable labels. This change has the potential to simultaneously improve patient safety and care. This shift will be the first step in the transformation of the alerts section of the EHR. This document provides a framework for categorizing what should be included in this section. Enacting these changes will require EHR and clinical decision support vendors, healthcare and data standard regulators, allergists, and the larger health care community to work together to bring about these important advances.

Background: Beta-lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of beta-lactam antibiotics.

Objective: This systematic review and meta-analysis aimed to identify sex and gender-based differences in the prevalence of immediate beta-lactam allergy.

Methods: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013-2023. Patients with a documented beta-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in beta-lactam allergy with meta-analysis.

Results: We included 69 primary studies, assessing 53,989 participants from outpatient and inpatient cohorts. 7,558 patients had a confirmed beta-lactam allergy. There was no difference in the prevalence of positive beta-lactam allergy test between males and females. Sub-group analysis of studies that performed oral challenges did show a higher risk of beta-lactam allergy in females than males (RR 1.40, 95% CI 1.18-1.66, p < 0.001, I² =77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in beta-lactam allergy studies.

Conclusions: Our findings suggest both sex-based and gender-based differences in the prevalence of immediate beta-lactam allergy. Both biological factors, such as sex hormones, and gender-based behaviors, including increased healthcare utilization, may contribute to higher rates of beta-lactam allergy diagnosis in females.