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

Accurate identification of allergy-eliciting stinging insect(s) is essential to ensuring effective management of Hymenoptera venom-allergic individuals with venom-specific immunotherapy. Diagnostic testing using whole-venom extracts with skin tests and serologic-based analyses remains the first level of discrimination for honeybee versus vespid venom sensitization in patients with a positive clinical history. As a second-level evaluation, serologic testing using molecular venom allergens can further discriminate genuine sensitization (honeybee venom: Api m 1, 3, 4, and 10 vs yellow jacket venom/Polistes dominula venom Ves v 1/Pol d 1 and Ves v 5/Pol d 5) from interspecies cross-reactivity (hyaluronidases [Api m 2, Ves v 2, and Pol d 2] and dipeptidyl peptidases IV [Api m 5, Ves v 3, and Pol d 3]). Clinical laboratories use a number of singleplex, oligoplex, and multiplex immunoassays that employ both extracted whole-venom and molecular venom allergens (highlighted earlier) for confirmation of allergic venom sensitization. Established quantitative singleplex autoanalyzers have general governmental regulatory clearance worldwide for venom-allergic patient testing with maximally achievable analytical sensitivity (0.1 kU_A/L) and confirmed reproducibility (interassay coefficient of variation <10%). Emerging oligoplex and multiplex (fixed-panel) assays conserve on serum and are more cost-effective, but they need regulatory clearance in some countries and are prone to higher rates of detecting asymptomatic sensitization. Ultimately, the patient's clinical history, combined with proof of sensitization, is the final arbiter in the diagnosis of Hymenoptera venom allergy.

Patients with Hymenoptera venom allergy (HVA), especially those with severe anaphylaxis, frequently have concomitant clonal mast cell disease (MCD) in the form of systemic mastocytosis or monoclonal mast cell activation syndrome. Detection of clonal MCD is important because it will have significant consequences for managing HVA. Therefore, we recommend patients with HVA be systematically screened for clonal MCD. The pretest probability of clonal MCD can be assessed in a stepwise fashion starting with examination of the skin for typical monomorphic maculopapular cutaneous mastocytosis lesions; measurement of the baseline serum tryptase (BST) and tryptase genotyping for patients with BST greater than 11 ng/mL; followed by the Red Española de Mastocitosis score, which is calculated using anaphylaxis clinical features, BST, and the patient's sex. A bone marrow biopsy should be performed in patients with monomorphic maculopapular cutaneous mastocytosis, a Red Española de Mastocitosis score of 2 or greater, or an elevated BST based on tryptase genotype. Patients with HVA and a clonal MCD should be treated with immunotherapy directed against the Hymenoptera venom for which they are sensitized. For this high-risk subgroup of patients with HVA, it is recommended to continue immunotherapy for more than 5 years or indefinitely and to carry at least three epinephrine autoinjectors. Future studies should determine whether KIT D816V-selective tyrosine kinase inhibitors are effective at preventing or reducing the severity of Hymenoptera-venom triggered anaphylaxis in patients with clonal MCD.

Stinging ants represent a wide range of over 200 different species across the world, of which Solenopsis, Myrmecia, Pogonomyrmex, and Brachyponera genera account for a substantial economic and healthcare burden. S. invicta (red imported fire ant [IFA]) and M. pilosula (jack jumper ant [JJA]) are 2 species of high clinical importance, known to cause anaphylaxis in humans, with numerous reported fatalities. Diagnostic testing should be performed in patients with a history of a systemic reaction with skin testing and/or in vitro specific immunoglobulin E (IgE) testing. In vitro testing is commercially available for IFA through whole-body extract specific IgE and JJA venom-specific IgE, but not widely available for other stinging ant species. Commercial venom component testing for IFA and JJA is currently not available. Patients with a clinical history and positive specific IgE testing should undergo treatment with specific immunotherapy, which is currently available for IFA and JJA. Buildup may be performed using conventional, semi-rush, rush, or ultra-rush schedules with similar risk profiles for IFA. Optimal duration for whole=body extract immunotherapy for IFA and specific JJA venom immunotherapy is not well studied, but generally recommended for at least 3 to 5 years. Sting challenges are used in research settings, primarily to assess treatment efficacy of immunotherapy.

Evaluation and management of insect sting allergy are often not straightforward when there is uncertainty about the history of reaction, the significance of test results, and the risk of severe reaction to future stings. Patients encounter misinformation about the chance of reaction and may have strong beliefs about the need for treatment. Shared decision-making encourages the clinician to listen to the patients' concerns and beliefs, share relevant information and evidence, and partner with patients to incorporate their values and preferences. This review discusses some major decision points in diagnosis and treatment of insect-allergic patients, with attention to the potential burdens or harms that are important to patients and factors that relate to patients' values and preferences concerning the choices they must make. This is especially true in patients with no history of moderate to severe sting anaphylaxis in whom the risk may be overestimated, but it can also be important in patients who underestimate the risk associated with severe sting anaphylaxis. Clinicians should become more knowledgeable about patient-important beliefs and outcomes and engage in shared decision-making to help patients understand and be comfortable with the choices they must make.

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. Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count 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 institutional review board-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 y), the most common prescribing indication for dupilumab was chronic rhinosinusitis with nasal polyps (n = 11). Twenty-three patients (82%) showed significant clinical improvement on dupilumab. Hypereosinophilia (absolute eosinophil count > 1.5 × 10⁹/L) recurred or worsened in 9 of 20 patients on dupilumab monotherapy. Moreover, 4 of 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 hematological remission on an eosinophil-lowering biologic developed hypereosinophilia or an eosinophil-related complication. Serum immunoglobulin E and eotaxin levels decreased on dupilumab therapy.

Conclusions: 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: Although respiratory viruses are common triggers of asthma exacerbations, the influence of viral infection characteristics on exacerbation presentation and treatment response in the pediatric emergency department (ED) is unclear.

Objective: To assess viral infection characteristics of children experiencing ED asthma exacerbations and to test their associations with severity and treatment response.

Methods: This is a prospective study of children, aged 4 to 18 years, who received standard ED asthma exacerbation treatment with inhaled bronchodilators and systemic corticosteroids. Nasal swabs collected for viral metagenomic analyses determined virus presence, load, and species. Outcomes included exacerbation severity (Pediatric Asthma Severity [PAS] score, clinician impression, and vital signs) and treatment response (discharge home without needing additional asthma therapies).

Results: Of 107 children, 47% had moderate/severe exacerbations by PAS and 64% demonstrated treatment response. Viral metagenomic analysis on nasal swabs from 73 children detected virus in 86%, with 10 different species identified, primarily rhinovirus A (RV-A), RV-C, and enterovirus D68. Exacerbations involving RV-A were milder (odds ratio [OR] = 0.25; 95% confidence interval [CI] = 0.07-0.83) and tended to be more responsive to treatment than non-RV-A infections, whereas exacerbations involving enterovirus D68 were more severe (OR = 8.3; 95% CI = 1.3-164.7) and had no treatment response association. Viral load was not associated with treatment response but exhibited a strong linear relationship with heart rate (r_partial = 0.48), respiratory rate (r_partial = 0.25), and oxygen saturation (r_partial = -0.25), indicative of severity.

Conclusions: The majority of ED asthma exacerbations are triggered by respiratory viruses. Viral species are associated with severity and treatment response, suggesting that early pathogen detection could inform ED treatment decisions. Additional studies are needed to identify differences in pathobiology underlying exacerbations triggered by different viral species, and how to effectively treat these heterogeneous exacerbations.

Background: Small-airway function assessment is crucial for asthma diagnosis and management. Abnormalities in terminal airflow deserve attention.

Objective: This study investigated whether (FEV₃-FEV₁)/FVC correlates with airway hyperresponsiveness (AHR) and inflammation in patients with preserved spirometry.

Methods: This cross-sectional study enrolled patients with FEV₁ of 80% predicted or greater, FEV₁/FVC of 0.7 or greater, and recurring asthma-like symptoms. Data included demographics, FeNO, impulse oscillometry, and spirometry. Univariate and combined models predicting AHR were analyzed in 553 patients and validated in 561. We also assessed correlations between sputum inflammation and spirometrics.

Results: Airway-hyperresponsive patients exhibited higher (FEV₃-FEV₁)/FVC ratios compared with those who were negative for AHR. This ratio showed the strongest association with the methacholine dose causing a 20% FEV₁ decrease and the response dose ratio (r = -0.26 and 0.39, respectively; P < .001 for both). The area under the receiver operating characteristic curve for AHR diagnosis using (FEV₃-FEV₁)/FVC was 0.751, increasing to 0.821 when it was combined with FeNO, as confirmed in the validation cohort. Moreover, (FEV₃-FEV₁)/FVC was superior to maximal expiratory flow at 50% of FVC for identifying eosinophilic airway inflammation characterized by elevated FeNO levels. It correlated better with sputum eosinophil count than with the other spirometrics.

Conclusions: Elevated (FEV₃-FEV₁)/FVC levels were evident in AHR-positive patients with preserved FEV₁/FVC ratios. They serve as a sensitive marker of AHR and airway inflammation correlating with the response dose ratio, a provocative dose causing a 20% fall in FEV₁, and sputum eosinophils, suggesting their utility in monitoring patients at risk for uncontrolled asthma.

Background: In cholinergic urticaria (CholU), itchy wheal and flare-type skin reactions are triggered by sweat-inducing activities. The CholU activity score (CholUAS) is used to assess disease activity but has not yet been validated. The aim of the study was to validate the CholUAS, develop an English version, and provide instructions for scoring.

Methods: Cognitive debriefing of CholUAS was performed. Patients with CholU (n = 75) used the CholUAS on 7 consecutive days, underwent provocation testing, completed additional anchor instrument questionnaires including global evaluation tools, and established quality of life instruments. A scoring protocol for the calculation of the weekly CholUAS, the CholUAS7, was developed. The CholUAS7 was tested for validity, reliability, and influencing factors. An English version of the CholUAS was developed.

Results: The final CholUAS contains 3 questions that are used for scoring as well as 1 global question. The weekly CholUAS, CholUAS7, showed excellent test-retest reliability and good correlations with anchor instruments. Statistical analysis showed no significant influence of age or duration of disease on CholUAS7 results.

Conclusion: The validated CholUAS is ready for use in clinical trials and routine clinical practice.