Allergy and asthma proceedings最新文献

Background: Beta-lactam allergy (BLA) labels are common in children but often disproven when formally evaluated. This diagnostic discrepancy leads to higher health-care costs and increased adverse outcomes. Beta-lactam antibiotics are associated with a variety of adverse reactions in children. A serum sickness-like reaction (SSLR) is one adverse reaction that is complex in its diagnosis and management due to its heterogeneous clinical presentation and poorly understood mechanism. This unclear presentation and diagnostic criteria can be confusing for patients, families, and health-care professionals, leading to allergy evaluation hesitancy. With updated drug practice parameters that support the utility of oral drug challenges for patients with SSLRs related to beta-lactams, barriers remain for these patients to seek allergy evaluation. Objectives: The objective was to assess caregiver perspectives on BLA delabeling and identify barriers to drug challenge testing in children with a history of SSLRs. Methods: We conducted an 18-question telephone survey with 14 caregivers of children with a history of beta-lactam-associated SSLR. The survey assessed attitudes toward allergy delabeling, understanding of challenge testing, and perceived barriers to testing. Results: Most caregivers demonstrated an understanding of the importance of allergy delabeling; however, the comfort level with challenge testing varied, depending on the setting, provider, and perceived risk of SSLR recurrence. Of the caregivers, 62.4% reported feeling comfortable with their child's pediatrician performing the testing. When asked about their concerns about testing, nearly 50% of caregivers expressed concern about the possibility of a repeated SSLR. Conclusion: The overall positive attitude toward BLA testing, especially in a primary care setting, highlights an opportunity to make testing more accessible for patients. However, the unpredictable nature of SSLRs seems to contribute to caregiver reservations about pursuing testing for their child. To mitigate this, targeted education from health-care professionals, such as physicians, advanced practice providers, and nurses, may reduce caregiver hesitancy and facilitate BLA delabeling for patients with SSLRs.

Background: Proton-pump inhibitors (PPI) are widely used in pediatric populations, although hypersensitivity reactions (HSR) to these agents are rare and not well characterized in children. Objective: This study aimed to evaluate the clinical characteristics and diagnostic findings of pediatric patients with suspected HSRs to PPIs. Methods: Pediatric patients referred to our allergy clinic with suspected PPI-related HSRs between January 2012 and October 2023 were retrospectively analyzed. Data on demographics, reaction characteristics, comorbidities, and diagnostic test outcomes (skin-prick test, intradermal test, and drug provocation test) were collected. Results: Twenty-two patients (median age, 12 years; 81% girls) were included. Lansoprazole was the most commonly implicated PPI (64%). Clinical manifestations included urticaria (41%), anaphylaxis (36%), maculopapular eruption (14%), angioedema (4.5%), and toxic epidermal necrolysis (4.5%). Most reactions (77%) occurred within 6 hours of drug intake. Among 18 patients undergoing diagnostic evaluation, 11 were tested with the suspected PPI and 7 were tested with an alternative PPI. One patient had a positive intradermal test result to omeprazole but tolerated lansoprazole. In total, 10 patients had their PPI allergy label removed after a negative diagnostic workup; 9 tolerated an alternative PPI. Conclusion: Urticaria and anaphylaxis were the most common presentations of PPI hypersensitivity. Lansoprazole was the most frequently suspected drug. Skin testing, followed by a drug provocation test with a tolerated alternative, remains essential for diagnostic clarification. Clinicians should be aware of possible cross-reactivity among PPIs. Further pediatric studies are needed to optimize diagnostic and management strategies for PPI-induced HSRs.

Background: Measurement of specific immunoglobulin E (sIgE) is often used interchangeably with a skin-prick test (SPT) to detect allergic sensitization. Evidence of concordance between the two methods for aeroallergens in children is limited. Potentially, discordance can lead to misclassification in atopy diagnosis and subsequent clinical management. The arbitrary sIgE cutoff value of 0.35 kUA/L is used uniformly for all allergens. Objective: The aim of the study was to evaluate the agreement between sIgE with a cutoff of 0.35 kUA/L and a positive SPT result (cutoff of 3 mm) for 10 aeroallergens and to investigate the sIgE level that corresponds best with a positive SPT result in school-age children. Methods: Measurement of sIgE and SPT for birch, Timothy grass, mugwort, horse, dog, cat, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Alternaria, and Cladosporium were performed in 300 children ages 6 to 14 years: 132 children with asthma and 168 controls. The agreement between sIgE and SPT results for the individual aeroallergens was assessed by using the Cohen κ coefficient with different sIgE cutoff values. Results: In total, the 300 children had 297 positive SPT results and 445 positive IgE analyses. The incidence of sensitization to Alternaria and Cladosporium was too low for further analysis. The agreement between the sIgE cutoff of 0.35 kUA/L and the SPT result cutoff of 3 mm was moderate to substantial for the remaining eight aeroallergens. The estimated optimal sIgE cutoff level that predicted an SPT result of ≥3 mm was 0.75 kUA/L for grass, horse, dog, and cat; 1.0 kUA/L for mugwort; 3.0 kUA/L for D. pteronyssinus; 5.0 kUA/L for birch; and 10.0 kUA/L for D. farinae. Using an sIgE cutoff of 0.75 kUA/L slightly increased the agreement for all eight allergens. Conclusion: Compared with an SPT result, a cutoff of 3 mm, analysis of our data suggests that an sIgE cutoff of 0.35 kUA/L is too low and that the optimal cutoff differs for the different aeroallergens.

Background: Sporadic reports have been published with regard to allergic reactions in patients with bovine milk allergy after receiving parenteral lactose-containing methylprednisolone. Persistent milk allergy is a risk factor for other atopic diseases, in which corticosteroids, e.g., methylprednisolone, are commonly an adjunctive treatment. Laboratory investigations to validate the presence of residual milk protein as the cause for reactions are scarce. Thus, individualized recommendations for the use of methylprednisolone in patients with milk allergy remain undefined. Objective: We hypothesized that excipient contaminants, e.g., residual caseins, may be responsible for these reactions. We sought to evaluate for the presence of casein proteins in lactose-containing methylprednisolone and provide recommendations with regard to its use in patients with milk allergy. Methods: To assess for incomplete purification of lactose from its bovine milk source, standardized enzyme-linked immunosorbent assay (ELISA) was performed from five vials across four lots of commercially available lactose-containing methylprednisolone to detect casein subtypes Bos d 9 and Bos d 11, the two most abundant milk proteins. Results: High-fidelity ELISA revealed no detectable Bos d 9 in any vials of lactose-containing methylprednisolone. Trace amounts of Bos d 11 were detected in all vials compared with Bos d 9 (p = 0.008). Molecular modeling revealed minimal similarity between Bos d 9 and Bos d 11. Conclusion: Undetectable Bos d 9 and trace Bos d 11 in lactose-containing methylprednisolone raises optimism but warrants further investigation of immunoglobulin E binding epitopes and the clinical relevance of casein subtypes. It is reassuring that milk protein eliciting doses are usually 10⁶-fold higher than the nanogram quantities of Bos d 11 detected in our study, although this is limited by exposure route. Vaccines and medications with possible trace milk proteins remain largely well tolerated in patients with milk allergy. Lactose-containing methylprednisolone can likely be used with low risk of adverse reaction in most patients with milk allergy.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease of the nasal and paranasal sinuses. In phase III clinical trials, dupilumab significantly improved objective and patient-reported measures of CRSwNP versus placebo. However, a real-world evidence gap exists between efficacy and effectiveness data for dupilumab in CRSwNP, particularly in the United States. Objective: Assessing Long-teRm Outcomes of dupiluMAb Treatment in Adult Patients With CRSwNP (AROMA) aims to characterize patients who receive dupilumab for CRSwNP in a real-world setting and evaluate long-term effectiveness. Methods: AROMA is a prospective global registry study that is recruiting adult patients with uncontrolled CRSwNP who were initiating dupilumab and following them for up to 36 months. Baseline demographics and disease characteristics were assessed for all patients entering the registry. Results: As of February 2023, the study had recruited 303 patients of a target enrollment of 700, with a mean age of 50.8 years, and 57.1% were recruited in the United States. A history of asthma was reported in 70.6% of the patients and a history of allergic rhinitis in 70.6% of the patients. In the 24 months before enrollment, 61.7% of the patients had at least one sinonasal surgery and 68.6% used systemic corticosteroids. At baseline, 35.0% of the patients were receiving intranasal corticosteroids and 33.3% were receiving leukotriene receptor antagonists. In the Global Patient Assessment, 31.7% and 29.7% of the patients reported moderate and severe CRSwNP symptoms, respectively, during the past week. Conclusion: Patients in AROMA had a high disease burden in terms of symptoms, comorbidities, and treatment burden. Nearly two-thirds of patients with CRSwNP had at least one sinonasal surgery before initiating dupilumab.Clinical trial NCT04959448 (AROMA), www.clinicaltrials.gov.

Background: Ondansetron is a common antiemetic that rarely causes hypersensitivity. Skin-prick testing (SPT) and intradermal testing (IDT) may assist in diagnosing ondansetron hypersensitivity; however, their sensitivity, specificity, and optimal concentrations remain unclear. To our knowledge, drug provocation testing (DPT), the criterion standard for diagnosis, has not been previously applied in pediatric cases. Objective: In this study, we aimed to evaluate ondansetron hypersensitivity in children by using a preliminary diagnostic approach that incorporated SPT, IDT, and DPT. Methods: We retrospectively reviewed pediatric patients who were evaluated for suspected ondansetron hypersensitivity between 2019 and 2025. We performed an SPT by using an ondansetron concentration of 2 mg/mL, followed by an IDT with concentrations of 0.02 and 0.2 mg/mL in patients with negative SPT results. In cases of patients with negative skin test results, we conducted DPTs. Results: We included seven pediatric patients ages 3-16 years. All had negative SPT results, which underscores its limited sensitivity. IDT results were positive in three patients with a history of anaphylaxis (one at 0.02 mg/mL, two at 0.2 mg/mL); DPT was not performed in these patients. Among the four with negative skin test results, DPT was performed in three and yielded negative results. We confirmed hypersensitivity in three patients. In another three, no clinical reactivity was observed at the time of DPT, and the diagnosis remained inconclusive in one patient. Conclusion: To our knowledge, this is the first pediatric case series to propose a preliminary diagnostic approach that incorporated DPT in the evaluation of suspected ondansetron hypersensitivity. The findings highlight the limited sensitivity of SPT, emphasize the diagnostic value of IDT, particularly in patients with anaphylaxis, and support the safe applicability of DPT in patients with negative skin test results, with all three DPTs yielding negative results.

Substantial progress in our understanding of chronic urticaria has been accomplished in recent years. We now recognize the heterogeneity of this condition, which is comprised of a number of endotypes and phenotypes. Laboratory testing to identify a cause for chronic urticaria has been discouraged, as this does not lead to improved outcomes and is not cost-effective; however, evidence has shown selected laboratory tests are important for their prognostic value. Therapeutic options for chronic urticaria, particularly for patients who are antihistamine-resistant, have also improved. Despite this, chronic urticaria has continued to be a vexatious condition for both patients and health care providers, and many patients continue to experience unmet needs. Guidelines recommend a step-care approach for management of chronic urticaria that can encourage substantial improvement in clinical course and quality of life. Use of anti-IgE therapy for more than the past decade has enabled many patients with antihistamine-resistant chronic urticaria to achieve improved outcomes; however, a substantial proportion continue to experience ongoing symptoms and impaired quality of life. The armamentarium for management of patients with refractory chronic urticaria has recently expanded, and will soon expand further. This article focuses on the approach to management of antihistamine-resistant patients who continue to experience poorly controlled chronic urticaria despite anti-IgE therapy prescribed at FDA-approved doses.

Background: The Urticaria Patient Daily Diary (UPDD) assesses patient-reported symptoms (itch, hives, angioedema) and impacts in adults and adolescents with chronic spontaneous urticaria (CSU). Objective: The objective was to adapt the UPDD for caregiver completion for patients ages 2-11 years. Methods: To inform modification of the UPDD, two iterative rounds of hybrid concept-elicitation/cognitive-debriefing interviews were conducted with clinical experts and caregivers of children with CSU recruited via patient organizations in the United States and Canada. After concept elicitation, the participants reviewed a draft UPDD-Caregiver Version with initial modifications for caregiver completion. Data were analyzed by using thematic analysis. Results: Four clinicians and 12 caregivers were interviewed (round 1:4 clinicians, 5 caregivers; round 2:7 caregivers). Key symptoms reported by the caregivers were itch (n = 12), hives (n = 12), and swelling and/or angioedema (n = 7). All four clinicians confirmed itch and hives to be key symptoms in children ages 2-11 years with CSU, with associated angioedema for some. Scratching was confirmed as the key observable sign of itch. Caregiver-reported impacts included waking in the night (n = 10); difficulty getting to sleep (n = 8); and daily life impacts, including activities at school (n = 10), play (n = 8), with family and/or friends (n = 4), and sports (n = 3). After round 1, minor revisions were made to enhance comprehension of the UPDD-Caregiver Version, and an overall symptom severity item was added. Relevance, acceptability, and comprehension of the final measure were confirmed by round 2 participants; no further changes were required. Conclusion: The UPDD-Caregiver Version is a relevant and acceptable measure for caregiver completion to assess symptoms and impacts of CSU in children ages 2-11 years.

Background: Common variable immunodeficiency (CVID) and selective immunoglobulin G (IgG) deficiency (sIgGD) are primary antibody deficiencies with divergent clinical trajectories. CVID is characterized by recurrent infections and systemic noninfectious complications, whereas sIgGD typically follows a milder course. Despite sharing clinical features such as recurrent infections, comparative data on complications and mortality remain limited, which hinders risk-stratified management. Objective: This study compared the prevalence, clinical impact, and mortality associated with noninfectious complications in CVID and sIgGD, and identified predictors of adverse outcomes to support risk-stratified management and examined clinical differences within the CVID group based on baseline serum IgM levels. Methods: A single-center retrospective cohort study (2018-2024) included 111 patients with CVID and 19 patients with sIgGD. Diagnostic criteria for CVID included hypogammaglobulinemia (IgG level < 400 mg/dL with low IgA/IgM), impaired vaccine responses, and exclusion of secondary causes. The sIgGD required isolated IgG deficiency with normal IgA/IgM and intact vaccine responses. Noninfectious complications, including organ-specific and systemic manifestations as well as bronchiectasis were evaluated. In patients with CVID, a predefined subgroup analysis was performed based on baseline serum IgM levels (normal versus <40 mg/dL). Multivariate logistic regression identified mortality predictors. Results: The patients with CVID exhibited significantly higher rates of recurrent sinopulmonary infections (70.3% versus 42.1%), bronchiectasis (46.8% versus 21.1%), and noninfectious complications (57.7% versus 31.6%), including autoimmune disorders such as hematologic manifestations (33.3% versus 10.5%). In the CVID group, the patients with low IgM levels exhibited a significantly higher prevalence of gastrointestinal involvement (24.0% versus 5.6%; p = 0.035). Bronchiectasis (odds ratio [OR] 5.22) and noninfectious complications (OR 7.95) independently predicted mortality in CVID. Male sex showed borderline risk. In contrast, no mortality was observed in the sIgGD cohort over the study period. Conclusion: CVID is associated with substantial noninfectious morbidity and mortality, which necessitates early identification and long-term monitoring. In contrast, sIgGD exhibits a milder clinical phenotype, although preventive care remains important. These findings support distinct management strategies and highlight the utility of clinical markers for risk stratification.

Background: Hypersensitivity reactions (HSR) to tumor necrosis factor α inhibitors (TNFi) can occur but data about skin testing in such reactions are limited. Objective: To evaluate skin testing in patients with HSRs to TNFi. Methods: A detailed review of demographics and clinical characteristics, features of index reactions, results of skin tests, and outcomes of desensitization protocols were obtained. Results: The cohort comprised 64 patients (women/men: 41/23). Treatment distribution included etanercept (n = 50 [78.1%]), adalimumab (n = 11 [17.2%]), and infliximab (n = 3 [4.7%]). HSRs were seen as an injection-site reaction (ISR) in 47 patients (73.4%), generalized urticaria in 8 patients (12.5%), and anaphylaxis in 3 patients (4.7%). Forty-four patients (44/64 [72%]) had positivity on skin tests as either skin-prick test (SPT) or intradermal test (IDT). Among other reaction types, the patients with ISRs exhibited the highest skin test positivity (p = 0.043). Among the 17 patients who underwent rapid subcutaneous or intravenous desensitization, 15 patients (88.2%) had positive skin test results, and all desensitization procedures were successfully completed, despite some experiencing local breakthrough reactions (BTR). Conclusion: This study, which includes the largest number of patients reported in the literature, highlights the important role of skin testing in diagnosing HSRs to TNFi. Notably, etanercept demonstrated the highest positivity rate. Successful completion of desensitization protocols despite some BTRs highlights the importance of desensitization in patients experiencing HSRs to these treatments.