World Allergy Organization Journal最新文献

Introduction: Hereditary angioedema (HAE) types 1 and 2 are caused by C1 inhibitor deficiency or dysfunction, leading to increased prekallikrein activity and bradykinin production. HAE causes vasodilation and edema resulting in obstruction of the upper airway, gastrointestinal symptoms, and skin swelling. Evidence of involvement of other organ systems has been sparse. Herein, we demonstrate evidence of creatinine kinase (CK) elevation in HAE patients suggesting an effect of bradykinin on skeletal muscle with subsequent improvement with long term prophylaxis (LTP).

Methods: CK levels from participants with type 1 or 2 HAE enrolled in the Phase 2 and 3 clinical trials evaluating the safety and efficacy of donidalorsen for LTP in patients with HAE, was measured at baseline (before treatment initiation) and Week 17 (for participants enrolled in Phase 2 Study) and Week 25 (for participants enrolled in Phase 3 study). Mixed effect model with repeated measures was used to assess the influence of time and treatment (donidalorsen vs. placebo) on serum CK levels.

Results: CK levels were available from 20 patients enrolled in the Phase 2 study and the mean CK level was numerically lower by Week 17; however, these results were not statistically significant. Among the 90 participants enrolled in the Phase 3 study who had CK levels checked at baseline and Week 25, a significantly lower CK level at Week 25 was observed among those receiving Q4W donidalorsen, but not among those receiving donidalorsen Q8W or placebo.

Conclusion: Bradykinin appears to cause instability of skeletal muscle, causing CK release with even minor exercise. The effect of increases in bradykinin in HAE on muscle needs further research but may account for some of the atypical HAE symptoms patients often describe and which are noted in quality-of-life assessments. LTP, therefore, may confer additional benefits beyond reduction of HAE symptoms, potentially contributing to stabilization of skeletal muscle and improvement of fatigue and weakness.

Hyper-IgE, generally defined as serum IgE levels exceeding 2000 IU/mL, presents a common yet complex diagnostic challenge in pediatric practice. While elevated serum IgE are frequently observed in atopic conditions such as food allergy or atopic eczema, or parasitic infections, they may also signal underlying monogenic immunological diseases, specifically inborn errors of immunity (IEI) categorized under hyper-IgE syndrome (HIES). Distinguishing between common atopic diseases and HIES is essential, especially in children with early-onset, severe, or treatment-resistant presentations. This review focuses on non-syndromic causes of hyper-IgE in children, aiming to provide a practical, structured framework for clinicians. A broad array of conditions, including allergic diseases, infections, inflammatory disorders, malignancies, drug reactions, and environmental exposures, can result in elevated IgE levels. Given this wide differential, a systematic approach that incorporates detailed clinical history, physical examination, and targeted investigations is critical to guide diagnostic reasoning. To aid clinical decision-making, the authors propose a stepwise diagnostic algorithm that prioritizes common causes while also alerting clinicians to red flags suggestive of IEI or other rare conditions. This approach facilitates timely referral for immunologic or genetic evaluation when appropriate and minimizes unnecessary testing. Increased awareness of the diverse etiologies of hyper-IgE can improve diagnostic accuracy, enhance early intervention, and reduce morbidity. Future research should aim to refine diagnostic strategies, validate clinical algorithms, and develop standardized guidelines. Moreover, long-term data regarding characterization and subsequent follow-up of children with an isolated increase in serum IgE levels is fundamental to understanding the clinical and immunological trajectories of these patients.

Background: The International Severe Asthma Registry (ISAR) reported a high rate of comorbidities differentially associated with clinical characteristics, biomarkers, and outcomes.

Methods: We aimed to compare the prevalences of comorbidities between global (ISARWORLD) and ITALY-derived ISAR cohorts and to explore characteristics of severe asthma (SA) patients progressively enrolled into the Severe Asthma Network Italy (SANI) registry over 5 years.

Results: T2-related SA comorbidities, including allergic rhinitis (AR), chronic rhinosinusitis (CRS) and nasal polyps (NPs) were more frequent (p < 0.001) in the ITALY cohort in addition to some oral corticosteroids (OCS)-related comorbidities, likely relating to the higher burden of OCS use. A comorbidity-dependent pattern of association for biomarkers and clinical outcomes with AR, CRS and NPs was identified in both ITALY-derived and ISARWORLD cohorts. In addition, a progressive decrease in the frequency of atopy, total IgE, number of exacerbations (AEs), chronic OCS treatment (p < 0.001) and a progressive increase in lung function and eosinophils count was reported longitudinally in the SANI registry. When stratifying by the presence of NPs, sex and smoking status, similar enrolment changes were identified with the additional findings of increased FeNO in NPs and Female cohorts and atopic eczema in smokers.

Conclusion: Longitudinal observation of enrolment characteristics from the Italian SANI registry and comparison with ISAR highlight changes influenced not only by regional population traits but also by the attitude of clinicians, biologics availability and eligibility and the OCS stewardship campaign.

Trial registration: The International Severe Asthma Registry (ISAR): EU PAS number EUPAS23651; Study ID 47596; registered April 16, 2018. Severe Asthma Network Italy (SANI): NCT number: NCT06625216. Retrospectively registered 2024-07-05.

Background and aim: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), are life-threatening hypersensitivity reactions often triggered by specific drugs. Accurate detection of drug culprits is critical for patient management and prevention of similar conditions. This study evaluates and compares the diagnostic performance of the Lymphocyte Transformation Test (LTT), Conventional IFN-γ ELISpot, and Modified IFN-γ ELISpot assays (anti-CD3/CD28 and IL-2) in detecting drug-induced immune responses in SJS/TEN patients.

Methods: The study involved 20 SJS/TEN patients who were diagnosed based on clinical features, causality assessment using the Naranjo algorithm, and SCORTEN scoring for severity. Blood samples were collected to isolate peripheral blood mononuclear cells (PBMCs), which were subjected to LTT and IFN-γ ELISpot assays that was assessed by conventional and modified assays, the latter involving T-cell pre-activation using anti-CD3/CD28 and IL-2. Drugs tested included carbamazepine, ciprofloxacin, phenytoin, sulphamethoxazole, clozapine, and gatifloxacin. Diagnostic parameters, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated. The influence of systemic corticosteroid use on assay performance was also evaluated.

Results: The Modified IFN-γ ELISpot assay demonstrated significantly higher sensitivity (80%) and NPV (88.2%) compared to the LTT (sensitivity: 30%, NPV: 68.2%) and Conventional IFN-γ ELISpot assay (sensitivity: 20%, NPV: 65.2%). All assays exhibited high specificity (100%) and PPV (100%). Among the 20 SJS/TEN patients, 7 (35%) were receiving systemic corticosteroids at the time of testing. Patients receiving systemic corticosteroids showed no significant differences in the 3 assays. Culprit drugs such as carbamazepine and ciprofloxacin elicited stronger immune responses compared to irrelevant drugs, highlighting assay specificity.

Conclusions: The Modified IFN-γ ELISpot assay outperformed the LTT and Conventional IFN-γ ELISpot in detecting drug-induced immune responses in SJS/TEN patients, particularly for high-risk drugs such as carbamazepine and sulphamethoxazole. Its superior sensitivity and reliability suggest it its role in identifying the culprit drugs in these patients.

Objective: This study aimed to construct a multi-dimensional risk prediction model for atopic dermatitis (AD) by integrating the maternal-fetal immune axis, genetic risk factors, and environmental exposures.

Methods: The study prospectively enrolled 503 full-term newborns, with parental allergic history collected via questionnaire, maternal/cord blood biomarkers (IL-4, IL-13, IL-31, IL-33, IgE, TSLP) quantified by ELISA, and dust mite exposure dynamically assessed through quarterly standardized sampling. A 1-year follow-up was conducted to assess AD incidence in the neonatal cohort. Variables were screened via univariate analysis, LASSO regression and multivariable logistic regression to construct a nomogram model, with performance evaluated by ROC curve, calibration curve, Hosmer-Lemeshow test, triple cross-validation (repeated 10-fold, leave-one-out and bootstrap), and decision curve analysis.

Results: A total of 456 infants were finally included (106 infants in the AD group and 350 infants in the non-AD group). Through a multi-stage screening process, 6 risk factors were identified, including cord blood IgE and TSLP, maternal blood IL-4 and IL-33, mother with allergic history, and dust mite exposure levels; subsequently, a predictive model was constructed based on these factors. Upon evaluation, the model showed good discriminatory ability, calibration degree, robustness, and clinical applicability.

Conclusions: Cord blood IgE and TSLP, maternal blood IL-4 and IL-33, mother with allergic history, and dust mite exposure levels have shown good predictive value for AD. However, multicenter studies will be required to verify the universality of the model.