Allergology International最新文献

Background: Data on the long-term efficacy and safety of topical therapy for atopic dermatitis (AD) remain limited.

Methods: This prospective cohort study included all children with AD who had their first visit to the Allergy Center at the National Center for Child Health and Development between December 2020 and September 2022. Participants were evaluated at enrollment, 6, and 12 months, and also monitored via questionnaires. We analyzed those with an Eczema Area and Severity Index (EASI) score ≥7.1 and complete EASI data at both follow-up points. The primary endpoint was the proportion achieving ≥75 % improvement in EASI from baseline (EASI-75) at 12 months. Secondary outcomes included other clinical endpoints, QOL scores, and skin and ocular complications.

Results: Of 763 enrolled children, 107 had EASI ≥7.1, and 77 (72.0 %) had complete follow-up data. Median age at enrollment was 57.0 months [quartile: 13.0-141.0], and 58.4 % were male. Fifty-three had moderate (7.1≤EASI≤21.0) AD, and 24 had severe to very severe (21.1≤EASI) AD. Only two children (2.6 %) required systemic therapy during the study period. Median EASI scores significantly improved from 14.8 at baseline to 0.8 at both 6 and 12 months (P < 0.001). EASI-75 was achieved by 80.5 % at 6 months and 85.7 % at 12 months. Other clinical endpoints, including POEM, pruritus and sleep-disturbance NRS, and QOL scores, were improved. New dermatologic complications were rare, and no ophthalmologic complications occurred.

Conclusions: Most pediatric AD cases with moderate or greater severity can be effectively and safely controlled with topical therapy alone.

Background: Severe Th2 inflammatory diseases, including food allergy, are known to be associated with osteoporosis. However, while IL-4 inhibits osteoclast differentiation, detailed mechanisms of osteoporosis caused under IL-4-excessive environments remain unclear.

Methods: OVA23-3 mice are transgenic mice expressing OVA-specific T-cell receptors and develop significant IL-4-producing T-cell responses resulting in food-allergic enteropathy associated with osteoporosis when fed an egg white (EW) diet. This enteropathy is characterized by phases of inflammation and desensitization; bone loss develops during the inflammatory phase with the onset of allergic enteropathy and is maintained during the desensitization phase when the enteropathy is alleviated by immunological tolerance induction by continuous EW-feeding. We used this model to elucidate the mechanism of food antigen-induced osteoporosis, particularly in an IL-4-dominant environment.

Results: During the inflammatory phase, EW-feeding promoted osteoclastogenesis with increased mast cells, suppressed by administering anti-IL-4 antibody to the model. This finding suggests a critical role for IL-4 in the induction of osteoclastogenesis, which may be associated with mast cells and eosinophils over-differentiation and lead to osteoporosis. However, during the desensitization phase, the bone loss mechanism switched to high metabolic bone turnover, maintaining osteoclast activity despite amelioration of the enteropathy by continuous EW feeding. The increased number of IL-10-producing Tregs from mesenteric lymph nodes may reduce osteoclastogenesis during the desensitization phase, but did not suppress osteoporosis.

Conclusions: The present study provides a new perspective on a poorly understood mechanism of osteoporosis in severe allergies, suggesting the importance of maintaining bone health in allergic patients, including food allergies.

Background: Dosing intervals are important in determining oral food challenge (OFC) safety; however, the optimal interval remains unclear. This study aimed to investigate symptom onset time in low-dose OFCs, utilizing 60-min intervals, involving four common pediatric allergens.

Methods: We retrospectively analyzed symptom onset time for low-dose OFCs involving two doses at 60-min intervals in children allergic to egg, milk, wheat, and peanut. Challenges were performed to diagnose allergies or confirm tolerance acquisition. Total challenge doses were 250, 102, 52, and 133 mg of egg, milk, wheat, and peanut proteins, respectively. OFCs were positive when objective symptoms were observed.

Results: Of the 1610 children (379, 430, 431, and 370 had allergies to egg, milk, wheat, and peanut, respectively), 552 (34 %) were OFC-positive: 103 (27 %) with egg allergy, 210 (49 %) with milk allergy, 105 (24 %) with wheat allergy, and 134 (36 %) with peanut allergy. The median (interquartile range) onset times of symptom were 45 (29-60) min for egg allergy, 30 (15-45) min for milk allergy, 42 (30-55) min for wheat allergy, and 30 (14-45) min for peanut allergy after the first dose, and 35 (17-60) min for egg allergy, 30 (15-45) min for milk allergy, 35 (24-55) min for wheat allergy, and 25 (15-40) min peanut allergy after the second dose. Late-onset reactions (≥30 min) occurred in 64 % of first doses and 54 % of second doses across all allergens.

Conclusions: OFC dose intervals at >30 min are necessary to ensure safety and accurate assessment.

Background: Anaphylaxis is a life threatening complication of allergy and one of the treatment approaches for allergy is immunotherapy. Allergen immunotherapy is the only treatment that can alter the natural history of allergic disease. Oral immunotherapy is a viable therapeutic route in patients with food allergies, during which peripheral plasmablasts, which are activated B cells, expand, and allergen-specific IgG4 is induced. We aimed to characterize the profile of plasmablasts undergoing oral immunotherapy.

Methods: A detailed profile of plasmablasts in 2 patients with milk allergies undergoing oral immunotherapy is provided by single cell analysis. The involvement of the subclasses and isotypes in plasmablasts in individuals undergoing oral immunotherapy was clarified by single-cell transcriptomics analysis and B cell immune receptor analysis and profile analysis of recombinant antibodies.

Results: Some clonally expanded antibodies and IgD clones were found to recognize allergens. Furthermore, constructing a clonal tree, over 80 % matched complementarity-determining region (CDR) clones were identified. Several IgA1 antibodies in the clonal trees were also found to recognize allergens.

Conclusions: Plasmablasts developed clonal differentiation in patients with milk allergy undergoing OIT. And somatic hypermutations and the allergen-positive rate of plasmablast are dependent on their subclasses and isotypes.

Background: In the era of asthma remission, quality of life (QOL) in daily activities is increasingly valued in addition to exacerbation control. However, the value of the Asthma Control Test (ACT) for assessing QOL remains unclear. This study compared the use of the ACT with the Asthma Quality of Life Questionnaire (AQLQ), with a focus on activity limitations.

Methods: We first analyzed biologic-treated asthma patients who were attending our institution and assessed the relationship between stable-phase ACT scores and AQLQ scores (including both overall scores and domain-specific scores). Receiver operating characteristic (ROC) curves were analyzed to identify the optimal ACT threshold for predicting favorable AQLQ scores. The findings were subsequently validated in a nonbiologic-treated group.

Results: Among biologic-treated patients (n = 69), the median ACT and AQLQ scores were 22 (IQR: 18-25) and 5.5 (IQR: 4.7-6.4), respectively. Discrepancies between the ACT and AQLQ were most evident in the activity limitation domain. Half of the patients with well-controlled ACT scores (≥20) reported difficulty with high-intensity exercise and avoiding environmental triggers, regardless of asthma duration. ROC curve analysis revealed that an ACT score ≥23 predicted favorable AQLQ activity limitation scores (≥6) (AUC: 0.83; sensitivity: 86 %; specificity: 76 %). Favorable scores were more commonly observed in the ACT ≥23 group than in the 20-22 group (p < 0.01). Similar findings were observed in the nonbiologic group (n = 123).

Conclusions: A cutoff score of ≥23 for the ACT may better reflect patient-perceived QOL than the conventional cutoff score of 20.

Background: Allergic diseases are highly prevalent chronic inflammatory conditions. They often co-occur because of shared immunological pathways. However, population-level studies covering a broad range of allergic diseases across the lifespan remain limited. The objective of this study was to examine the age-specific trends in allergic disease prevalence, patterns of multimorbidity, and longitudinal interrelationships among nine allergic conditions using a nationwide cohort.

Methods: We analyzed data from 1,137,861 individuals in the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2019. Nine allergic diseases were tracked: atopic dermatitis, asthma, allergic rhinitis, food allergies, drug allergies, anaphylaxis, allergic conjunctivitis, acute urticaria, and chronic urticaria. We assessed the annual prevalence, concurrent comorbidities, and estimated hazard ratios (HRs) for inter-disease associations using conditional Cox models adjusted for socioeconomic and geographic factors. Network graphs visualized significant associations (HR ≥ 2).

Results: The prevalence of most allergic diseases increased, including in children and older adults. The proportion of individuals with ≥2 allergic conditions rose from 0.7 % to 4.2 %. Chronic urticaria, atopic dermatitis, and asthma were major precursors of the development of additional allergic diseases. Disease-to-disease associations varied by age, with stronger interconnections observed in adulthood. Predictive modeling suggested increasing future burdens of chronic urticaria and late-onset asthma.

Conclusions: Allergic diseases exhibit increasing prevalence and multimorbidity across all ages, with strong age-dependent interrelationships. These findings highlight the need for integrated life-course-oriented strategies for allergic disease surveillance and management.

Background: Because different immunosuppressive therapies have their own characteristic properties to inhibit/enhance the production of various cytokines in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), cytokine profile dynamics could be used to predict and monitor the therapeutic response across different treatments, when assessed at baseline and following therapy.

Methods: This retrospective analysis was performed to assess how changes in cytokine profiles available in clinics contributed to an optimal therapeutic response in SJS/TEN patients. We included 31 patients with SJS/TEN, treated with standard corticosteroids (n = 9), pulse corticosteroids (n = 11), intravenous immunoglobulins (n = 4), plasmapheresis (n = 6), and supportive therapy (n = 1).

Results: High granulysin (≥ 1.6 ng/ml) and soluble Fas ligand (≥ 2540 pg/ml) levels at baseline were strong predictors for the failure of standard corticosteroid therapy. We found that standard corticosteroid treatment inhibited not only Th1 cytokines but also monocyte-derived cytokines in patients exhibiting an adequate treatment response. Although pulse corticosteroids have a fundamentally similar effect as standard corticosteroids on cytokine profiles, pulse corticosteroids more efficiently reduced monocyte-derived cytokines. Intravenous immunoglobulins suppressed interferon-γ and interleukin (IL)-12p40 production more efficiently compared with standard corticosteroids and other immunosuppressive agents. A profound decrease in granulocyte colony-stimulating factor and IL-10 associated with a marked increase in IL-12 was specifically detected in SJS/TEN patients treated with plasmapheresis.

Conclusions: We can select the most appropriate treatment option for individual patients following the failure of standard corticosteroids by examining treatment-relevant cytokine profiles before and after treatment. We propose a treatment algorithm that can serve as a decision-making tool for tailored therapy selection.

Background: Inducible co-stimulator (ICOS) regulates the proliferation and differentiation of a variety of T cells. It is considered to be a potential immunotherapy target and marker for many diseases. Its dual role is worthy of further study in allergic rhinitis (AR).

Methods: We quantified ICOS-expressing T helper (Th) cells and changes in the proportions of Th1/Th2/Th9/Th17/follicular helper T (Tfh) and regulatory T cells (Treg) in the peripheral blood of patients with AR and in healthy controls (HC). All participants completed the Total Nasal Symptom Scores (TNSS) questionnaire. Ten patients with AR who underwent subcutaneous immunotherapy (SCIT) were followed for 6, 12, 24 and 36 months after treatment. In functional experiments, peripheral blood from ten dust mite-sensitized AR patients was analyzed for key T-cell subsets and ICOS expression under different stimulation conditions.

Results: The patients with AR showed higher levels of Th2, Th9, Th17 and Tfh compared with HCs, while the levels of Th1 and Treg were lower. However, ICOS expression on these T-cell subsets was elevated. TNSS correlated positively with Th2 and ICOS-expressing Th2. TNSS and ICOS-expressing Th2 decreased significantly with the passage of SCIT time. Functional assays showed that ICOS/ICOS ligand (L) stimulation increased the level of Th2, while phosphatidyl inositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) inhibition reduced Th2 levels.

Conclusions: Our findings demonstrate that ICOS expression and effects are linked to the differentiation of T cells in AR, especially Th2 cells, which suggests ICOS-expressing Th2 cells as a potential therapeutic target for AR.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a severe T cell-mediated hypersensitivity reaction. T cells in DReSS are stimulated via the p-i mechanism (pharmacological interaction with immune receptors), where the drug shows an off-target binding to immune receptors (TCR and/or HLA) leading to an unorthodox activation of T cells. P-i stimulations are particularly strong in DReSS, as the causative drugs are typically administered at high doses for prolonged durations (>7 days) and bind with relatively high affinity to a specific HLA allele and/or TCR. This mechanism results in delayed yet profound immune activation, progressing through four distinct phases. The p-i concept provides a unifying explanation for many puzzling aspects of DReSS and has significant implications for diagnosis, management, and prevention. Recognizing drug concentration, therapy duration, and HLA affinity as key determinants of strong p-i-mediated immune activation can improve risk assessment, early diagnosis, and intervention strategies for DReSS.

Background: The conventional in vitro lymphocyte transformation test (LTT) for diagnosing drug hypersensitivity reactions (DHRs) is limited by low sensitivity. To improve detection and assess T cell activation strength, we adapted this test to a cytokine-based assay (Cyto-LTT) by measuring IL-5, IL-13, IFN-γ, granzyme B and granulysin secretion.

Methods: We retrospectively analyzed 851 positive Cyto-LTT results (from a total 6058 Cyto-LTT) from a Swiss drug hypersensitivity diagnostic laboratory's database, including 97 patients with Drug Rash with Eosinophilia and Systemic Symptoms (DReSS) and 754 patients with exanthems, including urticarial, maculo- and maculopapular-rash. Cytokine responses measured across three drug concentrations of amoxicillin (n = 734), aromatic sulfonamides (n = 81), or vancomycin (n = 36) were evaluated for dose-dependency and the correlation to the clinical manifestations. A grading system defined strong responses as cytokine stimulation indices (SI) above the 75th percentile (per cytokine) in the exanthem group which served as a comparator for the DReSS cases.

Results: Cytokine responses increased dose-dependently. DReSS cases exhibited significantly stronger cytokine secretions compared to exanthem cases (p < 0.001), with strong responses observed in 62.9 % of DReSS patients versus 33.6 % of exanthem cases.

Conclusions: Cyto-LTT reveals dose-dependent T cell activation in delayed drug hypersensitivity reactions, challenging the notion that drug allergic reactions are dose-independent. The assay not only identifies the culprit drug but also quantifies immune activation strength. Stronger responses were more frequent in DReSS, suggesting the test may also inform risk assessment-particularly in guiding caution with structurally related compounds or in patients at risk for severe or recurrent reactions.