The future of targeted therapy in chronic spontaneous urticaria.

Chronic urticaria can be divided into 2 subsets: chronic spontaneous urticaria (CSU) with skin lesions occurring without a specific trigger and chronic inducible urticaria, which has an identified specific stimulus. The annual prevalence of chronic urticaria is 0.5% to 2.3% globally. The CSU is a self-limited disorder in most cases, with an average duration of 2 to 5 years, but symptoms persist beyond 5 years in up to 30% of patients. The first line of treatment is a daily nonsedating, second-generation H1-antihistamine. The CSU guidelines recommend using oral nonsedating antihistamines up to 4 fold in patients with CSU unresponsive to standard doses as the next step in treatment. A meta-analysis found that the rate of response in patients with CSU who responded to updosing was 63.2%. Therefore, approximately 40% of patients continue to have persistent hives and itching requiring treatment with the biologic omalizumab, based on evidence from randomized controlled trials. Although omalizumab has been shown to markedly relieve symptoms of CSU, omalizumab is not effective in all patients and has not been shown to induce long-term disease remission. Thus, there is an unmet need for more effective treatments that can lead to cure or long-term remission. In this review, we will provide an overview of new treatment targets and biologics that are under investigation for the treatment of CSU.

Therapeutic effectiveness of probiotics for atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials with subgroup analysis.

BACKGROUND: The effect of probiotics in the treatment of atopic dermatitis (AD) is inconclusive, partially due to the heterogeneities of AD. OBJECTIVE: The aim of the present study was to investigate the efficacy of probiotics in the treatment of AD with a subgroup analysis according to country, severity of AD, duration of supplementation, and probiotic strain. METHODS: Original articles reporting the therapeutic efficacy of probiotics for AD were identified by searching PubMed, Cochrane Library databases, and Embase from inception to September 30, 2022. RESULTS: This meta-analysis included 1,382 patients with AD from 25 randomized controlled trials. Probiotic supplementation was effective for the treatment of AD, reflected in a significant decrease in the SCORing Atopic Dermatitis (SCORAD) index (SMD, -4.0; 95%CI, -7.3 to -0.7). The subgroup analysis showed a significant therapeutic effect for AD among patients with mild or moderate AD (SMD, -1.4; 95%CIs -2.2 to -0.7), in those supplemented for more than three months (SMD, -5.1; 95%CIs -9.7 to -0.4), and in those supplemented with a probiotic that contained Lactobacillus spp. strains combined with or without other strains (SMD, -4.4; 95%CIs -8.0 to -0.8). In addition, the therapeutic effects of probiotics showed differences according to country and geographic region. CONCLUSIONS: Probiotics can be beneficial for the treatment of AD, and their therapeutic effect may be individually tailored to improve it based on the severity of AD, strain of probiotics, duration of supplementation, and geographic region.

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea. METHODS: AD patients aged 6-18 years who presented to 18 hospitals nationwide were surveyed. The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites, treatment history and quality of life were collected. The results of the patient's allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschool-onset (2-5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups. RESULTS: A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancy-onset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group. CONCLUSION: This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.

Clinical Characteristics of Oral Allergy Syndrome in Children with Atopic Dermatitis and Birch Sensitization: a Single Center Study.

BACKGROUND: Oral allergy syndrome (OAS) is an immunoglobulin E (IgE)-mediated hypersensitivity that occurs frequently in older children with pollen sensitization. This study focused on the clinical characteristics of OAS in children with atopic dermatitis (AD) and birch sensitization. METHOD: s: A total of 186 patients aged 2-18 years with AD and birch sensitization were enrolled in this study between January 2016 and March 2017. Their levels of serum total IgE and birch- and ragweed-specific IgE (sIgE) were measured using ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden). Information regarding causative foods and symptoms were obtained via interviews. The patients were divided into 3 groups according to their ages (group 1, 2-6 years; group 2, 7-12 years; and group 3, 13-18 years). RESULTS: Eighty-one of the 186 (43.5%) children with AD who were sensitized to birch pollen were diagnosed as having OAS. The prevalence of OAS in group 1 (the children who had AD and birch sensitization aged 2-6 years) was 36.6%. A greater predominance of men was noted in the non-OAS group (77.1%) compared to the OAS group (60.5%). Apples were the most common causative food in group 2 and 3 while kiwis were the most common cause of OAS in group 1. There was a statistically significant correlation between birch-sIgE levels and the prevalence of OAS (P = 0.000). The cut-off value was 6.77 kUA/L with 55.6% sensitivity and 79.0% specificity (area under the curve 0.653). CONCLUSION: In our study, the prevalence of OAS in children with AD and birch sensitization was 43.5%. Even in the preschool age group, the prevalence of OAS was considerable. Patients with high levels of birch-sIgE were more likely to have OAS. Clinicians should therefore be vigilant about OAS in patients with a high degree of sensitization to birch pollen and even young children if they have birch sensitization.

Infantile Anaphylaxis in Korea: a Multicenter Retrospective Case Study.

BACKGROUND: Anaphylaxis is increasing in young children. The aim of the present study was to analyze the clinical characteristics of anaphylaxis in Korean infants, with a focus on food triggers. METHODS: The study analyzed the medical records of infants aged 0 to 2 years old who had been diagnosed with anaphylaxis in 23 secondary or tertiary hospitals in Korea. RESULTS: We identified 363 cases of infantile anaphylaxis (66.9% male). Cutaneous symptoms were most prevalent (98.6%), followed by respiratory (83.2%), gastrointestinal (29.8%), and neurologic (11.6%) symptoms. Cardiovascular symptoms were noted in 7.7% of the cases. Most of the cases of anaphylaxis (338; 93.1%) were induced by foods. The most common trigger food was cow's milk and cow's milk products (43.8%), followed by hen's eggs (21.9%), walnuts (8.3%), wheat (7.7%), peanuts (4.8%), other nuts (3.0%), and fish (2.1%). In cow's milk-induced anaphylaxis cases, more than half the cases had cow's milk specific immunoglobulin E (sIgE) levels that were lower than the diagnostic decision points (DDPs), which is 5 kUA/L for those under the age of 1 and 15 kUA/L for those over the age of 1. In anaphylaxis induced by hen's egg, most of the cases (91.8%) had hen's egg sIgE levels that were higher than the DDP, which is 2 kUA/L for those under the age of 2 and 7 kUA/L for those over the age of 2. Of the infantile anaphylaxis cases, 46.8% had been treated with epinephrine, and 25.1% had been prescribed an epinephrine auto-injector. CONCLUSION: Cow's milk is the most frequent trigger food of anaphylaxis in Korean infants. However, we found no significant correlation between the sIgE level and clinical severity. Education is required regarding the importance of epinephrine as the first line therapy for anaphylaxis and on properly prescribing epinephrine for infants with a history of anaphylaxis.

Agreement between the skin prick test and specific serum IgE for egg white and cow's milk allergens in young infant with atopic dermatitis.

BACKGROUND: The skin prick test (SPT) for detecting atopic sensitization is not preferred in young infants with atopic dermatitis (AD) because of concerns about poor skin reactivity. This study aimed to evaluate whether the results of SPT agreed well with those of specific serum immunoglobulin E (sIgE) antibody test in young infants with AD. METHODS: This study included 2,077 eligible infants (age, <12 months) with AD who were tested by either SPT or sIgE between 2007 and 2011. Among them, 199 infants tested for egg white (EW) and 192 infants tested for cow's milk (CM), by both SPT and sIgE on the same day were identified and reviewed retrospectively. Kappa statistics and tests for equal kappa statistics were used to evaluate the agreement between the SPT and sIgE. RESULTS: The mean wheal diameter and the allergen-to-histamine ratio of SPT showed substantial agreement with those of sIgE for EW (κ = 0.62, 0.69) and CM (κ = 0.34, 0.47). The agreement for EW was significantly higher <6-month-old than in ≥6-month-old infants (κ = 0.79 vs. 0.54, P = 0.02), and that for CM was similar (P = 0.60). The mean wheal diameters for EW and CM were evenly distributed, and did not show increasing trends regardless of age in months (Ptrend = 0.13 and 0.06, respectively). CONCLUSIONS: The results of SPT agreed well with those of sIgE. This finding provides a rationale for using SPT, and suggests that SPT can be used along with sIgE to detect food sensitization in young infants with AD.

Evidence-based management guidelines for noncystic fibrosis bronchiectasis in children and adolescents.

Noncystic fibrosis bronchiectasis is a chronic respiratory disease that carries high socioeconomic and medical burdens and is caused by diverse respiratory illnesses. To improve clinical outcomes, early recognition, active treatment of exacerbations, and prevention of further exacerbations are essential. However, evidence for the treatment and prevention of acute exacerbation of noncystic fibrosis bronchiectasis, especially in children, is lacking. Therefore, the evidence- and consensus-based guidelines for medical and nonmedical treatment strategies for noncystic fibrosis bronchiectasis in children and adolescents were developed by the Korean Academy of Pediatric Allergy and Respiratory Disease using the methods recommended by the Grading of Recommendations Assessment, Development, and Evaluation working group with evidence published through July 2, 2020. This guideline encompasses evidence-based treatment recommendations as well as expert opinions, addressing crucial aspects of the treatment and management of non-cystic fibrosis bronchiectasis in children. This includes considerations for antibiotics and airway clearance strategies, particularly in areas where evidence may be limited. Large, well-designed, and controlled studies are required to accumulate further evidence of management strategies for noncystic fibrosis bronchiectasis in children and adolescents.

Diagnostic Decision Point for IgE-Mediated Wheat Allergy in Children.

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children.

Acute Urticaria and Anaphylaxis: Differences and Similarities in Clinical Management.

Acute urticaria is a common condition that presents with wheals and/or angioedema. However, these symptoms are also frequent in anaphylaxis, a life-threatening reaction that should be immediately diagnosed and treated. In both, mast cells play a central role in the physiopathology. Causes and triggers of acute urticaria and anaphylaxis are similar in general, but some peculiarities can be observed. The diagnostic approach may differ, accordingly to the condition, suspicious causes, age groups and regions. Adrenaline is the first-line treatment for anaphylaxis, but not for acute urticaria, where H1-antihistamines are the first choice. In this paper, we review the main aspects, similarities and differences regarding definitions, mechanisms, causes, diagnosis and treatment of acute urticaria and anaphylaxis.

A partially hydrolyzed whey formula provides adequate nutrition in high-risk infants for allergy.

BACKGROUND/OBJECTIVES: Hydrolyzed formula is often fed to infants with gastrointestinal or immune issues, such as malabsorption or cow's milk allergy, because enzymatic treatment has rendered it more digestible and less allergenic than standard cow's milk formula (SF). Partially hydrolyzed formula (PHF) should be considered for those infants who are intolerant to extensively hydrolyzed formula. However, there are concerns about the nutritional insufficiencies of PHF. We aimed to evaluate the effects of PHF on the growth and health indicators in infants who were at high-risk of allergic disease and potential candidates for consuming PHF. SUBJECTS/METHODS: A total of 83 infants aged 0-2 mon with a family history of allergies were assigned to consume either PHF or SF until 24 weeks of age. Anthropometric measures were obtained at baseline, 12 weeks, and 24 weeks; blood samples were drawn and evaluated at the end of the study. RESULTS: No significant differences were observed in weight, height, and weight-for-height at any time point in each sex between the PHF and SF groups. At 24 weeks of age, the weight-for-age and height-for-age z-scores of the SF group were higher than those of the PHF group, but there was no significant difference in the weight-for-height z-score. There were no significant differences in levels of white blood cells, hemoglobin, ferritin, protein, albumin, aspartate aminotransferase, alanine aminotransferase, eosinophil cationic protein, and immunoglobulin E. CONCLUSIONS: In this study, there were no differences in growth and blood panels between the infants consuming PHF or SF. Therefore, infants who are unable to tolerate SF can be fed PHF without nutritional concerns about growth.

Maternal Posttraumatic Stress Symptoms and Psychological Burden in Mothers of Korean Children With Anaphylaxis.

PURPOSE: Anaphylaxis is a severe allergic reaction that is potentially life-threatening, but post-traumatic stress symptoms (PTSS) in the caregivers of children with anaphylaxis have not been evaluated. This study aimed to investigate the psychological burden on mothers of children with recent anaphylaxis. METHODS: A total of 188 children with recent anaphylaxis was recruited from 13 hospitals in Korea. Validated questionnaires, including the Korean versions of the Beck Anxiety Inventory (K-BAI), the Beck Depression Inventory (K-BDI), and the Impact of Event Scale Revised-Korean version (IES-R-K), were used to evaluate maternal anxiety, depression, and PTSS. RESULTS: The median ages of children and their mothers were 4 and 36 years, respectively. PTSS (IES-R-K ≥ 25) were identified in 56.9% of mothers, and 57.9% of them showed severe PTSS. The proportions of mothers who had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17) were 18.6% and 33.0%, respectively. Multivariable logistic regression analysis indicated that the patient's history of asthma (adjusted odds ratio [aOR], 5.46; 95% CI, 1.17-25.59) and the presence of central nervous symptoms (aOR, 3.27; 95% CI, 1.07-9.96) were associated with PTSS. Age of 2 or older (aOR, 2.87; 95% CI, 1.10-7.52) and eggs, milk, or wheat as the cause of anaphylaxis (aOR, 2.87; 95% CI, 1.10-7.52) increased the risk of severe PTSS. CONCLUSIONS: The rate of PTSS among mothers of children with recent anaphylaxis was high at 56.9%. Clinicians who care for pediatric anaphylaxis patients should be aware of the psychological burden on their caregivers.

COVID-19 Vaccine-associated Anaphylaxis and Allergic Reactions: Consensus Statements of the KAAACI Urticaria/Angioedema/Anaphylaxis Working Group.

In the era of novel coronavirus epidemics, vaccines against coronavirus disease 2019 (COVID-19) have been recognized as the most effective public health interventions to control the pandemic. An adverse event following immunization (AEFI) is defined as any untoward occurrence following immunization, and the majority of AEFIs are caused by protective immune responses stimulated by vaccines. Most of the reported AEFIs are not serious, and many are not immunologically mediated or even reproducible on re-exposure. However, uncommon severe allergic adverse reactions, such as anaphylaxis or other allergic reactions, can occur after vaccinations. Confirmed allergic reactions to vaccines may be caused by residual non-human protein, preservatives, or stabilizers in the vaccine formulation (also known as excipients). There are 2 main potential allergenic/immunogenic excipients in COVID-19 vaccines, polyethylene glycol (PEG) and polysorbate 80. PEG, also known as macrogol, is an ingredient in various laxatives and injectable formulations, such as depot steroids. Polysorbate 80 is present in various medical products, creams, ointments, lotions, and medication tablets. Contraindications to the administration of COVID-19 vaccines include a previous history of severe allergic reactions to the first dose of COVID-19 vaccine or proven hypersensitivity to a vaccine component, such as PEG or polysorbate 80. Anaphylaxis or other allergic reactions following immunization can cause fear and loss of confidence in the safety of vaccines among the public. A better understanding of these events is thought to help alleviate concerns about the current COVID-19 vaccines and provide reassurance to the general population by analyzing the exact incidence of anaphylaxis and potential risk factors. COVID-19 vaccine-associated anaphylaxis could be prevented and managed by risk stratification based on our local and global experience.

Long-term macrolide treatment for non-cystic fibrosis bronchiectasis in children: a meta-analysis.

Recurrent bacterial infection causes frequent bronchiectasis (BE) exacerbations. The effectiveness and safety of long-term administration of macrolides in BE remain controversial, especially in children who require minimal treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide use in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) which elucidated long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged < 18 years. The primary outcome was frequency of acute exacerbation; secondary outcomes included changes in pulmonary function, sputum scores, and adverse events including bacterial resistance. We included four RCTs. Long-term macrolide treatment showed a significant decrease in the frequency of exacerbation (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.10-0.87), mean number of exacerbations per patient (mean difference, - 1.40; 95% CI, - 2.26 to - 0.54), and sputum purulence score (mean difference, - 0.78; 95% CI, - 1.32 to - 0.24). However, long-term macrolide treatment was accompanied by an increased carriage of azithromycin-resistant bacteria (OR, 7.13). Long-term macrolide administration prevents exacerbation of BE in children; however, there are risks of increasing antibiotic resistance. Benefits and risks should be weighed and determined on a patient-by-patient basis.

Diagnostic Models for Atopic Dermatitis Based on Serum Microbial Extracellular Vesicle Metagenomic Analysis: A Pilot Study.

PURPOSE: Associations between a wide variety of diseases and the microbiome have been extensively verified. Recently, there has been a rising interest in the role the microbiome plays in atopic dermatitis (AD). Furthermore, metagenomic analysis of microbe-derived extracellular vesicles (EVs) has revealed the importance and relevance of microbial EVs in human health. METHODS: We compared the diversity and proportion of microbial EVs in the sera of 24 AD patients and 49 healthy controls, and developed a diagnostic model. After separating microbial EVs from serum, we specifically targeted the V3-V4 hypervariable regions of the 16S rDNA gene for amplification and subsequent sequencing. RESULTS: Alpha and beta diversity between controls and AD patients both differed, but only the difference in beta diversity was significant. Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in healthy controls and AD patients, accounting for over 85% of the total serum bacterial EVs. Also, Proteobacteria, Firmicutes, Actinobacteria, Verrucomicrobia, and Cyanobacteria relative abundances were significantly different between the AD and control groups. At the genus level, the proportions of Escherichia-Shigella, Acinetobacter, Pseudomonas, and Enterococcus were drastically altered between the AD and control groups. AD diagnostic models developed using biomarkers selected on the basis of linear discriminant analysis effect size from the class to genus levels all yielded area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of value 1.00. CONCLUSIONS: In summary, microbial EVs demonstrated the potential in their use as novel biomarkers for AD diagnosis. Therefore, future work should investigate larger case and control groups with cross-sectional or longitudinal clinical data to explore the utility and validity of serum microbiota EV-based AD diagnosis.

A multicenter anaphylaxis registry in Korea: Clinical characteristics and acute treatment details from infants to older adults.

BACKGROUND: Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. METHODS: Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. RESULTS: Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged <18 years. In children and adolescents, foods (84.8%) were the most common cause of anaphylaxis, followed by drugs (7.2%); in adults, drugs (58.3%) were the most common cause, followed by foods (28.3%) and insect venom (8.1%). The onset time was ≤10 min in 37.6% of patients. Among the 351 cases registered via the emergency department (ED) of participating hospitals, epinephrine was administered to 63.8% of patients. Among those receiving epinephrine in the ED, 13.8% required 2 or more epinephrine shots. Severe anaphylaxis accounted for 23.5% cases (38.1% in adults; 13.7% in children); patients with drug and insect venom-induced anaphylaxis had higher rates of severe anaphylaxis. CONCLUSION: This multicenter registry provides data on anaphylaxis for all age groups for the first time in Asia. The major causes and severity of anaphylaxis were remarkably different according to age group, and the acute treatment features of anaphylaxis in the EDs were examined in detail.

Emerging Therapies in Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is characterized by typically short-lived and fleeting wheals, angioedema or both, which occur spontaneously and persist for longer than 6 weeks. This term is applied to the most common subtype of chronic urticaria. The underlying pathophysiology for CSU involves mast cell and basophil degranulation with release of histamine, leukotrienes, prostaglandins and other inflammatory mediators. Although a variety of treatments exist, many patients do not tolerate or benefit from the existing therapies and even require more effective treatments. Omalizumab is currently the only licensed biologic for antihistamine-refractory CSU, and novel drugs are under development. This article reviews its current status regarding pathogenesis and approach to treatment as well as therapeutic agents that are under development for the treatment of CSU.

Lactobacillus plantarum-derived Extracellular Vesicles Protect Atopic Dermatitis Induced by Staphylococcus aureus-derived Extracellular Vesicles.

PURPOSE: The microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV composition. METHODS: Twenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively. RESULTS: The proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level. CONCLUSIONS: We suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.

A Metagenomic Analysis Provides a Culture-Independent Pathogen Detection for Atopic Dermatitis.

PURPOSE: Atopic dermatitis (AD) is an inflammatory skin disease, significantly affecting the quality of life. Using AD as a model system, we tested a successive identification of AD-associated microbes, followed by a culture-independent serum detection of the identified microbe. METHODS: A total of 43 genomic DNA preparations from washing fluid of the cubital fossa of 6 healthy controls, skin lesions of 27 AD patients, 10 of which later received treatment (post-treatment), were subjected to high-throughput pyrosequencing on a Roche 454 GS-FLX platform. RESULTS: Microbial diversity was decreased in AD, and was restored following treatment. AD was characterized by the domination of Staphylococcus, Pseudomonas, and Streptococcus, whereas Alcaligenaceae (f), Sediminibacterium, and Lactococcus were characteristic of healthy skin. An enzyme-linked immunosorbent assay (ELISA) showed that serum could be used as a source for the detection of Staphylococcus aureus extracellular vesicles (EVs). S. aureus EV-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) were quantified in the serum. CONCLUSIONS: A metagenomic analysis together with a serum detection of pathogen-specific EVs provides a model for successive identification and diagnosis of pathogens of AD.

Age-Based Causes and Clinical Characteristics of Immediate-Type Food Allergy in Korean Children.

PURPOSE: Age-based causes and clinical characteristics of immediate-type food allergy (FA) have not been sufficiently studied. Therefore, we investigated age-dependent clinical profiles of FA in Korean children through an extensive multicenter investigation. METHODS: Using a case report form developed by the authors, a retrospective medical record review was performed of patients (0-18 years old) diagnosed with immediate-type FA between September 2014 and August 2015 in 14 tertiary hospitals in Korea. RESULTS: A total of 1,353 children and adolescents, 93% younger than 7 years, were enrolled in the present study, and 1,661 cases of immediate-type FA were recorded in these patients. The 7 major causative foods were cow's milk (28.1%), hen's eggs (27.6%), wheat (7.9%), walnuts (7.3%), peanuts (5.3%), buckwheat (1.9%), and shrimps (1.9%). Categorizing the patients into 4 age groups revealed that the most common causative food was different for each age group: cow's milk (<2 years), walnuts (2-6 years), walnuts (7-12 years), and buckwheat (13-18 years). The onset time of symptoms was less than 10 minutes in 49%, between 10 and 30 minutes in 17%, and between 30 minutes and 2 hours in 34% of cases. Food-induced anaphylaxis was reported in 506 (30.5%) out of 1,661 cases, and the 7 major causes of food-induced anaphylaxis was cow's milk (27.5%), hen's eggs (21.9%), wheat (11.3%), walnuts (10.5%), peanuts (5.9%), buckwheat (4.2%), and pine nuts (3.0%). The proportion of anaphylaxis was highest in the patients allergic to buckwheat (67.7%), followed by those allergic to pine nuts (57.7%), walnuts (43.8%), wheat (43.5%), and peanuts (34.1%). CONCLUSIONS: The 5 major causative foods of immediate-type FA in Korean children were cow's milk, hen's eggs, wheat, walnuts, and peanuts. The distribution of causative foods was considerably distinctive according to different age groups. Anaphylaxis was reported in 30.5% of immediate-type FA cases.