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 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

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

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

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 &lt;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 wa

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 (&lt; 2 years of age), preschool-onset (2-5 years of age), and childhood-onset (&gt;/= 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

A Multicenter Retrospective Case Study of Anaphylaxis Triggers by Age in Korean Children

PURPOSE: Although anaphylaxis is recognized as an important, life-threatening condition, data are limited regarding its triggers in different age groups. We aimed to identify anaphylaxis triggers by age in Korean children. METHODS: We performed a retrospective review of medical records for children diagnosed with anaphylaxis between 2009 and 2013 in 23 secondary or tertiary hospitals in South Korea. RESULTS: A total of 991 cases (mean age=5.89+/-5.24) were reported, with 63.9% involving patients younger than 6 years of age and 66% involving male children. Food was the most common anaphylaxis trigger (74.7%), followed by drugs and radiocontrast media (10.7%), idiopathic factors (9.2%), and exercise (3.6%). The most common food allergen was milk (28.4%), followed by egg white (13.6%), walnut (8.0%), wheat (7.2%), buckwheat (6.5%), and peanut (6.2%). Milk and seafood were the most common anaphylaxis triggers in young and older children, respectively. Drug-triggered anaphylaxis was observed more frequently with increasing age, with antibiotics (34.9%) and nonsteroidal anti-inflammatory drugs (17.9%) being the most common causes. CONCLUSIONS: The most common anaphylaxis trigger in Korean children was food. Data on these triggers show that their relative frequency may vary by age

Oral food challenges in children

Many patients assume that allergic reactions against foods are responsible for triggering or worsening their allergic symptoms. Therefore, it is important to identify patients who would benefit from an elimination diet, while avoiding unnecessary dietary restrictions. The diagnosis of food allergy depends on the thorough review of the patients’s medical history, results of supplemented trials of dietary elimination, and in vivo and in vitro tests for measuring specific IgE levels. However, in some cases the reliability of such procedures is suboptimal. Oral food challenges are procedures employed for making an accurate diagnosis of immediate and occasionally delayed adverse reactions to foods. The timing and type of the challenge, preparation of patients, foods to be tested, and dosing schedule should be determined on the basis of the patient’s history, age, and experience. Although double-blind, placebo-controlled food challenges(DBPCFC) are used to establish definitively if a food is the cause of adverse reactions, they are time-consuming, expensive and troublesome for physician and patients. In practice, An open challenge controlled by trained personnel is sufficient especially in infants and young children. The interpretation of the results and follow-up after a challenge are also important. Since theses challenges are relatively safe and informative, controlled oral food challenges could become the measure of choice in children

소아의 즉시형 우유와 난백 알레르기의 임상 특성과 식품 노출 형태

Purpose: The aim of this study was to evaluate the details of the clinical characteristics and food exposure types at the first symptom onset in immediate-type cow's milk allergy (CMA) and egg white allergy (EWA) in Korean children. Methods: This study included children with immediate-type CMA (n=288) or EWA (n=233) with symptom onset time of 2 hours or less, who visited Samsung Medical Center, Ajou University Hospital, and Soonchunhyang University Seoul Hospital between September 2014 and August 2015. The details of clinical features and food exposure types at the first symptom onset were evaluated by retrospective medical record review using a standardized case report form. Results: The median ages of first symptom onset were 10 months in CMA and 12 months in EWA. The most common types of exposure at the first symptom in CMA were formula milk (29.5%) and milk (29.5%), followed by cheese (17.7%) and yogurt (14.2%). The most common type of exposure in EWA was boiled eggs (35.6%), followed by rice/porridge/soup containing eggs (27.5%), pan-fried eggs (17.6%), and baked goods (9.9%). Cutaneous symptoms were most common in both CMA and EWA, and anaphylaxis was noticed in 36.1% and 30.3%, respectively. Baked goods containing milk or eggs also induced anaphylaxis. The symptom onset time was less than 30 minutes in the majority of patients and the most common place of occurrence was home in both CMA and EWA. Conclusion: This study provides comprehensive information on CMA and EWA, and therefore helps clinicians diagnose and guide appropriate food restriction in children with CMA and EWA

An Important Role of alpha-Hemolysin in Extracellular Vesicles on the Development of Atopic Dermatitis Induced by Staphylococcus aureus

Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated alpha-hemolysin derived from S. aureus in AD pathogenesis. alpha-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of alpha-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated alpha-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of alpha-hemolysin were evaluated by application of soluble and EV-associated alpha-hemolysin on the mouse skin. The present study showed that increased alpha-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. alpha-hemolysin production was also related to AD severity. In addition, EV-associated alpha-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble alpha-hemolysin, and alpha-hemolysin-negative EVs did not induce keratinocyte death. EV-associated alpha-hemolysin induced necrosis, but soluble alpha-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated alpha-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated alpha-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by alpha-hemolysin-negative EVs. Taken together, alpha-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated alpha-hemolysin is a novel diagnostic and therapeutic target for the control of AD.open111618sciescopu