Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Tolerance development in cow's milk-allergic children receiving amino acid-based formula with synbiotics: 36-Months follow-up of a randomized controlled trial (PRESTO Study).

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.

Growth Patterns of 11-29-Month-Old Children Consuming Young Child Formula: Secondary Analysis of a Randomized, Controlled Study.

INTRODUCTION: The impact of young child formula (YCF) consumption on children's growth, particularly under suboptimal conditions, has scarcely been studied. In the current study, weight-for-age (WAZ), length-for-age (LAZ), and BMI-for-age (BAZ) z-score development was evaluated in children from five different countries (n = 668) who participated in a double-blind, randomized, controlled trial. METHODS: The children (1-3 years old) were randomized to one of two intervention YCFs (with presence or absence of prebiotics and n-3 LCPUFAs) during 52 weeks of intervention. Additional stratified analyses evaluated the growth patterns of underweight, overweight, or stunted children. RESULTS: No apparent differences in anthropometric measurements were observed between the intervention groups. In both YCF intervention groups, mean WAZ, LAZ and BAZ development was indicative of adequate growth during the intervention period. Stratified analyses showed stable WAZ and BAZ development among children with a healthy weight or overweight at baseline. Among underweight and stunted children, normalization in mean weight (∼1 SD) and length (∼0.8 SD) gain, respectively, was observed. CONCLUSION: The current study suggests that consumption of YCF, either or not containing prebiotics and n-3 LCPUFAs, is associated with adequate growth among young children. This association may depend on the child's baseline nutritional status. Future studies to assess the potential role of YCF in supporting adequate weight/length gain among children at risk for undernutrition are warranted.

A germline STAT6 gain-of-function variant is associated with early-onset allergies.

BACKGROUND: The signal transducer and activator of transcription 6 (STAT6) signaling pathway plays a central role in allergic inflammation. To date, however, there have been no descriptions of STAT6 gain-of-function variants leading to allergies in humans. OBJECTIVE: We report a STAT6 gain-of-function variant associated with early-onset multiorgan allergies in a family with 3 affected members. METHODS: Exome sequencing and immunophenotyping of T-helper cell subsets were conducted. The function of the STAT6 protein was analyzed by Western blot, immunofluorescence, electrophoretic mobility shift assays, and luciferase assays. Gastric organoids obtained from the index patient were used to study downstream effector cytokines. RESULTS: We identified a heterozygous missense variant (c.1129G>A;p.Glu377Lys) in the DNA binding domain of STAT6 that was de novo in the index patient's father and was inherited by 2 of his 3 children. Severe atopic dermatitis and food allergy were key presentations. Clinical heterogeneity was observed among the affected individuals. Higher levels of peripheral blood TH2 lymphocytes were detected. The mutant STAT6 displayed a strong preference for nuclear localization, increased DNA binding affinity, and spontaneous transcriptional activity. Moreover, gastric organoids showed constitutive activation of STAT6 downstream signaling molecules. CONCLUSIONS: A germline STAT6 gain-of-function variant results in spontaneous activation of the STAT6 signaling pathway and is associated with an early-onset and severe allergic phenotype in humans. These observations enhance our knowledge of the molecular mechanisms underlying allergic diseases and will potentially contribute to novel therapeutic interventions.

A large scale multicentre randomized, placebo-controlled subcutaneous house dust mite allergen immunotherapy (HDM SCIT) in allergic rhinitis: MITAR Study.

BACKGROUND: Previous house dust mite subcutaneous immunotherapy (HDM SCIT) placebo-controlled trials have small sample sizes and lack a consensus on baseline treatment. OBJECTIVE: To determine the efficacy of HDM SCIT in moderate-to-severe allergic rhinitis (AR) patients treated with an intranasal corticosteroid at baseline. METHODS: We conducted a randomized, placebo-controlled trial comparing HDM SCIT against placebo in Dermatophagoides pteronyssinus (Der p) sensitized. All patients received standard of care according to Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, including an intranasal steroid (INCS) at baseline. The primary endpoint was the comparison of a composite score, combining the total nasal symptom score and medication score, assessed at the twelfth month post-treatment. RESULTS: Of the 144 subjects, 108 received HDM-SCIT and 36 received a placebo. The median age was 30 years (range 11-61), with 60% being female. The mean Der p wheal diameter was 9.4 mm (SD 4.4). After one year of treatment, the composite score median (IQR) in the HDM SCIT group and the placebo group was 0.75 (0.50-1.13) and 0.63 (0.50-1.25), respectively (p > 0.05). Both groups exhibited a significant mean change in the composite score from baseline (p < 0.001), but there was no significant difference between the groups. The median (IQR) serum Der p-specific immunoglobulin G4 level significantly increased only in the HDM SCIT arm (p ≤ 0.001). CONCLUSION: One-year HDM SCIT significantly reduced both symptoms and medication use in HDM-allergic rhinitis patients. However, the changes were not significantly different from those in the placebo group, who also received an INCS at baseline. A longer-term study is warranted to assess disease modification factors.

The effect of applied force and device design on skin prick test performance.

BACKGROUND: Skin prick tests (SPTs) are difficult to standardize, and SPT performance mainly relies on the clinician's expertise. So far, the effect of various factors such as device types, shape, variety of material type, and applied force on the performance of SPT has not been extensively investigated. OBJECTIVE: To investigate the effect of various factors, including type or shape of devices, material type, and applied force, on the performance of SPT. METHODS: Four SPT devices with different shapes and materials were applied on 12 subjects under 3 different applied forces (30, 45, and 60 g). The results were compared with standard method using an ALK lancet pricked by an experienced clinician. RESULTS: A total of 480 pricks were conducted on 12 subjects. The wheal sizes and sensitivities of all devices increased with higher applied forces. The thinner lancets with a long sharp tip had relatively higher analytical sensitivities and provided 100% sensitivity at applied forces of 45 g and above. The pain scores of all devices at applied forces of 30 to 60 g ranged from 1.00 to 1.81 with minimal incidences of bleeding (0%-4.17%), whereas the pain score of the standard method by the ALK lancet was 2.08 with much higher incidences of bleeding at 27.08%. CONCLUSION: The type/shape of the SPT device and applied force are the essential factors affecting the performance of SPT. The study result could pave the way toward higher performance and standardized SPT. TRIAL REGISTRATION: The Thai Clinical Trials Registry identification number: TCTR20220627004 (https://www.thaiclinicaltrials.org/show/TCTR20220627004).

Tolerance development in cow's milk-allergic infants receiving amino acid-based formula: A randomized controlled trial.

BACKGROUND: Tolerance development is an important clinical outcome for infants with cow's milk allergy. OBJECTIVE: This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acid-based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy. METHODS: Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n = 80) or AAF (n = 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. A logistic regression model used the all-subjects randomized data set. RESULTS: At baseline, mean ± SD age was 9.36 ± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P = .036). CONCLUSIONS: After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.

Outcomes of young children hospitalized with acute wheezing.

BACKGROUND: Wheezing in preschool children is a common symptom. OBJECTIVE: The study aimed to determine an incidence of recurrent wheezing among young children who had been hospitalized with acute wheezing after 12 months. Factors associated with recurrent wheezing were explored. METHODS: A longitudinal study was conducted among 236 children, aged between 6 months and 5 years, who were hospitalized with acute wheezing in 4 hospitals located in Bangkok and adjacent provinces, Thailand. Demographics, house environments and clinical characteristic data were collected at entry. Serum specific IgE levels against common food and inhalant allergens and serum 25-hydroxyvitamin D (25OHD) concentrations were measured. RESULTS: At entry, the mean age was 24.4 months (SD = 15.7 months). Of 236 hospitalized children with acute wheezing, ninety-four cases (39.8%) were the first wheezing episode of life. By laboratory results, 197 (83.5%) and 56 (23.7%) children were atopic and had vitamin D insufficiency respectively. There were 195 cases completely followed for 12 months. One-year risk of emergency visits and hospitalization due to recurrent wheezing were 49.7% and 23.1% respectively. By multivariable analysis, being the second born child or more, vitamin D insufficiency, "ever wheeze", and allergic rhinitis were significantly associated with recurrent wheezing within 12 months with adjusted odds ratios of 2.5 (95% confidence interval: 1.3-5.3), 2.3 (95% confidence interval: 1.1-4.4), 1.9 (95% confidence interval: 1.2-3.5), and 1.6 (95% confidence interval: 1.3-2.9) respectively. CONCLUSIONS: Being the second born child or more, vitamin D insufficiency, ever wheeze, and allergic rhinitis were significant risks of recurrent wheezing.

Practical recommendations for home-nebulized corticosteroid use in children aged ≤ 5 years with asthma: A review and advisory group consensus.

BACKGROUND: Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce. OBJECTIVE: To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma. METHODS: A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients. RESULTS: Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years. CONCLUSIONS: ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.

Characteristics and Laboratory Findings of Food-Induced Anaphylaxis in Children: Study in an Asian Developing Country.

INTRODUCTION: Food allergy is the major cause of pediatric anaphylaxis. Characteristics and triggers may be different in different geographical regions. Studies focusing on food-induced anaphylaxis (FIA) in Asian developing countries are limited. Our study aimed to study characteristics of FIA in a tertiary care center in an Asian developing country. METHODS: Retrospective review of pediatric anaphylaxis admission and outpatient visit at a tertiary care hospital in Bangkok, Thailand during 2008-2018 was performed. Data regarding clinical presentation, place reaction occurred, time of onset, investigations (serum tryptase, specific immunoglobulin E, and skin test), treatment, and follow-up periods were collected. RESULTS: One hundred seventy-four anaphylaxis admission records of which 61 episodes of FIA were retrieved. Data from outpatients visit consisted of 17 patients. Most patients were male (76.7%). The median age was 7.1 years (interquartile range 1.9-12.4). The major causes of FIA were shrimp/shellfish (37%), wheat (15.1%), and cow's milk (11%). Food causing anaphylaxis varied according to age-group: infants had anaphylactic reactions to egg, wheat, and cow's milk, preschools to wheat and peanut, and older children to shrimp/shellfish. Cutaneous manifestations occurred in all patients, followed by lower respiratory tract symptoms (83.6%) and gastrointestinal symptoms (50.8%). There was no biphasic anaphylaxis reported. Elevated serum tryptase was found in only 4 patients (7%). CONCLUSION: Recognizing characteristics of pediatric FIA is crucial. The common causes of FIA in our study in Asian children were egg in infants, wheat and peanut in preschool children, and shrimp/shellfish in school-age children and adolescents. Skin manifestation presented in all patients with FIA.

Phenotypic heterogeneity and genotypic spectrum of inborn errors of immunity identified through whole exome sequencing in a Thai patient cohort.

BACKGROUND: Inborn errors of immunity (IEI) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunologic, and genetic features of Thai pediatric patients with IEI. The use of whole-exome sequencing (WES) in diagnosis and clinical decision making was also assessed. METHODS: Thirty six unrelated patients with clinical and laboratory findings consistent with IEI were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. RESULTS: The median age of disease onset was 4 months (range: 1 month to 13 years), and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). CONCLUSION: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in IEI genes were identified. The clinical usefulness of WES in IEI was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

Food allergy across the globe.

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.

Practical considerations of nebulized corticosteroid in children with acute asthmatic exacerbation: A consensus.

BACKGROUND: Acute asthmatic exacerbation in children causes economic burdens both directly and indirectly. The GINA guideline does mention the use of inhaled or oral corticosteroids in the treatment of asthmatic exacerbation, it provides little practical guidance on the use of nebulized corticosteroid. OBJECTIVE: To review and recommend the practical considerations in the use of nebulized corticosteroid in children with acute asthmatic exacerbation. METHODS: This consensus was developed by a group of expert pediatricians in respiratory and allergy fields in Thailand. The recommendations were made based on a review of published studies and clinical opinions. The eligible studies were confined to those published in English, and randomized controlled trials and meta-analyses involving nebulized corticosteroids in asthmatic exacerbation in children aged between 1-18 years. RESULTS: There were 13 randomized controlled-trial studies published from 1998 to 2017. Nine of the 13 studies compared nebulized with systemic corticosteroid conducted in moderate to severe exacerbation, while the remaining four compared nebulized corticosteroid with placebo conducted in mild to severe exacerbation. The admission rate was significantly lower in severe exacerbation (one study) and pooled four mild to severe exacerbation studies comparing with placebo (p 0.022). Other clinical parameters were significantly improved with nebulized corticosteroid such as clinical scores, systemic corticosteroid/bronchodilator use, or shorter ER stays. Only one study used fluticasone, while the other 12 studies conducted by budesonide (92.31%). CONCLUSIONS: Nebulized corticosteroid may offer an effective therapeutic option for the management of acute exacerbation of asthma in all severities. Nebulized budesonide is the preferred corticosteroid.

Clinical practice guidelines for the diagnosis and management of atopic dermatitis.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.

COVID-19 in children: Heterogeneity within the disease and hypothetical pathogenesis.

The disease course of coronavirus disease 2019 (COVID-19) is usually mild and self-limiting in previously healthy children, but they may also develop severe disease. Severe COVID-19 infection is especially observed in very young children or those with underlying comorbidities. Moreover, a multisystem inflammatory syndrome that mimics the Kawasaki disease shock syndrome can develop in children that are genetically predisposed to displaying an overactive immune response to SARS-CoV-2 infection. In this review, we describe the clinical phenotypes of mild and severe COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We also discuss the possible immunobiological mechanisms that may be involved in the protection of children against COVID-19 and the development of multisystem inflammatory syndrome.

Randomized comparison of caregivers' ability to use epinephrine autoinjectors and prefilled syringes for anaphylaxis.

BACKGROUND: Caregivers often incorrectly use epinephrine autoinjectors. It is unclear whether this is due to insufficient training or a difficult-to-use tool. Furthermore, the high costs of epinephrine autoinjectors may limit their availability; so low-cost prefilled syringes may be the alternative. OBJECTIVES AND METHODS: We performed a prospective randomized trial to compare successful epinephrine administration at four stages: after reading written instructions, and immediately after, 6 weeks, and 3 months following video training. The time required for successful epinephrine administration and failed steps in the administration of epinephrine autoinjectors and prefilled syringe were also investigated. RESULTS: Complete data analysis of 113 participants (prefilled syringe group, n=57; EpiPen, n=56) was performed. Significantly more participants correctly demonstrated the use of prefilled syringes compared to EpiPen after reading instructions, and immediately following 6 weeks, and 3 months after video training. ((adjusted OR 26.17 (95%CI 8.2583.04), adjusted OR 4.07 (95%CI 1.29-12.86), adjusted OR 14.01 (95%CI 3.62-54.22)) and adjusted OR 31.44 (95%CI 5.73172.39), respectively) Four key step errors would likely result in failure of administration and were more common with EpiPen (14.0% vs. 2.3%, p<0.001). There were no statistically significant differences in time of successful administration between the two groups (p>0.05). CONCLUSION: Epinephrine prefilled syringe was significantly easier to use with a higher rate of correct use compared to EpiPen over time. All four key step errors in the administration were more likely with EpiPen. The time required for successful epinephrine administration was not significantly different.

Comparison of specific IgE detection by immunoblotting and fluorescence enzyme assay with in vivo skin prick test.

BACKGROUND: Diagnostic tools to identify allergens that cause allergic symptom is important part in the care of allergic patients. Detection of causative allergen can be performed by in vivo skin prick test (SPT) or in vitro tests for detection serum specific immunoglobulin E (sIgE). The common methods used are fluorescent enzyme assay and immunoblotting assay. OBJECTIVE: We aim to evaluate performance of the two sIgE determination systems, immunoblotting assay (Euroline) and fluorescent enzyme assay (ImmunoCAP) in comparison with SPT. METHODS: Two hundred and two participants with allergic diseases were enrolled. Sensitization to common allergens was identified using skin prick test and serum specific IgE assays with Euroline and ImmunoCAP. Both systems provide the result in the same unit and the same cut-off value (0.35 kUA/L). The specific IgE levels of 4 aeroallergens, 6 food allergens and 3 food allergen components were analyzed to evaluate the performance of both sIgE assays with SPT. RESULTS: When compared with the result of SPT, ImmunoCAP has 63.9-93.2% agreement and Euroline has 68.4-86.2% agreement for allergen detection. Both sIgE assays have significant correlation in measuring sIgE of almost all allergens (r=0.626-0.901, p< 0.001) except for dog. For food allergen components, both sIgE tests have outstanding correlation and agreement (r=0.816-0.952, p< 0.001; agreement =87.0-92.9%, respectively). The receiver-operating characteristic curve analysis indicated slight discrepancy of both sIgE assays. CONCLUSIONS: Both sIgE determination systems demonstrate fair to good performance when compared to SPT depending on type of allergens. The two sIgE determination systems had favorable correlation and agreement.

Mechanisms of Tolerance Induction.

Food allergy results from failure in oral tolerance that usually occurs in infancy or early childhood. Exposure to peanut and hen's egg via the inflamed and disrupted epithelial barrier in children with severe atopic dermatitis is a risk factor for the development of allergy to these foods and supports the hypothesis that epicutaneous exposure in the absence of oral feeding is an important pathway of allergic IgE sensitization in infants. In recent years, the collective evidence has pointed toward the protective effect of an early feeding with peanut and egg in children with eczema, taking advantage of the pathways underlying oral tolerance to counteract epicutaneous exposure. An addendum to the NIAID food allergy guidelines recommends introduction of peanut into the diet of 4- to 6-month-old infants with severe eczema or egg allergy as an effective strategy to prevent peanut allergy. Strategies aimed at restoring the skin barrier are currently explored as an alternative approach of prevention of eczema and allergic sensitization. Manipulation of the diet via supplementation with probiotics and prebiotics to restore the healthy gut microbiota represents another potential pathway to induction of tolerance in the gut. Oral, epicutaneous, and sublingual routes of food immunotherapy are promising and induce desensitization in the majority of the treated subjects with food allergy but are not proven to restore permanent oral tolerance. Rigorous multicenter randomized clinical trials are necessary to elucidate the optimal timing, dose, duration, as well as the preventive and therapeutic effects of these diverse approaches.

Clinical practice guideline for diagnosis and management of urticaria.

Urticaria is a common skin condition that can compromise quality of life and may affect individual performance at work or school. Remission is common in majority of patients with acute spontaneous urticaria (ASU); however, in chronic cases, less than 50% had remission. Angioedema either alone or with urticaria is associated with a much lower remission rate. Proper investigation and treatment is thus required. This guideline, a joint development of the Dermatological Society of Thailand, the Allergy, Asthma, and Immunology Association of Thailand and the Pediatric Dermatological Society of Thailand, is graded and recommended based on published evidence and expert opinion. With simple algorithms, it is aimed to help guiding both adult and pediatric physicians to better managing patients who have urticaria with/without angioedema. Like other recent guideline, urticaria is classified into spontaneous versus inducible types. Patients present with angioedema or angioedema alone, drug association should be excluded, acetyl esterase inhibitors (ACEIs) and non-steroidal anti-inflammatory drugs (NSAIDs) in particular. Routine laboratory investigation is not cost-effective in chronic spontaneous urticaria (CSU), unless patients have clinical suggesting autoimmune diseases. Non-sedating H1-antihistamine is the first-line treatment for 2-4 weeks; if urticaria was not controlled, increasing the dose up to 4 times is recommended. Sedating first-generation antihistamines have not been proven more advantage than non-sedating antihistamines. The only strong evidence-based alternative regimen for CSU is an anti-IgE: omalizumab; due to very high cost it however might not be accessible in low-middle income countries. Non-pharmacotherapeutic means to minimize hyper-responsive skin are also important and recommended, such as prevention skin from drying, avoidance of hot shower, scrubbing, and excessive sun exposure.