Safety of House Dust Mite Subcutaneous Immunotherapy with a rush and cluster combination protocol in the build-up phase.

BACKGROUND: Conventional and cluster subcutaneous immunotherapy (SCIT) are effective but may be time-consuming. Rush SCIT may offer a more convenient treatment option to patients and be of shorter duration; however, it is also associated with a higher incidence of systemic adverse reactions. Therefore, a combination of protocols between rush and cluster SCIT could have a superior risk-benefit ratio. OBJECTIVE: To determine the safety of the combination of rush and cluster HDM-SCIT and to identify the risk factors for local and systemic adverse reactions. METHODS: We retrospectively reviewed the charts of patients who received HDM-SCIT, with rush and cluster combination protocols, at a tertiary care hospital between January 2009 and December 2020. Data were collected at the initial visit (demographic data; underlying allergic disease; current medication; and laboratory investigation results including skin prick test, serum specific IgE (sIgE) levels to aeroallergen, total IgE, and eosinophil count) and follow-up visits (rate and severity of local and systemic adverse reactions). RESULTS: In total, 698 injections (28 patients) were reviewed. Overall, 13 patients developed systemic adverse reactions, at 3% (21/698) per injection visit. All reactions occurred within 60 minutes. In total, 6 patients experienced large local reactions, at 1.1% (8/698) per injection visit. A high level of sIgE to D. pteronyssinus was significantly associated with systemic adverse reactions (HR = 1.02; P = 0.009). CONCLUSIONS: HDM-SCIT with a combination of rush and cluster schedules in the build-up phase could be used as an alternative protocol, given its acceptable systemic adverse reaction rate and shortened duration.

Risk factors of uncontrolled symptoms using the standard dose of second-generation H1 -antihistamines in chronic spontaneous urticaria children.

BACKGROUND: A standard dose of second-generation H1 -antihistamines is recommended as the first-line treatment of chronic spontaneous urticaria (CSU), previous studies have found that approximately 20-50% of CSU children fail to control their symptoms and required step-up treatments. OBJECTIVE: To evaluate the predictors of uncontrolled symptoms with first-line medication and describe the treatment outcomes of CSU children in the southern region of Thailand. METHODS: This retrospective chart review of CSU patients, aged 2-18 years, who were initially treated with the standard dose of second-generation H1 -antihistamine at the Pediatric Allergy Clinic, Songkhlanagarind Hospital, from January 2008 to July 2018. The data were collected at the initial visit (demographic data, onset of rash, frequency of urticaria, presence of angioedema, previous resolved CU, laboratory investigation results) and follow-up visits (treatment outcome, time to controlled urticaria). RESULTS: The medical records of 192 CSU children were reviewed; their median age were 8.5 years and the mean frequency of rash was 4 days/week. Forty-seven children (24.4%) fail to controlled symptoms with a standard dose of second -generation H1 -antihistamines and a factor significantly associated was frequency of rash for more than 4 days per week (OR = 4.36, P < 0.001). The median time to controlled urticaria was 1.28 months. CONCLUSIONS: Most of CSU children in the southern region of Thailand experienced controlled symptoms with a standard dose of second-generation H1 -antihistamines, and the frequency of urticaria for more than 4 days per week was a factor associated with uncontrolled symptoms that regimen.

Safety of direct oral provocation testing using the Amoxicillin-2-step-challenge in children with history of non-immediate reactions to amoxicillin.

BACKGROUND: Previous studies have shown that direct oral provocation tests, without prior skin testing, in children having delayed onset, benign rashes to beta-lactam antibiotic is safe and effective. Although, this test is useful in confirming drug hypersensitivity reactions, there is no standard protocol recommendation of drug provocation tests. This study aimed to evaluate the safety of the direct oral provocation test, using the Amoxicillin-2-step-challenge without prior skin testing, in children with history of non-immediate reactions to amoxicillin. METHODS: The Amoxicillin-2-step-challenge protocol was performed in children with history of non-immediate reactions to amoxicillin. This protocol is composed of 2 doses of amoxicillin, with a 30-min interval; continued for a total of 5 days. All of the patients had not undergone skin testing before the oral provocation test. RESULTS: This study included 54 children, having a median age of 6.6 years, with 70.4% being male. Amoxicillin and amoxicillin-clavulanic acid were reported as the culprit drug in 75.9% and 24.1%, respectively. The index reactions were maculopapular (MP) rash in 79.6% and delayed urticarial rash/angioedema in 20.4%. Five patients (9.3%) had a reaction during the provocation test, all of these patients had delayed urticaria and were treated with oral antihistamine. However, 1 patient developed a fever alongside an MP rash. Laboratory investigation for this patient showed increased atypical lymphocytes and liver enzymes elevation. CONCLUSIONS: Direct oral provocation tests, using the Amoxicillin-2-step-challenge, without prior skin testing, revealed good, immediate safety for the diagnosis of amoxicillin hypersensitivity in children with history of non-immediate reactions to amoxicillin.

Risk factors of food sensitization in young children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic and relapsing skin disease in children and food allergies have been well documented in one-third of children. However, there are limit data about the risk factors of food sensitization in children with AD. OBJECTIVE: The aim of this study was to evaluate the risk factors associated with food sensitization, among AD children. METHODS: A cross-sectional study, from the electronic medical records of 119 AD patients, aged from 2 to 5 years were reviewed. The demographic data, onset and severity of AD, family history of atopy, age of first antibiotic usage, age of first applying and frequency of moisturizer used, age of introduction to allergenic foods and food specific IgE levels were recorded. RESULTS: The prevalence of food sensitization was; 60%. The most common food allergens were egg white (56.8%), cow's milk (40%) and wheat (34.7%). The significant factors associated with overall food sensitization were; history of parent-reported food allergies (OR = 4.4, P = 0.001), severe AD (OR = 4.5, P = 0.03) and breast feeding > 6 months (OR = 3.5, P = 0.002). Factors associated with egg white allergies were the history of parent-reported food allergies (OR = 3.8, P = 0.02), and severe AD (OR = 4.2, P = 0.04). There were also significant factors associated with cow's milk allergies this being; severe AD (OR = 6, P = 0.03) and a maternal history of asthma (OR = 10.9, P = 0.01). CONCLUSIONS: Severe AD was a factor associated with all food sensitization, egg allergy and cow's milk allergy. Maternal asthma was also significantly associated with cow's milk allergy.

Characteristics and Contributing Factors Related to Nonsteroidal Anti-Inflammatory Drugs Hypersensitivity.

INTRODUCTION: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is reported to be the most common drug hypersensitivity. The aim of this study was to evaluate the characteristics of self-reported NSAID hypersensitivity and identify patients at high risk of NSAID hypersensitivity. METHODS: Patients who presented at a single tertiary care hospital between January-December 2017 with reported NSAID hypersensitivity were evaluated. Clinical information obtained from a review of medical records was further supplemented with data gained from a telephone-administered questionnaire. RESULTS: From a total of 535 patients with reported NSAID hypersensitivity, 301 were included in the study. The mean age of onset of NSAID hypersensitivity reaction was 30.3 ± 14.9 years old. A total of 84 patients (27.9%) were hypersensitive to 2 or more chemically unrelated NSAIDs. The leading NSAID hypersensitivity was to propionic acid derivatives (73%) followed by acetic acid derivatives (28.9%). Immediate reaction (≤1 h) was identified in 171 patients (57.8%), and angioedema was the most frequently reported symptom (179 patients, 59.5%), followed by urticaria and anaphylaxis in 85 (28.2%) and 62 (20.6%) patients, respectively. A drug provocation test was performed on 53 patients, and NSAID hypersensitivity was confirmed in 38 patients (71.6%). The independent factors identified, which could predict NSAID hypersensitivity, were personal history of allergic rhinitis/chronic rhinosinusitis (AR/CRS), onset of NSAID hypersensitivity over 15 years old, and immediate reaction. CONCLUSION: Angioedema was the most typical symptom, and propionic acid derivatives were the most frequently reported culprit drugs. The significant risk factors predicting NSAID hypersensitivity were personal history of AR/CRS, onset of NSAID hypersensitivity reaction over 15 years old, and immediate reaction.

Utility of an educational video on epinephrine prefilled syringe usage for anaphylaxis: a randomized control trial.

BACKGROUND: Anaphylaxis is a serious allergic reaction that needs early administration of intramuscular epinephrine for treatment. Currently, structured education on epinephrine prefilled syringe usage for anaphylaxis does not exist. OBJECTIVE: This study aimed to examine the effectiveness of the epinephrine prefilled syringe usage video, compared with routine teaching method. METHODS: This was a randomized controlled trial. A total of 129 medical students were assigned either to the routine teaching group or the video teaching group. The main outcome is the total number of medical students who passed (>70%) the test. The pre-, posttest, and objective structured clinical examination (OSCE) were used to evaluate the students. RESULTS: At the 2-week follow-up, the individual scores increased significantly after both interventions (p < 0.001). The percentages of medical students who passed the exam in the pre-, posttests, and OSCE were not significantly different between the groups. In the routine teaching group and video teaching group, the percentages of students who passed increased from 32.2% to 96.6% and 28.1% to 95.3%, respectively (p = 0.99). Using univariate logistic regression analysis, previous knowledge of anaphylaxis was a factor to pass the test (odds ratio, 5.07; 95% confidence interval, 1.93-13.31; p < 0.01). CONCLUSION: The study demonstrated that the scores after the video education intervention were not inferior to the routine teaching group. This technique might be applied for patients in clinical practice. However, the further researches in general population are needed to confirm the efficacy of this method.

Quality of life among caregivers and growth in children with parent-reported food allergy.

BACKGROUND: Some caregivers who believe their children have food allergy avoid feeding certain foods to their children without proper allergy tests. Such actions made without a proper diagnosis can negatively impact the child's health and impose an unnecessary burden on the caregivers. OBJECTIVE: This study aimed to evaluate the caregiver quality of life (QoL) and growth in children with a parent-reported food allergy. METHODS: An observational cross-sectional study was performed in 200 children younger than five years who had a parent-reported food allergy. The caregivers' QoL was evaluated by two questionnaires: the Food Allergy Quality of Life -Parental Burden and the Scale of Psychosocial Factors in Food Allergy. Growth of the children was evaluated by their weight-for-age and length/height-for-age percentiles. RESULTS: Among the caregivers, 50% expressed worry that their children might be allergic to some foods and 30% were concerned about leaving their children in the care of others. According to the QoL scores, caregivers whose children underwent an oral food challenge (OFC) test were significantly less stressed, while caregivers whose children had multiple food allergies and had experienced at least one anaphylactic reaction were significantly more stressed. The distributions of both weight-for-age and length/height-for-age percentiles were 50th comparable to the general population. CONCLUSIONS: Parent-reported food allergy could put caregivers under high stress, but the OFC test could reduce stress among anxious, over-parenting caregivers. Parent-reported food allergy had no impact on a child's growth in our study.

Achieving good adherence to inhaled corticosteroids after weighing canisters of asthmatic children.

Background: The metered-dose inhalers (MDIs) currently available for inhaled corticosteroid delivery do not offer an integrated dose counter; therefore, it is difficult to evaluate adherence of patients. The present authors developed a linear regression equation using canister weight to calculate the number of doses actuated from the MDIs. This study aimed to assess medical adherence after the integration of regular weighing of the canisters into the routine service.  Methods: A cohort study was carried out between May 2013 and April 2014. Children aged less than 8 years with a diagnosis of asthma were recruited. The duration of adherence assessment was 24 weeks. Participants had a regular schedule every 8 weeks to obtain a new FLIXOTIDE® 125 inhaler. Parents were asked to collect the discarded MDI canisters, which were then weighed by a laboratory scale. The weight of each canister was replaced in the regression equation to calculate the number of doses actuated from the MDIs.  Results: A total of 52 asthmatic children participated in the study. The median age was 52.7 months. At the end of 24 weeks, 44, 33, and 23 discarded MDI canisters were collected from visits 1, 2, and 3, respectively. The median percentages of adherence were 96.8%, 96.3%, and 96.3%, respectively. In 11 discarded canisters (11%), the remaining medication was more than 30% of the labeled doses. Approximately 90% of the participants had no asthma exacerbation during 24-week study period.  Conclusion: High adherence rates were achieved after integration of canister weighing into the asthma care service.

Component-resolved diagnostics in Thai children with cow's milk and egg allergy.

BACKGROUND AND OBJECTIVE: Component-resolved diagnostics (CRD) have garnered a lot of attention in recent years in the diagnosis of food allergies. We aimed to investigate sensitization against cow's milk and egg white components, and to study the clinical usefulness of serum food-specific immunoglobulin E (sIgE) to cow's milk and egg white components in Thai children with cow's milk and egg allergies. METHOD: Children with IgE-mediated cow's milk and/or egg allergy were enrolled. Clinical reactions were determined. Specific IgE against cow's milk, egg white, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG), casein, ovomucoid, ovalbumin and conalbumin were measured. RESULTS: Thirteen cow's milk allergic subjects and 32 egg allergic subjects were identified. The sensitization rate to BLG and casein was 91.7%, followed by ALA (66.7%) for cow's milk, and the sensitization rate to ovalbumin was 93.8%, followed by ovomucoid (81.3%) and conalbumin (37.5%) for egg. Patients in the urticaria group had a higher level of casein sIgE than the atopic dermatitis (AD) group but this difference was not significant (9.8 kUA/L vs. 0.9 kUA/L, p = 0.11). The level of ovomucoid sIgE was significantly higher in the non-AD group than in the AD group (3.8 kUA/L vs. 1.3 kUA/L, p = 0.048). CONCLUSIONS: BLG and casein for cow's milk and ovomucoid and ovalbumin for egg were the common components causing sensitization in cow's milk and egg allergic patients. Among the patients with cow's milk allergy, the level of casein sIgE in the urticaria group tended to be higher than the AD group, and in egg allergic patients, the non-AD group had a significantly higher ovomucoid sIgE level compared with the AD group.

Peanut T-cell epitope discovery: Ara h 1.

BACKGROUND: Identification of potential T-cell epitopes in the peanut major allergens is essential for development of peptide-based immunotherapy. Traditional methods of T-cell epitope discovery use overlapping short peptides spanning the full length of the protein in T-cell proliferation assays. Because large proteins, such as Ara h 1, require a large number of peptides, this limits screening to a small number of allergic subject-derived T-cell lines. OBJECTIVE: We sought to identify candidate peptides of Ara h 1 that display promiscuous binding to MHC class II and induce TH2 cytokine production by T cells. METHODS: In silico MHC class II binding prediction was performed with NetMHCIIpan 2.0 (peptide length, 15; 1-mer offset) and the most abundant class II alleles in the North American population and with an in vitro MHC class II peptide reporter assay performed in parallel, which used synthetic 15-mer peptides offset by 5 mer spanning the protein. High-resolution MHC class II typing and a T-cell proliferation assay using preselected peptides were performed with PBMCs from 98 subjects with peanut allergy and 14 healthy control subjects. IL-4, IL-13, IL-5, IFN-γ, and TNF-α levels were measured in culture supernatants. RESULTS: Thirty-six Ara h 1 peptides were identified by using in silico predictions and MHC class II binding assays. In combination with T-cell proliferation and cytokines secreted in T-cell assays, we have identified 4 vaccine candidate Ara h 1 peptides. CONCLUSIONS: Preselection of peptides by using in silico and in vitro approaches in combination with conventional methods appears to be an effective strategy for identifying peanut T-cell peptide vaccine candidates.

Recent 5-year trends of asthma severity and allergen sensitization among children in southern Thailand.

BACKGROUND: Asthma is a major public health issue that affects morbidity. The greater severity of asthma requires more health care resource utilization. OBJECTIVE: To investigate the possible changes in disease severity and allergen sensitization of children with asthma in an interim period of 5 years. METHODS: We retrospectively reviewed the charts of 200 patients with established asthma in the pediatric allergy clinic. The data were collected in different time periods with 100 consecutive cases in each group starting in January of 2004 and in January of 2009. All patients underwent a skin prick test (SPT) to common allergens, with positive and negative controls. SPTs with a mean wheal diameter 3 mm greater than a negative control were considered test-positive. RESULTS: The mean ages of patients in the 2004 and 2009 groups were 7.54 and 7.73 years. Compared with patients in the 2004 group, the 2009 group had more severe asthma (p = 0.006). The distribution of asthma severity was mild (intermittent and mild persistent) 98.0% in 2004 and 87.9% in 2009, and moderate to severe persistent 2.0% in 2004 and 12.1% in 2009. The prevalence of patients sensitized to both house dust (HD) and house dust mites (HDM) increased from 21.2% in 2004 to 34.3% in 2009 (p =0.007). Sensitization to allergens of HD, HDM and cockroach increased to 14.1% in 2009 from 9.1% in 2004 (p =0.021). CONCLUSIONS: During the years between 2004 and 2009, asthma severity increased with increasing sensitization to HD, HDM and cockroach. Awareness of these changes and further studies are required.

A population-based study of fish allergy in the Philippines, Singapore and Thailand.

BACKGROUND: Fish allergy is the third most common food allergy after milk and egg in parts of Europe, but there is little data about prevalence in South East Asia where it is an important part of regular diets. OBJECTIVE: We aimed to obtain an estimate of the population prevalence of fish allergy among older children in the Philippines, Singapore and Thailand. METHODS: The population prevalence of fish allergy in 14- to 16-year-old children in the 3 countries was evaluated using a structured written questionnaire which was distributed to students of randomly selected secondary schools. An extended questionnaire to determine convincing fish allergy on the basis of typical clinical manifestations within 2 h of ingestion was administered to those with positive responses. RESULTS: From a cohort of 25,842 students, responses were 81.1% in the Philippines (n = 11,434), 67.9% in Singapore (n = 6,498) and 80.2% (n = 2,034) in Thailand. Using criteria for convincing food allergy, fish allergy was much higher in the Philippines [2.29%, 95% confidence interval (CI) 2.02-2.56] than in Singapore (0.26%, 95% CI 0.14-0.79) and Thailand (0.29%, 95% CI 0.06-0.52). Weighted multiple logistic regression analyses showed that compared to the Philippines, prevalence rates were lower in Singapore [odds ratio (OR) 0.40, 95% CI 0.27-0.60, p < 0.0001] and Thailand (OR 0.13, 95% CI 0.05-0.33, p < 0.0001). Females were more likely to have fish allergy compared to males for all children combined (OR 1.32, 95% CI 1.11-1.58, p = 0.002). Most allergies appeared mild, as only 28% of cases sought medical consultation at the time of the reaction and 31.2% of cases reported continued exposure despite allergic symptoms. CONCLUSION: Fish allergy in late childhood is more common in the Philippines compared to Singapore and Thailand. Differences in food processing, dietary habits and other cultural practices might be important risk factors for the development of fish allergy in these populations.

Comparison of skin test reactivity to histamine on back and forearm in young children.

RATIONALE: Skin responses to standardized positive and negative controls are important in the interpretation of a skin prick tests (SPT). However, this information in young children is lacking. We aimed to determine skin reactivity and compare the skin responses to these controls on the upper back and forearm in young children. METHODS: SPTs for histamine hydrochloride 1 mg/ml (positive control) and 50% glycerol-saline (negative control) were performed on the upper back and forearm of children aged 6-25 months who came to the well-child clinic at Songklanagarind Hospital. SPTs to common allergens (cow's milk, soybean, egg white and house dust mite) were also evaluated. RESULTS: A total of 133 children with a mean age of 12.4 months were enrolled in the study. Seventy-five children (56.4%) were male. The results from the upper back and the forearm of the histamine-induced mean wheal diameter + standard deviation (SD) were 4.74+1.37 mm and 3.86+1.82mm (p < 0.0001). The mean flare responses to histamine on the upper back and the forearm were 18.47 +/- 4.28 mm and 16.37 +/- 5.50 mm (p < 0.0001). The SPT results from the negative control on the upper back and forearm also had significant differences among the sizes of the wheal (0.57+1.17 vs. 0.34+0.89 mm, p = 0.007) and flare (4.57 +/- 3.04 mm vs. 3.34 +/- 1.91 mm, p < 0.0001). CONCLUSIONS: Our study showed regional differences in wheal and flare responses to standardized positive and negative controls in young children. The upper back is more reactive than the forearm and is the preferred SPT site in young-aged children.