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.

Asia Pacific perspectives on the second year of the COVID-19 pandemic: A follow-up survey.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic is currently in its third year. This follow-up survey was commissioned by the Asia Pacific Association of Allergy Asthma and Clinical Immunology (APAAACI) Task Force on COVID-19 to compare and contrast changes in the epidemiology, clinical profile, therapeutics and public health measures of the pandemic in the Asia Pacific region. METHODS: A questionnaire-based survey comprising 32 questions was electronically sent out to all 15 member countries of APAAACI using Survey Monkey® from 1 December 2021 to 28 February 2022. RESULTS: Seventeen responses were received from 14/15 (93.4%) member countries and 3 individual members. Mild-to-moderate COVID-19 predominated over severe infection, largely contributed by COVID-19 vaccination programmes in the region. The incidence of vaccine adverse reactions in particular anaphylaxis from messenger ribonucleic acid (mRNA) vaccines was no longer as high as initially anticipated, although perimyocarditis remains a concern in younger males. Novel therapeutics for mild-to-moderate disease including neutralizing antibodies casirivimab/imdevimab (REGEN-COV®) and sotrovimab (Xevudy®), anti-virals Paxlovid® (nirmatrelvir and ritonavir) and Molnupiravir pre-exposure prophylaxis for high-risk persons with Tixagevimab and Cilgavimab (Evusheld) are now also available to complement established therapeutics (e.g., remdesivir, dexamethasone and baricitinib) for severe disease. In the transition to endemicity, public health measures are also evolving away from containment/elimination strategies. CONCLUSIONS: With access to internationally recommended standards of care including public health preventive measures, therapeutics and vaccines among most APAAACI member countries, much progress has been made over the 2-year period in minimizing the morbidity and mortality from COVID-19 disease.

Successful haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide in a child with X-linked chronic granulomatous disease: A first report in Asia.

BACKGROUND: HLA-matched hematopoietic stem cell transplantation (HSCT) is the curative treatment for chronic granulomatous disease (CGD). OBJECTIVE: To report a case of X-linked CGD with active infection successfully treated by haploidentical HSCT with post-transplant high dose cyclophosphamide (PTCY). METHODS: A 5-year-old Thai boy with CGD was undergone for haploidentical HSCT using PTCY with correction of the phagocytic function. He presented with Chromobacterium violaceum liver abscess at the age of 9 months and experienced recurrent perianal abscess and invasive pulmonary aspergillosis even receiving antimicrobial prophylaxis. PTCY was given on day 3 and 4, after CD34+ cells infusion. RESULTS: The peripheral blood-nucleated cell chimerism showed 100% on day 16 and remained 100%. Dihydrorhodamine (DHR) assay on day 108 and day 214 showed normal results. Currently at 22 months post HSCT, he does not receive antibiotic and anti-fungal prophylaxis. CONCLUSIONS: Haploidentical HSCT with PTCY could be an effective treatment option for children with CGD.

Effect of vitamin D on lung function assessed by forced oscillation technique in asthmatic children with vitamin D deficiency: A randomized double-blind placebo-controlled trial.

BACKGROUND: The role of vitamin D and asthma in pulmonary function changes showed conflicting result. OBJECTIVE: To evaluate if vitamin D treatment would improve lung function assessed by forced oscillation technique (FOT) in vitamin D deficient asthmatic children. METHODS: A randomized double-blind placebo-controlled trial was performed in children, aged 3-18 years with well controlled asthma. Serum total 25(OH)D and FOT parameters including respiratory resistance at 5 Hz (R5), at 20 Hz (R20), respiratory reactance at 5 Hz (X5) and area of reactance (ALX), resonance frequency (Fres) were evaluated at baseline, 1 month and 3 months. Vitamin D deficient patients (serum total 25(OH)D < 20 ng/ml) were randomized to receive treatment with vitamin D2 (tVDD) or placebo (pVDD). Non-vitamin D deficient patients (nVDD) received placebo as a control group. RESULTS: A total of 84 children were recruited, 43 patients in nVDD group, 20 in tVDD group and 21 in pVDD group. There were no significant differences in age, sex, height and weight among groups. There were no significant differences of FOT parameters among groups at all visits. There was a trend toward decrease in R5/R20 from baseline to 1 month and 3 months visit in all groups, but the statistically significant improvement was observed only in nVDD group. Serum 25(OH)D showed no correlation with % predicted of FOT measures. CONCLUSIONS: Vitamin D treatment in asthmatic children who had vitamin D deficiency may have no short term beneficial effect on pulmonary function assessed by FOT. Vitamin D supplementation in all asthmatic patient needs further study.

Asia-Pacific survey of physicians' perceptions and managements of chronic rhinosinusitis.

BACKGROUND: The diagnosis and management of patients with chronic rhinosinusitis (CRS) may vary between otolaryngologists and allergists. Moreover, the adherence of different practitioners to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 guideline recommendations has not been previously ascertained in Asia-Pacific regions. OBJECTIVE: Different specialists' perceptions and managements of CRS in Asia-Pacific regions were assessed in an attempt to gauge these practices against EPOS 2020 guidelines. METHODS: A transregional, cross-sectional survey was conducted to assess otolaryngologists' and allergists' perceptions and managements of CRS with regard to diagnosis, management and adherence to EPOS 2020 guidelines. RESULTS: Sixteen physicians in Asia-Pacific regions responded to the questionnaire. A total of 71.4% of otolaryngologists preferred to diagnose CRS with a combination of positive nasal symptoms and nasal endoscopy plus sinus CT, whereas 22.2% of allergists took such criterion to diagnose CRS. Compared to allergists, otolaryngologists more often considered the endotype classification (85.8% versus 55.5%). For the preferred first-line treatment, in addition to intranasal corticosteroids recommended by all respondents, 66.7% of allergists preferred antihistamines, whereas 71.4% of otolaryngologists preferred nasal saline irrigation. Regarding the proper timing of surgery, 71.5% of otolaryngologists reported 8-12 weeks of treatment after the initiation of medication, while more than half of the allergists recommended 4-6 weeks of medical treatment. CONCLUSIONS: This survey shows that variable perceptions and practices for CRS may exist between physicians with different specialties and highlights the need for increased communication and awareness between otolaryngologists and allergists to improve the diagnosis and treatment of CRS.

An online survey of clinical practice for allergic rhinitis among the Asia-Pacific representatives.

BACKGROUND: Physicians' knowledge and practice which are consistent with evidence-based guidelines can improve allergic rhinitis (AR) patients' care. Compared with western countries, the available literature about Asian doctors' perceptions and clinical practices regarding Allergic Rhinitis and its Impacts on Asthma (ARIA) guidelines is limited. OBJECTIVE: To collect detailed information about the practical management patterns specific for AR patients and investigate compliance with ARIA in the clinical practice of Asian physicians and elucidate the possible inadequacy in the existing ARIA guidelines. METHODS: An e-mail with a structured questionnaire was sent to members of the Asia-Pacific Association of Allergy, Asthma and Clinical Immunology. The questionnaire consisted of doctors' characteristics, environment of medical practice, routine clinical practice following ARIA guidelines and patients' adherence to the prescription. RESULTS: Physicians from 14 countries and regions sent valid questionnaires back, 94.12% of whom were senior doctors with more than 10 years of experience. 88.24% of doctors diagnosed AR depending on the history combined with allergy tests. 82.35% of participants employed the classification criteria by ARIA. 94.12%, 88.24% and 41.8% of respondents recommended intranasal corticosteroids, oral antihistamines and leukotriene receptor antagonists as first-line medications. 5.88% treated perennial AR by intranasal corticosteroids alone. 11.76% of clinicians recommended no allergen immunotherapy (AIT) or biologics and 58.82% of interviewees reported AR patients occasionally or sometimes agreed with the recommendation of AIT. CONCLUSIONS: There was high compliance with ARIA guidelines in Asian senior physicians' actual notion and practice in the management of AR. New-generation ARIA guidelines are imperative for unmet needs.

Reference value of Forced Oscillation Technique for healthy preschool children.

BACKGROUND: The reference values of Forced Oscillation Technique (FOT) parameters of the inspiratory and expiratory phase for preschool children have not yet been established. OBJECTIVE: To evaluate FOT measures in Thai healthy preschool children. METHODS: Preschool children, aged 3-6 years, were screened. Children who were positive for the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire for asthma, positive family history of allergic diseases, recent lower respiratory tract infections, and environmental tobacco smoke were excluded. FOT parameters, including resistance (Rrs), reactance (Xrs), frequency of resonance (Fres) and area of reactance (ALX), were measured. RESULTS: A total of 390 healthy children with the mean age of 5.1 ± 0.9 years were enrolled. FOT was successfully performed in 378 children (96.9%). The mean (SD) for the whole breath (WB) resistance at 5Hz (R5), 20 Hz (R20) and R5-20 were 11.49 (2.69) cmH2O/L/s, 9.46 (2.19) cmH2O/L/s and 2.02 (0.82) cmH2O/L/s, respectively. The median (IQR) for WB reactance at 5Hx (X5), Fres and ALX were -1.51 (-2.37 to -0.96) cmH2O/L/s, 11.17 (8.50-15.65) Hz, and 7.53 (3.72-14.32) cmH2O/L/s, respectively. Significantly difference in WB R5, R20, X5, Fres and ALX between male and female children were demonstrated. The expiratory phase R5, R20, R5-20 were significantly higher than those of the inspiratory phase (p < 0.001). There are significant correlations between the height and FOT parameters. Reference curve for the FOT parameters was generated based on height using the lambda-mu-sigma (LMS) method. CONCLUSIONS: Reference curve of FOT parameters measured in healthy preschool children were demonstrated. Majority of preschool children could perform FOT method.

Association of HLA genotypes with Beta-lactam antibiotic hypersensitivity in children.

BACKGROUND: Beta-lactam (BL) antibiotics hypersensitivity is common in children. Clinical manifestation of BL hypersensitivity varies from mild to severe cutaneous adverse drug reactions (SCARs). OBJECTIVE: To determine the association of HLA genotype and BL hypersensitivity and the prevalence of true drug allergy in patients with history of BL hypersensitivity. METHODS: A case-control study was performed in 117 children with aged 1-18 years. Children with history of non-SCARs BL hypersensitivity were evaluated for true drug hypersensitivity including skin test and drug provocation test. Tolerant control patients were children who could tolerate BL for at least 7 days without hypersensitivity reaction. HLA genotype (HLA-A, HLA-B, HLA-C and HLA-DRB1) were performed in 24 cases and 93 tolerant controls using PCR-SSO (polymerase chain reaction - sequence specific oligonucleotide probes). RESULTS: There were association of HLA-C*04:06 (OR = 13.14, 95%CI: 1.3-137.71; p = 0.027), and HLA-C*08:01 (OR = 4.83, 95%CI: 1.93-16.70; p = 0.016) with BL hypersensitivity. HLA-B*48:01 was strongly associated with immediate reaction from BL hypersensitivity (OR = 37.4, 95%CI: 1.69-824.59; p = 0.016) while HLA-C*04:06, HLA-C*08:01 and HLA-DRB1*04:06 were associated with delayed reaction (p < 0.05). Among 71 cases who were newly evaluated for BL hypersensitivity, only 7 cases (9.8%) had true BL hypersensitivity. CONCLUSIONS: Less than 10% of children with suspected of BL hypersensitivity have true hypersensitivity. There might be a role of HLA-B, HLA-C and HLA-DRB1 genotype in predicting BL hypersensitivity in Thai children.

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.

Needle length for epinephrine prefilled syringes in children and adolescents: Is one inch needle appropriate?

BACKGROUND: Intramuscular epinephrine is the first line drug in the treatment of anaphylaxis. This study was to identify the appropriateness of 1 inch needle length for epinephrine prefilled syringes in children. METHODS: Children aged 1 month to 18 years were enrolled. Skin to muscle depth (STMD) and skin to bone depth (STBD) were measured using an ultrasonography at the mid-anterolateral thigh. A 1 inch needle was considered as being appropriate if the STBD was more than 1 inch and the STMD was less than 1 inch. RESULTS: Seventy five infants, 75 pre-school aged children, 75 school aged children and 147 adolescent were enrolled: 196 (52.7%) children were male. A 1 inch needle length was appropriate for 61% of the infants, for 88% of the preschool children, for 99% of the school aged children and for 95% of the adolescents. Thigh circumference ≥23 cm, BMI ≥16 kg/m2 and BW ≥ 6 kg in infants provided the sensitivity of 74%-96% in predicting the appropriateness of 1 inch needle. In preschool group, thigh circumference ≥25 cm, BMI ≥13.5 kg/m2 and BW ≥ 10 kg provided the sensitivity of 98.5-100% in predicting the appropriateness of 1 inch needle. Thigh circumference ≥ 49 cm in adolescents provided the sensitivity of 75% in predicting that a 1 inch needle was too short. CONCLUSION: One inch needle length may not be appropriated for intramuscular injection at thigh in all children. Thigh circumference, BMI and body weight are useful for predictor for using the 1 inch needle.

De novo food allergy in pediatric liver transplantation recipients.

BACKGROUND: Food allergy (FA) prevalence is increasing in pediatric liver transplantation (LT). However, the clinical course is still limited. OBJECTIVE: This retrospective cohort study aimed to identify the prevalence, risk factors, and the natural history of de novo FA in children post LT. METHODS: Medical records of pediatric LT recipients from Jan 2001 - Dec 2014 were reviewed. De novo FA was diagnosed by symptoms after exposure to culprit food occurring after LT, and improvement after diet elimination. FA was confirmed if reproduced symptoms after re-challenge or documented sensitization or indicated gastrointestinal eosinophilia. RESULTS: Among 46 post LT children, 54.3% developed de novo FA at a median time of 12.2 months [Interquartile range (IQR) 6.2, 21.3 months] post LT. The confirmed FA was 39.1%. Gastrointestinal symptom was the most common manifestation followed by skin, anaphylaxis, and others. Culprit foods were cow's milk, shellfish, egg, wheat, soybean, peanut, coconut, fish and monosodium glutamate. The risk factors of FA were transplantation during age below 2 years [hazard ratio (HR), 2.62; 95% confidence interval (CI), 1.04 - 6.59; p = 0.03), atopic history in family (HR, 5.67; 95% CI, 1.33 - 24.12; p = 0.01), and Epstein-Barr (EBV) viremia (HR, 2.39; 95% CI, 1.02 - 5.63; p = 0.04). CONCLUSIONS: de novo FA in pediatric LT is not uncommon. Age at LT younger than 2 years, family history of atopy, and EBV viremia are associated with developing FA. Development of tolerance after elimination culprit diets for 3 years is similar to general population.

Safety and efficacy of ant rush immunotherapy in children.

BACKGROUND: The Rush Immunotherapy (RIT) protocol is a valid alternative in order to reach the maintenance phase early. However, there are scarce studies in the literature that have evaluated the safety and the efficacy of an ant RIT process in children. OBJECTIVE: To evaluate the safety and the efficacy of an ant RIT protocol and to identify the risk factors for systemic reactions (SRs) during an RIT procedure in children. METHOD: A retrospective review was conducted for those children who were receiving an ant RIT procedure. The 3-day RIT protocol consisted of hourly subcutaneous injections in order to achieve a 0.5 ml maintenance dose of a 1:100 weight/ volume (wt/vol) of the Solenopsis invicta whole body extract. The safety for an RIT procedure was monitored by using the World Allergy Organization Subcutaneous Immunology Systemic Reaction Grading System. The efficacy was assessed by the reactions after a field ant re-sting. RESULT: A total of 20 children who were receiving an ant RIT therapy were reviewed. The mean age was 9.5±3.07 years. There were 6 systemic reactions (SRs) from 324 injections during the RIT procedure (1.85%). All of the systemic reactions were Grade 1-2. There were no associations of SRs regarding age, gender, an atopic history, or the levels of immunoglobulin E (IgE) sensitization to the ants. Among the 14 patients who experienced a field ant re-sting, 4 (28.5%) patients developed Grade 3 SRs. These Grade 3 reactions were resolved after an increase of the maintenance dose to 0.5 ml of a 1:50 wt/vol. There was a significant difference in the mean age of those children who had ant re-sting systemic reactions and those who had no reactions (6.75±0.95 year vs. 10.8±3.29, p=0.036). CONCLUSION: Rush immunotherapy with ant in children is safe and it has a low occurrence of severe systemic reactions. It is an alternative treatment for those patients requiring a rapid protection.

Mosquito allergy in children: Clinical features and limitation of commercially-available diagnostic tests.

OBJECTIVE: To determine the clinical features of mosquito allergy in children and the ability of commercially available mosquito allergy tests to detect children with mosquito allergy in Thailand. METHODS: Patients with mosquito allergy aged 1 month to 18 years were recruited. Demographic data, history of mosquito allergy (onset of the reaction, reaction type) and clinical features were recorded. A skin prick test using a commercially available whole body allergen extract from Culex pipiens was performed, and serum was tested for specific IgE antibodies to Aedes communis whole body extract. RESULTS: A total of 50 patients with mosquito allergy were enrolled. The median age of enrolled children was 6.2 years with an average age of onset of 2 years [interquartile range (IQR) 1-6]. Half of the children were female. The most common skin lesion from mosquito allergy was erythematous papules (n = 45, 76.3%). The majority of children (58%) were in stage 3 (immediate and delayed type of reactions). One child (2%) was in the desensitization stage after 4.6 years of symptoms. The causative mosquito species could be identified only in 26 (52%) children: 16 (32%) children were positive for Aedes communis, 17 (34%) children were positive for Culex pipiens and 7 (14%) children were positive for both Aedes communis and Culex pipiens. Having positive IgE antibodies against Aedes communis was significantly more common in boys (n = 13, 48.1%) than girls (n = 3, 13%) (p < 0.01). CONCLUSIONS: Immediate and delayed skin reaction is the most common manifestation in mosquito allergy children. Commercially available tests for mosquito allergy can detect only 30-50% of children with mosquito allergy.

Blood Coagulation and Asthma Exacerbation in Children.

BACKGROUND: Recent studies have demonstrated the activation of coagulation pathways in asthmatic airways. This study aimed to determine systemic blood coagulation during asthma exacerbation compared with the stable state in children. METHODS: Pediatric patients (aged between 5 and 15 years) suffering from asthma exacerbation were enrolled. von Willebrand factor (vWF), plasminogen activator inhibitor type-1 (PAI-1), protein C, D-dimer, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and C-reactive protein (CRP) levels were measured during asthma exacerbation and stable state. RESULTS: A total of 22 patients were enrolled. The median vWF, PAI-1, and CRP during asthma exacerbation were significantly higher than those of the stable state: 147.5% (interquartile range, IQR: 111.05-196.57) versus 94% (IQR: 69.72-109.62, p < 0.001), 41.9 ng/ml (IQR: 21.91-48.61) versus 26.17 ng/ml (IQR: 15.89-34.44, p < 0.03), and 4.46 mg/l (IQR: 2.15-16.23) versus 0.87 mg/l (IQR: 0.20-3.89, p < 0.015), respectively. However, the median protein C during asthma exacerbation was significantly lower than that of the stable state: 99.5% (IQR: 86.75-117) versus 113% (IQR: 94-115.25), p = 0.01. No significant difference was found between the levels of D-dimer, F1 + 2, and TAT during asthma exacerbation and stable state. Ultimately, D-dimer was positively correlated with asthma exacerbation score (R = 0.466, p = 0.027). A significant correlation was observed between vWF and CRP (R = 0.527, p = 0.012). CONCLUSION: Evidence was found of increased endothelial activation and increased PAI-1 during asthma exacerbation. This may emphasize the potential role of blood coagulation in asthma exacerbation.

Association of HLA genotypes with phenobarbital hypersensitivity in children.

OBJECTIVE: Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. METHODS: The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. RESULTS: The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). SIGNIFICANCE: An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children.

Skin testing with ß-lactam antibiotics for diagnosis of ß-lactam hypersensitivity in children.

OBJECTIVE: Skin testing with penicilloyl-polylysine (PPL) and a minor determinant mixture (MDM) were previously recommended for evaluating ß-lactam hypersensitivity. However, PPL and MDM have not been commercially available. This study was to determine the negative predictive value (NPV) of skin testing with ß-lactam antibiotics for the diagnosis of ß-lactam hypersensitivity. METHOD: Patients age 1-18 years old with a history of ß-lactam hypersensitivity were evaluated by skin tests (a skin prick test, an intradermal test) with penicillin G, ampicillin, amoxicillin-clavulanic acid, and the suspect ßlactam. The patients who had a negative skin test were performed with a drug provocation test (DPT) in a 3-dose-graded challenge. The hypersensitivity reactions were classified into immediate and non-immediate reactions. RESULTS: A total of 126 patients were evaluated for ß-lactam hypersensitivity. Twenty two patients (17.4%) were confirmed with a ?-lactam hypersensitivity. 12 (54.54 %) of them were confirmed by a skin test. There was no systemic reaction occurring after the skin tests. Ten patients (9.6%) from 104 patients with a negative skin test showed reactions after a DPT providing the NPV of the skin test with a 91.2% value. CONCLUSIONS: Among those children with a history of ß-lactam hypersensitivity, skin testing with penicillin G, ampicillin, amoxicillin-clavulanic acid, and the suspect ß-lactam was safe and provided a good NPV when PPL and MDM were unavailable. However, a skin test with ß-lactam antibiotics alone did not provide a high sensitivity, thus a DPT procedure was necessary in order to confirm the diagnosis of ß-lactam hypersensitivity.

Association analysis of CYP2C9*3 and phenytoin-induced severe cutaneous adverse reactions (SCARs) in Thai epilepsy children.

CYP2C9 is the key enzyme in aromatic antiepileptic drugs (AEDs) metabolism. CYP2C9*3 is a loss of function polymorphism. This study was designed to investigate genetic association between CYP2C9*3 and aromatic AED-induced severe cutaneous adverse reactions (SCARs) in Thai children. The 37 aromatic AED-induced SCARs patients (20 phenobarbital and 17 phenytoin) and 35 tolerances (19 phenobarbital and 16 phenytoin) were enrolled. CYP2C9*3 was genotyped by allele-specific PCRs. The association between CYP2C9*3 with phenytoin-induced SCARs and phenobarbital-induced SCARs were analyzed in comparison with tolerances and healthy samples. Significant association between phenytoin-induced SCARs and CYP2C9*3 was discovered (odds ratio=14.52; 95% confidence interval (CI)=1.18-∞, P-value=0.044). CYP2C9*3 was not associated with phenobarbital-induced SCARs. This study is the first report of CYP2C9*3 association to phenytoin-induced SCARs in Thai epileptic children. The CYP2C9*3 is a reasonable predictive genetic marker to anticipate SCARs from phenytoin.

Pediatric anaphylaxis: triggers, clinical features, and treatment in a tertiary-care hospital.

BACKGROUND: Anaphylaxis is a life-threatening condition. There are limited data about its etiology and clinical characteristics in Asian children with anaphylaxis. OBJECTIVE: To investigate triggers, presenting symptoms, treatment and clinical course of anaphylaxis in Thai children. METHOD: Medical record of children who were diagnosed with anaphylaxis between 2004 and 2013 at Ramathibodi Hospital, Bangkok, Thailand were reviewed. RESULTS: One hundred-seventy two episodes of anaphylaxis occurred in 160 children (91 boys, 69 girls) aged 3 months to 18 years. Anaphylaxis increased from 2.7 cases/1000 pediatric admission to 4.51 cases/1000 pediatric admission between 2004-2008 and 2009-2013. The main causes were food (34.92%), drug (33.1%), blood components (23.8%), insect sting (9%), and unidentified causes (2.8%). Allergy to the triggers was known prior to anaphylaxis in 42 episodes (24.6%). Treatment consisted of epinephrine intramuscularly (93.8%), corticosteroids (92.5%), H1antihistamines (96%), H2antihistamines (50%), and ß2agonists nebulization (35.1%). Biphasic anaphylaxis occurred in 8.7% of the documented episodes and severe anaphylaxis in 34.3% of the documented episodes. Biphasic anaphylaxis and severe anaphylaxis were associated with fewer administrations of intramuscular epinephrine (OR 0.08 [95% CI 0.014-0.43]; p =0.01 and OR 9.36 [95% CI 2.5-34.7]; p <0.001 respectively). There were no fatality cases. There were associations between triggers of anaphylaxis and atopic histories, patients with severe anaphylaxis and cardiovascular involvement (p <0.01). CONCLUSIONS: The incidence of anaphylaxis in Thai children is increasing. Anaphylaxis in children commonly occurred without the histories of prior reaction to the causative agent. Less frequent treatment with intramuscular epinephrine was associated with biphasic and severe anaphylaxis. A better knowledge of patterns and causes of anaphylaxis might contribute to a better management.