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The Association of HLA-B* 5101 and Phenobarbital-Induced Severe Cutaneous Adverse Drug Reactions in Thai Children
Abstracts AB115
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
The Association of HLA-B* 5101 and Phenobarbital-Induced Severe Cutaneous Adverse Drug Reactions in Thai Children Plernpit Likkasittipan, MD1, Wiparat Manuyakorn, MD2, Surakameth Mahasirimongkol3, Suwat Benjaponpitak, MD1, Anannit Visudtibhan4, Nuanjun Wichukchinda3, Sukanya Wattanapokayakit3; 1Division of Pediatric Allergy/Immunology/Rheumatology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand, 2Division of Pediatric Allergy/Immunology/Rheumatology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, 3Medical genetic center, Medical Life Science Institute, Department of Medical Science, Ministry of Public Health, Nonthaburi, Thailand, 4Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. RATIONALE: Adverse drug reactions to phenobarbital (PB), the firstline aromatic anticonvulsant drug, are maculopapular rash (MP) and severe cutaneous adverse drug reactions (SCARs) including drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These conditions have high mortality rate and are usually unpredictable. This preliminary study aims to investigate the association between variations of HLA genotypes and phenobarbitalinduced SCARs among Thai children. METHODS: Thai children aged between 0-18 years who were diagnosed with phenobarbital hypersensitivity from 2004-2014. Control patients were phenobarbital-tolerant Thai children with corresponding age groups. Their HLA-B locus was genotyped using a PCR technique. RESULTS: A total of 45 Thai children were enrolled. Thirteen children were diagnosed with phenobarbital hypersensitivity (7 with MP and 6 with SCARs). Thirty two phenobarbital-tolerant children were recruited as control. The frequency of HLA-B*5101 in phenobarbital-induced SCARs was 50% (3/6) while only 6% (2/32) was found in the drug-tolerant children (OR515, 95% CI (1.75-128) p5 0.02). No patient with phenobarbital-induced MP was found to carry HLA-B*5101. The frequency of HLA-B*1502 in phenobarbital-induced MP was 14.3%, phenobarbitalinduced SCARs was 16.7% and drug tolerant was 12.5%. We did not find any association between phenobarbital-induced MP and SCARs and HLA-B*1502, a known HLA genotype associated with anticonvulsant hypersensitivity in previous study. CONCLUSIONS: Our preliminary study shows an association between HLA-B*5101 and phenobarbital-induced SCARsamong Thai children.
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Antibiotic Allergies in a Birth Cohort from 2007 Jay Jin, MD, PhD1, Sara M. May, MD1, Megan S. Motosue, MD1, Miguel A. Park, MD2; 1Mayo Clinic, Rochester, MN, 2 Department of Internal Medicine: Division of Allergic Diseases, Mayo Clinic, Rochester, MN. RATIONALE: The epidemiology of antibiotic allergies in pediatric populations is not well characterized. METHODS: With IRB approval and written informed consent from all patients, a cohort of children born at Mayo Clinic in 2007 and subsequently living in Olmsted County, Minnesota were retrospectively identified by chart review. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for developing an adverse drug reaction (ADR) to penicillins compared to other antibiotics. Antibiotic reactions and exposures were identified by searching Allergy and Medication sections of clinical notes between 01/01/2007 and 12/31/2013. RESULTS: Eighty patients (60.0%male) with 86 ADRs to antibiotics were identified in 925 children (51.6%male). Six patients had two or more ADRs. Among the 80 patients with ADRs, 72(90.0%) were to penicillins (PCNs), 5(6.3%) cephalosporins, 3(3.8%) macrolides, 3(3.8%) sulfonamides, and 1(1.3%) fluoroquinolones. Of the 925 patients, 604 were exposed to PCNs, 229 macrolides, 140 cephalosporins, 77 fluoroquinolones, and 39 sulfonamides. When adjusted for these exposures, 11.9%(72/ 604) reacted to PCNs, 7.7%(3/39) sulfonamides, 3.6%(5/140) cephalosporins, 1.3%(3/229) macrolides, and 1.3%(1/77) fluoroquinolones. PCNs were more likely to cause ADRs compared to other antibiotics [OR 10.0
(95%CI 3.1-32.2) versus macrolides; OR 3.6(1.4-9.1) cephalosporins; and OR 10.1(1.4-73.9) fluoroquinolones]. Rashes 68.8%(55/80) and hives 26.3%(21/80) were most commonly documented. No anaphylactic reactions or angioedema occurred. Penicillin skin testing was negative in 9 of 10 tested. CONCLUSIONS: In this cohort, penicillins were most likely to cause an ADR by age 7. Penicillin skin testing was useful to rule out allergy. Future studies should focus on the identification of risk factors contributing to antibiotic allergies. :Assessing Immediate and Delayed Reactions in Children Presenting to an Allergy Clinic with a Suspected Allergy to Amoxicillin Christopher Mill, BSc1, Marie-Noel Primeau, MD2, Elaine J. Medoff3, Christine Lejtenyi, MD3, Nofar Kimchi4, Elena Netchiporouk5, Alizee Dery6, Moshe Ben-Shoshan, MD, MSc7; 1School of Population and Public Health, University of British Columbia, Vancouver, BC, 2McGill University Health Center, Montreal, QC, Canada, 3Montreal Children’s Hospital, Montreal, QC, Canada, 4Technion American Medical Students Program, Israel, 5Division of Dermatology, Montreal Children’s Hospital, Montreal, QC, Canada, 6Department of Experimental Medicine, Mc Gill University, Montreal, QC, Canada, 7McGill University, Montreal, QC, Canada. RATIONALE: To assess the presence of immediate and delayed reactions through the use of provocative challenges among children referred to an allergy clinic due to potential allergy to Amoxicillin. METHODS: Children referred to the Montreal Children’s Hospital allergy clinic with suspected antibiotic allergy to Amoxicillin were approached. After parents consented, the treating allergist filled a standardized questionnaire on the clinical characteristics, suspected antibiotic exposure and management of the reaction and all children were offered an oral antibiotic challenge. Descriptive statistics were used to characterize the reactions. RESULTS: Among 419 patients assessed between March 2012 and August 2014, the majority (51.3%) reported reactions after 1-3 days of treatment and in 61.9% symptoms persisted for 1-3 days. The most common symptom was hives (60.4%), almost half (44.3%) were seen in a healthcare facility and 59.1% were treated there with antihistamines. Among 398 consenting to challenge (95.0%), 24 (6.0%) were positive. We identified four groups of patients: 94.0% were tolerant to challenge, 1.6% reacted immediately (within 1 hour, skin prick tests and intradermal tests with penicillin G 10 000 UI/ml and Pre-Pen tests were negative for immediate reactions), 3.8% had late reactions late and one patient tolerated the oral challenge to Amoxicillin but not the full treatment. All immediate reactions consisted of hives, delayed reactions were either hives or a maculopapular rash and both types were treated only with antihistamines. CONCLUSIONS: Challenges provide an accurate and safe confirmatory test for skin-related reactions to Amoxicillin. Further studies are required to assess factors associated with the challenge outcome groups.
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J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
The Association of HLA-B* 5101 and Phenobarbital-Induced Severe Cutaneous Adverse Drug Reactions in Thai Children Plernpit Likkasittipan, MD1, Wiparat Manuyakorn, MD2, Surakameth Mahasirimongkol3, Suwat Benjaponpitak, MD1, Anannit Visudtibhan4, Nuanjun Wichukchinda3, Sukanya Wattanapokayakit3; 1Division of Pediatric Allergy/Immunology/Rheumatology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand, 2Division of Pediatric Allergy/Immunology/Rheumatology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, 3Medical genetic center, Medical Life Science Institute, Department of Medical Science, Ministry of Public Health, Nonthaburi, Thailand, 4Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. RATIONALE: Adverse drug reactions to phenobarbital (PB), the firstline aromatic anticonvulsant drug, are maculopapular rash (MP) and severe cutaneous adverse drug reactions (SCARs) including drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These conditions have high mortality rate and are usually unpredictable. This preliminary study aims to investigate the association between variations of HLA genotypes and phenobarbitalinduced SCARs among Thai children. METHODS: Thai children aged between 0-18 years who were diagnosed with phenobarbital hypersensitivity from 2004-2014. Control patients were phenobarbital-tolerant Thai children with corresponding age groups. Their HLA-B locus was genotyped using a PCR technique. RESULTS: A total of 45 Thai children were enrolled. Thirteen children were diagnosed with phenobarbital hypersensitivity (7 with MP and 6 with SCARs). Thirty two phenobarbital-tolerant children were recruited as control. The frequency of HLA-B*5101 in phenobarbital-induced SCARs was 50% (3/6) while only 6% (2/32) was found in the drug-tolerant children (OR515, 95% CI (1.75-128) p5 0.02). No patient with phenobarbital-induced MP was found to carry HLA-B*5101. The frequency of HLA-B*1502 in phenobarbital-induced MP was 14.3%, phenobarbitalinduced SCARs was 16.7% and drug tolerant was 12.5%. We did not find any association between phenobarbital-induced MP and SCARs and HLA-B*1502, a known HLA genotype associated with anticonvulsant hypersensitivity in previous study. CONCLUSIONS: Our preliminary study shows an association between HLA-B*5101 and phenobarbital-induced SCARsamong Thai children.
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Antibiotic Allergies in a Birth Cohort from 2007 Jay Jin, MD, PhD1, Sara M. May, MD1, Megan S. Motosue, MD1, Miguel A. Park, MD2; 1Mayo Clinic, Rochester, MN, 2 Department of Internal Medicine: Division of Allergic Diseases, Mayo Clinic, Rochester, MN. RATIONALE: The epidemiology of antibiotic allergies in pediatric populations is not well characterized. METHODS: With IRB approval and written informed consent from all patients, a cohort of children born at Mayo Clinic in 2007 and subsequently living in Olmsted County, Minnesota were retrospectively identified by chart review. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for developing an adverse drug reaction (ADR) to penicillins compared to other antibiotics. Antibiotic reactions and exposures were identified by searching Allergy and Medication sections of clinical notes between 01/01/2007 and 12/31/2013. RESULTS: Eighty patients (60.0%male) with 86 ADRs to antibiotics were identified in 925 children (51.6%male). Six patients had two or more ADRs. Among the 80 patients with ADRs, 72(90.0%) were to penicillins (PCNs), 5(6.3%) cephalosporins, 3(3.8%) macrolides, 3(3.8%) sulfonamides, and 1(1.3%) fluoroquinolones. Of the 925 patients, 604 were exposed to PCNs, 229 macrolides, 140 cephalosporins, 77 fluoroquinolones, and 39 sulfonamides. When adjusted for these exposures, 11.9%(72/ 604) reacted to PCNs, 7.7%(3/39) sulfonamides, 3.6%(5/140) cephalosporins, 1.3%(3/229) macrolides, and 1.3%(1/77) fluoroquinolones. PCNs were more likely to cause ADRs compared to other antibiotics [OR 10.0
(95%CI 3.1-32.2) versus macrolides; OR 3.6(1.4-9.1) cephalosporins; and OR 10.1(1.4-73.9) fluoroquinolones]. Rashes 68.8%(55/80) and hives 26.3%(21/80) were most commonly documented. No anaphylactic reactions or angioedema occurred. Penicillin skin testing was negative in 9 of 10 tested. CONCLUSIONS: In this cohort, penicillins were most likely to cause an ADR by age 7. Penicillin skin testing was useful to rule out allergy. Future studies should focus on the identification of risk factors contributing to antibiotic allergies. :Assessing Immediate and Delayed Reactions in Children Presenting to an Allergy Clinic with a Suspected Allergy to Amoxicillin Christopher Mill, BSc1, Marie-Noel Primeau, MD2, Elaine J. Medoff3, Christine Lejtenyi, MD3, Nofar Kimchi4, Elena Netchiporouk5, Alizee Dery6, Moshe Ben-Shoshan, MD, MSc7; 1School of Population and Public Health, University of British Columbia, Vancouver, BC, 2McGill University Health Center, Montreal, QC, Canada, 3Montreal Children’s Hospital, Montreal, QC, Canada, 4Technion American Medical Students Program, Israel, 5Division of Dermatology, Montreal Children’s Hospital, Montreal, QC, Canada, 6Department of Experimental Medicine, Mc Gill University, Montreal, QC, Canada, 7McGill University, Montreal, QC, Canada. RATIONALE: To assess the presence of immediate and delayed reactions through the use of provocative challenges among children referred to an allergy clinic due to potential allergy to Amoxicillin. METHODS: Children referred to the Montreal Children’s Hospital allergy clinic with suspected antibiotic allergy to Amoxicillin were approached. After parents consented, the treating allergist filled a standardized questionnaire on the clinical characteristics, suspected antibiotic exposure and management of the reaction and all children were offered an oral antibiotic challenge. Descriptive statistics were used to characterize the reactions. RESULTS: Among 419 patients assessed between March 2012 and August 2014, the majority (51.3%) reported reactions after 1-3 days of treatment and in 61.9% symptoms persisted for 1-3 days. The most common symptom was hives (60.4%), almost half (44.3%) were seen in a healthcare facility and 59.1% were treated there with antihistamines. Among 398 consenting to challenge (95.0%), 24 (6.0%) were positive. We identified four groups of patients: 94.0% were tolerant to challenge, 1.6% reacted immediately (within 1 hour, skin prick tests and intradermal tests with penicillin G 10 000 UI/ml and Pre-Pen tests were negative for immediate reactions), 3.8% had late reactions late and one patient tolerated the oral challenge to Amoxicillin but not the full treatment. All immediate reactions consisted of hives, delayed reactions were either hives or a maculopapular rash and both types were treated only with antihistamines. CONCLUSIONS: Challenges provide an accurate and safe confirmatory test for skin-related reactions to Amoxicillin. Further studies are required to assess factors associated with the challenge outcome groups.
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