Rutherford Exius1, Sofianne Gabrielli2, Elissa M Abrams3, Andrew O'Keefe4, Jennifer L P Protudjer5, Elana Lavine6, Tracy Pitt7, Adelle Atkinson8, Thomas Eiwegger8, Christine McCusker9, Moshe Ben-Shoshan2. 1. Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada; Infectious Diseases and Immunity in Global Health Program, The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada. Electronic address: rutherford.exius@mail.mcgill.ca. 2. Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada; Infectious Diseases and Immunity in Global Health Program, The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada. 3. Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, MB, Canada; Department of Pediatrics, Division of Allergy and Immunology, University of British Columbia, Vancouver, BC, Canada. 4. Department of Pediatrics, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada. 5. Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, MB, Canada; George and Fay Yee Centre for Healthcare Innovation, Winnipeg, MB, Canada; The Children's Health Research Institute of Manitoba, Winnipeg, MB, Canada; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Food and Human Nutritional Sciences, The University of Manitoba, Winnipeg, MB, Canada. 6. Division of Allergy and Clinical Immunology, Department of Paediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, Queen's University, Kingston, ON, Canada; Department of Pediatrics, Humber River Hospital, Toronto, ON, Canada. 7. Department of Pediatrics, Queen's University, Kingston, ON, Canada; Department of Pediatrics, Humber River Hospital, Toronto, ON, Canada; Department of Pediatrics, St Joseph's Hospital, Toronto, ON, Canada. 8. Division of Allergy and Clinical Immunology, Department of Paediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada. 9. Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada.
Abstract
BACKGROUND: Data on the diagnostic properties of direct oral challenges without the use of skin tests in children with suspected amoxicillin allergy are sparse. OBJECTIVE: Assess the use of direct oral challenges. METHODS: A cohort study was conducted between March 2013 and March 2020, in Montreal and Winnipeg. All children referred with reported history of benign reactions (ie, limited to the skin with no mucosal lesions and no vesicles) to amoxicillin were recruited and a 2-step graded oral challenge (GOC) was conducted. Data were collected on demographic characteristics, clinical characteristics, and comorbidities. Eligible children were followed to assess reactions to subsequent use of amoxicillin and to assess the safety of cephalexin use in children with a positive GOC. RESULTS: Among 1914 children recruited, 1811 (94.6%) tolerated the GOC, 42 (2.2%) developed mild immediate reactions, and 61 (3.2%) developed mild nonimmediate reactions. Among 265 participants who had a negative GOC and reused amoxicillin, 226 (85.3%) reported tolerance and 39 (14.7%) had mild cutaneous reactions. Chronic urticaria (adjusted odds ratio [aOR], 1.16; 95% CI, 1.09-1.23) and an index reaction occurring within 5 minutes of exposure (aOR, 1.09; 95% CI, 1.04-1.14) were associated with immediate reactions during the GOC. Symptoms lasting longer than 7 days (aOR, 1.05; 95% CI, 1.02-1.09) and parental drug hypersensitivity (aOR, 1.04; 95% CI, 1.03-1.06) were associated with nonimmediate reactions. Among those reacting to the GOC, 12.5% reacted with mild cutaneous reactions to cephalexin challenge. CONCLUSIONS: Direct GOCs are an accurate and safe confirmatory to establish true hypersensitivity among children reporting benign reactions to amoxicillin.
BACKGROUND: Data on the diagnostic properties of direct oral challenges without the use of skin tests in children with suspected amoxicillin allergy are sparse. OBJECTIVE: Assess the use of direct oral challenges. METHODS: A cohort study was conducted between March 2013 and March 2020, in Montreal and Winnipeg. All children referred with reported history of benign reactions (ie, limited to the skin with no mucosal lesions and no vesicles) to amoxicillin were recruited and a 2-step graded oral challenge (GOC) was conducted. Data were collected on demographic characteristics, clinical characteristics, and comorbidities. Eligible children were followed to assess reactions to subsequent use of amoxicillin and to assess the safety of cephalexin use in children with a positive GOC. RESULTS: Among 1914 children recruited, 1811 (94.6%) tolerated the GOC, 42 (2.2%) developed mild immediate reactions, and 61 (3.2%) developed mild nonimmediate reactions. Among 265 participants who had a negative GOC and reused amoxicillin, 226 (85.3%) reported tolerance and 39 (14.7%) had mild cutaneous reactions. Chronic urticaria (adjusted odds ratio [aOR], 1.16; 95% CI, 1.09-1.23) and an index reaction occurring within 5 minutes of exposure (aOR, 1.09; 95% CI, 1.04-1.14) were associated with immediate reactions during the GOC. Symptoms lasting longer than 7 days (aOR, 1.05; 95% CI, 1.02-1.09) and parental drug hypersensitivity (aOR, 1.04; 95% CI, 1.03-1.06) were associated with nonimmediate reactions. Among those reacting to the GOC, 12.5% reacted with mild cutaneous reactions to cephalexin challenge. CONCLUSIONS: Direct GOCs are an accurate and safe confirmatory to establish true hypersensitivity among children reporting benign reactions to amoxicillin.