Accepted Article
Received Date : 16-Aug-2014 Accepted Date : 23-Oct-2014 Article type
: Original Article: Experimental Allergy and Immunology
Editor
: Pascal Demoly
Title: Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria
Short Title: Aspirin hypersensitive children with chronic urticaria
Ozlem Cavkaytar, Ebru Arik Yilmaz, Betul Buyuktiryaki, Bulent E. Sekerel, Cansin Sackesen, *Ozge U. Soyer Hacettepe University, School of Medicine, Department of Pediatric Allergy
Corresponding author: *
Assoc. Prof. Ozge Uysal Soyer, MD Hacettepe University School of Medicine Department of Pediatric Allergy 06100, Ankara, Turkey Tel: +90 312 3051700 Fax: +90 312 3112357 e-mail: [email protected]
Challenge-Proven Aspirin Hypersensitivity in Children with Chronic Spontaneous Urticaria
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/all.12539 This article is protected by copyright. All rights reserved.
Accepted Article
Abstract Background:NSAIDs-exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define “aspirin hypersensitive” children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Methods:Eighty-one children with an history of CSU were enrolled over a three year period. The daily, or almost daily (>4 days a week) presence of urticaria was defined as “chronic persistent urticaria” (CPU), while presence of urticaria for 2–4 days a week was defined as “chronic recurrent urticaria” (CRU). Single blind placebo controlled provocation tests (SBPCPT)s with aspirin were performed for children with CSU. Results:Patients with CRU had a longer duration of cutaneous symptoms [1.6(0.5–4) vs. 0.6(0.3–1.5) years] and stress was less frequently experienced as an eliciting factor in patients with CRU compared to the patients with CPU (p2 points (moderate to severe urticaria). All the above mentioned clinical, demographical variables and laboratory values were compared between the two groups. The follow-up time was defined as the follow-up period during which patients-were regularly examined for ongoing symptoms in our department after aspirin challenge. At the last follow-up visit, patients were asked if they had any exposure to any of the drugs that may be cross-reactive to aspirin (8). Additionally, they were asked about the frequency of appearance of residual urticarial plaques, which was defined as the ‘frequency of residual symptoms’. This study was approved by the Ethics Committee of the Hacettepe University Medical Faculty, and parents and children provided written informed consent. Details of the diagnosis of asthma and allergic rhinitis are given in the ‘Supplementary Methods’ section.
Study measurements Oral provocation test with aspirin SBPCPT with aspirin was performed under medical supervision in a clinical setting and the patients were observed for an additional six hours. Then, the patients were taught about the symptoms of having a positive provocation test and admitted again in case of the occurrence of allergic symptoms within 24 hours. The baseline forced expiratory volume in one second (FEV1) was measured by spirometry for all the patients older than five years of age. On the first day of the challenge protocol, four placebo capsules were administered at 1.5 hour intervals; additionally, FEV1 was measured 30 minutes before and after each consecutive dose. If the patient had no exacerbation of cutaneous lesions and stayed in a stable clinical condition, the challenge continued on the second day with the ingestion of capsules containing aspirin in a single blind fashion. Aspirin was administered at four exponentially increasing doses (27 mg, 44 mg, 117 mg, 312 mg) (19) until the cumulative dose of 10 mg/kg (the usual pediatric dose for pain or fever) (20) or the maximum dose of 500 mg was reached. The oral provocation test (OPT) was recorded as positive if one of the following clinical reactions took place (19) :i) unequivocal worsening of urticaria (defined as pruritic and erythematous areas raised over
This article is protected by copyright. All rights reserved.
Accepted Article
normal skin) ii) apparent angioedema (defined as swelling of the skin and/or external mucosa), iii) a minimum 15% decrease in FEV1 on spirometry and iv) extracutaneous symptoms and signs (rhinorrhea, nasal congestion, conjunctivitis or bronchospasms). In vivo and in vitro tests are detailed in the methods section of ‘Supporting Information’.
Statistical Analysis All statistical analysis was performed using SPSS 21 software program (SPSS, Inc.-Chicago, Illinois, USA). Descriptive data for categorical variables was expressed as frequencies and numerical variables as mean (±standard deviation) or median (interquartile range) according to normal or non-normal distribution respectively. Group comparisons were constructed by using the ANOVA or KruskalWallis test for normally or non-normally distributed numerical variables respectively, and by the chisquare test or the Fisher test for categorical variables. A p value
Received Date : 16-Aug-2014 Accepted Date : 23-Oct-2014 Article type
: Original Article: Experimental Allergy and Immunology
Editor
: Pascal Demoly
Title: Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria
Short Title: Aspirin hypersensitive children with chronic urticaria
Ozlem Cavkaytar, Ebru Arik Yilmaz, Betul Buyuktiryaki, Bulent E. Sekerel, Cansin Sackesen, *Ozge U. Soyer Hacettepe University, School of Medicine, Department of Pediatric Allergy
Corresponding author: *
Assoc. Prof. Ozge Uysal Soyer, MD Hacettepe University School of Medicine Department of Pediatric Allergy 06100, Ankara, Turkey Tel: +90 312 3051700 Fax: +90 312 3112357 e-mail: [email protected]
Challenge-Proven Aspirin Hypersensitivity in Children with Chronic Spontaneous Urticaria
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/all.12539 This article is protected by copyright. All rights reserved.
Accepted Article
Abstract Background:NSAIDs-exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define “aspirin hypersensitive” children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Methods:Eighty-one children with an history of CSU were enrolled over a three year period. The daily, or almost daily (>4 days a week) presence of urticaria was defined as “chronic persistent urticaria” (CPU), while presence of urticaria for 2–4 days a week was defined as “chronic recurrent urticaria” (CRU). Single blind placebo controlled provocation tests (SBPCPT)s with aspirin were performed for children with CSU. Results:Patients with CRU had a longer duration of cutaneous symptoms [1.6(0.5–4) vs. 0.6(0.3–1.5) years] and stress was less frequently experienced as an eliciting factor in patients with CRU compared to the patients with CPU (p2 points (moderate to severe urticaria). All the above mentioned clinical, demographical variables and laboratory values were compared between the two groups. The follow-up time was defined as the follow-up period during which patients-were regularly examined for ongoing symptoms in our department after aspirin challenge. At the last follow-up visit, patients were asked if they had any exposure to any of the drugs that may be cross-reactive to aspirin (8). Additionally, they were asked about the frequency of appearance of residual urticarial plaques, which was defined as the ‘frequency of residual symptoms’. This study was approved by the Ethics Committee of the Hacettepe University Medical Faculty, and parents and children provided written informed consent. Details of the diagnosis of asthma and allergic rhinitis are given in the ‘Supplementary Methods’ section.
Study measurements Oral provocation test with aspirin SBPCPT with aspirin was performed under medical supervision in a clinical setting and the patients were observed for an additional six hours. Then, the patients were taught about the symptoms of having a positive provocation test and admitted again in case of the occurrence of allergic symptoms within 24 hours. The baseline forced expiratory volume in one second (FEV1) was measured by spirometry for all the patients older than five years of age. On the first day of the challenge protocol, four placebo capsules were administered at 1.5 hour intervals; additionally, FEV1 was measured 30 minutes before and after each consecutive dose. If the patient had no exacerbation of cutaneous lesions and stayed in a stable clinical condition, the challenge continued on the second day with the ingestion of capsules containing aspirin in a single blind fashion. Aspirin was administered at four exponentially increasing doses (27 mg, 44 mg, 117 mg, 312 mg) (19) until the cumulative dose of 10 mg/kg (the usual pediatric dose for pain or fever) (20) or the maximum dose of 500 mg was reached. The oral provocation test (OPT) was recorded as positive if one of the following clinical reactions took place (19) :i) unequivocal worsening of urticaria (defined as pruritic and erythematous areas raised over
This article is protected by copyright. All rights reserved.
Accepted Article
normal skin) ii) apparent angioedema (defined as swelling of the skin and/or external mucosa), iii) a minimum 15% decrease in FEV1 on spirometry and iv) extracutaneous symptoms and signs (rhinorrhea, nasal congestion, conjunctivitis or bronchospasms). In vivo and in vitro tests are detailed in the methods section of ‘Supporting Information’.
Statistical Analysis All statistical analysis was performed using SPSS 21 software program (SPSS, Inc.-Chicago, Illinois, USA). Descriptive data for categorical variables was expressed as frequencies and numerical variables as mean (±standard deviation) or median (interquartile range) according to normal or non-normal distribution respectively. Group comparisons were constructed by using the ANOVA or KruskalWallis test for normally or non-normally distributed numerical variables respectively, and by the chisquare test or the Fisher test for categorical variables. A p value
