CUTANEOUS ADVERSE DRUG REACTIONS IN CHILDREN: AN ANALYSIS OF REPORTS FROM THE CANADIAN PHARMACOGENOMICS NETWORK FOR DRUG SAFETY (CPNDS)
Main Article Content
Keywords
Adverse drug reactions, cutaneous, skin reaction, surveillance, children, pharmacovigilance
Abstract
Cutaneous adverse drug reactions (CADRs) are the most prevalent adverse drug reactions (ADRs) in hospitalized children, with an estimated rate of 2-3%. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) is a pan-Canadian active surveillance network identifying genomic biomarkers of risk for serious ADRs. The purpose of this paper is to describe the characteristics of paediatric CADR cases reported to the CPNDS from February 2005 to December 2008. The CPNDS database was mined and details of CADRs and key clinical data from cases were extracted. Reports were individually analyzed and classified in two main groups: severe and non-severe CADRs, with subcategories. In total, 326 CADR cases were included in the study; 214 (65.6%) severe and 112 (34.4%) non-severe CADRs. Overall L-asparaginase (n=56, 16%), amoxicillin (n=29, 8.3%), cotrimoxazole (n=25, 7.2%), carbamazepine (n=17, 4.9%) and lamotrigine (n=13, 3.7%) accounted for 40% of all suspected medications. We have demonstrated the ability to comprehensively collect clinical data on a wide range of severe and non-severe CADRs to drugs commonly used in the care of children. Our study provides additional real world evidence to promote the proactive detection, collection, reporting and assessment of CADRs in children.
References
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3. Gonzalez-Martin G, Caroca CM, Paris E. Adverse drug reactions (ADRs) in hospitalized pediatric patients. A prospective study. International Journal of Clinical Pharmacology and Therapeutics 1998 Oct; 36(10):530-3.
4. Martinez-Mir I, Garcia-Lopez M, Palop V, Ferrer JM, Rubio E, Morales-Olivas FJ. A prospective study of adverse drug reactions in hospitalized children. British Journal of Clinical Pharmacology 1999 Jun;47(6):681-8.
5. Gruchalla RS, Beltrani VS. Drug-induced cutaneous reactions. In: Leung DYM, Greaves MW, eds. Allergic Skin Disease: A Multidisciplinary Approach. [place of publication unknown]: Informa Healthcare 2000;307-309.
6. Bordet R, Gautier S, Louet HL, et al. Analysis of the direct cost of adverse drug reactions in hospitalized patients. Eur J Clin Pharmacol 2001; 56:935-941.
7. Kushwaha KP, Verma RB, Singh YD, et al. Surveillance of drug induced diseases in children. Indian J Pediatr 1994; 61:357-365.
8. Dos Santos BD, Coelho HLL. Adverse drug reactions in hospitalized children in Fortalez, Brazil. Pharmacoepidemiol Drug Saf 2006; 15:635-640.
9. Kidon MI, See Y. Adverse drug reactions in Singapore children. Sing Med J 2004;45:574- 577.
10. Bigby M, Jick S, Jick H, Arndt K. Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,238 consecutive inpatients, 1975 to 1982. JAMA 1986;256:3358-3363.
11. Stewart RB, May FE, Cullen SI. Dermatologic adverse drug reactions in hospitalized patients. Am J Hosp Pharm 1979;36:609-612.
12. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331 (19):1272-1285.
13. Johnson ML, Johnson KG, Engel A. Prevalence, morbidity, and cost of dermatologic diseases. J Am Acad Dermatol 1984;11:930-936.
14. Härmark L, van Grootheest AC. Pharmacovigilance: methods, recent developments and future perspectives. Euro J Clin Pharmacol 2008;64(8):743-752.
15. Ross CJ, Carleton B, Warn DG, Stenton SB, Rassekh SR, Hayden MR. Genotypic approaches to therapy in children: A national active surveillance network (GATC) to study the pharmacogenomics of severe adverse drug reactions in children. Annals of the New York Academy of Sciences 2007 Sep11;10:177-92.
16. Carleton BC, Poole RL, Smith MA, Leeder JS, Ghannadan R, Ross CJD, Phillips MS, Hayden MR. Adverse drug reaction active surveillance: developing a national network in Canada’s children’s hospitals. Pharmacoepidemiol Drug Saf 2009. Published Online: Jun 8 2009.
17. Wolff K, Johnson RA, Suurmond D: Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology, 5th Edition. Available at: http://www.accessmedicine.com/content.aspx?aI D=754605 Accessed: April 2009.
18. Leaute-Labreze C, Lamireau T, Chawki D, Maleville J, Taieb A. Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome. Arch Dis Child 2000; 83(4): 347-52.
19. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, Auquier A, Bastuji-Garin S, Correia O, Locati F, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333(24):1600-7.
20. Wolkenstein PE, Roujeau JC, Revuz J. Druginduced Toxic Epidermal Necrolysis. Clinics in Dermatology 1998;16:399-409.
21. Segal AR, Doherty KM, Leggott J, Zlotoff B. Cutaneous reactions to drugs in children. Pediatrics 2007;120:e1082-1096.
22. Cotliar J. Approach to the patient with a suspected drug eruption. Semin Cutan Med Surg 2007;26:147-154.
23. Rook's Textbook of Dermatology 7th Edition. Edited by D.A. Burns, S.M. Breathnach, Neil Cox, and Christopher E. Griffiths. Oxford, England ; Blackwell Publishing ; 2004.
24. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.
25. The use of the WHO-UMC system for standardized case causality assessment [monograph on the Internet]. Uppsala: The Uppsala Monitoring Centre; 2005. Available from: http://www.who-umc.org/graphics/4409.pdf. [cited on 2009 June].
26. Greinix HT, Pohlreich D, Maalouf J, et al. A single-centered pilot validation study of a new chronic GVHD skin scoring system. Biology of Blood and Marrow Transplantation 2007; 13(6):715-723.
27. WHO (2009) WHO Collaboration Centre for Drug Statistics Methodology. ATC/DDD index 2009. Available at: http://www.whocc.no/atcddd/ Accessed June, 2009.
28. Planchamp F, Nguyen KA, Vial T, Nasri S, Javouhey E, Gillet Y, Ranchin B, Villard F, Floret D, Cochat P, Gueyffier F, Kassai B, Groupe de travail pharmacovigilance en pediatrie. Active drug monitoring of adverse drug reactions in pediatric emergency department. Archives de Pediatrie 2009;16(2): 106-11.
29. Haffner S, von Laue N, Wirth S, Thurmann PA. Detecting adverse drug reactions on paediatric wards: intensified surveillance versus computerised screening of laboratory values. Drug Safety 2005;28(5):453-64.
30. Salvo F, Polimeni G, Cutroneo PM, Leone R, Confortic A, Moretti U, Motola D, Tuccori M, Caputi AP. Allergic reactions to oral drugs: A case/non-case study from an Italian spontaneous reporting database (GIF). Pharmacological Research 2008;58(3-4):202-207.
31. Naldi L, Conforti A, Venegoni M, Troncon MG, Caputi A, Ghiotto E, Cocci A, Moretti U, Velo G, Leone R. Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions. Br J Clin Pharmacol 1999;48:839-846.
32. Lange L, Koningsbruggen SV, Rietschel E. Questionnaire-based survey of lifetimeprevalence and character of allergic drug reactions in German children. Pediatr Allergy Immunol 2008;19:634-638.
33. Orhan F, Karakas T, Cakir M, Akkol N, Bahat E, Sonmez FM, Gedik Y. Parental-reported drug allergy in 6- to 9-yr-old urban schoolchildren. Pediatric Allergy & Immunology 2008;19(1): 82-5.
34. Levi N, Bastuji-Garin S, Mockenhaupt M, Roujeau JC, Flahault A, Kelly JP, Martin E, Kaufman DW, Maison P. Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: A pooled analysis. Pediatrics 2009;123(2):e297-304.
35. Pirmohamed M. Genetic factors in the predisposition to drug-induced hypersensitivity reactions. AAPS J 2006;8(1):e20-26.
36. Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, Sidoroff A, Schneck J, Roujeau JC, Flahault A. Stevens- Johnson syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 2008; 128(1):35-44.
37. Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, Naldi L, Bouwes-Bavinck JN, Sidoroff A, de Toma C, Schumacher M, Roujeau JC, Hovnanian A, Mockenhaupt M; for the RegiSCAR study group. A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 2008;18(2): 99-107.
38. Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, LeLouet H, Graf E, Schumacher M, Hovnanian A, Mockenhaupt M, Roujeau JC; RegiSCAR Group. A marker for Stevens- Johnson syndrome: Ethnicity matters. Pharmacogenomics J 2006;6(4):265-8.
39. Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau JC; SCAR Study Group. Severe Cutaneous Adverse Reactions. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol 2002;138(8): 1019-24.
40. Bousquet PJ, Demoly P, Romano A, Aberer W, Bircher A, Blanca M, Brockow K, et al. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GA2LEN platform. The Galenda project. Allergy 2009;64:194-203.
41. Buajordet I, Wesenberg F, Brors O, Langslet A. Adverse drug events in children during hospitalization and after discharge in a Norwegian university hospital. Acta Paediatrica 2002; 91(1): 88-94.
42. Mitchell AA, Lacouture PG, Sheehan JE, Kauffman RE, Shapiro S. Adverse drug reactions in children leading to hospital admission. Pediatrics 1988;82(1):24-9.
43. Sanborn RE, Sauer DA. Cutaneous reactions to chemotherapy: commonly seen, less described, little understood. Dermatol Clin 2008;26:103- 119.
44. Wyatt AJ, Leonard GD, Sachs DL. Cutaneous reactions to chemotherapy and their management. Am J Clin Dermatol 2006;7(1): 45-63.
45. Soyer OU, Aytac S, Tuncer A, Cetin M, Yetgin S, Sekerel BE. Alternative algorithm for Lasparaginase allergy in children with acute lymphoblastic leukaemia. J Allergy Clin Immunol 2009;123: 895-9.
46. Graham ML. Pegaspargase: a review of clinical studies. Advanced Drug Delivery Reviews 2003; 55:1293-1302.
47. DeShazo RD, Kemp SF. Allergic reactions to drugs and biologic agents. JAMA 1997;278: 1895–1906.
48. Khotaei GT, Fattahi F, Pourpak Z, Moinfar Z, Aghaee FM, Gholami K, Moin M. Adverse reactions to antibiotics in hospitalized Iranian children. Journal of Microbiology, Immunology & Infection 2008; 41(2):160-4.
49. Morales-Olivas FJ, Martinez-Mir I, Ferrer JM, Rubio E, Palop V. Adverse drug reactions in children reported by means of the yellow card in Spain. Journal of Clinical Epidemiology 2000; 53(10): 1076-80.
50. Cutroneo PM, Arcoraci V, Cucinotta G, Inferrera G, Galante F, Sofia A, Ferrera E, Napolitano T, Mazzaglia G, Caputi AP. Adverse drug reactions in childhood. A drug surveillance study in Sicily. Recenti Progressi in Medicina 1998; 89(6):290-5.
51. Salvo F, Polimeni G, Moretti U, Conforti A, Leone R, Leoni O, Motola D, Dusi G, Caputi AP. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. Journal of Antimicrobial Chemotherapy 2007; 60(1):121-6.
52. Levine LR. Quantitative comparison of adverse reactions to cefaclor vs. amoxicillin in a surveillance study. Pediatr Infect Dis 1985;4: 358-361.
53. Ibia EO, Schwartz RH, Wiedermann BL. Antibiotic rashes in children. A survey in a private practice setting. Arch Dermatol 2000; 136:849-854.
54. Hernandez-Salazar A, Rosales SP, Rangel- Frausto S, Criollo E, Archer-Dubon C, Orozco- Topete R. Epidemiology of adverse cutaneous drug reactions. A prospective study in hospitalized patients. Archives of Medical Research 2006;37(7):899-902.
55. Macy E. Multiple antibiotic allergy syndrome. Immunol Allergy Clin North Am 2004;24:533- 43.
56. Park J, Matsui D, Rieder MJ. Multiple antibiotic sensitivity syndrome in children. Can J Clin Pharmacol 2000;7(1):e38-41.
57. Sharma VK, Dhar S. Clinical pattern of cutaneous drug eruption among children and adolescents in north India. Pediatric Dermatology 1995;12(2):178-83.
58. Martin-Munoz F, Moreno-Ancillo A, Dominguez-Noche C, Diaz-Pena JM, Garcia- Ara C, Boyano T, Ojeda JA. Evaluation of drugrelated hypersensitivity reactions in children. Journal of Investigational Allergology & Clinical Immunology 1999;9(3):172-7.
59. Khoo BP, Giam YC. Drug eruptions in children: a review of 111 cases seen in a tertiary skin referral centre. Singapore Med J 2000;41(11): 525-529.
60. Arif H, Buchsbaum R, Weintraub D, Koyfman S, Salas-Humara C, Bazil CW, Resor SR, Hirsch LJ. Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology 2007;68: 1701-1709.
61. Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in paediatric in/out-patients: a systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol 2001; 52:77-83.
62. Davies EC, Green CF, Mottram DR, Pirmohamed M. Adverse Drug Reactions in Hospitals: A Narrative Review. Current Drug Safety 2007;2:79-87.
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