Introduction: Toxic epidermal necrolysis (TEN) is a life-threatening adverse drug reaction (ADR) that is primarily the result of drug exposure (incidence 0.4–1.3 per million person-years). Life-threatening ADRs such as TEN should be reported to ADR monitoring programmes, which collect reports for suspected ADRs and alert the public and medical practitioners to new drug hazards. In Canada, reports are made to the Canadian Adverse Drug Reaction Monitoring Program (CADRMP).
Objective: To examine the extent of under-reporting for TEN in Canada.
Design: A retrospective case series design was used to collect all TEN cases for the period January 1995 to December 2000.
Methods: The CADRMP and 22 burn centres across Canada were contacted for all TEN patients treated during the specified time period.
Patient Groups Studied: The study population consisted of patients admitted to burn treatment sites across Canada, patient cases reported to the CADRMP and patient cases recorded by the Canadian Institute for Health Information (CIHI) hospital discharge summaries as the International Classification of Diseases Version 9 Clinical Modification (ICD-9-CM) code 695.1.
Results: Twenty-five TEN cases (six fatal) were reported to CADRMP from January 1995 to December 2000. During this period, 14 (63.6%) burn treatment sites reported admission of 250 TEN cases. Hospital discharge summaries using the ICD-9-CM code 695.1 indicated that 4349 cases were admitted to hospital during this time period and it was estimated that 15.5% (n = 674) of these cases were TEN. Using the burn facility data as the denominator, 10% (25 of 250) of TEN cases were reported to CADRMP. Using CIHI data as a denominator, only 4% (25 of 674) of TEN cases were reported to CADRMP.
Conclusions: There is serious under-reporting of TEN. Lack of reporting of life-threatening ADRs can compromise population safety. There is a need to increase awareness of ADR reporting programmes.
Roujeau J, Guillaume J, Fabre J, et al. Toxic epidermal necrolysis (Lyell syndrome): incidence and drug etiology in France, 1981-1985. Arch Dermatol 1990; 126: 37–42PubMedCrossRefGoogle Scholar
Schopf E, Stuhmer A, Rzany B, et al. Toxic epidermal necrolysis and Steven’s Johnson syndrome: an epidemiologic study from West Germany. Arch Dermatol 1991; 127: 839–42PubMedCrossRefGoogle Scholar
Chan H, Stern R, Arndt K, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis: a population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990; 126: 43–7PubMedCrossRefGoogle Scholar
Palmieri T, Greenhalgh D, Saffle J, et al. A multicentre review of toxic epidermal necrolysis treated in US burn centres at the end of the twentieth century. J Burn Care Rehabil 2002; 23: 87–96PubMedCrossRefGoogle Scholar
Revuz J, Penso D, Roujeau J, et al. Toxic epidermal necrolysis: clinical findings and prognosis factors in 87 patients. Arch Dermatol 1987; 123: 1160–5PubMedCrossRefGoogle Scholar
Heimach D, Engrav L, Marvin J, et al. Toxic epidermal necrolysis: a step forward in treatment. JAMA 1987; 257: 2171–5CrossRefGoogle Scholar
Halebian P, Madden M, Finkelstein J, et al. Improved burn centre survival of patients with toxic epidermal necrolysis managed without corticosteroids. Ann Surg 1986; 204: 503–12PubMedCrossRefGoogle Scholar
Stern R, Chan H. Usefulness of case report literature in determining drugs responsible for toxic epidermal necrolysis. J Am Acad Dermatol 1989; 21: 317–22PubMedCrossRefGoogle Scholar
Roujeau J, Kelly J, Naldi L, et al. Medication use and risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333: 1600–7PubMedCrossRefGoogle Scholar
MEDWATCH. The clinical impact of adverse event reporting. Washington, DC: Department of Health and Human Services, 1996Google Scholar
Naranjo C, Busto U. Adverse drug reactions. In: Kalant H, Roschlau W, editors. Principles in medical pharmacology. 5th ed. Toronto: BC Decker, 1989: 658–65Google Scholar
Canadian Institute for Health Information (CIHI) [online]. Available from URL: http://www.cihi.ca [Accessed 2004 Apr]Google Scholar
Statistics Canada, Population Estimates [online]. Available from URL: http://www.statcan [Accessed 2004 Apr 21]. ca/Daily/English/00 0926, 2000Google Scholar
Health Canada. Canadian adverse drug reaction newsletter. Ottawa (ON): Therapeutic Products Programme, 2003Google Scholar
US FDA Annual Adverse Drug Experiences Report 1996 [online]. Available from URL: http://www.fda.gov/medwatch/articles.htm [Accessed 2004 Apr]Google Scholar
Venning G. Identification of adverse reactions to new drugs III: altering process and early warning. BMJ 1983; 286: 458–60PubMedCrossRefGoogle Scholar
Capella D, Laporte J, Vidal X, et al. European network for the case-population surveillance of rare disease (Euronet): a prospective feasibility study. Eur J Clin Pharmacol 1998; 53: 299–302PubMedCrossRefGoogle Scholar
Mockenhaupt M, Schopf E. Epidemiology of drug-induced severe skin reactions. Semin Cutan Med Surg 1996; 15(4): 236–43PubMedCrossRefGoogle Scholar
Meyboom R, Egberts A, Edwards I, et al. Principles of signal detection on Pharmacovigilance. Drug Saf 1997; 16(6): 355–65PubMedCrossRefGoogle Scholar
Olsson S. The role of the WHO programme on international drug monitoring in coordinating world-wide drug safety efforts. Drug Saf 1998; 19(1): 1–10PubMedCrossRefGoogle Scholar
Ionnidis J, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA 2001; 285: 437–43CrossRefGoogle Scholar
Inman W. Study of fatal bone marrow depression with special reference to phenylbutazone and oxybutazone. BMJ 1977; 1: 1500–5PubMedCrossRefGoogle Scholar
Scott H, Rosenbaum S, Waters W, et al. Rhode Island physician’s recognition and reporting of adverse drug reactions. R I Med J 1987; 70: 311–6PubMedGoogle Scholar
Alvarez-Requejo A, Carvajal A, Begaud B, et al. Under-reporting of adverse drug reactions: estimate based on a spontaneous reporting scheme and a sentinel system. Eur J Clin Pharm 1998; 54: 483–8CrossRefGoogle Scholar
Moride Y, Haramburu F, Requejo A, et al. Under-reporting of adverse drug reactions in general practice. Br J Clin Pharmacol 1997; 43: 177–81PubMedCrossRefGoogle Scholar
Belton K. Attitude survey of adverse drug-reaction reporting by healthcare professionals across the European Union. Eur J Clin Pharm 1997; 52(6): 423–7CrossRefGoogle Scholar
LaCalamita S. Top 10 reasons for not reporting adverse drug reactions. Hosp Pharm 1995; 30(3): 245–6PubMedGoogle Scholar
Colodny L, Spillane J. Toward increased reporting of adverse drug reactions. Hosp Pharm 1999; 34(10): 1179–85Google Scholar
Mittmann N, Liu BA, Iskedjian M, et al. Drug-related deaths in Canada (1984-1994). Pharmacoepidemiol Drug Saf 1997; 6: 157–68PubMedCrossRefGoogle Scholar
Statistics Canada Population, 2000 [online]. Available from URL: http://www.statcan [Accessed 2004 Apr 21]Google Scholar