Table 3.

Summary of epidemiological studies on severe cutaneous adverse reactions (SCAR)

Year	Author	Type of study	Period of study	Country	Number of cases	Age (range)	Sex F : M	Systemic manifestations	Causes	Outcome measures
1986	Guillaume et al. [6]	Prospective, TEN	13 years	France	87	Unknown	Unknown	Unknown	Sulfonamides (20.7%) – sulfamethoxazole/trimethoprim (67%)Anticonvulsants (8%) – barbiturates and carbamazepine only NSAIDs (33.3%) -phenylbutazone, oxicam derivatives Allopurinol (3.4%) Chlormezanone (3.4%)	Unknown
1990	Chan et al. [79]	Retrospective, EM/SJS/TEN	14 years	United States	37 EM/SJS /TEN	Unknown	Unknown	Unknown	43% attributed to drugs Drug therapies with reaction rates in excess of 1 per 100 000 exposed individuals include phenobarbital (20 per 100 000), nitrofurantoin (7 per 100 000), sulfamethoxazole and trimethoprim, and ampicillin (both 3 per 100 000), and amoxicillin (2 per 100 000).	Incidence of TEN alone due to all causes was 0.5 per 106 person-years. Incidence of EM, SJS, or TEN associated with drug use were 7.0, 1.8, and 9.0 per 106 person-years, respectively, for persons younger than 20 years of age, 20 to 64 years of age, and 65 years of age and older.
1990	Schopf et al.[81]	Retrospective, SJS/TEN	5 years	Germany	259 TEN 315 SJS	Mean age 63 years (TEN); 25 years (SJS)	TEN: 2:1; SJS: 1:2	Unknown	Antibiotics (TEN, 40%; SJS, 34%) Analgesics (TEN, 23%; SJS, 33%)	TEN: Annual risk of 0.93 per million, mortality 34%SJS: Annual risk 1.1 per million, mortality 1%
1990	Roujeau et al.[82]	Retrospective, TEN	5 years	France	399 TEN	Unknown	Unknown	Unknown	Sulfadiazine Isoxicam Oxyphenbutazone Phenytoin Fenbufen Cotrimoxazole	Incidence 1.2 cases per million per year
1993	Leenutaphong et al.[84]	Retrospective, SJS and TEN	9 years	Thailand	Total = 7858 SJS, 20 TEN	Unknown	Unknown	Unknown	Antibiotics (41%) – penicillin, sulfonamides, tetracycline, erythromycin Anticonvulsants (11.5%) – phenytoin, carbamazepine barbiturates Antitubercular drugs (10.3%) – thiacetazone	Mortality rate 14%; 40% TEN, 5% SJS
1995	Roujeau et al. [85]	Retrospective, Case-control study	4 years	France, Germany, Italy, and Portugal	Total = 245 SJS 89 SJS-TEN overlap 76 TEN 80	Unknown	Unknown	Unknown	Sulfonamides, trimethoprim-sulfamethoxazole Carbamazepine Oxicam NSAIDs Chlormezanone Phenytoin Allopurinol	Unknown
1996	Rzany et al. [86]	Retrospective, dZh German population-based registry for severe skin reactions.	2 years 8 months	Germany	SJS 139 SJS-TEN overlap 95 TEN 56	Unknown	Unknown	Unknown	Unknown	Incidence of SJS/TEN Up to 1.89 per 1 million inhabitants per year
1998	Kamaliah et al. [87]	Retrospective, EM/SJS/TEN (EM excluded in this table)	8 years	East Malaysia	Total = 2522 SJS, 3 TEN	19 adult and 6 paediatric Paed: 10 month–12 years Adult: 15–65 years	0.73:1	Fever (62.1%) Leukocytosis (34.5%) Hepatitis (31%)	Antibiotics (36%) Cotrimoxazole Ampicillin/amoxicillin Anticonvulsants (32%) Allopurinol (4%)	Mortality: TEN 37.3%, SJS 4.5%
1999	Wong et al. [87]	Retrospective, SJS/TEN	12 years	Australia	Total = 1710 SJS, 7 TEN	Mean age 61.5 years	0.5:1	Unknown	Betalactam antibiotics (52.9%)	Mortality: 28.6% TEN 10% SJS
2007	Gerdts et al. [89]	Retrospective	15 years	The Netherlands	19	Adult and paediatric Mean age 45.6 ± 23.9 years (5–70)	1.6:1	Unknown	Anticonvulsants – phenytoin/ carbamazepine (36.8%) Amoxicillin (10.5%)	Mortality (15.8%)
2007	Yamane et al. [90]	Retrospective, all cases published from Japan	6 years	Japan	Total = 11752 SJS, 65 TEN	SJS: mean 45.2 years TEN: mean 45.7 years	SJS 1.7:1 TEN	Hepatitis (55.6%) Respiratory (25.6%) Renal dysfunction (19.7%)	Anticonvulsants (17.9%) Antibiotics (17.1%) NSAIDs (12.8%)	Mortality: SJS 1.9% TEN 6.2%
2008	Sharma et al. [91]	Retrospective	3 years	India	Total = 3015 TEN, 9 SJS-TEN overlap and 6 SJS	Paediatric and adult Mean age 22.3 ± 15.4 years (4–65)	1.2:1	Haematological (86.7%) Hepatitis (36.7%) Renal (13.3%) Pnemonitis (10%)	Anticonvulsants (35.1%) – phenytoin 45%, carbamazepine 30%Antibiotics (33.3%) – cephalosporins 26% NSAIDS (24.6%).	Mortality 16.7% 13.3% TEN, 3.3% SJS-TEN overlap
2008	Mockenhaupt et al. [92]	Retrospective, case-control (EuroSCAR)	Unknown	Europe	Total = 379 134 SJS, 136 SJS/TEN-overlap, 109 TEN	Paediatric and adult Median 50 years (IQR 28–68) (1–95)	1.6:1	Unknown	Nevirapine Lamotrigine Carbamazepine Phenytoin Phenobarbital Cotrimoxazole and other anti-infective sulfonamides Sulfasalazine Allopurinol Oxicam-NSAIDs	Unknown
2010	Wetter et al. [93]	Retrospective	8 years	United States	27 SJS	Paediatric and adult Mean 28.1 ± 22.3 years	0.7:1	Fever (70%) Hepatitis (37%) Leukocytosis (22%)	74% drug related Antibiotics (35%) – cotrimoxazole Anticonvulsants (35%) – phenytoin, lamotrigine NSAID (10%)	Mortality 5%