title: Incidence, causative factors and mortality rates of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in northern Italy: data from the REACT registry.
abstract: OBJECTIVE
  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions. We assessed incidence, drug exposure and mortality, analysing data obtained from the Lombardy Registry of Severe Cutaneous Reactions (REACT).
  
  
  METHODS
  Data were collected from hospitals in the Italian Lombardy region (9,502,272 people). A trained monitor was sent to the reporting hospital to collect data on drug exposure and clinical features. The algorithm for drug causality for epidermal necrolysis algorithm was applied to assess drug causality. Defined Daily Dose (DDD) was used to express drug consumption.
  
  
  RESULTS
  From April 2009 to November 2014, 17 cases of TEN and 59 cases of SJS were collected. The overall incidence rate was 1.40 cases (95%CI, 1.12-1.76) per million people per year. A total of 15 cases died during hospitalization with a mortality rate of 16.9% for SJS and 29.4% for TEN. Overall, 55.4% of cases had a probable or very probable relation with drug exposure. In a total of five patients (6.6%), no causative drug for the reaction was identifiable. Allopurinol contributed to the highest number of cases (23 cases), while the highest incidence based on more than one case reported was observed for cotrimoxazole and lamotrigine, with 5.37 cases (95%CI, 2.09-13.80) and 3.54 (95%CI, 1.21-10.42) per 10 million DDD/year, respectively.
  
  
  CONCLUSIONS
  We confirmed that SJS and TEN are rare adverse cutaneous reactions. As expected, mortality was influenced by the degree of skin detachment. The profile of drugs associated with the reactions was in agreement with data from other surveillance systems.
authors.affiliation: Department of Dermatology, Papa Giovanni XXIII Hospital, Bergamo, Italy.|Centro Studi GISED, Bergamo, Italy.|Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Janouk
authors.initials: J
authors.lastname: Diphoorn
authors.affiliation: Centro Studi GISED, Bergamo, Italy.|Department of Dermatology, Inselspital University Hospital, Bern, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Cazzaniga
authors.affiliation: Department of Dermatology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gamba
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milano, Italy.
authors.forename: Jan
authors.initials: J
authors.lastname: Schroeder
authors.affiliation: Burn/Intensive Care Department, Niguarda Ca' Granda Hospital, Milano, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Citterio
authors.affiliation: Regional Center of Pharmacovigilance, Lombardy Region, Milano, Italy.
authors.forename: Alma Lisa
authors.initials: AL
authors.lastname: Rivolta
authors.affiliation: Quality, Privacy and Clinical Risk Unit, Niguarda Ca' Granda Hospital, Milano, Italy.
authors.forename: Giuseppe Danilo
authors.initials: GD
authors.lastname: Vighi
authors.affiliation: Department of Dermatology, Papa Giovanni XXIII Hospital, Bergamo, Italy.|Centro Studi GISED, Bergamo, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldi
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000639:trends*; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D012042:Registries; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis / Q000401:mortality*; D014227:Triazines / Q000009:adverse effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D014227:Triazines; D000493:Allopurinol; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000077213:Lamotrigine
keywords: Stevens-Johnson syndrome (SJS); causal factors/aetiology; incidence; mortality; pharmacoepidemiology; pharmacovigilance; toxic epidermal necrolysis (TEN)