Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Supplementary online-material Supplementary Table S1: Detailed descriptive analysis regarding patient management Supplementary Table S2: Pre-selected variables and their definitions for the main analysis Supplementary Table S3: Definitions of SJS/TEN-specialised units and other dermatologic units per country 1
Supplementary Table S1: Detailed descriptive analysis regarding patient management other countries Overall n=120 n=263 n=59 n=442 treating unit 1 (frequency, percentage) dermatologic unit SJS/TEN-specialised unit thereof with prior stay on a dermatologic unit other unit (only) delay between onset of reaction and admission to (in days) (median, range) hospital (any unit) (n=442) dermatologic unit (n=178) (including patients further transferred) SJS/TEN-specialised unit (n=150) delay between admission to dermatologic unit and further transfer to specialised unit (n= 21) (median, range) therapies 2 (per drug) corticosteroids intraveus immuglobulins ciclosporin any other immumodulating drug 3 therapy combinations 2 (per patient) supportive therapy only corticosteroids only intraveus immuglobulins only ciclosporin only combination of drugs 4 33 (28%) 61 (51%) 4 ( 7%) 26 (22%) 102 (39%) 76 (29%) 17 (22%) 85 (32%) 22 (37%) 13 (22%) 0 ( 0%) 24 (41%) 157 (36%) 150 (34%) 21 (14%) 135 (31%) 3 (0-18) 2 (0-20) 2 (0-23) 2 (0-23) 4 (0-12) 4 (0-20) 4 (1-15) 4 (0-20) 5 (2-19) 5 (1-26) 7 (1-23) 5 (1-26) 3 (2-5) 2 (1-9) - 2 ( 1-9) 33 (28%) 249 (95%) 35 (59%) 317 (72%) 12 (10%) 52 (20%) 17 (29%) 81 (18%) 17 (14%) 1 ( 0%) 1 ( 2%) 19 ( 4%) 1 ( 1%) 4 ( 2%) 0 ( 0%) 5 ( 1%) 66 (55%) 12 ( 5%) 19 (32%) 97 (22%) 25 (21%) 196 (75%) 23 (39%) 244 (55%) 6 ( 5%) 2 ( 1%) 5 ( 8%) 13 ( 3%) 15 (12%) 0 ( 0%) 0 ( 0%) 15 ( 3%) 8 ( 7%) 53 (20%) 12 (20%) 73 (17%) 1 see supplementary table S3 for a description of variable definition 2 therapy: any immumodulating drug started at/after onset of reaction or, if administered before, when dosage/frequency was increased 3 any other immumodulating drug: daclizumab+etanercept (1), hydroxylcarbamide (1), infliximab (3) 4 combination of drugs: corticosteroids + 1 other immumodulating drug (68), corticosteroids + 2 other immumodulating drugs (5) 2
Supplementary Table S2: Pre-selected variables and their definitions for the main analysis variable (including explanation) levels missing values (%) 1 HR for death (95%CI) 2 country other countries 2.1 (1.3-3.2) 2.1 (1.2-3.7) age in years 4 (1.03-1.05) (at time of reaction) gender male female 0.87 (0.63-1.20) development of reaction (onset of reaction before hospitalisation, community in-hospital 2.6 (1.9-3.6) onset of reaction during hospitalisation due to ather disease) severity of reaction (defined by the extent of skin detachment related to the body surface are: SJS <10%, SJS/TEN overlap 10-30%, TEN >30%) SJS SJS/TEN overlap TEN 2.1 (1.5-3.1) 2.9 (1.9-4.6) severe liver disorder [n=51] including liver dysfunction/failure [21], liver steatosis/cirrhosis [17], viral 3.1 (2.1-4.7) hepatitis [8], tumour/metastases [3], amyloidosis [1], autoimmune liver disorders [1] severe kidney disorder [n=56] including (chronic) renal insufficiency/failure (including diabetic neuropathy) 2 1.0 3.8 (2.7-5.6) [45], acute renal failure (before onset of reaction) [9], amyloidosis [1], autoimmune kidney disorders [1] collagen-vascular disorder [n=27] 3 including rheumatoid arthritis [13], systemic lupus erythematosus [5], 0.99 (0.48-2.02) systemic scleroderma [4], connective tissue disease [2], psoriasis arthropathica [2], ankylosing spondylitis [1], Morbus Wegener [1] recent malignancy [n=72] 4 diagsis of any malignant disorder diagsed within the last two years or 4 1.0 2.6 (1.8-3.7) still under treatment; including primary CNS tumours [13], urogenital cancer [13], hematologic malignancies [12], breast cancer [10], ENT carcima [6], lung cancer [6], gastrointestinal-tract cancer [5], cancer of unkwn primary [4], melama [3], sarcoma [2], Merkel cell carcima [1] HIV infection [n=20] (assuming HIV infection even if recent serology test was available) - 1.0 1.3 (0.6-3.0) (continued) 3
recent infection [n=78] 5 present in 4 weeks before start of reaction, excluding long-lasting infections, n-severe/n-promoting infections, infections with start within 3 days before onset of the reaction; - respiratory tract infection [40] (including pneumonia, acute bronchitis, influenza/-like illness, infectious exacerbated COPD, pneumocystosis) - septicaemia, before onset of reaction [11] - CNS infection [8] (including cerebral toxoplasmosis, meningitis, ventriculitis) - miscellaneous infection [6] (including fever of unkwn origin) - tuberculosis [4] (including open, closed, and lymph de tuberculosis) - bone infection [3] (including coxitis, implant infection) - gastrointestinal infection [3] (including pseudomembraus colitis induced by clostridium difficile toxins, peritonitis) - heart infection [3] (including endocarditis) - viral infection [2] (including acute cytomegalovirus infection, infectious monucleosis) - ENT infection [1] (including ethmoiditis/spheiditis) - skin infection [1] (including psoas abscess) - urogenital infection [1] (including pyonephrosis) 5 1.0 2.2 (1.5-3.2) recent radiation therapy [n=36] (radiation therapy for any reason within the last three months) 1.7 (1.1-2.9) prior steroid use [n=96] (steroid use in the week before onset) 1 1.0 2.0 (1.4-2.9) 1: proportion of missing values in follow-up cohort of 460 patients 2: univariable hazard ratios (HR) and 95% confidence interval (95%CI) based on complete case analysis 3: 1 patient had two different collagen-vascular disorders (rheumatoid arthritis+systemic lupus erythematosus) 4: 3 patients had recent malignancies at two different sites (breast+hematologic, breast+urogenital, hematologic+urogenital) 5: 5 patients had two infections CNS: central nervous system; ENT: ears, se, throat 4
Supplementary Table S3: Definitions of SJS/TEN-specialised units and other dermatologic units per country country SJS/TEN-specialised unit* dermatologic unit Austria any burn unit; any ICU at a university hospital any dermatologic unit any burn unit; dermatologic unit or ICU at the Hospital Henri Mondor, Creteil any burn unit; any ICU at a university hospital; any ICU with dermatologic consultation dermatologic unit at any hospital except Hospital Henri Mondor, Creteil any dermatologic unit Israel any ICU at a university hospital with dermatologic consultation any dermatologic unit Italy any burn unit; any ICU at a university hospital any dermatologic unit Netherlands any burn unit; dermatologic unit at the University Medical Center Groningen (UMCG); any unit with specialised supervision by UMCG dermatologic unit at any hospital except UMCG ICU: intensive care unit * SJS/TEN-specialised unit: In addition to the country-specific definition, 5 or more cases had to be treated in the unit over the whole study period in order to distinguish units with more practical experience from other units that only provide technical facility. 5