Uncovering histologic criteria with prognostic significance in toxic epidermal necrolysis

Objective: To identify histologic criteria and prognostic significance in patients with toxic epidermal necrolysis (TEN), a frequently lethal disease that usually represents an adverse drug reaction. Design: Retrospective analysis of clinical records and histologic material from a 10-year period (1994-2004). Two investigators blinded to clinical data reviewed hematoxylin-eosin-stained sections. Setting: North American tertiary care, universitybased burn unit. Patients: Thirty-seven patients treated for TEN between 1994 and 2004 who had sloughing of 30% or more of their total body surface area and who underwent skin punch biopsies immediately following admission. Main Outcome Measure: The degree of dermal mononuclear (DM) inflammation was graded (sparse, moderate, or extensive) at least 2 high-power fields (HPF) away from the perimeter of epidermal detachment, and the mean number of DM cells/5 HPF was quantified for each patient. Clinical records were reviewed and the following data extracted: age, history of cancer, percentage of total body surface area slough, heart rate, and serum glucose, bicarbonate, and serum urea nitrogen values on admission. Severity scores for TEN (SCORTEN) were calculated, and clinical outcome was recorded as survived or died during hospitalization. Results: Extent of inflammation was assessed by categorizing the mean±SD DM cell counts as follows: sparse, 161±36 cells/HPF (n=15); moderate, 273 ±76 cells/HPF (n=15); and extensive, 392±124 cells/HPF (n=7). There was good concordance between observer ratings (P<.001). While 73% of patients (n=11) with sparse inflammation survived, only 47% (n=7) with moderate and 29% (n=2) with extensive inflammation survived. The accuracy in predicting patient outcome was 65% using grade of inflammation, 68% with mean cell count, and 71% with SCORTEN. Conclusions: There is a histologic spectrum with TEN that ranges from sparse to extensive DM inflammation, and degree of inflammation predicts clinical outcome approximately as well as SCORTEN. Future clinical trials should consider the possibility that various patient subsets exist within the TEN population, and a role for immunocytes needs to be critically reevaluated in this devastating disease.