Histopathological Characterization of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Comparison with Maculopapular Drug Rash (MPDR)

INTRODUCTION: Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction (cADR) associated with significant systemic involvement and greater mortality. Variable patterns of inflammation are reported in the histopathology of DRESS. However, the role of histopathology in predicting systemic involvement and thus final outcome remains elusive. In the present study, we aim to review clinical and histopathological characteristics of patients with DRESS and compare their histopathology with that of maculopapular drug rash. MATERIALS AND METHODS: A retrospective analysis of cases of cADRs diagnosed from July 2014 to July 2020 at a single tertiary care institute was performed. A RegiSCAR score of ≥4 was used to recruit patients as DRESS. Patients with a probable/definite diagnosis of cADR on the basis of Naranjo criteria and presenting with exanthem attaining a RegiSCAR score of ≤3 were categorized as MPDR. Correlation of histopathology characteristics with the investigative profile of patients with DRESS was done. MPDR and DRESS were also compared for histopathological characteristics using Chi-square test. Further histopathology of patients with drug rash (both DRESS and MPDR) having systemic involvement was compared with those without systemic involvement to identify specific predictors. RESULTS: Eighteen patients of DRESS and 20 of MPDR fulfilled the inclusion criteria. Most common drugs implicated were anticonvulsants (27.8%). Characteristic findings seen on histopathology in patients with DRESS were epidermal spongiosis (94.5%), epidermal dyskeratosis (33.3%), lymphocytic exocytosis (88.9%), interface vacuolization (77.8%), papillary dermal edema (100%). and perivascular lymphocytic infiltrate (100%). Findings in favor of DRESS compared to MPDR were lymphocytic exocytosis (P < 0.001), interface vacuolization (P = 0.002), severe spongiosis (P = 0.046), severe papillary dermal edema (P = 0.018), and higher density of dermal infiltrate (P = 0.005). Lymphocyte exocytosis and distribution and density of dermal inflammatory infiltrate correlated significantly with deranged kidney function. CONCLUSION: Histopathology revealing prominent basal vacuolization, spongiosis, and dense dermal infiltrate suggests DRESS. Lymphocyte exocytosis and distribution and density of dermal inflammatory infiltrate predict renal involvement.