Histopathology of drug rash with eosinophilia and systemic symptoms syndrome: a morphological and phenotypical study

Background The histopathological features of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome remain poorly characterized. Objectives To better characterize the histopathological features of DRESS syndrome, and define the phenotype of the effector cells in the skin and compare it with maculopapular rash (MPR). Methods We conducted a retrospective study on 50 skin biopsies from patients with DRESS syndrome (n = 36). Histopathological and immunophenotypical features were studied and compared with a series of MPRs (n = 20). Results Foci of interface dermatitis, involving cutaneous adnexae, were frequently seen in cases of DRESS. Eosinophils were seen in only 20% of cases and neutrophils in 42%. Eczematous (40%), interface dermatitis (74%), acute generalized exanthematic pustulosis-like (20%) and erythema multiforme-like (24%) patterns were observed. The association of two or three of these patterns in a single biopsy was significantly more frequent in cases of DRESS than in a series of nondrug-induced dermatoses (P < 0.01), and appeared to be more marked in DRESS syndrome with severe cutaneous lesions (P = 0.01) than in less severe cases of DRESS and MPR. A higher proportion of CD8(+) and granzyme B+ lymphocytes was observed in cases of DRESS with severe cutaneous eruptions (erythroderma and/or bullae). Atypical lymphocytes were found in 28% of biopsies, and expressed CD8 in most cases; a cutaneous T-cell clone was rarely found (6%). Conclusions The histopathology of DRESS syndrome highlights various associated inflammatory patterns in a single biopsy. Cutaneous effector lymphocytes comprise a high proportion of polyclonal CD8(+) granzyme B+ T lymphocytes.