Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study

TLDR

Cases of severe drug hypersensitivity, including drug reaction with eosinophilia and systemic symptoms (DRESS), present a variable spectrum of cutaneous and systemic manifestations. The study used RegiSCAR, a multinational registry that prospectively enrolled 201 potential cases from 2003 to mid‑2009, to analyze the spectrum of signs and symptoms of DRESS and the distribution of causative drugs. Among 117 validated DRESS cases, the syndrome was characterized by a high prevalence of eosinophilia (95%), visceral involvement (91%), fever (90%), and atypical lymphocytes (67%), with a protracted course in nearly all patients, an 88 % plausibility of drug causality (most commonly antiepileptics 35 %, allopurinol 18 %), a median onset of 22 days, and a mortality rate lower than previously reported.

Abstract

Cases of severe drug hypersensitivity, demonstrating a variable spectrum of cutaneous and systemic involvement, are reported under various names, especially drug reaction with eosinophilia and systemic symptoms (DRESS). Case definition and overlap with other severe cutaneous adverse reactions (SCAR) are debated.To analyse the spectrum of signs and symptoms of DRESS and distribution of causative drugs in a large multicentre series.RegiSCAR, a multinational registry of SCAR, prospectively enrolled 201 potential cases from 2003 to mid-2009. Using a standardized scoring system, 117 cases were validated as showing probable or definite DRESS.The male/female ratio was 0.80; females were borderline significantly younger than males. Next to the ubiquitous exanthema, the main features were eosinophilia (95%), visceral involvement (91%), high fever (90%), atypical lymphocytes (67%), mild mucosal involvement (56%) and lymphadenopathy (54%). The reaction was protracted in all but two patients; two patients died during the acute phase. Drug causality was plausible in 88% of cases. Antiepileptic drugs were involved in 35%, allopurinol in 18%, antimicrobial sulfonamides and dapsone in 12% and other antibiotics in 11%. The median time interval after drug intake was 22 days (interquartile range 17-31) for all drugs with (very) probable causality, with differences between drugs.This prospective observational study supports the hypothesis that DRESS is an original phenotype among SCAR in terms of clinical and biological characteristics, causative drugs, and time relation. The diversity of causative drugs was rather limited, and mortality was lower than that suggested by prior publications.