Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multiorgan hypersensitivity reaction mostly caused by a limited number of eliciting drugs in patients with a genetic predisposition. Patients with DRESS syndrome present with characteristic but variable clinical and pathological features. Reactivation of human herpesviruses (HHV), especially HHV-6, is the hallmark of the disease. Anti-viral immune responses intertwined with drug hypersensitivity make the disease more complicated and protracted. In recent years, emerging studies have outlined the disease more clearly, though several important questions remain unresolved. In this review, we provide an overview of DRESS syndrome, including clinical presentations, histopathological features, pathomechanisms, and treatments.

Keywords: drug reaction with eosinophilia and systemic symptoms; drug-induced hypersensitivity syndrome; histopathology; human herpesviruses-6; pathogenesis; prognosis; treatment.

Figure 1

Cutaneous presentations in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. (a) Widespread purpuric papules and plaques on the trunk and limbs; (b) Infiltrative lesions on the trunk; (c) Facial edema with peri-orbital sparing; (d) Erosions on the lips; (e) Desquamation in the stage of resolution.

Figure 2

Clinical courses of patients with DRESS syndrome.

Figure 3

Histopathological patterns in skin lesions of patients with DRESS syndrome. (a) Spongiosis with focal subcorneal pustules; (b) Erythema multiforme-like interface dermatitis: basal vacuolar change and multiple scattered apoptotic keratinocytes in the epidermis; (c) Lichenoid dermatitis: prominent infiltrations of cells in the upper dermis and basal vacuolar change; (d) Vascular damage: perivascular infiltration with prominent endothelial cells, red blood cell extravasation, and some extent of vessel wall damage, resembling a feature of lymphocytic vasculitis; (e) Leukocytoclastic vasculitis: frank fibrinoid necrosis, leukocytoclasia, and red blood cell extravasation; and (f) Superficial perivascular dermatitis. All panels were prepared using H&E stain, with a magnification of 200×. Scale bar = 50 μm

Figure 4

Possible pathomechanisms of DRESS syndrome. Drugs or their metabolites (a) may accumulate in some persons due to altered activity of metabolizing enzymes; (b) Evoking drug-specific T lymphocytes in persons with certain genetic backgrounds; (c) Causing the clinical presentations of DRESS syndrome; On the other hand, (d) viral reactivations, which result from a direct effect of the inciting drugs or their metabolites or from a “cytokine storm” caused by anti-drug immune responses; and (e) May induce robust anti-viral responses contributing to the development of the disease.