title: Drug reaction with eosinophilia and systemic symptoms (DRESS): a multiorgan antiviral T cell response.
abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, drug-induced reaction that involves both the skin and the viscera. Evidence for reactivation of herpes family viruses has been seen in some DRESS patients. To understand the immunological components of DRESS and their relationship to viral reactivation, we prospectively assessed 40 patients exhibiting DRESS in response to carbamazepine, allopurinol, or sulfamethoxazole. Peripheral blood T lymphocytes from the patients were evaluated for phenotype, cytokine secretion, and repertoire of CD4+ and CD8+ and for viral reactivation. We found Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), or HHV-7 reactivation in 76% of the patients. In all patients, circulating CD8+ T lymphocytes were activated, exhibited increased cutaneous homing markers, and secreted large amounts of tumor necrosis factor-alpha and interferon-gamma. The production of these cytokines was particularly high in patients with the most severe visceral involvement. In addition, expanded populations of CD8+ T lymphocytes sharing the same T cell receptor repertoire were detected in the blood, skin, liver, and lungs of patients. Nearly half of these expanded blood CD8+ T lymphocytes specifically recognized one of several EBV epitopes. Finally, we found that the culprit drugs triggered the production of EBV in patients' EBV-transformed B lymphocytes. Thus, cutaneous and visceral symptoms of DRESS are mediated by activated CD8+ T lymphocytes, which are largely directed against herpes viruses such as EBV.
authors.affiliation: INSERM U905, Rouen University Hospital, Rouen 76000, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Picard
authors.forename: Baptiste
authors.initials: B
authors.lastname: Janela
authors.forename: Vincent
authors.initials: V
authors.lastname: Descamps
authors.forename: Michel
authors.initials: M
authors.lastname: D'Incan
authors.forename: Philippe
authors.initials: P
authors.lastname: Courville
authors.forename: Serge
authors.initials: S
authors.lastname: Jacquot
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rogez
authors.forename: Laurent
authors.initials: L
authors.lastname: Mardivirin
authors.forename: Hélène
authors.initials: H
authors.lastname: Moins-Teisserenc
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Jacques
authors.initials: J
authors.lastname: Benichou
authors.forename: Pascal
authors.initials: P
authors.lastname: Joly
authors.forename: Philippe
authors.initials: P
authors.lastname: Musette
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004802:Eosinophilia / Q000139:chemically induced*; D000939:Epitopes / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology; D016199:Herpesvirus 7, Human / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D000939:Epitopes