학술논문
Retrospective study on the association of human herpesvirus reactivation with severe DRESS: A description of blood and skin reactivations.
Document Type
Academic Journal
Author
Marcombes C; Department of Dermatology, AP-HP, Bichat Hospital, Paris, France.; Ingen-Housz-Oro S; Department of Dermatology, AP-HP, Henri-Mondor Hospital, Créteil, France.; Reference Center for Toxic Bullous Dermatoses and Severe Drug Reactions TOXIBUL, Créteil, France.; Epiderme, Paris Est Créteil University, Créteil, France.; FISARD Study Group (French Investigators for Skin Adverse Reactions to Drugs) of the French Dermatology Society, Paris, France.; Dezoteux F; FISARD Study Group (French Investigators for Skin Adverse Reactions to Drugs) of the French Dermatology Society, Paris, France.; Department of Dermatology, CHU Lille, Univ Lille, INSERM U1286, Lille Inflammation Translational Research Institute (INFINITE), Lille, France.; Staumont-Sallé D; FISARD Study Group (French Investigators for Skin Adverse Reactions to Drugs) of the French Dermatology Society, Paris, France.; Department of Dermatology, CHU Lille, Univ Lille, INSERM U1286, Lille Inflammation Translational Research Institute (INFINITE), Lille, France.; Milpied B; Reference Center for Toxic Bullous Dermatoses and Severe Drug Reactions TOXIBUL, Créteil, France.; FISARD Study Group (French Investigators for Skin Adverse Reactions to Drugs) of the French Dermatology Society, Paris, France.; Department of Dermatology, UHC Bordeaux, Bordeaux, France.; Tetart F; Reference Center for Toxic Bullous Dermatoses and Severe Drug Reactions TOXIBUL, Créteil, France.; FISARD Study Group (French Investigators for Skin Adverse Reactions to Drugs) of the French Dermatology Society, Paris, France.; Department of Dermatology, UHC Rouen, Rouen, France.; de Prost N; Reference Center for Toxic Bullous Dermatoses and Severe Drug Reactions TOXIBUL, Créteil, France.; Intensive Care Unit, AP-HP, Henri-Mondor Hospital, Créteil, France.; Fourati S; Virology Department, AP-HP, Henri-Mondor Hospital, Créteil, France.; Ortonne N; Department of Pathology, Henri-Mondor Hospital, Créteil, France.; Kasimir F; Institute for Virology and Immunobiology, Julius-Maximilians-UniversitätWürzburg, Würzburg, Germany.; Prusty BK; Institute for Virology and Immunobiology, Julius-Maximilians-UniversitätWürzburg, Würzburg, Germany.; Descamps V; Department of Dermatology, AP-HP, Bichat Hospital, Paris, France.; FISARD Study Group (French Investigators for Skin Adverse Reactions to Drugs) of the French Dermatology Society, Paris, France.
Source
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9216037 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-3083 (Electronic) Linking ISSN: 09269959 NLM ISO Abbreviation: J Eur Acad Dermatol Venereol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe adverse event (mortality of 10%). Its pathophysiology involves herpesviruses, particularly HHV-6, but the exact mechanisms are still poorly understood.
Objective: To describe severe cases of DRESS and especially their association with herpesvirus reactivation.
Methods: This study was a multicentre case series conducted between 2007 and 2021 at five University Hospital Centres in France. The study included patients who had severe DRESS, which was defined as death, transfer to the intensive care unit (ICU), or severe damage to internal organs. We excluded patients without blood PCR sample, without a drug formally attributed or with RegiSCAR score < 6. We collected data on severity, causative drug, associated visceral damage and results of viral blood PCRs. HHV-6 reactivation was studied in skin biopsies by detection of small non-coding transcripts (HHV-6 miR-aU14) and a late viral protein (GP82/105).
Results: Fifty-two patients were included (29 female, median age 62, interquartile range (IQR) [37;72]). Eight patients (15%) died, 13 (27%) were admitted to ICU. Most patients (n = 34; 65%) had multisystem involvement: most frequent was liver (n = 46; 88%), then renal failure (n = 24; 46%). Forty patients (77%) had at least one blood viral reactivation among HHV-6, EBV or CMV, of which 21 (53%) had at least two. Median time of blood HHV-6 reactivation was 24 days (IQR [20;35]). HHV-6 reactivation was demonstrated in 15 out of 20 skin biopsies, with a median time of 11 days [9;17].
Conclusions: We confirmed the high rate of HHV-6 reactivation in severe DRESS and demonstrated cutaneous HHV-6 reactivation using small non-coding transcripts (HHV-6 miR-aU14), which preceded viral PCR positivity in blood. These results suggest that HHV-6 reactivation during DRESS may start in skin. Furthermore, search for miR-aU14 in skin biopsy could become a useful diagnostic tool for early detection of HHV-6 reactivation.
(© 2023 European Academy of Dermatology and Venereology.)
Objective: To describe severe cases of DRESS and especially their association with herpesvirus reactivation.
Methods: This study was a multicentre case series conducted between 2007 and 2021 at five University Hospital Centres in France. The study included patients who had severe DRESS, which was defined as death, transfer to the intensive care unit (ICU), or severe damage to internal organs. We excluded patients without blood PCR sample, without a drug formally attributed or with RegiSCAR score < 6. We collected data on severity, causative drug, associated visceral damage and results of viral blood PCRs. HHV-6 reactivation was studied in skin biopsies by detection of small non-coding transcripts (HHV-6 miR-aU14) and a late viral protein (GP82/105).
Results: Fifty-two patients were included (29 female, median age 62, interquartile range (IQR) [37;72]). Eight patients (15%) died, 13 (27%) were admitted to ICU. Most patients (n = 34; 65%) had multisystem involvement: most frequent was liver (n = 46; 88%), then renal failure (n = 24; 46%). Forty patients (77%) had at least one blood viral reactivation among HHV-6, EBV or CMV, of which 21 (53%) had at least two. Median time of blood HHV-6 reactivation was 24 days (IQR [20;35]). HHV-6 reactivation was demonstrated in 15 out of 20 skin biopsies, with a median time of 11 days [9;17].
Conclusions: We confirmed the high rate of HHV-6 reactivation in severe DRESS and demonstrated cutaneous HHV-6 reactivation using small non-coding transcripts (HHV-6 miR-aU14), which preceded viral PCR positivity in blood. These results suggest that HHV-6 reactivation during DRESS may start in skin. Furthermore, search for miR-aU14 in skin biopsy could become a useful diagnostic tool for early detection of HHV-6 reactivation.
(© 2023 European Academy of Dermatology and Venereology.)