Journal Article10.1111/BJD.18942
The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms.
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TL;DR: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug‐induced immune response and the exact role of IP‐10 in DRESS and Stevens–Johnson syndrome/toxic epidermal necrolysis (TEN) has remained unknown.
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Abstract: BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug-induced immune response. Previous reports have found that CXCL10, also known as interferon-γ-induced protein (IP)-10, may participate in the pathogenesis of cutaneous adverse drug reactions. However, the exact role of IP-10 in DRESS and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) has remained unknown. OBJECTIVES This comparative prospective cohort study aimed to ascertain the roles of the IP-10/CXCR3 axis in DRESS and SJS/TEN. METHODS Plasma IP-10 levels were analysed, and univariate analyses were conducted to assess the relationship between IP-10, human herpesvirus (HHV)-6 reactivation and the development of long-term sequelae. We also performed immunohistochemical staining using skin specimens and flow cytometry to determine the expression of CXCR3 in peripheral blood mononuclear cells (PBMCs). RESULTS Significantly higher plasma IP-10 levels were observed in patients with DRESS with long-term sequelae (effect size 0·81) and also in those with HHV-6 reactivation (effect size 0·83). By immunohistochemistry, more abundant IP-10+ and CXCR3+ cells were demonstrated in the skin lesions of patients with DRESS with HHV-6 reactivation. The percentages of CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were also higher in the PBMCs of HHV-6-reactivated patients with DRESS than in those of patients with SJS/TEN. CONCLUSIONS Higher plasma IP-10 levels are associated with the development of long-term sequelae in DRESS. Higher IP-10/CXCR3 expression in skin and more abundant CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were observed in patients with DRESS with HHV-6 reactivation. The IP-10/CXCR3 axis is associated with HHV-6 reactivation and development of long-term sequelae in DRESS. What is already known about this topic? Elevated levels of interferon-γ-induced protein-10 (IP-10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Patients with DRESS tend to develop long-term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP-10 has been associated with these autoimmune diseases in previous studies. What does this study add? The patients with DRESS with HHV-6 reactivation exhibited higher levels of IP-10 in the plasma and skin than the patients with DRESS without HHV-6 reactivation and the patients with SJS/TEN. Patients with DRESS with higher plasma IP-10 levels tended to develop sequelae during long-term follow-up. What is the translational message? IP-10 is a useful biomarker to predict the development of long-term sequelae in patients with DRESS. Linked Comment: Belloon and Kardaun. Br J Dermatol 2020; 183:804-805.
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Citations
Current Perspective Regarding the Immunopathogenesis of Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms (DIHS/DRESS).
Fumi Miyagawa,Hideo Asada +1 more
TL;DR: A recent review as mentioned in this paper describes the clinical features of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) including complications and sequelae, and discusses recent advances in understanding of the immunopathogenic mechanisms of DIHS/drESS.
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Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles.
Vivian E. Saper,Michael J. Ombrello,Adriana H. Tremoulet,Gonzalo Montero-Martín,Sampath Prahalad,Scott W. Canna,Chisato Shimizu,Gail H. Deutsch,Serena Y Tan,Elaine F. Remmers,Dimitri S. Monos,Timothy Hahn,Omkar Phadke,Elaine Cassidy,Ian Ferguson,Vamsee Mallajosyula,Jianpeng Xu,Jaime S. Rosa Duque,Gilbert T. Chua,Debopam Ghosh,Ann Marie Szymanski,Danielle Rubin,Jane C. Burns,Lu Tian,Marcelo Fernandez-Vina,Elizabeth D. Mellins,Jill A. Hollenbach +26 more
TL;DR: In this article, a case/control study of patients with Still's disease with severe delayed hypersensitivity reaction (DRESS) was conducted, where they were treated with IL-1/IL-6 inhibitors and associated with common HLA-DRB1*15 haplotypes.
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A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?
TL;DR: Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, it is suggested a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities.
Drug-induced Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms. Part I. Epidemiology, Pathogenesis, Clinicopathological Features, and Prognosis.
Brian M. Wei,Lindy P. Fox,Benjamin H. Kaffenberger,Abraham Korman,Robert G. Micheletti,Arash Mostaghimi,Megan H. Noe,Misha Rosenbach,Kanade Shinkai,Jason Kwah,Elizabeth J. Phillips,Jean L. Bolognia,William Damsky,Caroline A. Nelson +13 more
TL;DR: This continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.
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Advances in understanding of the pathogenesis and therapeutic implications of drug reaction with eosinophilia and systemic symptoms: an updated review
TL;DR: In this paper , the authors provided an update on the current understanding of the pathogenesis, potential biomarkers, and the relevant therapeutic rationales of DRESS/DIHS, and some predictors of disease severity and prognosis were also reported.
References
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TL;DR: A case of SCAR is reported in an 86-year-old patient probably induced by allopurinol and simultaneously fulfilling the diagnostic criteria for DRESS and SJS, thus considered as an overlapping case ofSCARs.
SCORTEN: A Severity-of-Illness Score for Toxic Epidermal Necrolysis
Sylvie Bastuji-Garin,Nathalie Fouchard,M Bertocchi,Jean-Claude Roujeau,Jean Revuz,Pierre Wolkenstein +5 more
TL;DR: It is demonstrated that the risk of death of toxic epidermal necrolysis patients can be accurately predicted by the toxic epidescent severity-of-illness score, and the Simplified Acute Physiology Score and burn score appear to be less adequate.
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CXCR3 in T cell function.
Joanna R Groom,Andrew D. Luster +1 more
TL;DR: CXCR3 is a chemokine receptor that is highly expressed on effector T cells and plays an important role in T cell trafficking and function, facilitating the interaction of T cells with antigen presenting cells leading to the generation of effector and memory cells.
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Variability in the clinical pattern of cutaneous side‐effects of drugs with systemic symptoms: does a DRESS syndrome really exist?
S. H. Kardaun,A. Sidoroff,L. Valeyrie-Allanore,Sima Halevy,Batya Davidovici,M. Mockenhaupt,Jean-Claude Roujeau +6 more
TL;DR: Nicorandil may be associated with gastrointestinal ulceration and perforation of the terminal ileum: a possible complication of nicor andil therapy.
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Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis
Wen-Hung Chung,Wen-Hung Chung,Shuen-Iu Hung,Shuen-Iu Hung,Jui-Yung Yang,Shih-Chi Su,Shien-Ping Huang,Chun-Yu Wei,See-Wen Chin,Chien-Chun Chiou,Sung-Chao Chu,Hsin-Chun Ho,Chih-Hsun Yang,Chi-Fang Lu,Jer-Yuarn Wu,You-Di Liao,Yuan-Tsong Chen,Yuan-Tsong Chen +17 more
TL;DR: It is demonstrated that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS-TEN and this work highlights a mechanism for CTL- or NK cell—mediated cytotoxicity that does not require direct cellular contact.