Skin recruitment of monomyeloid precursors involves human herpesvirus‐6 reactivation in drug allergy

Hashizume, Hideo; Fujiyama, Toshiharu; Kanebayashi, J; Kito, Yukiko; Hata, Maki; Yanagimoto, Hiroaki

doi:10.1111/all.12138

Cited by 30 publications

(28 citation statements)

References 36 publications

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“…Hashizume et al . also found that monomyeloid precursor cells harboring HHV‐6 are navigated by high‐mobility group box‐1, which is a crucial event for HHV‐6 reactivation in skin lesion of DIHS patients …”

Section: Environmental and Non‐genetic Factorsmentioning

confidence: 84%

Severe cutaneous adverse drug reactions

Chung

Wang

Dao

2016

The Journal of Dermatology

184

163

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The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved.

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Section: Environmental and Non‐genetic Factorsmentioning

confidence: 84%

Severe cutaneous adverse drug reactions

Chung

Wang

Dao

2016

The Journal of Dermatology

184

163

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“…Monomyeloid cells are one of the reservoirs of latent HHV-6 infection in humans [106]. One previous study has shown that circulating CD11b + CD13 + CD14 − CD16 high monomyeloid precursor cells in patients with DRESS syndrome, or DiHS, harboring HHV-6 express a skin homing molecule, C-C motif chemokine receptor (CCR) 4 [107]. These circulating monomyeloid precursors respond to high-mobility group box (HMGB)-1, which has been found in high levels in the skin and blood in patients with DRESS syndrome [108], and then infiltrate into the skin.…”

Section: Pathomechanismsmentioning

confidence: 99%

“…These circulating monomyeloid precursors respond to high-mobility group box (HMGB)-1, which has been found in high levels in the skin and blood in patients with DRESS syndrome [108], and then infiltrate into the skin. These skin-infiltrated monomyeloid precursor cells may then transmit HHV-6 to skin resident CD4 + T cells [107]. CD4 + T cells in the acute phase of DRESS syndrome, or DiHS, have been found to express a higher level of CD134, which is a cellular receptor for HHV-6, than those in SJS and MPE [109].…”

Section: Pathomechanismsmentioning

confidence: 99%

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

Cho

Yang

Chu

2017

IJMS

212

276

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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.

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“…It is possible that herpes virus reactivation, most notably HHV-6, was the common underlying factor for the multiple drug reactions [38][39][40][41][42], although that was not proven in our case. We conclude that the HLA-B*58 haplotype may be a risk factor for drug hypersensitivity syndrome with imatinib therapy in patients who react to allopurinol, but this needs to be confirmed in further studies.…”

Section: Discussionmentioning

confidence: 68%

Multiple Drug Induced Hypersensitivity Syndrome Reactions in a Patient with Drugs that Have Known HLA Associations for Reactions

Khan¹,

Bhartia²,

S³

2014

General Med

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We report a rare case of a patient with chronic myeloid leukaemia (CML) who had severe drug hypersensitivity reactions with not only allopurinol and imatinib therapies for the CML, but also to a non-steroidal anti-inflammatory drug and an antibiotic. Each of the drugs (allopurinol and imatinib) when used alone, and in combination, had caused various combinations of fever (hyperpyrexia), rash and/or generalized edema. The patient had the HLA-B*58 haplotype that is associated with allopurinol induced Steven-Johnson syndrome. However, in our case, imatinib alone also caused a similar reaction. We discuss the other 'at-risk' HLA alleles and known drug reactions and that our patient was unfortunate to have all of these HLA alleles. Further studies are required to confirm whether the HLA-B*58 haplotype is a risk factor for imatinib induced adverse cutaneous drug reactions.

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Skin recruitment of monomyeloid precursors involves human herpesvirus‐6 reactivation in drug allergy

Cited by 30 publications

References 36 publications

Severe cutaneous adverse drug reactions

Severe cutaneous adverse drug reactions

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

Multiple Drug Induced Hypersensitivity Syndrome Reactions in a Patient with Drugs that Have Known HLA Associations for Reactions

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