Elevated serum thymus and activation-regulated chemokine (TARC/CCL17) relates to reactivation of human herpesvirus 6 in drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS)

Ogawa, Kohei; Morito, Hironori; Hasegawa, Ayako; Miyagawa, Fumi; Kobayashi, Nobuhiko; Watanabe, Hideaki; Sueki, Hirohiko; Tohyama, Mikiko; Hashimoto, Koji; Kano, Yoko; Shiohara, Tetsuo; Ito, Kenichi; Fujita, Hiroyuki; Aihara, Michiko; Asada, Hideo

doi:10.1111/bjd.12948

Cited by 45 publications

(42 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…LTG contains a triazine ring that is metabolized at the 2-position by UGT to form a quaternary ammonium glucuronide. Moreover, both previous investigations 19,20 and our own suggest that elevated serum TARC levels during the early stage of disease is a useful marker for early recognition of HHV-6 reactivation. 29 It has therefore been hypothesized that unmetabolized LTG is the cause of the ADR.…”

Section: Discussionsupporting

confidence: 50%

“…19,20 In our patients, mean serum TARC levels were significantly lower in the LTG group than in the UD group (4442.0 AE 1027.8 vs 14 736.3 AE 3334.6 pg/mL, P < 0.05; Fig. 19,20 In our patients, mean serum TARC levels were significantly lower in the LTG group than in the UD group (4442.0 AE 1027.8 vs 14 736.3 AE 3334.6 pg/mL, P < 0.05; Fig.…”

Section: Dihs/dress-related Serum Tarc/ccl17 Levels Are Significantlymentioning

confidence: 99%

See 1 more Smart Citation

Drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs

Tashiro

Azukizawa

Asada

et al. 2019

The Journal of Dermatology

View full text Add to dashboard Cite

Drug‐induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multi‐organ systemic drug reaction characterized by hematological abnormalities and reactivation of human herpesvirus‐6 (HHV‐6). DIHS/DRESS is typically associated with a limited number of drugs, such as the anticonvulsants. Our group has treated 12 patients for DIHS/DRESS due to lamotrigine (LTG), but their presentation differed from that of patients with DIHS/DRESS caused by other drugs. The aim of the present study was to identify significant differences between DIHS/DRESS caused by LTG versus other drugs. We retrospectively reviewed data of 12 patients with DIHS/DRESS caused by LTG and 32 patients with DIHS/DRESS due to other drugs. The increase in alanine aminotransferase level was significantly milder in the LTG group than the DIHS/DRESS group due to other drugs. The percentage of atypical lymphocytes in the blood during DIHS/DRESS was lower in the LTG group. Serum levels of lactate dehydrogenase and thymus and activation‐regulated chemokine were also lower in the LTG group. There were fewer DIHS/DRESS patients with HHV‐6 reactivation in the LTG group than in the group treated with other drugs. Lymphocyte transformation after DIHS/DRESS onset was faster in the LTG group. The two groups did not differ with respect to the interval from first drug intake to rash, white blood cell count, blood eosinophilia or DRESS score. There were no significant histopathological differences between the two groups. The features of LTG‐associated DIHS/DRESS and DIHS/DRESS due to other drugs differ.

show abstract

Section: Discussionsupporting

confidence: 50%

Section: Dihs/dress-related Serum Tarc/ccl17 Levels Are Significantlymentioning

confidence: 99%

Drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs

Tashiro

Azukizawa

Asada

et al. 2019

The Journal of Dermatology

View full text Add to dashboard Cite

show abstract

“…This reduced number of pDCs in circulation has been thought to be related to the reactivation of viruses [113]. In addition, serum thymus and activation-regulated chemokine (TARC) levels are markedly elevated in the acute stage of DRESS syndrome, or DiHS [115,116]. The levels of TARC are even significantly higher in those with HHV-6 reactivation than in those without HHV-6 reactivation [115].…”

Section: Pathomechanismsmentioning

confidence: 99%

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

Cho

Yang

Chu

2017

IJMS

205

276

View full text Add to dashboard Cite

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.

show abstract

“…Tumor necrosis factor (TNF)‐α and IL‐6, which are pro‐inflammatory cytokines, are increased in the DIHS patients with human herpesvirus (HHV)‐6 reactivation . One chemokine, thymus and activation‐regulated chemokine, was also found to be upregulated when reactivation of HHV‐6 occurred …”

Section: Immune‐mediated Mechanismsmentioning

confidence: 99%

Severe cutaneous adverse drug reactions

Chung

Wang

Dao

2016

The Journal of Dermatology

179

163

View full text Add to dashboard Cite

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.

show abstract

Elevated serum thymus and activation-regulated chemokine (TARC/CCL17) relates to reactivation of human herpesvirus 6 in drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS)

Cited by 45 publications

References 8 publications

Drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs

Drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs

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

Severe cutaneous adverse drug reactions

Contact Info

Product

Resources

About