Histopathological study of six types of adverse cutaneous drug reactions using granulysin expression

Weinborn, Marie; Barbaud, A.; Truchetet, F.; Beurey, Philippe; Germain, Louis; Cribier, B.

doi:10.1111/ijd.13350

Cited by 33 publications

(23 citation statements)

References 33 publications

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“…We found a nonsignificant association between dermal infiltrates without epidermal alterations and viral MPEs, whereas the most consistent features of drug‐induced MPEs were epidermal changes. However, as previously reported, we confirmed the lack of a specific histopathological feature of MPEs, although some features may suggest the aetiology …”

Section: Discussionsupporting

confidence: 91%

Acute exanthemas: a prospective study of 98 adult patients with an emphasis on cytokinic and metagenomic investigation

et al. 2019

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Summary Background Acute exanthemas (AEs) are frequently seen; they can be caused by drugs or viruses but often the cause is unknown. Objectives To describe the clinical, virological and histological aspects of AEs and explore their cytokinic and metagenomic profiles. Methods This prospective study examined 98 patients with AE, from February to July 2014. Clinical data were recorded in a standardized chart. Virological investigation and skin biopsies were performed. In addition, blood and skin samples were analysed for cytokines and then by a shotgun metagenomic approach. We identified five groups of patients: those with maculopapular exanthemas (MPEs) that were virally induced (group 1); those with drug‐induced MPEs (group 2), those with MPEs that were both viral and drug induced (group 3), those with idiopathic MPEs (group 4) and those with pityriasis rosea (group 5). Results A virus was identified in 29 cases (human herpesvirus 6, 72%). Cytokinic analysis of the skin (n = 23 MPEs) showed higher levels of interferon‐γ and interleukin‐1 receptor‐α in viral MPEs, higher interleukin‐33 levels in idiopathic MPEs, and higher macrophage inflammatory protein 1α levels in drug‐induced MPEs. By metagenomics analysis (n = 10 MPEs), viruses identified with routine practice methods were not found in group 1 (n = 4 MPEs). However, Enterovirus A was detected in two cases, especially in a group 1 patient for whom metagenomic analysis rectified the diagnosis of the culprit agent. Conclusions Human herpesvirus 6 was the virus most frequently identified, and histology did not discriminate MPEs. In addition, the level of interleukin‐33 seen in idiopathic MPEs suggests that an environmental factor may be the trigger for these. The results bring into question the utility of routine polymerase chain reaction analysis and viral serology for determining cause in AE. What's already known about this topic? Acute exanthemas, especially maculopapular exanthemas, are a frequent reason for patients consulting emergency and dermatology departments. It is difficult to evaluate the aetiology of acute exanthema based on the clinical aspects. Few data are available on the investigations needed in routine practice, and no prospective series have been published. What does this study add? Our study provides a global and prospective description of acute exanthemas. Cytokine analysis could help to investigate the pathophysiology of idiopathic eruptions. Metagenomic analysis provides new insights about the value of routine practice virological investigations. We show for the first time the feasibility of metagenomics analysis in the skin, which results question the interest of routine PCR and viral sérologies for the exploration of such acute exanthemas.

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Section: Discussionsupporting

confidence: 91%

Acute exanthemas: a prospective study of 98 adult patients with an emphasis on cytokinic and metagenomic investigation

et al. 2019

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“…To examine whether CTLs are involved in the pathogenesis of dapsone SCAR, we first detected the granulysin level (a specific cytotoxic protein of SJS/TEN [Chung et al, 2008;Wang CW et al, 2013] and DRESS [Weinborn et al, 2016], mainly released from CTLs) in the plasma of dapsone DRESS patients. (Figure 1a).…”

Section: Plasma Granulysin Level and In Vitro Lymphocyte Activation Tmentioning

confidence: 99%

The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced Severe Cutaneous Adverse Reactions

Chen

Wang

et al. 2018

Journal of Investigative Dermatology

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Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remain unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells involved in the pathogenesis of dapsone-induced severe cutaneous adverse reactions. We enrolled patients from Taiwan and Malaysia with DRESS and maculopapular eruption with chronic inflammatory dermatoses. Our results showed that the HLA-B*13:01 allele was present in 85.7% (6/7) of patients with dapsone DRESS (odds ratio = 49.64, 95% confidence interval = 5.89-418.13; corrected P = 2.92 × 10) but in only 10.8% (73/677) of general population control individuals in Taiwan. The level of granulysin, the severe cutaneous adverse reaction-specific cytotoxic protein released from cytotoxic T cells, was increased in both the plasma of DRESS patients (36.14 ± 9.02 ng/ml, P < 0.05) and in vitro lymphocyte activation test (71.4%, 5/7 patients) compared with healthy control individuals. Furthermore, dapsone-specific cytotoxic T cells were significantly activated when co-cultured with HLA-B*13:01-expressing antigen presenting cells in the presence of dapsone (3.9-fold increase, compared with cells with no HLA-B*13:01 expression; P < 0.01). This study indicates that HLA-B*13:01 is strongly associated with dapsone DRESS and describes a functional role for the HLA-restricted immune mechanism induced by dapsone.

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“…However clinical pattern seen in their study was mainly papular scaly eczema and erythema multiforme with most frequently involved drug being captopril 15 . A study conducted by Weyers et al, in which authors examined 300 consecutive cases 16 and a study conducted by Weinborn et al, in which authors examined 106 slides 17 retrospectively, authors concluded that there was marked overlap of histological features. Thus it is often difficult to attach individual cases to one of the set of patterns.…”

Section: Fig 1: Clinical Pattern Of Cadrs Fig 2: Drug Class and Sevmentioning

confidence: 99%

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2018

IJPSR

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To assess clinical and histopathological patterns, causative drugs, causality, severity and cost of treating Cutaneous Adverse Drug Reactions (CADRs) among patients admitted in tertiary care teaching hospital. Methods: In a prospective hospital-based study over a period of one year (June 2015-June 2016), CADRs of patients admitted to the dermatology department were recorded. The data was subjected to descriptive analysis. Results: Of the total 39 cases, 24 (61.54%) were male and 15 (38.46%) were female. Maximum patients (48.7%) belonged to 21-40 years age group. On causality analysis, 23 cases (58.33%) were of probable type whereas 16 (41.02%) of possible type. Steven Johnson syndrome (46.15%), maculopapular drug rash (20.51%) and drug reaction with eosinophilia and systemic symptoms (15.38%) were common CADRs. There were total 55drugs which could account for observed CADRs mostly belonging to anti-epileptic (32.72%), anti-microbial (29.09 %) and NSAIDs (21.81%) classes. The most frequent offending drug was phenytoin (18.18%) followed by paracetamol (10.91%) and carbamazepine (7.27%). Maximum CADRs were of severe type (66.67%) but no mortality was observed. In all the cases where histopathological examination was done initial diagnosis made after clinical examination did not change. The average cost of hospitalization per day was Rs 535.95. Conclusion: In our study the CADRs patterns found were similar to that seen in previous studies but most common causative class responsible was antiepileptics. Knowledge about the varied clinical presentations and the common putative drugs for CADRs will enable physicians in early diagnosis, prompt treatment and reduce economic burden.

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Histopathological study of six types of adverse cutaneous drug reactions using granulysin expression

Abstract: We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types.

Cited by 33 publications

References 33 publications

Acute exanthemas: a prospective study of 98 adult patients with an emphasis on cytokinic and metagenomic investigation

Acute exanthemas: a prospective study of 98 adult patients with an emphasis on cytokinic and metagenomic investigation

The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced Severe Cutaneous Adverse Reactions

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