Kazuhisa Hirahara

Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity : dependence on its timing and the type of drug eruption

Background:  Lymphocyte transformation test (LTT) is a safety and reproducible test to assess activation of drug‐specific T cells in vitro; however, there are several practical concerns such as the time of testing and the influence of treatment. Our aim was to define the right timing to perform LTT for determining the causative agent in various types of drug reactions.

Visceral Involvements and Long-term Sequelae in Drug-induced Hypersensitivity Syndrome

Drug-induced hypersensitivity syndrome (DIHS) is a severe systemic reaction with several herpesvirus reactivations. Multiple organ failures appear during the course of the disease. The severity of DIHS is determined by the degree of visceral involvement. Autoimmune diseases also develop several months to years after the apparent clinical resolution of DIHS.

Short- and long-term outcomes of 34 patients with drug-induced hypersensitivity syndrome in a single institution.

BACKGROUND Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe systemic hypersensitivity reaction caused by specific drugs, in which herpesvirus reactivations and organ dysfunction occur during the course of the disease. Although recent reports have documented the development of autoimmune disease after complete resolution of DIHS/DRESS, relatively little is known about long-term outcomes after complete resolution of the disease. OBJECTIVE The aim of this study was to retrospectively analyze complications and sequelae in the early and late phases of DIHS/DRESS according to treatment. METHODS In all, 34 patients were classified into 2 groups: 14 patients with oral corticosteroid treatment; and 20 with noncorticosteroid treatment. The disease time course was divided into 2 periods: the first 6 months after onset of the drug reaction (early phase); and the period thereafter (late phase). Investigations to detect the presence of viral/bacterial infectious diseases, organ dysfunction, and autoantibodies were performed in both early and late phases. RESULTS Herpesvirus infections and pneumonia were detected in 6 and 2 patients, respectively, in the corticosteroid treatment group in the early phase. In the noncorticosteroid treatment group, 2 patients developed autoimmune diseases, namely lupus erythematosus and autoimmune thyroiditis. Autoantibodies were detected in 44.4% of patients examined in the late phase of the disease. LIMITATIONS This study only evaluated a small number of autoantibodies. CONCLUSION The need for anti-inflammatory effects from systemic corticosteroids should be balanced with the risk of infectious diseases and the benefits of preventing the appearance of later autoimmune conditions in patients with DIHS/DRESS.

Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: Is cytokine expression analysis useful in predicting its therapeutic efficacy?

Toxic epidermal necrolysis (TEN) is a life‐threatening, drug‐induced disorder characterized by severe epidermal injury. Although there is no standard therapeutic intervention in TEN, plasmapheresis (PP) is being used increasingly to treat extremely ill TEN patients. In addition to conventional PP, double‐filtration PP (DFPP) has been recently used for severe and refractory TEN. In this review, we focus on the clinical usefulness of PP by both demonstrating three cases of TEN refractory to conventional therapies, who were successfully treated with conventional PP or DFPP, and evaluating its therapeutic efficiency. We also provide evidence to suggest the mechanisms of action of PP by investigating the correlation between disease intensity and serum cytokine levels before and after treatment with PP or DFPP in these patients with TEN. At present, PP is a much more effective option for treatment of severe and/or recalcitrant TEN than any other treatment, such as pulsed corticosteroids and i.v. immunoglobulin.

Differences in immunological alterations and underlying viral infections in two well-defined severe drug eruptions

Background.  Similar drugs (e.g. anticonvulsants) have been implicated in the development of two distinct forms of severe cutaneous drug reactions, Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug–induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS).

Human Herpesvirus 6 Reactivation in Drug-induced Hypersensitivity Syndrome and DRESS Validation Score

We read with great interest the article entitled, “The DRESS Syndrome: A Literature Review” by Cacoub et al. The authors classified 172 cases reported as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in the literature by using the RegiSCAR scoring system. They concluded that the vast majority of cases could be defined as “probable/definite” DRESS cases. Among various terms to refer to this syndrome, the criteria for drug-induced hypersensitivity syndrome (DIHS) proposed by a Japanese severe cutaneous adverse reaction

Differences in Clinical Features and Outcomes between Group A- and Group G Streptococcus-Induced Cellulitis

Background: Streptococci are the main causative agents of cellulitis, and group G Streptococcus (GGS) shares many important virulent factors with group A Streptococcus (GAS). The difference in the clinical features of GAS- and GGS-induced cellulitis, however, has not been thoroughly characterized. Objective: Our aim was to recognize the differences in the clinical manifestations and outcomes of lower limb cellulitis caused by GAS and GGS. Methods: We retrospectively analyzed a total of 29 patients diagnosed with GAS- or GGS-induced lower limb cellulitis during the period from January 2008 to September 2013. Results: While the clinical manifestations of GAS-induced cellulitis were likely to be uniform, those of GGS-induced cellulitis were variable, depending on the predisposing factors. GGS-induced cellulitis occurred more frequently in older person who had chronic underlying illness. Conclusion: We identified clinical predisposing factors that can predict the clinical course and outcomes of GGS-induced cellulitis.

Relationship between cytomegalovirus reactivation and dermatomyositis.

Dermatomyositis (DM) is an autoimmune disease manifested by muscle weakness and characteristic cutaneous eruptions. Cytomegalovirus (CMV) belongs to the β-herpesvirinae subfamily of herpesviridae that cause morbidity and mortality in immunocompromised patients. With respect to the relationship between CMV and DM, it remains unknown whether CMV plays a pathogenetic role or whether CMV disease is an opportunistic infection due to immunosuppressive treatment. We report two patients with DM who developed cutaneous CMV ulcers within one month after the initiation of systemic corticosteroid treatment. In this context, we retrospectively studied the clinical characteristics of six DM patients with CMV reactivation and the effect of corticosteroid treatment on CMV reactivation in these patients. We also examined possible predictive parameters of CMV reactivation during the course of DM. Our results suggest that CMV reactivation occurs more frequently in DM patients than previously recognized; CMV reactivation occurs regardless of the dosage and duration of corticosteroid administration or the presence of underlying disease. Furthermore, our study shows that a reduction in platelets, serum globulin and IgG levels during the course of DM may be useful predictive parameters for CMV reactivation in patients with DM.

Prediction and management of drug reaction with eosinophilia and systemic symptoms (DRESS)

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a lifethreatening, drug-induced, multi-organ system reaction, which is characterized by sequential reactivations of herpesviruses [1,2]. Because this syndrome is initiated by fever of >38°C and maculopapular morbilliform exanthema, viral infections could be a potential consideration at onset. The delayed onset of clinical symptoms of DiHS/DRESS, usually 2–6 weeks after starting therapy, often causes the potential diagnostic delay (Figure 1). Paradoxical worsening of clinical symptoms often occurs 3–4 days after withdrawal of the causative drug, a quite unusual finding for drug eruption: owing to increasing concern of infections, unnecessary empirical antibiotic therapy may be started, thereby increasing the risk of developing additional sensitization to these drugs. Importantly, patients with DiHS/DRESS often show unexplained cross-reactivity to multiple drugs with different chemical structures, including nonsteroidal anti-inflammatory drugs (NSAIDs) [1,3]. A detailed drug history is very important to identify the causative drugs. This editorial presents a management-based approach to the diagnosis and treatment.

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) severity score: A useful tool for assessing disease severity and predicting fatal cytomegalovirus disease

Background: The prognosis of drug‐induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is highly unpredictable. Severe complications, either related or unrelated to cytomegalovirus (CMV) reactivation, are a highly probable cause of death. Objectives: The aim was to establish a scoring system for DiHS/DRESS that can be used to monitor severity, predict prognosis, and stratify the risk of developing CMV disease and complications. Methods: A retrospective analysis of 55 patients with DiHS/DRESS was performed. A composite score was created using clinical data. DiHS/DRESS patients were also stratified into 3 groups based on the scores to predict the risk of CMV reactivation and complications. Results: This scoring system made it possible to predict CMV disease and complications. Scores ≥4 were associated with the later development of CMV disease and complications, while no patients with scores <4 developed complications. Limitations: This was a single‐institution study with a relatively small patient cohort that lacked a validation cohort. Conclusions: Our scoring system may be useful for predicting CMV‐related complications, and early intervention with anti‐CMV agents should be considered in patients with scores ≥4 or with evidence of CMV reactivation.