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As DIHS/DRESS severity with histopathology, an EM-like findings5 or the intensity of the lymphocyte infiltrate6 is prognostic factor of DIHS/DRESS severity, namely severe hepatic involvement. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity score: a useful tool for assessing disease severity and predicting fatal cytomegalovirus disease. I Dear Editor, i Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characterized by persistent eruption associated with reactivation of herpesviruses. [Extracted from the article]

We have read with great interest the publication by Herman I et al i .,1 which reported occurrence of drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DiHS), in a COVID-19 patient: the patient developed DiHS/DRESS 17-18 days after starting azithromycin and hydroxychloroquine. A recent report also describes co-reactivation of herpes simplex virus-1 and VZV in a critically ill COVID-19 patient.8 Because HHV-6 has been shown to be associated with chronic spontaneous urticaria, herpesvirus reactivations including HHV-6 could be involved in diverse cutaneous manifestations previously attributed to SARS-CoV-2. Thus, severe COVID-19 symptoms appear to be driven by a complex interplay involving reactivations of latent herpesviruses, antiviral immune responses and dug-driven immune responses, as demonstrated in DiHS/DRESS. [Extracted from the article]

COVID-19-related cutaneous manifestations associated with multiple drug sensitization as shown by lymphocyte transformation test Patients with novel coronavirus disease 2019 (COVID-19) can present with a wide variety of cutaneous manifestations.1,2 Drug-induced eruptions, however, are often indistinguishable from the COVID-19-related rash. Such "multiple drug hypersensitivity" can be most efficiently proven by LTTs.5 Interestingly, such "multiple drug hypersensitivity" was often observed associated with I mycoplasma pneumoniae i infection.6 No previous reports, however, described the occurrence of multiple drug hypersensitivity in patients with SARS-CoV-2 infection. [Extracted from the article]

Background Drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms ( DIHS/ DRESS) and Stevens-Johnson syndrome ( SJS)/toxic epidermal necrolysis ( TEN) represent contrasting poles of severe drug eruptions, and sequential reactivations of several herpesviruses have exclusively been demonstrated in the former. No previous studies, however, were extended beyond the acute stage. We sought to investigate whether herpesvirus reactivations could also be observed in SJS/ TEN and beyond the acute stage of both diseases. Methods Patients with SJS ( n = 16), SJS/ TEN overlap ( n = 2), TEN ( n = 10), and DIHS/ DRESS ( n = 34) were enrolled. We performed a retrospective analysis of Epstein-Barr virus ( EBV), human herpesvirus 6 ( HHV-6), and cytomegalovirus ( CMV) DNA loads sequentially determined by real-time polymerase chain reaction during a 2-year period after onset. Results Persistently increased EBV loads were detected in SJS during the acute stage and long after resolution, but not in others. In contrast, high HHV-6 loads were exclusively detected in DIHS/ DRESS during the acute stage. The dynamics of herpesvirus reactivation varied in DIHS/ DRESS according to the use of systemic corticosteroids: While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher in those receiving them. Conclusions Distinct patterns of herpesvirus reactivation according to the pathological phenotype and to the use of systemic corticosteroids were observed during the acute stage and follow-up period, which may contribute, at least in part, to the difference in the clinical manifestations and long-term outcomes. Systemic corticosteroids during the acute stage may improve the outcomes in DIHS/ DRESS. [ABSTRACT FROM AUTHOR]

Confluent and reticulated papillomatosis (CRP) is a rare skin disorder that develops in young adults and presents as persistent brown papules and plaques predominantly affecting the intertriginous areas, however, its etiopathogenesis remains elusive. Herein, we report a probable case of CRP with lesional hypohidrosis as detected by sweat test and provide insight into the pathomechanism. A 23-year-old man presented with nine-months history of painful sensation on his trunk without any skin change. The result of sweat test was compatible with acquired idiopathic generalized anhidrosis. Topical heparinoid and physical exercise improved the symptoms. However, he started to notice asymptomatic brownish reticulated macules on the trunk. Intriguingly, focal hypohidrosis, as detected by sweat test was evident on the macules. In histology, the lesional skin demonstrated hyperkeratosis, acanthosis, basal melanosis, mild papillomatosis, and obstruction of the sweat duct in the upper dermis, which were not observed in the peri-lesional skin. Accumulation of the sweat in the luminal aspect of the secretory portion and dilation of the sweat duct in the deeper dermis was detected in the lesional skin, as highlighted by anti-dermcidin staining. Aquaporin 5 expression in the secretory portion was more confined to the cell membrane in the lesional skin. Both brownish macules and lesional hypohidrosis simultaneously improved in summer and exacerbated in winter. Literature review found nine reports on recurrent CRP, and obesity was thought to be a major comorbidity in recurrent CRP cases. Obesity is often associated with sweat dysregulation. This, together with the findings in our case, implied the possible contribution of focal sweating abnormality in the pathogenesis of reticulated skin lesion in our case., (© 2022 Japanese Dermatological Association.)

Subcutaneous injection of azacitidine (AZA) is an important treatment option for myelodysplastic syndrome (MDS), which improves overall survival. In hematology, the incidence of AZA-induced cutaneous adverse events (AE) has been known to be relatively high, which has not been well recognized by dermatologists. Discontinuation of AZA can result in the deterioration of MDS disease activity. Therefore, on dermatological consultation, precise evaluation of AE severity and careful consideration is required for post-AE medication management. To enhance our understanding of AZA-induced cutaneous AE, we report four cases with two representative cutaneous AE subtypes and summarize the clinicopathological phenotypes and courses of the cases in the published work. Case 1, a 71-year-old man, developed neutrophilic dermatosis involving the dermis and subcutaneous tissue. The other three cases, a 75-year-old man, a 78-year-old woman and a 68-year-old man, presented injection-site erythema associated with flare-up reaction. Discontinuation of AZA was necessary for case 1 alone. The published work review delineated three major subtypes of AZA-induced cutaneous AE: systemic cutaneous reaction, neutrophilic dermatosis type and erythematous type injection-site reaction. Histologically, the first two subtypes are mostly characterized by neutrophil infiltration, while the third subtype presents lymphocytic cell infiltration. Neither AZA discontinuation nor intensive interventions were required for the erythematous type injection-site reaction, while AZA termination or systemic treatments, represented by corticosteroid administration, were preferentially conducted for the systemic cutaneous reaction or the neutrophilic dermatosis type injection-site reaction subgroup. These observations support the necessity of subtype-dependent treatment strategies for the management of AZA-induced cutaneous AE., (© 2020 Japanese Dermatological Association.)

The clinical classification of cutaneous adverse reactions by drugs should be clearly distinguished to avoid conceptual confusion and inconsistency. Although dermatologists appear to have established a roughly common consensus for cutaneous adverse reactions, some types are more rigorously defined than other, possibly misleading classifications. To assess the consensus on the clinical classifications, we investigated the concordance rate of diagnosis by Japanese experts through a snap visual inspection of various clinical pictures exhibiting erythema multiforme and maculopapular eruption types of cutaneous adverse reactions. The experts were shown images on a screen and were then asked to decide whether to classify cases as maculopapular eruption or erythema multiforme type, and the concordance rates were calculated. Overall, the mean concordance rate was 71.6% (standard deviation, 17.3%), and only 33.8% of cases had a 90% or more concordance rate. Our study shows that the determinations of erythema multiforme and maculopapular eruption types by the existing classification criteria were confusing even among experts, which prompted us to standardize the terminology. We propose clinically defining erythema multiforme type as generalized macules mainly of 1 cm or more with a tendency of elevation and coalescence, and maculopapular eruption type as generalized erythema other than erythema multiforme type. Currently, the clinical definitions of cutaneous adverse reactions are poorly described, which may be problematic upon analyzing large volumes of data. Our proposal for a new terminology will enhance the accuracy and consistency of information for the correct analysis of cutaneous adverse reactions., (© 2019 Japanese Dermatological Association.)

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., (© 2019 Japanese Dermatological Association.)

Immune reconstitution inflammatory syndrome (IRIS) represents a clinical phenomenon of immune-mediated inflammation against various antigens, including pathogenic microorganisms, drugs and unknown autoantigens, during recovery from immunosuppressed conditions. IRIS has become well recognized in HIV-infected populations. However, IRIS has seldom been recognized in HIV-negative immunocompromised patients. In the last 15 years, the immunopathogenesis of drug-induced hypersensitivity syndrome (DIHS) has been largely determined. Laboratory data and clinical observations support the idea that DIHS represents a prototype of non-HIV IRIS. Primary diseases in which non-HIV IRIS is secondary include severe cutaneous adverse drug reactions, such as DIHS, autoimmune diseases, collagen diseases, pregnancy and internal malignancies. Potential triggers of recovery from an immune deterioration state include a discontinuation or abrupt tapering of systemic steroids and/or immunosuppressants, withdrawal or reduced effects of anti-tumor necrosis factor-α antibodies, and the use of immune-checkpoint antagonists for the advanced stages of malignancies. Wide use of IRIS across large populations risks oversimplification but highlights a key unifying principle. Balanced sensitivity and specificity for its diagnostic criteria and classification are necessary for the establishment of clinical practice guidelines for non-HIV IRIS. Additionally, the development of a useful combination of biomarkers is currently an urgent issue., (© 2017 Japanese Dermatological Association.)

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., (© 2011 Japanese Dermatological Association.)