Yung-Tsu Cho

Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: A retrospective cohort study from Taiwan

BACKGROUND The development of autoimmune sequelae is one of the characteristic features of drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome; however, the incidence of sequelae and prognosis of patients with DRESS are unknown. OBJECTIVE We sought to investigate the incidence of sequelae, including less well-known sequelae, and long-term prognosis in patients with DRESS/drug-induced hypersensitivity syndrome. METHODS A retrospective cohort study was conducted at a medical center in northern Taiwan using a DRESS/drug-induced hypersensitivity syndrome database. Patients who were followed up for at least 1 year were included in the study. RESULTS Nine patients died before interview, whereas 43 patients completed a specially designed questionnaire. The overall cumulative incidence of long-term sequelae was 11.5% (6 of 52 patients). Four patients developed autoimmune diseases, specifically Graves disease (n = 2), type 1 diabetes mellitus (n = 1), and autoimmune hemolytic anemia (n = 1). Alopecia areata was also noted in 1 of the 2 patients with Graves disease. The other 2 patients developed renal failure after visceral involvement and required lifetime hemodialysis. LIMITATIONS Our study included a small number of patients. Further, viral studies were not performed. CONCLUSION The sequelae of DRESS can be divided into 2 major types that appear to occur in different age groups: young patients tend to develop autoimmune diseases, whereas elderly patients are more vulnerable to end-organ failure.

Human herpes virus reactivations and dynamic cytokine profiles in patients with cutaneous adverse drug reactions --a prospective comparative study.

Sequential human herpes virus (HHV) reactivation is well known in drug reaction with eosinophilia and systemic symptom (DRESS), but such a phenomenon has seldom studied in other types of cutaneous adverse drug reactions (cADRs). Moreover, the association between viral reactivations and cytokine or chemokine changes is largely unknown. We aimed to evaluate the viral reactivation rates of HHV‐6, HHV‐7, Epstein–Barr virus (EBV), and cytomegalovirus (CMV) in different cADRs and their impacts on clinical prognosis. Cytokine and chemokine changes with viral reactivations were also examined.

First‐line combination therapy with rituximab and corticosteroids provides a high complete remission rate in moderate‐to‐severe bullous pemphigoid

R .G. NEWCOMB E S . KHOT C . MART IN Research and Development and Research Associate, St Mary’s Pharmaceutical Unit, Cardiff and Vale University Health Board, Cardiff, U.K. Department of Dermatology, Prince Philip Hospital, Hywel Dda University Health Board, Carmarthenshire, U.K. Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, U.K. Complex Pain Clinic, Department of Anaesthesia, Intensive Care and Pain Medicine; Cardiff and Vale University Health Board, Cardiff, U.K. E-mail: sarah.hiom@wales.nhs.uk

Long-term Sequelae of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions characterized by different extents of epidermal necrosis and mucosal breakdown. A limited number of studies have reported the long-term patterns of SJS and TEN complications in patient populations over long follow-up periods. The aim of this retrospective study was to collect data on long-term sequelae in patients admitted for SJS, SJS/TEN overlap, or TEN between 1998 and 2012. Among all 102 patients eligible for analysis, the 2 most common sequelae were cutaneous and ocular problems, both with incidences of 44.1%. Visceral organ involvement was observed in 2 patients with irreversible deterioration of chronic kidney disease and in one patient with interstitial lung disease. Autoimmune disease was present in 6 patients: Sjögrens syndrome or Sjögren-like syndrome in 5 patients and concomitant systemic lupus erythematosus and Hashimoto thyroiditis in one patient.

First-line combination therapy with rituximab and corticosteroids is effective and safe for pemphigus.

Pemphigus is a life-threatening autoimmune blistering disease. Systemic corticosteroids have been the mainstay and first-line treatment with success. However, longterm use of corticosteroids results in significant morbidities and mortalities. Much effort has been focused on searching alternative or corticosteroids-sparing agents. Rituximab (MabTheraTM; Roche, Basle, Switzerland), a chimeric anti-CD20 monoclonal antibody has been shown to be effective for refractory pemphigus with acceptable side effects (1, 2). Herein, we reported our successful experience with rituximab and corticosteroids as first-line combination therapy for pemphigus.

Comparison of Skin Toxic Effects Associated With Gefitinib, Erlotinib, or Afatinib Treatment for Non–Small Cell Lung Cancer

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used to treat non–small cell lung cancer. Four major skin toxic effects with different incidences have been reported from clinical studies, including acneiform eruption (60%-94%), pruritus (16%-60%), xerosis (4%-38%), and paronychia (6%-12%). 1,2 However, a direct comparison of the incidences and severities of the 4 types of skin toxic effects for 3 different EGFR-TKIs in the same patient cohort has been lacking to date. Methods | This retrospective study was approved by the research ethics committee of National Taiwan University Hospital. We recruited patients within a named patient program for compassionate use before registration who had ever received afatinib treatment for non–small cell lung cancer between November 1, 2007, and April 30, 2013. Most of the pa

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

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.

Co-existence of histopathological features is characteristic in drug reaction with eosinophilia and systemic symptoms and correlates with high grades of cutaneous abnormalities

Only few studies had investigated the histopathological presentations of drug reaction with eosinophilia with systemic symptoms (DRESS). The results of these studies were diverse and not conclusive. A characteristic histopathological feature is still lacking.

High serum anti-BP180 IgE levels correlate to prominent urticarial lesions in patients with bullous pemphigoid.

In animal models of bullous pemphigoid (BP) [1], anti-BP180 immunoglobulin class E (IgE) antibodies have been shown to account for the urticarial lesions and histopathological infiltrations of eosinophils, which are lacking in the IgG-mediated models. Clinically, the presence of serum anti-BP180 IgE has been linked to higher disease severity [2]. However, some other studies showed inconsistent results regarding to this association [3–5]. To resolve the discrepancy, we performed a study to examine the role of IgE auto-antibodies in BP. We retrospectively selected patients with BP who had visited a referral center in Taiwan from 2009 through 2014. All the patients were diagnosed with BP using generally accepted criteria, as described in our previous study [6]. Because of the fluctuating nature of the disease, only patients for whom complete data was obtained on a single day were enrolled. For each patient, we

Treatments for Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations.