Che-Wen Yang

Fixed erythrodysaesthesia plaque due to intravenous injection of docetaxel.

Docetaxel (Taxotere®), a semisynthetic taxoid, acts as an antimicrotubule agent and is considered to have great potential in the treatment of non‐small cell lung cancer, advanced breast cancer, ovarian cancer and some other tumours. Well‐recognized side‐effects include dose‐limiting neutropenia, fluid retention, myalgia, neuropathy, hypersensitivity reaction, alopecia, mucositis, nail changes and cutaneous reactions such as acral erythema. We describe a unique docetaxel‐induced cutaneous reaction presenting as fixed erythematous plaque(s) unrelated to extravasation or previous skin injury; histopathological studies were performed in three of the four cases.

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.

Docetaxel-induced recall dermatitis on previous laser treatment sites

correlation between infectious diseases and cold urticaria has been speculated, no direct relation could be found in our study. Anthistamine receptor blockers showed the best effects, albeit only symptomatic, with no obvious preference towards one particular type of drug. Although the most causally oriented therapy, cold tolerance induction seems much more sensitive to low patient compliance and discontinuation follows as a result. In summary, in support of the literature on cold urticaria, comprehensive testing seems secondary to a thorough individual case history. At the same time, few patients were satisfied with the therapeutic possibilities offered. Consequently, pathogenetic knowledge and resulting therapeutic approaches need to be improved to tackle this greatly distressing form of urticaria to the satisfaction of patient and physician.

Purpuric Drug Eruptions Caused by Epidermal Growth Factor Receptor Inhibitors for Non–Small Cell Lung Cancer: A Clinicopathologic Study of 32 Cases

Importance Purpuric skin lesions have only rarely been reported in patients receiving epidermal growth factor receptor inhibitors. However, their clinical and histopathologic presentations have varied considerably. Objective To characterize purpuric skin eruptions caused by epidermal growth factor receptor inhibitors. Design, Setting, and Participants This prospective study enrolled 32 patients who presented to an integrated dermato-oncologic clinic in a tertiary referral medical center with purpuric skin lesions after using epidermal growth factor receptor inhibitors from January 1, 2013, through December 31, 2015. Exposures Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, erlotinib, and afatinib. Main Outcomes and Measures Clinical presentations, histopathologic features, laboratory examinations, and treatment outcomes of patients with purpuric drug eruptions. Results Thirty-two patients, 14 with purpuric drug eruptions without pustules (mean [SD] age, 60 [11] years; 12 female and 2 male) and 18 with purpuric drug eruptions with pustules (mean [SD] age, 64 [11] years; 12 female and 6 male), were identified. The median time to development of skin lesions was 3.5 months. The clinical presentations were characterized by purpuric macules, papules, and confluent plaques predominantly on the lower extremities. Pustules in various sizes could be found in 18 patients (56%). Eleven patients (34%) had skin lesions that covered places other than the lower extremities. Eczema craquelé–like features developed in 13 patients (41%). Bacterial pathogens were frequently identified in these skin lesions. Among them, Staphylococcus aureus was the most predominant and was found in 20 patients (63%), commonly in those with cutaneous pustules. Epidermal dysmaturation, neutrophil exocytosis, perivascular infiltration of lymphocytes and neutrophils, red blood cell extravasation, and plumping endothelium were the main histopathologic features. The expressions of filaggrin and human &bgr;-defensin 2 in lesional skin of these patients were markedly reduced. All patients improved after receiving at least 1 week of systemic antibiotic treatment; the doses of epidermal growth factor receptor inhibitors were also changed for 14 patients (44%). Conclusions and Relevance Purpuric drug eruptions caused by epidermal growth factor receptor inhibitors are uncommon and have characteristic clinical and histopathologic presentations. The role of bacterial pathogens in this reaction is important and requires further exploration.

The Role of Viral Reactivation in Drug Reaction with Eosinophilia and Systemic Symptoms and Other Cutaneous Adverse Drug Reactions (cADRs)

Cutaneous adverse drug reactions (cADRs) encompass many types of clinical presentations, ranging from benign maculopapular eruption (MPE) to severe cutaneous adverse reactions (SCARs). The relationship between viral reactivation and drug eruptions has been widely observed and has provided a new direction for researchers to explore. In recent years, a number of studies have focused in particular on sequential human herpes virus (HHV) reactivation in drug reaction with eosinophilia and systemic symptoms (DRESS), and these studies have provided crucial evidence demonstrating that clinical presentations can be closely related to the dynamics of viral activity. The DRESS patients with long-term sequelae tended to present with viral activation, including sequential changes in serum cytokines, chemokines, and immune cells. Moreover, other cADRs might also be influenced by the reactivation of different viruses. In this study, we discuss recent progress in understanding the role of viral reactivation in cADRs and the possible pathomechanism underlying the drug-induced immune response.

Differential cytokine/chemokine profiles and reactivation of human herpes viruses in various forms of cutaneous adverse drug reactions. A comparative study in Taiwan

Background Sequential human herpes virus (HHV) reactivation is wellknown in drug reaction with eosinophilia and systemic symptoms (DRESS), but a comparison study to investigate the association of HHV reactivation with other types of cutaneous adverse drug reactions (cADRs) is still lacking. Besides, the pathomechanisms or mediators of viral reactivations are largely unknown. In this study, we aimed to investigate the cytokine/chemokine profiles before or concurrent with HHV reactivations. Method We conducted a prospective study to evaluate HHV-6, Epstein–Barr virus (EBV) and cytomegalovirus (CMV) reactivation rates in various cADRs. Dynamic changes of cytokines and chemokines were also determined by sequential blood tests during acute stages. Interleukin-1 £] (IL-1£]), IL-1 receptor antagonist (IL-1Ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, basic fibroblast growth factors, eotaxin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-£^ (IFN-£^), interferon £^-induced protein-10 (IP-10), monocyte chemoattractant protein-1, macrophage inflammatory protein-1£\ (MIP-1£\), MIP-1£], platelet-derived growth factor, chemokine (C-C motif) ligand 5 (CCL5), tumor necrosis factor-£\ (TNF-£\) and vascular endothelial growth factor were measured using the Bio-Plex Human Cytokine 27-Plex panel. Results A total of 62 patients were enrolled in this prospective study including 23 DRESS, 17 SJS/TEN, 13 MPE, 5 GBFDE and 4 EMM. HHV-6 reactivation was observed in ten DRESS patients (43.5%) but in none of the other cADR patients. In contrast, EBV reactivation was detected in 35 patients distributed in every cADR groups. EBV reactivation rates were 73.9% for DRESS (17 in 23 patients), 29.4% for SJS/TEN (5 in 17 patients), 53.8% for MPE (7 in 13 patients), 80% for GBFDE (4 in 5 patients), and 50% for EMM (2 in 4 patients). CMV reactivation rates were 43.5% in DRESS (10 in 23 patients) and 11.8% in SJS/TEN (2 in 17 patients) respectively, but none of the other cADRs. HHV-6 reactivation in DRESS patients was associated with decreased proinflammatory cytokines and chemokines (IL-1£], IL-1Ra, IL-2, TNF-£\, IFN-£^, and MIP-1£\) before viral reactivations. Only one chemokine, IP-10, was expressed higher in the HHV-6 reactivation group (P = 0.018).