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Cutaneous immune-related adverse events are common in cancer patients receiving immunotherapies but seldom studied in a comprehensive way of collecting all cancer types with comparisons between different immune-oncology drugs and correlation to patient survival. In this retrospective cohort study, we recruited 468 cancer patients receiving immunotherapies in a tertiary referral center in Taiwan and try to determine real-world incidence of cutaneous immune-related adverse events and their associations with the survival rates. Among them, 128 patients (27.4%) had cutaneous immune-related adverse events, with maculopapular eruption (10.6%) and pruritus (10.1%) most frequently identified in the monotherapy group. The incidence of these cutaneous immune-related adverse events was highest in patients receiving pembrolizumab (34.1%, P P P

Background/Objective There is a rising awareness of drug reaction with eosinophilia and systemic symptoms (DRESS) due to its possible morbidity and mortality. Early diagnosis of DRESS is crucial for administering timely treatment; however, prompt diagnosis based on its early presentation can be quite problematic due to its clinical resemblance to common maculopapular eruptions (MPE). Methods A retrospective cohort study of patient data from September 2010 to June 2016 was conducted to compare the clinical presentations of DRESS and MPE validated by the RegiSCAR scoring system. The demographic data, clinical presentations, and histopathological patterns were reviewed. Results Fifty-eight patients with DRESS and 29 patients with MPE were included. The mean age at diagnosis of DRESS was 47 years (range: 2–82 years), and female patients predominated by a ratio of 2.2:1. The three most common culprit medications for DRESS were allopurinol, sulfasalazine, and trimethoprim/sulfamethoxazole. The most significant differences between the DRESS and MPE groups were the presence of fever, peripheral blood eosinophilia and atypical lymphocytosis, characteristic skin lesions, abnormal liver functions, and prolonged resolution of skin lesions for more than 15 days in the DRESS patients. The most common histologic features in the DRESS patients were coexistent eczematous, interface dermatitis, and vascular damage patterns, or interface dermatitis alone. The concurrence of fever, peripheral blood eosinophilia, and abnormal liver function within three days of visiting a medical facility were more common in cases of DRESS than of MPE (24.1% vs. 0%, P = 0.004). Conclusion Although DRESS and MPE look similar, especially in the early stage of DRESS, the concurrence of fever, peripheral blood eosinophilia, and abnormal liver functions within three days of visiting a medical facility might aid in the early diagnosis of DRESS.

Background/Objectives Accumulating evidence has shown that omalizumab is an effective and safe treatment for chronic spontaneous urticaria (CSU), but there is little information regarding the use of omalizumab to treat CSU in Taiwan. Reports on clinical experiences with using omalizumab for CSU for more than 6 months are also lacking. Methods A retrospective review of medical records of consecutive CSU patients receiving omalizumab treatment in the Urticaria Special Clinic of one tertiary referral center in Taiwan was conducted. We analyzed clinical features of the patients, treatment efficacy and safety, and also long-term outcomes after omalizumab treatment. An Urticaria Activity Score over 7 days (UAS7) was recorded at each visit. Results A total of 17 CSU patients were identified (11 females and 6 males, age range: 21–83 years) with a baseline mean UAS7 of 29.8 ± 8.9 despite antihistamine treatment. All patients were treated with at least 3 doses of monthly subcutaneous injections of omalizumab. Fifteen patients achieved a UAS7 of 6 or less after 3 doses of monthly omalizumab injections. Seven of those 15 patients received an additional 1 to 3 doses and all ended up with a UAS7 of less than 2 at the 24-week follow-up. A sustained response to maintenance treatment after 24 weeks was observed in 5 patients with individual tailoring of treatment duration and dosing interval. Conclusion Omalizumab is an effective and safe treatment for antihistamine refractory CSU. Maintenance therapy with individual tailoring of the treatment duration and interval is possible.

Background: Plasmacytoid dendritic cells (pDCs) are implicated in the reactivation of human herpesvirus 6 (HHV-6) in drug reaction with eosinophilia and systemic symptoms (DRESS). Objectives: We aimed at identifying the alterations of circulating pDCs, basophils, and myeloid dendritic cells (mDCs) during the active stage of drug eruptions and the relationship between pDC alteration and HHV-6 reactivation in DRESS patients. Methods: Nine DRESS patients and twelve patients of other drug eruptions (ODE, including five cases of maculopapular eruptions (MPEs), five cases of Stevens–Johnson syndrome, and two cases of fixed drug eruption) were prospectively recruited. Blood samples were collected weekly for 2 consecutive weeks for flow cytometry of pDC, basophil, mDC, and detection of HHV-6 reactivation by serum anti-HHV-6 immunoglobulin G, or whole blood HHV-6 viral DNA by quantitative polymerase chain reaction. Results: The HHV-6 reactivation was exclusively seen in DRESS, and the pDC levels decreased in DRESS compared with ODE (P = 0.002) and (MPE, P = 0.021), with the timing of such decrease preceding HHV-6 reactivation. Conclusion: The decrease of pDC levels is significantly more common in DRESS patients and occurs before HHV-6 reactivation. The chronological sequence implies that the decrease of pDC may be crucial in the pathogenesis of viral reactivation.

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: Sjögren's syndrome or Sjögren-like syndrome in 5 patients and concomitant systemic lupus erythematosus and Hashimoto thyroiditis in one patient.

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.

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

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 craquele–like features developed in 13 patients (41%). Bacterial pathogens were frequently identified in these skin lesions. Among them,Staphylococcus aureuswas 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 β-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.

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).