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Background: In JADE COMPARE, abrocitinib improved severity of atopic dermatitis (AD) and demonstrated rapid itch relief. Objectives: We examined clinically meaningful improvements in selected patient-reported outcomes (PROs). Methods: JADE COMPARE was a multicentre, phase 3 randomized, double-blind, placebo-controlled trial. Adults with moderate-to-severe AD were randomized 2:2:2:1 to receive 16 weeks of oral abrocitinib 200 or 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo, with background topical therapy. PROs included Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Night Time Itch Scale (NTIS), Pruritus and Symptoms Assessment for Atopic Dermatitis, Patient Global Assessment, SCORing Atopic Dermatitis, and Hospital Anxiety and Depression Scale. Results: At week 16, the proportion of patients achieving POEM scores

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Background The common contact allergens may change over time as the environmental exposure changes. Objectives To identify the prevalence rates and changing trends of contact allergens in Taiwan over a 40-year period. Materials & methods The patch testing results of a referral centre from 1978 to 2018 were retrospectively reviewed. The study population was divided into four groups according to 10-year intervals. The prevalence rates of contact sensitization to each agent and the clinical relevance were analysed. For patients with positive reactions to relevant allergens, the occupations and sites of dermatitis were analysed. Results From 1978 to 2018, a total of 4005 patients underwent patch testing. Successively increasing trends of positive reactions to cobalt, fragrance mix I, and para-phenylenediamine (PPD) were found. Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) was an emerging contact allergen. Hairdressers, cosmetologists, and aromatherapists became the occupations most commonly having positive reactions in the most recent 10 years. In the first two decades, the face and neck were the most commonly affected areas. Later, hands became the most commonly affected sites. Conclusions The prevalence rates of positive reactions to cobalt, fragrance mix I, and PPD increased successively. MCI/MI was an emerging contact allergen of special concern.

Background: Ligelizumab, a next-generation, humanized anti-immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard-of-care therapy. Objective: To evaluate the long-term safety and re-treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods: This open-label, single-arm, long-term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose-finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post-treatment for 48 weeks. Results: Overall, ligelizumab was well-tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment-emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks. Conclusion: The long-term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re-treatment efficacy was shown. Trial registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218.

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

Background Oncologic treatments may lead to the development of paronychia, which may cause severe pain and disability. However, a detailed objective scoring system is lacking. Objective To develop an objective scoring system to quantify the severity of paronychia and also examine the correlation of this score with a pain index and patients' quality of life. Methods A novel scoring system for paronychia related to oncologic treatments (SPOT), consisting of four parameters, namely redness, oedema, discharge and granulation tissue, was designed to assess the severity of paronychia. The visual analogue scale (VAS) and Dermatology Quality of Life Index (DLQI) were recorded, and their association with the SPOT scores was analysed. Results Ninety patients were enrolled from three medical centres in Taiwan. Severity of paronychia was determined by the scores of SPOT. Patients in the severe group had higher DLQI scores (severe vs. mild: P = 0.0018; severe vs. moderate: P = 0.0015). Both the DLQI and pain index scores were significantly higher in patients with higher dominant hand SPOT scores. Conclusions The SPOT scores demonstrated the association of the paronychia severity with DLQI and pain. It may thus be useful in clinical practice and future studies.

The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio‐probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (ReI) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, ReI‐diimine complex already exhibits excellent emission yield (34%, λ em = 583 nm) and large two‐photon absorption cross‐sections (σ 2 = 300 GM @ 800 nm) in water (pH 7.4). After extravasation, remarkably, the collagen‐bound probes further enhanced their excitation efficiency by increasing the deoxygenated lifetime from 4.0 to 7.5 µs, paving a way to visualize tumor hypoxia and tissue ischemia in vivo. The post‐extravasation functionalization of extracellular matrixes demonstrates a new methodology for biomaterial‐empowered phosphorescence sensing and imaging., Biocompatible rhenium (ReI) diimine carbonyl complexes functionalize the extravascular collagen matrixes as in situ oxygen sensor. After tail‐vein delivery and vessel penetration, the probe can bind extravascular collagens and achieve stabilization enhanced two‐photon phosphorescence yields. Increased deoxygenated phosphorescence lifetime from 4.0 to 7.5 µs paves a way to visualize tumor hypoxia and tissue ischemia in vivo.

Background Treatment guidelines for chronic spontaneous/idiopathic urticaria (CSU) are available; however, only 50% of patients are well controlled with approved doses of H1-antihistamines, and certain patients remain symptomatic despite receiving up to 4× the approved dose of H1-antihistamines plus H2-antihistamines and/or leucotriene-receptor antagonists. Objectives To highlight real-life clinical practice in Taiwan and to understand the unmet medical needs of CSU patients. Methods A nationwide cross-sectional, observational survey of 50 dermatologists and 200 CSU patients was conducted between June 2013 and November 2013. Face-to-face interviews of dermatologists and online interviews of CSU patients were conducted independently. Results Dermatologists reported that dermographism and blood tests were the most commonly used diagnostic methods to confirm the diagnosis. The key driving factor for most clinic-based dermatologists (70%) in choosing a treatment was ‘response to my medicines’, and most preferred H1-antihistamines and steroids for treating CSU patients, whereas most hospital-based dermatologists (85%) gave higher priority to ‘severity and impact of the conditions’. Patients were reported to have high psychological pressures and significant impact of CSU on their daily activity. In addition, CSU patients were not satisfied with their current treatment and 69% of patients switched their first-consulted physician. Furthermore, lack of information and concerns about side-effects were major factors which held back patients from seeking Western treatment. Conclusions There is an unmet medical need of CSU patients in Taiwan highlighting gaps among guidelines, real-life clinical practice, patients' perceptions and patients' knowledge of their disease.

Background 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. Methods A prospective study was conducted to monitor the viral statuses of patients with different cADRs by polymerase chain reaction and serum-specific antibody titers. Changes in plasma cytokine and chemokine levels were also evaluated by sequential blood samples. Results Among the various cADRs, HHV-6 reactivation was only observed in DRESS, but EBV and CMV could be detected in other cADRs. Many proinflammatory cytokines and chemokines, including interleukin (IL)-1β, IL-2, IL-6, interferon-γ, tumor necrosis factor-α, were significantly lower in DRESS patients with HHV-6 reactivation when compared to those without HHV-6 reactivation. In addition, these mediators were significantly lower before and during HHV-6 reactivation, compared to cytokine levels after HHV-6 reactivation in the same patient. Conclusion HHV-6 reactivation was only observed in DRESS patients, not in any other cADR. In DRESS patients, some proinflammatory cytokines were significantly lower before or during HHV-6 reactivation.

Background Melanoma is a heterogeneous group of diseases with distinct sets of genetic changes. Recurrent and mutually exclusive C>T or CC>TT transition mutations were identified in the promoter region of the reverse transcriptase catalytic subunit of the telomerase gene (TERT) in melanoma recently, and it was suggested that they enhanced the expression of TERT gene and played important roles in the melanoma pathogenesis. These mono or di-nucleotide transitions were ultraviolet (UV)-signature mutations. Methods In this study, polymerase chain reaction and direct sequencing of TERT promoter using formalin-fixed and paraffin-embedded tissue was performed to investigate whether these UV-signature mutations were also present in acral lentiginous melanoma. Results TERT promoter mutation was identified in only 2 of the 32 cases (6%) of acral lentiginous melanomas while it was identified in 3 of the 9 cases (33%) of non-acral cutaneous melanomas. The difference was statistically significant (p = 0.028). Conclusions The rarity of TERT promoter mutation in the acral lentiginous melanoma was consistent with the supposed role of UV light in the melanoma pathogenesis and also corroborated the view that acral lentiginous melanomas have a different pathogenesis with the melanomas from sun-exposed sites.

The Penicillium genus of fungi is a frequently reported cause of allergic reactions. However, only a limited number of allergens have been reported. In Penicillium spp., many allergens show higher IgE-binding activity in culture filtrate extracts than in cellular extracts. In order to investigate the IgE-reactive profile of mold-sensitized patients, secreted IgE-reactive proteins from Penicillium citrinum were identified by 2-DE, serum immunoblotting, and nanoLC-MS/MS. Among the IgE-reactive spots, one known allergen, Pen c 13, and four novel allergens were identified. The cDNAs coding for Pen c 32 and Pen c 30 were cloned using designed primers based on nanoLC-MS/MS analysis. The amino acid sequences of Pen c 32 and Pen c 30 were, respectively, found to have extensive similarity with those of pectate lyases and catalases from various fungi. Native Pen c 30 was shown to have catalase activity and to bind to serum IgE from 48% of mold-allergic patients and induced immediate type skin reactions in a sensitized patient. Here, we present a proteome approach which resulted in the identification of four novel secreted allergens. These novel allergens might be useful in allergy diagnosis and in the treatment of mold-allergic disorders.

An outbreak of suspected contact dermatitis among subway construction workers was suspected to be due to a new bisphenol A/F-based epoxy resin system (ERS). The construction workers used ERSs during the insertion of iron bars into concrete walls. The objective of the study was to determine the components (if any) of the ERS responsible for the contact allergy. Patch testing was performed on 20 of the 22 construction workers who had had contact with the ERS, and to the various subcomponents of component A on 5 of the 7 who reacted to this component. 9 patients (9/22, 40.9%) had clinical symptoms and signs of suspected contact dermatitis at presentation. 7 of these 9, but none of the 11 asymptomatic individuals, were positive to component A, while all were negative to component B. Of the 5 cases receiving further patch testing, all reacted to m-xylylene diamine, 4 to 1,6-hexanediol diglycidyl ether, 3 to epoxy resins of the bisphenol F-type and trimethylolpropane triglycidyl ether 0.25% petrolatum, and only 1 to epoxy resins of the bisphenol A-type. Contact allergy to ERSs may involve hardeners and diluents as well as resins, and patch testing for reaction to all components should be performed.

Method To investigate the types of liver injury and factors involved, including the chronology, recovery time, relationship with culprit drugs and the pathology correlations, a retrospective study was conducted by reviewing all medical records of DRESS patients diagnosed between Dec. 2000 and Jan. 2013 in the National Taiwan University Hospital Database. DRESS was defined according to the International Registry of Severe Cutaneous Adverse Reactions (RegiSCAR). The pattern of liver damage is classified according to the International Consensus Meeting criteria.

Background Steroid-induced rosacea-like eruption is characterized by facial rosacea-like dermatitis in patients that have been treated with topical steroids for relatively long periods. Objective To evaluate the efficacy and tolerability of 1% pimecrolimus topical cream for steroid-induced rosacea-like eruption. Methods In an open-label pilot study, 40 patients were enrolled and instructed to apply 1% pimecrolimus cream twice daily for 6 weeks. Patients were evaluated by a rosacea clinical score, investigator's global assessment, overall erythema severity, and tolerability at weeks 0, 2, and 6. Results In 35 patients, the rosacea clinical score decreased significantly from 16.0 ± 4.3 at baseline to 8.1 ± 3.3 at week 2 and 4.2 ± 2.5 at week 6 (P