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Background/purpose Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan. Methods Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed. Results A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively. Conclusions The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety.

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.

Atopic dermatitis (AD) is generally considered a T helper type 2-dominated disease. Pediatric AD is usually less severe than adult AD, but it may present as moderate to severe lesions that are inadequately managed by current modalities including emollients/moisturizers, topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and even systemic immunosuppressants (such as cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil). In addition, systemic immunosuppressants are often not recommended for childhood AD by the current guidelines due to their toxicities. Therefore, there is still an unmet need for a safe and effective long-term therapy for pediatric AD patients whose disease is inadequately controlled or who are intolerant to current treatments. The emerging therapeutics for AD focuses on intervening in the inflammatory pathway by targeting specific cytokines/chemokines or their receptors. Monoclonal antibodies against immunoglobulin E (IgE), interleukin (IL)-4 receptor subunit α, IL-5, IL-13, IL-31 receptor subunit α, IL-33, and thymic stromal lymphopoietin (TSLP) have been evaluated clinically for AD. Encouraging results have been reported for many of the biologics, of which the most exciting is dupilumab. Other emerging systemic therapies include small molecules such as baricitinib, abrocitinib, upadacitinib, and tradipitant. Several novel topical agents are under clinical investigation for the treatment of AD, including topical phosphodiesterase 4 (PDE4) inhibitors, Janus kinase (JAK) inhibitors, aryl hydrocarbon receptor (AhR) modulating agents, and transient receptor potential vanilloid subfamily member 1 (TRPV1) antagonists. Accompanied by thorough characterization of different phenotype and endotype subsets, the application of precision medicine could provide new prospects for the optimal treatment of AD.

Atopic dermatitis (AD, also called atopic eczema) is a long-term skin disease that causes intensely itchy, red skin. Healthcare providers can prescribe medicated creams and ointments to reduce the signs and symptoms of AD. However, these treatments are not always enough to provide relief. A new medicine called abrocitinib, which is taken every day as a tablet, reduces part of the body’s immune response that happens in AD. The clinical study described in this plain language summary, called JADE COMPARE, investigated how well and how safely 16 weeks of treatment with abrocitinib worked in adults with AD compared to placebo (‘dummy treatment’) and a medicine that is already approved for AD, called dupilumab. The study showed that abrocitinib was better than placebo in improving the signs and symptoms of AD after 16 weeks. In addition, patients who were taking abrocitinib 200 mg for 2 weeks experienced greater relief from itch than patients who were taking abrocitinib 100 mg, placebo, or dupilumab. More people who took abrocitinib 200 mg reported side effects than those taking abrocitinib 100 mg, placebo, or dupilumab, but most of these side effects were mild or moderate. ClinicalTrials.gov NCT number: NCT03720470 .

Atopic dermatitis has a substantial impact on work and activity impairment according to studies from Western communities. Prospective studies of work productivity and activity impairment in Asian patients with atopic dermatitis are lacking. The aims of this study were to investigate the impacts of atopic dermatitis on work productivity and activity impairment among Taiwanese patients, and to stratify the analyses by disease severity. One-third of employed participants reported missing work (absenteeism) in the preceding week due to atopic dermatitis, while 88.5% of the remaining two-thirds reported impaired work effectiveness (presenteeism). In addition, 92.5% of all participants reported impaired daily activities. Overall work impairment (aggregate productivity loss from absenteeism and presenteeism) was 1.8- and 2.6-fold greater in subjects with moderate and severe atopic dermatitis, respectively, compared with those with mild atopic dermatitis. Presenteeism, but not absenteeism, contributes to the majority of total work impairment in this cohort. Daily activity impairment was 1.5-fold greater in moderate atopic dermatitis, and 2.0-fold greater in severe atopic dermatitis, compared with mild atopic dermatitis. Both work and activity impairment showed significant positive correlations with atopic dermatitis severity scores (SCORing Atopic Dermatitis; SCORAD). In conclusion, work productivity and activity impairment is significantly correlated with disease severity in this Taiwanese atopic dermatitis cohort. In order to obtain a full picture of disease burden to patients and caregivers, patients with atopic dermatitis should be monitored for disease activity as well as corresponding impacts on quality of life.

Background/purpose: Rituximab is effective in treating pemphigus both as the first-line treatment and as an add-on treatment for refractory disease. A high rate of relapse among patients receiving rituximab means that maintenance therapy is frequently required. Therefore, we aimed to evaluate the use of azathioprine as maintenance therapy for patients receiving rituximab and to investigate the efficacy and safety of one or multiple cycles of rituximab treatment. Methods: We retrospectively collected data regarding pemphigus patients treated with rituximab from 2008 to 2015 with at least one year of follow-up at a referral center in Northern Taiwan. The medical records and clinical data were reviewed to determine the efficacy and complication rate of the treatment. Results: A total of 78 pemphigus patients were identified. Ninety-one percent of the patients achieved complete remission after the first cycle of rituximab with a relapse rate of 67.9%. Repeated cycles of rituximab showed a trend to shorten the time to next complete remission and to reduce the rate of subsequent relapses. The adverse events were usually not severe and were manageable. Use of azathioprine significantly prolonged the duration of remission (21.98 ± 16.24 vs. 9.98 ± 7.93 months, P = 0.0232). This effect of azathioprine usage remained after univariate and multivariate logistic regressions. Conclusion: This study provides an insight that azathioprine could serve as a good choice of maintenance therapy for patients receiving rituximab. The efficacy and safety of rituximab remain favorable even with repeated administration. Keywords: Azathioprine, Maintenance, Pemphigus, Rituximab

Objective: To examine the difference in levels of fear of cancer progression (FoP), anxiety, depression between presence/absence of the target-adverse events (AEs); and to examine the differences in incidence rate of AEs and FoP, anxiety, and depression among three generations of EGFR-TKIs therapy (first, gefitinib and erlotinib [G1]; second, afatinib [G2]; third, osimertinib [G3]) in non-small-cell lung cancer (NSCLC) patients.Methods: A cross-sectional study design. NSCLC patients (n=128) were recruited from a medical center in Taiwan. A set of structured questionnaires assessing AEs, FoP, anxiety and depression. Results: Parts of AEs, such as photosensitivity, paronychia, and alopecia, exhibited significantly higher levels of FoP, anxiety, and depression. Less patients experienced AEs in the G3 group than those in the G1 or G2 group but still reported experiencing itching, dry skin with grade 3 severity. The incidence rates of mouth/throat sores, and cheilosis/cheilitis in the G2 group was significantly higher than those in the G1 or G3 group. The incidence rate of FoP, anxiety and depression were 13.8-26.3%, 23.8-40.4% and 16.7-42.1%, respectively.Conclusions: The priorities of care among three generations of EGFR-TKIs in patients with NSCLC were established. FoP, anxiety and depression were present among different targeted therapies and require further attention.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).

Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis.Measure Up 1 and Measure Up 2 were replicate multicentre, randomised, double-blind, placebo-controlled, phase 3 trials; Measure Up 1 was done at 151 clinical centres in 24 countries across Europe, North and South America, Oceania, and the Asia-Pacific region; and Measure Up 2 was done at 154 clinical centres in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. Eligible patients were adolescents (aged 12-17 years) and adults (aged 18-75 years) with moderate-to-severe atopic dermatitis (≥10% of body surface area affected by atopic dermatitis, Eczema Area and Severity Index [EASI] score of ≥16, validated Investigator's Global Assessment for Atopic Dermatitis [vIGA-AD] score of ≥3, and Worst Pruritus Numerical Rating Scale score of ≥4). Patients were randomly assigned (1:1:1) using an interactive response technology system to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks, stratified by baseline disease severity, geographical region, and age. Coprimary endpoints were the proportion of patients who had achieved at least a 75% improvement in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 [clear] or 1 [almost clear] with ≥2 grades of reduction from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2), and are both active but not recruiting.Between Aug 13, 2018, and Dec 23, 2019, 847 patients were randomly assigned to upadacitinib 15 mg (n=281), upadacitinib 30 mg (n=285), or placebo (n=281) in the Measure Up 1 study. Between July 27, 2018, and Jan 17, 2020, 836 patients were randomly assigned to upadacitinib 15 mg (n=276), upadacitinib 30 mg (n=282), or placebo (n=278) in the Measure Up 2 study. At week 16, the coprimary endpoints were met in both studies (all p0·0001). The proportion of patients who had achieved EASI-75 at week 16 was significantly higher in the upadacitinib 15 mg (196 [70%] of 281 patients) and upadacitinib 30 mg (227 [80%] of 285 patients) groups than the placebo group (46 [16%] of 281 patients) in Measure Up 1 (adjusted difference in EASI-75 response rate vs placebo, 53·3% [95% CI 46·4-60·2] for the upadacitinib 15 mg group; 63·4% [57·1-69·8] for the upadacitinib 30 mg group) and Measure Up 2 (166 [60%] of 276 patients in the upadacitinib 15 mg group and 206 [73%] of 282 patients in the upadacitinib 30 mg group vs 37 [13%] of 278 patients in the placebo group; adjusted difference in EASI-75 response rate vs placebo, 46·9% [39·9-53·9] for the upadacitinib 15 mg group; 59·6% [53·1-66·2] for the upadacitinib 30 mg group). The proportion of patients who achieved a vIGA-AD response at week 16 was significantly higher in the upadacitinib 15 mg (135 [48%] patients) and upadacitinib 30 mg (177 [62%] patients) groups than the placebo group (24 [8%] patients) in Measure Up 1 (adjusted difference in vIGA-AD response rate vs placebo, 39·8% [33·2-46·4] for the upadacitinib 15 mg group; 53·6% [47·2-60·0] for the upadacitinib 30 mg group) and Measure Up 2 (107 [39%] patients in the upadacitinib 15 mg group and 147 [52%] patients in the upadacitinib 30 mg group vs 13 [5%] patients in the placebo group; adjusted difference in vIGA-AD response rate vs placebo, 34·0% [27·8-40·2] for the upadacitinib 15 mg group; 47·4% [41·0-53·7] for the upadacitinib 30 mg group). Both upadacitinib doses were well tolerated. The incidence of serious adverse events and adverse events leading to study drug discontinuation were similar among groups. The most frequently reported treatment-emergent adverse events were acne (19 [7%] of 281 patients in the upadacitinib 15 mg group, 49 [17%] of 285 patients in the upadacitinib 30 mg group, and six [2%] of 281 patients in the placebo group in Measure Up 1; 35 [13%] of 276 patients in the upadacitinib 15 mg group, 41 [15%] of 282 patients in the upadacitinib 30 mg group, and six [2%] of 278 patients in the placebo group in Measure Up 2), upper respiratory tract infection (25 [9%] patients, 38 [13%] patients, and 20 [7%] patients; 19 [7%] patients, 17 [16%] patients, and 12 [4%] patients), nasopharyngitis (22 [8%] patients, 33 [12%] patients, and 16 [6%] patients; 16 [6%] patients, 18 [6%] patients, and 13 [5%] patients), headache (14 [5%] patients, 19 [7%] patients, and 12 [4%] patients; 18 [7%] patients, 20 [7%] patients, and 11 [4%] patients), elevation in creatine phosphokinase levels (16 [6%] patients, 16 [6%] patients, and seven [3%] patients; nine [3%] patients, 12 [4%] patients, and five [2%] patients), and atopic dermatitis (nine [3%] patients, four [1%] patients, and 26 [9%] patients; eight [3%] patients, four [1%] patients, and 26 [9%] patients).Monotherapy with upadacitinib might be an effective treatment option and had a positive benefit-risk profile in adolescents and adults with moderate-to-severe atopic dermatitis.AbbVie.

Background/Purpose: Atopic dermatitis (AD) is a common skin disease. At present, there is little evidence regarding its impact on patients' health-related quality of life (HRQoL) in Taiwan. Therefore, this study investigated the relationship between AD severity and patients’ HRQoL in Taiwan. Methods: Patients with AD were recruited from three hospitals in Taiwan from April 2018 to April 2019. AD severity was measured using the Scoring of AD (SCORAD) scale, and HRQoL was assessed using the Dermatology Life Quality Index (DLQI) and the five-level version of EuroQol five-dimension questionnaire (EQ-5D-5L). Results: A total of 200 patients (mean age: 34.4 years) were recruited, including 103 males and 97 females. They were further classified as 79 mild, 72 moderate, and 58 severe AD patients according to their SCORAD scores. There was a positive correlation between their SCORAD and DLQI scores (Spearman's r = 0.77, p

Background Atopic dermatitis has been linked to increased risk of many comorbidities. However, the risks of certain comorbidities are still debated. Objective To better characterize the basic demographics, treatment patterns, and associations between atopic dermatitis and comorbidities and to further investigate the influence of severity on comorbidities. Methods We used a sample cohort of 999,992 people from the National Health Insurance Research Database of Taiwan to evaluate atopic dermatitis in the general population. Results A total of 12,780 patients with atopic dermatitis in 2010 were identified. The prevalence was 1.28%. The proportions of severe and moderate cases were 7.43% and 19.26%, respectively. The most commonly used systemic treatment was corticosteroids. Compared with the general population, atopic dermatitis patients showed increased risks of all 9 groups of comorbidities, including autoimmune disorders, atopic disorders, chronic urticaria, ocular disorders, metabolic disorders, hypertensive disorders, ischemic heart disorders, cerebrovascular disorders, and psychiatric disorders. The severity and persistence of atopic dermatitis were correlated with the development of certain comorbidities. Limitations Miscoding and misclassification might have occurred, and only patients with active disease were enrolled. Conclusion Patients with atopic dermatitis have higher risks of various comorbidities. Comprehensive monitoring and treatment plans are needed to better manage these patients., Graphical abstract

A 40-year-old female presented with rapid-onset generalized erythematous eruption with pustules agminated over the flexural areas and the flanks for 2 days. In skin histopathology, extensive subcorneal pustules, spongiosis and neutrophilic exocytosis, papillary dermal edema, and perivascular and interstitial mixed-cell infiltrates were observed. No psoriasis history but irregular intake of numerous kinds of Chinese herbal medications and the last-modified regimen including Radix Aucklandiae 14 days before the onset of pustular eruption were unveiled. Patch test showed positive result with only Radix Aucklandiae. Thus, acute generalized exanthematous pustulosis induced by Radix Aucklandiae was diagnosed.

Atopic dermatitis (AD) is generally considered a T-helper type 2-dominated disease. Adult AD is often more severe and less manageable by topical therapies and may require systemic immunosuppressants that bear notable side effects and organ toxicities. There is an unmet need for safe and effective long-term therapy in this population. Dupilumab, a fully human monoclonal antibody, dually inhibits interleukin (IL) IL-4 and IL-13 signaling and has demonstrated promising efficacy and acceptable safety profile in several Phase III trials, followed by recent Food and Drug Administration approval for the treatment of moderate-to-severe AD in adults whose disease is inadequately controlled with topical therapies. Dupilumab may also serve as a new treatment option when other systemic medications have failed or are inadvisable. Nevertheless, long-term safety data beyond 1 year and comparison with the existing therapies remain to be investigated. Other emerging agents targeting pruritogenic proteins, chronic inflammation, and epidermal hyperplasia are under vigorous clinical development. In particular, nemolizumab, blocking IL-31-mediated pruritus, has been reported in Phase II trials to provide symptom relief by interrupting the itch-scratch cycle. Accompanied by thorough characterization of different phenotype and endotype subsets, the era of precision medicine could bring new prospects in the optimal treatment of AD.

Background/Purpose Atopic dermatitis (AD) is a chronic inflammatory disease commonly seen in children and increasingly recognized in adults. With recent advances in the therapeutic development for AD, the Taiwanese Dermatological Association (TDA) established a committee to update the consensus for AD management in Taiwan. This report describes the 2020 updated consensus for the management of AD. Methods A panel of 11 core members was convened to review and discuss aspects of AD management and draft recommendation during the first two meetings. The 2015 TDA consensus and the 2017 European guideline, along with recent peer-reviewed articles, serve as the foundation for the update. In the third meeting, AD expert dermatologists selected on a national scale were invited to vote on the final statements. A total of 27 dermatologists attended the final meeting. The consensus was achieved when ratings of 7–9 (out of a total score of 9) accounted for ≥ 75% of the total votes. Results Consensus was achieved on the therapeutic options for AD by lines of treatment. A treatment algorithm was presented to illustrate the place of each modality in terms of basic care, acute disease control, and maintenance therapy. Special considerations for the pediatric population, as well as for women during pregnancy and lactation, are discussed. Conclusion Topical corticosteroids with long-term emollient-based therapies remain the cornerstone of AD treatment. Systemic treatments are indicated when topical therapies and phototherapy fail to control the disease. The recent approval of dupilumab and emerging targeted therapies are expected to bring significant clinical benefit for patients whose disease is inadequately managed by existing options.

BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug-induced immune response. Previous reports have found that CXCL10, also known as interferon-γ-induced protein (IP)-10, may participate in the pathogenesis of cutaneous adverse drug reactions. However, the exact role of IP-10 in DRESS and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) has remained unknown. OBJECTIVES This comparative prospective cohort study aimed to ascertain the roles of the IP-10/CXCR3 axis in DRESS and SJS/TEN. METHODS Plasma IP-10 levels were analysed, and univariate analyses were conducted to assess the relationship between IP-10, human herpesvirus (HHV)-6 reactivation and the development of long-term sequelae. We also performed immunohistochemical staining using skin specimens and flow cytometry to determine the expression of CXCR3 in peripheral blood mononuclear cells (PBMCs). RESULTS Significantly higher plasma IP-10 levels were observed in patients with DRESS with long-term sequelae (effect size 0·81) and also in those with HHV-6 reactivation (effect size 0·83). By immunohistochemistry, more abundant IP-10+ and CXCR3+ cells were demonstrated in the skin lesions of patients with DRESS with HHV-6 reactivation. The percentages of CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were also higher in the PBMCs of HHV-6-reactivated patients with DRESS than in those of patients with SJS/TEN. CONCLUSIONS Higher plasma IP-10 levels are associated with the development of long-term sequelae in DRESS. Higher IP-10/CXCR3 expression in skin and more abundant CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were observed in patients with DRESS with HHV-6 reactivation. The IP-10/CXCR3 axis is associated with HHV-6 reactivation and development of long-term sequelae in DRESS. What is already known about this topic? Elevated levels of interferon-γ-induced protein-10 (IP-10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Patients with DRESS tend to develop long-term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP-10 has been associated with these autoimmune diseases in previous studies. What does this study add? The patients with DRESS with HHV-6 reactivation exhibited higher levels of IP-10 in the plasma and skin than the patients with DRESS without HHV-6 reactivation and the patients with SJS/TEN. Patients with DRESS with higher plasma IP-10 levels tended to develop sequelae during long-term follow-up. What is the translational message? IP-10 is a useful biomarker to predict the development of long-term sequelae in patients with DRESS. Linked Comment: Belloon and Kardaun. Br J Dermatol 2020; 183:804-805.

Acrylates are esters of acrylic acid, which are potent sensitizers that can cause occupational allergic contact dermatitis (ACD) in dental personnel. More recently, an increasing number of cases of both occupational and non-occupational ACD in beauty industry are observed. Here we present three cases of ACD to acrylate and its derivatives in both nail beauticians and do-it-yourself gel nail users due to exposure to nail cosmetics presenting with chronic hand eczema with severe pulpitis and even nail dystrophy with patch-test-confirmed diagnosis. Chemical analysis of commercial nail cosmetic products has been done in one of the patients and successfully identified 2-hydroxypropyl acrylate as the contact allergen. Keywords: Acrylic acid, Acrylate, Allergic contact dermatitis (ACD), Methacrylate, Nail cosmetic products

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.

Background/Objective Since 2005, there has been a significant increase in contact allergy to methylisothiazolinon (MI)/methylchloroisothiazolinone (MCI) incidences in European countries, but there has been no documented large-scale studies of such incidences in Taiwan. Methods From 1987 to 2015, a total of 2590 patients received patch testing in our Contact Dermatitis Clinic. Analyzed were patients with positive reactions to MI/MCI (Kathon CG) in patch testing and with suspected allergy to MI/MCI. Results Among the total 2590 patients, 2388 received patch testing during 1987–2005, while 202 received patch testing during 2006–2015. Because Kathon CG was not routinely patch tested for all patients from 1987 to 2005, the incidence of contact allergy to MI/MCI was thus corrected to 3/145 (2.1%) for this time period. After 2005, there were 11 patients (11/202, 5.4%) who showed positive reactions to MI/MCI. Amongst the 14 patients who showed positive reactions to MI/MCI, 12 of them were females (85.7%). The majority of the lesions was located on the hands (10 patients, 71.4%), along with the face (3 patients, 21.4%). Interestingly, 6 patients (42.9%) who showed positive reactions to MI/MCI were associated with contact allergy to essential oils, and five of them were aromatherapists. Conclusion According to our study, the incidence of MI/MCI contact allergy in a referral center in Taiwan was 5.4%. A trend of increasing incidence of contact allergy to MI/MCI was noted after 2005, which is consistent with the findings in Europe. Allergic contact dermatitis to MI/MCI should be suspected in patients who have eczema on the hands and face, especially those who are aromatherapists.

Background Comprehensive data regarding the epidemiology of chronic urticaria (CU) in general populations are scant. Objectives To investigate the prevalence, incidence, and comorbidities of CU in general population. Methods The data were sourced from the National Health Insurance Research Database (NHIRD) for 2009–2012. Patients who had a primary/secondary ICD-9-CM diagnosis code of 708.1, 708.8, or 708.9 during the year with at least two outpatient visits and an antihistamine prescription, were identified as the cases of CU for each year. The incidence, persistence and comorbidities of CU were examined. Results The prevalence of CU ranged from 0.69% to 0.79% for each year from 2009 to 2012, and the incidence was around 0.50% per year from 2010 to 2012. Comparing to the Standard Population, the standardized prevalence ratios (SPRs) for the rheumatic diseases, thyroid disorders, inflammatory diseases, and psychiatric disorders among CU patients were 2.74, 1.81, 1.57 and 1.87, respectively. Conclusion The prevalence of CU in Taiwan is about 0.69-0.79%. CU is associated with a significantly increased risk of psychiatric disorders, inflammatory diseases, thyroid disorders, and rheumatic diseases. Except for thyroid disorders, the prevalence of these comorbidities tends to increase the longer CU persists.

Background/Purpose This report describes the 2016 consensus of the Taiwanese Dermatological Association (TDA) regarding the definition, classification, diagnosis, prevention, and management of skin toxicities resulting from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This consensus is distributed to practices throughout Taiwan to provide recommendations for the diagnosis and treatment of such skin toxicities in order to improve the quality of life of patients undergoing EGFR-TKI treatment. The consensus thus serves as an important reference for dermatologists and other interested clinicians, such as oncologists, throughout Taiwan. Methods All the consensus contents were voted on by the participating experts, with approval by no less than 75% required for inclusion. Results The consensus provides a comprehensive overview of EGFR-TKI skin toxicities, including recent advances in identifying their causes and the processes by which they develop. Conclusion All the consensus meeting attendees agreed that there are several major EGFR-TKI-related skin toxicities, including acneiform rash (i.e., papulopustular rash), xeroderma, pruritus, paronychia, stomatitis, mucositis, and hair changes (such as hair loss, slowed hair growth, and trichomegaly). The experts were also generally unanimous in their voting on the specific definitions, onset times, and care suggestions for each of those skin toxicities. Furthermore, the recommended treatment algorithms for the various skin toxicities were ultimately approved by 100% (15/15) of the consensus attendees.

Background Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. Objectives To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. Methods We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. Results Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild-type (triple-WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell-cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell-cycle aberrations were independent prognostic factors of melanoma-specific survival. Conclusions This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell-cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival. These observations should be explored further for future drug development.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used as a treatment for non-small-cell lung cancer. There have been some reports of EGFR-TKIs being associated with vascular adverse events. We found that EGFR-TKIs decreased the proliferation of HMEC-1s (immortalized human dermal microvascular endothelial cells) and HMVECs (human dermal microvascular endothelial cells), and also inhibited the phosphorylation of EGFR and ERK. We examined the mRNA expression profile of erlotinib-treated HMEC-1s and identified IQ motif containing GTPase activating protein 1 (IQGAP1) as the most consistently up-regulated transcript and protein. IQGAP1 was also overexpressed and co-localized with endothelial cells in the lesional skin. Notably, increased IQGAP1 expression was associated with decreased transendothelial electrical resistance and increased vascular permeability in vitro. Erlotinib treatment enriched the staining of IQGAP1 and reduced the intensities of α-catenin at the sites of cell-cell contact. In conclusion, erlotinib induces adherens junction dysfunction by modulating the expression of IQGAP1 in dermal endothelial cells. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

BACKGROUND The prevalence of psychiatric comorbidities in patients with chronic urticaria (CU) in a national population is largely unknown. OBJECTIVES To investigate the prevalence of psychiatric disorders and psychiatric medication use in patients with CU in Taiwan. METHODS Data were sourced from Taiwan's National Health Insurance Research Database for 2011. Patients who had a primary/secondary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of 708·1, 708·8 or 708·9 during 2011 with at least two outpatient visits and an antihistamine prescription were identified as CU cases. Patients with CU were classified into three disease severity groups according to their medication types. Psychiatric disorders were identified by patients having three outpatient visits with a primary or secondary diagnosis of a given psychiatric disease. Psychiatric medication use was defined by having at least four outpatient visits with prescriptions for anxiolytics, antidepressants or sleeping pills in 2010 or 2011. RESULTS Of the 167 132 patients with CU, 82·5% had mild CU, 17·0% had moderate CU and 0·4% had severe CU. Patients with CU had a higher prevalence of psychiatric disorders and psychiatric medication prescription than control groups. The relative risk (RR) of psychiatric disorders was 1·43 for patients with mild, 1·50 for patients with moderate and 2·32 for patients with severe CU vs. the controls (P < 0·001). For psychiatric medication prescription, the RRs were 1·95, 2·70 and 2·09, respectively, vs. controls (P < 0·001). CONCLUSIONS Patients with CU had a higher prevalence and risk of psychiatric disorders and psychiatric medication prescription than control groups. What's already known about this topic? Previous studies have shown a high prevalence of psychiatric comorbidities in patients with chronic urticaria (CU), with rates ranging from 35% to 60%. Anxiety, depression and somatoform disorders have been reported as the most prevalent mental disorders in patients with CU. What does this study add? Patients with CU had a higher prevalence of psychiatric disorders and psychiatric medication use than control groups in the general population. The relative risk (RR) of psychiatric disorders was 1·43 for those with mild CU, 1·50 for those with moderate CU and 2·32 for those with severe CU vs. controls. The RR for psychiatric medication use was 1·95 for those with mild CU, 2·70 for those with moderate CU and 2·09 for those with severe CU vs. controls. Mental health evaluations and management are important elements in CU management.

Atopic dermatitis is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions. It is considered one of the most common chronic conditions, with an estimated global prevalence of nearly 230 million. As in the rest of the world, prevalence of atopic dermatitis has been increasing in Asian countries over the last few decades. This increased prevalence in Asian countries has been attributed to factors such as rapid urbanization, increasingly Westernized lifestyles, and improved standards of living and education. As a result, it is important to understand the increasing burden of disease in Asian countries and the differences between the countries in terms of epidemiology, diagnostic criteria, management, quality of life and economic burden.

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.

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.

Background /Purpose BRAF and NRAS mutations have been described in melanomas among Caucasians and some Asian populations. However, few large-scale studies have investigated the status and clinical significance of BRAF and NRAS mutations in a Taiwanese population. Methods Melanoma samples ( n = 119) were analyzed for mutations in exons 11 and 15 of the BRAF gene, and in exons 1 and 2 of the NRAS gene. The samples were studied in genomic DNA, using polymerase chain reaction amplification and Sanger sequencing. Mutations of the BRAF and NRAS genes were then correlated with clinicopathological features and patients' prognosis. Results The incidence of somatic mutations within the BRAF and NRAS genes was 14.3% (17/119 patients) and 10.1% (12/119 patients), respectively. Among the 17 patients with BRAF mutations, 15 (88.2%) had V600E mutations. BRAF mutation was frequently detected in younger patients ( p = 0.0035), in thin melanomas ( p = 0.0181), and in melanomas with less ulceration ( p = 0.0089). NRAS mutation was more often seen in patients with lymph node metastasis ( p = 0.0332). Both BRAF and NRAS mutations were not significantly correlated with overall survival and disease-free survival. Conclusion As BRAF and NRAS mutations are rare in Taiwan, BRAF- or NRAS- targeted therapies may be effective only for selected Taiwanese melanoma patients.

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.

Background/Objective This report describes the 2014 consensus of the Taiwanese Dermatological Association (TDA) regarding the treatment of atopic dermatitis (AD). The TDA consensus is distributed to practices throughout Taiwan to provide recommendations for therapeutic approaches for AD patients to improve their quality of life. Methods The information in the consensus was agreed upon by a panel of national experts at TDA AD consensus meetings held on March 16, May 4, and June 29, 2014. The consensus was in part based on the 2013 Asia–Pacific AD guidelines and the guidelines of the American Academy of Dermatology, with modification to reflect the clinical practice in Taiwan. Results The amendments were drafted after scientific discussions focused on the quality of evidence, risk, and benefits; all the consensus contents were voted on by the participating dermatologists, with approval by at least 75% for inclusion. Conclusion The consensus provides a comprehensive overview of treatment for AD, with some local and cultural considerations for practitioners in Taiwan, especially the use of wet dressings/wraps, systemic immunomodulatory agents, and complementary therapies.

Background/objective Contact dermatitis to topical medicaments is commonly encountered in daily practice of dermatologists. The incidence and ranking of common allergens in topical medicaments may vary depending on local prescription and self-medication behavior. The objective of this study is to investigate the clinical features and common allergens of contact dermatitis to topical medicaments in Taiwan. Methods From 1978 to 2005, a total of 3717 patients had been patch tested in our Contact Dermatitis Clinic. Any case with suspected contact allergy to topical medicaments receiving patch testing was included in this study. Results During this period, a total of 608 patients were included and 603 of them completed the patch tests. Of the 603 patch-tested patients, 397 (66%) were positive for at least one antigen, and all patch tests were negative in 206 (34%). Patients with positive patch testing were characterized by younger age and location on the limbs and skin folds, while sex and atopy were not different among the two groups. A total of 1076 positive reactions to identifiable medicaments or main ingredients were recorded in 397 patients with positive patch testing. Among these positive reactions, 701/1076 counts (65%) were read as relevant. Traditional herbal medicaments (50%), antiseptics (21%), vehicle ingredients (9%), antibiotics (8%), corticosteroids (2%), anesthetics (2%), and nonsteroidal anti-inflammatory drugs (1%) were the most common sensitizers in this study, and the common concomitant allergens were fragrance (52%) and metal (20%). Conclusion The results emphasized the special cultural consideration in Taiwanese patients with contact dermatitis to topical medicaments.

Background/aims Ultraviolet light-signature mutations in the telomerase reverse transcriptase ( TERT ) gene promoter have been identified in cutaneous melanomas, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs). Whether these mutations also occur in periocular tumours, including periocular sebaceous carcinomas (PSCs) and in situ tumours, has not been studied. Methods DNA extraction, PCR and Sanger sequencing were used to determine the frequency of TERT promoter mutations in periocular tumours. The presence of mutations was correlated with histological evidence of solar elastosis. Results Sixty-three tumours were analysed. TERT promoter mutations were identified in 18 of 22 BCCs (82%), 6 of 10 SCCs (60%), 1 of 2 in situ SCCs (50%), 4 of 9 grade III conjunctival intraepithelial neoplasia (CIN III) (44%) and 0 of 20 PSCs (0%). For BCCs, TERT promoter mutations were not associated with the histological risk categories of the tumours. For CIN III cases, all of the three lesions with solar elastosis had TERT promoter mutations, whereas the mutation was found in only one of the six CIN III cases without solar elastosis. Conclusions We demonstrate that ultraviolet light-signature TERT promoter mutations are very common in periocular BCCs, SCCs and CIN III lesions, indicating important roles of ultraviolet light in the pathogenesis of these tumours. In addition, the mutations are present in in situ stage. By contrast, no TERT promoter mutation is found in PSCs.

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a syndrome involving multiple systems. Liver injury is the most common visceral manifestation. Objective The purpose of this study was to investigate the types of liver injury and factors associated with DRESS. Methods A retrospective cohort study was conducted in Taiwan using a DRESS database compiled from December 2000 to March 2013. Results Seventy-two cases were included in this study. Among them, 62 (86.1%) cases involved liver injury, 6 of which (9.7%) were liver injury before skin presentation. The distribution of liver injury patterns at initial presentation was 23 cholestatic type (37.1%), 17 mixed type (27.4%), and 12 hepatocellular type (19.4%). Patients with hepatocellular-type injuries were younger, with a median age of 31.5 ( P = .044). Individuals with liver function results more than 10 times the upper limit were more likely to have fever ( P = .026), took more time to recover, and had fewer eosinophils in the dermis ( P = .002). Limitations The study was a retrospective cohort study with limited cases. Conclusions Liver injury is common in DRESS and frequently associated with atypical lymphocytosis. The cholestatic type is the most common type. Patients with cholestatic-type injuries were older and more frequently had interface changes in skin pathology.

olmutinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of non-small cell lung cancer (NSCLC), especially for those harboring T790M mutations, the most common reason for other EGFR-TKI resistance. We describe three patients who developed acquired palmoplantar keratoderma (PPK) after taking olmutinib, an adverse event which has not been reported in previous generations of EGFR-TKIs. This article is protected by copyright. All rights reserved.

Dermatologic adverse events (dAEs) are common with the use of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. First- and second-generation agents (erlotinib, gefitinib, and afatinib) are frequently associated with acneiform rash, pruritus, xerosis, and paronychia; the incidence and characterization of these dAEs have been well described. However, there is evidence that the dAE profile is different with third-generation EGFR-TKIs. Herein, we describe the dAEs associated with third-generation EGFR-TKIs and our clinical experience with osimertinib, a third-generation EGFR-TKI approved by the U.S. Food and Drug Administration for the treatment of metastatic, EGFR T790M mutation-positive non-small cell lung cancer in patients whose disease has progressed on or after EGFR-TKI therapy. Case summaries of patients from two of our institutions who received osimertinib and were referred to a dermatologist for dAEs are also presented. Overall, the evidence suggests that osimertinib is associated with less severe and less frequent dAEs than first- and second-generation EGFR-TKIs and that therefore a different approach is warranted. Finally, we outline dAE management approaches for osimertinib in the context of those typically employed with first- and second-generation EGFR-TKIs. Implications for Practice Appropriate prevention and management of dermatologic adverse events (dAEs) associated with the use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) may help patients to continue therapy and lessen any negative impact on their quality of life. EGFR-TKIs are frequently associated with acneiform rash, pruritus, xerosis, and paronychia; however, dAEs associated with third-generation EGFR-TKIs are lower in frequency and severity. Before therapy, health care providers should discuss the potential osimertinib-associated dAEs and encourage patients to report their dAEs. Patients should also be educated on prophylactic measures to minimize the severity of dAEs and the importance of adherence to the treatment regimen.

BACKGROUND: Adherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries.METHODS: This was a prospective multicentre feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire.RESULTS: A total of 1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear, and 79% reported that it took less than 5 minutes to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7%±20.5. Mean TOPICOP subscores were 37.0±22.8% for knowledge and beliefs, 54.7±27.8% for fears and 50.1±29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country.CONCLUSIONS: The TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.

The pathogenesis of melanomas emerging in plantar surfaces remains unclear; however, mechanical stress has been reported to increase the formation of melanomas. In this study, we conducted a multicenter retrospective analysis of 153 acral melanomas diagnosed between 2000 and 2015 in Taiwan. The male-to-female ratio of the patients in question was 1:1.28, and the mean age at diagnosis was 68 years. We examined whether melanomas which developed in different areas of the patients’ soles differed in their associations with various clinicopathological characteristics and survival. Testing by goodness of fit indicated that stress-bearing areas were significantly more conducive to the generation of melanomas than non-stress-bearing areas (P P P