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Background Clear cell acanthoma (CCA) of the nipple/areola has been reported. The CCA-like histology more likely represents a feature of eczematous dermatitis of the nipple/areola. Objective We reviewed cases of CCA-like lesions of the nipple/areola and compared them with classic CCA to clarify their relationship. Methods The clinicopathological features of 12 cases of CCA-like lesions of the nipple/areola were compared with classic CCA. The literature on this condition was reviewed, and the results of various treatments were analyzed. Results CCA-like lesions of the nipple/areola were clinically different from those of classic CCA. Although they shared the glycogen-rich clear epidermal cells with neutrophilic exocytosis, dermal eosinophils appeared to be a distinctive feature. The anatomic site and association with atopic dermatitis suggested that CCA-like lesions of nipple/areola might represent a manifestation of atopic eczema involving nipple/areola. Topical steroids could be effective. Limitations This was a retrospective study with limited cases. Conclusions Although CCA-like lesions of the nipple/areola shared histopathological features with classic CCA, their clinical changes were consistent with dermatitis. We propose to name this condition CCA-like eczematous dermatitis of the nipple/areola.

Background Chronic rhinosinusitis (CRS) is a multi-factorial disorder that causes systemic symptoms beyond rhinologic symptoms alone. A possible association between autonomic nervous system (ANS) dysfunction and CRS has been identified; however, few studies have confirmed this observation. In this study, we prospectively measured changes in ANS dysfunction symptoms following functional endoscopic sinus surgery (FESS) and explored the impact of ANS dysfunction on surgical outcomes of CRS. Methodology Patients diagnosed with CRS who consented to surgical intervention were included prospectively. All patients completed the Sino-nasal Outcome Test-22 (SNOT-22) and the 31-item Composite Autonomic Symptom Score (COMPASS 31) questionnaires before the operation and during the follow-up period. Clinical demographic data, Lund-Mackay, and modified Lund-Kennedy scores were recorded and measured. Results A total of 102 patients were enrolled. The median SNOT-22 and COMPASS 31 scores significantly improved following FESS from 43.0 to 14.0 and 21.0 to 11.2 (all P less than 0.001), respectively. FESS led to a significant reduction in the prevalence of various ANS dysfunction symptoms. In multivariate analyses, revision surgeries (odds ratio [OR] 5.012, 95% confidence interval [CI] 1.52416.489; P=0.008), CRS with nasal polyps (OR 4.071, 95% CI 1.454-11.40; P=0.008), and higher Pre-FESS COMPASS 31 scores (OR 1.043, 95% CI 1.003-1.084; P=0.036) were independent risk factors for uncontrolled inflammation following FESS. Conclusions ANS dysfunction symptoms are prevalent in CRS and higher preoperative COMPASS 31 scores correspond with poor surgical outcomes. Following FESS, the majority of ANS dysfunction symptoms can be alleviated. Further investigations are required to explore the possible mechanism of how ANS is involved in the pathogenesis of CRS.

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.

We studied a family with Gorlin-Goltz syndrome. The novel mutations of our cases were located on the 21st exon of the PTCH1 gene (c.3450C>G). The father, who received a strategic 56-day vismodegib treatment for disease control, was the first patient with Gorlin syndrome treated with the hedgehog inhibitor in Taiwan. The lesions regressed gradually, with scar formation, and were subsequently removed via a wide excision. Further details are provided below.

The expanding use of novel targeted anticancer agents such as sorafenib has led to an increasing number of dermatologic adverse events. Although cutaneous adverse events are commonly described in patients taking sorafenib, there are few reports describing psoriasis secondary to this medication. In this report, we describe 3 patients with sorafenib-induced psoriasiform drug eruption and review the available literature of similar patient cases. Our findings highlight shared characteristics among affected patients and potential treatment options for patients in whom sorafenib cannot be discontinued. Increased awareness of such drug eruptions and management options is critical to prevent suboptimal dosing and decreased quality of life.

Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remain unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells involved in the pathogenesis of dapsone-induced severe cutaneous adverse reactions. We enrolled patients from Taiwan and Malaysia with DRESS and maculopapular eruption with chronic inflammatory dermatoses. Our results showed that the HLA-B*13:01 allele was present in 85.7% (6/7) of patients with dapsone DRESS (odds ratio = 49.64, 95% confidence interval = 5.89–418.13; corrected P = 2.92 × 10–4) but in only 10.8% (73/677) of general population control individuals in Taiwan. The level of granulysin, the severe cutaneous adverse reaction-specific cytotoxic protein released from cytotoxic T cells, was increased in both the plasma of DRESS patients (36.14 ± 9.02 ng/ml, P

INTRODUCTION Medical students and residents will encounter many cutaneous fungal infections in medical practice. However, the training for identification of medical fungi has been insufficient due to limited lecture-based courses. The objective of this study was to evaluate the impact of using smartphone-based wallpapers in learning the microscopic morphology and colony characteristics of medical fungi for medical students and residents. METHODS A smartphone-based wallpaper learning module using a wallpaper-changing software application (app) was introduced in this 3-week training course. Twenty-six participants were enrolled and divided into two groups: nondermatology trainees, including medical students and postgraduate year one (PGY-1) doctors who have not yet specialized, and dermatology trainees (dermatology residents). All of the participants completed a 3-week training course, and the effectiveness of the module was evaluated by pre- and post-course multiple-choice examinations. RESULTS Both nondermatology and dermatology trainees scored significantly higher in post-course examinations than pre-course examinations (P < 0.001). The dermatology trainees performed better than nondermatology trainees in the pre-course examinations (P < 0.001). In the post-course examinations, no significant difference in scores was noted between dermatology and nondermatology trainees (P = 0.573). DISCUSSION The smartphone-based wallpaper learning module was effective in helping medical students and residents learn and memorize morphologic characteristics of fungi. In comparison to conventional lecture-based learning, this new mobile module was more readily accessible and convenient for learners to engage in learning.

Chromoblastomycosis (CBM) is an implantation mycosis characterized by the presence of pigmented muriform cells in tissue. CBM is endemic in Taiwan, but only three formal cases have been reported to date because of underreporting. To describe and update its epidemiologic features, we report a series of 30 cases between 2003 and 2016 at a single medical center. Patients were predominately male (2.75:1). The mean age of onset was 65.9 years, and disease duration ranged from 2 months to 20 years. Diabetes was the most common comorbidity, and extremities were the most frequent sites of involvement. The lesions presented as papuloplaque, verrucous, cicatricial, targetoid, or mixed types. The dermoscopic features were variable, including red dots, white vague areas, black globules, and sand-like patterns. Among 10 Fonsecaea isolates further identified by sequencing the ITS regions of ribosomal DNA, nine were F. monophora and one was F. nubica. All but one patient received either systemic antifungal agents, surgical excision, or both. Surgical excision achieved a higher complete remission rate than the other forms of treatment did.

Background Mycobacterium abscessus complex (MABC) is the most common non-tuberculous mycobacterium that causes complicated skin and soft tissue infections (cSSTIs). The selection of antimycobacterial agents for successful treatment of such infections is a critical issue. Objectives To investigate the antimicrobial susceptibility patterns of MABC isolates from skin and soft tissue to a variety of antimycobacterial agents. Methods Sixty-seven MABC isolates were collected and partial gene sequencing of secA1, rpoB and hsp65 was used to classify them into three subspecies: M. abscessus subsp. abscessus (MAB), M. abscessus subsp. massiliense (MMA) and M. abscessus subsp. bolletii (MBO). The MICs of 11 antimycobacterial agents for these 67 isolates were determined using a broth microdilution method and commercial Sensititre RAPMYCOI MIC plates, as recommended by CLSI. Results In total, 28 MAB, 38 MMA and 1 MBO were isolated from patients with cSSTIs at our hospital. Most MABC strains were resistant to ciprofloxacin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin and trimethoprim/sulfamethoxazole. In addition, most MABC strains were intermediately susceptible or resistant to cefoxitin. Eighteen of the 28 MABs and 1 MBO isolate harboured the T28 polymorphism in the erm(41) gene. Two of the 38 MMA isolates had an rrl A2059G point mutation. Most of the MABC strains were susceptible to amikacin and tigecycline. Conclusions In Taiwan, amikacin, clarithromycin and tigecycline have good activity against MMA and MAB erm(41) C28 sequevar isolates, whereas amikacin and tigecycline, rather than clarithromycin, have good activity against both MBO and MAB erm(41) T28 sequevar isolates. Clinical trials are warranted to correlate these data with clinical outcomes.

Background Effective management of psoriasis is a cause for much concern. In Taiwan, there is a lack of consensus on management strategies for psoriasis, especially the principles of drug prescribing in psoriatic patients. Objectives The Taiwanese Dermatological Association convened Expert Panel meetings three times between 2012 and 2015 to discuss the management strategies for treatment of psoriasis in order to fill the knowledge gap and provide a reference tool for Taiwanese dermatologists. Results This paper reports the final output from the three meetings, with the aim of aiding clinical decision making in terms of principles of prescribing, including dosing strategies, efficacy profiles, and safety concerns in connection with eight categories of antipsoriatic treatment: topical agents, phototherapy, nonbiologic conventional systemic agents, licensed biologic systemic agents, newly emerging therapies, combination therapy, transitional therapy, and traditional Chinese medicine. Conclusion The Expert Panel, comprising distinguished Taiwanese dermatologists, succeeded in developing a consensus about the management of psoriasis in Taiwanese patients. Unavailability of data in certain areas may suggest a possibility of new directions in research.

Background/purpose This report describes the 2014 consensus of the Taiwanese Dermatological Association regarding the definition, classification, diagnosis, and management of urticaria. This consensus is distributed to practices throughout Taiwan to provide recommendations for diagnostic and therapeutic approaches for common subtypes of urticaria, in order to improve the quality of life of urticaria patients. The consensus, thus, serves as an important reference for dermatologists throughout Taiwan. Methods All the consensus contents were voted on by the participating dermatologists, with approval by no less than 75% being required for inclusion. The consensus provides a comprehensive overview of urticaria, including recent advances in identifying its causes and the processes by which it develops. Results All the consensus meeting attendees agreed to a definition of urticaria, which states that it is characterized by the sudden appearance of wheals (also known as hives), angioedema, or both. Most of the experts (16 out of 19, or 84.2%) agreed that chronic urticaria is defined as the sudden occurrence of wheals and/or angioedema for a period of ≥ 6 weeks. In addition, the consensus attendees also approved the Urticaria Activity Score system or the Urticaria Activity Score for 7 days system as the recommended method for assessing disease activity in spontaneous urticaria. Conclusion It was also determined that the treatment goal for patients with any form of urticaria should be complete cessation of suffering from all urticaria symptoms. The recommended treatment algorithms for chronic spontaneous urticaria and acute urticaria were finally proposed and approved by 100% (19/19) and 84.2% (16/19) of the consensus attendees, respectively.

PURPOSE The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype ( P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

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.

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5-91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.

BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%–62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS. The anti–TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01276314","term_id":"NCT01276314"}}NCT01276314. FUNDING. Ministry of Science and Technology of Taiwan.

Background/Objective The incidence of psoriasis vulgaris in Asians is estimated at 0.05–0.30%. Studies in North America and Europe demonstrated that adalimumab, a fully human monoclonal IgG1 antibody, is an efficacious treatment for psoriatic arthritis and chronic plaque psoriasis. The aim of this study was to evaluate the efficacy and safety of adalimumab in treating psoriatic arthritis (PsA) in patients who have moderate to severe psoriasis. Methods This was a retrospective study comprising 12 patients with chronic plaque psoriasis and psoriatic arthritis who were treated with adalimumab between October 2008 and February 2013. All had failed treatment with conventional systemic agents. Patients were started on adalimumab 40 mg every other week. Results At week 12, 3 of 12 patients (25%) achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75). With regard to PsA, at week 12, the improved Psoriatic Arthritis Response Criteria (PsARC) response was experienced by 75% (9 of 12) of the patients. Mean improvement in Dermatology Life Quality Index (DLQI) was 42%. Five of 12 patients (42%) experienced adverse events, which were generally mild. Conclusion Patients with refractory psoriatic arthritis appeared to be responsive to adalimumab. The achievement rate of PsARC in our study was comparable to the efficacy reported in previous literature. Detection of antinuclear antibodies was not associated with the responsiveness in this trial, nor did it influence the potential for adverse effects. Adalimumab as a monotherapy is generally effective and safe.

Psoriasis is a chronic debilitating disease that impairs patients' physical and social functioning. The assessment of health-related quality of life (HRQoL) provides a comprehensive insight into the actual disease burden that are not captured by the traditional clinical parameters. The objective of this study is to identify factors that may impact patients' HRQoL. We conducted a cross-sectional study, recruiting a total of 414 psoriasis vulgaris patients between January 2008 and December 2011. Our study found no significant correlation between disease severity or duration of psoriasis with HRQoL. Female patients have poorer HRQoL. Psoriatic arthritis, nail involvement, burning and itching sensation have a detrimental effect on HRQoL. This study highlighted that specific disease-associated symptoms such as itching and burning sensation, nail involvement and/or concomitant arthritis were important factors that may impact patients' HRQoL devoid of clinical severity. Physicians should carefully consider these factors when treating psoriasis patients.

Background Previous studies of microfocused ultrasound with visualization (MFU-V) on facial and neck laxity were largely based on masked physician assessments, histological analysis, and safety profile. More quantitative studies are needed. Objective To evaluate the 800 treatment lines of MFU-V on skin tightening effect of face and neck in Asians using 2 quantitative analysis systems at 0, 90, and 180 days after treatment. Materials and methods Total 25 subjects were recruited in this prospective study. Subjects were treated with MFU-V to the face and neck using 2 different transducers: 4 MHz, 4.5-mm focal depth and 7 MHz, 3.0-mm focal depth with total 800 lines. The subjects were evaluated by skin complexion analysis and 3-dimensional imaging system at 0, 90, and 180 days. Mean brow height lift and submental lift were calculated. Results All 25 subjects completed treatment and received the follow-up examinations at 90 and 180 days. Two of the 25 subjects were male. Mean patient age was 53.3 years (range: 39.8-61.1 years). Wrinkles, texture, and pores were 3 variables relevant to analysis of skin laxity. Only mean wrinkles score reduction at 90 days was statistically significant (p = .0222). There was a mean 0.47 mm brow lift at 90 days (p = .0165), but there was a 0.12 mm decrease in brow height compared to baseline at 180 days (p = .6494). At 90 days, a mean 26.44 mm submental lift was noted (p = .0217). And at 180 days, a mean 13.76 mm submental lift was noted (p = .243). Conclusion This study showed that the most prominent change after the 800-line MFU-V treatments in Asians was the significant submental lift at 90 days. Other noninvasive or minimally invasive treatment modalities can be considered to combine with MFU-V for the optimal treatment response. Additional MFU-V treatments can be considered 3 months after the first treatment.

Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

The nail provides a functional protection to the fingertips and surrounding tissue from external injuries. Nail plate divided into three layers including dorsal, intermediate, and ventral layers. The dorsal layer consists of compact, hard keratins, limiting topical drug delivery through the nail. In this study, we investigate the application of fractional CO2 laser that produces arrays of microthermal ablation zones (MAZs) to facilitate drug delivery in the nails. Moreover, optical coherence tomography (OCT) is implemented for real-time monitoring of the laser–skin tissue interaction, sparing the patient from invasive surgical sampling procedure. Observations of drug diffusion through the induced MAZ array are achieved by evaluating the time-dependent OCT intensity variance. Subsequently, nails are treated with cream and liquid topical drugs to investigate the feasibility and diffusion efficacy of laser-assisted drug delivery. Our results show that fractional CO2 laser improves the efficacy of topical drug delivery in the nail plate, and that OCT could potentially be used for in vivo monitoring of the depth of laser penetration as well as real-time observations of drug delivery.

// Cheng-Lung Hsu 1 , Jai-Shin Liu 1,3 , An-Chi Lin 1 , Chih-Hsun Yang 2 , Wen-Hung Chung 2 , Wen-Guey Wu 3 1 Division of Hematology-Oncology, Departments of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan, ROC; 2 Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan, ROC; 3 Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan, ROC Correspondence: Cheng-Lung Hsu, email: // Wen-Guey Wu, email: // Keywords : minoxidil, androgen, androgen receptor, androgenetic alopecia, prostate cancer Received : February 10, 2014 Accepted : April 07, 2014 Published : April 08, 2014 Abstract Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a K d value of 2.6 µM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases.

Background Systemic antibiotics are a major cause of severe cutaneous adverse reactions (SCARs). The selection of alternative antibiotics and management for SCARs patients with underlying infections can be challenging. Methods We retrospectively analyzed 74 cases of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), related to use of systemic antibiotics in Taiwan from January 2006 to January 2012. We analyzed the causative antibiotics, clinical features, organ involvements, and mortality. We also assessed patient tolerability to alternative antibiotics after the development of antibiotic-related SCARs. Results The most common causes of SCARs were penicillins and cephalosporins for SJS/TEN and AGEP; glycopeptides for DRESS. Fatality was more frequent in the SJS/TEN group. In patients with SJS/TEN, higher mortality was associated with old age and underlying sepsis before the development of SCARs. The majority of patients with penicillin- or cephalosporin-related SCARs were able to tolerate quinolones, glycopeptides, and carbapenems. Conclusions Complicated underlying conditions and infections may increase mortality in patients with antibiotic-related SCARs. The selection of structurally different alternative drugs is important to avoid recurrence.

Background Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective To carry out a comprehensive analysis on the clinical spectrum and HLA genotype–phenotype correlations in CBZ-induced hypersensitivity reactions. Methods We analyzed the clinical information of 194 patients with CBZ hypersensitivity (51 MPE, 23 DRESS, 112 SJS/TEN, and 8 cases with other phenotypes), and 152 CBZ-tolerant controls. All are Han Chinese. We examined the HLA-A/HLA-B genotypes, gene dosage, and drug dosage effects. Results CBZ-SJS/TEN showed the strongest association with the HLA-B*15:02 allele (Pc=5.8×10 −43 ; odds ratio (OR) (95% CI)=97.6(42.0–226.8)), in which HLA-B*15:02 was identified in all patients (25/25) with SJS/TEN with >5% body surface area (BSA) skin detachment, but lost its 100% association (85.1%, 74/87) in SJS with HLA-B*40:01 showed negative association with CBZ-induced SJS/TEN ((Pc=8.3×10 −5 ; OR (95% CI)=0.22(0.1–0.4)). By comparison, CBZ-induced MPE/DRESS had no association with HLA-B*15:02 , but linked to HLA-A*31:01 (Pc=2.7×10 −3 ; OR (95% CI)=6.86(2.4–19.9), and HLA-B*51:01 (Pc=0.01; OR (95% CI)=4.56(2.0–10.5)). No gene dosage or CBZ dosage effects was observed. Conclusion This study reported the different strength of HLA association with CBZ hypersensitivity in Han Chinese. With the increasing application of pharmacogenetic markers, the HLA genotype–phenotype correlations and the results of the test need to be carefully interpreted for CBZ-induced hypersensitivity reactions.