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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., (Copyright © 2015. Published by Elsevier B.V.)

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Allopurinol, an antihyperuricaemic agent, is one of the common causes of life-threatening severe cutaneous adverse reactions (SCAR), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The prognostic factors for allopurinol-related SCAR remain unclear. This study aimed to investigate the relationship of dosing, renal function, plasma levels of oxypurinol and granulysin (a cytotoxic protein of SJS/TEN), the disease severity and mortality in allopurinol-SCAR., Methods: We prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and granulysin were determined., Results: In this cohort, HLA-B*58:01 was strongly associated with allopurinol-SCAR (p<0.001, OR (95% CI) 109 (25 to 481)); however, the initial/maintenance dosages showed no relationship with the disease. Poor renal function was significantly associated with the delayed clearance of plasma oxypurinol, and increased the risk of allopurinol-SCAR (p<0.001, OR (95% CI) 8.0 (3.9 to 17)). Sustained high levels of oxypurinol after allopurinol withdrawal correlated with the poor prognosis of allopurinol-SCAR. In particular, the increased plasma levels of oxypurinol and granulysin linked to the high mortality of allopurinol-SJS/TEN (p<0.01), and strongly associated with prolonged cutaneous reactions in allopurinol-DRESS (p<0.05)., Conclusions: Impaired renal function and increased plasma levels of oxypurinol and granulysin correlated with the poor prognosis of allopurinol-SCAR. Allopurinol prescription is suggested to be avoided in subjects with renal insufficiency and HLA-B*58:01 carriers. An early intervention to increase the clearance of plasma oxypurinol may improve the prognosis of allopurinol-SCAR., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background/purpose: Sentinel lymph node biopsy (SLNB) is a standard procedure in the management of clinically node-negative melanoma. However, few studies have been performed on SLNB in Asia, which is an acral melanoma-prevalent area. This study evaluated the clinicopathologic prognostic factors of disease-free survival (DFS) and overall survival (OS) in Taiwanese patients with cutaneous melanoma who received wide excision and SLNB. The prognosis of patients with false-negative (FN) SLNB was also evaluated., Methods: Malignant melanoma cases were reviewed for 518 patients who were treated between January 2000 and December 2011. Of these patients, 127 patients with node-negative cutaneous melanoma who received successful SLNB were eligible for inclusion in the study., Results: The SLNB-positive rate was 34.6%. The median DFS was 51.5 months, and the median OS was 90.9 months at the median follow-up of 36.6 months. Multivariate analysis revealed that patients whose melanoma had a Breslow thickness greater than 2 mm had a significantly shorter DFS than patients whose melanoma had a Breslow thickness of 2 mm or less [hazard ratio (HR), 3.421; p = 0.005]. Independent prognostic factors of OS were a Breslow thickness greater than 2 mm (HR, 4.435; p = 0.002); nonacral melanoma (HR, 3.048; p = 0.001); and an age older than 65 years (HR, 2.819; p = 0.036). During the follow-up period, 13 of 83 SLN-negative patients developed a regional nodal recurrence. The SLNB failure rate was 15.7% and the FN rate was 22.8%. Compared to patients with a true-positive SLNB, patients with FN SLNB had a significantly shorter DFS (p = 0.001) but no significant difference in OS (p = 0.262)., Conclusion: Except for the pathologic subtypes, prognostic factors in Taiwan are similar to those used in other melanoma-prevalent countries. Identifying and closely monitoring patients at risk of nodal recurrence after a negative SLNB is important., (Copyright © 2013. Published by Elsevier B.V.)

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: Everolimus has been approved for second-line treatment of patients with metastatic renal cell carcinoma (mRCC) after failure of sorafenib or sunitinib. The purpose of this retrospective study was to assess the efficacy and safety of everolimus in Taiwanese patients with mRCC., Methods: Between March 2009 and August 2011, 24 mRCC patients treated with everolimus were analyzed. Prior to everolimus, each patient had received therapy with at least one vascular endothelial growth factor receptor-tyrosine kinase inhibitor. Progression-free survival (PFS) and overall survival (OS) were estimated according to the Kaplan-Meier method., Results: Fifteen patients (62.5%) achieved stable disease. The median PFS was 7.1 months (95% confidence interval, 3.6-10.5 months). The median OS was 20.7 months (95% confidence interval, 5.0-36.4 months). The most frequent non-hematologic adverse events with everolimus were mucositis, rash, epistaxis and pneumonitis., Conclusions: Everolimus is an effective second-line treatment for Taiwanese patients with mRCC. The toxicity is tolerable and manageable.

Background: Livedoid vasculopathy (LV) is a disease characterized by multiple painful and recurrent ulcerations on the feet, accompanied by atrophic scars. Many researchers suggest that a hypercoagulable status is the pathogenetic factor for LV. However, the cause of LV remains elusive., Objective: We sought to determine if endothelial dysfunction is present in patients with LV., Methods: This prospective study included 16 patients with LV and active ulcers and 16 matched control subjects. We reviewed detailed clinical parameters, including antinuclear antibody, high-sensitivity C-reactive protein, protein C, protein S, homocysteine, anti-SSA, anti-SSB, anticardiolipin antibody, and serum lipid profiles. Flow-mediated vasodilation of the brachial artery was used as an indicator of vascular endothelial function using high-resolution 2-dimensional ultrasonic imaging., Results: Blood pressure, blood biochemistry, high-sensitivity C-reactive protein, and homocysteine were not significantly different in patients with LV and control subjects. Nitroglycerin-mediated vasodilation was not significantly different in patients with LV and control subjects. However, flow-mediated vasodilation was much less in patients with LV than in the control group (3.58 ± 2.32% vs 7.51 ± 2.40%, P < .001)., Limitations: The study was performed at a single site with a limited sample size., Conclusion: Peripheral vascular endothelial dysfunction was demonstrated in patients with LV by reduction of brachial flow-mediated vasodilation., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Eccrine angiomatous hamartoma (EAH) comprises a rare nevoid proliferation of normal eccrine glands and small blood vessels and occasionally other elements in the middle and deep dermis with variable clinical manifestations. Case series have rarely been published except for case reports and literature reviews. The aims of this article were to investigate the clinical and pathologic features of patients with EAH in Taiwan and to compare our results with the results of previous studies., Methods: A retrospective review of medical records and histopathological findings was performed on patients diagnosed with EAH in a medical center in Taiwan between 1994 and 2010., Results: Fifteen patients with pathologically diagnosed EAH were collected. The mean age at the time of diagnosis was 38.6 years (range, birth to 67 years). The male to female ratio was 3 to 2. In most cases, EAH arose as a single lesion on a lower extremity. The symptoms and signs most commonly associated with EAH were pain (60%), hypertrichosis (13.3%), itching (13.3%) and hyperhidrosis (6.7%). Additional pathological findings included hemangioma (13.3%), verrucous hemangioma (6.7%), arteriovenous malformation (6.7%), and angiokeratoma (6.7%). None of the patients experienced spontaneous regression of the lesions before excision. Excisions were done in one patient under general anesthesia, and ten patients with local anesthesia. Four patients were kept under observation. Tumor recurrences were noted in two out of the eleven patients whose lesions were excised., Conclusion: Compared with cases in the literature, we found additional histopathological findings and an increased tumor recurrence risk in our cohort. EAH remains a benign and uncommon hamartomatous condition. Further multi-center, retrospective studies with larger case numbers are needed to better characterize the disease presentation in Asian populations.

Background and Purpose: Lymphoscintigraphy has been considered a useful tool for sentinel lymph node (SLN) mapping for malignant melanoma. This study evaluated the usefulness of SLN detection by lymphoscintigraphy and excision with intraoperative gamma probe in Taiwanese patients with malignant melanoma., Methods: Thirty six malignant melanoma patients in clinical stage I and II were enrolled. The Breslow thickness of the primary melanomas was /= 4 mm in 3 patients, and unknown in 4 patients who were transferred from other hospitals and had no nodal or distant metastasis. SLN lymphoscintigraphy was performed with filtered 99mTc-sulfur colloid. An intraoperative gamma probe was used to identify the SLN for dissection., Results: A total of 44 SLNs were detected in 36 patients, with a mean of 1.22 SLNs per patient. The SLN detection rate by lymphoscintigraphy was 100%. During surgery, 39 of the 44 SLNs (88.6%) in 33 of 36 patients (91.7%) were identified. SLN metastasis was found in 8 of 39 dissected SLNs (20.5%) or in 8 of 36 patients (22.2%). The SLN metastatic rate in the patients with primary melanoma with Breslow thickness 2.0 mm was 41.7% (5/12)., Conclusions: Lymphoscintigraphy and intraoperative gamma probe are useful in localizing and dissecting SLN in patients with malignant melanoma. SLN mapping changed the clinical stage in 22.2% of melanoma patients.

Recombinant interferon beta-1b (INF-beta-1b) has been proven to be an effective means of treating relapsing-remitting multiple sclerosis (MS). Adverse reactions to interferon therapy have been well documented. The most common side effects are transient influenza-like symptoms, including fever, fatigue, nausea, and myalgia. Cutaneous necrosis has occasionally been reported, mostly involving small and limited lesions. This article describes an MS patient who developed multiple large, deep cutaneous ulcers on INF-beta-1b injection sites, which subsequently required surgical treatment. Vessel thrombosis in the subcutaneous fatty layer and the clinical appearance of livedoid erythema beside the ulcers indicated that INF-3-1b may have caused skin necrosis through its vascular effects.