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Background: The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality., Methods: We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemistry and electron microscopy analyses., Results: Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%-98.1%) to CVA6 strains reported from Finland at 2008., Conclusions: This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.

To recognize patients with inhibitory and neutralizing auto-antibodies to interferon-γ (AutoAbs-IFN-γ) presenting with the sporadic phenotype of Mendelian Susceptibility to Mycobacterial Disease (MSMD) mainly characterized by recurrent intracellular mycobacterium or/and salmonella infections, we comprehensively investigated IL12/23-IFN-γ signaling, candidate genetic sequencings or/and protein expressions of IL12RB1, IFNRG1, IL12p40, IFNRG2, STAT1, IKKA, NEMO, CYBB and IRF8 in four patients. Their serum was further titrated to detect AutoAbs-IFN-γ, for which the biological activity was assessed in Jurkat T cells. The patients mainly presented with recurrent non-tuberculous mycobacterium osteomyelitis and lymphadenopathy (Mycobacterium abscessus, chelonae and avium intracellular complex), and salmonella sepsis (S. enterica serogroup B, C2 and D). Additionally, Penicillium marneffei, varicella-zoster virus, and herpes simplex virus infections occurred. Inhibitory and neutralizing IFN-γ downstream signaling was elucidated in Jurkat cell lines as decreased MHC class I and phosphorylated STAT1 expression. Together with 24 patients from the PubMed search, the majority of the AutoAbs-IFN-γ patients were Asian (25/28). The most common involvement was lymph nodes (in 22/28), lungs (19/28) and bones (12/28). Mycobacterium avium complex (in 14) and chelonae (7) were the most common pathogens from 40 isolations. In contrast to those with the mild form of MSMD phenotype, AutoAbs-IFN-γ patients, in the absence of BCG-induced diseases, had a more persistent course and poor response to IFN-γ treatment. In conclusion, AutoAbs-IFN-γ patients may have a sporadic adult-onset MSMD phenotype in Asian regions endemic for mycobacterial infections., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

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: Hyper-immunoglobulin E recurrent infection syndromes (HIES) has characteristic features and identified mutations. This study investigated clinical features and causal candidate mutations in Taiwanese patients with the HIES phenotype on referral base over 23 million inhabitants., Patients and Methods: Clinical manifestations of the HIES phenotype, severity scoring, immunological functions and candidate genes of signal transducer and activator of transcription 3 (STAT3), tyrosine kinase 2 (TYKZ), and dedicator of cytokineses 8 (DOCK8) were analyzed., Results: Between 1985 and 2009, six sporadic and two siblings met HIES criteria (onset age: 2-54 months; severity score: 31-65) out of 187 patients with primary immunodeficiencies. Five patients with the autosomal dominant (AD)-HIES phenotype presented as pneumatocoele, bronchiectasis, retained primary teeth, minor trauma fracture, scoliosis, coronary aneurysm, and lymphoma. Three with the autosomal recessive (AR)-HIES phenotype and impaired lymphocyte proliferation function had herpes simplex virus infection, molluscum contagiosum, and cerebral vasculitis. Notably in one patient with the AR-HIES phenotype, unintentional lead component in traditional application herbs for accelerating wound healing deposited in basal ganglia and aggravated involuntary movement relative to cerebral vacculitis. Those with mildly elevated memory T cells and decreased memory B cells trended to develop arteritis. Of five AD-HIES patients, three were mortalities from acute myocardial infarction, Proteus mirabilis, and Staphylococcus aureus sepsis. Only one had de novo novel STAT3 (Gln 469 Arg) mutation with "relative" lower HIES STAT3 score., Conclusions: Known genetic defects responsible for the HIES phenotype are not so common in Taiwan. This may infer genetic variations in different ethnicities although selection bias and under-diagnosis for HIES with known genetic defects could be contribution factors.

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.