Fluvoxamine-induced bullous eruption mimicking hand-foot syndrome and intertrigo-like eruption: rare cutaneous presentations and elusive pathogenesis.
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Publications and source records attributed to Gwo-Shing Chen.
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OBJECTIVE: The purpose of this study is to evaluate the effect of linear polarized light irradiation near the stellate ganglion area on cutaneous blood flow in fingers of patients with progressive systemic sclerosis. BACKGROUND DATA: Sympathetic overactivity is known to be present in patients with progressive systemic sclerosis. Recently introduced linear polarized light irradiation is designed to simulate noninvasive stellate ganglion block to decrease sympathetic output. METHODS: Five patients with progressive systemic sclerosis and three normal healthy controls were studied. Linear polarized light (Super Lizer) was irradiated near the stellate ganglion on the right side of the neck at 358 J/cm(2) for 10 min. Then, laser Doppler flowmetry, laser Doppler imager, and capillary microscopy were used to measure the cutaneous blood flow of the right fourth finger for 30 min. RESULTS: No significant alternations of the skin blood flow between normal controls and patients with progressive systemic sclerosis after linear polarized light irradiation were detected. The effect of linear polarized light on the microcirculation of patients with progressive systemic sclerosis was minimal and transient. CONCLUSION: The effect of linear polarized light in treating patients with progressive systemic sclerosis may not result from the improvement of skin blood flow. Therefore, the use of linear polarized light in those patients to increase cutaneous blood flow should not be overemphasized.
The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.
BACKGROUND: beta1-integrins, which localize to the basolateral surface of basal keratinocytes, are important in the differentiation control and proliferation of the epidermis. Many cutaneous diseases with perturbed differentiation, including arsenical keratosis, show altered patterns of integrin distribution and expression. Arsenic may induce arsenical keratosis through the differentiation and apoptosis aberration by integrins. The purpose of this study is to investigate the role of integrin and arsenic in the pathogenesis of arsenical keratosis. METHODS: Twenty-five specimens obtained from 25 patients with arsenical keratosis disease were studied. Immunohistochemistry staining to beta1, alpha2beta1, or alpha3beta1 integrins was performed in arsenical keratosis and clinically normal perilesional skin. Western blotting was used to assess the expression of integrin beta1 and focal adhesion kinase (FAK) in arsenic-treated cultured keratinocytes. RESULTS: A decreased expression of beta1, alpha2beta1, or alpha3beta1 integrins was demonstrated in arsenical keratosis and clinical normal perilesional skin in a large proportion of arsenical keratosis cases studied. The expressions of integrin beta1 and FAK were both decreased in arsenic-treated keratinocytes. CONCLUSIONS: Our results suggest that arsenic induces abnormal differentiation in arsenical keratosis via the effects of integrin expression in keratinocytes.
To address whether matrix metalloproteinase (MMP)-2 expression by mesenchymal fibroblasts may be differentially modulated by interactions with normal or malignant epidermal cells, we set up a fibroblast co-culture model separately with keratinocytes, basal cell carcinoma cells and melanoma cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and gelatin zymography were used to detect and quantify the expression of MMP-2 by these different kinds of cells. In independent cultures, MMP-2 was highly expressed by fibroblasts and melanoma cells constitutively, but barely expressed by keratinocytes and basal cell carcinoma (BCC) cells. MMP-2 expression by fibroblasts was downregulated in co-cultures with keratinocytes or BCC cells, but not with melanoma cells. These results indicate that epidermal-mesenchymal interactions are important modulators for MMP-2 expression by cutaneous cells and suggest a host-defense mechanism against the tumor progression of BCC.
Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe blistering diseases generally considered to be hypersensitivity reaction to drugs. The aim of this study is to explore the diagnostic role of soluble Fas ligand secretion by peripheral blood mononuclear cells (PBMCs) in patients with previous drug-induced blistering diseases with or without stimulation with the offending drug. The results revealed that PBMCs from the patient group showed significant soluble Fas ligand secretion after stimulation with 100 microg/ml culprit drug (p<0.05). No significant change was seen in the control groups (p>0.05). Taken as a group, PBMCs from the patient group secreted more soluble Fas ligand than the normal control group regardless of drug stimulation. These results indicate that individuals whose PBMCs are high secretors of soluble Fas ligand are prone to severe toxic epidermal necrolysis/Stevens-Johnson syndrome. The possibility of using soluble Fas ligand secretion as a tool for retrospective determination of culprit drugs in patients with previous drug-induced blistering disease awaits further investigation.
We present the case of a 40-year-old woman who had a flesh-colored asymptomatic plaque-like lesion above her chin since she was 30 years old. She was generally healthy and physical examination revealed no congenital abnormalities. Histopathology revealed a normal epidermal surface, mature striated muscle fibers arranged randomly within the dermis, and subcutaneous tissue associated with normal-appearing mesenchymal elements such as adipose tissue, collagen, blood vessels, and mature hair follicles. This fits the diagnosis of rhabdomyomatous mesenchymal hamartoma. Our case was different from previously reported cases with regards to the age of onset and clinical presentation. We report this rare adult case and discuss its differential diagnosis.
Inorganic arsenic is an environmental toxin and a human carcinogen. Being a co-mutagen, arsenic enhances carcinogenesis of ultraviolet irradiation on the mouse skin. Apoptosis, a well-regulated cell death process, is essential for cell development and tissue homeostasis. Dysregulation of apoptosis will lead to various kinds of pathological conditions, such as cancers. The purpose of this study is to investigate the apoptotic effect induced by the interactions of arsenic and UVB on cultured human keratinocytes. Cultured keratinocytes were treated with sodium arsenite (1 microM) and/or UVB 50 mJ/cm2 irradiation in different combinations, including arsenic alone (As group), UVB alone (UVB group), arsenic followed by UVB (As/UVB group), and UVB followed by As (UVB/As group) treatments. Our results revealed that a low concentration of sodium arsenite did not induce keratinocytes apoptosis. The UVB group showed obvious elevation of caspase-8, -9, and -3 activities in addition to strong induction of apoptosis as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling (TUNEL) assay. Similar pro-apoptotic effects were observed in the UVB/As group. In contrast, only subtle changes of cell morphology and survival rate were noticed in the As/UVB group. In addition, the results of Western blot and activity assay of caspase-8, -9, and -3 revealed that neither the receptor nor the mitochondrial apoptotic signaling pathway was activated in the As/UVB group. Therefore, we conclude that the pretreatment of keratinocytes with sodium arsenite decreased the pro-apoptotic effects induced by UVB. This finding corroborated with the animal model studying the effects of arsenic and UVB on carcinogenesis. The molecular mechanisms by which arsenic decreased UVB-induced apoptosis remain to be elucidated.
Basal cell carcinoma (BCC) is the most prevalent malignant skin tumor. In Asian patients, marked pigmentation in BCC lesions is often observed. Recently, endothelins (ETs) have been implicated to participate in the pigmentation process of BCC. Therefore, we set out to investigate the involvement of ET in the pigmentation process of BCC and the potential regulators in the pigmentation pathway. We explored the effects of an established BCC cell line on melanocytes. The growth factor profiles of BCC culture supernatant and effects of supernatant on melanocytes were documented. Potential regulators involved in the pigmentation pathway were also studied. The immunohistochemical staining of pigmented and non-pigmented BCC specimens was performed to confirm our in vitro findings. Our results showed that BCC supernatant contained significant amount of ET-1, basic fibroblast growth factor, and nerve growth factor. Furthermore, BCC supernatant stimulated melanin formation of cultured melanocytes. Addition of ET-receptor antagonist abrogated the melanogenic effect of BCC supernatant on melanocytes. Introduction of UVB irradiation decreased the ET-1 secretion by BCC cells. Immunohistochemical staining of the pigmented facial BCC specimens showed prominent expression of ET-1 on pigmented BCC, while the non-pigmented facial BCC specimens showed little ET-1 reactivity. Tumor necrosis factor-alpha (TNF-alpha) staining showed little expression on BCC specimens, regardless of pigmentation status. In summary, our results indicate that enhanced ET-1 expression in pigmented BCC plays an important role in the hyperpigmentation of this tumor. Moreover, this enhanced ET-1 cascade showed little correlation with UV irradiation and TNF-alpha expression in our study.
Heterotopic salivary gland tissue (HSGT) in the lower neck is an unusual developmental anomaly with characteristic clinical and microscopic findings. The exact embryogenesis remains unclear. This rare entity must be considered in the differential diagnosis of neck mass with fistula. We present a typical HSGT totally removed using the stepladder excision technique and showing an internal fistula. Interpretation of this case from the anatomical and pathological points of view, we support the argument that the embryogenesis of HSGT is more probably related to ectodermal heteroplasia of the precervical sinus of His and further conclude that an association with branchial cleft sinus may exist and cannot be seen as an exclusion criteria for diagnosis of HSGT. Due to possible but infrequent neoplastic transformation, it is important to check HSGT in every encountered cervical anomaly related to any branchial apparatus derived lesion.
Indeterminate cell histiocytosis is a rare neoplasm composed of cells with mixed characteristics of Langerhans cells and non-Langerhans cells. An otherwise healthy, 36-year-old woman presented with asymptomatic generalized papules and nodules that had appeared on all four extremities, the trunk, and cheeks in the previous 6 months. The lesions were firm, painless, non-pruritic, and slightly flesh-yellow or reddish-brown in color. Histopathologic, immunohistochemical examination and electron microscopic studies showed characteristic findings of indeterminate cell histiocytosis: diffuse proliferative histiocytes infiltrating the dermis without epidermotropism or atypia; neoplastic cells expressing markers characteristic of both Langerhans cells (CD1a, S-100) and focal monocytes/macrophages (Factor XIIIa, CD68); and no Birbeck granules within the cytoplasm of the neoplastic cells. Flow cytometry revealed more CD34+ cells in the peripheral blood of the patient than in peripheral blood from a control. Interestingly, the patient responded favorably to psoralen ultraviolet A-range treatment. Herein, we present this case and review the literature.
Although arsenic and ultraviolet light B (UVB) are both causes for skin cancers, lesions of arsenic-induced Bowen's disease are often confined to sun-protected skin. UVB may play a modulatory role in skin carcinogenesis by arsenic. The purpose of this study was to evaluate the effects and interactions of arsenic and UVB on cell cycle progression and apoptosis. Cultured human keratinocytes were treated with sodium arsenite (1 microM) and/or UVB (50 mJ/cm(2)) irradiation in different combinations: (i) arsenic alone, (ii) UVB alone, (iii) arsenic followed by UVB (As-UVB), and (iv) UVB followed by arsenic (UVB-As) treatments. Cell cycle analysis and BrdU pulsing revealed S phase arrest in all treatment groups and growth arrest in As-UVB and UVB-As groups. The terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling assay showed a higher apoptosis rate in the UVB-As group as compared to that of the As-UVB and UVB groups. UVB irradiation significantly decreased Bcl-2 expression. In either the As-UVB or the UVB-As group, the expression of Bcl-2 was further suppressed as compared to the UVB group. The caspase-3, -8, and -9 relative activities were all increased in the UVB group; however, arsenic significantly enhanced caspase-8 and -3 relative activities in UVB-irradiated keratinocytes (the UVB-As group). Pretreatment with the caspase inhibitor(s) rescued the keratinocytes viability to different degrees with the least in the UVB-As group. Our findings revealed that arsenic enhances UVB-induced keratinocyte apoptosis via suppression of Bcl-2 expression and stimulation of caspase-8 activity. Combined UVB and arsenic treatment resulted in the antiproliferative and proapoptotic effects in keratinocytes. Our results provide the explanation for the rare occurrences of arsenical cancers in the sun-exposed skin and the potential therapeutic role of UVB in arsenic-induced Bowen's disease.
BACKGROUND: Sentinel lymphadenectomy has been associated with fewer complications in evaluating regional lymph nodes from melanoma or squamous cell carcinoma. It may also be employed in other malignancies such as localized cutaneous lymphoma. This is the first report demonstrating sentinel lymphadenectomy may be useful on primary cutaneous anaplastic large-cell lymphoma. OBJECTIVE: The objective was to assess the efficacy of sentinel lymphadenectomy on primary cutaneous anaplastic large-cell lymphoma. METHODS: Sentinel lymphadenectomy was performed on a patient with a localized CD30+ primary cutaneous anaplastic large-cell lymphoma. After preoperative lymphoscintigraphy, sentinel lymph node was identified by the gamma probe, excised totally, and sent for histopathologic examination. RESULTS: Sentinel lymphadenectomy was negative for tumor metastasis to sentinel lymph node. Total excision was performed without systemic chemotherapy or immunotherapy. This patient remained tumor-free 36 months after operation. CONCLUSION: Sentinel lymphadenectomy on patients with circumscribed restricted primary cutaneous lymphoma may be beneficial for staging and prognostication of the disease.
Atopic dermatitis (AD) is a pruritic recurring inflammatory skin disease. Recently, topical tacrolimus has been developed to treat AD. This report presents the first clinical experience with topical tacrolimus in Taiwan. This open-label, single-arm study was conducted at three centers from February to May 2002. The duration of each individual treatment was 4 weeks. Two groups were defined: pediatric and adult. Efficacy was evaluated on the basis of the physician's global evaluation at the end of treatment. Success was defined as at least 50% improvement. Other evaluations included the Eczema Area and Severity Index (EASI), the percentage of body surface area (BSA) involved, the patient's assessment of pruritus, and the patient's assessment of overall response. Safety profile was established by monitoring changes in hematology and biochemistry profiles and tacrolimus concentration in blood. All adverse events were recorded. Twenty-six pediatric patients and 42 adult patients were enrolled. Overall success rates were 80.8% and 82.1% in the pediatric and adult groups, respectively. The declines in EASI, percentage of BSA affected, and patient's assessment of pruritus were significant (p < 0.001); 88% and 100% of pediatric and adult patients, respectively, reported a favorable response to treatment. Changes in blood samples were unremarkable. Of pediatric and adult patients, 61.5% and 76.2%, respectively, reported adverse events. The most common adverse event reported was skin burning, which did not result in discontinuation of therapy. This report reveals that tacrolimus ointment is effective and safe for the treatment of AD in Taiwanese patients.
A 33-year-old Taiwanese man presented at our clinic with multiple erythematous ulcerated papules over his bilateral hands. CD30-positive anaplastic large cell lymphoma (CD30+ ALCL) was diagnosed by an incisional biopsy. After a thorough survey for extracutaneous involvement, the diagnosis of primary cutaneous CD30+ ALCL was established. Due to spontaneous regression of some skin lesions, the patient refused therapeutic intervention. Subsequently, an ulcerative nodule arose over the scrotum. It spontaneously regressed 5 weeks later. Although histologically alarming, this particular lymphoma bears favorable prognosis. Thus, recognition of this entity is of great importance, because it may prevent patients from undergoing unnecessary aggressive treatment. To our knowledge, CD30+ ALCL has not been reported to evolve in the pattern similar as observed in our patient. Thus, this Asian man presents a rare presentation of CD30+ ALCL.
Long-term exposure to arsenic induces arsenical cancers in human beings. Arsenic has been shown to induce apoptosis in a variety of cell systems. Previous studies revealed that patients with arsenic-induced Bowen's disease showed a defective cell-mediated immunity and decreased percentages of T cell and T helper cell subpopulations in peripheral mononuclear cells. The purpose of this study was to investigate the effects of arsenic on T cell survival and function in mononuclear cells. Arsenic concentrations higher than 1 micro M induced tumor necrosis factor alpha release from mononuclear cells and caused a cytotoxic effect on T cells. When exposed to higher concentrations of arsenic, apoptosis was induced. CD4+ cells were the major apoptoic population in mononuclear cells. Tumor necrosis factor receptor 1 expression on CD4+ cells, but not Fas/FasL, was significantly enhanced by arsenic treatment compared to other mononuclear cells. Increased expressions of tumor necrosis factor receptor 1 related death domain proteins and activated caspases were observed. These findings indicate that tumor necrosis factor receptor 1 signaling is the major pathway in arsenic-induced T helper cell apoptosis.
Drinking water contaminated by arsenic remains a major public health problem. Long-term arsenic exposure has been found to be associated with peripheral vascular diseases in a variety of studies. Reports of vascular effects of arsenic in drinking water, which span almost 100 years, have been published in Taiwan, Chile, Mexico, and China. This paper reviewed the association of peripheral vascular diseases resulting from arsenic exposure to drinking water from the clinical and pathological points of view. An endemic peripheral vascular disorder called "blackfoot disease" has been noticed in a limited area in Taiwan. This disease results in gangrene in the extremities. It has been associated with the ingestion of high concentrations of arsenic-tainted artesian well water. Epidemiological studies confirmed a dose-response relationship between long-term arsenic exposure and the occurrence of blackfoot disease. Whereas arsenic has induced various clinical manifestations of vascular effects in Chile, Mexico and China, they do not compare in magnitude or severity to the blackfoot disease found in Taiwan. The pathogenesis of vascular effects induced by arsenic is still controversial. The possible mechanisms include endothelial cell destruction, arsenic-associated atherogenesis, carotene and zinc deficiency, and/or some immunological mechanism. Microcirculatory assessments revealed that deficits of capillary blood flow and permeability exist in clinically normal skin of patients with chronic arsenical poisoning. The vascular effects of chronic arsenic poisoning may involve cardiovascular and cerebrovascular systems as well. In view of the increasing public health problems caused by arsenic exposure, vascular effects should be included in the future study of health effects of arsenic.
The levels of seven trace elements such as copper, iron, zinc, selenium, cadmium, chromium, and nickel were determined by graphite furnace-atomic absorption spectrometry in the cervical mucus of 45 women residing in Taiwan, Republic of China. These women were in good health and had no precancerous or cancerous lesions on their cervix. The women were separated into four age groups to establish if there was a relationship between the age of the subjects and the values of these elements in the cervical mucus. By one-way analysis of variance, significant differences in the selenium and nickel concentrations were found among the four age groups (p < 0.05). The mean concentration of selenium in each age group was significantly higher for the older women. A significant correlation between age and selenium concentration was found by linear regression (r = 0.23, p = 0.00048). No significant differences among the concentrations of copper, iron, zinc, cadmium, and chromium were found among these four age groups (p > 0.05). The results presented in this work may be considered as baseline values for these elements in the cervical mucus of healthy Taiwanese women for use as reference in studies on cervical diseases and tissue damage.