RESUMO
Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-α blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-α milieu in PsA. We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-α exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-α in MDOC from PsA patients. The number of CD68+WNT5A+ osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-α but not IL-17. We conclude that TNF-α recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.
Assuntos
Artrite Psoriásica/patologia , Quimiocina CCL2/metabolismo , Osteoclastos/patologia , Fator de Necrose Tumoral alfa/metabolismo , Proteína Wnt-5a/metabolismo , Adulto , Artrite Psoriásica/metabolismo , Estudos de Casos e Controles , Movimento Celular , Quimiocina CCL2/genética , Feminino , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Osteoclastos/citologia , Osteoclastos/metabolismo , Células THP-1 , Regulação para Cima , Proteína Wnt-5a/genéticaRESUMO
In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.
Assuntos
Artrite Psoriásica , Psoríase , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Humanos , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Reumatologia , Taiwan/epidemiologiaRESUMO
Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.
Assuntos
Artrite Psoriásica/etiologia , Artrite Psoriásica/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , Monócitos/metabolismo , Osteoclastos/metabolismo , Proteínas Wnt/metabolismo , Adulto , Idoso , Artrite Psoriásica/diagnóstico , Reabsorção Óssea/genética , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Máquina de Vetores de SuporteRESUMO
A murine repeated protein-patch model has been established to study epicutaneous sensitization in atopic dermatitis. This model has shown a predominant Th2 and a weak Th1 response in both BALB/c and C57BL/6 mice. However, Th responses induced in the repeated model are not consistent with the generally accepted theory that BALB/c and C57BL/6 mice are Th2 and Th1 prone and are representatives of human atopy and non-atopy, respectively. In this study, a single protein-patch model was established, which showed in addition to the Th2 response, a remarkable Th1 response in C57BL/6 mice, but not in BALB/c mice. Moreover, using muLangerin-DTR mice, we demonstrated that dermal dendritic cells, but not Langerhans cells, are critical in single epicutaneous sensitization in both strains of mice.
Assuntos
Células Dendríticas/citologia , Células de Langerhans/citologia , Pele/imunologia , Alérgenos/imunologia , Animais , Antígenos CD/metabolismo , Movimento Celular , Células Cultivadas , Citocinas/imunologia , Dermatite Atópica/imunologia , Humanos , Cadeias alfa de Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pele/patologia , Células Th1/citologia , Células Th2/citologiaRESUMO
IMPORTANCE: The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. OBJECTIVE: To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. MAIN OUTCOMES AND MEASURES: Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. RESULTS: The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. CONCLUSIONS AND RELEVANCE: This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.
Assuntos
Anticonvulsivantes/efeitos adversos , Hidrocarboneto de Aril Hidroxilases/genética , Eosinofilia/induzido quimicamente , Fenitoína/efeitos adversos , Síndrome de Stevens-Johnson/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/farmacocinética , Estudos de Casos e Controles , Citocromo P-450 CYP2C9 , Eosinofilia/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Japão , Malásia , Masculino , Pessoa de Meia-Idade , Farmacogenética , Fenitoína/farmacocinética , Polimorfismo de Nucleotídeo Único , Taiwan , Adulto JovemRESUMO
Glucagonoma syndrome encompasses necrolytic migratory erythema (NME), hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, angular cheilitis, steatorrhea, diarrhea, venous thrombosis, and neuropsychiatric disturbance. Of all the symptoms, NME is a rare skin disorder which is pathognomonic for glucagonoma. We present a 61-year-old woman diagnosed initially as pancreatic head adenocarcinoma with liver metastasis prior to the skin eruption. From the dermatologic finding and other clues, glucagonoma was diagnosed finally.
Assuntos
Glucagonoma/diagnóstico , Eritema Migratório Necrolítico/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Feminino , Glucagonoma/patologia , Humanos , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Eritema Migratório Necrolítico/patologiaRESUMO
Psoriasis is a chronic inflammatory skin disease with a profound effect on quality of life and psychosocial stress. The relationship between clinical improvement and psycho-social impact after treatment is complex. The objective of this study was to compare changes in quality of life and psychosocial distress, and overall cost-effectiveness, in patients with psoriasis receiving the modified Goeckerman regimen (UV irradiation and coal tar) with those receiving conventional treatment. Patients with moderate/severe psoriasis receiving the Goeckerman regimen were followed from admission to discharge. Clinical severity, was evaluated weekly using the Psoriasis Area and Severity Index (PASI). Psoriasis Disability Index (PDI) and Hospital Anxiety and Depression Scale (HADS) questionnaires were applied at admission and one month after discharge. Thirty-six patients with psoriasis receiving conventional treatment and 48 patients receiving the Goeckerman regimen were recruited to the study. The mean PASI score in the Goeckerman group decreased from 27.1 to 6.9 and PDI scores decreased from 25.3 to 13.8. HADS scores for anxiety and depression decreased significantly from 9.8 to 6.3 and 9.1 to 6.8, respectively. In comparison with conventional therapy, the modified Goeckerman regime showed similar clinical efficacy, with additional benefits in improving overall quality of life and psychosocial distress in patients with moderate/severe psoriasis, and more cost-effectiveness.
Assuntos
Alcatrão/uso terapêutico , Ceratolíticos/uso terapêutico , Psoríase/terapia , Qualidade de Vida , Estresse Psicológico/prevenção & controle , Terapia Ultravioleta , Adulto , Ansiedade/etiologia , Ansiedade/prevenção & controle , Estudos de Casos e Controles , Alcatrão/economia , Terapia Combinada , Análise Custo-Benefício , Depressão/etiologia , Depressão/prevenção & controle , Avaliação da Deficiência , Feminino , Custos de Cuidados de Saúde , Humanos , Estimativa de Kaplan-Meier , Ceratolíticos/economia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/economia , Psoríase/psicologia , Índice de Gravidade de Doença , Estresse Psicológico/economia , Estresse Psicológico/etiologia , Inquéritos e Questionários , Taiwan , Fatores de Tempo , Resultado do Tratamento , Terapia Ultravioleta/economiaRESUMO
Melanoma metastasis signals dismal prognosis even with current checkpoint inhibitors. Long noncoding RNAs (lncRNAs) regulate dynamic metastasis in several cancers, including melanoma. We became interested in a lncRNA, steroid receptor RNA activator (SRA), because it is the first lncRNA also encoding a conserved protein, SRAP, and it regulates progression of prostate and breast cancers. We investigated how SRA mediates melanoma proliferation, migration, invasion, epithelial-mesenchymal transformation (EMT), and metastasis by RNA interference. The expression of SRAP was measured in melanoma tissue and in human and mouse B16 melanoma cells by immunofluorescence and PCR. The results showed that SRA knockdown decreased B16 cell and A375 cell proliferation and inhibited B16 cell migration significantly. Transwell analysis revealed that CCL21-mediated invasion was abolished in SRA-deficient B16 cells. In parallel, p38 dephosphorylation and reciprocal phosphorylation of B-Raf and mitogen-activated protein kinase kinase 1/2 were present in B16-SRA inhibited cells. The induction of EMT markers, ß-catenin and N-cadherin, by CCL21 was reduced in B16-SRA inhibited cells, suggesting that SRA promotes the EMT process. In vivo experimental metastasis showed that B16-SRA inhibited cells formed significantly fewer tumor nodules in the lungs grossly and microscopically. In summary, our results showed that SRA expression is increased in melanoma tissue and that SRA mediates p38 activation, cell invasion, and proliferation and regulates EMT and distant metastasis.
Assuntos
Melanoma/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Cutâneas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Caderinas/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Nucleares/metabolismo , Fosforilação , Interferência de RNA , Transdução de Sinais , beta Catenina/metabolismoRESUMO
Abnormal skin melanin homeostasis results in refractory pigmentary diseases. Melanogenesis is influenced by gene regulation, ultraviolet radiation, and host epigenetic responses. Steroid receptor RNA activator (SRA), a long noncoding RNA, is known to regulate steroidogenesis and tumorigenesis. However, how SRA contributes to melanogenesis remains unknown. Using RNA interference against SRA in B16 and A375 melanoma cells, we observed increased pigmentation and increased expression of TRP1 and TRP2 at transcriptional and translational levels only in B16 cells. The constitutive phosphorylation of p38 in B16-shCtrl cells was inhibited in cells with knocked down SRAi. Moreover, the melanin content of control B16 cells was increased by SB202190, a p38 inhibitor. Furthermore, reduced p38 phosphorylation, enhanced TRP1 expression, and hypermelanosis were observed in A375 cells with RNA interference. These results indicate that SRA-p38-TRP1 axis has a regulatory role in melanin homeostasis and that SRA might be a potential therapeutic target for treating pigmentary diseases.
Assuntos
Oxirredutases Intramoleculares/metabolismo , Melaninas/metabolismo , Melanoma Experimental/patologia , Glicoproteínas de Membrana/metabolismo , Oxirredutases/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Oxirredutases Intramoleculares/genética , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Glicoproteínas de Membrana/genética , Camundongos , Oxirredutases/genética , Fosforilação , RNA Longo não Codificante/genética , RNA Interferente Pequeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14⺠monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in circulatory CD14⺠monocytes collected from 34 PsA patients, 17 psoriasis without arthritis (PsO) patients, and 34 normal controls (NCs). CD14⺠monocytes were cultured with media containing TNF-α and RANKL to differentiate into osteoclasts. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that the miR-146a-5p expression was higher in PsA patient-derived CD14⺠monocytes compared to PsO and NCs. Activation and bone resorption were selectively enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-146a-5p. More importantly, after clinical improvement using biologics, the increased miR-146a-5p expression in CD14⺠monocytes from PsA patients was selectively abolished, and associated with blood CRP level. Our findings indicate that miR-146a-5p expression in CD14⺠monocytes derived from PsA patients correlates with clinical efficacy, and induction of osteoclast activation and bone resorption.
RESUMO
BACKGROUND: Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown. OBJECTIVE: We aimed to investigate the molecular mechanisms of macrophage polarization in psoriasis. METHODS: 8 patients with moderate to severe psoriasis (Male/Female: 4/4, average age: 47.9 years old) and 8 healthy controls (Male/Female: 4/4, average age: 49.3 years old) were recruited. Their peripheral CD14+ monocytes were isolated with magnetic beads and then were differentiated into macrophages. The differential macrophage polarization was compared among normal controls, psoriatic patients before and after TNF-α inhibitors. The U937 cells were used to investigate the mechanisms by which TNF-α altered the macrophage polarization. RESULTS: The ratio of M1 to M2a macrophage polarization was higher in psoriatic patients comparing with that in controls. The decreasing M1/M2a ratio was parallel to decreasing PASI severity score after adalimumab treatment. Consistently, TNF-α blockage decreased M1/M2a ratio in U937 cells. The induction of STAT1 and IRF-1 in polarized U937 M1 cells was inhibited by TNF-α inhibitor. However, STAT1 and/or IRF-1 interference could not resume M1 polarization. In skin, the increased M1 and M2 infiltration in lesions returned to baseline after successful treatment with TNF-α inhibitor. CONCLUSIONS: Increased M1 polarization is associated with higher disease severity in psoriasis, resuming to baseline after successful treatment by TNF-α inhibitors. TNF-α blockage inhibits M1 polarization through STAT1- and IRF-1-independent pathways. Macrophage polarization may contribute to disease progression in psoriasis.
Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Plasticidade Celular/efeitos dos fármacos , Fator Regulador 1 de Interferon/metabolismo , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Psoríase/tratamento farmacológico , Fator de Transcrição STAT1/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Fenótipo , Psoríase/imunologia , Psoríase/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Células U937RESUMO
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 NCT01276314. FUNDING: Ministry of Science and Technology of Taiwan.
Assuntos
Etanercepte/uso terapêutico , Pele/efeitos dos fármacos , Pele/imunologia , Síndrome de Stevens-Johnson/tratamento farmacológico , Linfócitos T Citotóxicos/citologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Cutânea , Corticosteroides/farmacologia , Adulto , Idoso , Antígenos de Diferenciação de Linfócitos T/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Feminino , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Deep cutaneous fungal infections, including subcutaneous mycoses and systemic fungal infection with cutaneous involvement, cause significant morbidity and mortality in light of increasing immunocompromised patients and global warming. Although a few studies reviewed deep fungal infections in temperate regions, a relevant study in tropical regions is lacking. We evaluated features of deep cutaneous fungal infections in southern Taiwan among the tropical regions. METHODS: We retrospectively reviewed all histopathological specimens with deep cutaneous fungal infections in a single referral center from 2001 to 2014 and successfully identified 23 cases. Medical chart review revealed patient demographic data, clinical presentation, underlying disease, microbiological culture reports, and treatment outcomes. RESULTS: The average patient age was 52 years. Fourteen cases had primary subcutaneous mycoses, and nine had systemic mycoses. Fifteen patients were immunocompromised, including hematological malignancies. Acquired immune deficiency syndrome (AIDS) and long-term steroid use were most commonly associated with deep fungal infections. The positive culture growth rate was 63%. Fonsecaea sp. was most frequently identified by tissue culture. Aspergillosis, mucormycosis, and disseminated cryptococcosis were particularly fatal. CONCLUSIONS: Diabetes and long-term steroid use appear as major risk factors for advanced mycoses in this region. Rapid diagnosis with skin biopsy and tissue culture along with appropriate treatment of deep cutaneous fungal infection are necessary.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Corticosteroides/uso terapêutico , Dermatomicoses/microbiologia , Complicações do Diabetes/complicações , Hospedeiro Imunocomprometido , Antifúngicos/uso terapêutico , Ascomicetos , Aspergilose/complicações , Criptococose/complicações , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/complicações , Estudos Retrospectivos , Fatores de Risco , Tela Subcutânea/microbiologia , Taiwan , Resultado do Tratamento , Clima TropicalRESUMO
Psoriasis is associated with atherosclerosis, in which circulating microparticles play an important role. In severe psoriasis, there was an increase of endothelial- and platelet- microparticles which could be decreased by anti-TNFα. However, whether anti-IL-12/23 treatment would decrease the level of microparticles remains unknown. Our study showed that, despite the clinical improvement of psoriasis after IL-12/13 blockage, the increased levels of circulating CD41a and CD31 microparticles were unchanged after anti-IL-12/23. This result suggested that anti-IL12/23 treatment may not alter the development of cardiovascular disease in patients with psoriasis.
Assuntos
Plaquetas/patologia , Micropartículas Derivadas de Células/patologia , Células Progenitoras Endoteliais/patologia , Psoríase/sangue , Psoríase/terapia , Ustekinumab/administração & dosagem , Adulto , Idoso , Plaquetas/efeitos dos fármacos , Plaquetas/imunologia , Micropartículas Derivadas de Células/efeitos dos fármacos , Micropartículas Derivadas de Células/imunologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/imunologia , Feminino , Humanos , Subunidade p40 da Interleucina-12/imunologia , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Resultado do Tratamento , Ustekinumab/imunologiaRESUMO
Background. In Asians, most basal cell carcinomas (BCCs) are pigmented with clear borders. The consensus of 4 mm surgical margin for BCC largely depends on studies in nonpigmented BCCs in Caucasians. However, little is known about recurrences of pigmented BCCs with a narrower surgical margin. We aimed to investigate 5-year recurrence of BCCs, either pigmented or nonpigmented, in Taiwanese with 3 mm surgical margin. Materials and Methods. 143 patients with BCC (M/F = 66/77, average 64 years) were confirmed pathologically from 2002 to 2013. Based on the pathological margin (>1 mm, ≤1 mm, and involved), patients were categorized into the complete excision group (n = 77), histology with close proximity group (n = 43), and unclear surgical margin group (n = 23). Results. Among 143 cases, 105 were pigmented. With standard 3 mm excision, there were 7 recurrences, with 6 of them from nonpigmented BCC group. Logistic regression showed that pigmentation was associated with lower recurrence. Interestingly, 5-year recurrence of completely excised and histology with close proximity BCC (0/77 versus 1/43) was not different statistically. Conclusions. A 3 mm surgical margin is adequate for pigmented BCC. A "wait and see" approach rather than further wide excision is appropriate for BCC with <1 mm free margin.
Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Idoso , Povo Asiático/estatística & dados numéricos , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgiaRESUMO
For the past decades, although the rash at the bacillus Calmette-Guérin (BCG) inoculation site has been recognized as a diagnostic clue in Kawasaki disease, the present study is the first known one attempting to characterize BCG inoculation by dermatoscopy in Kawasaki disease and correlate the grade of BCG reaction with systemic involvement. Thirty-four patients diagnosed with Kawasaki disease by pediatric specialists were enrolled. We performed detailed history taking, laboratory examination, physical examination and dermatoscopy examinations. Based on the BCG reaction pattern by dermatoscopy, we were able to characterize three patterns: (A) Bull's eye pattern in 18 patients; (B) faint homogenous erythema in nine; and (C) central white patch in seven. Patients from group A exhibited the highest elevation of blood aspartate aminotransferase levels (P < 0.05). Notably, three patients from group A had a significantly dilated coronary artery despite i.v. immunoglobulin injection. We concluded that the bull's eye dermatoscopy sign is not only a useful diagnostic clue but also a severity biomarker in patients with Kawasaki disease.
Assuntos
Aspartato Aminotransferases/sangue , Vacina BCG/imunologia , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Síndrome de Linfonodos Mucocutâneos/imunologia , Vacina BCG/administração & dosagem , Biomarcadores , Criança , Pré-Escolar , Dermoscopia , Eritema/diagnóstico por imagem , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/sangueRESUMO
TRP channels are expressed in various cells in skin. As an organ system to border the host and environment, many nonneuronal cells, including epidermal keratinocytes and melanocytes, express several TRP channels functionally distinct from sensory processing. TRPV1 and TRPV3 in keratinocytes of the epidermis and hair apparatus inhibit proliferation, induce terminal differentiation, induce apoptosis, and promote inflammation. Activation of TRPV4, 6, and TRPA1 promotes regeneration of the severed skin barriers. TRPA1 also enhances responses in contact hypersensitivity. TRPCs in keratinocytes regulate epidermal differentiation. In human diseases with pertubered epidermal differentiation, the expression of TRPCs are altered. TRPMs, which contribute to melanin production in melanocytes, serve as significant prognosis markers in patients with metastatic melanoma. In summary, not only act in sensory processing, TRP channels also contribute to epidermal differentiation, proliferation, barrier integration, skin regeneration, and immune responses. In diseases with aberrant TRP channels, TRP channels might be good therapeutic targets.
RESUMO
PURPOSE: To investigate the disease characteristics of sarcoidosis in southern Taiwan, and to investigate diagnostic methods. METHODS: We retrospectively reviewed the medical records of all patients diagnosed with sarcoidosis at Chang Gung Memorial Hospital, Kaohsiung, from March 1988 to February 2002. RESULTS: A total of 12 patients (3 men, 9 women), with a mean age of 44.5 years, and a diagnosis of sarcoidosis by positive histology and either a typical chest roentgenogram or clinical presentation were included. All 12 patients had intrathoracic involvement (hilar or mediastinal lymph nodes, 12; lungs, 5), eight had skin involvement, and two had extrathoracic lymph node involvement. The most frequent biopsy specimens were from the skin (n = 10), followed by the intrathoracic lymph nodes (n = 4), lungs (n = 2), and extrathoracic lymph nodes (n = 2). Four patients had positive biopsies from two organs. Our data showed an older age distribution and a greater female predominance of the disease compared with Western countries. A higher rate of intrathoracic and skin involvement was also found, but the reason for this was not clear. CONCLUSIONS: Greater awareness of possible skin involvement may enable chest physicians and clinical practitioners to suspect this condition earlier. A histologic diagnosis from skin biopsy should then be made, rather than using more invasive procedures.
Assuntos
Sarcoidose/epidemiologia , Adulto , Distribuição por Idade , Biópsia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sarcoidose/diagnóstico , Distribuição por Sexo , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Taiwan/epidemiologiaRESUMO
Acne is a common disease in adolescence with female preponderance. It could cause poor self-esteem and social phobia. Previous studies based on questionnaires from several thousands of adolescents showed that acne is associated with major depression and suicide. However, the gender- and age-specific risk of depression and suicide in patients with acne remain largely unknown. Using a database from the National Health Insurance, which included 98% of the population of Taiwan in 2006, we identified patients of acne, major depression, and suicide based on ICD-9-CM codes. Totally 47111 patients with acne were identified (16568 males and 30543 females) from 1 million subjects. The youths of 7-12 years had the highest prevalence of acne (14.39%). Major depression was more common in those with acne (0.77%) than controls (0.56% , P < 0.0001) regardless of gender. Multiple logistic regression showed an increased risk of major depression in women without acne (OR = 1.85, 95% CI 1.75-1.96). The risk is additive in women with acne (OR = 2.78, 95% CI 2.43-3.17). Similar additive risk of suicide was noticed in women with acne. In conclusion, acne and gender, independently and jointly, are associated with major depression and suicide. Special medical support should be warranted in females with acne for the risk of major depression and suicide.