RESUMO
BACKGROUND: Cell adhesion molecules are essential to lymphocyte migration in neoplastic and inflammatory skin diseases. Our aim was to investigate possible differences in cell adhesion molecule expression between mycosis fungoides (MF) and inflammatory skin diseases (drug reactions and allergic contact dermatitis). METHODS: We selected 33 biopsies from patients with MF and 10 biopsies of patients with inflammatory skin diseases from Department of Pathology-Universidade Federal de São Paulo (UNIFESP) from January 1997 to December 2013. Expression of α4ß1 integrin and αEß7 integrin was assessed by immunohistochemistry in intraepidermal lymphocytes by counting 4 microscopic epidermal fields (×400) and comparing those between the 2 groups. RESULTS: We observed increased expression of integrin αEß7 in intraepidermal lymphocytes in advanced stages of MF (T3 and T4). αEß7 expression was detected in intraepidermal dendritic cells of MF and inflammatory diseases samples. The expression of E-cadherin in epidermal cells in MF outlined Pautrier microabscesses, whereas in inflammatory diseases, spongiosis reduced its expression in keratinocytes. CONCLUSIONS: The findings presented here support the idea that the lymphocyte migratory mechanism observed in neoplasms is similar to that of inflammatory processes of the skin.
Assuntos
Biomarcadores Tumorais/análise , Moléculas de Adesão Celular/análise , Dermatite/patologia , Integrinas/metabolismo , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/genética , Biópsia por Agulha , Brasil , Estudos Transversais , Dermatite/genética , Progressão da Doença , Feminino , Hospitais Universitários , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Neoplasias Cutâneas/genéticaRESUMO
Resumo A Síndrome de Blau é uma doença de caráter hereditário autossômico dominante a qual também pode ocorrer de forma esporádica via mutação "de novo". Em geral, tem aparecimento precoce ainda na primeira infância e sua tríade clássica inclui artrite, dermatite e uveíte. Este trabalho visa relatar as manifestações clínicas e principalmente oftalmológicas de uma paciente diagnosticada com Síndrome de Blau com ênfase ao achado incomum de infiltrados corneanos subepiteliais, raramente descrito na literatura.
Abstract The Blau syndrome is an autosomal dominant hereditary disease which can also occur sporadically via "de novo" mutation. Overall it has early onset and its classic triad includes arthritis, dermatitis and uveitis. This paper describes clinical and mainly especially ophthalmologic manifestations of a patient diagnosed with Blau syndrome with emphasis on an uncommon finding of corneal subepithelial infiltrates, rarely described in the literature.
Assuntos
Humanos , Feminino , Adolescente , Artrite/genética , Uveíte/etiologia , Uveíte/genética , Córnea , Dermatite/genética , Mutação , SíndromeRESUMO
BACKGROUND: Ticks attach to and penetrate their hosts' skin and inactivate multiple components of host responses in order to acquire a blood meal. Infestation loads with the cattle tick, Rhipicephalus microplus, are heritable: some breeds carry high loads of reproductively successful ticks, whereas in others, few ticks feed and reproduce efficiently. METHODS: In order to elucidate the mechanisms that result in the different outcomes of infestations with cattle ticks, we examined global gene expression and inflammation induced by tick bites in skins from one resistant and one susceptible breed of cattle that underwent primary infestations with larvae and nymphs of R. microplus. We also examined the expression profiles of genes encoding secreted tick proteins that mediate parasitism in larvae and nymphs feeding on these breeds. RESULTS: Functional analyses of differentially expressed genes in the skin suggest that allergic contact-like dermatitis develops with ensuing production of IL-6, CXCL-8 and CCL-2 and is sustained by HMGB1, ISG15 and PKR, leading to expression of pro-inflammatory chemokines and cytokines that recruit granulocytes and T lymphocytes. Importantly, this response is delayed in susceptible hosts. Histopathological analyses of infested skins showed inflammatory reactions surrounding tick cement cones that enable attachment in both breeds, but in genetically tick-resistant bovines they destabilized the cone. The transcription data provided insights into tick-mediated activation of basophils, which have previously been shown to be a key to host resistance in model systems. Skin from tick-susceptible bovines expressed more transcripts encoding enzymes that detoxify tissues. Interestingly, these enzymes also produce volatile odoriferous compounds and, accordingly, skin rubbings from tick-susceptible bovines attracted significantly more tick larvae than rubbings from resistant hosts. Moreover, transcripts encoding secreted modulatory molecules by the tick were significantly more abundant in larval and in nymphal salivary glands from ticks feeding on susceptible bovines. CONCLUSIONS: Compared with tick-susceptible hosts, genes encoding enzymes producing volatile compounds exhibit significantly lower expression in resistant hosts, which may render them less attractive to larvae; resistant hosts expose ticks to an earlier inflammatory response, which in ticks is associated with significantly lower expression of genes encoding salivary proteins that suppress host immunity, inflammation and coagulation.
Assuntos
Doenças dos Bovinos/imunologia , Predisposição Genética para Doença , Rhipicephalus/imunologia , Pele/imunologia , Infestações por Carrapato/veterinária , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Bovinos , Doenças dos Bovinos/genética , Doenças dos Bovinos/parasitologia , Citocinas/genética , Dermatite/genética , Dermatite/imunologia , Dermatite/parasitologia , Dermatite/veterinária , Suscetibilidade a Doenças/parasitologia , Perfilação da Expressão Gênica , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Inflamação/genética , Interleucina-6/genética , Larva/fisiologia , Ninfa/fisiologia , Pele/parasitologia , Pele/patologia , Infestações por Carrapato/genética , Infestações por Carrapato/imunologiaRESUMO
The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1α, IL-1ß, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature.
Assuntos
Antígenos CD4/análise , Ciclo-Oxigenase 2/análise , Dermatite/imunologia , Mediadores da Inflamação/análise , Interleucina-17/análise , Melanose/imunologia , Pele/imunologia , Imunidade Adaptativa , Adulto , Doenças Assintomáticas , Biomarcadores/análise , Estudos de Casos e Controles , Ciclo-Oxigenase 2/genética , Dermatite/enzimologia , Dermatite/genética , Dermatite/patologia , Feminino , Humanos , Imunidade Inata , Imuno-Histoquímica , Interleucina-17/genética , Melanose/enzimologia , Melanose/genética , Melanose/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Pele/enzimologia , Pele/patologia , Regulação para CimaRESUMO
Lipid mediators derived from 5-lipoxygenase (5-LO) metabolism can activate both pro- and anti-inflammatory pathways, but their role in wound healing remains largely unexplored. In this study we show that 5-LO knockout (5-LO(-/-)) mice exhibited faster wound healing than wild-type (WT) animals, and exhibited upregulation of heme oxygenase-1 (HO-1). Furthermore, HO-1 inhibition in 5-LO(-/-) mice abolished the beneficial effect observed. Despite the fact that 5-LO(-/-) mice exhibited faster healing, in in vitro assays both migration and proliferation of human dermal fibroblasts (HDFs) were inhibited by the 5-LO pharmacologic inhibitor AA861. No changes were observed in the expression of fibronectin, transforming growth factor (I and III), and α-smooth muscle actin (α-SMA). Interestingly, AA861 treatment significantly decreased ROS formation by stimulated fibroblasts. Similar to 5-LO(-/-) mice, induction of HO-1, but not superoxide dismutase-2 (SOD-2), was also observed in response to 5-LO (AA861) or 5-LO activating protein (MK886) inhibitors. HO-1 induction was independent of nuclear factor (erythroid derived-2) like2 (Nrf-2), cyclooxygenase 2 (COX-2) products, or lipoxin action. Taken together, our results show that 5-LO disruption improves wound healing and alters fibroblast function by an antioxidant mechanism based on HO-1 induction. Overexpression of HO-1 in wounds may facilitate early wound resolution.
Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Dermatite/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Cicatrização/fisiologia , Adulto , Animais , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/imunologia , Dermatite/genética , Dermatite/imunologia , Derme/citologia , Derme/imunologia , Derme/metabolismo , Modelos Animais de Doenças , Fibroblastos/imunologia , Fibroblastos/metabolismo , Heme Oxigenase-1/imunologia , Humanos , Masculino , Proteínas de Membrana/imunologia , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , Estresse Oxidativo/fisiologia , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismoRESUMO
Acute primary cutaneous leishmaniasis typically presents microscopically with a lymphohistiocytic infiltrate containing admixed plasma cells, parasitized macrophages and abundant organisms. Tuberculoid granulomatous changes may occur in the later phases of primary infection. A 23-year-old male presented 1 month after visiting Peru with classic clinical findings of acute primary cutaneous leishmaniasis, while histopathology showed a tuberculoid granulomatous process that lacked any organisms in hematoxylin-eosin and fungal stains. Polymerase chain reaction (PCR) analysis and tissue cultures confirmed the diagnosis of cutaneous leishmaniasis with Leishmania (Viannia) panamensis infection. A pauci-organism tuberculoid granulomatous process may uncommonly be the presenting histopathology in the acute infectious phase of cutaneous leishmaniasis. Clinicians and dermatopathologists should be aware of this atypical presentation, which may cause diagnostic confusion and delay proper treatment. PCR testing should be employed in cases with high clinical suspicion when histopathology is not definitive.
Assuntos
Dermatite , Granuloma , Leishmania guyanensis/genética , Leishmaniose Mucocutânea , Reação em Cadeia da Polimerase , Tuberculose Cutânea , Adulto , Dermatite/genética , Dermatite/parasitologia , Dermatite/patologia , Diagnóstico Diferencial , Granuloma/genética , Granuloma/parasitologia , Granuloma/patologia , Humanos , Leishmaniose Mucocutânea/genética , Leishmaniose Mucocutânea/parasitologia , Leishmaniose Mucocutânea/patologia , Masculino , Peru , Tuberculose Cutânea/genética , Tuberculose Cutânea/parasitologia , Tuberculose Cutânea/patologiaRESUMO
BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis (IDH) is a chronic and recurrent eczema occurring during childhood and adolescence. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy of adulthood, presenting with slowly progressive spastic paraparesis and sphincter dysfunction with mild sensory involvement. There are few reports describing an association between IDH and HAM/TSP. The objective of this study was to evaluate the occurrence of HAM/TSP in patients with IDH and in seropositive members of their families and to determine the blood levels of antibodies against HTLV-1 in patients with HAM/TSP. METHODS: Twenty patients with IDH and their seropositive mothers and siblings underwent clinical, neurological, and laboratory evaluations. The diagnosis of HAM/TSP was made in accordance with the World Health Organization criteria. RESULTS: Nine individuals had HAM/TSP (6 of the patients with IDH, 2 mothers, and 1 seropositive brother). In 3 families, > 1 individual had HAM/TSP. The serum antibody titers of the patients with HAM/TSP varied from 1 : 3.125 to 1 : 78.125. CONCLUSIONS: A strong association was observed between IDH and HAM/TSP. The familial clustering of both diseases suggests a genetic background. Serological screening for HTLV-1 in children with symptoms of myelopathy is essential in areas where HTLV-1 is endemic.
Assuntos
Dermatite/virologia , Infecções por HTLV-I/complicações , Infecções por HTLV-I/genética , Paraparesia Espástica Tropical/complicações , Paraparesia Espástica Tropical/genética , Dermatopatias Virais/complicações , Dermatopatias Virais/genética , Adolescente , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Líquido Cefalorraquidiano/virologia , Criança , Análise por Conglomerados , Dermatite/genética , Família , Feminino , Infecções por HTLV-I/diagnóstico , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Masculino , Exame NeurológicoRESUMO
A spontaneous recessive mutation named nackt (symbol: nkt) affecting hair growth and T-cell development was discovered in a moderately inbred stock of mice. Skin lesions were characterized by sparse rough coat, bare patches around the eyes and neck, and a scratching behavior throughout life. Fluorescence-activated cell sorter analysis indicated a deficiency in the CD4(+) 8(-) T-cell subset in the thymus and a marked decrease in CD4(+) T cells in peripheral lymphoid organs. Linkage analysis using a set of molecular markers and an F2 intersubspecific cross indicated that the mutation maps to the central region of mouse chromosome 13, in a region homologous to human chromosome 5q22-q35.
Assuntos
Alopecia/genética , Antígenos CD4/genética , Dermatite/genética , Camundongos Mutantes , Mutação , Animais , Comportamento Animal , Mapeamento Cromossômico , Genes Recessivos , Ligação Genética , Haplótipos , Camundongos , Subpopulações de Linfócitos T , Timo/citologia , Timo/imunologiaRESUMO
A possible causal association between infective dermatitis and HTLV-I infection was reported in 1990 and confirmed in 1992. We now report familial infective dermatitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major histocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune response to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I-seropositive younger son requires close clinical follow-up.
Assuntos
Dermatite/etiologia , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Infecções por HTLV-I/imunologia , Paraparesia Espástica Tropical/imunologia , Dermatopatias Infecciosas/etiologia , Adulto , Criança , Pré-Escolar , Dermatite/genética , Dermatite/imunologia , Feminino , Genótipo , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Infecções por HTLV-I/complicações , Infecções por HTLV-I/genética , Haplótipos , Teste de Histocompatibilidade , Humanos , Jamaica , Masculino , Paraparesia Espástica Tropical/epidemiologia , Linhagem , Valor Preditivo dos Testes , Dermatopatias Infecciosas/genética , Dermatopatias Infecciosas/imunologiaRESUMO
A possible causal association between infective dematitis and HTLV-I infection was reported familial infective dematitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major hitocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB*DQBI* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune repsonse to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I seropositive younger son requires close clinical follow-up. (AU)