Assuntos
Embolia , Borracha , Corantes , Embolia/diagnóstico , Humanos , Polímeros/efeitos adversos , Coloração e RotulagemRESUMO
Pralatrexate has been approved for the treatment of relapsed/refractory peripheral T cell lymphomas. Studies in the U.S. also support the clinical efficacy of pralatrexate to treat advanced-stage cutaneous T-cell lymphomas, but outcomes in Japanese patients have not yet been reported. We herein describe two Japanese patients with heavily-pretreated relapsed/refractory mycosis fungoides that were successfully controlled by pralatrexate.
Assuntos
Micose Fungoide , Neoplasias Cutâneas , Aminopterina/análogos & derivados , Humanos , Japão , Micose Fungoide/tratamento farmacológico , Recidiva Local de Neoplasia , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
Anticorpos Antinucleares/imunologia , Cistadenocarcinoma Seroso/complicações , Dermatomiosite/etiologia , Neoplasias Ovarianas/complicações , Fatores de Transcrição/imunologia , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Biópsia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/terapia , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva , Resultado do TratamentoRESUMO
Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS patients show multiple anomalies including intellectual disability, a distinctive facial appearance, microcephaly, congenital heart defects and Hirschsprung disease. However, the skin manifestation(s) of patients with MOWS has not been documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, such as collagens, whereas molecules involved in degradation of the ECM, such as matrix metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations or deletions.
Assuntos
Colágeno , Derme , Síndrome de Ehlers-Danlos , Fácies , Doença de Hirschsprung , Deficiência Intelectual , Microcefalia , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Animais , Criança , Pré-Escolar , Colágeno/genética , Colágeno/metabolismo , Derme/metabolismo , Derme/patologia , Síndrome de Ehlers-Danlos/genética , Síndrome de Ehlers-Danlos/metabolismo , Síndrome de Ehlers-Danlos/patologia , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Doença de Hirschsprung/genética , Doença de Hirschsprung/metabolismo , Doença de Hirschsprung/patologia , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Deficiência Intelectual/patologia , Masculino , Camundongos , Camundongos Knockout , Microcefalia/genética , Microcefalia/metabolismo , Microcefalia/patologia , Proteólise , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismoAssuntos
Doença de Bowen/epidemiologia , Doença de Bowen/virologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Dedos/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/virologia , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus/isolamento & purificação , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: Dorfman-Chanarin syndrome (DCS), also referred to as neutral lipid storage disease with ichthyosis, is a rare autosomal recessive form of nonbullous congenital ichthyosiform erythroderma, characterized by the presence of intracellular lipid droplets in multiorgans. DCS patients often have mutations in CGI-58, which is an activator of adipose triglyceride lipase (ATGL), leading to accumulation of triglycerides (TG). OBJECTIVE: To study whether a patient with DCS demonstrates TG accumulation in the epidermis and to analyze whether TG levels are correlated with skin disease activity. METHODS: Skin specimen from a 62-year-old man with DCS was stained with oil red O, and analyzed on electromicrographs. Sequencing analysis of CGI-58 was performed using the patient's blood cells. The scales from the lesion were subject to lipid analysis by high-performance thin-layer chromatography (HPTLC). RESULTS: The patient demonstrated ichthyoform erythroderma with a distinct seasonal fluctuation: his skin lesions were aggravated in summer but resolved during winter. Epidermis of the lesion showed intracellular lipid droplets. Sequencing analysis revealed a novel missense mutation in the exon 3 of CGI-58 gene. Lipid analysis of the scales from his lesions, compared with those from normal human control, revealed increased levels of triglycerides (TG) but, in turn, decreased levels of free fatty acids, suggesting dysfunction of adipose TG lipase. Notably, the TG levels in the scales from the patient were positively correlated with the severity of ichthyosis. CONCLUSION: These results suggest that TG accumulation by epidermal keratinocytes directly contributes to ichthyosiform phenotype of DCS.