RESUMO
Acquired circumscribed hyperpigmented patches and plaques have various differential diagnoses, including post-inflammatory hyperpigmentation and mycosis fungoides (MF). Leukomelanoderma is an uncommon cutaneous condition in which the pathogenesis is not fully elucidated. It has been reported that leukomelanoderma occurs after allergic contact dermatitis from hydroquinone or acute cutaneous graft-versus-host disease (1,2). Hyperpigmented MF is a cutaneous T-cell lymphoma with a frequent CD8+ phenotype (3). Herein, we report a case of leukomelanoderma clinically and histologically resembling hyperpigmented MF. A 55-year-old Japanese woman was referred to our department for evaluation of reticulate pigmentation with pruritic erythema on the face. She had used commercially available depigmenting cosmetic reagents for 20 years and ointment containing 10% hydroquinone for 3 months. Physical examination revealed diffuse hyperpigmentation and demarcated hypopigmented macules on the face and neck (Figure 1, a). Dermoscopy showed depigmented spots and reticulated plus dotted hyperpigmentation; it presented a pseudo-pigment network (Figure 1, b). Histological examination of a tissue specimen biopsied from the lesion showed superficial band-like lymphocytic infiltration in dermis accompanying single cells or small clusters in epidermis (Figure 1, c). Interface changes were observed together with melanophages in the dermis. Melan-A-positive melanocytes were absent. Immunohistochemical analysis demonstrated that the epidermotropic lymphocytes were CD3+CD7-, and they had predominance of CD8+ cells (Figure 1, d). These immunohistochemical results mimicked MF. However, PCR analysis of the T-cell receptor g-gene rearrangement was negative. Closed patch test result with hydroquinone (5% pet.) was graded D2 (+?) and D3 (+). Ten months after discontinuing cosmetic reagents and hydroquinone, the pigmentary changes showed improvement. The pathomechanism of leukomelanoderma is unclear. Although post-inflammatory pigmentation due to allergic or contact dermatitis together with direct depigmenting effects from hydroquinone use has been suggested (1), the immunophenotype of T-cells has not been examined. As observed in our patient, interface changes with melanophages, in addition to frequent CD8+ phenotype of the epidermotropism and dermal infiltrate of lymphocytes, were characteristic for hyperpigmented MF (3). Moreover, minimal CD7 expression was a specific finding for MF (4). T-cell receptor clonality was negative in our patient, but the clonality appears to be detected by PCR in up to 50% of the patients with early MF (3). In contrast, the closed patch test was positive for hydroquinone in our patient, and it is reported that CD8+ T-cells are recruited to the interphase between the epidermis and the dermis of the patients with allergic contact dermatitis (5). CD8+ T-cells might contribute to acute cutaneous graft-versus-host disease-like interface changes and destroy melanocytes in the leukomelanoderma lesion. Allergic contact dermatitis presenting as leukomelanoderma was thus suggested in our patient. However, further reports and studies are required to support this issue. Therefore, we considered it necessary to follow the patient, since MF was not absolutely eliminated.
Assuntos
Hiperpigmentação , Micose Fungoide , Neoplasias Cutâneas , Humanos , Feminino , Pessoa de Meia-Idade , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Hiperpigmentação/patologia , Hiperpigmentação/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Diagnóstico DiferencialRESUMO
BACKGROUND: Cutavirus (CuV) is associated with mycosis fungoides; however, the CuV status in parapsoriasis en plaques (PP), a premalignant inflammatory condition of mycosis fungoides, has not been fully delineated. METHODS: Fifty-five Japanese patients with chronic inflammatory skin diseases, including 13 patients with PP, were studied. RESULTS: CuV DNA was detected significantly more frequently in biopsies of the lesional skin from patients with PP (38%; 4 of 13) than in those from patients with other inflammatory skin diseases (2%; 1 of 42; P = .009). All CuV-positive PP cases were of the large-plaque parapsoriasis (LPP) subtype. The viral loads ranged from 83 450 to 2 164 170 copies/103 cells. We recovered near-full-length CuV sequences from the CuV-positive LPP biopsies, all of which were of the Japanese/Asian genotype. The CuV genome appeared to be present within lymphoid cells infiltrating the epidermis and dermis. CuV NS1 and VP1 gene transcripts were also detected in the affected tissues. CONCLUSIONS: The detection of high levels of CuV DNA with the expression of viral mRNA suggests a potential role for CuV in the pathogenesis of LPP, making it necessary to study further the impact of CuV, especially regarding the viral genotype, on the outcomes of patients with CuV-positive LPP.
Assuntos
Micose Fungoide , Parapsoríase , Humanos , Micose Fungoide/virologia , Micose Fungoide/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Parapsoríase/virologia , Parapsoríase/patologia , Adulto , DNA Viral/genética , Pele/patologia , Pele/virologia , Carga Viral , Japão , Idoso de 80 Anos ou mais , Biópsia , Neoplasias Cutâneas/virologia , Neoplasias Cutâneas/patologia , Lesões Pré-Cancerosas/virologia , Lesões Pré-Cancerosas/patologia , Vírus de DNA/genética , Vírus de DNA/isolamento & purificação , Vírus de DNA/classificaçãoRESUMO
BACKGROUND: Cutavirus (CuV) is associated with mycosis fungoides; however, the CuV status in parapsoriasis en plaques (PP), a premalignant inflammatory condition of mycosis fungoides, has not been fully delineated. METHODS: Fifty-five Japanese patients with chronic inflammatory skin diseases, including 13 patients with PP, were studied. RESULTS: CuV DNA was detected significantly more frequently in biopsies of the lesional skin from patients with PP (38% [4/13]) than in those from patients with other inflammatory skin diseases (2% [1/42]; P = 0.009). All CuV-positive PP cases were of the large plaque parapsoriasis (LPP) subtype. The viral loads ranged from 83,450 to 2,164,170 copies/103 cells. We recovered near-full-length CuV sequences from the CuV-positive LPP biopsies, all of which were of the Japanese/Asian genotype. The CuV genome appeared to be present within lymphoid cells infiltrating the epidermis and dermis. CuV NS1 and VP1 gene transcripts were also detected in the affected tissues. CONCLUSIONS: The preferential detection of high levels of CuV DNA with the expression of viral mRNA suggests a potential role for CuV in the pathogenesis of LPP, making it necessary to study further the impact of CuV, especially regarding the viral genotype, on the outcomes of patients with CuV-positive LPP.
RESUMO
BACKGROUND: European studies suggest an association between cutavirus (CuV) and cutaneous T-cell lymphoma (CTCL); however, the worldwide prevalence of CuV in patients with CTCL and its prognostic impact remain unknown. METHODS: We investigated the prevalence and viral loads of CuV DNA using biopsy specimens from the lesional skins of 141 Japanese patients with cutaneous malignancies, including 55 patients with various types of CTCL. RESULTS: CuV DNA was detected significantly more frequently in biopsies from patients with mycosis fungoides (MF) (38% [13/34]; the most common subtype of CTCL) than in those from patients with other cutaneous malignancies (6% [6/107]; P<0.001). The viral-load range in patients with CuV DNA-positive MF was 23-3922 copies/103 cells and 8-65 copies/µg of DNA. A phylogenetic analysis using the partial sequences of the CuV viral capsid protein 1 (VP1)/VP2 genes revealed that the CuV sequences identified here were clustered in a Japanese-specific clade distinct from that comprising CuV sequences from European patients with MF. Kaplan-Meier curves and a log-rank test showed that CuV positivity was associated with a shorter disease-specific survival in patients with MF (P = 0.031), whereas no significant difference in overall survival was observed (P = 0.275). No significant correlation was observed between CuV DNA load and survival in patients with CuV-positive MF. CONCLUSIONS: Our results suggest that CuV is associated with MF in a subset of Japanese patients. Large-scale prospective studies are warranted to clarify the role of CuV status, especially regarding the viral genotype, on adverse outcomes in patients with CuV-positive MF.
Assuntos
Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Humanos , Filogenia , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/genética , Micose Fungoide/metabolismo , Micose Fungoide/patologia , PrognósticoRESUMO
BACKGROUND: Schnitzler syndrome is a rare disorder with chronic urticaria, and there is no report summarizing the current status in Japan. METHODS: A nationwide survey of major dermatology departments in Japan was conducted in 2019. We further performed a systematic search of PubMed and Ichushi-Web, using the keywords "Schnitzler syndrome" and "Japan" then contacted the corresponding authors or physicians for further information. RESULTS: Excluding duplicates, a total of 36 clinically diagnosed cases were identified from 1994 through the spring of 2022, with a male to female ratio of 1:1. The median age of onset was 56.5 years. It took 3.3 years from the first symptom, mostly urticaria, to reach the final diagnosis. The current status of 30 cases was ascertained; two patients developed B-cell lymphoma. SchS treatment was generally effective with high doses of corticosteroids, but symptoms sometimes recurred after tapering. Colchicine was administered in 17 cases and was effective in 8, but showed no effect in the others. Tocilizumab, used in six cases, improved laboratory abnormalities and symptoms, but lost its efficacy after several years. Rituximab, used in five cases, was effective in reducing serum IgM levels or lymphoma mass, but not in inflammatory symptoms. Four cases were treated with IL-1 targeting therapy, either anakinra or canakinumab, and achieved complete remission, except one case with diffuse large B-cell lymphoma. CONCLUSIONS: Since Schnitzler syndrome is a rare disease, the continuous collection and long-term follow-up of clinical information is essential for its appropriate treatment and further understanding of its pathophysiology.
Assuntos
Urticária Crônica , Síndrome de Schnitzler , Urticária , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome de Schnitzler/diagnóstico , Síndrome de Schnitzler/tratamento farmacológico , Urticária/diagnóstico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Urticária Crônica/tratamento farmacológico , Japão/epidemiologiaAssuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Humanos , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Autoanticorpos , Helicase IFIH1 Induzida por Interferon , Progressão da DoençaRESUMO
Background Liver cancer (LC) is a serious late complication after the Fontan operation. However, the incidence, predictors, and prognosis remain unknown. The purpose of our study was to determine these clinical characteristics. Methods and Results We assessed liver function in 339 consecutive patients who had undergone the Fontan procedure from 2005 to 2019. LC was histologically diagnosed in 10 patients after a median period of 2.9 years (range: 0.3-13.8; median age: 29.9 years [range: 14.4-41.5 years]; overall median post-Fontan procedure follow-up: 25.6 years [range: 13-32.1 years]), and the annual incidence was 0.89%. Over the entire post-Fontan follow-up period, the annual incidences of new-onset LC in the second, third, and fourth decades were 0.14%, 0.43%, and 8.83%, respectively. The patients with LC had longer follow-up periods, higher levels of AFP (α-fetoprotein), and higher values of liver fibrosis indices (P<0.01-0.0001). Moreover, all indices were predictive of new-onset LC (P<0.01-0.0001). The LC treatments were surgical resection (n=3), transarterial chemoembolization (n=3), radiofrequency ablation (n=2), and hospice care (n=2). During a median follow-up of 9.4 months, 4 patients died; the survival rate at 1 year was 60%, and it was better among asymptomatic patients (P<0.01). Conclusions The LC incidence rapidly increased ≥30 years after the Fontan procedure, and liver fibrosis indices and AFP were predictive of new-onset LC. These LC-predictive markers should be monitored closely and mandatorily for early LC detection and better prognosis.
Assuntos
Técnica de Fontan/efeitos adversos , Previsões , Cardiopatias Congênitas/cirurgia , Neoplasias Hepáticas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
Post-inflammatory hyperpigmentation (PIH) is a common cutaneous condition that can cause a disfigured appearance. However, the pathophysiology of PIH remains poorly understood, at least in part, because an appropriate animal model for research has not been established. In order to analyze the pathomechanism of PIH, we successfully induced PIH in a hairless version of transgenic mice (hk14-SCF Tg/HRM) that have a human-type epidermis containing melanin by repeated hapten application of 2,4-dinitrofluorobenzene. Histopathologic observation showed epidermal hyperplasia, predominant infiltrations of inflammatory cells, and melanin-containing cells in the dermis just after elicitation of the atopic dermatitis-like condition. At week 2, the findings were similar to the characteristics of PIH, that is, an increase of melanin without spongiosis or liquid degeneration in the epidermis and an increase in dermal melanophages. Dynamic analysis of melanin showed that the melanin in the dermis remained for a longer duration than in the epidermis. Furthermore, immunohistochemical staining revealed that the majority of cells containing melanin were positive for the anti-CD68 antibody, but negative for the anti-F4/80 antibody. These data suggest that novel treatments of PIH should be targeted against macrophages and should eventually lead to the development of new treatment modalities.
Assuntos
Modelos Animais de Doenças , Epiderme/patologia , Hiperpigmentação/patologia , Inflamação/complicações , Melaninas/metabolismo , Animais , Epiderme/imunologia , Epiderme/metabolismo , Feminino , Humanos , Hiperpigmentação/etiologia , Hiperpigmentação/metabolismo , Masculino , Camundongos , Camundongos TransgênicosRESUMO
BACKGROUND: Human polyomaviruses (HPyVs) have been associated with several cutaneous inflammatory conditions. More investigation is needed to identify further presentations of cutaneous pathology associated with HPyVs. Our aim was to investigate the possible association of skin-tropic HPyVs with folliculitis, particularly eosinophilic pustular folliculitis (EPF). METHODS: This study included 55 Japanese patients, comprising 13 patients with EPF and 42 patients with suppurative folliculitis. HPyV DNAs were detected by quantitative polymerase chain reaction. Expression of viral antigen and geographically related viral genotypes were also assessed. RESULTS: Human polyomavirus 6 (HPyV6) DNA was found in 9 of 13 (69%) patients with EPF, a rate significantly higher than that found in suppurative folliculitis (1/42; 2%). Of the 7 HPyV6 DNA-positive EPF specimens analyzed, 4 were positive for HPyV6 small tumor antigen. All the HPyV6 strains detected in this study were of the Asian/Japanese genotype. CONCLUSIONS: The predominant detection of HPyV6 DNA and the expression of viral antigen suggest a possible association between HPyV6 infection and EPF in a subset of patients. Worldwide studies are warranted to determine whether Asian/Japanese genotype HPyV6 is associated preferentially with the incidence and pathogenesis of this eosinophil-related skin disease that has an ethnic predilection for the East Asian population.
Assuntos
Eosinofilia/virologia , Foliculite/virologia , Polyomaviridae/isolamento & purificação , Infecções por Polyomavirus , Dermatopatias Vesiculobolhosas/virologia , Antígenos Virais , DNA Viral/genética , Humanos , Infecções por Polyomavirus/diagnósticoAssuntos
AMP Cíclico/metabolismo , Mediadores da Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/farmacologia , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linhagem Celular , Ciclopropanos/farmacologia , Ciclopropanos/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Humanos , Interleucina-18/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-8/metabolismo , Queratinócitos/imunologia , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases/imunologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/imunologia , Talidomida/análogos & derivados , Talidomida/farmacologia , Talidomida/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Cantu syndrome is an autosomal dominant disorder, first described by Cantu in 1982, that is characterized by congenital hypertrichosis, characteristic facial anomalies and cardiomegaly. Recent investigations have revealed that this syndrome is caused by mutations of ABCC9, which encodes a regulatory subunit of SUR2, an adenosine triphosphate-mediated potassium channel opener, expressed not only in smooth muscle but also in hair follicles. However, the abnormalities of skin and hair in patients with Cantu syndrome have not been well explored. We herein report three Japanese patients with Cantu syndrome and describe their specific skin manifestations and alterations in the histopathology of their hair follicles and sebaceous glands. Similar alterations were shared among those three patients and may be related to the function of SUR2, namely the regulation of hair follicle growth, because SUR2 is a known pharmacological target of minoxidil.
Assuntos
Cardiomegalia/patologia , Folículo Piloso/patologia , Hipertricose/patologia , Osteocondrodisplasias/patologia , Glândulas Sebáceas/patologia , Anti-Hipertensivos/efeitos adversos , Biópsia , Cardiomegalia/genética , Criança , Pré-Escolar , Feminino , Hirsutismo/induzido quimicamente , Humanos , Hipertricose/genética , Masculino , Minoxidil/efeitos adversos , Mutação , Osteocondrodisplasias/genética , Receptores de Sulfonilureias/genéticaAssuntos
Hiperplasia Angiolinfoide com Eosinofilia/virologia , Doença de Kimura/virologia , Polyomaviridae/genética , Adulto , Idoso , Hiperplasia Angiolinfoide com Eosinofilia/imunologia , Hiperplasia Angiolinfoide com Eosinofilia/patologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Antígenos Virais/isolamento & purificação , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Técnicas de Genotipagem , Humanos , Japão , Doença de Kimura/imunologia , Doença de Kimura/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfonodos/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Polyomaviridae/imunologia , Polyomaviridae/isolamento & purificação , Estudos Retrospectivos , Pele/imunologia , Pele/patologia , Pele/virologiaRESUMO
Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for albinism have been identified; thus, the accurate diagnosis of albinism requires next-generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous albinism (OCA)1-4 and Hermansky-Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS-based targeted resequencing. We identified a genetic background for albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in albinism-related genes. Furthermore, most patients who were not diagnosed with albinism by the NGS analysis showed mild manifestations of albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin-color associated gene variants.
Assuntos
Albinismo/diagnóstico , Albinismo/genética , Povo Asiático/genética , Sequenciamento de Nucleotídeos em Larga Escala , Adulto , Sequência de Bases , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Pessoa de Meia-Idade , Mutação/genética , Fenótipo , Sítios de Splice de RNA/genética , Adulto JovemRESUMO
A 67-year-old man, who had been diagnosed with psoriasis 30 years prior, visited our hospital with a complaint of verrucous nodules in the lower legs, which had developed 15 years previously. We diagnosed him as having psoriasis verrucosa of the legs and plaque psoriasis of the torso. Because the lesions were resistant to topical glucocorticoids and vitamin D3 , a verrucous lesion in the right leg was treated with surgical ablation, which resulted in the development of generalized pustular psoriasis. After pustular lesions were cleared by systemic glucocorticoids and methotrexate, we treated him with etretinate and cyclosporin, but the verrucous lesions accompanied by chronic bacterial infection persisted over time. One year ago, treatment with recently-approved apremilast was started. It immediately attenuated the plaques and erythropapular lesions of the trunk. Surprisingly, the verrucous nodules of both legs showed reduction in size in 2 months.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fármacos Dermatológicos/farmacologia , Psoríase/tratamento farmacológico , Talidomida/análogos & derivados , Verrugas/tratamento farmacológico , Administração Cutânea , Administração Oral , Idoso , Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Dermatológicos/uso terapêutico , Resistência a Medicamentos , Humanos , Masculino , Psoríase/diagnóstico , Psoríase/patologia , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/patologia , Talidomida/farmacologia , Talidomida/uso terapêutico , Resultado do Tratamento , Verrugas/diagnóstico , Verrugas/patologiaRESUMO
BACKGROUND: Human skin microorganisms have been associated with various skin diseases. However, most studies have focused on bacterial communities, and little is known about normally resident skin viruses such as the Polyomaviridae and their association with cutaneous disorders. METHODS: We investigated the infection levels of Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7), using triplet skin swabs collected from lesional and nonlesional skins of 86 Japanese patients with inflammatory skin diseases and mycosis fungoides, and from 149 healthy control individuals. RESULTS: This age-matched case-control study provides the first analyses of the loads of polyomaviruses in association with various skin diseases. The viral loads were significantly higher for HPyV6/HPyV7 and lower for MCPyV in patients with psoriasis. The viral load variation was observed not only at lesion sites, but also at clinically unaffected skin sites in most of the patients. The viral strains tested were all of the Asian/Japanese genotype. CONCLUSIONS: Our findings suggest a covariation in the infection levels of cutaneous polyomaviruses in certain inflammatory skin conditions. Worldwide prospective longitudinal studies are warranted to understand the influence of such alterations on the pathogenesis of inflammatory skin disorders.
Assuntos
Infecções por Polyomavirus/epidemiologia , Polyomavirus/isolamento & purificação , Dermatopatias/epidemiologia , Pele/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA Viral/isolamento & purificação , Feminino , Humanos , Japão/epidemiologia , Masculino , Poliomavírus das Células de Merkel/isolamento & purificação , Pessoa de Meia-Idade , Micose Fungoide/epidemiologia , Micose Fungoide/virologia , Prevalência , Psoríase/virologia , Dermatopatias/virologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Carga ViralRESUMO
BACKGROUND: Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial. OBJECTIVES: To elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model. METHODS: Two lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer. RESULTS: LCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasis patients produced IL-23. CONCLUSIONS: Our study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.
Assuntos
Interleucina-23/imunologia , Queratinócitos/patologia , Células de Langerhans/imunologia , Psoríase/imunologia , Fator de Transcrição STAT3/metabolismo , Animais , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Biópsia , Células Cultivadas , Modelos Animais de Doenças , Voluntários Saudáveis , Humanos , Interleucina-1alfa/imunologia , Interleucina-1alfa/metabolismo , Interleucina-23/metabolismo , Queratinócitos/imunologia , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/genética , Lectinas de Ligação a Manose/metabolismo , Camundongos , Camundongos Transgênicos , Cultura Primária de Células , Psoríase/patologia , Pele/citologia , Pele/patologiaAssuntos
Hemangiossarcoma/complicações , Hemangiossarcoma/patologia , Hipertricose/complicações , Hipertricose/diagnóstico , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Feminino , Hemangiossarcoma/tratamento farmacológico , Humanos , Hipertricose/patologia , Imuno-Histoquímica , Pessoa de Meia-Idade , Pescoço , Prognóstico , Doenças Raras , Medição de Risco , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Background: Merkel cell polyomavirus (MCPyV) is a ubiquitous cutaneous virus that causes Merkel cell carcinoma, which develops preferentially in white populations from Europe and North America. However, the genomic variations of MCPyV among ethnic groups have not been well delineated, and even less is known regarding alterations in the noncoding control region (NCCR) in the general population. Methods: MCPyV strains recovered from skin swab specimens from 250 healthy participants with distinct ethnicities and geographic origins were subjected to sequencing analysis of the NCCR. Results: A 25-base pair tandem repeat caused by a 25-base pair insertion within the NCCR was found predominantly in Japanese and East Asian individuals. Based on the presence of 2 other insertions and a deletion, the NCCR could be classified further into 5 genotypes. This tandem repeat was also found exclusively in the NCCR from Japanese patients with Merkel cell carcinoma, while other genotypes were detected in white patients from Europe and North America. Conclusions: Our results suggest that the MCPyV NCCR varies according to ethnicity and that assessing the short NCCR sequence provides a rapid and simple means for identification of the Japanese and East Asian variant genotype. It remains to be established whether these NCCR variations are associated differentially with the pathogenesis of MCPyV-driven Merkel cell carcinoma between regions with varying endemicity.