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1.
PLoS Negl Trop Dis ; 14(6): e0008051, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32569298

RESUMO

BACKGROUND: In Japan, Buruli ulcer cases are often advanced, requiring surgical treatment. However, extensive debridement is often difficult because of cosmetic and functional sequelae. Moreover, the lesions are complicated and composed of edematous erythema, necrotic ulcer, and erythematous skin lesions caused by a paradoxical reaction, which also make it difficult to perform adequate debridement. METHODOLOGY/PRINCIPAL FINDINGS: We performed quantitative polymerase chain reaction (PCR) analysis for IS2404 using 29 samples taken from mapping biopsy. We evaluated the relationship among mycobacterial burden, histopathological findings, and clinical outcomes using 83 tissue samples taken from mapping biopsy and debrided Buruli ulcer. On quantitative PCR, the Cp values of IS2404 amplification were substantially different in each site. The major histological findings could be divided into massive subcutaneous necrosis with scant inflammatory cell infiltration and dense inflammatory cell infiltration. Of the 84 sites, 34 were subjected to repeated histological evaluations. In these sites, histological necrosis did not disappear over time despite standard antibiotic treatment. In contrast, the ulcers were cured and no recurrences were observed without resecting the 11 biopsied sites that lacked histological necrosis. Although quantitative PCR revealed that a lower Cp value of IS2404 was associated with histological massive necrosis, sites that showed lower Cp values clinically did not always need debridement. CONCLUSION/SIGNIFICANCE: Our descriptive study revealed that the histological findings and amounts of mycobacterial DNA differed according to the sites despite being found in one lesion. Our results showed that the need for surgical debridement in each site was correlated with histological necrosis without inflammatory cell infiltration, as the inflammation is supposed to represent an active host immune response rather than mycobacterial burden. We suggest that the debridement of lesions with histological necrosis in mapping biopsy may be useful for Japanese cases with unsuccessful standard antibiotic treatment to achieve sufficient clinical improvement.


Assuntos
Carga Bacteriana , Úlcera de Buruli/microbiologia , Úlcera de Buruli/patologia , Histocitoquímica , Mycobacterium ulcerans/isolamento & purificação , Adulto , Biópsia , Elementos de DNA Transponíveis , DNA Bacteriano/análise , DNA Bacteriano/genética , Humanos , Japão , Masculino , Mycobacterium ulcerans/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
3.
J Dermatol Sci ; 85(2): 77-84, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27876358

RESUMO

BACKGROUND: Patients with steroid-resistant bullous pemphigoid (BP) require an appropriate treatment option. OBJECTIVE: A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of high-dose intravenous immunoglobulin (IVIG; 400mg/kg/day for 5days) in BP patients who showed no symptomatic improvement with prednisolone (≥0.4mg/kg/day) administered. METHODS: We evaluated the efficacy using the disease activity score on day15 (DAS15) as a primary endpoint, and changes in the DAS over time, the anti-BP180 antibody titer, and safety for a period of 57days as secondary endpoints. RESULTS: We enrolled 56 patients in this study. The DAS15 was 12.5 points lower in the IVIG group than in the placebo group (p=0.089). The mean DAS of the IVIG group was constantly lower than that of the placebo group throughout the course of observation, and a post hoc analysis of covariance revealed a significant difference (p=0.041). Furthermore, when analyzed only in severe cases (DAS≥40), the DAS15 differed significantly (p=0.046). The anti-BP180 antibody titers showed no difference between the two groups. CONCLUSION: IVIG provides a beneficial therapeutic outcome for patients with BP who are resistant to steroid therapy.


Assuntos
Resistência a Medicamentos , Glucocorticoides/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Penfigoide Bolhoso/terapia , Prednisolona/farmacologia , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoantígenos/imunologia , Método Duplo-Cego , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/efeitos adversos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Resultado do Tratamento , Colágeno Tipo XVII
5.
J Cutan Pathol ; 43(10): 898-902, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27256924

RESUMO

Intralymphatic histiocytosis represents a rare reactive disorder, which is characterized by the accumulation of macrophages within lymphatic vessels and observed predominantly in upper extremities. The infiltration and preferential M2 differentiation of macrophage are observed in chronic lymphedema, and lymphedema is considered a causative factor of intralymphatic histiocytosis. However, what causes accumulation of histiocytes in the lymphatic vessels remains unclear, and investigation regarding the characteristics of the macrophages has not been evaluated. We present a case of intralymphatic histiocytosis, in which immunohistochemical staining for both macrophages and lymphatic vessels was performed to evaluate the nature of macrophages within lymphatic vessels and to determine the causative factor. Aggregated macrophages were shown to be M2 macrophages positive for CD68, CD163 and CD206 but negative for inducible nitric oxide synthase. Thick lymphatic vessels positive for D2-40 and α-SMA in the superficial dermis were observed. We speculate that chronic lymphedema leads to hypertrophy of lymphatic vessels with smooth muscle in the superficial dermis, which may be a kind of malformation, and these lymphatic vessels produce some chemokines that induce intralymphatic aggregation of macrophages.


Assuntos
Derme , Histiocitose , Vasos Linfáticos , Linfedema , Macrófagos , Músculo Liso , Idoso , Doença Crônica , Derme/metabolismo , Derme/patologia , Feminino , Histiocitose/metabolismo , Histiocitose/patologia , Humanos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Linfedema/metabolismo , Linfedema/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Músculo Liso/metabolismo , Músculo Liso/patologia
7.
Diagn Pathol ; 11: 24, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26932148

RESUMO

BACKGROUND: Atrophic variant of dermatofibrosarcoma protuberans (DFSP) is a distinct form of DFSP. CASE PRESENTATION: Here, we report the case of a 19-year-old woman with a small congenital atrophic plaque on the right precordium. The lesion remained atrophic for more than 10 years. Several years earlier, a portion of the plaque became tuberous and enlarged. Physical examination revealed a 25 × 30 mm erythematous atrophic plaque surrounded by three hard, smooth, and orange-colored nodules of varying sizes on the right precordium, along with visible subcutaneous adipose tissue and cutaneous veins. Biopsy of the nodule and atrophic plaque revealed dense proliferation of spindle-shaped tumor cells from the dermis to the subcutaneous adipose tissue, and positive immunostaining for CD34 and vimentin in addition to negative staining for factor XIIIa and α-smooth muscle actin. Reverse transcription polymerase chain reaction (RT-PCR) of the tumor tissue revealed the presence of a COL1A1-PDGFB fusion gene. Thus, congenital atrophic dermatofibrosarcoma protuberans was diagnosed. No metastasis to the lungs or regional lymph nodes was found on magnetic resonance imaging. Wide local excision and split-thickness skin grafting was performed and neither recurrence nor metastasis has been observed for 5 years and 8 months since the surgery. CONCLUSION: This case indicates that a congenital atrophic lesion could represent a quiescent phase of DFSP. Awareness of this rare condition can aid with early diagnosis and thereby improve the prognosis of DFSP.


Assuntos
Biomarcadores Tumorais/genética , Colágeno Tipo I/genética , Dermatofibrossarcoma/genética , Rearranjo Gênico , Proteínas Proto-Oncogênicas c-sis/genética , Neoplasias Cutâneas/genética , Atrofia , Biomarcadores Tumorais/análise , Biópsia , Cadeia alfa 1 do Colágeno Tipo I , Dermatofibrossarcoma/química , Dermatofibrossarcoma/patologia , Dermatofibrossarcoma/cirurgia , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Fenótipo , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Transplante de Pele , Resultado do Tratamento , Adulto Jovem
8.
J Dermatol ; 42(5): 496-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25708589

RESUMO

We present a cases of Merkel cell carcinoma (MCC) with Merkel cell polyomavirus that showed complete regression after biopsy. The exact mechanism of regression in MCC has remained unclear. It has been reported that apoptosis caused by T-cell immunity was implicated in the regression, and programmed cell death 1 (PD-1), an inhibitory receptor, was expressed in approximately half of tumor-infiltrating T cells in MCC. However, the contribution of PD-1-positive cells for the regression of MCC has not been evaluated. We examined the rate of PD-1-positive cells among the peritumoral mononuclear cells, which showed that the percentage of PD-1-positive cells in the case was significantly lower compared with in MCC without regression. We propose that PD-1-positive cells suppress tumor immunity for MCC, and that reduction of PD-1-positive cells may be associated with tumor regression.


Assuntos
Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/patologia , Receptor de Morte Celular Programada 1/análise , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Idoso , Biópsia , Carcinoma de Célula de Merkel/virologia , Humanos , Masculino , Remissão Espontânea , Neoplasias Cutâneas/virologia
16.
J Dermatol ; 41(2): 157-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24387075

RESUMO

Lymphedema is classified as a congenital disorder or acquired disorder. Common causes of acquired genital lymphedema include surgery, trauma, radiotherapy, neoplastic infiltration, venereal diseases and filariasis. Acquired idiopathic cases are also sometimes observed among genital lymphedema. There is no standard algorithm for the treatment of genital lymphedema. Surgical management for penile lymphedema in the chronic phase was discussed in many previous articles, however, management to prevent progression in the acute phase has been rarely mentioned. We present a case of acquired idiopathic penile lymphedema, in which histological examination was performed and acute phase progression was successfully ceased with low-dose corticosteroids. This is the first report that proposes the usefulness of low-dose systemic glucocorticoids for acquired idiopathic penile lymphedema showing rapid progression and histopathological lymphocytic inflammation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Betametasona/administração & dosagem , Linfedema/tratamento farmacológico , Doenças do Pênis/tratamento farmacológico , Adulto , Humanos , Linfedema/cirurgia , Masculino , Doenças do Pênis/cirurgia
18.
Eur J Dermatol ; 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23644544

RESUMO

Human papillomavirus-associated warts (HPV-warts) are persistent, evading host immune surveillance. However, these warts sometimes disappear spontaneously, following inflammation. Non-inflamed HPV-warts demonstrated decreased numbers of epidermal Langerhans cells (LCs), low expression levels of MIP3α and E-cadherin, and no apoptotic cells. In the inflamed HPV-warts, on the other hand, various dendritic cell (DC) subsets and many CD8+ cytotoxic T lymphocytes (CTLs) were recruited in association with epidermal MIP3α expression. Many apoptotic keratinocytes were observed in the dermo-epidermal junction. Cellular events were different in HPV-induced Bowen disease (HPV-Bowen): a few LCs were retained in the lesional epidermis, and considerable numbers of B-cells and plasma cells were also observed in the infiltrates, with little or no infiltration of plasmacytoid DCs or dermal/mature DCs. Multiple HPV16-Bowen diseases in the same individuals showed the presence of different sizes of E6/E7-containing cellular transcripts, which indicated that HPV genomes were integrated into the different sites of chromosomes. Toll-like receptor (TLR) 3 was expressed by the lesional keratinocytes even in the non-inflamed HPV-warts, and type 1 interferons (IFNs) were produced in cultured keratinocytes by TLR3 stimulation. HPV-warts are protected from host immune responses and apoptotic signals because they are surrounded by LC-depleted epidermal walls, and viral anti-apoptotic molecules. The up-regulation of epidermal TLR3 signaling might inhibit further HPV spreading.

20.
J Dermatol ; 40(4): 272-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23398170

RESUMO

Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis caused by mutations of the NEMO gene, which is required for activation of the nuclear factor-κB signaling pathway. NEMO gene rearrangement, exon 4-10 deletion, is the most common mutation with a frequency of 60-80%. Only four case reports about NEMO rearrangement in Japanese IP cases have been published. In our study, NEMO gene rearrangement was examined in 10 Japanese IP patients and their mothers and was revealed in five of 10 patients and three of their mothers. Interestingly, NEMO gene rearrangement was confirmed in the mothers of two patients without clinical symptoms; thus, NEMO mutation analysis is helpful to detect subclinical IP patients. The clinical symptoms of recently diagnosed Japanese IP patients were summarized for examination of the phenotype-genotype relationship and for comparison between those with and without NEMO gene rearrangement. Results revealed no definite difference in extracutaneous manifestations between the patients with NEMO rearrangement in our study and in other Japanese IP patients previously reported in both Japanese and English-language published work. However, there is higher frequency of ocular manifestation in our study than in other reports. Furthermore, evaluation of dental and nail abnormalities was difficult because most of our patients were observed for 1 year only. Long-term observation is needed for proper evaluation of the clinical status and phenotype-genotype relationship in IP patients.


Assuntos
Éxons/genética , Deleção de Genes , Rearranjo Gênico , Estudos de Associação Genética , Quinase I-kappa B/genética , Incontinência Pigmentar/genética , Povo Asiático/genética , Análise Mutacional de DNA , Feminino , Humanos , Incontinência Pigmentar/diagnóstico , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase Multiplex , Linhagem
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