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1.
Dermatol Online J ; 26(3)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32609447

RESUMO

A widespread form of eruptive collagenomas in a 12-year-old man is presented for the impressive iconography, challenging differential diagnosis, and histopathological considerations associated with such rare connective tissue disorders. Syndromic forms should be carefully investigated for the different course and prognosis. Treatment is a major unsolved issue as aesthetic concerns are significant, especially in young adults.


Assuntos
Doenças do Tecido Conjuntivo/patologia , Derme/patologia , Nevo/patologia , Neoplasias Cutâneas/patologia , Dorso/patologia , Biópsia/métodos , Corantes , Fibroblastos/patologia , Humanos , Masculino , Adulto Jovem
2.
Dermatol Online J ; 26(4)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621685

RESUMO

Mid-dermal elastolysis is a rare acquired elastic tissue disorder with about 100 cases reported in the literature. It is characterized by localized patches of finely wrinkled skin on the shoulder and upper extremities and a band-like loss of elastic tissue in the mid-dermal layer on biopsy. Some patients may have symptoms of discomfort, erythema, and/or pruritis. Mid-dermal elastolysis is predominantly seen in young to middle-aged Caucasian females and extensive skin involvement may lead to cosmetic concerns. Furthermore, it is important to rule out other disorders of elastic fiber that are associated with systemic involvement. We present a case of MDE, discuss the differential diagnosis, and describe characteristic clinical features and histology findings of each condition.


Assuntos
Cútis Laxa/patologia , Derme/patologia , Tecido Elástico/patologia , Adulto , Braço/patologia , Biópsia , Feminino , Humanos
3.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(3): 196-204, abr. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-191522

RESUMO

Las dermatosis purpúricas pigmentadas son un grupo de enfermedades benignas y de curso crónico. Las variantes descritas representan distintas formas clínicas de una misma entidad con unas características histopatológicas comunes para todas ellas. Exponemos a continuación un resumen de las variedades más frecuentes, sus características clínicas, dermatopatológicas y de epiluminiscencia. Al tratarse de una entidad clínica poco frecuente, benigna, y no conocerse claramente los mecanismos patogénicos de la misma, no existen tratamientos estandarizados. Se revisan los tratamientos publicados hasta el momento, la mayoría de ellos basados en casos aislados o pequeñas series de casos, sin poder establecer un nivel de evidencia suficiente como para ser recomendado ninguno de ellos como tratamiento de elección


The pigmented purpuric dermatoses are a group of benign, chronic diseases. The variants described to date represent different clinical presentations of the same entity, all having similar histopathologic characteristics. We provide an overview of the most common PPDs and describe their clinical, dermatopathologic, and epiluminescence features. PPDs are both rare and benign, and this, together with an as yet poor understanding of the pathogenic mechanisms involved, means that no standardized treatments exist. We review the treatments described to date. However, because most of the descriptions are based on isolated cases or small series, there is insufficient evidence to support the use of any of these treatments as first-line therapy


Assuntos
Humanos , Dermatopatias/diagnóstico , Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/terapia , Púrpura/diagnóstico , Transtornos da Pigmentação/patologia , Púrpura/terapia , Derme/anatomia & histologia , Derme/patologia , Diagnóstico Diferencial , Fototerapia , Terapia PUVA
6.
An Bras Dermatol ; 95(3): 386-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32312547

RESUMO

We report a 74-year-old male presented to an outpatient dermatology clinic in Manaus, Amazonas, with a one-year history of pruritic, keloidal lesions on his left lower extremity. Histopathology showed round structures in reticular dermis. Grocott methenamine silver stain revealed numerous round yeasts with thick double walls, occurring singly or in chains connected by tubular projections. The diagnosis was lobomycosis. Although the keloidal lesions presented by this patient are typical of lobomycosis, their linear distribution along the left lower limb is unusual.


Assuntos
Queloide/diagnóstico , Queloide/patologia , Dermatoses da Perna/diagnóstico , Dermatoses da Perna/patologia , Lobomicose/diagnóstico , Lobomicose/patologia , Idoso , Biópsia , Derme/microbiologia , Derme/patologia , Humanos , Masculino
8.
An Bras Dermatol ; 95(2): 247-249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32111413

RESUMO

Pseudoxanthoma elasticum-like papillary dermal elastolysis is an acquired elastic tissue disorder clinically similar to pseudoxanthoma elasticum in the absence of systemic involvement. Histopathologically, special staining of elastic fibers demonstrates a total or partial band-like loss of elastic fibers in the papillary dermis. Although ultraviolet radiation seems to be one of the main etiological factors in this entity, we report a case of pseudoxanthoma elasticum-like papillary dermal elastolysis on the neck of a woman who wore hijab.


Assuntos
Derme/patologia , Tecido Elástico/patologia , Pseudoxantoma Elástico/patologia , Idoso , Biópsia , Dermoscopia , Feminino , Humanos
10.
An Bras Dermatol ; 95(1): 102-104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31932163

RESUMO

White fibrous papulosis of the neck is a rare entity, with fewer than 50 cases described. It is a benign pathology whose main interest lies in its broad differential diagnosis, especially with pseudoxanthoma elasticum. The authors report the case of a 77-year-old woman with multiple yellow-white monomorphic papules on the posterior cervical region, with years of evolution. Cutaneous biopsy revealed a nodular area in the superficial and middle reticular dermis, with slight thickening of the collagen fibers and focally enlarged elastic fibers, aspects highlighted in the Verhoeff staining that additionally showed absence of elastic fibers in the papillary dermis.


Assuntos
Pescoço/patologia , Dermatopatias Papuloescamosas/patologia , Idoso , Biópsia , Derme/patologia , Tecido Elástico/patologia , Feminino , Fibrose , Humanos
12.
PLoS One ; 15(1): e0227674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929578

RESUMO

INTRODUCTION: We characterized dermal innervation in patients with fibromyalgia syndrome (FMS) as potential contribution to small fiber pathology. METHODS: Skin biopsies of the calf were collected (86 FMS patients, 35 healthy controls). Skin was immunoreacted with antibodies against protein gene product 9.5, calcitonine gene-related peptide, substance P, CD31, and neurofilament 200 for small fiber subtypes. We assessed two skin sections per patient; on each skin section, two dermal areas (150 x 700 µm each) were investigated for dermal nerve fiber length (DNFL). RESULTS: In FMS patients we found reduced DNFL of fibers with vessel contact compared to healthy controls (p<0.05). There were no differences for the other nerve fiber subtypes. DISCUSSION: We found less dermal nerve fibers in contact with blood vessels in FMS patients than in controls. The pathophysiological relevance of this finding is unclear, but we suggest the possibility of a relationship with impaired thermal tolerance commonly reported by FMS patients.


Assuntos
Derme/inervação , Derme/patologia , Fibromialgia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Derme/irrigação sanguínea , Epiderme/inervação , Epiderme/patologia , Feminino , Humanos , Perna (Membro) , Pessoa de Meia-Idade , Adulto Jovem
13.
J Cutan Pathol ; 47(1): 27-30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31589777

RESUMO

BACKGROUND: Although diffuse dermal angiomatosis (DDA), a rare acquired reactive cutaneous vascular disorder, has been previously reported in association with calciphylaxis (CP), the clinical significance of this relationship has not yet been elucidated. METHODS: A total of 24 cases of CP diagnosed from 2013 to 2018 were retrospectively reviewed for the presence of associated DDA. Pertinent clinical information for each patient was also collected, and statistical analysis was performed using multivariable logistic regression, Student t test and Fisher exact test. RESULTS: African American race and comorbid congestive heart failure were the only variables that demonstrated independent, statistically significant association with the presence of DDA. End-stage renal failure, diabetes mellitus, immunosuppressive and hypercoagulable states, arrhythmia, body mass index, hypertension, coronary artery disease, patient age, duration of CP symptoms, gender, time interval from biopsy to death, anticoagulation therapy and sodium thiosulfate administration at the time of biopsy did not demonstrate a statistically significant association with DDA. CONCLUSION: DDA does not appear to be associated with disease severity or prognosis in cases of CP; however, in our population CP with concurrent DDA was more prevalent in African Americans and individuals with congestive heart failure.


Assuntos
Afro-Americanos , Angiomatose , Calciofilaxia , Derme , Insuficiência Cardíaca , Dermatopatias Vasculares , Idoso , Angiomatose/etnologia , Angiomatose/metabolismo , Angiomatose/patologia , Calciofilaxia/etnologia , Calciofilaxia/metabolismo , Calciofilaxia/patologia , Derme/metabolismo , Derme/patologia , Feminino , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatopatias Vasculares/etnologia , Dermatopatias Vasculares/metabolismo , Dermatopatias Vasculares/patologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-31851533

RESUMO

The systemic delivery of bleomycin (BLM) to mice through subcutaneously implanted osmotic minipumps may be used to experimentally mimic the typical features of systemic sclerosis and related interstitial lung diseases. The published studies on this model principally have focused on induced dermal modifications, probably because lung lesions are typically mild, subpleurally localized, and difficult to analyze. The use of high BLM doses to increase their severity has been proposed but is ethically questionable because of the compromising of animal welfare. We propose a tailored histomorphometric method suitable to detect and quantify this type of mild lung lesions. Using a two-step automated image analysis, a peripheral region of interest with a depth of 250 µm from the pleural edge was defined on whole slide images, and the fibrotic foci were histomorphometrically characterized. The effects of different BLM doses on lung alterations were evaluated in C57BL/6 mice and 60 U/kg resulted in a fair compromise between fibrotic lesions and animal welfare. This dose was also tested in time course experiments. The analysis revealed a peak of histological fibrotic-like alterations, cytokine expression, metalloprotease, and macrophagic activation between the 21st and 28th day after pump implant. The induced dermal fibrosis was characterized by the progressive loss of the white dermal adipose layer, an increase in dermal thickness, dermal hyperplasia, and more compacted collagen fibers. Despite the trend toward spontaneous resolution, our model allowed a double organ readout of the BLM effect and the identification of a therapeutic window for testing pharmacological compounds without using life-threatening doses.


Assuntos
Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Bombas de Infusão , Fibrose Pulmonar/tratamento farmacológico , Animais , Derme/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/patologia , Fatores de Tempo
15.
Biomed Pharmacother ; 123: 109797, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31874445

RESUMO

BACKGROUND: Non-allergic angioedema is largely driven by increased plasma levels of bradykinin and over-activation of bradykinin receptor type II (B2), but the specific downstream signalling pathways remain unclear. The aim of this study was to identify signal transduction events involved in bradykinin-induced dermal extravasation. METHODS: Quantification of dermal extravasation was accomplished following intradermal (i.d.) injection of bradykinin or the B2 agonist labradimil in mice with endothelial NO-synthase (eNOS) deficiency and in C57BL/6J mice pre-treated with vehicle, NO-synthase or cyclooxygenase (COX) inhibitors. In the multicentre clinical study ABRASE, 38 healthy volunteers received i.d. bradykinin injections into the ventral forearm before and after oral treatment with the COX inhibitor ibuprofen (600 mg). The primary endpoint of ABRASE was the mean time to complete resolution of wheals (TTCR) and the secondary endpoint was the change of maximal wheal size. RESULTS: Neither NOS inhibitors nor eNOS deficiency altered bradykinin-induced extravasation. In striking contrast, the COX inhibitors ibuprofen, diclofenac, SC560 and celecoxib significantly diminished this extravasation when given before injection. As for diclofenac, a similar but significantly lower effect was observed when given after i.d. injection of bradykinin. Similar results were obtained when bradykinin was replaced by labradimil. In volunteers, ibuprofen significantly reduced TTCR (P < 0.001) and maximal wheal size (P = 0.0044). CONCLUSION: These data suggest that COX activity contributes to bradykinin-induced dermal extravasation in mice and humans. In addition, our findings may open new treatment options and point to a potential activity of drugs interfering with the release of the COX substrate arachidonic acid, e.g. glucocorticoids.


Assuntos
Bradicinina/farmacologia , Derme/patologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Inibidores de Ciclo-Oxigenase/farmacologia , Extravasamento de Materiais Terapêuticos e Diagnósticos , Humanos , Camundongos Endogâmicos C57BL
16.
An Bras Dermatol ; 94(6): 754-756, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31789264

RESUMO

A 28-year-old white female patient presented with multiple erythematous-to-violaceous, painful, suppurative nodules on the buttocks and thighs that appeared after two weeks of mesotherapy with deoxycholate, caffeine, sunflower liposomes, and sinetrol for localized fat. She was treated for atypical mycobacteriosis, but with no satisfactory response after antibiotic therapy. Bacterial, mycobacterial, and fungal culture were all negative. Histopathologic examination of the biopsy showed noninfectious suppurative panniculitis. It resolved after treatment with methotrexate, prednisone, and hydroxychloroquine. This report highlights the rarity of this complication, the importance of its early recognition, and differentiation with atypical fast growing mycobacterioses.


Assuntos
Ácido Desoxicólico/efeitos adversos , Mesoterapia/efeitos adversos , Paniculite Nodular não Supurativa/induzido quimicamente , Paniculite Nodular não Supurativa/patologia , Adulto , Biópsia , Derme/patologia , Feminino , Humanos , Paniculite Nodular não Supurativa/tratamento farmacológico , Resultado do Tratamento
17.
Arthritis Res Ther ; 21(1): 290, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842999

RESUMO

BACKGROUND: Systemic sclerosis is a multisystem inflammatory and vascular lesion leading to extensive tissue fibrosis. A reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, DZ2002, modulates the pathologic processes of various inflammatory diseases and autoimmune diseases. This study is designed to investigate the therapeutic potentiality of DZ2002 for experimental systemic sclerosis models. METHODS: The anti-inflammatory and anti-fibrotic features of DZ2002 and its mechanisms were investigated in a bleomycin (BLM)-induced dermal fibrosis mice model. The effects of DZ2002 on expression of extracellular matrix components and TGF-ß signaling in human dermal fibroblasts were analyzed. Simultaneously, the effects of DZ2002 on macrophage activation and endothelial cell adhesion molecule expression were also evaluated. RESULTS: DZ2002 significantly attenuated dermal fibrosis in BLM-induced mice. Consistently, DZ2002 inhibited the expression of various molecules associated with dermal fibrosis, including transforming growth factor ß1, connective tissue growth factor, tumor necrosis factor-α, interferon-γ, IL-1ß, IL-4, IL-6, IL-10, IL-12p40, IL-17A, and monocyte chemotactic protein 1 in the lesional skin of BLM-induced mice. Furthermore, DZ2002 decreased the proportion of macrophages, neutrophils, and T cells (especially T helper cells) in the skin tissue of BLM-induced mice. In addition, DZ2002 attenuated both M1 macrophage and M2 macrophage differentiation in vivo and in vitro. Importantly, DZ2002 directly reversed the profibrotic phenotype of transforming growth factor-ß1-treated dermal fibroblasts and suppressed ICAM-1, VCAM-1, VEGF, bFGF, and ET-1 expression in endothelial cells. Finally, our investigations showed that DZ2002 relieved systemic sclerosis by regulating fibrosis TGF-ß/Smad signaling pathway. CONCLUSIONS: DZ2002 prevents the development of experimental dermal fibrosis by reversing the profibrotic phenotype of various cell types and would be a potential drug for the treatment of systemic sclerosis.


Assuntos
Adenina/análogos & derivados , Butiratos/farmacologia , Derme/efeitos dos fármacos , Inflamação/prevenção & controle , Escleroderma Sistêmico/prevenção & controle , Doenças Vasculares/prevenção & controle , Adenina/farmacologia , Animais , Bleomicina , Linhagem Celular , Células Cultivadas , Derme/metabolismo , Derme/patologia , Modelos Animais de Doenças , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose/induzido quimicamente , Fibrose/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/metabolismo , Macrófagos/classificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Escleroderma Sistêmico/induzido quimicamente , Escleroderma Sistêmico/metabolismo , Células THP-1 , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Doenças Vasculares/genética , Doenças Vasculares/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Int J Mol Sci ; 20(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703303

RESUMO

Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production, and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca2+ concentration in NHDFs. These results indicated that PGE2 is directly associated with EP1 pathway-regulated ERK1/2 and inositol trisphosphate (IP3) signaling in NHDFs.


Assuntos
Sinalização do Cálcio , Derme/metabolismo , Dinoprostona/metabolismo , Fibroblastos/metabolismo , Sistema de Sinalização das MAP Quinases , Transdução de Sinais , Envelhecimento da Pele , Linhagem Celular , Colágeno Tipo I/biossíntese , Derme/patologia , Fibroblastos/patologia , Regulação da Expressão Gênica , Humanos , Metaloproteinase 1 da Matriz/biossíntese , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo
19.
Nat Commun ; 10(1): 5023, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685822

RESUMO

Melanoma, the deadliest skin cancer, remains largely incurable at advanced stages. Currently, there is a lack of animal models that resemble human melanoma initiation and progression. Recent studies using a Tyr-CreER driven mouse model have drawn contradictory conclusions about the potential of melanocyte stem cells (McSCs) to form melanoma. Here, we employ a c-Kit-CreER-driven model that specifically targets McSCs to show that oncogenic McSCs are a bona fide source of melanoma that expand in the niche, and then establish epidermal melanomas that invade into the underlying dermis. Further, normal Wnt and Endothelin niche signals during hair anagen onset are hijacked to promote McSC malignant transformation during melanoma induction. Finally, molecular profiling reveals strong resemblance of murine McSC-derived melanoma to human melanoma in heterogeneity and gene signatures. These findings provide experimental validation of the human melanoma progression model and key insights into the transformation and heterogeneity of McSC-derived melanoma.


Assuntos
Carcinogênese/patologia , Melanócitos/patologia , Melanoma/patologia , Células-Tronco Neoplásicas/patologia , Animais , Carcinogênese/metabolismo , Transformação Celular Neoplásica/patologia , Derme/patologia , Modelos Animais de Doenças , Epiderme/patologia , Homeostase , Humanos , Melanócitos/metabolismo , Camundongos , Mutação/genética , Células-Tronco Neoplásicas/metabolismo , Fenótipo , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Microambiente Tumoral , Via de Sinalização Wnt
20.
An. bras. dermatol ; 94(6): 754-756, Nov.-Dec. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1054889

RESUMO

Abstract A 28-year-old white female patient presented with multiple erythematous-to-violaceous, painful, suppurative nodules on the buttocks and thighs that appeared after two weeks of mesotherapy with deoxycholate, caffeine, sunflower liposomes, and sinetrol for localized fat. She was treated for atypical mycobacteriosis, but with no satisfactory response after antibiotic therapy. Bacterial, mycobacterial, and fungal culture were all negative. Histopathologic examination of the biopsy showed noninfectious suppurative panniculitis. It resolved after treatment with methotrexate, prednisone, and hydroxychloroquine. This report highlights the rarity of this complication, the importance of its early recognition, and differentiation with atypical fast growing mycobacterioses.


Assuntos
Humanos , Feminino , Adulto , Paniculite Nodular não Supurativa/induzido quimicamente , Paniculite Nodular não Supurativa/patologia , Ácido Desoxicólico/efeitos adversos , Mesoterapia/efeitos adversos , Biópsia , Paniculite Nodular não Supurativa/tratamento farmacológico , Resultado do Tratamento , Derme/patologia
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