Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 13.490
Filtrar
1.
Acta Derm Venereol ; 100(15): adv00249, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32812055

RESUMO

Only recently histopathological studies of patients with dermatosis and concomitant SARS-Cov-2 viral infection were published. Seven months into the COVID-19 pandemic, more skin biopsies of COVID-19 positive patients are taking place. We examined the histological features of 30 skin biopsies from two groups of patients: Ten specimens of patients tested positive for COVID-19 with an active systemic infection and associated dermatosis. Twenty specimens were from patients not considered COVID-positive (due to PCR swab negativity or not tested at all) with cutaneous lesions either showing viral infection symptoms (fever, cough, ageusia and severe immunocompromised condition due to HIV infection and malignancies), or presented a high risk of being infected (such as cohabitation with COVID-19 positive parents and siblings with simultaneous chilblains). This study analyses the histological and immunohistochemical (SARS-CoV-2 2019-nCoV nucleocapsid antibody) characteristics of the two groups and identifies 4 histopathological patterns. The histopathological features of the two groups present similar features that may help to identify an ongoing COVID-19 infection even in asymptomatic carriers with dermatosis.


Assuntos
Doenças Assintomáticas/epidemiologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Dermatopatias/patologia , Biópsia por Agulha , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pandemias , Reação em Cadeia da Polimerase/métodos , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Dermatopatias/epidemiologia , Manejo de Espécimes
2.
Am J Hum Genet ; 107(3): 527-538, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758447

RESUMO

Generalized pustular psoriasis (GPP) is a severe multi-systemic inflammatory disease characterized by neutrophilic pustulosis and triggered by pro-inflammatory IL-36 cytokines in skin. While 19%-41% of affected individuals harbor bi-allelic mutations in IL36RN, the genetic cause is not known in most cases. To identify and characterize new pathways involved in the pathogenesis of GPP, we performed whole-exome sequencing in 31 individuals with GPP and demonstrated effects of mutations in MPO encoding the neutrophilic enzyme myeloperoxidase (MPO). We discovered eight MPO mutations resulting in MPO -deficiency in neutrophils and monocytes. MPO mutations, primarily those resulting in complete MPO deficiency, cumulatively associated with GPP (p = 1.85E-08; OR = 6.47). The number of mutant MPO alleles significantly differed between 82 affected individuals and >4,900 control subjects (p = 1.04E-09); this effect was stronger when including IL36RN mutations (1.48E-13) and correlated with a younger age of onset (p = 0.0018). The activity of four proteases, previously implicated as activating enzymes of IL-36 precursors, correlated with MPO deficiency. Phorbol-myristate-acetate-induced formation of neutrophil extracellular traps (NETs) was reduced in affected cells (p = 0.015), and phagocytosis assays in MPO-deficient mice and human cells revealed altered neutrophil function and impaired clearance of neutrophils by monocytes (efferocytosis) allowing prolonged neutrophil persistence in inflammatory skin. MPO mutations contribute significantly to GPP's pathogenesis. We implicate MPO as an inflammatory modulator in humans that regulates protease activity and NET formation and modifies efferocytosis. Our findings indicate possible implications for the application of MPO inhibitors in cardiovascular diseases. MPO and affected pathways represent attractive targets for inducing resolution of inflammation in neutrophil-mediated skin diseases.


Assuntos
Inflamação/genética , Interleucinas/genética , Peroxidase/genética , Psoríase/genética , Dermatopatias/genética , Adulto , Animais , Citocinas/genética , Armadilhas Extracelulares/genética , Feminino , Humanos , Inflamação/patologia , Interleucina-1/genética , Interleucinas/metabolismo , Masculino , Camundongos , Mutação/genética , Neutrófilos/metabolismo , Psoríase/patologia , Doenças Raras/enzimologia , Doenças Raras/genética , Doenças Raras/patologia , Pele/enzimologia , Pele/patologia , Dermatopatias/patologia
3.
Am J Hum Genet ; 107(3): 539-543, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758448

RESUMO

The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.2031-2A>C) in MPO. This encodes myeloperoxidase, an essential component of neutrophil azurophil granules. MPO screening in conditions phenotypically related to GPP uncovered further disease alleles in one subject with acral pustular psoriasis (c.2031-2A>C;c.2031-2A>C) and in two individuals with acute generalized exanthematous pustulosis (c.1705C>T;c.2031-2A>C and c.1552_1565del;c.1552_1565del). A subsequent analysis of UK Biobank data demonstrated that the c.2031-2A>C and c.1705C>T (p.Arg569Trp) disease alleles were also associated with increased neutrophil abundance in the general population (p = 5.1 × 10-6 and p = 3.6 × 10-5, respectively). The same applied to three further deleterious variants that had been genotyped in the cohort, with two alleles (c.995C>T [p.Ala332Val] and c.752T>C [p.Met251Thr]) yielding p values < 10-10. Finally, treatment of healthy neutrophils with an MPO inhibitor (4-Aminobenzoic acid hydrazide) increased cell viability and delayed apoptosis, highlighting a mechanism whereby MPO mutations affect granulocyte numbers. These findings identify MPO as a genetic determinant of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored.


Assuntos
Doenças Neurodegenerativas/genética , Peroxidase/genética , Psoríase/genética , Dermatopatias/genética , Ácido 4-Aminobenzoico/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular/efeitos dos fármacos , Feminino , Genótipo , Humanos , Mutação com Perda de Função/genética , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Neutrófilos/efeitos dos fármacos , Peroxidase/antagonistas & inibidores , Fenótipo , Psoríase/tratamento farmacológico , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/patologia , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia
4.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815688

RESUMO

Calcinosis cutis, although common in systemic sclerosis, has been rarely reported in patients with morphea. We describe four patients with calcinosis cutis arising within morphea plaques, discuss their treatments and outcomes, and review previously published cases. Current management recommendations for concomitant morphea and dystrophic calcinosis cutis are based on limited data and expert opinion, which has primarily focused on reduction of active inflammation and reduction of symptoms related to calcinosis or ulceration. In most cases, no improvement of calcinosis was noted. The use of intralesional corticosteroids to active lesions in conjunction with systemic treatment, including methotrexate when indicated, appear promising treatments to halt progression of the disease. Surgical excision seems to be the most definitive treatment for calcinosis affecting morphea plaques, but the current literature lacks details regarding disease recurrence following operative management.


Assuntos
Calcinose/etiologia , Esclerodermia Localizada/complicações , Dermatopatias/patologia , Pele/patologia , Corticosteroides/uso terapêutico , Calcinose/patologia , Calcinose/cirurgia , Criança , Feminino , Humanos , Injeções Intralesionais , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Esclerodermia Localizada/tratamento farmacológico , Esclerodermia Localizada/patologia , Dermatopatias/terapia
5.
Acta Derm Venereol ; 100(15): adv00249, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: covidwho-722469

RESUMO

Only recently histopathological studies of patients with dermatosis and concomitant SARS-Cov-2 viral infection were published. Seven months into the COVID-19 pandemic, more skin biopsies of COVID-19 positive patients are taking place. We examined the histological features of 30 skin biopsies from two groups of patients: Ten specimens of patients tested positive for COVID-19 with an active systemic infection and associated dermatosis. Twenty specimens were from patients not considered COVID-positive (due to PCR swab negativity or not tested at all) with cutaneous lesions either showing viral infection symptoms (fever, cough, ageusia and severe immunocompromised condition due to HIV infection and malignancies), or presented a high risk of being infected (such as cohabitation with COVID-19 positive parents and siblings with simultaneous chilblains). This study analyses the histological and immunohistochemical (SARS-CoV-2 2019-nCoV nucleocapsid antibody) characteristics of the two groups and identifies 4 histopathological patterns. The histopathological features of the two groups present similar features that may help to identify an ongoing COVID-19 infection even in asymptomatic carriers with dermatosis.


Assuntos
Doenças Assintomáticas/epidemiologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Dermatopatias/patologia , Biópsia por Agulha , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pandemias , Reação em Cadeia da Polimerase/métodos , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Dermatopatias/epidemiologia , Manejo de Espécimes
6.
Dermatol Online J ; 26(3)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32609451

RESUMO

Eosinophilic dermatosis of hematologic malignancy (EDHM) is a dermatosis characterized by tissue eosinophilia that has been previously reported as insect bite-like reaction. It is a rare condition with a wide variety of clinical presentations ranging from papules, nodules, or blisters that simulate arthropod bites, to the formation of plaques of differing sizes. We report a case of eosinophilic dermatosis of hematologic malignancy in a patient with a hematoproliferative disorder.


Assuntos
Eosinofilia/patologia , Síndromes Mielodisplásicas/complicações , Síndromes Paraneoplásicas/patologia , Dermatopatias/patologia , Idoso , Eosinofilia/etiologia , Humanos , Masculino , Dermatopatias/etiologia
7.
Medicine (Baltimore) ; 99(29): e20867, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702828

RESUMO

RATIONALE: Phagocytosis is an important physiological process for eliminating unnecessary substances or dead cells after tissue damage, such as inflammation or infarction. Phagocytosis was previously considered to be mainly performed by professional phagocytotic cells, such as macrophages. In contrast, we previously demonstrated that the phagocytosis of dead cells and unnecessary substances by myofibroblasts is as important as that by professional phagocytotic cells in myocardial infarction. Based on our discovery, we speculated that phagocytosis by myofibroblasts may be a more common pathological phenomenon also in other diseases than previously believed. PATIENT CONCERNS: A 44-year-old male patient with atopic dermatitis developed a cutaneous reddish nodule with an underlying induration on his thigh. INTERVENTIONS: The cutaneous lesion was surgically removed. DIAGNOSES: Histopathological examination demonstrated that the cutaneous lesion had solid infiltration by inflammatory cells, namely, plasma cells, histiocytes, and lymphocytes, in the dermis. The cutaneous lesion included mucinosis in the dermis. Inside the mucinosis, we detected cells with clear areas of mucinous substances. Some of the cells were α-smooth muscle actin-positive myofibroblasts. Electron microscopic images demonstrated that there were collagen bands in the cells with mucinous engulfment. Based on these pieces of evidence, we conclude that these mucinous phagocytotic cells were myofibroblasts, not professional phagocytotic cells, such as macrophages. OUTCOMES: There was no recurrence of the lesion. LESSONS: The clinical appearance of this case resembled that of previously reported solitary cutaneous focal mucinoses. However, our case had distinctive characteristics, such as the phagocytosis of mucinous substances by myofibroblasts, multiple mucinous lesions in a single eruption, and the presence of inflammatory cells, which have not been previously reported. For this distinct cutaneous lesion, a clear dermatological and pathological name has yet to be determined. We propose "myofibroblast phagocytic cutaneous mucinosis" as a candidate name. In addition, our discoveries suggest that phagocytosis by myofibroblasts is not rare but rather is a common pathological phenomenon that has been undetected or unrecognized.


Assuntos
Mucinoses/patologia , Miofibroblastos/fisiologia , Fagocitose , Dermatopatias/patologia , Adulto , Humanos , Masculino , Microscopia Eletrônica , Mucinoses/cirurgia , Dermatopatias/cirurgia
9.
PLoS One ; 15(7): e0235410, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726308

RESUMO

Patient satisfaction is an important indicator of health care quality, and it remains an important goal for optimal treatment outcomes to reduce the level of misdiagnoses and inappropriate or absent therapeutic actions. Digital support tools for differential diagnosis to assist clinicians in reaching the correct diagnosis may be helpful, but how the use of these affect patients is not clear. The primary objective of this feasibility study was to investigate patient experience and satisfaction in a primary care setting where general practitioners (GPs) used a visual clinical decision support system (CDSS) compared with standard consultations. Secondary objectives were diagnostic accuracy and length of consultation. Thirty-one patients with a dermatologist-confirmed skin diagnosis were allocated to consult GPs that had been randomized to conduct either standard consultations (SDR, n = 21) or CDSS (n = 16) on two separate study days one week apart. All patients were diagnosed independently by multiple GPs (n = 3-8) in both the SDR and CDSS study arms. Using the CDSS, more patients felt involved in the decision making (P = 0.05). In addition, more patients were exposed to images during the consultations (P = 6.8e-27), and 83% of those that were shown images replied they felt better supported in the consultation. The use of CDSS significantly improved the diagnostic accuracy (34%, P = 0.007), and did not increase the duration of the consultation (median 10 minutes in both arms). This study shows for the first time that compared with standard GP consultations, CDSS assist the GP on skin related diagnoses and improve patient satisfaction and diagnostic accuracy without impacting the duration of the consultations. This is likely to increase correct treatment choices, patient adherence, and overall result in better healthcare outcomes.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Sistemas Especialistas , Satisfação do Paciente , Dermatopatias/diagnóstico , Adulto , Erros de Diagnóstico/prevenção & controle , Estudos de Viabilidade , Feminino , Clínicos Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Encaminhamento e Consulta , Dermatopatias/epidemiologia , Dermatopatias/patologia
13.
J Am Acad Dermatol ; 83(3): 870-875, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32502585

RESUMO

BACKGROUND: During the coronavirus disease 2019 pandemic, several acral chilblain-like lesions were observed in young patients with suspected, but mostly unconfirmed, infection with severe acute respiratory syndrome coronavirus 2. The histopathologic aspect of these lesions is as yet poorly known. OBJECTIVE: To investigate the pathologic features of chilblain-like lesions. METHODS: Biopsies were obtained from 17 cases of chilblain-like lesions during the coronavirus disease 2019 pandemic in France and were studied by routine histologic examination, immunohistochemistry, and direct immunofluorescence. The patients had suspected but unconfirmed infection with severe acute respiratory syndrome coronavirus 2 (negative nasopharyngeal polymerase chain reaction and serologic test results). RESULTS: Chilblain-like lesions showed many features in common with those reported in idiopathic and autoimmune-related chilblains, including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4+) inflammation, and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, and immunoreactant deposits on vessels). CONCLUSIONS: Chilblain-like lesions show histopathologic features similar to those of idiopathic and autoimmune-related chilblains, with a high rate of vascular changes and direct immunofluorescence positivity. The role of severe acute respiratory syndrome coronavirus 2 in the development of these puzzling lesions remains to be elucidated.


Assuntos
Betacoronavirus/isolamento & purificação , Pérnio/diagnóstico , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Dermatopatias/diagnóstico , Pele/patologia , Adolescente , Adulto , Betacoronavirus/imunologia , Biópsia , Pérnio/imunologia , Pérnio/patologia , Pérnio/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diagnóstico Diferencial , Feminino , Imunofluorescência , França , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pele/imunologia , Pele/virologia , Dermatopatias/imunologia , Dermatopatias/patologia , Dermatopatias/virologia , Dedos do Pé , Adulto Jovem
14.
Toxicol Appl Pharmacol ; 401: 115078, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32479919

RESUMO

Sulfur mustard (SM) is a highly toxic blistering agent thought to mediate its action, in part, by activating matrix metalloproteinases (MMPs) in the skin and disrupting components of the basement membrane zone (BMZ). Type IV collagenases (MMP-9) degrade type IV collagen in the skin, a major component of the BMZ at the dermal-epidermal junction. In the present studies, a type IV collagenase inhibitor, N-hydroxy-3-phenyl-2-(4-phenylbenzenesulfonamido) propanamide (BiPS), was tested for its ability to protect the skin against injury induced by SM in the mouse ear vesicant model. SM induced inflammation, epidermal hyperplasia and microblistering at the dermal/epidermal junction of mouse ears 24-168 h post-exposure. This was associated with upregulation of MMP-9 mRNA and protein in the skin. Dual immunofluorescence labeling showed increases in MMP-9 in the epidermis and in the adjacent dermal matrix of the SM injured skin, as well as breakdown of type IV collagen in the basement membrane. Pretreatment of the skin with BiPS reduced signs of SM-induced cutaneous toxicity; expression of MMP-9 mRNA and protein was also downregulated in the skin by BiPS. Following BiPS pretreatment, type IV collagen appeared intact and was similar to control skin. These results demonstrate that inhibiting type IV collagenases in the skin improves basement membrane integrity after exposure to SM. BiPS may hold promise as a potential protective agent to mitigate SM induced skin injury.


Assuntos
Benzopiranos/uso terapêutico , Substâncias para a Guerra Química/toxicidade , Colágeno Tipo IV/antagonistas & inibidores , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Gás de Mostarda/toxicidade , Dermatopatias/tratamento farmacológico , Animais , Benzopiranos/farmacologia , Colágeno Tipo IV/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/patologia , Masculino , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos , Dermatopatias/induzido quimicamente , Dermatopatias/metabolismo , Dermatopatias/patologia
16.
Medicine (Baltimore) ; 99(22): e20391, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481426

RESUMO

INTRODUCTION: Acquired reactive perforating collagenosis (ARPC) is a rare skin disorder, which is associated with various internal diseases and even malignant neoplasms. A comprehensive knowledge of the concomitant diseases in ARPC patients is helpful to decrease the misdiagnosis. Although the treatment of ARPC is challenging, systemic assessment of existing regimens is not available. PATIENT CONCERNS: A 50-year-old woman was admitted to the hospital due to cutaneous pruritus and papules all over the body. DIAGNOSIS: Physical examination showed various sized papules on the lower limbs, buttocks, back, chest, and upper arms with keratotic plugs in the center. Histopathology showed typical collagenous fiber perforation. The diagnosis of ARPC was made according to histopathology, onset age and typical skin lesions. Type 2 diabetes mellitus (T2DM), chronic renal failure (CRF), and hypothyroidism simultaneously presented in this patient. INTERVENTIONS: This patient was initially treated with topical corticosteroids and oral antihistamines for the skin lesion and pruritus. Medications for glucose control and recovery of renal and thyroid functions were also applied. On the second admission, the combined therapy of topical retinoic acid, Chinese medicinal herb-Qingpeng ointment, and Zinc oxide ointment was added. OUTCOMES: Papules and pruritus were improved significantly after the second hospitalization. CONCLUSION: We present a case of ARPC associated with T2DM, CRF, and hypothyroidism, which has rarely been described. There is no standardized treatment for ARPC. Co-administration of two or more agents for dermatologic interventions and treatment for associated diseases may help to improve skin symptoms.


Assuntos
Doenças do Colágeno/diagnóstico , Dermatopatias/diagnóstico , Doenças do Colágeno/tratamento farmacológico , Doenças do Colágeno/etiologia , Doenças do Colágeno/patologia , Fármacos Dermatológicos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Falência Renal Crônica/complicações , Pessoa de Meia-Idade , Pele/patologia , Dermatopatias/tratamento farmacológico , Dermatopatias/etiologia , Dermatopatias/patologia
18.
Clin Dermatol ; 38(2): 223-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32513402

RESUMO

Langerhans cell histiocytosis (LCH) is an uncommon but serious inflammatory neoplasia that affects many organs, including the skin. Though uncommon, it should remain high on a clinician's differential diagnosis in treatment-resistant cases of conditions, such as seborrheic dermatitis, diaper dermatitis, arthropod bites, and many more. A thorough history nd physical examination for each patient can aid in the diagnosis; however, if clinically suspicious for LCH, a punch biopsy should be performed. Histologic evaluation of LCH is often enough to differentiate it from the many clinical mimickers. Characteristic findings include a histiocytic infiltrate with "coffee bean"-cleaved nuclei, rounded shape, and eosinophilic cytoplasm. Immunohistochemical stains, including CD1a, S100, and CD207 (langerin) are often needed for a definitive diagnosis. Electron microscopy also demonstrates the ultrastructural presence of Birbeck granules, but this is no longer needed due to immunohistochemical staining. Treatment is often necessary for LCH, if systemic involvement exists.


Assuntos
Histiocitose de Células de Langerhans/diagnóstico , Dermatopatias/diagnóstico , Pele/patologia , Antígenos CD/análise , Antígenos CD1/análise , Biomarcadores/análise , Biópsia por Agulha , Diagnóstico Diferencial , Histiocitose de Células de Langerhans/patologia , Humanos , Lectinas Tipo C/análise , Lectinas de Ligação a Manose/análise , Microscopia Eletrônica , Proteínas S100/análise , Pele/ultraestrutura , Dermatopatias/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA