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1.
Hautarzt ; 2020 Feb 17.
Artigo em Alemão | MEDLINE | ID: mdl-32065247

RESUMO

Anal intraepithelial neoplasia (AIN) and 89-100% of anal cancers are caused by persistent infections with high-risk (HR) human papillomaviruses (HPV). In HIV-positive patients, anal HPV infection and AIN are very common and these patients have a greatly increased risk of developing anal cancer. However, a continuous increase in the incidence of anal cancer has also been observed in the general population in recent decades. AIN can clinically present in diverse manners. In HIV-positive patients AIN can be hidden in condylomas. Furthermore, 3-14% of high-grade AIN progress to anal cancer within 5 years. Therefore, screening examinations should be offered to patients with an increased risk for anal cancer. The treatment options for AIN are similar to those for condylomas. HIV-positive patients with controlled immune status and HIV-negative patients with anal cancer respond comparably well to combined radiochemotherapy. A German-language AWMF S3 guideline for anal cancer will be available in 2020. In HIV-positive patients over 26 years of age, HPV vaccination showed no effect in a controlled phase­3 study. To prevent AIN and anal cancer in the future, HPV vaccination rates need to be increased in HPV-naïve girls and boys.

4.
Hautarzt ; 70(12): 964-968, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31342101

RESUMO

An atypical variant of hand-foot-mouth disease (HFMD) has sporadically been reported in recent years, with outbreaks in Europe, Asia, the USA and South America. A new lineage of Coxsackie virus A6 has been identified as the causative agent, a virus-type belonging to the group of enteroviruses. HFMD is transmitted through droplet infection or through faecal-oral transmission. The disease may begin with a prodromal stage and is often accompanied by fever and malaise. Typical skin findings include a papular and vesiculobullous exanthema that might be accompanied by confluent blisters (bullae), crusting, and ulceration. In contrast to "classic" HFMD, predilection sites include the dorsal aspects of the hands and feet, forearms, lower legs, neck and trunk. Oral lesions may be present, but are less often seen compared to "classic" HFMD. The course of the disease is self-limiting, with complete resolution usually within 7-14 days after disease onset. The treatment of atypical HFMD is usually symptomatic. A diagnosis of atypical HFMD might be challenging due to the polymorphous presentation of the disease. This review describes a rarely reported but more frequently diagnosed viral condition.


Assuntos
Exantema , Doença de Mão, Pé e Boca , Dermatopatias Vesiculobolhosas , Surtos de Doenças , Europa (Continente) , Exantema/etiologia , Doença de Mão, Pé e Boca/complicações , Doença de Mão, Pé e Boca/patologia , Humanos , Dermatopatias Vesiculobolhosas/patologia
6.
Emerg Infect Dis ; 25(8): 1600-16002, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31310208

RESUMO

Cutavirus was previously found in cutaneous melanoma. We detected cutavirus DNA in only 2/185 melanoma biopsies and in 0/52 melanoma metastases from patients in Germany. Viral DNA was localized in the upper epidermal layers. Swab specimens from healthy skin were cutavirus positive for 3.8% (9/237) of immunocompetent and 17.1% (35/205) of HIV-positive men.


Assuntos
Melanoma/epidemiologia , Melanoma/etiologia , Infecções por Parvoviridae/complicações , Parvovirus , Biópsia , DNA Viral , Alemanha/epidemiologia , Humanos , Melanoma/diagnóstico , Estadiamento de Neoplasias , Infecções por Parvoviridae/virologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Carga Viral
9.
Ann Rheum Dis ; 78(9): 1269-1273, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177096

RESUMO

OBJECTIVES: Systemic sclerosis (SSc) is characterised by aberrant hedgehog signalling in fibrotic tissues. The hedgehog acyltransferase (HHAT) skinny hedgehog catalyses the attachment of palmitate onto sonic hedgehog (SHH). Palmitoylation of SHH is required for multimerisation of SHH proteins, which is thought to promote long-range, endocrine hedgehog signalling. The aim of this study was to evaluate the role of HHAT in the pathogenesis of SSc. METHODS: Expression of HHAT was analysed by real-time polymerase chain reaction(RT-PCR), immunofluorescence and histomorphometry. The effects of HHAT knockdown were analysed by reporter assays, target gene studies and quantification of collagen release and myofibroblast differentiation in cultured human fibroblasts and in two mouse models. RESULTS: The expression of HHAT was upregulated in dermal fibroblasts of patients with SSc in a transforming growth factor-ß (TGFß)/SMAD-dependent manner. Knockdown of HHAT reduced TGFß-induced hedgehog signalling as well as myofibroblast differentiation and collagen release in human dermal fibroblasts. Knockdown of HHAT in the skin of mice ameliorated bleomycin-induced and topoisomerase-induced skin fibrosis. CONCLUSION: HHAT is regulated in SSc in a TGFß-dependent manner and in turn stimulates TGFß-induced long-range hedgehog signalling to promote fibroblast activation and tissue fibrosis. Targeting of HHAT might be a novel approach to more selectively interfere with the profibrotic effects of long-range hedgehog signalling.

10.
Lancet Infect Dis ; 19(8): 799-800, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31204305
12.
J Rheumatol ; 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30936287

RESUMO

OBJECTIVE: Scleroderma renal crisis (SRC) is a severe life-threatening manifestation in patients with systemic sclerosis (SSc). However, the knowledge about risk factors for SRC is limited. We determined here the frequency of SRC and identified risk factors for the prediction of SRC. METHODS: Based on regular followup data from the German Network for Systemic Scleroderma, we used univariate and multivariate generalized estimating equations to analyze the association between clinical variables, SSc subsets, therapy [i.e., angiotensin-converting enzyme inhibitors (ACEi), corticosteroids], and the occurrence of SRC. RESULTS: Data of 2873 patients with 10,425 visits were available for analysis with a mean number of registry visits of 3.6 ± 2.8 and a mean time of followup of 3.6 ± 3.8 years. In total, 70 patients developed SRC (70/2873, 2.4%). Of these patients, 57.1% (40/70) were diagnosed with diffuse cutaneous SSc, 31.4% (22/70) with limited cutaneous SSc, and 11.4% (8/70) with SSc-overlap syndromes. Predictive independent factors with the highest probability for SRC were positive anti-RNA polymerase antibodies (RNAP), a history of proteinuria prior to SRC onset, diminished DLCO, and a history of hypertension. Interestingly, positive antitopoisomerase autoantibodies did not predict a higher risk for SRC. Further, patients with SRC were significantly more frequently treated with ACEi and corticosteroids without being independently associated with SRC. CONCLUSION: In this cohort, SRC has become a rare complication. By far the highest risk for SRC was associated with the detection of anti-RNAP and proteinuria.

15.
Nature ; 566(7744): 344-349, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30700907

RESUMO

Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs.


Assuntos
Diferenciação Celular/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose/genética , Fibrose/patologia , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/metabolismo , Animais , Sequência de Bases , Epigênese Genética , Feminino , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Camundongos , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Transativadores/antagonistas & inibidores
18.
J Dtsch Dermatol Ges ; 17(1): 15-23, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30480868

RESUMO

Scabies has been diagnosed surprisingly frequently in Germany in recent years, and the use of acaricides has risen markedly. Present figures indicate an increase in the prevalence/incidence of scabies, but do not prove or quantify it for the following reasons: (a) scabies is not a notifiable disease in Germany; (b) the diagnosis is not always confirmed lege artis by means of light microscopy or dermatoscopy (which may lead to a comparatively high proportion of false­positive diagnoses due to the low overall prevalence of scabies); (c) repeated treatments of the same patient and treatment of contact persons are included in the total number of prescriptions. Therefore, there are no valid data on disease occurrence, either in the current situation or from previous periods. Observations of ineffective treatment with permethrin have led to speculations that Sarcoptes mites are developing resistance to this drug. However, there is little evidence for this assumption. We discuss risk groups (children, elderly people in need of care, migrant health personnel in nursing institutions, refugees, sexually active young adults) and evaluate their possible contribution, albeit in the absence of evidence. None of the groups would be solely responsible for an increased frequency. We have compiled recommendations on how the management of scabies could be improved, and present a way of differentiating permethrin resistance from application errors and/or lack of compliance. The goal is to solve the epidemiological and parasitological questions mentioned above.


Assuntos
Resistência a Inseticidas , Inseticidas , Ivermectina , Ácaros , Escabiose , Animais , Alemanha , Humanos , Inseticidas/farmacologia , Ivermectina/farmacologia , Ácaros/efeitos dos fármacos , Permetrina/farmacologia , Escabiose/tratamento farmacológico , Escabiose/epidemiologia
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