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2.
J Eur Acad Dermatol Venereol ; 33(7): 1281-1289, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30811675

RESUMO

BACKGROUND: Risk factors for primary non-melanoma skin cancer (NMSC) in organ transplant recipients (OTR) have been well described. Data for subsequent NMSC and dynamics in their occurrence in OTR are limited. OBJECTIVE: To study long-term risks of primary and subsequent NMSC and associated risk factors in OTR. METHODS: A retrospective single-centre cohort study analysing medical records from a dermato-oncological specialty clinic. RESULTS: Of 464 OTR 110 (23.7%) developed at least one, 73 (15.7%) two and 51 (11%) three NMSC during a median follow-up of 9.6 years. Cumulative incidences at 5, 10 and 15 years were 14.7%, 23.5% and 34.5% for the first and 75.8%, 86.5% and 93.3% for the second. Median time-to-diagnosis declined from 22 years (95% CI 19-25) to 2 years (1-3) and about 1 year (0-2) for the first, second and third NMSC. Risk for subsequent NMSC only partially related to risk factors for the primary NMSC. Histologic type of the first NMSC predicted subtype and time-to-diagnosis of the subsequent NMSC. CONCLUSIONS: A first post-transplant NMSC, particularly a SCC, confers a high risk for subsequent NMSC arising with accelerated dynamics. Risk-adapted dermato-oncologic surveillance is advisable for all OTR.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Transplante de Órgãos , Neoplasias Cutâneas/epidemiologia , Adulto , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Segunda Neoplasia Primária/patologia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/patologia , Fatores de Tempo , Adulto Jovem
4.
Br J Dermatol ; 179(2): 405-412, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29479687

RESUMO

BACKGROUND: The inflammatory tumour microenvironment is crucial for effective tumour control, and long-term immunosuppression has been identified as a major risk factor for skin carcinogenesis. In solid organ transplant recipients (OTRs) undergoing long-term pharmacological immunosuppression, an increased incidence of cutaneous squamous cell carcinoma (SCC) and more aggressive tumour growth compared with immunocompetent patients has been reported. OBJECTIVES: To determine the density and phenotype of immune cells infiltrating SCC and surrounding skin in OTRs, and to characterize the microanatomical distribution patterns in comparison with immunocompetent patients. METHODS: We analysed immune cell infiltrates within SCC and at defined regions of interest (ROIs) of tumour-surrounding skin in formalin-fixed paraffin-embedded tissue of 20 renal transplant patients and 18 carefully matched immunocompetent patients by high-resolution semiautomated microscopy on complete tissue sections stained for CD4, CD8, CD20 and CD68. RESULTS: The overall immune cell density of SCC arising in OTRs was significantly reduced compared with immunocompetent patients. Particularly CD4+ infiltrates at the directly invasive margin and tumour vicinity, intratumoral CD8+ T-cell densities and the overall density of CD20+ tumour-infiltrating B cells were significantly reduced in the tissue of OTRs. CONCLUSIONS: Immune cell infiltrates within SCC and at defined ROIs of tumour-surrounding skin in OTRs differ markedly in their composition and microanatomical distribution compared with tumours arising in immunocompetent patients. Our findings substantially broaden the understanding of how long-term systemic immunosuppression modulates the local inflammatory microenvironment in the skin and at the site of invasive SCC.


Assuntos
Carcinoma de Células Escamosas/imunologia , Terapia de Imunossupressão/efeitos adversos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Cutâneas/imunologia , Pele/citologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Carcinoma de Células Escamosas/patologia , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pele/imunologia , Pele/patologia , Neoplasias Cutâneas/patologia , Linfócitos T/imunologia , Transplantados , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
5.
Br J Dermatol ; 178(1): 207-214, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28733990

RESUMO

BACKGROUND: Neutrophil (polymorphonuclear) granulocytes (PMN) have been shown to contribute to the pathogenesis of psoriasis by releasing interleukin-17 and LL37-DNA complexes via neutrophil extracellular traps (NETs), webs of chromatin strands decorated with antimicrobial peptides, in psoriatic skin. Fumaderm® , a fumaric acid ester (FAE) formulation consisting of different FAE salts, has been successfully used to treat psoriasis for decades. Most recently, FAE treatment was reported to inhibit NET formation in murine epidermolysis bullosa acquisita. OBJECTIVES: To elucidate the effect of FAE treatment on human psoriasis and healthy donor NET formation. RESULTS: Among the compounds present in the FAE formulation, dimethyl fumarate (DMF) pretreatment of human psoriasis and healthy donor PMN resulted in a consistent inhibitory effect on NET formation in response to phorbol 12-myristate 13-acetate but not to platelet activating factor and ionomycin. This effect was l-glutathione (GSH) dependent and involved a decrease in reactive oxygen species (ROS) production, a key event in NET formation. In contrast, G-protein-coupled signalling and protein synthesis were not involved. Monomethyl fumarate (MMF) was found to slightly reduce ROS production without affecting NET formation. CONCLUSIONS: We report DMF as a potent, stimulus-specific, GSH- and ROS-dependent modulator of NET formation. Our results support the notion that modulation of NET formation contributes to the beneficial effects of FAEs in a variety of inflammatory conditions.


Assuntos
Fármacos Dermatológicos/farmacologia , Fumarato de Dimetilo/farmacologia , Armadilhas Extracelulares/efeitos dos fármacos , Psoríase/tratamento farmacológico , Análise de Variância , Antioxidantes/farmacologia , Caspases/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Fumaratos/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Glutationa/metabolismo , Humanos , Ionomicina/farmacologia , Fator de Ativação de Plaquetas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
7.
J Eur Acad Dermatol Venereol ; 31(11): 1912-1915, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28342182

RESUMO

BACKGROUND: Several autosomal dominant disorders may manifest in mosaic patterns with cutaneous involvement. Genomic mosaicism results from postzygotic autosomal mutations, giving rise to clonal proliferation of two genetically distinct cell groups, which clinically present as lesions following the lines of Blaschko. OBJECTIVE: To increase the awareness of the clinical variability of mosaic manifestations in autosomal dominant skin disorders in order to avoid delayed diagnosis. METHODS: Clinicopathologic correlation in a case series including three patients with mosaic manifestations of different autosomal dominant skin diseases. RESULTS: Here, we describe a patient with type 1 segmental mosaicism of epidermolytic ichthyosis (case 1) and two patients with either type 1 (case 2) or type 2 (case 3) segmental neurofibromatosis 1 (NF1). CONCLUSION: Dermatologists should be familiar with mosaic manifestations of autosomal dominant skin diseases to ensure appropriate guidance of the affected patient. Genetic counselling is mandatory as even limited forms of mosaicism may involve the patient's germline with a moderately increased risk to transmit the mutation to their offspring, resulting in a more severe, generalized form of the respective disease.


Assuntos
Genes Dominantes , Mosaicismo , Dermatopatias/patologia , Adolescente , Criança , Feminino , Humanos , Masculino , Dermatopatias/genética
8.
Immunotherapy ; 8(9): 1033-44, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27485076

RESUMO

BACKGROUND: Ipilimumab is a cytotoxic T-lymphocyte antigen-4 antibody that enhances T-cell activity and proliferation. METHODS: In a retrospective analysis of 86 patients the clinical benefits of ipilimumab treatment were correlated with laboratory and clinical data. RESULTS: A lactate dehydrogenase (LDH) value within the normal range before the start of therapy was significantly correlated with better OS (p ≤ 0.009). An increase in LDH level after two cycles was indicative of a poor outcome, and was significantly negatively correlated with treatment response and overall survival and progression-free survival. 42% of all patients suffered from autoimmune toxicity (CTCAE grades 2-4). The occurrence of autoimmune toxicity clearly correlated with clinical benefit. CONCLUSION: Changes in LDH level and side effects correlate with response to therapy and survival.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , L-Lactato Desidrogenase/metabolismo , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/mortalidade , Biomarcadores Farmacológicos/metabolismo , Proteína C-Reativa/metabolismo , Antígeno CTLA-4/imunologia , Proliferação de Células , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Feminino , Humanos , Ipilimumab , Ativação Linfocitária , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
J Eur Acad Dermatol Venereol ; 30(10): 1657-1669, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27406069

RESUMO

BACKGROUND: The treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe clinical cases, the use of immunoglobulin is not generally based on data from randomized controlled trials that are usually required for the practice of evidence-based medicine. Owing to the rarity of the indications for the use of IVIg, it is also unlikely that such studies will be available in the foreseeable future. Because the high costs of IVIg treatment also limit its first-line use, the first clinical guidelines on its use in dermatological conditions were established in 2008 and renewed in 2011. MATERIALS AND METHODS: The European guidelines presented here were prepared by a panel of experts nominated by the EDF and the EADV. The guidelines were developed to update the indications for treatment currently considered as effective and to summarize the evidence base for the use of IVIg in dermatological autoimmune diseases and TEN. RESULTS AND CONCLUSION: The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases.


Assuntos
Doenças Autoimunes/terapia , Imunoglobulinas Intravenosas/administração & dosagem , Dermatopatias/terapia , Europa (Continente) , Humanos , Imunoglobulinas Intravenosas/uso terapêutico
12.
J Eur Acad Dermatol Venereol ; 30(4): 619-23, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26508040

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a highly effective treatment option for actinic keratosis (AK). Hyperkeratosis of the AK impairs penetration of the photosensitizer and light and leads to a reduced efficacy of PDT. Therefore, it is commonly recommended to perform curettage of the AK prior to treatment. OBJECTIVE: This observational, monocentric, retrospective study sets out to compare the effects of curettage (CUR), chemical keratolytic pretreatment with salicylic acid 10% (SA), and urea cream 40% (UR) on the efficacy and tolerability of PDT. METHOD: A total of 44 subjects aged 73.2 ± 7.7 years (mean ± SD) with multiple AKs (mean 11.1 per patient) in face and scalp were analysed. In 15 patients, CUR was performed prior to PDT while 15 and 14 patients underwent keratolytic pretreatment with SA and UR, respectively, 1 day prior to PDT. All patients underwent one session of methylaminolaevulinate (MAL) PDT using a 630-nm LED lamp at 37 J/cm(2) , pain was measured using a visual analogue scale. The response rate was calculated using the documented number of AKs prior and 4 weeks after PDT. RESULTS: Mean lesion response rates were 68.5%, 61.4% and 60.8% for CUR, SA and UR respectively. Differences were not significant. Patients with SA or UR experienced significantly more pain (SA: 6.3 ± 2.7, P = 0.02; UR: 6.1 ± 1.8, P = 0.04) than patients with curettage (4.4 ± 2.1). The cosmetic result and the patients' satisfaction 4 weeks after PDT were good to excellent in all three groups without a significant difference. However, pretreatment with SA or UR led to pronounced local reactions compared to CUR. CONCLUSION: Keratolytic therapy with SA or UR is an effective pretreatment for PDT. However, it leads to an increase in pain during PDT and pronounced local reactions.


Assuntos
Ácido Aminolevulínico/análogos & derivados , Ceratose Actínica/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Ácido Salicílico/uso terapêutico , Ureia/uso terapêutico , Idoso , Ácido Aminolevulínico/uso terapêutico , Feminino , Humanos , Ceratose Actínica/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Br J Dermatol ; 165(6): 1355-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21801160

RESUMO

BACKGROUND: Infliximab is successfully used to treat psoriasis and psoriatic arthritis. However, some patients lose therapeutic response after several cycles. Antibodies to infliximab (infliximab-Abs) are induced during treatment in a subgroup of patients and are thought to be associated with loss of response (LOR). Routine screening for infliximab-Abs is expensive and not regularly performed. A reliable and affordable method for identifying patients who are at risk for LOR to infliximab is desirable. OBJECTIVES: To analyse the development of antinuclear antibodies (ANA)/antidouble-stranded DNA antibodies (anti-dsDNA) over time in patients with psoriasis receiving infliximab. To analyse if there is an association between ANA titres/anti-dsDNA concentrations, infliximab-Ab status and LOR. METHODS: A retrospective data analysis of 29 patients with psoriasis receiving infliximab was carried out. ANA titres and anti-dsDNA concentrations were regularly monitored in these patients and sera were tested for infliximab-Abs by enzyme-linked immunosorbent assay. RESULTS: Median ANA titres increased from 1 : 80 [interquartile range (IQR) 0 to 1 : 320, n = 29] pretreatment, to 1 : 1280 (IQR 1 : 640 to 1 : 1920, n = 15) after infusion 10, and 1 : 1920 (IQR 1 : 1280 to 1 : 2560, n = 10) after infusion 20. Infliximab-Abs were found in 21% of patients. Infliximab-Ab-positive patients and patients with LOR had significantly higher pretreatment anti-dsDNA concentrations and higher pretreatment ANA titres than infliximab-Ab-negative and responsive patients, respectively. CONCLUSIONS: The results of this study suggest a role for autoantibodies in the identification of patients with psoriasis at higher risk of developing infliximab-Abs and of LOR under treatment with infliximab.


Assuntos
Anticorpos Antinucleares/metabolismo , Anticorpos Monoclonais/imunologia , Autoanticorpos/metabolismo , Fármacos Dermatológicos/imunologia , Resistência a Medicamentos/imunologia , Psoríase/imunologia , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Estudos de Casos e Controles , DNA/imunologia , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Psoríase/tratamento farmacológico , Estudos Retrospectivos
15.
Hautarzt ; 60(1): 32-41, 2009 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-19099271

RESUMO

Eczema is one of the most common skin diseases in dermatological practice. The broad medical definition of eczema includes any acute but non-infectious inflammatory reaction of the skin. The relative homogeneity of both the clinical and histological manifestations of eczema is in stark contrast to the profound pathogenetic differences of its various forms. The group of contact dermatitis can be divided into two main categories: irritant and allergic. Irritant contact dermatitis is due to a principally non- immunological inflammatory reaction of the skin to various physical or chemical irritants. In sharp contrast, allergic contact dermatitis is an antigen-specific cellular immune response of the skin, which in general requires prior antigen-recognition and priming of immune cells. A comprehensive understanding of the complex interactions between immune cells, inflammatory mediators and adhesion molecules in the underlying pathogenesis of allergic contact dermatitis is key for a better functional understanding and the development of new therapeutic strategies.


Assuntos
Dermatite Alérgica de Contato/imunologia , Eczema/imunologia , Imunidade Inata/imunologia , Modelos Imunológicos , Pele/imunologia , Humanos
16.
Clin Infect Dis ; 48(1): 83-5, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19035775

RESUMO

Diagnosis and treatment of syphilis are challenging because of the condition's diverse clinical symptoms, histopathological variance, and the lack of definite tests for treatment follow-up. We report a case of secondary pustular-ulcerative malignant syphilis with ocular involvement in a human immunodeficiency virus-infected patient. It was striking to find that ulcerative lesions can be highly organism depleted.


Assuntos
Oftalmopatias/etiologia , Sífilis/complicações , Oftalmopatias/microbiologia , Oftalmopatias/patologia , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Sífilis/microbiologia , Sífilis/patologia , Úlcera/microbiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-16329648

RESUMO

Regulatory T cells (Treg) in broader terms consist of different subsets of T cells that are characterized by their ability to suppress proliferation of conventional effector T cells by various means. To date, three main groups of Treg can de distinguished, mainly by their functional properties (for review see Jonuleit and Schmitt 2003) Briefly, T regulatory (Tr)-1 cells as well as T helper (Th)-3 T cells express common T cell markers such as CD4 and are characterized by secretion of IL-10 and TGF-beta, which provides a means by which proliferation of conventional CD4+ cells is blocked. In contrast, genuine Treg that are characterized by their expression of CD25 block T cell proliferation by an unknown cell-to-cell contact-dependent mechanism. However, there are many overlapping features shared by the different subtypes of regulatory T cell and the common denominator is the production of regulatory cytokines such as IL-10 and TGF-beta.


Assuntos
Citocinas/imunologia , Células Dendríticas/imunologia , Ativação Linfocitária , Linfócitos T Reguladores/imunologia , Animais , Células Dendríticas/efeitos dos fármacos , Tolerância Imunológica/fisiologia , Imunossupressores/farmacologia , Interleucina-10/imunologia , Fator de Crescimento Transformador beta/imunologia , Fator de Necrose Tumoral alfa/imunologia
19.
Curr Top Microbiol Immunol ; 293: 133-50, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15981479

RESUMO

Even though dendritic cells (DCs) are well known for their capacity to induce immune responses, recent results show that they are also involved in the induction of tolerance. These two contrary effects of otherwise homologous DCs on a developing immune response maybe explainedby different DC developmental stages, i.e., different subsets of DCs may exist and/or different spatial distribution of DCs in the body might influence their function. However, independently from the subtype(s), it is obvious that the ability of DCs to act in a tolerogenic fashion depends on the maturation status, since immature DCs are prone to induce regulatory T cells and hence promote tolerance, whereas mature DCs stimulate effector T cells, facilitating immunity. The means by which DCs convey tolerance are not entirely clear yet, but secretion of suppressive cytokines such as IL-10 and induction of regulatory lymphocytes are involved. In this review we focus on the interaction between DCs and T cells and highlight some mechanisms in the decision-making process of whether immunity or tolerance is induced.


Assuntos
Células Dendríticas/imunologia , Linfócitos T/imunologia , Animais , Citocinas/fisiologia , Células Dendríticas/efeitos dos fármacos , Retroalimentação Fisiológica , Humanos , Tolerância Imunológica , Imunidade
20.
Gene Ther ; 10(3): 243-50, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12571632

RESUMO

In recent years, vaccination strategies using antigen-presenting cells (APC) have been under investigation. Antigen delivery using genetic immunization through ex vivo transduction of dendritic cells (DC) is supposed to enhance the induction of antitumor responses in humans by activating a broad range of peptide-specific CD8+ T cells. In this study, we compared the potential of adenoviral (Ad)-transduced versus peptide-pulsed DC to induce melanoma-antigen (Ag)-specific T-cell responses in vitro. Whereas gp100-peptide-pulsed DC induced long-lasting specific CD8+ T-cell responses against single peptides, Ad-transduced DC induced broad and strong, specific immunity against various peptides of the gp100-Ag. Surprisingly, several restimulations led to decreasing gp100-specific and in parallel to increasing anti-adenoviral T-cell responses. Nevertheless, those anti-adenoviral T-cell responses provided an "adjuvant" effect by inducing an early release of high amounts of IL-2/IFN-gamma, therewith enhancing CTL induction in the initiation phase. Based on these data, we suggest a prime/boost vaccination strategy in melanoma patients--combining the use of Ad-DC and peptide-pulsed DC--to obtain efficient and long-term antitumor T-cell responses.


Assuntos
Células Dendríticas/imunologia , Epitopos/genética , Terapia Genética/métodos , Melanoma/terapia , Glicoproteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/terapia , Adenoviridae/genética , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer , Linhagem Celular , Vetores Genéticos/administração & dosagem , Humanos , Interferon gama/imunologia , Interleucina-2/imunologia , Melanoma/imunologia , Glicoproteínas de Membrana/administração & dosagem , Proteínas de Neoplasias/administração & dosagem , Neoplasias Cutâneas/imunologia , Transdução Genética/métodos , Antígeno gp100 de Melanoma
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