RESUMO
BACKGROUND: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety. OBJECTIVES: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability. METHODS: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically. RESULTS: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions. CONCLUSIONS: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Imidazóis/administração & dosagem , Ceratose Actínica/tratamento farmacológico , Adjuvantes Imunológicos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Imidazóis/efeitos adversos , Ceratose Actínica/imunologia , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Placebos/efeitos adversos , Fatores de Tempo , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/imunologia , Receptor 8 Toll-Like/agonistas , Receptor 8 Toll-Like/imunologia , Resultado do TratamentoRESUMO
The topical calcineurin antagonist tacrolimus plays an important role in the treatment of different forms of eczema because of its favorable risk profile. In addition, different off-label indications have been clinically tested where tacrolimus ointment has achieved clinical improvement. This article discusses off-label treatment of vitiligo, seborrheic dermatitis, steroid rosacea, perioral dermatitis, rosacea and lichen sclerosus.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medicina Baseada em Evidências , Uso Off-Label , Dermatopatias/tratamento farmacológico , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Administração Tópica , Doença Crônica , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Resultado do TratamentoRESUMO
In order to assess the prevalence of human papillomavirus (HPV) infection, the HPV genotypes and factors associated with infection, we conducted a population-based survey in a small municipality in north east Brazil among women aged between 12 and 49 years. A questionnaire regarding socioeconomic variables, reproductive life and sexual behaviour was used, and women were examined gynaecologically, followed by collection of vaginal lavage with saline solution for HPV DNA determination. HPV DNA was detected by the Digene(®) SHARP Signal(TM)-System, and further genotyped by INNO-LiPA Genotyping System(®). Of 579 women, HPV infection was present in 68 (prevalence: 11.7%; 95% CI: 9.3-14.7). The most common HPV types were 16, 31 and 74, each accounting for 14.7% of infections. Of all HPV-positive women, 35.3% showed multiple HPV genotypes. Variables independently associated with HPV infection were: ≥3 partners in life (adjusted OR [aOR]: 3.06; 95% CI: 1.68-5.60) and the use of oral contraception in the last 12 months (aOR: 2.39; 95% CI: 1.33-4.30). Previous participation in a cervical cancer screening programme was protective (aOR: 0.28; 95% CI: 0.13-0.60). HPV infection is common among women from rural Brazil, and HPV genotypes identified indicate that immunization could be an important preventive measure in this population.
Assuntos
Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Brasil/epidemiologia , DNA Viral/análise , Feminino , Genótipo , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , População Rural/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Fatores SocioeconômicosAssuntos
Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Educação , Fumaratos/administração & dosagem , Fumaratos/efeitos adversos , Psoríase/tratamento farmacológico , Administração Oral , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/epidemiologia , Alopecia em Áreas/psicologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/psicologia , Disponibilidade Biológica , Ensaios Clínicos como Assunto , Comorbidade , Fármacos Dermatológicos/farmacocinética , Fumarato de Dimetilo , Relação Dose-Resposta a Droga , Esquema de Medicação , Etanercepte , Seguimentos , Fumaratos/farmacocinética , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/efeitos adversos , Taxa de Depuração Metabólica/fisiologia , Terapia PUVA/métodos , Projetos Piloto , Estudos Prospectivos , Psoríase/epidemiologia , Psoríase/psicologia , Qualidade de Vida , Receptores do Fator de Necrose Tumoral/administração & dosagem , Sistema de Registros , Papel do DoenteRESUMO
Skin infections are more frequent in immunodeficient patients, seniors and infants than in healthy individuals with an intact immune system. The severity of infections ranges from localized, self-limiting cutaneous infections to widespread necrosis of the skin, muscle, and fascia. The most frequent infections of the skin and mucous membranes are caused by bacterial and viral infectious agents. Fungal infection are also important especially in immunocompromised patients. In particular, viruses play an important and increasing role in the development of several tumors including HPV-associated cervical, anal and penile cancer or HHV-8-induced Kaposi sarcoma.
Assuntos
Mucosa/microbiologia , Mucosa/virologia , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/microbiologia , Dermatopatias Virais/diagnóstico , Dermatopatias Virais/virologia , HumanosRESUMO
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.
Assuntos
Micose Fungoide/patologia , Micose Fungoide/cirurgia , Transplante de Células-Tronco/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Resultado do TratamentoRESUMO
Trombiculiasis is an epizoonosis that occurs worldwide and is caused by various types of chiggers. Clinical findings after accidental contact with the parasitic mite larvae include erythematous papules and urticarial plaques, to some extent with vesicular transformation, which can lead to excoriations due to the intense pruritus. Prophylaxis against exposure is recommended when visiting areas known to be colonized by mites. Reactions to bites can be treated by local application of alcohol compresses or zinc lotions and external application of agents containing polidocanol or glucocorticosteroid. Systemic antihistamines are indicated to control itching.
Assuntos
Eritema/tratamento farmacológico , Eritema/prevenção & controle , Trombiculíase/diagnóstico , Trombiculíase/tratamento farmacológico , Adulto , Fármacos Dermatológicos/uso terapêutico , Humanos , MasculinoRESUMO
Side effects after tattoos are being observed with greater frequency in dermatological practice. The complications that occur can be classified into systemic and local reactions. The time course of cutaneous side effects ranges from direct complications during or following tattooing to reactions that first appear several years thereafter. The majority of allergic complications can be explained by the delayed degradation of the color pigment used for the tattoo and then release of potent allergens sometimes not until years later.
Assuntos
Corantes/efeitos adversos , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/etiologia , Tatuagem/efeitos adversos , Adulto , Humanos , MasculinoRESUMO
Leishmaniasis includes a spectrum of different diseases that differ in their clinical appearance and severity and influence the patient's health to varying degrees. All the diseases are caused by parasites of the genus Leishmania. The simplest and most widely used classifications use the clinical features and the geographic distribution. Cutaneous leishmaniasis can be divided into localized, diffuse, recurrent or post-kala-azar. Using the geographic distribution leishmaniasis of the Old World, is found in Africa, Asia, Middle East, Mediterranean basin and India. Both, cutaneous and visceral leishmaniasis, may develop. In contrast, New World leishmaniasis is caused by leishmania found in Central and South America and cause may cutaneous, mucocutaneous and visceral findings.
Assuntos
Leishmaniose Cutânea/diagnóstico , Viagem , Clima Tropical , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Estudos Transversais , Diagnóstico Diferencial , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/terapiaRESUMO
As a result of the rise of mass tourism with increasingly cheap and exotic destinations, tropical diseases are becoming an increasingly important part of dermatology. Infection with cutaneous larva migrans is one of the most common "souvenirs" from the tropics. The disease is caused by the nematode infection with dog or cat hookworm parasites (Ancylostoma braziliense or A. caninum). The characteristic manifestation is a gyrated, serpiginous and in some cases vesicular erythema, which appears after penetration of the epidermis by the parasite and the subsequent intraepidermal migration of the larva. This is often accompanied by intense pruritus in the affected skin. The infection is usually found in those areas of the foot, calf or buttocks exposed by walking or sitting on sand. Although subjectively very unpleasant, the disease is self-limiting and resolves after several weeks; it is treated locally in most cases (e.g. using cryotherapy). The prognosis of the disease is excellent, but a prolonged course or complications have been observed, e.g. due to superinfection.
Assuntos
Ancilostomíase/diagnóstico , Larva Migrans/diagnóstico , Viagem , Clima Tropical , Ancylostoma , Ancilostomíase/tratamento farmacológico , Animais , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/uso terapêutico , Diagnóstico Diferencial , Humanos , Ivermectina/efeitos adversos , Ivermectina/uso terapêutico , Larva Migrans/tratamento farmacológico , Prurido/etiologiaRESUMO
Tourists in the tropics often develop reactions to bites or stings of mosquitoes, fleas, mites, ants, bedbugs, beetles, larva, millipedes, spiders and scorpions. In addition, they may have fresh or salt water exposure to sponges, corals, jellyfish and sea urchins with resultant injury and inflammation. Bacterial skin infections (pyodermias) can follow bites or stings as well as mechanical trauma. The most common bacteria involved in skin infections are staphylococci and streptococci. For tourists, bacterial infections are often complicating a pruritic bite reaction and scratching. It is important to know the cause of the bite reaction and pyoderma in order to take appropriate therapeutic measures.
Assuntos
Artrópodes , Mordeduras e Picadas de Insetos/diagnóstico , Pioderma/diagnóstico , Picada de Aranha/diagnóstico , Viagem , Clima Tropical , Animais , Diagnóstico Diferencial , Humanos , Mordeduras e Picadas de Insetos/etiologia , Pioderma/etiologia , Picada de Aranha/etiologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/etiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/etiologiaRESUMO
The molecular causes for resistance of melanoma to apoptosis are currently only partly understood. In the present study, we examined gene transfer and expression of the proapoptotic BH3-only protein Noxa as an alternative approach to chemotherapy and investigated the molecular mechanisms regulating Noxa-induced apoptosis. Noxa gene transfer caused dysregulation of both mitochondria and, as shown for the first time, also the endoplasmic reticulum, resulting in the accumulation of reactive oxygen species. Interestingly, expression of Noxa not only triggered the classical mitochondrial caspase cascade, but also resulted in the activation of apoptosis signal-regulating kinase1 and its downstream effectors c-Jun N-terminal kinase and p38. The activation of these kinases was abolished by antioxidants. Moreover, inhibition of the kinases by RNA interference or pharmacological inhibitors significantly attenuated Noxa-induced apoptosis. Thus, our data provide evidence for the involvement of multiple pathways in Noxa-induced apoptosis that are triggered at mitochondria and the endoplasmic reticulum, and suggest Noxa gene transfer as a complementary approach to chemotherapy.
Assuntos
Apoptose , Retículo Endoplasmático/metabolismo , Sistema de Sinalização das MAP Quinases , Melanoma/metabolismo , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/genética , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Caspases/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Retículo Endoplasmático/genética , Técnicas de Transferência de Genes , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase Quinase 5/genética , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Melanoma/genética , Melanoma/terapia , Mitocôndrias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Interferência de RNA , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoAssuntos
Infecções por Proteus , Sarcoma de Kaposi , Neoplasias Cutâneas , Infecções Estafilocócicas , Superinfecção , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Proteus/isolamento & purificação , Infecções por Proteus/diagnóstico , Infecções por Proteus/tratamento farmacológico , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/microbiologia , Sarcoma de Kaposi/patologia , Pele/patologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/microbiologia , Neoplasias Cutâneas/patologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Fatores de Tempo , Resultado do TratamentoAssuntos
Adenocarcinoma/diagnóstico , Neoplasias da Mama Masculina/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Penfigoide Bolhoso/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/patologia , Idoso de 80 Anos ou mais , Biópsia , Mama/patologia , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/patologia , Diagnóstico Diferencial , Quimioterapia Combinada , Humanos , Imunossupressores/uso terapêutico , Masculino , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Síndromes Paraneoplásicas/tratamento farmacológico , Síndromes Paraneoplásicas/patologia , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Pele/patologiaAssuntos
Escabiose/diagnóstico , Administração Tópica , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/tratamento farmacológico , Masculino , Permetrina/administração & dosagem , Ácido Salicílico/administração & dosagem , Escabiose/tratamento farmacológico , Escabiose/patologia , Pele/patologia , Urticária/etiologiaRESUMO
Many forms of topical chemo- and immunotherapy are employed to treat skin cancers. Topical treatment is particularly attractive for field cancerization involving multiple non-melanoma skin cancers. The dermatologist must identify such patients and lesions and provide the most suited therapy.
Assuntos
Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Induzidas por Radiação/terapia , Neoplasias Cutâneas/terapia , Raios Ultravioleta/efeitos adversos , Terapia Combinada , Criocirurgia , Procedimentos Cirúrgicos Dermatológicos , Humanos , Terapia a Laser , Fotoquimioterapia , Lesões Pré-Cancerosas/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The suppressors of cytokine signalling (SOCS) are inhibitors of cytokine signalling; methylation of SOCS-3 has been implicated in the tumorigenesis of liver as well as head and neck cancer. AIMS: This study was performed to elucidate the role of SOCS-1 and SOCS-3 in Barrett's adenocarcinoma and its precursor lesions. METHODS: DNA of specimens from 19 Barrett's adenocarcinomas, 56 Barrett's intraepithelial neoplasias (n = 29 low grade and n = 27 high grade), 30 Barrett's mucosa without neoplasia, 20 samples of normal squamous and gastric epithelium and four cell lines were studied using methylation specific PCR for the SOCS-1 and SOCS-3 promoter following microdissection. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real time PCR, and the SOCS-3 protein was analysed immunohistochemically. RESULTS: In normal squamous epithelium and normal gastric mucosa, neither SOCS-3 nor SOCS-1 methylation was observed. In Barrett's mucosa without intraepithelial neoplasia, SOCS-3 methylation occurred in 4/30 cases (13%) whereas SOCS-1 was unmethylated. A hypermethylated SOCS-3 promoter was found in 14/19 Barrett's adenocarcinomas (74%) and in 20/29 high and 6/27 low grade intraepithelial neoplasias (69% and 22%, respectively). SOCS-1 promoter hypermethylation occurred in 8/19 adenocarcinomas (42%) and in 6/29 high grade and 1/27 low grade intraepithelial neoplasias (21% and 4%, respectively). Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumours and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased after treatment with the demethylation compound 5-aza-2-deoxycytidine. CONCLUSIONS: These data indicate that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of Barrett's adenocarcinoma.
Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Adenocarcinoma/metabolismo , Esôfago de Barrett/metabolismo , Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Ilhas de CpG/genética , DNA de Neoplasias/genética , Neoplasias Esofágicas/metabolismo , Humanos , Metilação , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas/genética , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Transcrição Gênica/genéticaAssuntos
Anfotericina B/administração & dosagem , Eritema Multiforme/diagnóstico , Eritema Multiforme/tratamento farmacológico , Fluconazol/administração & dosagem , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisolona/administração & dosagem , Adulto , Anti-Inflamatórios/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Pescoço/patologia , SíndromeRESUMO
A 72-year-old patient with esophageal carcinoma developed a severe hand-foot syndrome during second-line therapy with the oral fluoropyrimidine capecitabine. We also summarize the current knowledge with regard to the hand-foot syndrome and distinguish it from palmoplantar erythrodysesthesia.