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INTRODUCTION: Mucocutaneous Behcet's disease is often a therapeutic challenge. Roflumilast has shown promise in other inflammatory dermatological conditions. The objective of this study is to evaluate the characteristics, effectiveness and safety of roflumilast in the treatment of Behçet's Disease-associated aphthosis in routine clinical practice. METHODS: Single cohort ambispective observational study. 11 patients with Behçet disease treated with roflumilast participated. Data collection included demographic, clinical and outcome variables. Statistical analysis compared 12 weeks of treatment with roflumilast with a previous period without treatment and with a period with the previous treatment. RESULTS: During treatment with roflumilast, a reduction in flare-ups and oral ulcers was observed compared to the untreated period and the previous treatment period. A reduction in genital ulcers, pain and ulcer duration was observed between the Whitout treatment period and the Roflumilast treatment period.Adverse effects occurred in 54% of patients, most of which were self-limiting or manageable with dose adjustment. No patient withdrew treatment. DISCUSSION: Roflumilast appears a promising option in the treatment of Behçet's disease with favourable effectiveness, safety and tolerability profiles. Although further research is needed, roflumilast offers a promising treatment option for Behçet's Disease-associated aphthosis, which could improve patients' quality of life and address unmet therapeutic needs.
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Biological therapies are safer and more effective against psoriasis than conventional treatments. Even so, 30-50% of psoriatic patients show an inadequate response, which is associated with individual genetic heterogeneity. Pharmacogenetic studies have identified several single nucleotide polymorphisms (SNPs) as possible predictive and prognostic biomarkers for psoriasis treatment response. The objective of this study was to determine the link between several SNPs and the clinical response to biological therapies in patients with moderate-severe psoriasis. A set of 21 SNPs related to psoriasis and/or other immunological diseases were selected and analysed from salivary samples of patients (n = 88). Treatment effectiveness and patient improvement was assessed clinically through Relative Psoriasis Area and Severity Index (PASI), also called 'PASI response', as well as absolute PASI. Associations between SNPs and PASI factors were assessed at 3 and 12 months for every treatment category of IL-17, IL-23, IL-12&23 and TNF-α inhibitors. Multivariate correlation analysis and Fisher's exact test were used to analyse the relationship between SNPs and therapy outcomes. Several SNPs located in the TLR2, TLR5, TIRAP, HLA-C, IL12B, SLC12A8, TNFAIP3 and PGLYRP4 genes demonstrated association with increased short and long-term therapy-effectiveness rates. Most patients achieved values of PASI response ≥75 or absolute PASI<1, regardless of the biological treatment administered. In conclusion, we demonstrate a relationship between different SNPs and both short- and especially long-term effectiveness of biological treatment in terms of PASI. These polymorphisms may be used as predictive markers of treatment response in patients with moderate-to-severe psoriasis, providing personalized treatment.
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Psoríase , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/genética , Interleucina-12/genética , Polimorfismo de Nucleotídeo Único , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Resultado do Tratamento , Psoríase/tratamento farmacológico , Psoríase/genética , Imunidade , Índice de Gravidade de DoençaRESUMO
Microorganisms colonize all possible ecological habitats, including those subjected to harsh stressors such as UV radiation. Hospitals, in particular the UV cabins used in phototherapy units, constitute an environment in which microbes are intermittently subjected to UV irradiation. This selective pressure, in addition to the frequent use of antibiotics by patients, may represent a threat in the context of the increasing problem of antimicrobial resistance. In this work, a collection of microorganisms has been established in order to study the microbiota associated to the inner and outer surfaces of UV cabins and to assess their resistance to UV light and the antibiotics frequently used in the Dermatology Service of a Spanish hospital. Our results show that UV cabins harbor a relatively diverse biocenosis dominated by typically UV-resistant microorganisms commonly found in sun-irradiated environments, such as Kocuria, Micrococcus or Deinococcus spp., but also clinically relevant taxa, such as Staphylococcus or Pseudomonas spp. The UV-radiation assays revealed that, although some isolates displayed some resistance, UV is not a major factor shaping the biocenosis living on the cabins, since a similar pool of resistant microorganisms was identified on the external surface of the cabins. Interestingly, some Staphylococcus spp. displayed resistance to one or more antibiotics, although the hospital reported no cases of antibiotic-resistance infections of the patients using the cabins. Finally, no association between UV and antibiotic resistances was found.
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Dermatologia , Microbiota , Humanos , Raios Ultravioleta , Antibacterianos/farmacologia , Hospitais , StaphylococcusRESUMO
INTRODUCTION: Due to its aggressiveness, cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. The origin of CM is closely linked to the appearance of UV-induced somatic mutations in melanocytes present in normal skin or in CM precursor lesions (nevi or dysplastic nevi). In recent years, new NGS studies performed on CM tissue have increased the understanding of the genetic somatic changes underlying melanomagenesis and CM tumor progression. METHODS: We reviewed the literature using all important scientific databases. All articles related to genomic mutations in CM as well as normal skin and nevi were included, in particular those related to somatic mutations produced by UV radiation. CONCLUSIONS: CM development and progression are strongly associated with exposure to UV radiation, although each melanoma subtype has different characteristic genetic alterations and evolutionary trajectories. While BRAF and NRAS mutations are common in the early stages of tumor development for most CM subtypes, changes in CDKN2A, TP53 and PTEN, together with TERT promoter mutations, are especially common in advanced stages. Additionally, large genome duplications, loss of heterozygosity, and copy number variations are hallmarks of metastatic disease. Finally, the mutations driving melanoma targeted-therapy drug resistance are also summarized. The complete sequential stages of clonal evolution leading to CM onset from normal skin or nevi are still unknown, so further studies are needed in this field to shed light on the molecular pathways involved in CM malignant transformation and in melanoma acquired drug resistance.
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Sonidegib is a Hedgehog signalling pathway inhibitor approved for use in patients with advanced basal cell carcinoma (BCC) not eligible for surgery or radiotherapy. This report describes clinical experience with sonidegib in two patients with locally advanced BCC (one with a tumour adjacent to the right eye and the other with a tumour associated with the left ear) and in one patient with Gorlin syndrome. Two of the patients had recurrent and intractable tumours. Treatment with sonidegib 200 mg/day led to remission in both patients with locally advanced BCC within 7 months and to a reduction in the size and number of lesions after 4 months in the patient with Gorlin syndrome. Adverse effects reported in these patients were cramps, alopecia, ageusia and weight loss, all of which were mild and consistent with the known toxicity profile for sonidegib. Sonidegib has an important role to play in the effective treatment of challenging cases of advanced BCC. In parallel, a need remains to improve management protocols for patients with advanced BCC, particularly through earlier intervention and a multidisciplinary team approach.
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Sonic hedgehog pathway inhibitor Vismodegib is the first systemic treatment to be approved for metastatic or locally advanced basal cell carcinoma non-subsidiary of surgical treatment, and appears to be a promising treatment option for patients with nevoid basal cell carcinoma syndrome. In these patients, where repeated or prolonged treatment may be necessary, the psychological exhaustion caused by the chronicity of less severe adverse effects appears as the main limiting factor in the persistence of the drug in the long term and in the willingness of patients to take the drug again after its suspension. We report our experience with three cases where a drug holiday approach was effective in decreasing the intensity of adverse effects or improving the patient's subjective tolerance to the drug while maintaining clinical response.
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Antineoplásicos , Síndrome do Nevo Basocelular , Carcinoma Basocelular , Preparações Farmacêuticas , Neoplasias Cutâneas , Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Síndrome do Nevo Basocelular/diagnóstico , Síndrome do Nevo Basocelular/tratamento farmacológico , Carcinoma Basocelular/tratamento farmacológico , Proteínas Hedgehog/uso terapêutico , Humanos , Piridinas , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
Melanoma/epidemiologia , Doenças da Unha/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias das Glândulas Sudoríparas/epidemiologia , Glândulas Sudoríparas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Pé , Mãos , Humanos , Masculino , Margens de Excisão , Melanoma/etiologia , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Doenças da Unha/patologia , Doenças da Unha/cirurgia , Unhas/patologia , Unhas/cirurgia , Pele/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias das Glândulas Sudoríparas/etiologia , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/cirurgia , Glândulas Sudoríparas/cirurgiaAssuntos
Erupções Acneiformes/induzido quimicamente , Inibidores da Angiogênese/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Erupções Acneiformes/patologia , Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento do Endotélio VascularRESUMO
Programmed cell death receptor 1 inhibitors (anti-PD-1) constitute a form of immunotherapy for the treatment of several cancers. They are associated with cutaneous immune-related adverse events (irAE), occurring in up to 50% of patients. Lichenoid dermatitis is frequent and several presentations have been described. Although attempts have been made to study these reactions, they are yet to be fully characterized and the relationship with tumor response is unclear. We describe a case of digital ulcerative lichenoid dermatitis resembling ulcerative cutaneous lichen planus that occurred during pembrolizumab therapy for oral squamous cell carcinoma. The patient developed a painful ulcer on his index finger 18 months into therapy. Biopsy revealed epidermal ulceration with intense lichenoid dermatitis. Immunohistochemical study revealed intense CD8 positivity at the ulcer's edges and marked CD163 positivity at its base. Although idiopathic forms of this type of lichenoid dermatitis are particularly recalcitrant, our case was successfully managed with topical therapy and oncologic treatment did not require modification. One year after ending treatment the patient remains free of disease progression. It is unclear if this reaction is associated with his favorable oncologic response. This report adds an undescribed reaction to the increasing diversity of cutaneous irAE associated with anti-PD-1 therapy.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Erupções Liquenoides/induzido quimicamente , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Úlcera Cutânea/induzido quimicamente , Administração Cutânea , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Betametasona/administração & dosagem , Betametasona/análogos & derivados , Carcinoma de Células Escamosas/tratamento farmacológico , Combinação de Medicamentos , Gentamicinas/administração & dosagem , Humanos , Erupções Liquenoides/tratamento farmacológico , Erupções Liquenoides/patologia , Masculino , Neoplasias Bucais/tratamento farmacológico , Pele/patologia , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/patologiaRESUMO
Cowden syndrome (CS) is an infrequent genodermatosis caused by mutations in the phosphatase and tensin homolog (PTEN) gene in the majority of cases. As such, it belongs to the PTEN hamartoma tumor syndrome spectrum. This disease has a variable clinical expression characterized by the development of multiple hamartomatous tumors in different organs, usually during the second and third decades of life, and a high cumulative risk of several malignancies. We present a case of Cowden syndrome with late diagnosis presenting with a florid dermatological expression and multiple benign tumors, but no malignancies. A novel PTEN mutation was identified.
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Fibroma/genética , Síndrome do Hamartoma Múltiplo/genética , Neoplasias Bucais/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias Cutâneas/genética , Feminino , Fibroma/diagnóstico , Fibroma/etiologia , Fibroma/patologia , Folículo Piloso , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/diagnóstico , Síndrome do Hamartoma Múltiplo/patologia , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologia , Mutação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologiaAssuntos
Antineoplásicos/efeitos adversos , Vasculite por IgA/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Sunitinibe/efeitos adversos , Adulto , Biópsia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Dermoscopia , Feminino , Humanos , Vasculite por IgA/diagnóstico , Vasculite por IgA/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Pele/diagnóstico por imagem , Pele/patologiaRESUMO
As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.
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Antígenos de Neoplasias/genética , Predisposição Genética para Doença , Melanoma/genética , Proteínas de Membrana Transportadoras/genética , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Variação Genética , Genótipo , Haplótipos , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Mutação , Risco , EspanhaRESUMO
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.
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Encéfalo/patologia , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/mortalidade , Doença de Erdheim-Chester/patologia , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
Las mucopolisacaridosis son un grupo de enfermedades de depósito en las cuales el déficit de una determinada enzima lisosomal produce la acumulación de mucopolisacáridos en los lisosomas de las células de varios órganos, incluyendo la piel. El síndrome de Hunter o mucopolisacaridosis tipo II se debe al déficit de la iduronato 2 sulfatasa, que da lugar al depósito y aumento de la excreción urinaria de dermatán y heparán sulfato. Las manifestaciones del síndrome de Hunter incluyen disostosis múltiples, organomegalia, facies tosca, ausencia de opacidad corneal y retraso mental con deterioro neurológico progresivo en la forma grave. Cambios cutáneos no específicos que pueden verse en todas las mucopolisacaridosis son piel engrosada con pérdida de elasticidad en codos y rodillas, pelo áspero e hipertricosis. La presencia de pápulas de color marfil sobre la región escapular y las caras laterales externas de brazos y muslos son típicas y casi patognomónicas del síndrome de Hunter. Se presenta el caso de un niño con la forma moderada del síndrome de Hunter que presenta lesiones cutáneas características de este síndrome (AU)