Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

Realización de pruebas complementarias en cirugía dermatológica ambulatoria ¿existe indicación? / Are Additional Tests Indicated in Ambulatory Dermatologic Surgery?

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[The perception of care received by patients with actinic keratosis]. / La percepción del proceso asistencial de pacientes con queratosis actínica.

OBJECTIVE: To analyse barriers limiting an integral approach in the care process of patients with actinic keratosis, and to validate a questionnaire of their perception in order to assess this approach. METHOD: A qualitative study (Focus Group) was conducted to assess the perception of the healthcare process of professionals (dermatologists, family doctors, nurses, pharmacists and managers), and patients. A validation study of a new tool was conducted, defining the scope and contents of a questionnaire of perceived quality. Reliability, consistency and validity were analysed after inviting a convenience sample of 225 patients to respond. RESULTS: Underdiagnosis in primary care, a higher variability in resources, and access to the health care circuit, together with gaps in patient information about actinic keratosis, are relevant barriers to achieve comprehensive care in this disease condition. The result of the focus groups advised to elaborate 14 reactive items. A total of 224 patients responded (mean age 71.6, SD 11.1), of which 153 (68%) were men. Two factors were isolated including 12 items (explained variance of 58%). The consistency of this factorial solution was .87, the split-half reliability being .76, with the scores in the factors showing an adequate predictive capacity. CONCLUSIONS: The coordination between levels and to reduce to variability in equipment and clinical decision making in Primary Care are the most prominent barriers. The questionnaire has appropriate metric properties and it explores the information and care by the medical staff and the information and advice provided by the pharmacist.

Búsqueda de nuevas pautas terapéuticas de imiquimod 5% para el tratamiento de las queratosis actínicas / Imiquimoid 5%: In Pursuit of New Treatment Regimens for Actinic Keratosis

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Bases moleculares y aplicaciones farmacológicas de la vía de mTOR en dermatología / Elucidation of the mTOR Pathway and Therapeutic Applications in Dermatology

La molécula diana de la rapamicina en mamíferos es una cinasa perteneciente a la familia de fosfatidil-3-inositol que está involucrada en la regulación de diferentes procesos relacionados con el crecimiento y diferenciación celular, la angiogénesis y la modulación de la respuesta inflamatoria. En los últimos años hemos presenciado un profundo avance en el conocimiento de las bases moleculares de la vía de señalización de la molécula diana de la rapamicina en mamíferos y su implicación en multitud de enfermedades genéticas, inflamatorias o tumorales. El desarrollo de moléculas inhibidoras de esta vía ha propiciado una nueva posibilidad de abordaje terapéutico que ha permitido una mejora sustancial en muchas de estas enfermedades. En este artículo revisamos las implicaciones de la vía de la molécula diana de la rapamicina en mamíferos en las diferentes dermatosis con las que se ha relacionado, sus aplicaciones farmacológicas y las futuras direcciones que están tomando las diferentes líneas de investigación

The member of the phosphatidylinositol 3-kinase family, mammalian target of rapamycin, is involved in modulating inflammatory response and regulating cellular processes associated with growth, differentiation, and angiogenesis. Recent years have seen major advances in our understanding of the mammalian target of rapamycin signaling pathway and the implication of this pathway in multiple genetic and inflammatory diseases and tumors. The development of the mammalian target of rapamycin inhibitors has given rise to new treatment approaches that have led to substantially improved outcomes in many diseases. In this article, we review the role of the mammalian target of rapamycin signaling pathway in the different skin diseases with which it has been associated, examine the therapeutic applications of drugs targeting this pathway, and provide an overview of current trends and future directions in research

Elucidation of the mTOR Pathway and Therapeutic Applications in Dermatology. / Bases moleculares y aplicaciones farmacológicas de la vía de mTOR en dermatología.

The member of the phosphatidylinositol 3-kinase family, mammalian target of rapamycin, is involved in modulating inflammatory response and regulating cellular processes associated with growth, differentiation, and angiogenesis. Recent years have seen major advances in our understanding of the mammalian target of rapamycin signaling pathway and the implication of this pathway in multiple genetic and inflammatory diseases and tumors. The development of the mammalian target of rapamycin inhibitors has given rise to new treatment approaches that have led to substantially improved outcomes in many diseases. In this article, we review the role of the mammalian target of rapamycin signaling pathway in the different skin diseases with which it has been associated, examine the therapeutic applications of drugs targeting this pathway, and provide an overview of current trends and future directions in research.

Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.

BACKGROUND: Intralesional methotrexate (MTX-il) has been used as neoadjuvant therapy for keratoacanthoma but has only been utilized in a few isolated cases of cutaneous squamous cell carcinoma as neoadjuvant therapy (cSCC). OBJECTIVES: The objective of this study was to evaluate the effectiveness in clinical practice of presurgical MTX-il infiltration to reduce the size of the cSCC. Safety and the impact on subsequent reconstructive surgical techniques was also assessment. METHODS: Single, retrospective, observational study of two historical cohorts differentiated in time. Subjects included were diagnosed with infiltrating cSCC. Patients included in group-A received neoadjuvant MTX-il and patients included in group-B underwent scheduled surgery without prior infiltration. Univariate and multivariate analyses were performed. RESULTS: Group-A patients (n = 43) showed an average reduction in the tumour area of 0.52 cm(2) , while in group-B (n = 43), the area increased by 0.49 cm(2) . A multivariate linear regression analysis demonstrated that MTX-il was the only independent variable that significantly reduced the tumour size [mean 42.6% (95% CI: 31.17-54.03)]. Tumours ≥2 cm in size required significantly a lower percentage of complex reconstructions (P = 0.026). Lower lip tumours showed a higher reduction in group treated with MTX-il (P = 0.045). The only complication observed was discomfort during methotrexate infiltration (60.47%). CONCLUSIONS: Neoadjuvant MTX-il reduced the presurgical size of cSCC lesions and could simplify their subsequent surgery.

Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). AIM: To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. METHODS: We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. RESULTS: There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). CONCLUSIONS: The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients.

Opciones terapéuticas actuales para los angiofibromas faciales / Current Options for the Treatment of Facial Angiofibromas

Los angiofibromas faciales son tumoraciones hamartomatosas íntimamente relacionadas con el complejo de la esclerosis tuberosa, y representan uno de los criterios mayores para el diagnóstico de la enfermedad. Su aparición desde edades tempranas en la región facial, así como su naturaleza fibrovascular, producen importantes repercusiones físicas y psicológicas en estos pacientes, lo que ha motivado la utilización de múltiples tratamientos para su eliminación o mejora. Sin embargo, no existen guías de tratamiento que permitan establecer un protocolo de actuación común en este tipo de pacientes. El objetivo de este artículo es revisar los tratamientos utilizados hasta la fecha para los angiofibromas faciales en función de la evidencia científica demostrada e intentar aportar un protocolo terapéutico

Facial angiofibromas are hamartomatous growths that are closely associated with tuberous sclerosis complex and, in fact, they constitute one of the main diagnostic criteria for that disease. These lesions composed of blood vessels and fibrous tissue appear on the face at an early age. Since they have important physical and psychological repercussions for patients, several treatment options have been used to remove them or improve their appearance. However, the lack of treatment guidelines prevents us from developing a common protocol for patients with this condition. The present article aims to review the treatments for facial angiofibromas used to date and to propose a new evidence-based treatment protocol

Current options for the treatment of facial angiofibromas.

Facial angiofibromas are hamartomatous growths that are closely associated with tuberous sclerosis complex and, in fact, they constitute one of the main diagnostic criteria for that disease. These lesions composed of blood vessels and fibrous tissue appear on the face at an early age. Since they have important physical and psychological repercussions for patients, several treatment options have been used to remove them or improve their appearance. However, the lack of treatment guidelines prevents us from developing a common protocol for patients with this condition. The present article aims to review the treatments for facial angiofibromas used to date and to propose a new evidence-based treatment protocol.

Actualización en dermatitis atópica. Propuesta de algoritmo de actuación / Atopic Dermatitis: Update and Proposed Management Algorithm

La dermatitis atópica es una enfermedad inflamatoria crónica que afecta al 20% de los niños y casi al 3% de los adultos, produciendo un deterioro importante de la calidad de vida de los pacientes y sus familias. En más del 75% de los casos es autorresolutiva y mejora después de la pubertad. No obstante, hay casos que no consiguen esta mejoría o que en los primeros años de la vida alcanza niveles de severidad que afectan de forma importante la salud y el desarrollo social de los pacientes. Actualmente no contamos con guías terapéuticas adecuadas para solucionar estas situaciones que se escapan del manejo habitual. En el siguiente artículo repasamos las opciones terapéuticas de las que disponemos actualmente para afrontar casos de dermatitis atópica moderada-severa, aportamos nuestra experiencia y planteamos un posible algoritmo terapéutico (AU)

Atopic dermatitis is a chronic inflammatory disease that affects 20% of children and almost 3% of adults and is associated with considerable impairment of quality of life for both patients and their families. While the condition resolves spontaneously after puberty in over 75%of cases, it can persist into adulthood. Furthermore, in young children severe forms can have serious health consequences and affect social development. There are no appropriate guidelines on how to handle cases that do not respond to routine treatment. In this article, we review the current treatments for moderate to severe atopic dermatitis, describe our experience with this disease, and propose a management algorithm (AU)

Atopic dermatitis: update and proposed management algorithm.

Atopic dermatitis is a chronic inflammatory disease that affects 20% of children and almost 3% of adults and is associated with considerable impairment of quality of life for both patients and their families. While the condition resolves spontaneously after puberty in over 75% of cases, it can persist into adulthood. Furthermore, in young children severe forms can have serious health consequences and affect social development. There are no appropriate guidelines on how to handle cases that do not respond to routine treatment. In this article, we review the current treatments for moderate to severe atopic dermatitis, describe our experience with this disease, and propose a management algorithm.