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.

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.

Hipertricosis generalizada adquirida por diazóxido / Acquired Generalized Hypertrichosis Due to Diazoxide

No disponible

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.

Sustained clinical effectiveness and favorable safety profile of topical sirolimus for tuberous sclerosis - associated facial angiofibroma.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Facial angiofibroma appears in up to 80% of patients and has a considerable psychological impact. Various invasive procedures have been used, although they show limited effectiveness and potential adverse effects. OBJECTIVES: To evaluate the sustained clinical benefits and safety profile of topical sirolimus applied to treat facial angiofibromas. METHODS: This study was a non-blinded, uncontrolled case-series comprising 10 patients with TSC-associated facial angiofibroma that was treated with 0.4% sirolimus ointment 3 times a week for 9 months. Patients were clinically evaluated at baseline and at 6, 12, 24 and 36 weeks. Plasma levels of sirolimus were determined. RESULTS: A sustained improvement was observed in erythema and in the size and extension of the lesions as early as the first weeks of treatment. Sirolimus plasma levels remained below detection limits (0.3 ng/mL) in all cases. The formula was well-tolerated with no local or systemic adverse effects. CONCLUSIONS: Topical sirolimus seems to be an effective and safe medical alternative to surgery or laser-based treatments in patients with TSC-associated facial angiofibromas.