Effectiveness and safety of liposomal rapamycin for the treatment of facial angiofibromas in tuberous sclerosis.

AIM: Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was developed in our pharmacy service: rapamycin 0.4% liposomal formulation, with better organoleptic characteristics and a more favorable release profile of the active ingredient. The purpose of this study is to evaluate the effectiveness and safety of liposomal topical rapamycin for the treatment of facial injuries in this rare disease. METHOD: This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibromas severity index (FASI), investigator's global assessment (IGA) scores, and dermatology life quality index (DLQI) questionnaire. To assess the safety profile of rapamycin, adverse reactions were reported, and blood tests and blood rapamycin levels were performed during treatment. RESULTS: Eleven patients were included, of which 8/11 (73%) patients obtained successful treatment according to FASI and IGA scores after 24 weeks of treatment. Statistical analysis demonstrated a significant improvement (p<.05) in FASI and IGA scores, erythema, and FA size after treatment with rapamycin liposomal formulation (FASI before treatment, median (interquartile range): 6.0 (2.0), FASI after treatment: 3.5 (2.0), p=.0063). Five patients also improved their quality of life after treatment. Regarding safety profile of rapamycin, the most common adverse reaction was mild pruritus and 2 patients reported erythema, who discontinued treatment prematurely. All hematological tests were normal, and blood rapamycin levels were undetectable. CONCLUSIONS: After galenic improvements and clinical evaluations, the rapamycin liposomal formulation proved to be effective and safe for this therapeutic indication. This new formulation was included as a magistral formula in our hospital pharmacy service, now accessible for prescribing by dermatologists. Drug development in hospital pharmacy is often the only pharmacological alternative available to treat the symptoms of rare diseases, when treatment options are limited or inadequate.

Topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis: a systematic review based on evidence.

INTRODUCTION: facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition. PURPOSE: to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis. METHODS: a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies. RESULTS: thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA. CONCLUSIONS: Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol.KEY MESSAGEUpdated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.

Negative pressure therapy with instillation for the treatment of infected wounds: recommendations of utilization based on evidence.

OBJECTIVE: To establish recommendations related to negative pressure therapy  with instillation according to effectiveness, safety, efficiency, consensus guidelines and stability data of instillation solutions. METHOD: A literature search was conducted to compare the available evidence  regarding effectiveness, safety and efficiency of negative pressure therapy with  instillation, as well as the existence of consensus guidelines for use. The articles  were classified according to the "Scale of evidence classification for therapeutic  studies" of the American Society of Plastic and Reconstructive Surgery. RESULTS: A total of 13 studies were included, of which five were comparative cohort studies (level II and III of evidence), and the rest  corresponded to case series (level IV of evidence). Two consensus guidelines  were selected with recommendations regarding the type of wound, instillation solution, solution retention time, vacuum pressure and appropriate  vacuum time. According to literature and available evidence, recommendations were proposed and established on negative pressure therapy  with instillation in our hospital, including stability data of the proposed solutions. CONCLUSIONS: This paper provides preliminary guidelines on the application of  negative pressure therapy with instillation until new evidence supports or  modifies these recommendations.

Objetivo: Establecer recomendaciones relacionadas con la terapia de presión negativa con instilación según efectividad, seguridad, eficiencia, guías de  consenso y estabilidades contrastadas de las soluciones de instilación. Método: Se realizó una búsqueda bibliográfica para contrastar la evidencia disponible en cuanto a efectividad, seguridad y eficiencia de la terapia de presión negativa con instilación, así como la existencia de guías de consenso de utilización. Se clasificaron los artículos en función de la "Escala de clasificación de evidencia para estudios terapéuticos" según la  Sociedad Americana de Cirugía Plástica y Reconstructiva.Resultados: Se incluyeron 13 estudios, de los cuales cinco fueron estudios de  cohortes comparativos (nivel II y III de evidencia), y el resto correspondieron a  series de casos (nivel IV de evidencia). Se seleccionaron dos guías de consenso  con recomendaciones según tipo de herida, solución de instilación, tiempo de  retención de solución, presión de vacío y tiempo de vacío apropiado. Según la  literatura y la evidencia disponible, se propusieron y establecieron recomendaciones sobre la terapia de presión negativa con  instilación en nuestro hospital, incluyendo datos de estabilidad de las soluciones  propuestas.Conclusiones: Este manuscrito proporciona pautas preliminares para la aplicación de la terapia de presión negativa con instilación hasta que nuevas evidencias apoyen o modifiquen estas recomendaciones.