Treatment with oral or topical sirolimus in complex vascular anomalies in pediatrics. Experience in a third-level hospital. / Tratamiento con sirolimus oral o tópico en anomalías vasculares complejas en pediatría. Experiencia en un hospital terciario.

OBJECTIVE: The use of sirolimus in vascular anomalies is a special indication not authorized in its data sheet. The objective of this study was to increase the evidence of oral or topical use of sirolimus for this indication in the pediatric population. MATERIALS AND METHODS: An observational, retrospective study of patients under 18 years of age treated with oral or topical sirolimus for vascular anomalies was carried out. Diagnosis and location of lesions, administration route and dosage of sirolimus, blood levels of sirolimus in patients who received oral treatment, treatment duration, response, and toxicity were collected. RESULTS: 18 patients - 7 with oral treatment and 11 with topical treatment - were included. With oral sirolimus, the overall response rate was 85.7%. Sirolimus was discontinued in 2 cases - as a result of full resolution and progression. 57.1% of patients had adverse effects, most of which were mild. Dyslipidemia was the most frequent adverse effect. Blood levels were monitored in all patients for dose adjustment purposes. With topical treatment, the overall response rate was 72.7%. Sirolimus was discontinued in 3 cases -due to progression in 2 cases and to stability in 1. 27.3% of patients had adverse effects, with itching standing out as the most frequent one. CONCLUSIONS: The favorable results of sirolimus treatment in our patients seem to confirm its effectiveness and safety in vascular anomalies, which make it stand as a therapeutic option in pediatric patients. However, further research is required to establish the optimal treatment regimen, treatment duration, and potential long-term adverse effects.

OBJETIVO: El uso de sirolimus en anomalías vasculares es una indicación especial no autorizada en ficha técnica. El objetivo de este estudio es incrementar la evidencia del empleo por vía oral o tópica de sirolimus en esta indicación en población pediátrica. METODO: Estudio observacional retrospectivo de pacientes menores de 18 años tratados con sirolimus oral o tópico para anomalías vasculares recogiendo: diagnóstico y ubicación de lesiones, forma de administración y dosificación de sirolimus, niveles sanguíneos de fármaco en los pacientes con tratamiento oral, duración del tratamiento, respuesta y toxicidad. RESULTADOS: Se incluyeron 18 pacientes (7 con tratamiento oral y 11 tópico). Con sirolimus oral, la tasa de respuesta global fue 85,7%. Se interrumpió sirolimus en 2 casos: por resolución completa y por progresión. El 57,1% experimentó algún efecto adverso, en su mayoría leves; siendo la dislipemia el efecto adverso más frecuente. La monitorización de niveles sanguíneos fue empleada en todos los pacientes para el ajuste de dosis. Con el tratamiento tópico, la tasa de respuesta global fue 72,7%. Se interrumpió sirolimus en 3 casos: progresión en 2 casos y estabilidad en 1. El 27,3% experimentó algún efecto adverso, siendo el prurito el más frecuente. CONCLUSIONES: Los resultados favorables del tratamiento con sirolimus en nuestros pacientes parecen confirmar la efectividad y seguridad del fármaco en anomalías vasculares y lo posicionan como una opción terapéutica en pacientes pediátricos. Aun así, parece necesaria mayor investigación que trate de aclarar, entre otros, el régimen óptimo del tratamiento, la duración del mismo y los potenciales efectos adversos a largo plazo.

[Phenytoin: paradoxical toxicity; a discussion of 4 cases]. / Fenitoína: intoxicación paradójica; descripción de 4 casos.

INTRODUCTION: Phenytoin overdosing results in a wide variety of signs and symptoms - ataxia, nistagmus, loss of consciousness. On occasions increased frequence of seizures may be seen in patients with high phenytoin serum levels and no evidence of standard toxicity symptoms - paradoxical toxicity. OBJECTIVE: To study the frequency of phenytoin paradoxical toxicity, and to analyze patients" clinical status. PATIENTS AND METHOD: Prospective study of 100% of patients monitored by the Pharmacy Department during August-December, 1998 and who had phenytoin serum levels above therapeutic range and seizures. Laboratory determinations in samples was performed by polarized immunofluorescence analysis. The outcome of each patient was monitored through their pharmacotherapeutic record and clinical history. RESULTS: The number of patients was 1706; 124 of wich had serum levels above the therapeutic range. Out of this group, 3 males and 1 female, with ages ranging from 17 to 73, a diagnosis of epilepsy, and chronic therapy using phenytoin, come to our Emergency Department because of convulsions. Serum levels of phenytoin were ordered due to suspected lack of compliance or underdosing. In all 4 patients phenytoin was discontinued until the therapeutic range was reached, to be then reset with plasma level-adjusted dosages. CONCLUSIONS: Paradoxical toxicity may lead to errors, and therefore we should rule out such possibility in patients with exacerbated epilepsy undergoing treatment with phenytoin.