Frequency of the CYP2C19*17 polymorphism in a Chilean population and its effect on voriconazole plasma concentration in immunocompromised children.

Invasive fungal infections (IFIs) are the most frequent cause of morbidity and mortality in immunocompromised children. Voriconazole is the first-line antifungal choice in the treatment of IFIs like aspergillosis. Voriconazole pharmacokinetics vary widely among patients and voriconazole is metabolized mainly in the liver by the CYP2C19 enzyme, which is highly polymorphic. The CYP2C19*17 allele is characterized by the presence of four single nucleotide polymorphisms expressing an ultra-rapid enzyme phenotype with an accelerated voriconazole metabolism, is associated with low (sub-therapeutic) plasma levels in patients treated with the standard dose. Considering that in our center a high percentage of children have sub-therapeutic levels of voriconazole when treated with standard doses, we sought to determine the frequency of the CYP2C19*17 polymorphism (rs12248560) in a Chilean population and determine the association between voriconazole concentrations and the rs12248560 variant in immunocompromised children. First, we evaluated the frequency of the rs12248560 variant in a group of 232 healthy Chilean children, and we found that 180 children (77.6%) were non-carriers of the rs12248560 variant, 49 children (21.1%) were heterozygous carriers for rs12248560 variant and only 3 children (1.3%) were homozygous carriers for rs12248560 variant, obtaining an allelic frequency of 12% for variant in a Chilean population. To determine the association between voriconazole concentrations and the rs12248560 variant, we analyzed voriconazole plasma concentrations in a second group of 33 children treated with voriconazole. In these patients, carriers of the rs12248560 variant presented significantly lower voriconazole plasma concentrations than non-carriers (p = 0,011). In this study, we show the presence of the rs12248560 variant in a Chilean population and its accelerating effect on the pharmacokinetics of voriconazole in pediatric patients. From these data, it would be advisable to consider the variant of the patient prior to calculating the dosage of voriconazole.

[Cutaneous tuberculosis: two case reports and review]. / Tuberculosis cutánea: reporte de dos casos y revisión de la literatura.

Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. It is uncommon (1% of all cases of tuberculosis), but has increased due to the human immunodeficiency virus epidemic and to pharmacologic immunosuppression. It presents a wide variety of clinical forms depending on how bacteria reach the skin and on the immune status of the patient. We present two cases of cutaneous tuberculosis diagnosed in the Hospital Clínico de la Pontificia Universidad Católica de Chile. We emphasize the difficulty in diagnosis and classification of this disease and briefly discuss on the different diagnostic and therapeutic approaches.

Tuberculosis cutánea: reporte de dos casos y revisión de la literatura / Cutaneous tuberculosis: two case reports and review

Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. It is uncommon (1 percent of all cases of tuberculosis), but has increased due to the human immunodeficiency virus epidemic and to pharmacologic immunosuppression. It presents a wide variety of clinical forms depending on how bacteria reach the skin and on the immune status of the patient. We present two cases of cutaneous tuberculosis diagnosed in the Hospital Clínico de la Pontificia Universidad Católica de Chile. We emphasize the difficulty in diagnosis and classification of this disease and briefly discuss on the different diagnostic and therapeutic approaches.

La tuberculosis (TBC) cutánea es una enfermedad infecciosa crónica causada por Mycobacterium tubercu losis. Es una patología poco frecuente (1 por ciento de todos los casos de TBC); no obstante, ha aumentado debido a la epidemia del virus de la inmunodeficiencia humana y la presencia creciente de la inmunosupresión farmacológica. Presenta una gran variedad de formas clínicas que dependen de cómo llega el bacilo a la piel y del estado inmunológico del individuo. A continuación, presentamos dos casos clínicos de TBC cutánea vistos en el Hospital Clínico de la Pontificia Universidad Católica de Chile y una revisión del tema.