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ABSTRACT Objective: Encapsulating peritoneal sclerosis (EPS) is a rare, but potentially fatal complication of peritoneal dialysis. Currently, treatment of peritoneal fibrosis is not fully possible yet. In this study, we aimed to demonstrate the effects of tacrolimus therapy on peritoneal fibrosis and inflammation when administered alone or with mycophenolate mofetil (MMF) in the EPS model induced in rats. Methods: Thirty six Wistar albino rats were separated into six equal groups. Group I was the control group. Group II-VI were administered intraperitoneal chlorhexidine (CH) for induced EPS model in rats. Group II, IV, V, VI were administered isotonic liquid, tacrolimus, tacrolimus and concurrently with CH, tacrolimus and MMF together, respectively. Group III was not administered any drug. All peritoneal samples were stained immunohistochemically with matrix metalloproteinase-2 (MMP-2) antibody. Thickness of peritoneal fibrosis, subserosal large collagen fibers, subserosal fibroblast proliferation and subserosal fibrotic matrix deposition were evaluated. Results: Comparing the experimentally induced EPS groups, the best histopathological results and the largest staining with MMP-2 were achieved in Group VI. Furthermore, in all treatment groups (IV, V, VI) more staining with MMP-2 was detected compared to non-treatment groups (I, II, III) but no statistically significant differences were found among all groups. A statistically significant remission was observed in all histopathological parameters, primarily peritoneal thickness in rats that were administered MMF with tacrolimus, compared to rats which were administered tacrolimus only. Conclusion: Concurrent use of tacrolimus and MMF in the treatment of EPS may be a promising approach.
RESUMEN Objetivos: La esclerosis peritoneal encapsulante (EPE) es una complicación rara, peropotencialmente fatal de la diálisis peritoneal. Actualmente, el tratamiento de la fibrosis peritoneal aún no es posible. En este estudio, apuntamos a demostrar los efectos de la terapia con tacrolimus en la fibrosis peritoneal y la inflamación cuando se administran solos o con micofenolato de mofetilo (MMF) en el modelo EPE inducido en ratas. Métodos: Treinta y seis ratas Wistar albinas se separaron en seis grupos iguales. El Grupo I era el grupo de control. En los grupos II-VI se administró clorhexidina intraperitoneal (CH) para el modelo EPE inducido en ratas. En los Grupos II, IV, V, VI se administró respectivamente líquido isotónico, tacrolimus, tacrolimus y CH y finalmente tacrolimus y MMF juntos. El grupo III no recibió ningún medicamento. Todas las muestras peritoneales se tiñeron inmunohistoquímicamente con el anticuerpo Matrix Metaloproteinasa-2 (MMP- 2). Se evaluó el grosor de la fibrosis peritoneal, se evaluaron las fibras de colágeno grandes subserosas, la proliferación de fibroblastos subserosa y la deposición de la matriz fibrótica subserosa. Resultados: Comparando los grupos de EPE inducidos experimentalmente, los mejores resultados histopatológicos y la tinción con MMP- 2 más extensa se lograron en el Grupo VI. Además, en todos los grupos de tratamiento (IV, V, VI) se detectó más tinción con MMP-2 en comparación con los grupos de no tratamiento (I, II, III), pero no se encontraron diferencias estadísticamente significativas entre todos los grupos. Se observó una remisión estadísticamente significativa en todos los parámetros histopatológicos, principalmente el espesor peritoneal en ratas que recibieron MMF con tacrolimus, en comparación con las ratas que recibieron solo tacrolimus. Conclusión: El uso concurrente de tacrolimus y MMF en el tratamiento de EPS puede ser una aplicación prometedora.
RESUMO
Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.