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This study was designed to determine by histological evaluation and clinical correlation the most effective sclerosant concentration of Sotradecol® (sodium tetradecyl sulfate) and Asclera® (polidocanol) for the treatment of leg telangiectasia.Histological studies were completed on 40 patients, all of whom were female with a mean age of 53. After sclerotherapy with varying concentrations of sclerosant solutions for the treatment of 0.8 mm and 1 mm leg telangiectasia, histological specimens were examined for the following criteria: luminal changes, subintimal changes, smooth muscle wall alterations, and vessel wall integrity. Six patients from this group were also treated with sodium tetradecyl sulfate foam 0.1%–0.2% or polidocanol foam 0.31% for the treatment of 2 mm reticular veins. In a second group of 20 patients, clinical results after treatment with sodium tetradecyl sulfate 0.15% and polidocanol 0.31% were evaluated.Histological findings in patients treated with sodium tetradecyl sulfate 0.05% and polidocanol 0.25% were minimal. Sclerosant concentrations of sodium tetradecyl sulfate ≥0.2% revealed intraluminal debris and greater smooth wall damage. Polidocanol 0.5% was equivalent in strength to sodium tetradecyl sulfate 0.2% on histological evaluation. Sodium tetradecyl sulfate 0.15% and polidocanol 0.31% had similar findings on histological examination with mild smooth muscle wall changes, endothelial cell lysis, and subintimal layer damage. Reticular veins treated with 0.1%, 0.15%, and 0.2% sodium tetradecyl sulfate foam and 0.31% polidocanol foam produced identical histological findings.Sodium tetradecyl sulfate 0.15% and polidocanol 0.31% based on histological evaluations and clinical correlation are the best sclerosant concentrations for 0.8 mm to 1 mm leg telangiectasia. Sodium tetradecyl sulfate foam is comparable to polidocanol foam at these concentrations as well.