The effects of long-term low-dose cyclosporin A treatment on muscles and tendons: an experimental study

Limited studies report that patients receiving immunosuppressive therapy, including cyclosporin A (CsA), face muscle and/or tendon pathologies. The current study aimed (i) to investigate if CsA cause changes in the microscopic structure of striated muscle tissues and tendons after long-term low-dose therapy and (ii) to examine if the vehicle of CsA, Cremophor EL, or steroid administration might cause additional effects.

Twenty-four adult female Sprague-Dawley rats weighing 230-300 g were divided at random into four groups. Group 1 served as the control. Groups 2-4 received CsA intraperitoneally for 2.5 months: Group 2 received the oral form of CsA, Group 3 received the intravenous form of CsA, which contains Cremophor EL, and Group 4 received the intravenous form of CsA and prednisolone. Samples from the Achilles tendons and triceps surae muscles were examined at light microscope level.

Focal necrotic areas, enlargement of connective tissue and increase in mononuclear cells were clear on muscles in the experimental groups. No morphologic effects were observed on tendons.

Long-term low-dose CsA therapy causes focal microscopic changes in muscles but not in tendons. No additional effects were demonstrated with Cremophor EL or steroids. It should be noted that muscle tissue damage after trauma or surgeries in patients receiving CsA might be more dramatic due to the pathologic changes already caused by CsA, as supported by several case reports.