Clinical improvement in systemic sclerosis resulting from urokinase therapy explained by light and electron microscopy skin examination

Objective: In our previous work, patients affected by SSc were treated with intravenous urokinase and showed clinical improvement. In this study we used microscopy to document ultrastructural alterations occurring in sclerodermic skin from SSc patients treated with urokinase. Methods: Ten patients with SSc were selected for this study. Skin biopsies were taken from the medial side of the right forearm on the third proximal on the volar surface. The patients were then treated with urokinase for 7 consecutive days. At the end of the treatment, the patients were examined and a new skin biopsy was taken close to the above-mentioned zone of the forearm for optic and electron microscopy examination. Results: The patients showed a gradual improvement of the skin after urokinase treatment. Raynaud's appeared to be less intense, and they had an increased articular range, with the restoration of movements that had previously been limited. Histological findings showed that, after treatment, skin alterations appeared attenuated, in particular the connective tissue showed a decreased density and inflammatory infiltrate was slight. Electron microscopy findings showed that collagen fibres appeared to have a more regular diameter, and the capillary vessels' lining was thicker, with fewer pinocytotic vesicles. Conclusion: These observations show that urokinase treatment seems to be an interesting therapeutic strategy to consider for the treatment of SSc.