Impaired wound healing is a major complication of diabetes. Recent studies have reported reduced lymphangiogenesis and angiogenesis during diabetic wound healing, which are thought to be new therapeutic targets. Statins have effects beyond cholesterol reduction and can stimulate angiogenesis when used systemically. However, the effects of topically applied statins on wound healing have not been well investigated. The present study tested the hypothesis that topical application of simvastatin would promote lymphangiogenesis and angiogenesis during wound healing in genetically diabetic mice. A full-thickness skin wound was generated on the back of the diabetic mice and treated with simvastatin or vehicle topically. Simvastatin administration resulted in significant acceleration of wound recovery, which was notable for increases in both angiogenesis and lymphangiogenesis. Furthermore, simvastatin promoted infiltration of macrophages, which produced vascular endothelial growth factor C in granulation tissues. In vitro, simvastatin directly promoted capillary morphogenesis and exerted an antiapoptotic effect on lymphatic endothelial cells. These results suggest that the favorable effects of simvastatin on lymphangiogenesis are due to both a direct influence on lymphatics and indirect effects via macrophages homing to the wound. In conclusion, a simple strategy of topically applied simvastatin may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as that in diabetes.

Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of cutaneous T-cell lymphoma limited to the palms and soles that is not widely recognized because of its uncommon occurrence. We report a 73-year-old Japanese man who presented with an erosion on the left dorsal hand, a reddish tumor on the right palm, and hyperkeratotic erythematous plaques on the right sole. Skin biopsy showed histological features of mycosis fungoides (MF) with invasion into the deeper layers of skin. There was no visceral or lymph node invasion. We diagnosed this case as MFPP. External beam radiotherapy (EBRT) was performed to treat the hand lesions. Combination treatment with topical steroids and topical psoralen plus ultraviolet light therapy was performed to treat the right sole lesion, but was ineffective. Therefore, sequential EBRT was performed. Complete remission of all lesions was obtained. This is the first report of MFPP with a locally advanced tumor for which the efficacy of radiotherapy is described in detail. MFPP lesions occur on the dorsal aspect of hand or foot, and here we propose a classification of MFPP as hand and foot MF. The pathogenesis of MFPP is still unclear and further accumulation of data is required.

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