Systemic and topical factors involved in the production of experimental cutaneous calcinosis.

Extensive investigations dating back to 1932 (1, 2, 3) have shown that, in experimental animals, it is possible to produce cutaneous calcinosis reminiscent of calcifying scieroderma (the "sclérodermie calcaire" of French dermatologists) with certain calcification-promoting compounds, such as parathyroid hormone or dihydrotachysterol (DHT). However, irrespective of the evocative agent, the cutaneous lesions could not serve as practical models of disease, because they developed only on the scalp and neck (not wherever the experimenter wanted to induce them), occurred irregularly, were exclusive to very young animals, and the accompanying mortality was high. Still, these observations were repeatedly confirmed by others and eventually induced Leriche and co-workers (4, 5, 6) to remove the parathyroids in patients with severe scieroderma. The results of this operation were rather inconstant, but in some cases marked improvement did occur, so that further work designed to improve our experimental model was thought to be desirable. In the course of the following years, it was found that topical trauma can cause local calcification in the internal organs of DHT-treated rats (7). Since clinical scleroderma also tends to develop at sites of local injury (2), we were particularly interested to note that cutaneous calcinosis with sclerosis can be produced at will in predetermined skin regions, even in adult rats, if the selected area is lightly traumatized (e.g., by epilation) at a "critical time" of DHT treatment, usually the 4th day (5). Using this technic, the histogenesis of the cutaneous calcinosis induced by DHT + topical trauma was studied in detail (9), particularly in order to clarify the similarities and dissimilarities between this experimental condition and the clinical syndrome of calcifying scleroderma. While it remains questionable whether these two condi-