Peyronie's disease: an anatomically-based hypothesis and beyond.

In my opinion, Peyronie’s disease is aberrant wound healing in response to an inflammation trapped within the layers of tunica albuginea. The arrangement of the vessels traversing the tunica albuginea is unique in that a cuff of loose areolar tissue cushions the arteries while the veins are in direct contact with the fibrous tunica. As a result, the arterial flow into the erectile tissue continues during erection (except in the rigid phase when the intracavernous pressure exceeds the systolic blood pressure) while the venous channels are compressed. When a blunt trauma breaks the fibers of the tunica with extravasation, the resulting inflammatory response creates an area of edema and cell infiltration which compress the nearby venous channels and forming a ‘trapped’ inflammatory response. While the secretions from leukocytes and macrophages such as elastases break the elastic fibers, the cytokines such as transforming growth factor beta (TGFb) released by the same cells stimulate production of intercellular matrix and collagen fibers. Meanwhile, because the inflammation is trapped, TGFb and other cytokines cannot be dispersed and degraded, they stimulate the production of more TGFb, which in turn produces more matrix and collagen. In our cultured Peyronie’s fibroblasts, but to a much lesser degree on normal tunical fibroblasts, we also found that TGFb stimulates the production of monocyte chemotaxic protein 1 (MCP-1) and connective tissue growth factor (CTGF). MCP-1 would attract more monocytes to the area and CTGF would produce more fibrosis. Rajfer et al. recently performed microarray gene profiles and showed that osteoblast stimulating factor 1 was upregulated in Peyronie’s plaque, which explains the reported incidence of calcification in up to 1 of patients with Peyronie’s disease. All of the above ‘aberrations’ can be attributed to the unique anatomy of the tunica albuginea where the densely packed tunical layers trapped the inflammatory process, the venous outflow channels are compressed by the focal area of edema and cell infiltration while the immigration of leukocytes and macrophages continues because the arterial flow is not impeded. The unique ability of TGFb to produce more of itself forms a vicious cycle within this microenvironment and results in excessive production of intercellular matrix and collagen fibers. 1 The final outcome is a prolonged inflammatory response with total breakdown of the delicately arranged network of collagen and elastic fibers and excessive production of collagen fibers. In the early stage, the inflammatory process and irritation of the nerves may produce pain with or without erection. In most instances, the pain will subside either due to maturity of the inflammatory reaction or the death of the trapped nerve fibers. In chronic phase, if the fibrosis has begun to encroach upon the erectile tissue, erectile dysfunction may occur. These phenomena may contribute to the clinical presentation of Peyronie’s disease in which the early phase triad consists of pain, plaque and penile deformity and the late triad consists of plaque, penile deformity and erectile dysfunction.