PD affects the tunica albuginea, producing areas of local fibrosis and loss of tissue compliance (Gelbard 1993). The normal tunica albuginea is composed of a lattice of collagen and elastic fibers arranged in two layers: an outer longitudinal one responsible for elongation during erection and an inner circular layer for increasing the width. The tunica is separated from the erectile tissue by a loose connective tissue sleeve containing a network of vascular and lymphatic tributaries. The venous drainage of the erectile tissue is via the emissary veins that transverse through the tunica and into the dorsal vein. The movement of the two tunical layers across each other during erection, thereby compressing these veins, is the main feature of the veno-occlusive mechanism of erection.

The most widely accepted theory is that the disease process is initiated by mechanical trauma to the tunica albuginea of the erect penis, resulting in aberrant wound healing and subsequent scar tissue formation. As the penis engorges with blood during erection, it expands its girth and extends its length until the tunica and the strands of the septum in between the corpora cavernosa are stretched to the limit of their elasticity. If the penis is forcefully bent during vigor intercourse, the attachments of the septal fibers to the tunica are stressed, generating tension. In young men the elasticity of the tissues will permit the structures to deform and rebound without damage. However, as a man ages, the tunica albuginea becomes less elastic, and the tension associated with the same degree of distortion can delaminate its circular inner fibers (Devine and Jordan 1994). This tear causes bleeding and clot formation, leading to the deposition of fibrin, fibroblast activation and proliferation, enhanced blood vessel permeability, and generation of inflammatory cells. The infiltrate consists of T-lymphocytes, macrophages, and plasma cells surrounding the small vessels in the subtunical layer. This infiltrate is followed by focal areas of fibrosis that eventually develop into plaques. This active process lasts for 12–18 months. Most but not all patients have pain associated with the inflammation present in the active phase.

Histological examination of excised plaques shows fibrin deposition within the plaques and dense collagenous connective tissue and calcification. Calcification can occur early after the onset of a plaque and is not, as previously thought, an indication of mature disease. The fibrosis in PD does not invade or replace the spongious tissue of the corpora. Some inflammatory changes can be seen in the space between the tunica albuginea and Buck’s fascia, but fibrosis of Buck’s fascia itself does not occur except in patients treated by intralesional injections or radiotherapy.

Genetic predisposition plays a role in PD. PD is associated with other fibrotic conditions such as Dupuytren Disease (DD) and Ledderhose Disease. We evaluated the coexistence of DD in 415 consecutive patients with PD and found DD in 22 % of them (Nugteren et al. 2011). Previous reports concerning coexisting DD in smaller series of patients presenting with PD show ranges varying from 0.01 to 58.8 %, a positive family history for PD in 1–4 %, and a positive family history for DD in 9.8 %. DD is thought to be the most common hereditary connective tissue disorder in Caucasians. However, the true prevalence rate of PD may be even higher than DD because PD is underreported.

One study that compared the gene expression profiles of patients with PD and DD noted similar alterations in the genes responsible for collagen deposition degradation, ossification, and myofibroblast differentiation (Qian et al. 2004). Dolmans et al. observed significant association of PD with single nucleotide polymorphisms (SNP) rs4730775 at the (WNT2) locus on chromosome 7 (Dolmans et al. 2012). WNT means “wingless-type MMTV integration site family.” WNT2 is a member of this WNT gene family, which consists of structurally related genes that encode glycoproteins. These act as extracellular signaling factors. The best understood WNT signaling pathway is the canonical pathway, which activates the nuclear functions of b-catenin, leading to changes in gene expression that influence cell proliferation and survival (Moon et al. 2004). A recent study revealed increased levels of b-catenin, the end product of WNT signaling, in cells derived from plaque from PD patients compared with cells from normal tunica albuginea tissue (De Young et al. 2010). This suggests that the WNT signaling cascade is overstimulated in PD.

Patients with PD range in age from 20 to 80 years, with a median age of 53. PD prevalence rates range between 3 and 9 % of all adult men (Porst et al. 2012). PD presents in two distinctive phases, an inflammatory phase lasting 6–18 months with painful erections and the development of a penile curvature, followed by a chronic phase characterized by stable plaque formation and a variable degree of ED (Table 50.2). Patients are often anxious over real or imagined loss of sexual capacity and worry about the future course. Occasionally they think they have a tumor. The deformity is sometimes so severe that vaginal intromission becomes impossible. However, difficulties with penetration depend not only on the curvature but also on the anatomical condition and cooperation of the partner. A sexually active single man with marked deformity is likely to suffer more than a man within a stable and long-standing marital relationship.

PD can cause a great deal of functional and psychological distress to the patient and his partner. We insist that the partner accompanies the patient at an early visit, so that an explanation of PD can be given to both. Each patient is asked to bring or to send photographs of his erect penis to monitor disease progression. A picture of his full erect penis from above will document lateral curvature, lateral pictures dorsal or ventral curvature, and a frontal view right, left, or a combined curvature as well as penile shaft rotation. A PDE5 inhibitor or an intracorporeal injection with a vasodilating drug may be used in patients who have concomitant ED. The curvature is best measured by goniometry.

Physical examination must be precise. The glans is grasped with one hand and the penis gently stretched to the limit. During this maneuver, it is possible to assess the overall elasticity of the penile shaft. A marked loss of elasticity denotes scarring in the longitudinal axis. The stretched penile length is measured from the urethral meatus to the level of the abdominal skin. This is important because penile shortening usually occurs already before surgical intervention. The edges of the plaque are palpated between the index finger and the thumb of the other hand (without a glove) placed laterally on the shaft. Dorsal plaques are the most common and can be differentiated easily from ventral plaques. Lateral plaques may produce significant deviation of the natural angle of coitus, making intercourse particularly problematic. Circumferential plaques will result in an hourglass deformity with distal flaccidity. Plaque locations should be noted, but precise size assessment by palpation is not reliable. Clinical signs of DD and Ledderhose nodules should also be checked.