Complete Plaque Regression in Peyronie's Disease

A 50-year-old man presented to a urology clinic due to pain in his penis during erection; he explained that it had developed a curvature about 9 months previously. He was otherwise healthy and was a nonsmoker.

Evaluation of his pain level on the 10-point visual analog pain scale score was relatively low, at 2. The patient's responses to the International Index of Erectile Function (IIEF) questionnaire to assess erection yielded a score of 26, the lower end of the normal score range of 26 to 30. The penile deformity consisted of a dorsal curvature, with a 15° angle, and a lateral left curvature of 30°. Palpation of the penis identified a nodule about 15 mm long. The patient was given 10 mcg of alprostadil (Caverject, Edex) to induce an erection for physical examination and penile Doppler ultrasound assessment.

Cavernous artery flow and end-diastolic velocity were normal: peak systolic velocity was 65 cm/s (bilaterally) and end-diastolic velocity was 0 cm/s (bilaterally). The penile plaque, located dorsally and at the distal third of the penis, appeared heterogeneous on ultrasound. Penile plaque volume, calculated based on three-dimensional measurement using the ellipsoid formula (i.e., volume=0.524 × length × width × thickness) was 202 mm³ (13.4 × 9.78 × 2.94 mm); calcification noted within the plaque measured 3.42 × 3.43 × 1.50 mm.

Clinicians advised the patient of the lengthy treatment duration required to address Peyronie's disease (PD) as a chronic (and not acute) inflammatory disease. In January 2014, he was started on antioxidant supplements along with 4% topical diclofenac gel twice daily and perilesional penile injection pentoxifylline (100 mg, 1 ampule) with a 30 G needle every 2 weeks for 6 months.

Follow-up after completion of the first treatment cycle noted an improvement in the patient's erectile function from an IIEF score of 26 to 28. The dorsal curve had also disappeared, and the angle of the lateral left curvature reduced from 30° to 15°. The patient reported that the penile pain had resolved. On palpation, clinicians detected a smaller nodule; ultrasound showed it was 8.17 × 7.70 × 3.19 mm (volume 105 mm³) and contained a calcification of 2.83 × 2.44 × 1.5 mm, a 48% decrease from its size at presentation.

Based on the results of treatment, clinicians consulted with the patient, who opted to continue the oral treatment for another 12 months, and limit penile peri-plaque injections of pentoxifylline to 100 mg once monthly.

Evaluation after completion of second treatment cycle -- which marked approximately 18 months of treatment -- showed an IIEF score of 28 and complete resolution of the left curvature. Furthermore, palpation showed additional decrease in the size of nodule, to 5.04 × 5.18 × 2.00 mm (volume 27 mm³) on ultrasound. Similar improvement was noted in the calcification within the nodule (1.88 × 1.25 × 1.22 mm). This represented a decrease of 86.6% from its initial volume, with evidence of similar reduction in the calcification size.

Given the excellent response to treatment, clinicians suggested continuing the same oral treatment for the next 12 months, but with penile peri-plaque injections further reduced to once every 2 months.

At the end of the third cycle of treatment, after about 30 months of therapy, another follow-up confirmed that the treatment effects remained robust, with IIEF score of 28 maintained along with the absence of penile curvature. The nodule could not be detected on palpation. Ultrasound showed plaque dimensions of 4.05 × 4.69 × 1.87 mm (volume 19 mm³), and there was no remaining internal calcification. This represented an overall reduction of 90.6% in plaque size.

Given the patient's excellent response to treatment, clinicians continued the same oral and topical regimen for 6 more months but discontinued the pentoxifylline injections. At follow-up of the patient after 6 months of exclusive oral and topical diclofenac treatment, and more than 3 years of multimodal treatment with antioxidants, the patient had no remaining penile deformity or pain. His IIEF score was still 28. There was no evidence on palpation of any nodule, and ultrasound assessment showed no evidence of plaque or area affected by disease. Clinicians suspended treatment, with no subsequent reports of any adverse effects. Importantly, they reported using the same ultrasound machine (Philips HD 15) and the same operator at every examination.

Discussion

This is one of two similar cases of PD reported by these clinicians, who noted that "to the best of our knowledge, this is the first report in which complete plaque regression was achieved in patients with PD."

Symptoms of PD include penile deformity (94%), penile pain (20-70%), and erectile dysfunction (over 30%), case authors noted. About half of patients (48%) have depression, with a consistently high percentage of men scoring above the Center for Epidemiologic Studies Depression Scale cutoff for depression, with no significant difference across time since diagnosis.

PD is largely believed to be the result of an injury, which causes an accumulation of fibrin to accumulate at the site of the trauma and in turn triggers inflammation that leads to an overproduction of fibrogenic cytokines and free radicals, the authors noted.

Conservative medical treatment includes a wide range of oral therapies, intralesional injections, and physical treatment, such as extracorporeal shock wave therapy, vacuum devices, and penile traction devices.

Surgical treatment is indicated when the disease has been stable for at least 6 to 12 months, or when severe curvature or severe erectile dysfunction prevents complete sexual intercourse, according to a position statement from the European Society for Sexual Medicine. Notably, that position statement observes that more than 70% of surgical candidates report penile shortening due to PD prior to surgery.

While use of antioxidants was the focus of the treatment described here, "combined or multimodal treatment also implies the association of therapeutic agents administered in various ways, such as orally and by injection, without excluding the association of physical therapy with the aid of devices, such as iontophoresis, extenders, vacuum devices, and extracorporeal shock wave therapy," authors explained.

They wrote that these "very satisfactory results" achieved here with multimodal combined antioxidant treatment reaffirm their group's previous report on clinical experience in 120 patients showing potential to reduce the plaque size and, thus, improve the corresponding deformity.

Complete plaque regression was achieved in rats in one experimental study, they added. Of previous longer-term studies, the group published a report on treatment duration up to 18 months. In the present case report, they pointed out that the 3 years required for "disease regression in our patients" highlights the inherently lengthy nature of chronic inflammatory diseases and the importance of continuing therapy long enough to stop disease progression and allow plaque to be reabsorbed.

Authors noted that use of a similar multimodal approach to PD in their practice has led some patients to drop out of treatment, "because in their opinion it was too long," despite showing a reduction in plaque and penile curve. Nevertheless, overall, authors stated that they expect excellent results in patients who complete treatment.

They chalked the observed effect up to the antioxidants' ability "to stop the inflammatory process by countering the oxidative stress that plays an essential role in the pathogenesis of PD." They added that all the supplements used inhibit activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and block the production of pro-inflammatory cytokines.

They explained that they included topical diclofenac for its analgesic and anti-inflammatory properties, but also for its ability to scavenge free-radicals and interrupt "the pro-inflammatory cytokine cascade, including production of factor NF-kB." Diclofenac was also selected because it can be absorbed topically by subfascial as well as subcutaneous tissues. Authors cited evidence from a 1991 study that topically applied diclofenac can be absorbed into the capsular ligament of the knee, which they point out "is much thicker than the tunica albuginea of the corpora cavernosa of the penis."

While the clinicians continued with the same oral therapy and topical regimen throughout the treatment period, they reduced the frequency of pentoxifylline after the first treatment cycle, based on evidence of interrupted disease progression and clinical and imaging signs of partial regression. They also decided to reduce the use of penile injections, in consideration of the traumatic etiology often associated with PD, they wrote, observing that "even microtrauma can have serious consequences in patients genetically predisposed to the disease." However, the microtrauma in these patients would be very limited, they added, given their use of a very thin needle and peri-plaque injections.

In contrast to other researchers' perception of ultrasound imaging in PD as "incapable of providing accurate measurement of plaque," the authors stated that, with use of a "cutting-edge ultrasound machine" by an operator with substantial experience in imaging of PD, ultrasound measurement of plaque is very helpful in both the diagnostic assessment of patients and of post-treatment evaluation of outcomes, if not essential to treatment success.

"We believe the goal achieved in these patients with PD is useful for urology and andrology clinical practice," authors concluded, urging new larger, randomized, placebo-controlled studies of this topic.

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