Peyronie's Disease and It’s Management

Peyronie’s Disease

Peyronie’s disease (PD) was referred to as an induratio penis plastica. Its literal translation is ” penis becomes like plastic.” Peyronie’s disease is named after Francois Gigot de la Peyronie in 1743 (surgeon to King Louis XV of France). A plaque is formed in the penis, and the penis is a bit curved. The patients develop a lot of problems due to this.

Prevalence Of Peyronie’s Disease

• A population-based study was done, and the prevalence of Peyronie’s disease was found to be 0.5% to 13%.
• 0.5% are the ones who are living with the diagnosis of Peyronie’s disease.
• Approximately 10-13% of the patients in the entire population probably have some or other disease severity.
• In a study, the patients were evaluated and then divided into the diagnosis of a definitive Peyronie’s disease and Probable Peyronie’s disease.
• Definitive Peyronie's disease
  • A questionnaire is given to the patient. Based on the questionnaire, the responses to the survey questions were suggestive of Peyronie’s disease, and then these particular patients were evaluated by the physicians.
• Probable Peyronie's disease
  • The patients who took the questionnaire were suggestive of Peyronie’s disease. However, when the practicing physician evaluated the patient, it was not diagnosed as Peyronie’s disease.
  • The most common age group affected by this disease is the 5^th decade.
  • There is a linear increase in the prevalence from 30-49 years and exponentially increases after 50.

Natural History  Peyronie’s Disease

• Peyronie’s disease has 2 phases:
  • Active (acute) phase 
    • The disease is progressive 
    • The curvature is increasing.
    • The severity is increasing.
    • It is associated with a painful erection and changing deformity of the penis.
  • Stable (chronic) phase
    • There is stabilization of the deformity and disappearance of the painful erection.
    • When the erection occurs, the penis will be a bit curved but will not be painful.
• The mean age group is 52±22 years.
• The duration of Peyronie’s disease is 3-5 months. After that, the disease gets converted to a chronic or stabilized phase.
• The mean stretched flaccid penile length should be 12.2cm. When the penile is flaccid, it needs to be stretched, and the mean stretched flaccid penile length is taken.
• When a group suffering from Peyronie’s disease was tested, the mean stretched flaccid length was 12.2cm. This length is checked before proceeding with surgery.
• The mean curvature at the baseline was 42±22 degrees.
• The mean duration of the follow-up was 18±7 months.
• All the patients with penile pain had improvement, and 89% had complete resolution.
• Only 12% of patients showed improvement in curvature. 40% of patients remained stable, and 48% worsened. The curvature increased over some time.
• The mean improvement of the curvature is around 15 degrees.
• The curvature is worsening around 22 degrees.
• There are 2 aspects of Peyronie's disease:
  • Pain on erection
  • Curvature

Associated Conditions With Peyronie’s Disease

1. Aging – there is an exponential rise in the occurrence of Peyronie’s disease after 50 years of age.
2. Diabetes
   • Peyronie’s disease is referred to as a silent manifestation of diabetes.
   • In Diabetes Mellitus (DM), there is an exaggerated fibrogenic response.
   • Diabetic patients with Peyronie’s disease have a higher risk of severe deformity and erectile dysfunction.
   • For a patient having both Peyronie’s disease and Diabetes Mellitus, the deformity would be a bit more severe.
3. Erectile dysfunction
   • Evaluation of erectile dysfunction is important before proceeding to surgery in a patient with Peyronie’s disease.
   • The prevalence of erectile dysfunction in men with Peyronie’s disease is approximately 37% to 58% (Chung et al., Casabe et al.).
4. Psychological aspects
   • They might have diminished self-esteem, shame, embarrassment, self-disgust, anxiety, loss of sexual confidence, and depression.
5. Radical Prostatectomy
   • Peyronie’s disease may occur after the patient has been subjected to radical prostatectomy.
   • It can be due to some perioperative penile trauma, neurogenic consequences, or local release of cytokines.
6. Hypogonadism
7. Collagen disorders
   • A patient having some form of collagen disorder is an inappropriate feature associated with Peyronie’s disease.

Also Read: Prostatic Carcinoma: Screening, and Treatment Options

Penile Anatomy in Peyronie’s Disease

• Tunica albuginea
  • Tunica albugenia is a covering that surrounds the corpora cavernosa.
  • It is a multilayered structure, predominantly a type 1 collagen with inner circular and outer longitudinal fibers.
  • In between, there is an incomplete septum. This septum is anchored to the inner circular layer, which is very important for the structural integrity of the corpora cavernosa.
  • The outer longitudinal fibers are thinnest at around 3 and 9’o clock positions of the corpora and completely absent between 5 and 7’o clock positions. That is why the penis tends to undergo dorsal buckling.
  • Most patients with Peyronie’s disease exhibit dorsal curvature.
  • The normal architecture is essentially lost due to this disease, resulting in Peyronie’s plaque.
  • Histologically, this plaque demonstrates disorganization of the collagen fibrils and decrease and disorganization of the elastin.

Also Read: Undescended Testis: Causes, Treatment Options, and Risks

Impact Of Wound Healing On Peyronie’s Disease

• There is local trauma because of the dorsal buckling.
• Normal wound healing involves 3 phases:
  • Acute phase
  • The proliferative phase usually starts around 72 hours after the surgery and persists for around 2 weeks.
  • Remodeling phase: The collagen fibers are brought back to the normal level, which may last up to 1 to 2 years.

Molecular Mechanism of Plaque Formation in Peyronie’s Disease

• When there is a penile trauma, fibrin is deposited, and inflammatory cells and platelets are attracted.
• Due to the attraction of the inflammatory cells and platelets, there will be an increase in the fibrogenic cytokines (TGF-β1, PDGF-IL-1, TNF-α). Then, there is an attraction of the proliferation of the fibroblast and the myoblast.
• The reactive oxygen species are released, which leads to oxidative stress.
• All these ultimately cause excessive collagen production, which is deposited and leads to penile plaque.
• Over a while, this penile plaque can have osteogenic dedifferentiation, ultimately leading to plaque calcification.
• The increased amount of nitric oxide is associated with plaque formation.

Also Read: Injuries Of Testis And Testicular Torsion

Etiology Of Peyronie’s Disease

• Most agree that some kind of injury triggers the cascade of events that ultimately leads to Peyronie’s disease in the susceptible individual. It does not happen with the same severity in every individual.
• Trauma may be either a one-time trauma, which can be perceived as a single trauma, or there can be microtrauma at repeated intervals. Sometimes, it is linked with sexual intercourse. Micro-trauma happens during sexual intercourse, and over time, Peyronie’s disease may develop.
• Oxidative stress – the increase in free radicals induces the over-expression of fibrogenic cytokines and augmented transcription and synthesis of collagen.
• Nitric oxide, myofibroblasts, TGF—β1, and fibrotic gene expression all play key roles in the development of Peyronie’s disease.

Symptoms Of Peyronie’s Disease

1. Penile pain 
   • This pain usually occurs in the acute phase of the disease and can occur in the flaccid condition with palpation of the plaque with erection and during intercourse.
   • The torque pain is associated with a pulling sensation of the plaque when a strong erection occurs.
2. Erectile deformity
   • There is a classification known as Kelami classification for the deformity of the curvature.
     • It says that if the degree of bent is up to 30 degrees, it is a mild curvature.
     • If it is between 31 and 60 degrees, it is a moderate curvature.
     • If it is more than 60 degrees, it is a severe curvature.
     • Mild is the most common deformity.
     • Around 40% are mild, 35% are moderate, and 13-15% have severe deformity.
3. Palpable plaque
   • With a simple dorsal plaque apt to have a dorsal curvature.
   • If there is a transverse or spiraling scar, which can be partial or circumferential, it can result in varying degrees of indentation, including an hourglass deformity. 
   • Erection deformity

Evaluation Of Patient With Peyronie’s Disease

1. Careful history 
   • Ask the patient for the severity of the penile deformity, interference with intercourse, penile pain, and distress.
2. Physical examination
   • The penis is examined on stretch, which allows the easier identification of the plaque.
   • Stretched penile length is a critical parameter to measure at the initial consultation.
   • The plaque feels like a rocky, hard structure, which can be an indicator of calcification. A USG needs to confirm this.
3. Calcification – activation of the genes involved in the osteoblastic activity.
   • Intralesional injection therapy with Verapamil and interferon (IFN) does not help treat or prevent calcification and reduce the severity of plaque.
   • The plaque causes posterior acoustic shadowing.
   • The Goniometer is used to measure the curvature of the erect penis.

Penile Duplex Ultrasonography in Peyronie’s Disease

• It helps in the identification and measurement of plaque calcification.
• It helps in the identification of human fibrosis. MRI can also help in the identification of corporeal fibrosis.
• Observation of the erectile response to the vasoactive intracavernosal injection.
• Measurement of the penile vascular parameters (peak systolic velocity, end-diastolic velocity, and resistive index).
• Optimum objective measurement of the erect penile deformity (curvature, girth irregularity, and hinge effect).

Management of Peyronie’s Disease

Non-surgical Management of Peyronie’s Disease

Following are the different drugs used in the management of Peyronie’s Disease.

1. Potassium aminobenzoate (Potaba)
   • It helps in reducing the formation of collagen in the fibroblast cell culture.
   • It is impractical because it is very expensive and difficult to consume (24 tablets daily).
   • No relevant difference has been found regarding the pre-existing penile deviation.
   • A significant protective effect on the deterioration of the penile curvature could not be demonstrated.
   • There were some benefits to preventing the deterioration of the disease.
   • The study's outcome was that potassium para aminobenzoate appears to be useful in stabilizing the disorders and preventing the progression of penile curvature.
2. Vitamin E
   • It limits the oxidative stress of the radioactive substances that increase during the acute and proliferative phases of healing.
   • It was thought that vitamin E could help prevent or heal some aspects of Peyronie’s disease. However, it did not show any significant improvement in pain, curvature, or plaque size when compared with placebo. Thus, vitamin E is not used.
3. Tamoxifen
   • SERM – it is a Selective Estrogen Receptor Modulator.
   • It induces the production of TGF-β. Higher concentrations of TGF-β inhibit the inflammatory response by preventing further tissue fibrogenesis.
   • RCTs have demonstrated no significant improvement, so Tamoxifen is ineffective.
4. Colchicine
   • It binds to tubulin and causes depolymerization. It also inhibits cell mitosis mobility and adhesion of leukocytes, the transcellular movement of collagen, and the production of collagenase.
   • It has gastrointestinal side effects. It causes GI upset with diarrhea.
5. Carnitine
   • It increases mitochondrial respiration and decreases free radical formation.
   • It did not show any significant improvement in pain, curvature, or plaque size in the patients of Peyronie’s disease treated with propionyl-L-carnitine compared with those treated with a placebo.
6. Phosphodiesterase Type 5 inhibitors
   • It increases cyclic GMP levels, inhibits collagen synthesis, and induces fibroblast and myofibroblast apoptosis, thus acting as an anti-fibrotic agent.

Intralesional Injections In Peyronie’s Disease

1. Verapamil
   • It has been tried as an intralesional injection. It is injected directly into that plaque.
   • It affects the fibroblastic function on several levels, including cell proliferation, Extracellular Matrix protein synthesis and secretion, and collagen degradation.
   • 10 ml of Verapamil is mixed with 10 ml of saline and injected into the intralesional agent.
   • There are few people for whom this injection of Verapamil is not helpful. The poor candidates for trying this intralesional Verapamil injection are if there is extensive calcification, a curvature of >90 degrees, or ventral curvature.
   • It is very difficult to infiltrate the plaque adequately.
2. Clostridial Collagenase
   • It is FDA-approved.
   • It degrades the collagen types I and II in connective tissues despite the presence of TIMPs (Tissue Metalloproteinases).
   • It received FDA approval in December 2013 to treat Peyronie’s disease.
3. Nicardipine
4. Interferon alpha-2b 
   • Nicardipine and Interferon alpha-2b can also be used. They inhibit the fibroblast, decrease the rate of proliferation and production of extracellular collagen, and increase the production of collagenase.

Newer Modalities In the Treatment Of Peyronie’s Disease

1. Electromotive Drug Administration
2. Extracorporeal Shockwave Therapy 
   • There is direct damage to the penile plaque.
   • It increases the vascularity of the targeted area by generating heat, inducing an inflammatory reaction that lysis the plaque.
   • It could significantly increase the % of men with a lessening of penile plaque.
   • It can reduce the severity of the disease.
   • It can help in relieving pain or complete remission of pain.
   • However, insignificant differences have been found in improving penile curvature and sexual function.

Surgical Management Of Peyronie’s Disease

• The indications for surgical management:
  • Suppose the patient has a stable disease (the curvature is not increasing). Stable disease is defined as a disease at least a year from the onset and at least 6 months of stable deformity.
  • Deformity that comprises or makes it impossible for the patient’s ability to engage in sexual intercourse.
  • The patient in whom the conservative therapy has failed.
• Preoperative consent
  • Explain to the patient that there can be persistent or recurrence of the curvature. The reduction in the penile erect length, diminished rigidity (the rigidity of erection can be compromised a bit), and decreased sexual sensation.
  • According to the European Association of Urology (EAU), if the patient is operated on and the patient has residual deviation or a bend in the penis close to 15 degrees is acceptable.
  • 2 major surgeries are offered to the patients of Peyronie's disease:
    • Plication
      • The change in penile erect length is more likely with plication, as the risk of penile length reduction is higher during plication procedures.
    • Excision or incision, along with the grafting
      • The penile length might probably increase.
      • Stretched flaccid penile length documented pre-operatively permits in comparison with post-operative length.
      • It has decreased sexual sensation due to some amount of nerve damage during the surgery. This typically resolves in around 1-6 months. 
      • Rarely compromises orgasm and ejaculation.
      • Before taking the patient for surgery, it should be checked if the inherent erection of the patient is present or not.

1. If the patient has an adequate amount of erection

• Erection adequate for the penetration with or without PDE5 inhibitors – if the patient can maintain a good amount of erection or if the patient is satisfied with the erection, then a Duplex Ultrasound of deformity is performed.
• With duplex ultrasound and all the physical examinations, there are 2 scenarios:
  • A simple, uniplanar curve is <60-70 degrees, and there is no hourglass of the hinge deformity. It is a milder form of the disease. 
    • The patient is asked if he is okay with a slight reduction in the length. If the patient says yes, then the plication procedure is done.
    • If the patient says no, then plaque incision or partial excision and grafting are done.
  • A complex, multiplanar curve that is >60-70 degrees of deviation. There is either a hinge effect, an hourglass deformity, or a short phallus (the stretch length is <9cm).
    • In this case, the plication surgery is not offered.
    • The patient is asked if he is okay with the development of erectile dysfunction. If the patient says yes, then plaque incision or partial excision and grafting are done.
    • If the patient says no, then Penile Prosthesis is done.

2. If the patient does not have an adequate amount of erection

• Even if the surgery is done, it will not be useful.
• Preprosthesis plication or penile prosthesis is done.
• After penile prosthesis, it is seen whether the penis has become functionally straight (deformity of the deviation ≤15 degrees). If it is fine, then no further treatment is required.
• If the penis is not functionally straight, manual modeling is done to make the penis functionally straight.
• If the penis becomes functionally straight, it is good.
• If the penis does not become functionally straight after manual modeling, then a plaque incision with grafting is done if the defect is >2cm.

Tunical Shortening Procedures In Peyronie’s Disease

1. Penile Plication
   • Shortens the tunica albuginea's longer (or convex) side to match the shorter side's length.
   • It is preferred because
     • It has a short surgical time. 
     • It has good cosmetic outcomes. The chance of getting a functionally erect penis is more.
     • It has minimal effect on the rigidity.
     • It is a simple and safe surgery.
     • It is effectively straightening.
     • Drawback Of penile plication – the only drawback is that it shortens the penile length, and there is a failure to deform.
2. The Nesbit Procedure 

• It employs a transverse elliptical incision of the tunica albuginea.
• The transverse elliptical incision is put on the tunica albuginea and contralateral to the area of greatest curvature and closed transversely.

3. The Yachia Procedure

• It employs a full-thickness vertical incision. 
• A vertical incision is put contralateral to the area of greatest curvature and closed transversely without removal of the tunica albuginea.

4. The Dot procedure

• It employs no incision (given by Ebbehoj and Metz).
• The tunica albuginea is plicated with a permanent suture using an extended Lambert-type suture placement following four dots per plication.

5. Tunica Albuginea Plication Procedure (TAP)

• Two transverse parallel incisions are placed around 1-1.5cm apart and joined together.
• They do not violate the inner circular fibers of tunica.
• The underlying cavernosal tissue is not disturbed.
• It is thought to reduce the likelihood of postoperative erectile dysfunction.

6. Essed/Schroeder Plication Procedure

• The incision is given like a circumcision, and degloving of the entire penis is performed.
• The urethra is dissected off the corpora cavernosa.
• The remaining non-absorbable sutures are placed after identifying points that will result in penile straightening.

Tunical Lenthening Procedures In Peyronie’s Disease

• Plaque Incision and Grafting (PIG) – the plaque is incised, and grafting is put.
• Partial Plaque Excision and Grafting (PEG) – the plaque is excised, and grafting is put in.

• If the curvature is >60-70 degrees, tunical lengthening procedures are performed.
• One of the drawbacks is that it might lead to erectile dysfunction.
• Must have strong preoperative erections.

Properties Of An Ideal Graft

• An ideal graft should have the following:
  • The strength and elasticity should match the normal tunica albuginea.
  • It should have minimal morbidity and tissue reaction.
  • It should be readily available.
  • It should not be too thick. It should be pliable, easy to size and suture, and inexpensive.
  • It should be resistant to the infection.
  • It should preserve erectile capacity.
• Tutoplast (Coloplast), processed human and bovine pericardium, and porcine Small Intestinal Submucosa (SIS) grafts are the most commonly used grafts.

Clinical Questions

1) Which radiological investigation will you perform for calcifying the penile plaque?

Ans: USG.

2) What is the Goniometer used for?

Ans: To measure the degree of curvature in the erect penis.

3) Which is the most common curvature?

Ans: Dorsal curvature

4) Which drug is FDA approved?

Ans: Clostridial Collagenase

5) Which is the most preferred tunical shortening procedure?

Ans: Penile plication.

6) Why is manual modeling done?

Ans: To make the penis functionally straight.

7) What are the 2 major surgeries offered to the patients of Peyronie’s disease?

Ans: Plication and Excision or incision along with the grafting.

8) What are the 2 aspects of Peyronie’s disease?

Ans: Pain on erection and the Curvature. 

If you are preparing for NEET-SS 2024 and ahead, check out SS ELITE Plan (Version 3.0) and what makes it the perfect study resource for your super speciality preparation. 

Hope you found this blog helpful for your NEET SS Surgery urology preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.