AUTHOR AND EDITOR INFORMATION

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• Follow-up
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INTRODUCTION

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Background

In 1587, Guilio Cesare Aranzi was the first to formally describe Peyronie disease (PD) in his book Tumores praeter naturam. He called PD "a rare affection of the genitals in people with excessive sexual intercourse: a little penile tumor palpable like a bean in the flaccid penis causing a deformity similar to a ram horn during erection." The disease was not given its current name until 1743, when Francoise de La Peyronie described the cases of 3 men with fibrous thickening of the penile shaft, painful erections, and penile curvature.

Pathophysiology

Although the exact etiology of PD is not clear, trauma may cause perivascular inflammation. In ordinary tissue, the rupture of blood vessels leads to coagulation and fibrin deposition. Fibrinolysis of the deposited fibrin occurs as tissue cells proliferate to close the site of injury. In PD, the tunica albuginea may initially undergo microvascular trauma during sexual intercourse. Adequate postinjury fibrinolysis is prevented because the tunica albuginea is hypovascular.

After multiple microvascular trauma, large quantities of fibrin accumulate in the form of a plaque, generally along the dorsal and ventral midline aspects of the penile shaft. This deposition appears to be immune mediated. Some people may be genetically predisposed to this reaction. The plaque prevents the adequate expansion of the tissue during erection, leading to penile curvature and pain. The relationship of this condition to other fibromatoses suggests a predisposition to fibrous proliferation. Although these microtraumatic events are implicated in the current theory of the pathogenesis of PD, no etiology is proven.

Results of animal studies indicate that transforming growth factor-beta (TGF-beta) may be involved in the formation of the plaques via early inflammatory reactions. When TGF-beta analogs are injected into rat tunica albuginea, they form collagen bundles that are morphologically similar to those in PD.

PD starts in 1 of 2 ways. Most patients report the acute onset of pain accompanied by a lump in the shaft of the penis, followed by gradually increasing curvature with or without pain. Alternatively, a minority of the patients report curvature of the penile shaft that occurs suddenly, seemingly overnight, and remains stable once it occurs.

In the progressive form, the cycle of trauma, fibrin deposition, and attempts at fibrinolysis continue to escalate. Remodeling of the fibrin deposits can take as long as 2 years in the absence of further traumatic events.

Frequency

United States

The rate is 0.3-4% among white men.

International

This disease is less common in men of African or Asian heritage.

Mortality/Morbidity

• The disease spectrum ranges from asymptomatic plaques to mild penile curvature or severe curvature that results in a complete inability to have sexual intercourse.
• Erectile pain can range from none to severe, depending on the site and amount of plaque deposition.

Race

• PD is well documented in whites.
• PD may occur in black men, often in the presence of preexisting diabetes mellitus and erectile dysfunction.
• To our knowledge, no cases in Asians have been documented.

Sex

This disease occurs in males only.

Age

• PD predominantly occurs in men aged 40-60 years.
• The age range of affected persons is 30-80 years.

CLINICAL

Section 3 of 11  

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• Miscellaneous
• Multimedia
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History

• Usually, the penis hurts only during an erection. This pain occurs in one third of patients and is pathognomonic for PD.
• Penile curvature of varying degrees may be observed, only during an erection.
• No history of a congenital malformation of the penis or a metastatic cancer is present.

Physical

• On palpation, a fibrotic plaque, usually greater than 1.5 cm in diameter, is felt over the midline of the penile shaft, either ventrally or dorsally.
• The erect penis may be curved, or it may have an hourglass deformity with flaccidity of the distal penis.
• • The patient can obtain Polaroid photographs of the erect penis in private to demonstrate the increased curvature.
  • Self-taken photographs can be used to establish a reference point for subsequent observation or treatment.
• Evidence suggests that pain tends to improve with time, but fibrosis and/or deformity tend to worsen or persist. Waiting 12-24 months for the plaque to stabilize before surgical intervention is typical.

Causes

Although microtraumatic events are implicated is the current theory of the pathogenesis of PD, no etiology is proven. No risk factors are known, but associations do exist.

• PD occurs in men, particularly in older men with weak erections, who engage in frequent and vigorous intercourse (>4 times per wk).
• Whenever a familial predisposition has been found, it always had an autosomal dominant trait.
• In some studies, HLA-B7 and HLA-DQ5 appear to be correlated with the incidence of PD. Results of recent studies have not confirmed this finding.
• PD may be associated with erectile dysfunction, diabetes mellitus, and hypertension. Resultant partial erections may lead to buckling during intercourse.
• PD is associated with Dupuytren contracture. Among patients with PD, 10% have Dupuytren contracture, and 3% of patients with Dupuytren contracture have PD.
• Aponeurotic plantar fibrosis (ie, Ledderhose disease) may be found.
• PD is associated with sporadic and familial knuckle pads, which are circumscribed fibromatous thickenings overlying the finger joints.
• Systemic sclerosis has been seen with PD.
• Occasionally, PD is associated with fibromatous degeneration of the external ear cartilage.
• Antielastin antibodies, anti-DNA antibodies, and elevated antinuclear antibody (ANA) levels have been found in association with PD.
• PD itself is not associated with penile fracture.

DIFFERENTIALS

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Other Problems to be Considered

Congenital penile curvature
Artificial penile nodules (eg, tancho nodules, bulleetus)
Fracture of the penis
Penile dorsal vein thrombosis
Leukemic infiltrate of the penis
Late syphilitic lesions
Lymphogranuloma venereum infiltration of the penis

WORKUP

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Imaging Studies

• The diagnosis is based on the features of the history and the physical examination findings.
• Radiographs depict plaque calcifications in 20% of patients.
• • The presence of calcifications indicates advanced disease that is unlikely to regress spontaneously.
  • Calcifications on radiographs are an indication for surgical intervention.
• Doppler studies and dynamic-infusion pharmacocavernosometry can be performed on an artificially erect penis (see Procedures) to further identify lesions and any secondary filling defects.
• High-resolution ultrasonography is the definitive imaging study, although it is not frequently required to confirm the diagnosis. Ultrasonography may be helpful before definitive surgical intervention is planned.
• MRI of the plaques is experimental and unnecessary. It can be used to delineate inflamed plaques that are too soft or not dense enough to be detected with ultrasonography or radiography.
• The results from scintigraphy with technetium Tc 99m human immunoglobulin G were found in a recent study to correlate with unstable plaques that may respond to medical treatment. The lack of ^99mTc human immunoglobulin G positivity correlated with stable plaques, which are usually considered resistant to medical therapy and better suited for surgical intervention.

Procedures

• Diagnostic intracorporeal injection may be used if the history is not clear or if a comorbid disease is present.
• • An intracorporeal injection of a vasodilator can be used to determine the patient's erectile capability and the extent of penile distortion.
  • Alprostadil (prostaglandin E1) or various combinations of alprostadil, phentolamine, and/or papaverine can be used to induce this artificial erection.

Histologic Findings

In early PD, an inflammatory reaction occurs, with thickening of the tunica albuginea, the deposition of fibrin, and the loss of elastic fibers. Soon, nodular and/or diffuse bands of fibroblasts and myofibroblasts are surrounded by dense masses of collagen. These changes may extend into the underlying corpora cavernosa. Late-stage calcification or ossification may be seen.

TREATMENT

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Medical Care

Medical care is focused on patient education and anecdotally effective medical therapies. See Patient Education.

• Medical therapies are mostly of marginal and anecdotal benefit. Their effects are hard to evaluate because of the variable natural history of PD. Although many remedies exist, no one medical therapy is clearly superior to any other. Treatments range from oral vitamin E administration to low-dose radiation to intralesional injections of calcium channel blockers. A few interventions, such as collagenase, acetyl-L-carnitine, propionyl-L-carnitine, verapamil, and interferon alfa-2b, are considered active in the treatment of PD. These interventions have good data, often in the form of placebo-controlled studies, to support their use.
• If erectile dysfunction is present, the condition is unlikely to improve with treatment of the Peyronie plaque alone. The use of sildenafil with an intracavernous injection treatment or a vacuum device is indicated. Intracavernous injections may worsen penile scarring, and the treatments must be monitored carefully. Intralesional injections of interferon alfa-2a may be effective.
• Iontophoresis is the use of an electric current to pull medications through the skin to specific sites. This electromotive drug administration has been used to treat PD with various combinations of orgotein, dexamethasone, lidocaine, and verapamil. The technique is experimental. Since 2003, several studies have reported some success with a combination of verapamil, lidocaine, and iontophoresis.
• Therapies to avoid include intralesional steroid injections, which may induce more inflammation and oral procarbazine administration, which is not effective and may cause blood dyscrasias. Steroid injections (eg, triamcinolone injections) may be contraindicated in the treatment of PD. Conflicting reports demonstrating some efficacy to intralesional steroid injections may, in fact, represent the mechanical destruction of the plaques with the volume of fluid injected and not the actual compound itself.
• Another technique called extracorporeal shockwave therapy, similar to what is commonly used to destroy kidney and salivary gland stones, has been reported as another treatment modality. Conflicting reports and concerns over causing increased inflammation and damage limit the usefulness of this therapy.

Surgical Care

Surgical care is focused only on those with significant morbidity and PD that is resistant to medical treatment. Surgery may be indicated after a 12- to 18-month observational period during which the PD is shown to be stable.

• For the best results, the PD plaques and the angulation of the penis should be stable for several months prior to surgery. Unless the initial inflammatory phase of PD resolves, it continues after surgery and increases the likelihood of recurrence.
• Common surgical correction methods include the following:
• • The Nesbit tuck procedure: Unaffected tunica albuginea is removed from the side of the penile shaft immediately opposite the PD plaque to straighten and shorten the penis. For this procedure to work, potency should be normal, and the penile curvature should be less than 60°.
  • Tunica plication procedure: The tunica albuginea is plicated (not excised) to straighten the penis. This technique also causes penile shortening.
  • Plaque excision and grafting: This procedure may be performed to preserve penile length when the curvature is greater than 60°.
  • Plaque excision and penile prosthesis insertion: This method is useful when comorbid severe erectile dysfunction is present.
• New surgical techniques include the thinning of the plaque with carbon dioxide lasers.

Consultations

• Consultation with a urologist is mandatory for surgical management. Surgical management is indicated when medical management fails or when significant pain and/or a complete inability to have intercourse is present.
• A sex therapist may provide useful adjunct care, both to underscore the realistic expectations and to evaluate comorbid sexual dysfunction.

MEDICATION

Section 7 of 11  

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The following treatments are only temporizing.

Drug Category: Vitamins

The antioxidant properties of vitamin E may limit the extent of inflammation. Vitamin E is inexpensive, has few adverse effects, and has anecdotal usefulness.

Drug Category: Nutrients and nutritional agents

These agents may improve pain and lessening of penile curvature. Their efficacy is not clearly established.

Drug Category: Antihistamines

The initial stage of a PD plaque involves histamine-mediated inflammation. Anecdotal evidence suggests that an antihistamine may limit this inflammation.

Drug Category: Anti-inflammatory agents

These agents may help patients with PD by reducing inflammation.

Drug Category: Estrogen receptor antagonists

These agents inhibit TGF-beta actions and inflammatory reactions. TGF-beta and inflammatory mediators are involved in the production of PD plaques in animal studies. Only anecdotal evidence for use of these agents exists.

Drug Category: Calcium channel blockers

Anecdotal evidence shows some lessening of the scarring process after intralesional injections. The theory is based on the known action of verapamil in decreasing the production and secretion of extracellular matrix macromolecules by fibroblasts while increasing collagenase production in the same area.

Drug Category: Nonsteroidal anti-inflammatory agents (NSAIDs)

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well; these include the inhibition of the following: leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Drug Name	Acetaminophen (Tylenol, Feverall, Tempra, Aspirin Free Anacin)
Description	DOC for treatment of pain in patients with documented hypersensitivity to aspirin or NSAIDs or upper GI disease and who are taking oral anticoagulants.
Adult Dose	325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; known G-6-PD deficiency
Interactions	Rifampin can reduce analgesic effects; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hepatotoxicity possible in long-term alcoholism, at various dose levels; severe or recurrent pain or high or continued fever may indicate serious illness; many OTC products contain acetaminophen, and combined use may result in cumulative doses exceeding recommended maximum dose

Drug Name	Ibuprofen (Motrin, Ibuprin)
Description	DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult Dose	200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT with anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Drug Name	Naproxen (Aleve, Naprelan, Naprosyn, Anaprox)
Description	For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which decreases prostaglandin synthesis.
Adult Dose	500 mg PO followed by 250 mg q6-8h; not to exceed 1.25 g/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT with anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion are at risk for acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Drug Name	Etodolac (Lodine)
Description	Inhibits prostaglandin synthesis by decreasing activity of the enzyme, cyclo-oxygenase, which results in decreased formation of prostaglandin precursors, which in turn results in reduced inflammation.
Adult Dose	200-400 mg q6-8h prn; not to exceed 1200 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; do not administer into CNS; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, and high risk of bleeding
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT with anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels when administered concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low white blood cell counts are rare and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if leukopenia, granulocytopenia, or thrombocytopenia persists

Drug Name	Flurbiprofen (Ansaid)
Description	May inhibit cyclo-oxygenase enzyme, which, in turn, inhibits prostaglandin biosynthesis. These activities may result in analgesic, antipyretic, and anti-inflammatory effects.
Adult Dose	200-300 mg/d PO divided bid/qid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT with anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels when administered concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion are at risk for acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Drug Name	Ketoprofen (Actron, Orudis, Oruvail)
Description	For relief of mild to moderate pain and inflammation. Small doses initially indicated in small or elderly patients or those with renal or liver disease. Doses >75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe patient for response.
Adult Dose	25-50 mg PO q6-8h prn; not to exceed 300 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT with anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Drug Name	Piroxicam (Feldene)
Description	Decreases activity of cyclo-oxygenase, which, in turn, inhibits prostaglandin synthesis. These effects decrease formation of inflammatory mediators.
Adult Dose	10-20 mg/d PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active GI bleeding
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT with anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur, (discontinue if leukopenia, granulocytopenia, or thrombocytopenia persists)

Drug Category: Interferon intralesional injections

Interferon slows fibrogenesis, inhibits RNA synthesis, and inhibits oxidative stress

FOLLOW-UP

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• Follow-up
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Further Outpatient Care

• Radiation treatment may be recommended for early, especially painful situations.
• • Radiation from a beta-beam linear accelerator is used to reduce inflammation.
  • This treatment does not change or remove late-stage postinflammatory plaques.
• Extracorporeal shock-wave therapy may help in treating the curvature. This treatment does not help the pain and is still experimental.

Deterrence/Prevention

• Theoretically, the patient should avoid vigorous intercourse with a weak erection.
• If the patient has diabetes, it should be controlled.
• No method for absolute prevention is known.

Complications

• Complications include the complete inability to maintain sexual performance.

Prognosis

• PD only occasionally, if ever, disappears completely.
• • The pain may diminish or resolve after the early inflammatory phase, and as many as 13% of patients claim to have some improvement with time.
  • Approximately one half of the remaining individuals have progressive disease, whereas the other half have static disease.
• Variable degrees of morbidity may occur. Conditions range from a static painless plaque without penile angulation to painful erections with a curvature significant enough to prevent sexual activity.
• Recent data suggest a combination approach to therapy, such as the use of partially effective oral therapies with minimally invasive mechanical or intralesional treatments, may be more successful than the individual therapies on their own.

Patient Education

• Patient education includes the following:
• • Reassurance that lesions are not cancerous or fatal
  • An explanation that the condition is not curable but that it is treatable and possibly self-resolving
  • An open discussion about the problems with intercourse, the possibility of the resumption of satisfactory sexual activity, and the reduction of pain

MISCELLANEOUS

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Medical/Legal Pitfalls

• Performing surgery too soon, before the PD plaque is stable, before medical management is tried, or before an observation time of 12-18 months is complete may result in ongoing fibrosis around the surgical site.
• Failure to educate patients concerning the likely prognosis and reasonable expectations is a pitfall.

MULTIMEDIA

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Media file 1:  Lateral view demonstrates vertical curvature.
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Media file 2:  Superior view shows a full erection.
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Media file 3:  Postoperative picture after surgical repair demonstrates a straight erection.
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Media file 4:  Intraoperative picture of an artificial erection demonstrating lateral curvature.
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Media file 5:  Intraoperative picture after penile plication demonstrating a straight erection.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
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• Follow-up
• Miscellaneous
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• References

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Article Last Updated: Dec 4, 2006