Induration penis plastica (IPP) or Peyronie’s disease is named after a French surgeon Francois de la Peyronie (chief surgeon to Louis XV of France from 1736) who first described it. It is an idiopathic disease of the connective tissue of the penis. It is a fibrosis located in the tunica albuginea, the fibrous membrane that covers the corpora cavernosa.
Although the real incidence of Peyronie’s disease is unknown, a higher rate of incidence has been observed in men age between 50-59. In Italy the prevalence is about 7.1% in the age group of between 50 and 69. Other factors associated with it are invasive procedures of the penis such as catheterisation and cystoscopy, diabetes with erectile dysfunction (20% of patients), low level of testosterone and Dupuytren disease (6%).
The most common hypothesis is that IPP originates from abnormal repairing processes to repeated micro-trauma to the penis, which occur typically during sexual intercourses. According to Devine et al. repeated trauma to a completely or partially erected penis during sexual intercourse could cause ‘delamination’ of the layers of the tunica albuginea, provoking the formation of fibrous scar tissue.
Such delamination usually occurs at the junction of the fibres of the septum in the midline and the ventral circular layers of the tunica albuginea. Repeated trauma causes microvascular injuries with small bleeds in the inter-laminal space. After the breakdown of the clot the leftover fibrin activate fibroblasts, which in turn cause cell proliferation and inflammatory reaction. In this condition of local hypoxia reactive oxygen species (ROS) are released. They activate the Transforminggrowfactor (TGF-β1) which stimulates the proliferation of fibroblast and promotes the transformation of fibroblasts in myofibroblasts.
Fibroblast and myofibroblast are the cells that generate most collagen in the body. In the penis there are type I and type III collagen. These are genetically predetermined.
The formation of a plaque in the tunica albuginea with curvature of the penis causes the classical deformity of the penis which is also characterised by shrinking and shortening. The latter are the symptoms with which the patient presents himself first. This may also cause psychological problems, which in turn manifest themselves in relationship difficulties with the partner. The disease is also characterised by pain on erection which tends to subside within approximately three months. The pathology could cause erectile dysfunction.
Most of the plaques develop on the dorsal surface of the penis causing an upward curvature. Those plaques which develop on the ventral surface of the penis result in a downward curvature. Those plaques that develop on both sides of the penis cause its shortening and other malformations, such as ‘incision’ or ‘hourglass’ deformity. Peyronie’s disease is chronic and progressive for most patients with low probability of spontaneous resolution (13%).
Most of men undergo a medical examination during the acute phase that last up to 18 months, but 33% of patients do not seek medical advice until the chronic phase of the disease.
The curvature of the penis is classified using the Kelami system as slight (≤ 30 degree), moderate 31-60 degree) or severe (>60 degree).
Diagnosis of IPP is reached from the patient’s clinical history and the examination of the penis. The history taking needs to be accurate and to obtain information about the beginning of the symptoms, their possible relationship with trauma to the penis during coitus, progression or stability of the deformity and whether they interfere with the sexual intercourse. The possibility of presence of erectile dysfunction too needs to be elicited. As the pathology has a considerable psycho-social impact, the patient’s mood and potential relationship difficulties too need to be assessed in preparation for a multidisciplinary therapeutic approach. For this an evaluating questionnaire (PDQ) has been validated, which is able to assess the psycho-sexual effects of IPP and the possible response to treatment.
The examination of penis consists of:
Assessment of vascular structures of the penis via Doppler Ultrasound, which allows us to localise the plaques, measure their dimension and their calcification level.
Other possible areas of fibrosis are to be examined (palm of hand and sole of foot).
Blood tests are only necessary to confirm other risk factors of IPP such as diabetes or cardiovascular diseases.
The treatment of IPP is both with drug therapy and surgery. There are methods of non-surgical treatments (mechanical treatment and radiation). Drug therapy includes oral, topical and intralesional therapy. None of the treatments have been approved by the Food and Drug Administration (FDA of USA) and available studies are contradictory. Surgery becomes an option when the deformity has been stabilised for at least 3 months after the acute phase. For curvature of less then 60 degrees there are techniques that affect the convex side of the penis (opposite side of the plaque) with consequent shortening. For larger curvatures the plaque is excised from the concave side of the penis and the tunica is filled up with graft. However, the latter may present a higher risk for erectile capability. In case of erectile dysfunction the use of surgical prosthesis represents the gold standard.
Collagenase clostridium hisolyticum (XIAPEX) is a new drug treatment for adult men affected by IPP who present with a palpable plaque and a curvature of minimum of 30 degrees of the penis. It is the only therapy approved by the Food and Drug Administration (FDA) since December 2013 and by the European Medicines Agency (EMA) since 2015. XIAPEX is composed of two different types of collagenases (AUX-I and AUX III). Injection of XIAPEX in a plaque which is mostly formed by collagen can facilitate its enzymatic breaking down resulting in the reduction of penile curvature. A complete treatment consists of 4 cycles. Two injections and a modelling procedure of the penis are scheduled in every cycle. The second injection is given 24-72 hours after the first one. The modelling is to be initiated 24-72 hours after the second injection. The interval between cycles is six weeks. The procedure must be done by a specialist who is adequately trained in the correct administration of the therapy. We achieve improvements of 78% of the patients with this method. The penile curvature improves by 34% with a corresponding scale of 17 degree. The most common side effects are oedema and haematoma of the penis affecting appr. 50% of the patients. The erectile capability assessed by IIEF (International Index for Erectile Function) seems to be enhanced and the dimension of the penis increased from 12.9 to 13.3 cm. In a recent study assessing the female response to those men who underwent such treatment could be evaluated and indeed confirmed by the Female Sexual Functional Index.
MODELLING: The modelling of the penis is achieved by repeated exercises carried out by the patient at home several times of day. A vacuum device proves to be particularly useful in these exercises.
In Europe the protocol provides for 3 cycles, every cycle includes one injection with double dose. The results show an improvement of 31.4% of the curvature with a corresponding degree of 17,36.
Recently there is a new protocol which comprises of and evaluates a second and eventually a third cycle of injections on a case by case basis.
Following this protocol 800 patients with an average age of 54.3 years (range 23-74), with partners with an average age of 49.8 years (range 28-80) have been treated from November 2016 until March 2020. The curvature, according to Kelami classification, was under 30 degree for 51.7%; between 31-60 degrees for 25.8% and between 60-90 degrees for 22.3%. 80% of the treated patients were satisfied, while 20% responded that the increase was below their expectations. There was an average improvement of 19.3 degree (range 0-40).
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