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Chronic prostatitis: Current concepts

Feb 10, 2008 Viewed: 819

Chronic prostatitis (CP) is a common condition. It causes significant suffering to the patients and constitutes a sizeable workload for the urologists. The purpose of this review is to describe the currently accepted concepts regarding the aspects of CP.

Materials and Methods: Relevant papers on the epidemiology, etiology, diagnosis, evaluation and management of CP were identified through a search of MEDLINE using text terms “prostatitis”, “chronic prostatitis” and “chronic pelvic pain syndrome”. The list of articles thus obtained was supplemented by manual search of bibliographies of the identified articles and also by exploring the MEDLINE option “Related Articles”.

Results: The salient points of the relevant articles on each aspect of CP have been summarized in the form of a non-systematic narrative review.

Conclusion: Chronic prostatitis is caused by a variety of infective and non-infective factors and is characterized by a rather long remitting and relapsing clinical course. The diagnosis is based on symptoms comprising pain and nonspecific urinary and/or ejaculatory disturbances and microbiological tests to localize bacteria and/or leucocytes in segmented urinary tract specimens. The contemporary classification was proposed by the National Institutes of Health/National Institute of Diabetes Digestive Kidney Diseases (NIH/NIDDK). National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) is the patient evaluation tool used extensively in clinical practice and research. Management should be individualized, multimodal and of an appropriate duration.

Chronic prostatitis (CP) is a common, yet poorly understood condition. It spells misery not only for the patients who have to suffer, but also for the urologists looking after them. They often find themselves running out of ideas when faced with this difficult problem, as there are few effective treatment options available at their disposal. Research in this field in the last few years has centered on the generation of a new classification system and a symptom score to evaluate patients with. It is expected that better categorization of patients will result in more individualized use of the existing treatment modalities, some of which have recently been tested in a randomized controlled setting. The purpose of this update is to familiarize the reader with the currently accepted concepts in a continuously evolving area.

The term chronic prostatitis should be considered a misnomer in that the entity may not necessarily be inflammatory or exclusively prostatic in origin. Bearing in mind this caveat, CP can be defined as a clinical syndrome characterized by pain in the perineum, pelvis, suprapubic area or the external genitalia, with a variable degree of voiding and/or ejaculatory disturbance.

Epidemiology

Prostatitis is a significant health problem with prevalence rates of 11-16%. [2],[3] More than 2 million consultations for prostatitis are required every year in the United States [4] and each Canadian urologist treats about 262 such patients every year. [5] Prostatitis is the most common reason for men under 50 to consult a urologist [4] and indeed it generates more physician visits than benign prostatic hyperplasia or prostate cancer in the United States. [6] It has a significant impact on the quality of life (QoL) comparable to active Crohn’s disease or a recent myocardial infarction. [7] Up to 50% of men may be affected by it at some stage of their lives.

Classification

Rather than being a single entity, prostatitis encompasses a spectrum of closely related symptom complexes of varied etiopathogenesis. Any classification of this condition should recognize this fact. Drach et al. were the first to use a systematic approach to the diagnosis and management of patients with symptoms of prostatitis, based on the microscopic examination and cultures of segmented urogenital tract specimens. [10]

A workshop on prostatitis sponsored by National Institutes of Health/National Institute of Diabetes, Digestive and Kidney diseases (NIH/NIDDK) [11] in 1995 agreed on the standard contemporary classification system, which is Shown in [Table - 1].

Aetiopathogenesis

A myriad of etiological factors - some not even involving the prostate gland - have been postulated. The initiator of the inflammatory process could be a local infection, chemical irritation, dysfunctional voiding, intraductal reflux, neuromuscular disturbances or an immunological process. There may be an etiological link between Category III prostatitis and Interstitial cystitis (IC). The pathogenesis is not entirely certain, but the following may be a possible mechanism. Regardless of the triggering factor, the resultant inflammatory process causes tissue edema and increased intra-prostatic pressure leading to local hypoxia and varied mediator-induced tissue damage. This leads to altered neurotransmission in sensory nerve fibers thereby resulting in the pain and other symptoms associated with the condition.

Infection

Category I and II prostatitis are caused by bacterial infection. The role of infection in Category III prostatitis is not established although cryptic, non-culturable organisms may be responsible.

Bacteria can be isolated preferentially from an expressed prostatic secretion (EPS) or a post-prostatic massage urine specimen rather than from the mid-stream urine (MSU) sample [12] or can be demonstrated on the prostatic biopsy specimen. [13],[14] Common pathogens are aerobic gram-negative bacteria and gram-positive cocci including enterococci and staphylococci. Several other anterior urethral commensals can also cause prostatitis under special circumstances. [8]

In Category III prostatitis, although absence of bacterial infection is inherent in the definition, numerous investigators have proposed possible infection with atypical or fastidious organisms. [13],[15] Identification of bacterial DNA [16] and clinical improvement sometimes seen with antibiotic treatment [17] in this group provide justification for the trial of antibiotic treatment in these patients despite the lack of laboratory-proven infection.

Lack of uniformity in response to antibacterial treatment and the inability to consistently isolate any pathogenic organisms in the appropriate specimens in addition to the difficulties in determining the respective roles of commensal versus virulent organisms have led to the search for other etiological factors.

Dysfunctional high-pressure voiding

The NIH classification emphasized genitourinary pain as the main characteristic of CP. Pain and the lower urinary tract symptoms associated with CP are by no means specific to the condition and may be caused by either an anatomic or physiological cause of lower urinary tract obstruction such as bladder neck stenosis, [18] urethral stricture, detrussor sphincter dyssynergia [19] or a dysfunctional voiding pattern. [20] Video pressure flow studies with synchronous electromyography of external sphincter have demonstrated decreased flow rate and increased maximal urethral closure pressure. This was observed in both Category IIIA and IIIB patients. [21],[22] This explains why some of these patients respond favorably to the use of ?-blockers. [21]

Intraprostatic ductal reflux

Crystallographic analysis of prostatic calculi has shown them to be made exclusively of urinary constituents [23] and high levels of urate and creatinine have been found in EPS. [24] This suggests intraprostatic ductal reflux as another possible etiological factor in CP. As a result of urine reflux, chronic inflammation and tissue edema may lead to voiding disturbances with further reflux of urine perpetuating a vicious cycle.

Autoimmunity

Several authors [25],[26] have suggested the inflammation in CP to be caused by an autoimmune process or induced by an unknown antigen. Elevated levels of pro-inflammatory cytokines [25] are present in seminal plasma in patients with Category III prostatitis. Shoskes et al., [27] also found low levels of the anti-inflammatory cytokine IL-10 in men with prostatitis.

Immune response in CP seems to be T-cell mediated with cytotoxic (CD8) T cells predominating over helper (CD4) T cells. [28] COX 2 is undetectable in normal tissues but is over-expressed in tissues with inflammation and possibly upregulated by inflammatory cytokines IL-1B and TNF?. NSAIDs blocking COX 1 and 2 have been successfully used in the treatment of CP.

Interstitial cystitis

There are striking similarities in the clinical presentation of CP and IC. Occult infection, “leaky epithelium”, neurogenic inflammation, mast cell activation and autoimmunity have been implicated in the etiology of both conditions. Mastocytosis and elevated urinary histamine levels in patients with CP have been reported and Parsons potassium sensitivity test has been shown to be positive in over 80% of Category IIIA prostatitis. A trial of Pentosan polysulfate in Category IIIA prostatitis showed a significant difference in the symptom scores and there is a case for more extensive evaluation of the role of agents to restore the epithelial integrity. [29]

Neuromuscular problem

One of the several hypotheses suggests that chronic pain in CP is neuropathic in character and there is a neuromuscular etiology for both Type IIIA and IIIB prostatitis. Type IIIB prostatitis may be a manifestation of reflex sympathetic dystrophy. [30]

Neurogenic inflammation is a process by which nerves may secrete mediators producing local inflammation and /or hyperalgesia. This role of neurogenic inflammation in Category III prostatitis has not been extensively studied. However, symptomatic improvement with intravesical instillation of substances like dimethylsulfoxide [31] suggests that it may play a role in the symptomatic exacerbation in some patients.

Clinical Presentation and Evaluation

As mentioned at the outset, the symptoms of CP are non-specific and there is great overlap between this condition and other causes of lower urinary tract dysfunction. By definition, the symptoms must have been present for at least three months, though in practice, the patients have usually had them for several years. Waxing and waning of symptoms is a common occurrence.

Chronic prostatitis is essentially a diagnosis of exclusion. Thus the evaluation should aim at excluding other possible causes for the patients’ symptoms such as benign prostatic hyperplasia, urethral stricture, urinary infection etc. and a recommended workup is shown in [Table - 2].

Once these competing conditions have been excluded, the evaluation should be carried out using the National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) [Table - 3], which is a validated tool generated from the NIH/ NIDDK workshop and recommended for use in clinical practice as well as research. [11]

The NIH-CPSI examines the three main domains of prostatitis namely pain, urinary symptoms and QoL. It is a nine-item questionnaire that is simple, easy and quick to administer and should be used to establish the patients’ baseline bother, which should inform the requirement for treatment, to stratify patients on the basis of their predominant symptoms and accordingly to select the best treatment and to monitor the response to treatment.

Diagnosis

The diagnosis is based on symptomatology and localization of organisms and/or leucocytes in segmented urogenital tract specimens. Of all evaluation methods, the gold standard is the four glass test proposed by Meares and Stamey. [32] It involves obtaining the following specimens for microscopy and culture - the first voided 5-10 ml urine (VB1), midstream urine (VB2), pure prostatic secretion expressed by prostatic massage (EPS) and the first voided 5-10 ml urine after prostatic massage (VB3). The findings of organism(s) with or without WBCs, WBCs without organisms and neither WBCs nor organisms in EPS and/or VB3 indicate a diagnosis of Category II, IIIA and IIIB prostatitis respectively.

A less tedious, time-consuming and expensive but almost equally effective modification of the four glass test, the pre- and post-massage test (PMPT), has been proposed by Nickel. [33] The PMPT involves microscopy and culture of pre- and post-prostatic massage urine sample with a positive post-massage sample indicating the possibility of CP.

Conclusion

In summary, CP is a common problem affecting relatively younger men. It is characterized by a variable mix of pain, urinary and ejaculatory symptoms. The etiology is multifactorial. Diagnosis is based on symptoms and localization tests, which also provide the basis for classification. There are multiple options for treatment, which should be used according to the individual merit of each case to achieve what may often be only symptom control rather than eradication.

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