Prostatitis and Urethritis
Semir A. S. Al Samarrai
The prostatitis syndrome is of great significance for urologist as has been demonstrated in recent studies dealing with epidemiologic data. A new classification has been suggested. A detailed standardized diagnostic procedure remains mandatory to differentiate the various forms of prostatitis. Though new insights into pathogenic factors have been achieved the genesis of chronic prostatitis often remains uncertain. Treatment options must be considered according to the diagnostic results; however, they are often limited and aimed at improving symptoms. Logically, the therapy of infectious Urethritis should follow a standardized diagnostic procedure, so as to administer antimicrobials effective against the underlying etiologic cause.
Epidemiologic research during the last decade has indicated ‘prostatitis’ to be one of the major medical healthcare problems in urology. Recent data revealed that, in 1985, there were more office visits for protatitis than for BPH or prostate cancer resulting in 2 million office visits per year in the early 1990s and representing the most common urologic diagnosis in men less than 50 years of age.
Traditionally, prostatitis has been classified into four clinical entities: acute bacterial (ABP), chronic bacterial (CBP), non-or a bacterial prostatitis (NBP) and prostatodynia (Pd). Whereas the first three types had widely been accepted as being of inflammatory origin, Pd described a condition when, despite clinical symptoms, neither signs of inflammation nor infection have been recently been diagnosed.
Though they are believed to represent commensals of the anterior urethra, these bacteria may become pathogenic under certain circumstances. Sporadical incidences of Staphylococcus aureus and coagulase-negative staphylococci as well as Neisseria gonorrhea, Mycobacterium tuberculosis, Salmonella, Clostridia, and parasitic or mycotic organisms have been reported. Moreover, immunocompromised states, particularly, particularly HIV infection and AIDS, may well lead to an increase of bacterial forms of prostatitis and to an increasing significance of uncommon pathogens.
The role of Chlamydia trochamatis and mycoplasma, particularly Ureaplasma (U) urealyticum, in some cases of chronic prostatitis remains highly equivocal. Some authors were able to associate the finding of C. trachomatis and high numbers of U. urealyticum in prostatic secretions with the symptomatic disease whereas, in contrast, others did not confirm these results. In patients with NBP, some authors tried to demonstrate Chlamydial infection of the prostate by transrectal biopsy, open surgery and transurethral resection. However, results have remained contradictory. Culture for C. trochamatis or demonstration of the antigen by immunoflourence test was typically negative after transperenial puncture of the prostate. In contrast, after transrectal or transurethral procedures, positive results were obtained, which, unfortunately, did not exclude contamination via prostatic urethra or the rectum. Recently, new techniques (immunoflourescence, in situhybridization, and transmission electron microscopy) have shown evidence of a true infection of the prostate epithelium with C. Trochamatis.
The prostate gland is known to be capable of both a systemic and local immune response to invade pathogens. In acute bacterial prostatitis, serum and prostatic fluid antigen-specific IgG and IgA antibodies against gram-negative pathogens have been found, whereas, in CBP, serum antibodies were not detectable. On the other hand, antigen-specific antibodies were not increased in chronic prostatitis patients with mycoplasmal or chlamydial infection compared to those without evidence of these pathogens. In some cases “nonbacterial prostatitis” may be secondary to nonuropathogenic or cryptic microorganisms. In these cases, the term “nonbacterial” is not fully correct.
- The term “prostatodynia” has always provoked the most confusion. Though being defined by the absence of leukocytes in expressed prostatic secretions (EPS) it has never been validated it has been suggested that this entity may not be related to the prostate but rather to a neuromuscular disorder of the pelvic floor/pereneal neuromuscular unit.
- Finally, the occurrence of asymptomatic inflammation of the prostate noted histologically in BPH specimens, prostate biopsies or detected in EPS during evaluation for other disorders has not been addressed in the traditional nomenclature. This implies on the other hand that “symptomatic” disease should best be defined by a standardized questionnaire.
Therefore, In order to acquire a better definition and understanding of the prostatitis syndrome, a new classification system has recently been proposed by a meeting of the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) (table 1). This new classification system focuses on the clinical and diagnostic problems concerning chronic prostatitis and has become the reference standard for research studies on these diseases and disorders.
ABP, CBP and even more, prostatic abscess are important but uncommon diseases. The most common etiologic causes of bacterial prostatitis are gram-negative pathogens, predominantly strains of Escherichia coli which have been identified in 65-80% of infections. Pseudomonas aeruginosa, Serratia, Klebsiella and Enterobacter aerogenes have been isolated in 10-15%.
Controversies exist regarding the role of gram-positive bacteria as pathogens in bacterial prostatitis. Whereas enterococci may cause bacterial prostatitis and associated recurrent urinary tract infections (UTI), the significance of other gram-positive bacteria is doubtful.
- In bacterial prostatitis, the etiologic relevance of enterococci coagulase-negative staphylococci, Chlamydia and anaerobes has remained unsolved. In patients with an initial diagnosis of bacterial prostatitis and lack of positive cultures in case of symptom recurrence, it is not known whether the pathogen was eradicated (nonbacterial prostatitis). It might well be that due to antimicrobial and immunologic threat, bacteria have formed small microcolonies surrounded by protective coat of extrapolymeric slime (still: bacterial prostatitis) thus sustaining symptoms by plugging prostatic ducts.
- The origin of “nonbacterial prostatitis” has remained even more mysterious. Immunological and autoimmunological factors have been discussed. On the other hand, there has been evidence that in contrast, in chronic prostatitis, a Japanese study group has found a correlation with IgA antibodies specific for C. trachomatis and anti heat shock protein IgA in EPS by immunoblotting (Western Blot).
The role of U. urealyticum is still being discussed. It has been agreed that pathogen counts of <10³ cfu/ml should be judge as normal urethral contamination. Although several studies investigating prostatitis identified this pathogen with chronic idiopathic prostatitis has yet to be confirmed by further immunohistological, immunocytological or molecular biological studies.
Antibody-coated bacteria (ACB) have been described in the ejaculate of patients with CBP in contrast to patients with inflammatory and noninflammatory chronic pelvic pain syndrome (CPPS) or normal controls. A hypothesis of bacteria serving as an antigen atimulus and therby initiating an immunological process that results in (bacterial) prostatitis has been proposed. The known and unknown immunological aspects of chronic prostatitis have recently been re-evaluated (table 2).
Recent data indicate that bacteria may have an etiological role in patients with chronic idiopathic prostatitis after exclusion CBP.
Examination of men experiencing chronic pelvic pain prokaryotic 16s RNA has been found significantly more often in patients with increased leukocyte numbers in their prostatic secretions than those without. These findings suggest that the prostate may harbour microorganisms not detectable by traditional approaches. Even when analyzing transperenial prostate biopsies by traditional culture, Berger et al. demonstrated a significantly higher bacterial isolation, more positive cultures for anaerobic bacteria, higher bacterial counts, and more bacterial species isolation in men with inflammatory cells in their EPS. In patients with Pd, positive cultures of bacteria, mostly coagulae-negative staphylococci, were found in prostatic secretions. However, the significance of these findings remains uncertain for implanting a bacterial etiology in some cases of CPPS and needs further evaluation.
Only in ABP is it possible to establish the diagnosis on clinical grounds: Dysuria, pollakisuria and perineal pain as well as pain during defecation, and even acute urinary retention have been described. Systemic symptoms include fever and shivering rigors. Urosepsis may develop. Digital rectal examination (DRE) is extremely painful due to a markedly tender prostate. The clinical diagnosis of prostatic abscess is based on fluctuation during DRE and imaging procedures, especially transrectal ultrasonography (TRUS) (see following section).
The remaining forms of the prostatitis syndrome can not be differentiated on the basis of their clinical symptoms. They include typical local signs of inflammation, diffuse anogenital symptoms, bladder voiding disturbances, and sexual dysfunction. Chronic pelvic pain has been suggested to be a leading symptom. As there are multidimensional associations to physical and mental health status, a comprehensive symptomatic evaluation appears necessary using appropriate questionnaires with the aim of providing the possibility to ask for typical ‘true’ prostatitis symptoms and to quantify symptom severity.
As clinical symptomatology does not allow a differentiation, the only way to discriminate inflammatory CPPS or CBP from noninflammatory CPPS is the demonstration of leukocytes and lipid-laden macrophages in the case on inflammatory CPPS and CBP. Controversies exist on the criterion number of white blood cells indicative inflammation. The cut off point for inflammatory disease has been suggested at >10 and >15 white blood cells per high power field. When insufficient or no EPS is obtained for analysis, the presence of >10 granulocytes/high power fields in urine after prostatic massage has been proposed to be indicative of inflammation. In some cases, this technique appears to simplify the rationale of diagnostic staining procedures simplify identification. And quantification of leukocytes. Recent data indicate an increased sensitivity to detect inflammation when using a counting chamber.
Laboratory diagnosis of CBP is based on the four-specimen test for bacterial localization. Its principle is to perform sequential quantitative bacteriological cultures of the urethra, bladder urine and prostatic secretions both in EPS and urine after prostatic massage (VB 3). The diagnosis is confirmed when quantifiable pathogenic bacteria can clearly be ascribed to the prostate gland. The growth of only small numbers of bacteria of prostatic fluid is pathognomonic in CBP. There exists no absolute count in cfu/ml to diagnose CBP; instead, the counts of bacteria in the above-mentioned specimens must be compared. Demonstration of bacteria in EPS or VB 3, when the urethra and midstream urine show no growth, is highly suggestive of CBP. Alternatively, a significant increase of a log or more in the bacterial count in the prostatic specimens when compared to urethral and bladder specimens is considered diagnostic.
The hallmark of CBP is hampered by a high bacterial count in the midstream urine. In these cases, 3 days ‘administration of nitrofurantoin prior to the performance of the ‘four-specimens test’ has been recommended. Nitrofurantoin is able to clear the midstream urine pathogens, whereas the number of bacteria in prostatic secretions is untouched due to the inability of nitrofurantoin to penetrate prostatic tissue.
An ejaculate analysis is done to obtain further information about whether the prostate is part of a generalized infection of the male accessory sex glands. After exclusion of urethritis and bladder infection, the presence of >10 peroxidase-positive white blood cells/ml ejaculate indicates an inflammatory process. In these cases a culture should be performed. A concentration of >10³ cfu/ml of urinary tract pathogens in the ejaculate is regarded as a significant finding. It must be kept in mind that the ejaculate analysis does not allow a definitive localization of the inflammatory process, because the ejaculate represents a mixture of different genital secretions and is usually contaminated by pathogens from the anterior urethra.
In patients with inflammatory CPPS, increased perioxidase-positive leukocytes and PMN-elastase levels seems to be present as compared to noninflammatory CPPS and controls. Recently an increase in the concentration of interleukin-6 in seminal plasma has been described as indicator of accessory gland inflammation. In CBP, a significant bacteriospermia with the same pathogen as isolated by the four-specimen technique is demonstrable in about 50% of cases.
Some authors have reported on poor sperm quality (reduced sperm count, abnormal motility, morphologic defects), but these results remain controversial due to a possibly imprecise definition of the inflammatory patient groups.
SCREENING OF BLADDER VOIDING
The evaluation of the bladder emptying process is accepted to be a mandatory diagnostic step in patients with prostatitis-like symptoms. However, discrepancies exist about the prevalence of urodynamic abnormalities changes in approximately 33-45% of patients following the analysis of urinary flow patterns; other authors demonstrated a significant bladder outlet obstruction in only a few patients as assessed by a complete urodynamic evaluations.
TRUS has proven the best sonographic approach to visualize the prostate gland in case of acute or chronic inflammation. Today, 7.5 to 10-MHz transducers are used as standard.
TRUS has led to an increased sensitivity in detecting prostatic abscess and has turned out to be the preferable imaging procedure as it is the most cost-effective, has a better contrast resolution than CT/MRI, and is easily accessible. Typical signs of prostatic abscess are particularly a hypo-or anechoic area with think walls or perilocal edema.
Repeated examinations allow an exact observation of the success of therapeutical strategies. In case of drainage procedures, TRUS should be performed for correct placement of the needle.
CHRONIC bacterial prostatitis
A number of sonographic abnormalities have been used to identify patients with chronic prostatitis in contrast to normal controls. Some authors tried to compare sonographic irregularities to histological findings obtained by biopsy. However, most of these studies have been performed with old 3.5 to 4-MHz scanners which can not match the images of today’s high resolution transducers. Thus, these results remain questionable. The German Prostatitis Study Group demonstrated a significantly higher prevalence of prostatic calculi, particularly diffuse calcifications, in patients with inflammatory vs. noninflammatory CPPS. These results gain clinical importance, because infected prostatic stones, similar to kidney stone, may be impregnated with pathogens that are shielded from non antibacterial agents and thereby lead to recurrent prostatitis as well as to relapsing UTI.
Seminal vesicle asymmetry in case of inflammation is also a frequent finding. Asymmetry may be due to enlargement of one vesicle as consequences of ductal obstruction or due to shrinking on the part of one infected vesicle.
Once diagnosed, treatment consists of empiric therapy with antibiotics in combination with alpha 1-adrenergic-antagonist and herbal 5-reductase inhibitors.
Correspondence:Prof. Dr. SEMIR AHMED SALIM AL SAMARRAI
Professor Doctor of Medicine-Urosurgery, Andrology, and Male Infertility
Dubai Healthcare City, Dubai, United Arab Emirates.
Mailing Address: Dubai Healthcare City, Bldg. No. 64, Al Razi building, Block D,
2nd floor, Dubai, United Arab Emirates, PO box 13576