Etiologies of chronic prostatitis

The basic definition characterizing the process of acute prostatitis is the presence of polymorphonuclear leukocytes (PMNL) and macrophages in the glandular ducts, the epithelium and/or the adjacent stroma. As the disease becomes chronic, stromal involvement varies, and increases with the density of intraluminal inflammation. Periglandular accumulation of lymphocytes and monocytes, and occasionally plasma cells characterize the chronic phase of the infection. The inflammation starts from the central periurethral zone and spreads to the  peripheral zone.   

There is little or no correlation between the histological presence of chronic prostatitis and the clinical symptoms. The histological signs of chronic prostatitis also include distortion of the glandular ducts, disruption of the epithelium, atrophy and loss of the secretory activity of the epithelium, and hyperchromasia with polymorphism of the epithelial cell nuclei and cytoplasmic basophilia. These dysplastic changes can be misinterpreted as carcinoma of the prostate if the association with chronic prostatitis is not recognized. The situation can be worsened by changes such as squamous metaplasia, which occurs frequently in the inflamed areas of chronic prostatitis.
A fine-needle aspiration (FNA) method was developed to gage the type and extent of inflammation, but it is contraindicated in cases of acute symptomatic prostatitis due to the risk of sepsis, especially in patients with suppressed immune system.

Microbiological aspects of prostatitis

It is essential to be able to demonstrate bacteria reliably in the EPS, semen or both in order to reach the correct treatment decisions and to ensure a good outcome. Laboratory findings have shown in practice that almost all standard localization cultures are negative and that success in culturing bacteria from EPS is complicated by the presence of inhibitory substances known to exist in prostate secretion and by a history of multiple previous courses of antibiotics.

Clear confirmation of the pathogenicity of bacteria in prostate tissue and/or ducts has been obtained with a group of gram-negative uropathogens including E. coli, Klebsiella spp., Serratia and Pseudomonas spp. There can also sometimes be gram-positive uropathogens such as Enterococcus spp. and Staphylococcus spp. present.

                While acute prostatitis is characterized by polymorphonuclear leukocytic infiltration, the chronic phase of infection in chronic prostatitis is characterized by lymphocytic infiltrate. The degree of infiltration is not proportional to the clinical symptoms. The adjacent edema/collagen tissue formation depends on the nature of the bacteria, the host reaction to the infection, and the duration of the process. While mostly edema is seen in acute prostatitis, as the disease becomes chronic, fibrous collagen tissue will replace the prostatic tissues and later, nodular or symmetrical enlargement of the prostate will take place. Since the dawn of microbiology, repeated attempts have been made to isolate bacteria believed to be the cause of chronic prostatitis. 

                A number of studies implicate specific groups of bacteria but for one reason or another these studies are mostly inconclusive. Whether it was the sample size or the narrow spectrum of bacteria tested, the most these studies were able to establish was an association of a specific bacterium with prostatitis. Both gram negative and gram-positive bacteria have been implicated and are believed to be uropathogens. The anaerobic studies in most instances are hampered by the notorious difficulty encountered in isolating anaerobic bacteria. A number of studies implicate Ureaplasma/Mycoplasma as causative organisms. The same  bacteria believed to cause acute prostatitis, if incorrectly treated, will become the cause for chronic bacterial prostatitis. I will list these bacteria when dealing with acute prostatitis.

                Chlamydia trachomatis has been studied and implicated in a number of studies as well. As I mentioned before, in our clinic over 60% of patients presenting with the diagnosis of chronic prostatitis will reveal elementary bodies of Chlamydia in the smear prepared from a urethral swab. We use the fluorescence antibody technique to identify the elementary bodies. The antiserum is produced in animals and I believe it is more sensitive in detecting the  elementary bodies of Chlamydia than the widely used PCR or nucleic acid amplification technique. My belief stems from the simple observation that after a relatively short antibiotic course, PCR tests can rapidly turn negative while the fluorescence antibody test will still reveal elementary bodies. A persistent positive reading with the antibody test is in synchrony with the clinical course and it turns negative following the resolution of the clinical symptoms. It has been documented that an amplification test used in certain parts of Sweden was unable to identify Chlamydia. Its inability to identify Chlamydia was not due to an actual drop of newly infected cases but rather to Chlamydia’s ability to change its surface antigens targeted by the testing kit. Since the fluorescence antiserum is produced in animals the host is likely to produce antibodies against many surface markers of Chlamydia, thus making the fluorescence antibody technique the gold standard for detecting Chlamydia infection.Unfortunately the test requires an expert to read it, and it is time consuming.

            We believe that the most common cause of chronic prostatitis is a Chlamydia infection that is hardly ever treated properly at the time of the first visit.

              The clinical course of chronic prostatitis cannot be explained well without recalling the lifecycle of Chlamydia trachomatis. The quick response to relatively short courses of antibiotic therapy at the beginning of the infection only eliminates those extracellular elementary bodies that are sensitive to that particular antibiotic. The relatively quick recurrence of the infectious symptoms is best explained by either the fact that bacteria that were not sensitive to the original antibiotic are now selected out and start multiplying even before the first course of antibiotic is finished. The second time around,  therefore there is no symptomatic improvement from the same antibiotic,  even if longer courses are prescribed. The second reason is that most prescribed antibiotics will only affect the extra cellular phase of bacterial growth. The intracellular multiplication and emergence of the reticulate bodies, after a symptom free period of varying length can cause recurring symptoms long after the initial antibiotic therapy is completed.Chlamydia is known to change its antibiotic sensitivity and it will alter its growth rate after exposure to multiple antibiotics. Also, the state of the immune system and host of other factors can influence the effect of Chlamydia on the host’s tissues. As the growth rate of the intracellular forms of Chlamydia diminishes and eventually spore forms develop, the time interval between reoccurrences widens. Chlamydia is uniquely suitable to interact with intracellular nucleotides, thus, as it has been associated with increased female cervical cancer risk,it would not be an unreasonable speculation to associate chronic Chlamydia infection with the development of prostate cancer.

            It is good to remember that Chlamydia trachomatis is not one bacterium.  Within the family an infinite variety of different sub species can be found.  These bacteria differ not only in their size and multiplication rate but they can have different pathogenic potential, including different interaction with the immune system, different antibiotic sensitivity, different speed in developing resistance to antibiotics and different ways of coexisting, irritating or destroying the tissues they infect.

             It is good to remember that Chlamydia trachomatis is not one bacterium.  Within the family an infinite variety of different sub species can be found.  These bacteria differ not only in their size and multiplication rate but they can have different pathogenic potential, including different interaction with the immune system, different antibiotic sensitivity, different speed in developing resistance to antibiotics and different ways of coexisting, irritating or destroying the tissues they infect.