CP/CPPS

Background
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a condition which affects men of all ages. It has been estimated that more than 25% of men will be affected at some point in their lifetime (Lipsky 2010). Primary symptoms consist of chronic testicular and/or perineal pain (Zermann 1999, Alexander 1996), which usually self-resolve without treatment a few months to a few years after onset (Rosette 1993). Other common symptoms include lower back pain, lower abdomen pain, loss of erectile function, and post-ejaculatory pain most commonly located in the penis (Ilie 2007). Symptoms persist indefinitely in some men. Since this condition is only defined by symptoms, other conditions which have similar symptoms should be ruled out using lab tests prior to making a CP/CPPS diagnosis, including the four most common sexually transmitted microbes: Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and Trichomonas vaginalis

Though CP/CPPS has been studied for several decades by the research community, no causative microorganism has been strongly linked with this condition. Cell cultures and various other tests from urine, prostatic secretion and semen samples are completely negative in more than half of CP/CPPS patients (Nickel 2003). Etiological hypotheses involve either microorganisms undetectable using current tests or an autoimmune disease.

No treatment has been shown to be effective in curing CP/CPPS through double blind clinical trials. Anti-bacterial drugs have been extensively tested in these trials, and have broadly been shown to be non-effective (Lipsky 2010). Only a small minority of CP/CPPS cases appear to respond favorably to anti-bacterial drugs. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is the body responsible for researching and publishing guidelines about CP/CPPS in the United States. Their current treatment recommendations are to take warm baths and make dietary changes. All other treatments are deemed unproven, including all drugs and natural supplements.

Evidence of a fungal etiology
Fungal infections of the prostate are considered rare (Wise 2006). While this is a very plausible statement for fungal species that readily grow in culture (Rosette 1993), medically important fungi which do not grow in culture (Weber 1994, Paulino 2008Ghannoum 2010, Chabe 2011) have yet to be investigated in relation to diseases of the prostate. As of January 2013, no peer reviewed studies testing the link between fastidious fungal infections and diseases of the prostate could be found. Similarly, no peer reviewed double blind clinical trials using anti-fungal drugs to treat CP/CPPS patients could be found in the scientific literature. However, there are many leads which support a fungal involvement in CP/CPPS:

1. A study recently conducted in Egypt found that the anti-fungal drug fluconazole greatly improved the symptoms of CP/CPPS patients. While this study was published in a peer reviewed journal, it did not include a control group, so its results cannot be used to reach a definite conclusion (Fouad Kotb 2013).

2. Dr. Jordan Dimitrakov studied the effect of anti-fungal drugs on 147 chronic prostatitis patients, and noticed a marked improvement in symptoms (Dimitrakov 1999). There was no control group, and this study was only presented as a poster at a conference (it was not published in a peer reviewed journal). Dr. Dimitrakov is now a well respected researcher studying autoimmune pathways in CP/CPPS.

3. Dr. Antonio Feliciano confirmed in a private communication that administering anti-fungal drugs reduces the number of leukocytes in the prostatic secretion of chronic prostatitis patients (unpublished results).

4. The HLA-DRB1 gene is a key element of the immune system. The 1501 allele of this gene has been associated with an increased risk of granulomatous prostatitis (Alexander 2004), and a significantly decreased risk of life threatening fungal infections (Louie 1999), as well as an increased risk of oversensitivity to environmental fungal antigens (Slavin 2004). Interestingly, granulomatous prostatitis has been associated with antibodies which target intracellular "granules" within prostate epithelial cells (Cohen 2004), while inflammatory foci within the prostate have been shown to form around prostate epithelial cells containing intracellular "granules" of unknown origin (Maksem 1988).

5. Dr. Daniel Shoskes published a peer reviewed article in 2005 in which he described EDTA suppositories (plus antibiotics) as an effective treatment for chronic prostatitis (Shoskes 2005). Unfortunately there was no control group and no further clinical trials with EDTA were conducted. The mechanisms through which EDTA provided relief were not identified. PSP94 is a fungicidal protein secreted by the prostate whose fungicidal activity is greatly enhanced by EDTA's calcium ion sequestrating properties (Edstrom 2012).

6. Dr. Daniel Shoskes reported having experienced chronic prostatitis symptoms for a second time in his life while taking the anti-fungal drug terbinafine for a non-prostate related fungal infection (Shoskes 1999). Since Dr. Shoskes is one of the few CP/CPPS researchers in the world, this form of anecdotal evidence is subject to very little selection bias.

7. Two studies have shown that sinusitis is a major comorbidity of CP/CPPS (Pontari 2005, Clemens 2006). Many CP/CPPS patients report that their sinus symptoms occur (flare-up) at the same time as their prostate symptoms. In 1999, a study was published by Mayo clinic researchers which linked chronic sinusitis with too strong an immune response to fungi present in the respiratory system (Ponikau 1999). Here is an important followup study by the same group (Shin 2004). Note that everyone has fungi in their respiratory system (this is normal since many fungal spores are dispersed in the air): the appearance of symptoms depends on how the immune system reacts to fungi, which is mostly genetically determined.

8. PSP94 is highly fungicidal within the cytosol of prostate epithelial cells that synthesize this protein, yet fungal infections of the prostate are considered rare. Which intracellular fungal pathogen is PSP94 targeting in the prostate? Such pathogenic fungi must exist and reach the prostate, otherwise the fungicidal properties of PSP94 would have not been conserved (over an evolutionary significant time-scale). Men whose prostate secretes low amounts of PSP94 are at much higher risk of prostate cancer (see main page); men whose prostate secretes a non-fungicidal version of PSP94 have BPH (see BPH page). Epidemiologists have been predicting for over a decade the existence a yet-to-be-discovered sexually transmitted infection which is associated with prostate cancer (see the Strickler Goedert hypothesis page). This is supported by reactive arthritis researchers who have long suspected a sexually transmissible etiology, yet no pathogen can be found in many reactive arthritis cases (Butrimien 2006search "sexually acquired reactive arthritis" in Google Scholar for more details). The prevalence of elevated leukocytes in semen/EPS triples between ages 20 and 40, suggesting a sexually transmissible etiology (Nickel 2003Korrovits 2008). Elevated leukocytes are positively associated with CP/CPPS symptoms (odds ratio ~1.25, Nickel 2003). Together, these observations support the existence of a yet-to-be-discovered sexually transmitted fungus which is targeted by PSP94.

There may exist many other leads which link CP/CPPS to fungi. If you know of published evidence which supports or refutes the presence fungi in the prostate, please submit it using the Contact pageI have compiled some case evidence, though this type of evidence must be carefully interpreted as it is subject to severe selection bias.
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