CP/CPPS case evidence, analysis and mechanisms

Please read the main CP/CPPS page before reading further (if you have not done so already).

Case evidence

Case evidence is not a valid scientific proof of causation, though it gives researchers clues as to which types of studies have the potential to reveal hard evidence linking an infectious agent with a disease. While the onset of prostate cancer and BPH are predicted to be linked to sexual activity which occurred decades earlier, CP/CPPS symptoms are expected to be linked to recent sexual activity. CP/CPPS symptoms will develop rapidly after exposure to the yet-to-be-identified STI in some men.

Here are some of the case reports which I have gathered while performing this research. These cases have been selected because they support an infectious etiology for CP/CPPS. Thus, this list is a biased sample of CP/CPPS cases. Click through the Case column to read a detailed report for each case. Particularly interesting cases are in bold.

CaseTransmissibilityAntifungal
drug
Secondary symptomsComment
Andrew Sternick
  Reactive arthritisSymptoms progress to reactive arthritis.
Anon2uSexual (thrush)   
Attila Prazsak
 Reactive arthritisSymptoms progress to reactive arthritis.
Bienonstock
Fluconazole
CFS, IBS 
cg
Itraconazole, fluconazole
BalanitisNon-culturable fungi on glans. Very elevated antibodies to fungi; fungi in the stool; adverse reaction to antibacterial drugs.
damaja23Sexual (thrush)  Progression from epididymitis to prostatitis.
DG Sexual (thrush)ClotrimazoleSinusitis, systemicAntibacterial drugs caused thrush (partner); highly reactive to vaginal fluid of two women.
Dominic Anfiteatro AntifungalBalanitis 
Dr. Daniel Shoskes
Terbinafine 
dsharpSexual (?)
TerbinafineTinea pedis (?)
Symptoms permanently resolved by terbinafine.
Farry
Terbinafine, fluconazole
  
GolfgodSexual   
Graham
NystatinSystemicOral nystatin taken for gastrointestinal condition improved GU symptoms; Dismukes 1990 reports similar effect in women.
greeneSexual (thrush)
Nystatin, fluconazole
 
jefSexual 
 
JimSexual   
John GarstSexual (thrush)NystatinBalanitis, sinusitis
Non-culturable fungi on glans. Oral nystatin improved GU symptoms; Dismukes 1990 reports similar effect in women.
Kirschfeld
 Acetylcysteine
  
MarioSexual (thrush)Nystatin, terbinafineIBS, tinea pedis (?)
MavimanSexual

Rash 
Mike D 
SinusitisSymptoms triggered by certain foods.
NickFungi on skin
KetoconozoleBalanitis, sinusitisNon-culturable fungi.
NolandSexual
KetoconozoleBalanitis, systemicNon-culturable fungi.
Rob
Fluconazole  
scharkeSexual, both ways (thrush)

Tinea cruris 
ShawnSexual 
  
SteveSexual    
ts58Sexual

Balanitis
 
uppSexual   Worst case scenario.
vinculumSexual
Nystatin, fluconazole
Non-culturable fungi.
Wes
AntifungalBalanitis  
Zimmerman
Nystatin Non-culturable fungi.

If you would like to share your case data, please use the Contact page. Feel free to submit anonymously. These are the aspects that are of particular interest:
  1. Did your first symptoms appear in relation to new sexual factors (eg. new partner, start of unprotected sex with existing partner, etc)? Did your first symptoms coincide with anti-bacterial drug usage?
  2. What was the course of your symptoms? Sudden or gradual onset? Did all symptoms appear simultaneously or was there a progression? Typical symptoms include testicular pain and/or prostate/perineal pain, though you may only experience one of these symptoms (Zermann 1999). Other conditions of interest which may have developed simultaneously are chronic fatigue syndrome, fibromyalgia, bladder pain, irritable bowel syndrome, sinusitis and balanitis (red patches on the glans).
  3. Was your partner using anti-bacterial medication shortly before your symptoms developed? When your partner uses anti-bacterials, does she experience vaginal yeast infection symptoms as a side effect? If so, has this always been the case or did this start at a specific age? This is important because anti-bacterial drugs kill naturally occurring bacteria in the vagina which are necessary to prevent fungal growth.
  4. Did you use anti-fungal drugs (Lamisil/Terbinafine, Sporanox/Itraconazole, Nystatin/Fungicidin, etc) for any reason, and did these drugs have an effect on your symptoms? Please respond even if anti-fungal drugs had no effect or worsened your symptoms.
Analysis of the evidence
The case evidence presented on this page is subject to severe selection bias since most cases were "mined" using a search engine, bringing the subject population to about 10 million men. Given this huge pool of potential cases, it is plausible that the only cases reported are those which coincided with a new sexual partner, balanitis, or other factors which suggest a sexually transmissible fungal etiology.

However, four cases which suggest a sexually transmissible fungal etiology were not mined (they were personal contacts, not found with a search engine). These cases have much less selection bias since the pool of potential cases is much smaller (<1000 men), and thus are a more legitimate form of evidence of a fungal cause for CP/CPPS. Together, these four cases, the non-anecdotal evidence presented on the CP/CPPS page, and the evidence linking a fungal infection to other prostate diseases on the main page indicate that at least some CP/CPPS cases are caused by a fungal infection.

The fact that the loss of the fungicidal peptide of PSP94 coincides with BPH, and BPH affects >80% of men suggests that there is a sub-clinical fungal infection affecting the prostates most elderly men. Since CP/CPPS symptoms gradually diminish over a period of many months to many years, it is unlikely that this diminution is due to gradual clearing of the infectious agent; a more plausible explanation is that the infection continues unabated, but the immune system becomes gradually desensitized to fungal antigens. CP/CPPS symptoms and elevated leukocytes in semen/EPS persist indefinitely in some men, which supports the existence of a chronic infection that cannot be cleared by the immune system. Taken together, these facts suggest that BPH and CP/CPPS are likely caused by the same infection.

It is thus plausible that many CP/CPPS cases are caused by a fungal infection. This means the above anecdotal cases would be typical. It also means that the causative fungal organism cannot be cultured on conventional culture media (see John Garst's case and Nick's case, and section 8 of the monograph).

Hypothesized mechanisms
From the evidence I have seen so far, it seems that to get CP/CPPS symptoms one needs to satisfy four conditions (1,2a,2b,2c):
1. Have a chronic sub-clinical genitourinary infection caused by a sexually transmissible fungal species which is usually acquired by men through sexual activity, but transmission is probably not strictly sexual (see Nick's case). BPH prevalence shows that over 80% of elderly men satisfy this condition. This infection is readily transmissible to women (see scharke's case).
2. Have an immune system which is sensitive to the sexually transmissible fungus' antigens at a given point in time.
   a) This has an innate component: immune system has to react (strongly) to the sexually transmissible fungus' antigens (eg. HLA-DRB1*1501 and other similar alleles).
   b) This has an acquired component: immune system has to have "learned" that the sexually transmissible fungus' antigens are linked to infection. This can be triggered by the primary infection (onset of condition 1) or by an unrelated fungal infection which is presenting similar antigens (such a tinea pedis, tinea corporis, sinusitis, fungal overgrowth caused by antibiotics usage, having sex with a partner who has a yeast infection, etc).
   c) This has an activation component: the immune system has to "think" that there is a fungal infection going on right now (this may be triggered by unrelated fungi in the respiratory/digestive tract or elsewhere in the body which is presenting similar antigens).

The onset of CP/CPPS coincides with condition 1 or condition 2b. Relapses coincide with condition 2c. If other medical conditions suspected of being caused by an overactive immune system start quasi simultaneously with CP/CPPS symptoms (or flare-up simultaneously), these other conditions are likely caused by an oversensitivity to similar fungal antigens. Conditions which are known to be associated with CP/CPPS include interstitial cystitis, fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome. No study could be found which investigated if the onset of symptoms or flare-ups occurs simultaneously in CP/CPPS and any of these conditions.

Anti-fungal drugs may:
I. eliminate the genital infection (removing condition 1), though this seems to be a rare occurrence (see dsharp's case).
II. eliminate unrelated fungal infections (removing condition 2c), this appears to be fairly common (see John Garst's case and Dismukes 1990)
III. kill fungi in the prostate or elsewhere, spreading dead fungus debris and causing condition 2c (see Dr. Daniel Shoskes' case).

The immune system of some individuals can be particularly sensitive to fungal antigens, resulting in a strong reaction to yeast, mold or mildew. This means even trace amounts of fungi in or on the body may suffice to trigger inflammation. Anti-fungal drugs are known to cause id reactions, where inflammation appears in apparently non-infected parts of the body (Cheng 2011, Iilkit 2012). It is unclear why such reactions occur, though the immune response to dying fungi is a plausible trigger.

From an evolutionary biology standpoint, the immune system must strike a balance between ignoring the prostatic intracellular fungal infection (since it has no chance of clearing the infection) and efficiently clearing other fungal infections which could prove fatal (Louie 1999). This is a plausible explanation which would justify why condition 2a alleles still exists within the population today, despite negatively affecting many young men.


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