Prostatitis

Prostatitis is any form of inflammation of the prostate gland. Because women do not have a prostate gland, it is a condition only found in men.

Prostatitis may account for up to 25 percent of all office visits by young and middle-age men for complaints involving the genital and urinary systems.

Signs and symptoms
Inflammation of the prostate leads to pain, often during voiding but also in back and rectum. Frequent urination and increased urgency may suggest a cystitis (bladder inflammation). Ejaculation may be painful, as the prostate contracts during emission of semen, although nerve- and muscle-mediated post-ejaculatory pain is more common, and a classic sign of CP/CPPS.

Diagnosis
If prostatitis is suspected, urinalysis may show white blood cells, red blood cells, nitrite positivity and microorganisms. This is mainly so in acute prostatitis and asymptomatic inflammatory prostatitis (see below). In the other types, urinalysis may be unhelpful.

Prostate specific antigen levels may be elevated, although there is no malignancy. In acute prostatitis, a full blood count reveals increased white blood cells. Sepsis from prostatitis is very rare, but may occur in immunocompromised patients; high fever and malaise generally prompt blood cultures, which are often positive in sepsis.

Experimental tests that could be useful in the future include PCR to detect unculturable bacteria and tests to measure semen and prostate fluid cytokine and endotoxin levels.

Classification
There are four forms of prostatitis:
 * Acute prostatitis (bacterial)
 * Chronic bacterial prostatitis
 * Chronic prostatitis/chronic pelvic pain syndrome/Pelvic Myoneuropathy
 * Asymptomatic inflammatory prostatitis

Acute prostatitis
Acute prostatitis is relatively easy to diagnose due to its symptoms that suggest infection. Men with this disease often have chills, fever, pain in the lower back and genital area, urinary frequency and urgency often at night, burning or painful urination, body aches, and a demonstrable infection of the urinary tract, as evidenced by white blood cells and bacteria in the urine. Common bacteria are E. Coli, Klebsiella, Proteus, Pseudomonas, Enterobacter, Enterococcus, Serratia, and Staphylococcus aureus. Treatment is with appropriate antibiotics, such as ciprofloxacin and doxycycline if prostatitis is caused by ureaplasma or mycoplasma.

Chronic bacterial prostatitis
Chronic bacterial prostatitis (category II in the NIH classification system) is defined as recurrent urinary tract infections in men that originates from a chronic infection in the prostate. In between symptomatic infections, there are bacteria in the prostate but usually no symptoms. The prostate infection is diagnosed by culturing urine as well as prostate fluid (expressed prostatic secretions or EPS) which are obtained by the doctor doing a rectal exam and putting pressure on the prostate. If no fluid is recovered after this prostatic massage, a post massage urine should also contain any prostatic bacteria.

Therapy requires prolonged courses (4-8 weeks) of antibiotics that penetrate the prostate well. These include quinolones (ciprofloxacin, levofloxacin), sulfas (Bactrim, Septra) and macrolides (erythromycin, clarithromycin). Persistent infections may be helped by the use of alpha blockers (tamsulosin (Flomax), alfuzosin), prostate massage or long term low dose antibiotic therapy. Recurrent infections may be caused by inefficient urination (benign prostatic hypertrophy, neurogenic bladder) or prostatic stones.

Chronic prostatitis/Chronic Pelvic Pain Syndrome/Pelvic Myoneuropathy
According to many researchers, this is a poorly understood form of the disease. It is found in men of any age, with the peak onset age at the 30s; symptoms go away and then return without warning. It can range from mild discomfort to totally debilitating. Chronic prostatitis/chronic pelvic pain syndrome/pelvic myoneuropathy may be inflammatory or non-inflammatory. In the inflammatory form, urine, semen, and other fluids from the prostate show no evidence of a known infecting organism. In the non-inflammatory form, no evidence of inflammation, including infection-fighting cells, is present.

Theories behind the disease include autoimmune and neurogenic inflammation. In the latter, dysregulation of the local nervous system due to past traumatic experiences or an anxious disposition and chronic albeit unconscious pelvic tensing lead to inflammation that is mediated by substances released by nerve cells (such as substance P). The prostate (and other areas of the genitourinary tract: bladder, urethra, testicles) can become inflamed by the action of the chronically activated pelvic nerves on the mast cells at the end of the nerve pathways. Similar stress-induced genitourinary inflammation has been shown experimentally in other mammals.

Due to the dysfunction of the pelvic floor muscles, sufferers frequently report that they cannot sit continuously for even a moderate amount of time.

Various studies have shown increases in markers for inflammation such as elevated levels of cytokines, myeloperoxidase, and chemokines.

A September 2003 study by some of the world's top prostatitis researchers produced the seminal finding that normal men have slightly more bacteria in their semen than men with chronic prostatitis/pelvic myoneuropathy. It also showed the traditional Stamey 4-glass test to be invalid for diagnosis of this disorder, and that inflammation cannot be localized to any particular area of the lower GU tract.

Prostatitis researcher Dr Anthony Schaeffer commented in the editorial of The Journal of Urology (2003; 169(2):597-598) that: "It is well recognized that even if pathogenic bacteria are present in the prostate, as in men with established chronic bacterial prostatitis, they do not cause chronic pelvic pain unless acute urinary tract infection develops. Taken together, these data suggest that bacteria do not have a significant role in the development of the chronic pelvic pain syndrome. The clinical observation that antimicrobial therapy reduces symptomatology in men with chronic pelvic pain syndrome is being tested in a double-blinded NIH controlled study. Since antimicrobials may have anti-inflammatory activity, it is possible that these drugs may benefit the patient by reducing inflammation rather than eradicating bacteria."

A year after making that statement, Dr Schaeffer and his colleagues published studies showing that antibiotics are essentially useless for CP/CPPS/Pelvic Myoneuropathy.

The bacterial infection theory that for so long had held sway in this field was again shown to be unimportant in another 2003 landmark study from the University of Washington team led by Dr Lee and Professor Richard Berger. The study found that one third of both normal men and patients had equal counts of similar bacteria colonizing their prostates.

Since the publication of these studies, the focus has shifted from infection to neuromuscular and psychological etiologies for chronic prostatitis (CP/CPPS or pelvic myoneuropathy).

Asymptomatic inflammatory prostatitis
There is no pain or discomfort but there are white blood cells in the semen or in a biopsy specimen. Doctors usually find this form of prostatitis when looking for causes of infertility or testing for prostate cancer.

Role of unculturable bacteria in CPPS
There have been questions regarding the role of unculturable/ultra-fastidious organisms in prostatitis. A team led by Keith Jarvi reported the isolation of flavobacteria, proteobacteria and paenibacillus at AUA 2001, and although this was never published in any peer-reviewed journal, an item about it was published in Urology Times -  http://www.prostatitis.org/utnewbact.pdf. Subsequent PCR studies failed to replicate these findings.

Non-Bacterial prostatitis as a form of interstitial cystitis
Some researchers have suggested that non-bacterial prostatitis is a form of interstitial cystitis.Some studies have reported that elmiron is effective in treating non-bacterial prostatitis. A large multicenter prospective randomized controlled study however did not show that Elmiron was statistically significantly better than placebo in treating the symptoms of chronic prostatitis (Journal of Urology 2005 Apr;173(4):1252). Other therapies shown more effective in interstitial cystitis than Elmiron, such as quercetin and Elavil, can help with chronic prostatitis.

Therapy
Antibiotics are the first line of treatment in acute prostatitis, which is classified as a medical emergency. In chronic bacterial prostatitis, prolonged high-dose courses of antimicrobials, typically Ciprofloxacin, are often attempted to eradicate infection.

For chronic nonbacterial prostatitis (pelvic myoneuropathy or CP/CPPS), which makes up the vast majority of men diagnosed with "prostatitis", a treatment called "the Stanford Protocol", developed by Stanford Professor of Urology Rodney Anderson and psychologist David Wise around the year 2000, has become prominent. This is a combination of medication (using tricyclic antidepressant and benzodiazepines), psychological therapy (paradoxical relaxation, a type of progressive relaxation technique developed by Edmund Jacobson during the early 20th century), and physical therapy (Myofascial Trigger Point Therapy on Pelvic Floor and Abdominal muscles, and also yoga type exercises with the aim of relaxing pelvic floor and abdominal muscles).

Some patients report that the use of a biofeedback machine to relearn how to control pelvic floor muscles is useful, although the Stanford Protocol does not specifically recommend this.

The current line of thinking is that antibiotics resolve acute prostatitis infections in a very short period of time. The rather rare entity (<5% of patients with prostate-related non-BPH LUTS) of chronic bacterial prostatitis usually yields to long and repeated courses of antimicrobials, but there is often a structural abnormality that acts as a reservoir for infection in these cases.

The bulk of prostatitis patients fall into the Chronic Pelvic Pain Syndrome or Pelvic Myoneuropathy category, where there is no initial trigger other than anxiety (often with an element of Obsessive Compulsive Disorder or other anxiety-spectrum problem). This leaves the balance of the pelvic area in a sensitized condition resulting in a loop of muscle tension and heightened neurological feedback (neural wind-up). Current protocols largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as Trigger Points), physical therapy to the area, and progressive relaxation therapy to reduce causative stress.

Anecdotal evidence suggests that food allergies and intolerances may have a role in exacerbating CP/CPPS, perhaps through mast cell mediated mechanisms. Specifically patents with gluten intolerance or celiac disease report severe symptom flares after sustained gluten ingestion. Patients may therefore find an exclusion diet helpful in lessening symptoms by identifying problem foods.

A Japanese immunomodulator called suplatast tosilate has been studied in open pilot studies in CPPS and has been found to be effective.Double-blind placebo controlled studies are needed.Suplatast tosilate is currently approved in Japan for the treatment of allergies and asthma.

Alpha blockers (tamsulosin, alfuzosin) have been shown in randomized placebo controlled trials to be helpful for many men with CPPS. Duration of therapy needs to be at least 3 months.

Quercetin has shown effective in a randomized placebo controlled trial in chronic prostatitis but the study has been criticized because of small numbers. Subsequent studies showed that quercetin reduces inflammation and oxidative stress in the prostate. Bee Pollen (Cernilton) has also been shown effective in small studies but the active therapeutic constituent has not been isolated.