Chronic prostatitis/chronic pelvic pain syndrome
|Chronic nonbacterial prostatitis|
Chronic nonbacterial prostatitis or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a pelvic pain condition in men, and should be distinguished from other forms of prostatitis such as chronic bacterial prostatitis and acute bacterial prostatitis. This condition was formerly known as prostatodynia (painful prostate). CP/CPPS and interstitial cystitis are sometimes referred to jointly as "UCPPS" (urologic chronic pelvic pain syndrome).
- 1 Signs and symptoms
- 2 Cause
- 3 Diagnosis
- 4 Treatment
- 5 Epidemiology
- 6 Prognosis
- 7 Research
- 8 Society and culture
- 9 References
- 10 External links
Signs and symptoms
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pelvic or perineal pain without evidence of urinary tract infection, lasting longer than 3 months, as the key symptom. Symptoms may wax and wane. Pain can range from mild to debilitating. Pain may radiate to the back and rectum, making sitting uncomfortable. Pain can be present in the perineum, testicles, tip of penis, pubic or bladder area. Dysuria, arthralgia, myalgia, unexplained fatigue, abdominal pain, constant burning pain in the penis, and frequency may all be present. Frequent urination and increased urgency may suggest interstitial cystitis (inflammation centred in bladder rather than prostate). Post-ejaculatory pain, mediated by nerves and muscles, is a hallmark of the condition, and serves to distinguish CP/CPPS patients from men with BPH or normal men. Some patients report low libido, sexual dysfunction and erectile difficulties.
A 2016 review paper found that although the peripheral nervous system is responsible for starting the condition, the central nervous system (CNS) is responsible for continuing the pain even without continuing input from the peripheral nerves.
Nerves, stress and hormones
The symptoms of CP/CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological, and endocrine systems.
Theories behind the disease include stress-driven hypothalamic-pituitary-adrenal axis dysfunction and adrenocortical hormone (endocrine) abnormalities, and neurogenic inflammation. In the latter two categories, dysregulation of the local nervous system due to past trauma, infection 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. However, there is no correlation between inflammation on histological examination of the prostate and the National Institutes of Health Chronic Prostatitis Symptom Index.
The bacterial infection theory that for so long had held sway in this field was shown to be unimportant in a 2003 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. This view was endorsed by Dr Anthony Schaeffer, Professor and Chairman of the Department of Urology at Northwestern University, in a 2003 editorial of The Journal of Urology, in which he stated that "...these data suggest that bacteria do not have a significant role in the development of the chronic pelvic pain syndrome", and a year later with his colleagues he published studies showing that antibiotics are essentially useless for CP/CPPS. Since the publication of these studies, the research focus has shifted from infection to neuromuscular, behavioral, psychological, and genetic cause for UCPPS (CP/CPPS and IC/PBS), where the interplay between the lower urinary tract and other physiological systems is stressed. UCPPS is now studied as a systemic disorder. In support of this approach, a 2005 study showed that stress is correlated to Cat III prostatitis.
Overlap with BPS/IC
Some researchers have suggested that CPPS is a form of bladder pain syndrome/interstitial cystitis (BPS/IC). In 2007 the NIDDK began to group IC/PBS and CP/CPPS under the umbrella term Urologic Chronic Pelvic Pain Syndromes (UCPPS). Therapies shown to be effective in treating IC/PBS, such as quercetin, have also shown some efficacy in CP/CPPS. Recent research has focused on genomic and proteomic aspects of the related conditions.
Patients may experience pain with bladder filling, which is also a typical sign of IC.
The ambient temperature appears to play a role as cold is frequently reported as causing symptom aggravation and heat is often reported to be ameliorating. It appears that cold is one of the factors that can trigger a process resulting in CP/CPPS. Cold also causes aggravation of symptoms and can initiate a relapse. A survey showed that the occurrence of prostatitis symptoms in men living in northern Finland —a cold climate—is higher than that reported in other parts of the world. This could be partly caused by the cold climate.
Anecdotal evidence suggests that food allergies and intolerances may have a role in exacerbating CP/CPPS, perhaps through mast cell mediated mechanisms. There is also some evidence of an association between urologic pain syndromes, such as IC/BPS and CP/CPPS, with non-celiac gluten sensitivity in some patients. Patients may therefore find an elimination diet helpful in lessening symptoms by identifying problem foods. Studies are lacking in this area.
There are no definitive diagnostic tests for CP/CPPS. This is a poorly understood disorder, even though it accounts for 90–95% of prostatitis diagnoses. It is found in men of any age, with the peak incidence in men aged 35–45 years. CP/CPPS may be inflammatory (Category Ⅲa) or non-inflammatory (Category Ⅲb), based on levels of pus cells in expressed prostatic secretions (EPS), but these subcategories are of limited use clinically. In the inflammatory form, urine, semen, and other fluids from the prostate contain pus cells (dead white blood cells or WBCs), whereas in the non-inflammatory form no pus cells are present. Recent studies have questioned the distinction between categories Ⅲa and Ⅲb, since both categories show evidence of inflammation if pus cells are ignored and other more subtle signs of inflammation, like cytokines, are measured.
In 2006, Chinese researchers found that men with categories Ⅲa and Ⅲb both had significantly and similarly raised levels of anti-inflammatory cytokine TGFβ1 and pro-inflammatory cytokine IFN-γ in their EPS when compared with controls; therefore measurement of these cytokines could be used to diagnose category Ⅲ prostatitis. A 2010 study found that nerve growth factor could also be used as a biomarker of the condition.
For CP/CPPS patients, analysis of urine and expressed prostatic secretions for leukocytes is debatable, especially due to the fact that the differentiation between patients with inflammatory and non-inflammatory subgroups of CP/CPPS is not useful. Serum PSA tests, routine imaging of the prostate, and tests for Chlamydia trachomatis and Ureaplasma provide no benefit for the patient.
Extraprostatic abdominal/pelvic tenderness is present in >50% of patients with chronic pelvic pain syndrome but only 7% of controls. Healthy men have slightly more bacteria in their semen than men with CPPS. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS. By 2000, the use of the four-glass test by American urologists was rare, with only 4% using it regularly.
Experimental tests that could be useful in the future include tests to measure semen and prostate fluid cytokine levels. Various studies have shown increases in markers for inflammation such as elevated levels of cytokines, myeloperoxidase, and chemokines.
Some conditions have similar symptoms to chronic prostatitis: bladder neck hypertrophy and urethral stricture may both cause similar symptoms through urinary reflux (inter alia) and can be excluded through flexible cystoscopy and urodynamic tests.
A distinction is sometimes made between "IIIa" (Inflammatory) and "IIIb" (Noninflammatory) forms of CP/CPPS, depending on whether pus cells (WBCs) can be found in the expressed prostatic secretions (EPS) of the patient. Some researchers have questioned the usefulness of this categorisation, calling for the Meares–Stamey four-glass test to be abandoned.
In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) began using the umbrella term Urologic Chronic Pelvic Pain Syndromes (UCPPS), for research purposes, to refer to pain syndromes associated with the bladder (i.e. interstitial cystitis/painful bladder syndrome, IC/PBS) and the prostate gland (i.e. chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS).
Older terms for this condition are "prostatodynia" (prostate pain) and non-bacterial chronic prostatitis.
UPOINT symptom classification
A classification system called "UPOINT" was developed by urologists Shoskes and Nickel to allow clinical profiling of a patient's symptoms into six broad categories:
- Urinary symptoms
- Psychological dysfunction
- Organ-specific symptoms
- Infectious causes
- Neurologic dysfunction
- Tenderness of the pelvic floor muscles
The UPOINT system allows for individualized and multimodal therapy.
Some protocols focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points) including digital intrarectal massage, physical therapy to the area and progressive relaxation therapy to reduce causative stress. A device, that is typically placed in the rectum, has also been created for use together with relaxation. This process has been called the Stanford protocol or the Wise-Anderson protocol. The American Urological Association in 2014 listed manual physical therapy as a second line treatment. Kegel exercises are not recommended.
- Treatment with antibiotics is controversial. Some have found benefits in symptoms, while others have questioned the utility of a trial of antibiotics. Antibiotics are known to have anti-inflammatory properties and this has been suggested as an explanation for their partial efficacy in treating CPPS. Antibiotics such as fluoroquinolones, tetracyclines and macrolides have direct anti-inflammatory properties in the absence of infection, blocking inflammatory chemical signals (cytokines) such as interleukin-1 (IL-1), interleukin-8 and tumor necrosis factor (TNF), which coincidentally are the same cytokines found to be elevated in the semen and EPS of men with chronic prostatitis. The UPOINT diagnostic approach suggests that antibiotics are not recommended unless there is clear evidence of infection.
- The effectiveness of alpha blockers (tamsulosin, alfuzosin) is questionable in men with CPPS. A 2006 meta-analysis found that they are moderately beneficial when the duration of therapy was at least 3 months.
- An estrogen reabsorption inhibitor such as mepartricin improves voiding, reduces urological pain and improves quality of life in patients with chronic non-bacterial prostatitis.
- Therapies that have not been properly evaluated in clinical trials although there is supportive anecdotal evidence include gabapentin, benzodiazepines and amitriptyline.
The annual prevalence in the general population of chronic pelvic pain syndrome is 0.5%. 38% of primary care providers, when presented with a description of a man with CPPS, indicate that they have never seen such a patient. However, the overall prevalence of symptoms suggestive of CP/CPPS is 6.3%. The role of the prostate was questioned in the cause of CP/CPPS when both men and women in the general population were tested using the (1) National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) —with the female homologue of each male anatomical term used on questionnaires for female participants— (2) the International Prostate Symptom Score (IPSS), and (3) additional questions on pelvic pain. The prevalence of symptoms suggestive of CPPS in this selected population was 5.7% in women and 2.7% in men, placing in doubt the role of the prostate gland. New evidence from 2008 suggests that the prevalence of CP/CPPS is much higher in teenage males than once suspected.
In recent years, the prognosis for CP/CPPS has improved with the advent of multimodal treatment, phytotherapy, protocols aimed at quieting the pelvic nerves through myofascial trigger point release, anxiety control and chronic pain therapy.
In a preliminary 2005 open label study of 16 treatment-recalcitrant CPPS patients, controversial entities known as nanobacteria were proposed as a cause of prostatic calcifications found in some CPPS patients. Patients were given EDTA (to dissolve the calcifications) and 3 months of tetracycline (a calcium-leaching antibiotic with anti-inflammatory effects, used here to kill the "pathogens"), and half had significant improvement in symptoms. Scientists have expressed strong doubts about whether nanobacteria are living organisms, and research in 2008 showed that "nanobacteria" are merely tiny lumps of abiotic limestone.
The evidence supporting a viral cause of prostatitis and chronic pelvic pain syndrome is weak. Single case reports have implicated herpes simplex virus (HSV) and cytomegalovirus (CMV), but a study using PCR failed to demonstrate the presence of viral DNA in patients with chronic pelvic pain syndrome undergoing radical prostatectomy for localized prostate cancer. The reports implicating CMV must be interpreted with caution, because in all cases the patients were immunocompromised. For HSV, the evidence is weaker still, and there is only one reported case, and the causative role of the virus was not proven, and there are no reports of successful treatments using antiviral drugs such as aciclovir.
Due to the concomitant presence of bladder disorders, gastrointestinal disorders and mood disorders, research has been conducted to understand whether CP/CPPS might be caused by problems with the hypothetical bladder-gut-brain axis.
Research has been conducted to understand how chronic bladder pain affects the brain, using techniques like MRI and functional MRI; as of 2016, it appeared that people with CP/CPPS have increased grey matter in the primary somatosensory cortex, the insular cortex and the anterior cingulate cortex and in the central nucleus of the amygdala; studies in rodents have shown that blocking the metabotropic glutamate receptor 5, which is expressed in the central nucleus of the amygdala, can block bladder pain.
As of 2018 use of extracorporeal shockwave therapy had been studied as a potential treatment for this condition in three small studies; there were short term improvements in symptoms and few adverse effects, but the medium terms results are unknown, and the results are difficult to generalize due to low quality of the studies.
Society and culture
Notable cases have included:
- John Anderson – Deputy Prime Minister of Australia
- James Boswell – author of Life of Samuel Johnson
- John Cleese – British actor
- Vincent Gallo – movie director
- Glenn Gould – pianist
- John F. Kennedy – President of the United States of America
- Tim Parks – British novelist, translator and author.
- Howard Stern – radio personality
- William Styron – author (Sophie's Choice)
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