JEANNETTE POTTS, MD* RICHARD E. PAYNE, MD* Glickman Urological Institute, Clinical Instructor, Department of Family and Cleveland Clinic, Cleveland, OH Preventive Medicine, University of California, San Diego, La Jolla, CA Private Practice, North Coast Family Medical Group, Encinitas, CA : , neuromuscular disorder, or pain syndrome? Proper patient classification is key

■ ABSTRACT Prostatitis is a broad term used to describe inflamma- National Institutes of Health tion of the that may be associated with a classification system for prostatitis myriad of lower urinary tract symptoms and symptoms Category I: Acute bacterial prostatitis of sexual discomfort and dysfunction. The condition Category II: Chronic bacterial prostatitis affects 5% to 10% of the male population and is the most common urologic diagnosis in men younger than Category III: Chronic abacterial prostatitis/chronic pelvic 50 years. Prostatitis is classified into four categories, pain syndrome, which is subdivided into IIIA (inflamma- tory) and IIIB (noninflammatory) disease including acute and chronic bacterial forms, a chronic abacterial form, and an asymptomatic form. The bacte- Category IV: Asymptomatic prostatitis (histologic or rial forms are more readily recognized and treated, but andrologic diagnosis) symptoms in most affected men are not found to have an infectious cause. Indeed, chronic abacterial prostati- itancy, and frequency, as well as with sexual dysfunc- tis (also known as chronic pelvic pain syndrome) is tion or discomfort, including , both the most prevalent form and also the least under- painful ejaculation, and postcoital pelvic discomfort; stood and the most challenging to evaluate and treat. adverse sexual effects are reported in approximately This form of prostatitis may respond to non–prostate- half of men with prostatitis.1,2 centered treatment strategies such as physical ther- The International Prostatitis Collaborative Net- apy, myofascial trigger point release, and relaxation work and the National Institutes of Health (NIH) 3 techniques. Because the various forms of prostatitis have established a classification system for prostatitis. call for vastly different treatment approaches, appro- The system’s four categories, which are outlined in the priate evaluation, testing, and differential diagnosis sidebar above, describe acute and chronic infectious forms (NIH categories I and II) as well as the more are crucial to effective management. prevalent forms that have not been correlated with ■ DEFINITION OF THE CONDITION infectious etiologies (NIH categories III and IV). This article places particular emphasis on NIH cate- Prostatitis is defined as painful inflammation of the gory III, chronic abacterial prostatitis/chronic pelvic prostate that is often associated with lower urinary pain syndrome (CPPS), as it is both the most common tract symptoms (LUTS), such as urinary burning, hes- form of prostatitis and the most challenging to evaluate and treat. Because NIH category IV prostatitis describes * Dr. Potts reported that she has no financial relationships that pose a potential an asymptomatic form of this inflammatory disease, it is conflict of interest with this article. Dr. Payne reported that he has received a diagnosis unlikely to be addressed in the primary care honoraria, consulting fees, and an educational grant from Eli Lilly/ICOS for teaching/speaking, consulting, and contracted research; honoraria and con- setting and is therefore addressed only briefly here. sulting fees from Sanofi-Aventis for teaching/speaking and advisory board ■ membership; consulting fees from Boehringer Ingelheim for teaching/speaking PREVALENCE AND SOCIAL IMPLICATIONS and consulting; consulting fees from Pfizer, Johnson & Johnson, and Thomson Population-based estimates of the prevalence of pros- Healthcare for consulting; and consulting fees from Reliant Pharmaceuticals for serving on an advisory committee. He also reported having an ownership tatitis in the general male population range from 5% to interest in and receiving consulting fees from MedVantx. 10%.4,5 In one study of health care professionals, the

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self-reported incidence of prostatitis was approxi- in prostatic fluid, even after appropriate antimicrobial mately 16%.6 Prostatitis is the most common diagno- therapy. The organisms can be cultured and localized sis coded in outpatient urologic consultations in men to the prostate even in the setting of normal midvoid younger than 50 years.7 However, bacterial prostatitis urinalysis and negative midvoid urine cultures. represents merely 5% to 10% of cases.8 Recent inter- Chronic bacterial prostatitis is not usually suspected national collaborations reveal comparable estimated until a man experiences recurrent urinary tract infec- prevalence rates in other populations, including in tions, although clinicians must also consider persistent Europe and Asia.9 primary that were inadequately treated. Chronic prostatitis has substantial economic In contrast, chronic abacterial prostatitis is diagnosed impact. Men in the United States with chronic pros- when symptoms of pelvic or genital discomfort with or tatitis incur direct and indirect costs averaging more without LUTS persist for greater than 3 months in the than $4,000 annually, which is significantly greater setting of negative localized urine cultures. than the annual medical costs associated with a num- Chronic bacterial prostatitis is more common in ber of other pain-related conditions frequently men older than 50 years and should be suspected when encountered in primary care settings.10 a man has recurrent urinary tract infections as proven by urine cultures. Risk factors are similar to those for ■ PATHOGENESIS acute bacterial prostatitis. Instrumentation of the Although prostatitis is a relatively common urologic lower urinary tract may be considered a risk factor, as diagnosis, little is known about the pathogenesis of its catheterization or endoscopy can be a vector for bac- most common form, chronic abacterial prostatitis/CPPS terial seeding or can cause urethral strictures that (NIH category III). Indeed, prostatitis experts have could lead to reflux of -laden urine from the noted that NIH category III prostatitis has yet to be urethra to the prostatic ducts. Repeated isolation of proven an infectious disorder or even a malady of the the same organism (with the same susceptibility pro- prostate itself.3 file) in urine cultures is considered the hallmark of chronic bacterial prostatitis. Acute bacterial prostatitis Infection of the prostate occurs when bacteria-laden Chronic abacterial prostatitis/CPPS urine from the urethra refluxes into the intraprostatic The pathophysiology of abacterial prostatitis remains ducts. Most of the infectious agents are from the an enigma. Theories abound, and include nanobacteria, Enterobacteriaceae family, specifically elevated prostatic pressures, voiding dysfunction and and Klebsiella or Proteus species. These bacteria reflect bladder neck dyssynergia (nonrelaxation of the external the spectrum of organisms known to cause urethritis, urinary sphincter during urination), male interstitial urinary tract infection, or deeper genital infections. cystitis, pelvic floor myalgia, functional somatic syn- Other causative agents include , Pseudo- drome, and emotional disorders. It is helpful to review monas, and Staphylococcus species as well as gonococ- what has been proven or disproven thus far. cal organisms. The presence or absence of inflammatory cells in Recent catheterization, cystoscopy, or other instru- the expressed prostatic secretions (EPS) differentiates mentation of the urinary tract may be a precipitating chronic abacterial prostatitis into category IIIA event. Urethral strictures caused by prior urethritis (inflammatory) or IIIB (noninflammatory) disease. (typically as a result of gonococcal infection) can also However, this distinction is merely historical, and increase the likelihood of infection. Risk of infection (WBC) counts have not been shown to correlate with symptoms or with the presence or is increased in patients with impaired host defenses 11,12 (eg, due to diabetes or human virus absence of infection. Moreover, the relevance of infection). Men with spinal or neurologic disorders abnormal WBC counts in the EPS is questionable, that impair the detrusor or pelvic floor musculature given the prevalence of abnormal counts in the EPS may be at higher risk. Other purported risk factors, of asymptomatic men. In one study, for instance, 122 such as trauma due to bicycle riding, sexual absti- asymptomatic men underwent for nence, and dehydration, have not been supported by the retrieval of EPS during urologic consultation for well-controlled studies. elevated prostate-specific antigen (PSA) levels, and 42% of these asymptomatic men had abnormally ele- Chronic bacterial prostatitis vated WBC counts in their EPS specimens.13 Chronic bacterial prostatitis is differentiated from It has not been possible to histologically confirm a acute prostatitis when bacteria continue to be isolated correlation between prostatitic inflammation and

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symptoms. Histologic evidence of acute and chronic exclusion of genitourinary tract infections; however, inflammation is identified in prostate pathology spec- many patients have no evidence of infection. Still, imens with increasing prevalence over time, and the these patients may exhibit abnormally high WBC rate of identification can be as high as 90%. In a study counts in the semen (leukocytospermia) or abnormally of asymptomatic men without a history of chronic high levels of reactive oxygen species and oxidative prostatitis, transrectal (performed to stress. Although leukocytospermia is a known cause evaluate elevated PSA levels) revealed inflammation of oxidative stress, oxidative stress can be detected in in 50%.13 However, in a separate study evaluating the absence of high WBC counts.21 symptomatic men previously diagnosed with chronic In the second setting, acute or chronic inflamma- abacterial prostatitis/CPPS, only 5% of cases demon- tion is detected in pathology specimens obtained strated significant levels of inflammation by histol- through prostate biopsy performed to detect prostate ogy.14 The tremendous discord between the findings cancer, transurethral resection of the prostate to of these two studies13,14 underscores the importance of relieve obstructive uropathy, or prostatectomy for extending our focus beyond the prostate when evalu- treatment of benign prostatic hyperplasia or removal ating men with symptoms traditionally attributed to of cancer. This finding of inflammation is not uncom- an infected prostate. mon, as it is seen in 50% of prostate biopsy specimens Likewise, microbiologic studies do not support an and as many as 90% of prostatectomy specimens.22 infectious etiology. No correlation has been seen Because it is usually an incidental finding and is not between symptom severity and the results of cultures to correlated to symptoms, this form of prostatitis may not localize the area of infection with the Meares–Stamey be considered clinically relevant. However, inflamma- 4-glass test.15 (The 4-glass test involves collection of tory changes within the prostate architecture may be sequential urine specimens before and after prostate the cause of PSA elevation, leading to false-positive massage and of prostatic fluid during prostate mas- readings and potentially unnecessary biopsies.11 In sage.16) One large study found that normal controls one study, for instance, prospective detection of were just as likely as men with chronic prostatitis to inflammation via examination of EPS before prostate have positive localization cultures (incidence of 8% biopsy (> 10 WBCs per high-power field), followed by in both groups).17 A randomized, placebo-controlled 4 weeks of treatment, led to normalization of trial showed that 6 weeks of levofloxacin therapy for PSA levels in 45% of patients.13 It remains unclear, chronic prostatitis yielded no advantage over place- however, if this response was due to treatment of an bo,18 and a subsequent trial found that neither underlying infectious process or to a nonspecific anti- , the alpha-blocker tamsulosin, nor their inflammatory property of the antimicrobial agent. combination reduced symptoms of chronic prostatitis Alternatively, interest is growing in the theory that compared with placebo.19 inflammation may be a precursor to cancer, including Nickel et al followed 100 patients with chronic . Investigators have noted that at least prostatitis over 1 year, during which time they some high-grade prostatic intraepithelial neoplasias received sequential monotherapies that included and early adenocarcinomas appear to arise from pro- , alpha-blockers, and antiandrogen thera- liferative inflammatory atrophy. It is believed that pies.20 One third of patients showed modest symptom inflammation and other environmental factors may improvement, but only 19% experienced significant lead to destruction of prostate epithelial cells, and improvement (patients were not characterized in increased proliferation may occur as a response to this terms of NIH IIIA or IIIB subcategories).20 One might cell death. The decreased apoptosis associated with argue that this response rate is even less than the these events may also be related to increased expres- expected placebo response, which begs the question, sion of Bcl-2, which is implicated in other malignant What are we really treating? settings.23 However, no data yet indicate a higher incidence of prostate cancer in patients previously Asymptomatic prostatitis diagnosed with specific NIH categories of prostatitis. The diagnosis of prostatitic inflammation can be made Additionally, a review of epidemiologic data has in asymptomatic patients as well. Such cases are usu- found prostatitis and sexually transmitted infections ally identified in men who present because of infertil- to be correlated with increased prostate cancer risk, ity or are identified incidentally, through histologic and has likewise found intake of anti-inflammatory findings obtained through biopsy or prostatectomy. drugs and antioxidants to be correlated with Initial evaluations for involve decreased prostate cancer risk.24

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■ PRESENTING SYMPTOMS Infection is readily identified via a remarkable uri- nalysis demonstrating pyuria and organisms. Infection Acute bacterial prostatitis: and severe LUTS of the upper urinary tract may be differentiated from Patients presenting with acute bacterial prostatitis are acute bacterial prostatitis by more prominent back usually febrile and suffering severe LUTS, specifically pain and fewer or no LUTS. Blood cultures should be and urinary urgency, frequency, and hesitancy. obtained to rule out bacteremia. At times, inflammation of the prostate can be so PSA testing is not recommended unless a nodule is severe that patients present with . present on digital . Acute prostati- Gross hematuria is not uncommon. tis can raise the PSA level, which often does not Chronic bacterial prostatitis: return to normal until 1 month after therapy; the free Asymptomatic spells between urinary tract infections PSA remains low even 1 month after infection.28 Men with chronic bacterial prostatitis are usually One of the most serious complications of acute pros- asymptomatic in between episodes of urinary tract tatitis is the formation of prostatic . Because infections; however, the organism can still be found catheterization of the urethra increases the risk of and localized to the prostate. Episodes of urinary tract formation, suprapubic catheterization is recom- inflammation may occur with subtle LUTS but can mended in cases of associated urinary retention. Ab- also manifest with severe symptoms and urosepsis. scesses may be palpable during digital rectal examina- Therefore, patients with chronic bacterial prostatitis tion but are typically identified by computed tomogra- may be at risk for recurrent urinary tract infections phy (CT) in patients with persistent symptoms or fever. and bouts of acute prostatitis. Transrectal ultrasonography is not a routine part of the work-up for acute bacterial prostatitis.29 Chronic abacterial prostatitis/CPPS: Think beyond the prostate Chronic bacterial prostatitis: Patients suffering from chronic abacterial prostatitis Confirm with localization cultures often complain of associated LUTS. Kaplan et al Confirmatory tests for chronic bacterial prostatitis found that urodynamically proven voiding dysfunc- include localization cultures that involve retrieval of tion is often misdiagnosed as prostatitis.25 Other EPS via prostate massage (Figure 1), such as the 16 investigators have observed urodynamic abnormali- Meares-Stamey 4-glass test. A simplified version of ties, including detrusor-sphincter pseudodyssynergia, the 4-glass test is the “Pre and Post Massage Test” (2- 30 which is characterized by nonrelaxation of the exter- glass test) popularized by Nickel. It involves culturing nal urinary sphincter during urination. Normally, the a midvoid urine specimen before prostate massage external sphincter should exhibit relaxation during along with a postmassage specimen (typically only 10 urination when sustained detrusor contraction takes mL); the test is considered positive if there is growth of place.26,27 Although urodynamic testing has revealed a single organism in the postmassage specimen, even if voiding dysfunction previously diagnosed or misdiag- the midvoid specimen is sterile. The 2-glass test has a 30 nosed as prostatitis, clinicians must also consider reported sensitivity and specificity of 91% each. these urodynamic abnormalities as components of the Because of the risk of possible contamination, results more accurately redefined and expanded diagnosis of should be interpreted with caution and repeat cultures chronic abacterial prostatitis/CPPS. should be considered, if clinically feasible. Evaluation for underlying causes is appropriate, ■ EVALUATION and indications for evaluation are similar to those for acute bacterial prostatitis. Acute bacterial prostatitis: Exam is revealing, infection is readily identified Chronic abacterial prostatitis/CPPS: The history and physical examination are very reveal- Keep thinking beyond the prostate ing in acute bacterial prostatitis. A gentle digital rec- Evaluation of the patient with suspected chronic tal examination may reveal a soft, enlarged, boggy, abacterial prostatitis/CPPS should rule out risk factors and tender prostate. An overvigorous examination for bacterial prostatitis, remote or recent trauma, may cause undue pain and possibly increase the risk of exposure to a sexually transmitted disease, and instru- bacteremia. If the gland is enlarged and abdominal mentation-induced inflammation. examination shows a palpable or percussible bladder, History. Question patients about their occupation, urinary retention due to benign prostatic hyperplasia with the aim of identifying any repetitive tasks that should be considered. might affect the back and lower extremities, such as

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long bouts of sitting at a desk or behind the wheel (eg, truck driving) or performance of physical labor. Ask about exercise regimens to reveal any improper tech- niques during weight training or inadequate warm-up or stretching. Bladder Rectum Other findings from the history or physical exam- ination can further support the multiple facets of CPPS, such as migratory abdominal or pelvic dis- Prostate comfort or cramping, urinary hesitancy, bowel irreg- ularity, and nonrelaxation of the anal sphincter. Colorectal researchers have observed similar symp- toms (eg, pain of the perineum, fullness, pressure, or the sensation of “sitting upon a golf ball”) among men and women diagnosed with coccygodynia or levator ani syndrome.31 A psychosocial history should include a review of systems to reveal possible functional somatic syn- dromes, as psychological stress is common among men with prostatitis.32 In some cases, a formal psy- chological evaluation should be considered. FIGURE 1. Technique for prostate massage to elicit expressed Physical examination. The physical examination prostatic secretions (EPS) in the evaluation for chronic bacterial pros- should devote special attention to the back, tatitis. Gentle digital pressure is applied in movements along a lobe abdomen, and genitalia. If pain is present in the left of the prostate for approximately 1 minute. Within 2 to 3 minutes after the massage, several drops of EPS should be secreted from the lower quadrant, consider diverticular disease. An urethra. These secretions, together with the first 10 mL of urine after external and internal pelvic floor assessment should massage, represent the prostate’s microbiologic environment. be conducted; for the internal evaluation, place the patient in the lithotomy position to allow assessment of the striated muscles of the pelvic floor by digital examination techniques requires special interest and rectal examination. practice. To successfully carry out this form of evalua- Urinary retention often can be ruled out by per- tion or therapy, clinicians must acquire a gentle con- cussion or palpation of the abdomen, with confirma- fidence about these techniques. tion by ultrasonography or in-office Doppler imaging. The anal sphincter and anal vault should be exam- ■ DIFFERENTIAL DIAGNOSIS ined to rule out fissures, stenosis, and spasticity. Consider myofascial pain. Various pain syndromes, As alluded to above, the differential diagnosis of particularly those of the pelvis, have also been acute bacterial prostatitis includes urinary retention described as myofascial pain syndromes. Muscles with due to benign prostatic hyperplasia and infection of myofascial trigger points exhibit increased responsive- the upper urinary tract. Urinary tract infection also ness, delayed relaxation, referred spasm, and inhibi- figures into the differential diagnosis of chronic bac- tion. The occasional patient may have associated auto- terial prostatitis, which explains the need for localiza- nomic dysfunction (similar to the unexplained bowel tion culture techniques as detailed above. spasticity or urinary urgency/frequency syndromes). The differential diagnosis of chronic abacterial Painful contractions and referred pain are also charac- prostatitis/CPPS is more extensive, as outlined in teristic of myofascial trigger point disorders.33 Table 1, but begins with urinalysis and localization Sensitive examiners are able to detect taut bands, cultures to rule out infection. tender nodules, and even twitch responses in the ■ TREATMENT affected muscle groups. While this may seem like a daunting task, physicians can begin learning about Acute bacterial prostatitis: these techniques by consulting the manual on this Start with broad-spectrum intravenous antibiotics topic by Travell and Simons.33 Physical therapy work- Hospital admission is indicated for any patient with shops also can provide invaluable hands-on training. unstable vital signs, , or intractable pain. Like anything else, however, proficiency in these Other indications for admission include frailty,

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ment duration. However, when organism susceptibility TABLE 1 profiles dictate the use of antibiotics other than Differential diagnosis of chronic abacterial prostatitis/ quinolones or macrolides, we prefer a 6-week regimen. chronic pelvic pain syndrome We recommend avoiding any pain medications that could cause constipation or worsen urinary retention. Infection: Sexually transmitted diseases, chronic bacterial In cases of prostatic abscess, surgical drainage is prostatitis, fungal infection usually required along with extended antibiotic ther- Gastrointestinal: Appendicitis, diverticulitis, constipation, apy. In the case of microabscesses, there is evidence of anal fissures, hemorrhoids resolution without surgical intervention, which can Abdominal wall defects: Inguinal or ventral wall hernias, be observed via serial CT scans. Such close observa- myofascial trigger points tion would be reserved for patients who exhibit con- Musculoskeletal: Neoplasm (primary or metastatic), sistent improvement but may require longer courses degenerative joint disease of the hips, sacroileitis of antimicrobial therapy. Neurologic: Low thoracic or lumbar herniated nucleus pulposis, lumbar stenosis, Parkinson disease, diabetic cystopathy, demyelinating disease Chronic bacterial prostatitis: Urologic: Renal calculi, varicocele, , testicular Base treatment on culture and sensitivity testing neoplasm, interstitial cystitis For chronic bacterial prostatitis, treatment should con- sist of a 2- to 4-week regimen of appropriate antibiotics as dictated by culture and sensitivity testing of urine specimens from previous bouts of acute urinary tract infection and/or localization cultures that include mid- immunosuppression, diabetes, history or evidence of void and post–prostate massage urine specimens. renal insufficiency, and poor social support. In the only study of antibiotic therapy for chronic Treatment should be initiated using a broad-spec- bacterial prostatitis with long-term follow-up, cipro- trum antibiotic regimen similar to protocols estab- floxacin was given for 4 weeks to men with localiza- lished for acute febrile urinary tract infection. tion cultures positive for E coli.35 Three months after Ampicillin (or erythromycin for patients with peni- therapy, 92% of the men exhibited cure as demonstrated callin allergy) and gentamycin are given intravenously by negative EPS cultures and absence of symptoms. At until cultures confirm the organism and its suscepti- 24 months after therapy, 80% of patients remained bilities, which will enable more specific antibiotic tai- asymptomatic and had negative EPS cultures.35 loring and early conversion from intravenous to oral Suppressive therapy is a consideration in men who therapy. Usually fever abates and LUTS improve have three or more recurrences per year. Suppressive within 2 to 6 days of intravenous therapy initiation. therapy may be prescribed using one fourth or one The hospitalized patient may be converted to oral half of the treatment dose at bedtime for antibiotics therapy after he has been afebrile for 24 to 48 hours such as trimethoprim-sulfamethoxazole, trimetho- and his blood cultures are negative. Oral fluoro- prim, , amoxicillin, or nitrofurantoin. quinolones are the treatment of choice for most cases, We have initiated suppressive therapy even when as they effectively target the usual bacterial pathogens recurrences are less frequent than three times per in this setting. In otherwise healthy men, oral year, due to the gravity of the recurrences. This tactic quinolones can be prescribed as the initial, and usually merits consideration in patients who have comorbidi- definitive, oral therapy. Weak bases such as trimetho- ties that might lead to delayed diagnosis and treat- prim will not concentrate well in the alkaline envi- ment or in whom rapid progression to urosepsis has ronment of seminal fluid, especially during infection, occurred, such as in the setting of diabetes or other but because quinolones are neither pure acids nor states of immunocompromise. We also have recently bases, their concentrations in the prostate tissue com- implemented suppressive therapy in patients who are pare favorably with their plasma concentrations.34 on chronic warfarin therapy, as 2- to 4-week antibiotic The choice of antibiotic for treatment of entero- regimens can potentially elevate the prothrombin coccal prostatitis may differ and will be directed by time and the International Normalized Ratio beyond the results of urine culture. therapeutic levels, requiring close monitoring and fre- Duration of therapy varies in the literature from a quent alteration of the warfarin dose. With suppres- minimum of 2 weeks to a maximum of 6 weeks. In our sive therapy, long-term predictability is more feasible practice, we consider 4 weeks an appropriate treat- since treatments are daily and long-term.

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Chronic abacterial prostatitis/CPPS formed by specially trained physiotherapists General principles. From the outset, the management • Relaxation techniques, including paradoxical of patients with suspected chronic abacterial prostati- relaxation therapy, which instructs patients to pace tis should be guided by several general principles: their breathing rate according to their heart rate and • Antibiotics should be avoided in patients who is usually taught by a psychologist or biofeedback are afebrile and have normal urinalysis results. specialist • A brief course of anti-inflammatory therapy may • Thiele massages, which involve internal digital be tried until urine localization cultures are completed. manipulation of the pelvic floor muscles, usually in a There is no clear evidence that any particular anti- sweeping motion, parallel to muscle orientation.31 inflammatory agent is superior to others in this setting. Such alternate therapies can be considered, however, • An empiric trial of alpha-blocker therapy can be only after appropriate evaluation and consideration of considered, although the effectiveness of such therapy disorders affecting pelvic floor muscular function. is uncertain, according to a recent systematic review of Pelvic floor myalgia has long been suspected as the six randomized, placebo-controlled trials comprising cause of symptoms attributed to prostatitis,37 but only 386 patients with chronic abacterial prostatitis.36 While recently has this suspicion been studied in a longitudi- four of the six trials showed a statistically significant nal fashion in . Using both a neurobehavioral improvement in symptom scores with alpha-blocker component and a myofascial trigger point perspective therapy, two of these trials demonstrated no significant for the evaluation and treatment of chronic abacterial difference in quality-of-life scores. Of the remaining prostatitis/CPPS, investigators at Stanford University two studies, one showed no difference between alpha- studied 138 men who were refractory to traditional blocker therapy and placebo and the other had limita- therapy.38 All patients received at least 1 month of tions in statistical methodology. The authors noted pelvic floor myofascial trigger point release therapy that these trials used differing alpha-blockers (no head- combined with paradoxical relaxation therapy and were to-head studies have been reported) and lacked unifor- subsequently assessed using a pelvic pain symptom sur- mity in how they defined significant change.36 Alpha- vey and the NIH Chronic Prostatitis Symptom Index. blockers may exert their effects to varying degrees at By these measures, 72% of patients exhibited improve- sites besides the prostate and bladder neck, which ment consistent with clinical success as defined by the could potentially influence symptoms linked to recep- investigators. This case study analysis indicates that tor sites within the bladder or spinal cord. myofascial trigger point release therapy combined with • Contributing factors should be addressed, such as paradoxical relaxation therapy represents an effective stress, overlapping syndromes, and neuromuscular factors. therapeutic alternative for chronic abacterial prostati- • It is helpful to identify a team of physiothera- tis/CPPS.38 The significant response rate also helps to pists who specialize in myofascial pain syndromes dispel the belief that this disorder is caused by an infec- (discussed later in this section) and who are comfort- tious etiology or prostate abnormality. able dealing with male genitalia and the pelvic floor. Similar response rates were seen when myofascial • It is helpful to identify or establish a team of psy- trigger point release therapy was prescribed to patients, chotherapists or social workers who address stressful mostly female, diagnosed with interstitial cystitis.39 Of life events and offer relaxation therapy. Referral to the 42 patients treated, 83% reported moderate to such providers must be presented as a part of the marked symptom improvement. The amelioration of physician’s comprehensive treatment approach so as urinary urgency and frequency and pelvic pain were not to discredit the patient’s real physical suffering. attributed to the decrease in pelvic floor hypertonus.39 ‘Beyond-the-prostate’ treatment options. In gen- Interstitial cystitis and prostatitis share many char- eral, patients with chronic abacterial prostatitis/CPPS acteristics: chronic genital and/or pelvic pain, LUTS, who are conscientiously evaluated and provided with , disability, and reduced quality of a non–prostate-centric approach to their symptoms life. As with prostatitis and CPPS, the approach to can sooner explore more appropriate management the management of interstitial cystitis has broadened strategies, such as the following: in recent years and the condition itself is increasingly • Physical therapy considered a painful bladder syndrome (see the article • Myofascial trigger point release therapy, which in this supplement devoted to interstitial cystitis/ involves the methodical compression and massage of painful bladder syndrome). trigger points on the levator, obturator, adductor, and NIH-supported research is under way to study the gluteal muscles or on the abdominal wall, and is per- use of physical therapy and myofascial trigger point

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tainly, this notion would be validating to the primary TABLE 2 care provider, who may observe and intuit the overlap- Indications for referral of patients with a history ping nature of this phenomenon on a daily basis. of prostatitis ■ APPROPRIATE FOLLOW-UP Recurrent infection A single recurrence of a urinary tract infection in a History of urosepsis man is suspicious for bacterial prostatitis and, as such, Infection associated with gross hematuria requires additional testing. Indications for upper uri- Persistence of microscopic hematuria after adequate therapy nary tract studies depend on the patient’s history of Sterile pyuria surgery or renal calculi and the persistence of micro- Abnormal testicular examination scopic hematuria after treatment. Urinary retention Lower urinary tract evaluation with a cysto- Abnormal digital rectal examination urethroscope is strongly recommended for all patients Persistent or night sweats with recurrent infection or in whom hematuria, even microscopic, persists after treatment. This brief out- patient procedure, performed with appropriate antibi- otic prophylaxis and local anesthesia, can be most helpful in identifying abnormalities that may be cor- release therapy both in patients with chronic pros- rected to prevent subsequent recurrence or other tatitis/CPPS and in patients with interstitial cysti- pathologies such as bladder tumors, urethral stric- tis/painful bladder syndrome. tures, bladder calculi, or diverticulae. Should treatment address an overlapping somatic Adequate bladder emptying should be confirmed syndrome? Patients with chronic abacterial prostati- as well, using Doppler imaging or ultrasonography to tis/CPPS incur increased medical costs that are not measure the volume of urine remaining immediately directly attributable to prostatitis. It may be that these following normal urination. patients are more susceptible to comorbidities. A We recommend follow-up every 3 to 6 months to retrospective chart review of men with chronic abac- assess patient progress. It is also important for the patient terial prostatitis found that 45% of them had psycho- to have a sense of commitment from the caregiver who logical disorders and 65% met the criteria for other is orchestrating the multidisciplinary approach. functional somatic syndromes, such as fibromyalgia, ■ irritable bowel syndrome, chronic fatigue syndrome, WHEN TO REFER and multiple chemical sensitivities.40 This is a dra- Indications for referral are listed in Table 2. In general, matic observation, as the lifetime prevalence of func- because chronic prostatitis is a relapsing condition tional somatic syndromes in the general population is that is difficult to manage, referral of chronic cases to estimated to be much lower (> 4%).41 a urologist for comanagement should be considered. It Similarly, a comparative study of 127 twins with is important to seek out urologists who are interested chronic fatigue syndrome and their nonfatigued co- in and specialize in this diagnosis, as well as physical twins found that the prevalence of disorders such as therapists who are comfortable with pelvic floor reha- fibromyalgia, irritable bowel syndrome, chronic abac- bilitation and familiar with myofascial pain syn- terial prostatitis, pelvic pain, and interstitial cystitis dromes. Because of the stress associated with the was significantly higher in the chronically fatigued symptoms of chronic prostatitis and the tendency for twins than in their co-twins.42 In another study, many of these patients to “catastrophize,” referral for patients with interstitial cystitis were found to be 100 psychological assessment should be considered. times more likely than the general population to have inflammatory bowel disease, 30 times more likely to ■ REFERENCES have systemic lupus erythematosus, and also more 1. Shoskes DA, Landis JR, Wang Y, et al. Impact of post-ejaculatory likely to have fibromyalgia, allergies, skin sensitivity, pain in men with category III chronic prostatitis/chronic pelvic pain 43 syndrome. J Urol 2004; 172:542–547. and irritable bowel syndrome. 2. Sadeghi-Nejad H, Seftel A. Sexual dysfunction and prostatitis. Because many of these diagnoses coexist, we might Curr Urol Rep 2006; 7:479–484. consider a more global overlapping syndrome, as specific 3. Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis [letter]. JAMA 1999; 281:236–237. somatic syndromes may be “largely an artifact of med- 4. Roberts RO, Lieber MM, Rhodes T, et al. Prevalence of a physi- ical specialization,” as argued by Wessely et al.44 Cer- cian-assigned diagnosis of prostatitis: the Olmsted County Study of

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