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Acute and Chronic Epididymitis
EURSUP-740; No. of Pages 8 EUROPEAN UROLOGY SUPPLEMENTS XXX (2016) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Acute and Chronic Epididymitis Mete C¸ek a,*, Laura Sturdza b, Adrian Pilatz b a
Department of Urology, Trakya University, School of Medicine, Edirne, Turkey;
b
Department of Urology, Pediatric Urology and Andrology, Justus Liebig
University Giessen, Germany
Article info
Abstract
Keywords: Acute epididymitis Chronic epididymitis Chronic scrotal pain Sexually-transmitted infections Epididymo-orchitis
Epididymitis is a relatively common clinical condition presenting as acute or chronic forms. Acute epididymitis is the inflammation of epididymitis accompanied by pain and swelling, while chronic epididymitis may present only with pain. Etiological factors may be infectious or noninfectious, for example urinary obstruction, drug induced, or idiopathic. Bacterial ascent through the urogenital tract is the most common etiology in acute epididymitis, with Chlamydia trachomatis being isolated in all adult age groups. Diagnosis is generally based on patient history, symptoms, and clinical findings. Recent data indicate that sexually active patients with acute epididymitis should be screened for sexually-transmitted diseases, regardless of their age. Additional laboratory investigations and imaging may be required for differential diagnosis with other intrascrotal conditions, particularly with testicular torsion. Although no evidence-based recommendations can be given for the antimicrobial treatment of acute epididymitis, >85% of bacterial strains causing acute epididymitis are susceptible to fluoroquinoles and thirdgeneration cephalosporins. Chronic epididymitis has not been investigated as thorough as acute epididymitis; however, the development and use of a symptom index is promising in terms of achieving a widely-accepted standardization of diagnosis and evaluation. A conservative approach may be beneficial; medical treatment employing antibiotics, anti-inflammatory agents, pain medication, and others are also being utilized without any evidence-based data. Spermatic cord block with short-term and long-term acting agents as well as surgical treatment including epididymectomy microdenervation of the spermatic cord are other treatment alternatives in patients with chronic epididymitis. Patient summary: In this article, we provide an update on the definition, epidemiology, etiology, diagnostics, and therapy in terms of acute and chronic epididymitis.
Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Trakya University, School of Medicine, Rekto¨rlu¨g˘u¨, Edirne 22030, Turkey. Tel. +90 532 262 6032. E-mail address: [email protected] (M. C¸ek).
1.
Introduction
The epididymis is a coiled, tubular organ which is attached to the testis. The functions of the epididymis include transport, maturation, and storage of sperm. The epididymis may become the target of various inflammatory conditions which may or may not be associated with
infectious agents. The clinical picture of this inflammation is epididymitis. 2.
Epidemiology
Epididymitis is a common clinical condition with incidence rates ranging from 25 to 65 per 10 000 person-yr (Table 1).
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Please cite this article in press as: C¸ek M, et al. Acute and Chronic Epididymitis. Eur Urol Suppl (2017), http://dx.doi.org/10.1016/ j.eursup.2017.01.003
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Table 1 – Overview on epidemiologic studies investigations epididymitis Author
Koch et al (1980) Collins et al (1998) Bohm et al (2009) Nicholson et al (2010) Nickel et al (2005)
Period
Region
Age (yr)
Incidence/yr and 10 000 men
Comments
1977–1978 1990–1994 2001–2004 2003–2007 2004
US US US UK Canada
All ages 18–50 14–35 15–60 All ages
40 29 37 25 65
Estimation, about 60% follow-up investigations Consultations to general practitioners and urologists Insurance data analysis, only first event Consultations to general practitioners Consultations to urologists; chronic epididymitis?
However, most of the data are derived from coded diagnoses investigating largely different study populations. In this context, acute epididymitis, chronic epididymitis (CE), and recurrent epididymitis are not always strictly separated. Nickel et al [1] reported that more than 80% of all cases are chronic (defined as duration >3 mo). In summary, the reported prevalence includes the following figures: 0.29% of ambulatory office visits in men <50 yr of age [2] and <1% of men presenting to urology outpatient clinics [1]. It is the most common cause of scrotal pain in adults in the outpatients setting, reaching up to 600 000 cases/yr in the US [3]. In children, the incidence of epididymitis was found to be one per 1000 boys in a prospective, population based study [4]. Acute epididymitis can occur at any patient age and largely depends on the study population investigated [5–7]. Two different studies on CE reported the average age of patients as 49 15 yr (age range, 21–83 yr) and 41.1 yr (18–78 yr) [1,8], while the median age of patients with chronic scrotal pain was reported to be 34 yr (age range, 19–52) in another study [9]. This indicates that acute and CE are both an important issue in men within the reproductive ages. 3.
Acute epididymitis
3.1.
Definition
Acute epididymitis is the inflammation of the epididymis accompanied by pain and swelling with symptoms lasting <6 wk. This clinical picture usually develops within a few days and is typically unilateral. Without adequate therapy a further spread to the testis occurs within a couple of days. This is why several authors use the term epididymo-orchitis. 3.2.
Etiology/pathophysiology
Acute epididymitis can be related to different etiologies. The generally accepted route of infection in epididymitis is the ascent of microorganisms from the urethra. Already in 1927, Campbell [10] concluded that gonococcal epididymitis arose as a result of pathogen ascent starting as urethritis leading to epididymitis a couple of weeks later. Another finding was that from patients with indwelling urinary catheters bacterial pathogens could be isolated from the vas deferens and were identical with those isolated from the urine. The hypothesis was confirmed by studies investigating pathogens isolated simultaneously from the urine/ urethra and epididymis showing 84% identicalness [11–14]. Finally, the bacterial ascent model was underlined by
studies reporting an involvement of the prostate or seminal vesicles by biopsy, ultrasound, or measuring prostatespecific antigen changes [6,7,13]. However, the true incidence of bacterial origin in acute epididymitis is unknown. Before the breakthrough of identifying Chlamydia trachomatis as a major pathogen in young patients, studies investigating the etiology reported a high incidence of idiopathic cases with about 50% [15]. Nevertheless, important studies from the 80s and 90s still reported on 30% idiopathic cases [11,13,16–18]. The percentage of idiopathic cases could be clearly decreased to 13% in a recent study by applying modern molecular diagnostics including polymerase chain reaction analysis [7]. The pathogenic spectrum is related to the depth of microbiological investigations performed, as well as the study population investigated. Traditionally patients with epididymitis <35 yr were suspected to have a sexuallytransmitted disease (STD; eg, C. trachomatis) as an underlying cause while patients >35 yr were believed to have epididymitis caused by enteric pathogens (eg, Escherichia coli) [17]. Unfortunately, this cut-off is still present in international guidelines [3,19], whereas recent studies clearly provide evidence that sexually-transmitted infections (STIs) are not restricted to a specific age [7,16]. In addition, a systemic spread of viral pathogens appears a plausible cause of epididymitis, since about 5% of patients report a previous respiratory tract infection within the previous 14 d before the development of acute epididymitis [7]. However, studies on viral pathogens are scarce, but indicate that mumps virus and enterovirus epididymitis represent rare causative entities [4,7]. It is not conclusively clarified, if the epididymitis is a result of a direct viral infection or a postinfectious immunologic epididymal reaction [4,7]. 3.3.
Symptoms and signs
The presenting symptoms are usually pain and swelling [6,12]. In 96% of cases the epididymitis is unilateral [5,16,18,20]. From the first symptoms to medical consultation on average 2–4 d pass by [6,7,11,21]. Typical physical signs include unilateral swelling and tenderness of the involved epididymis. Swelling usually starts at the cauda epididymis before it ascends and involves the whole epididymis and finally reaches the testis [10]. The clinical spectrum of acute epididymitis ranges from mild epididymal tenderness to severe, febrile systemic disease including urosepsis [6,7,22,23]. In a recent
Please cite this article in press as: C¸ek M, et al. Acute and Chronic Epididymitis. Eur Urol Suppl (2017), http://dx.doi.org/10.1016/ j.eursup.2017.01.003
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Table 2 – Clinical and laboratory findings in epididymitis Positive urine culture (>10 000 cfu/ml) Fever >38.5 8C Erythema of the scrotal skin Leukocytosis (white blood count >11 000/mm3) CRP " Urethritis (>4 white blood cells/hpf) Involvement of the adjacent testis hpf = high power field.
series of 237 patients with acute epididymitis, Pilatz et al [7] reported fever, defined as body temperature >38 8C, to be present in 27.0% of cases. Hongo et al [23] reported age over 65 yr, history of diabetes mellitus, and fever >38 8C to be independent variables associated with severe disease in a series of 160 patients with acute epididymitis. Clinical and laboratory findings in epididymitis are summarized in Table 2. Interestingly, only 30% of patients report concomitant dysuria [6,21], while the presence of typical urethritis symptoms is much lower and largely depends on the study population, with prevalence rates from 0% to 73% [6,17,18,21]. Of note, patients suffering C. trachomatis epididymitis are usually asymptomatic in terms of urethral discharge [7]. In patients with mumps epididymo-orchitis, scrotal swelling occurs in about 40% of patients 5–10 d after initial parotitis and patients suffer typically unilateral a painful and enlarged testis [24]. However, large epidemiologic data evaluating several thousand cases in the area before vaccination clearly showed that mumps primarily involves the testis, while the epididymis is only secondarily affected [25]. 3.4.
Diagnostic considerations
3.4.1.
Medical history
A careful history is essential to detect possible comorbidities and risk factors [26,27]. In addition, symptoms of urethritis, history of urethral instrumentation, previous scrotal surgery, previous episodes, and recent sexual activity should be inquired. The sexual history is crucial, since various studies could show that up to 37.5% of men had multiple sexual partners in parallel [21], and up to 66% of men below 35 yr of age reported new sexual contacts within the previous 4 wk [21]. Further, sexual intercourse with professional sex workers as well as homosexual practices have to be considered [12,20]. Despite the importance of the sexual history, it is only inquired in about 50% of patients in the routine setting [26,28]. 3.4.2.
Physical examination
Patients should be examined for systemic signs like tachycardia or fever, which may indicate severe disease. Examination of the scrotum may reveal a tender spermatic cord. The epididymis is tender and swollen; an indurated cauda or the whole epididymis is frequently palpable [7,10]. Testicular swelling may occur in the early
3
stage as well as later on [6,20]. Cremasteric reflex (ipsilateral contraction of the cremasteric muscle resulting in ipsilateral testis elevation) is present in early stages of epididymitis. Prehn’s sign (relief of pain when the testes are elevated) should also be evaluated. Thus, in cases with isolated epididymitis palpation without ultrasound is sufficient to establish the correct diagnosis [16]. Since bacterial ascension is the major etiologic cause, a rectal examination to exclude prostatic abscess formation might be recommended [10]. 3.4.3.
Imaging
Ultrasound is the gold standard for the evaluation of scrotal disease. In virtually all patients with acute epididymitis, an epididymal enlargement associated with epididymal hyperperfusion can be detected [11,29]. Since most epididymitis cases can be diagnosed on the basis of clinical findings [6,16], scrotal ultrasound is not suggested in cases with simple epididymal enlargement [3,16,29]. However, ultrasound is essential in severe cases, persisting disease, or unclear findings when adequate palpation is hindered by pain, scrotal wall induration, or large reactive hydroceles [3]. Specifically, abscess formation and secondary testicular infarction can easily be detected. If a conservative therapy is chosen in severe cases, serial investigations are recommended [29]. 3.4.4.
Microbiological analysis
Since bacterial ascension through the urogenital tract is of major etiologic relevance, diagnostic studies are required to confirm the infectious etiology and to detect the causative pathogen. Urine analysis shows leukocyturia in up to 80% of patients and a positive test on nitrite in 30% of patients [6,16,30]. Current guidelines recommend urine culture and susceptibility testing in all patients with epididymitis [3,19,31]. In addition, STDs should be screened in at least all patients with a sexual history or signs of urethritis suggesting STDs. Even better would be to screen all sexual active patients, since STDs are frequently present in patients who did not report such risk [7]. Depending on the local facilities the urethritis diagnostics on STDs can apply urethral smears or first void urine. Possible procedures include a gram stain of urethral smears to screen for Neisseria gonorrhoeae, cultures, or polymerase chain reaction-based methods to detect N. gonorrhoeae, C. trachomatis, and Mycoplasma species [3,19,31]. Patients might be tested as well for other STDs, depending on the individual risk [3]. However, only 30% of patients under the age of 35 yr receive an adequate diagnostic when presenting with symptoms of urethritis in the clinical routine [26,28]. Currently, no clear recommendations can be given regarding postprostatic massage urine specimens for microbiological investigations. However, microbiological diagnostics on semen samples at the acute infection stage is not recommended, because of pain and the low additional benefit compared with adequate urine diagnostics [18,20]. Invasive procedures (eg, epididymal aspiration) are obsolete because of the risk of obstruction. Only in cases where surgical procedures are required (epididymectomy or
Please cite this article in press as: C¸ek M, et al. Acute and Chronic Epididymitis. Eur Urol Suppl (2017), http://dx.doi.org/10.1016/ j.eursup.2017.01.003
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orchiectomy) an isolation of the pathogen from that specimen should be aimed at in order to optimize antimicrobial therapy in the recovery phase [7,27]. Finally, it is of utmost importance to perform all microbiological investigations before starting any antimicrobial therapy, since afterwards a bacterial pathogen can only seldom be detected [7,20,26].
beneficial to reduce unnecessary scrotal explorations [33]. This concept has to be supported by the local infrastructure. Specifically, any relevant delay (eg, waiting for the radiologist) needs to be avoided to preserve testicular function in case of torsion [33,34]. In addition, investigators have to be experienced in scrotal ultrasound to minimize the risk of misdiagnosis [36].
3.4.5.
3.5.
Laboratory investigations
A systemic inflammation is regularly present in patients depending on the severity of the local findings. While leukocytosis has been described in only 20% of patients in older studies, recent data indicate that leukocytosis is common in about 70% of cases [7]. In addition, measurement of C-reactive protein is helpful for disease confirmation and monitoring [7,32]. In different studies mean C-reactive protein levels were reported to be 60 mg/l [7,32]. When applying a cutoff value of 20 mg/l, sensitivity and specificity have been described to be each 95% to rule out testicular torsion [32]. To date, a specific serum marker to confirm epididymitis is not available. 3.4.6.
Differential diagnosis
Differential diagnostic work up of acute epididymitis includes testicular torsion, torsion of the appendix testis, inguinal hernia, testicular carcinoma, painful varicocele, scrotal abscess, phlegmon, acute orchitis, and testicular trauma. Elimination of testicular torsion is the first step as this condition is a surgical emergency [33]. Although patient’s age, medical history, clinical signs, laboratory, and ultrasound findings normally allow a distinction between different entities (Table 3) [32,34], not uncommonly contrary constellation of findings occur [30,35]. This explains the high rate of surgical exploration in up to 60% in older studies, where ultrasound was not available [5,14]. A pooled analysis of 20 studies published after the year 2000 demonstrated a sensitivity of 90% and a specificity of 97% to detect testicular torsion by ultrasound [34]. Thus, the broad application of ultrasound was
Treatment
Treatment should aim to cure infection while improving symptoms. Thus, antimicrobial therapy is of utmost importance. Historically, bed rest, scrotal elevation, and local cooling were applied, since antimicrobials were not available [10]. Although randomized studies are missing, these recommendations are still widely applied. However, adjuvant corticoid therapy as well as spermatic cord infiltration have been abandoned due to a lack of efficacy and the upcoming availability of nonsteroidal anti-inflammatory drugs for analgesia [11,37]. Patients can safely be managed on an outpatient basis. Hospitalization will be limited to patients with multimorbidity, severe pain, high fever, or when patients are noncompliant [3,7]. When utilizing adequate diagnostics and antimicrobial therapy, surgical therapy is only rarely necessary and includes mainly epididymectomy, orchiectomy, or both [7]. These procedures should be limited to patients with refractory epididymitis and those with secondary testicular infarctions. While some authors suggest drainage of epididymal abscess formation [22], a recent large study showed epididymal abscess formation to resolve completely under conservative therapy [7]. 3.5.1.
Antimicrobial therapy
Antimicrobial therapy has to be chosen upon consideration of the most probable pathogens and epididymal drug penetration. Unfortunately, antimicrobial studies are rare. In those, tetracyclines have demonstrated good results in
Table 3 – Differential diagnosis of acute epididymitis Acute epididymitis Duration of symptoms Pain intensity Age group Swelling
Nausea/vomiting Cremasteric reflex Testicular position
Few d Moderate All ages Epididymal cauda, later on whole epididymis and/or testis Uncommon Present in mild forms Normal
Prehn’s sign Discharge or urinary symptoms Tenderness Fever Pyuria Leukocytosis Perfusion in ultrasound
Relief of pain (= positive) Common Local, then diffuse Possible Common Common Increased in epididymitis
Testicular torsion
Appendix testis torsion
Few h Severe Adolescents, young adults High-riding, transversally oriented testis
Few d Moderate Children Epididymal head
Possible Usually absent Abnormal axis Abnormal elevation Exacerbation of pain (= negative) Rare diffuse No Uncommon Uncommon Absent or decreased intratesticular flow
Uncommon Present Palpable nodule Blue dot sign Rare Local, then diffuse No Uncommon Uncommon Normal or increased epididymal head perfusion
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patients with suspected C. trachomatis involvement [11]. A clear advantage was the medication with fluoroquinolones starting in the 1980s, because of their efficiency against both C. trachomatis and common urinary pathogens [14]. In the only randomized controlled trial ciprofloxacin was clearly superior to pivampicillin with reported clinical failure rates of 20% and 40%, respectively [16]. These data are the basis of the current Centers for Disease Control and Prevention and European association of Urology guidelines’ recommending fluoroquinolones with activity against C. trachomatis as first choice, except in cases with N. gonorrhoeae [3,19]. A recent study confirmed the recommendations reporting that >85% of bacterial strains are still susceptible despite increasing antimicrobial resistance rates worldwide to both fluoroquinolones and thirdgeneration cephalosporins [7]. However, no evidence-based recommendations can be given for how long the antimicrobial therapy should be given. In patients with confirmed STIs, the therapy of sexual partners is mandatory to prevent reinfection and spread of STIs [18,21]. 4.
CE
4.1.
Definition
CE is defined as ‘‘symptoms of discomfort and/or pain in the scrotum, testicle, or epididymis, localized to one or each epididymis on clinical examination’’ [3,9,38]. Centers for Disease Control and Prevention definition requires a period of 6 wk for the duration of symptoms, while others accept a period of 3 mo with symptoms, relating this condition with chronic orchalgia [8]. 4.2.
Etiology/pathophysiology
Various etiological factors have been held responsible for the development of CE. Among these are inflammation, infection, and urinary obstruction [38]. However, the etiology cannot be identified in many patients. Strebel et al [9] suggested that postinfectious alterations/inflammatory reactions rather than ongoing bacterial infections play a major role in the etiology of CE. Granulomatous reaction, particularly tuberculosis, is one of the frequent causes of infectious CE. Intravesical instillations of Bacillus Calmette–Gue´rin can also induce CE [39]. Sarcoidosis, brucellosis, and other causes of granulomatous epididymitis are infrequent. Nickel et al [8] performed a survey to describe the main characteristics of patients with CE which revealed that certain conditions seem to be associated with CE: (1) having more sexual partners, (2) less often usage of STD protection, (3) general self-reported musculoskeletal, neurologic, and infectious and/or inflammatory medical problems, including a history of urinary tract infections, and depression, compared with men without this condition. However, these differences did not reach statistical significance. Of interest, a history of vasectomy did not have a major association with CE in this survey [8].
5
Epididymitis induced by drugs (eg, amiodarone) as well as associated with generalized diseases (eg, Behc¸et’s disease) have also been described in medical literature [40,41]. CE occurring after vasectomy has been described and is suggested to be associated with obstruction as a potential cause of chronic pain [42]. Finally, idiopathic cases are not uncommon. 4.3.
Clinical presentation and classification (symptoms and
signs)
Patients with CE, by definition, have at least 6 wk or longer a history of discomfort or pain in the epididymis. The epididymis may be felt normal or abnormal on physical examination. In addition, patients may experience testicular pain. While an infectious cause can be documented in some patients with CE, there are patients without any signs of infection. Obstruction due to vasectomy and reflux of urine into the ejaculatory ducts are two main causes of noninfectious CE [43,44]. CE has a negative impact on the quality of life, being sometimes associated with depression [8]. Tuberculous epididymitis has a rather subacute onset; swelling of the epididymis may or may not be painful. Systemic symptoms, scrotal thickening, and fistula may accompany tuberculous epididymitis [45]. After evaluating clinical features in 50 patients with chronic epididymitis, Nickel et al [8] have developed a classification for chronic epididymitis, aiming to provide a useful tool for future clinical studies [8] (Table 4). 4.4.
Diagnostic considerations
4.4.1.
Medical history
A thorough history is essential. The location, severity, and frequency of epididymal/scrotal pain as well as potential exacerbating activities/factors should be inquired. Particularly noninfectious epididymitis can be incited by prolonged periods of sitting or vigorous exercise. History of previous urinary tract infection, scrotal surgery (eg, vasectomy), and sexual history should be carefully inquired [8]. 4.4.2.
Chronic Epididymitis Symptom Index
Nickel et al [1] have developed a Chronic Epididymitis Symptom Index to provide a standard for the evaluation of patients with CE as well as guiding/comparing future
Table 4 – Classification of Chronic Epididymitis (CE) [38] 1) Inflammatory CE where the patient expresses pain and discomfort while the epididymis is swollen and indurated. a) Infective (eg, chlamydia) b) Postinfective (eg, after acute bacterial epididymitis) c) Granulomatous (eg, tuberculosis) d) Drug-induced (eg, amiodarone) e) Associated with a known syndrome (eg, Behc¸et’s disease) f) Idiopathic (ie, no identifiable etiology of inflammation) 2) Obstructive CE (eg, following vasectomy) 3) Chronic epididymalgia
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clinical trials. This symptom index has two questions about the severity of symptoms and three questions in the domain of quality of life. Pain scores range between 0 and 15, while quality of life impact scores vary between 0 and 12, resulting in a total score between 0 and 27. Wide acceptance and application of this symptom index may help investigators to achieve standardized evaluation and treatment protocols for the management of CE. The mean symptom score of patients with CE was reported to be 15.5.
one-fourth of these patients receive pain medication [38]. Unfortunately, these treatment modalities have not been compared in randomized, placebo controlled trials, to date. Patient-specific, tailored treatment regimens utilizing combinations of these modalities may be useful. Unresponsive patients may benefit from spermatic cord block with lidocaine. Encouraging results have been obtained with onabotulinum toxin A injections which provide long lasting pain reduction (3–6 mo) [48].
4.4.3.
4.5.3.
Physical examination
Physical examination should include careful examination of the scrotum as well as the lower abdomen and prostate. The presence of any induration on the epididymis and the testis, location of pain, any irregular finding on the spermatic cord, and signs of inflammation should be noted [8]. 4.4.4.
Laboratory tests
Initial laboratory analysis should include a urinalysis and midstream urine sample for culture. Further investigations should be tailored individually, such as STD screening in patients with urethral discharge and two/four glass test in patients with symptoms compatible with chronic pelvic pain syndrome [38,46]. CE may also induce changes in semen parameters which include a decrease in sperm count and motility as well as significant changes in sperm functions. These changes include atypical staining of flagella, disturbed DNA integrity, increased granulocyte elastase, and decreased a-glucosidase [47]. 4.4.5.
Differential diagnosis
Differential diagnosis of CE should be made with hydrocele, tumors of the testis and epididymis, painful varicocele, and chronic pelvis pain syndrome. 4.4.6.
Imaging
Doppler ultrasound imaging of the scrotum may be useful if the physical examination findings of an indurated epididymis require differential diagnosis with an epididymal and/ or testicular tumor as well as suspicion of painful varicocele. 4.5.
Treatment
4.5.1.
Conservative treatment
Patients with mild symptoms can be observed without any intervention. In this case, the patients should be reassured that the condition is benign in nature, and the clinical symptoms may fade away in time. Some patients in this group may benefit from conservative measures like scrotal support and local heat. Patients can be advised to avoid certain activities that seem to aggravate CE symptoms. 4.5.2.
Surgical treatment
Unfortunately, randomized controlled trials comparing surgical treatment (epididymectomy) with other modalities are lacking in this area. Various investigators evaluated the results of epididymectomy in a series of 16 to 53 patients with follow-up periods varying between 1 mo and 7.4 yr. Postoperative pain-free rates are reported to be between 5% and 59% [42,46,49]. Success rates are not strikingly different between postvasectomy or nonvasectomy series, although better results are obtained in the latter group [50]. Based on the published series, Laurence and Levine [50] reported that palpable painful epididymis and tender cystic lesions isolated to the epididymis predict good results after epididymectomy, while normal structural findings on physical examination and on ultrasonography predict unsuccessful results. The outcome of epididymectomy in patients with CE are summarized in Table 5. Microdenervation of the spermatic cord (MDSC) is a surgical treatment modality which is performed in patients not responding to any of the above-mentioned therapies. After receiving successful results with spermatic cord block,
Medical treatment
Due to the lack of evidence-based data for the treatment of CE, various modalities have been employed by clinicians. Among these are antibiotics, anti-inflammatory agents, phytotherapy, anxiolytics, narcotic analgesics, acupuncture, and injection therapy (steroid or anesthetic). Around
Table 5 – Outcomes of epididymectomy in patients with chronic epididymitis Author
Davis (1990) Davis & Noble (1993) Chen & Ball (1991) Padmore et al (1996)
West et al (2000) Hori et al (2009)
Sweeney et al (2008) Calleary et al (2009)
Siu et al (2007) Sweeney et al (1998)
No. patients undergoing epididymectomy
Results
10
Relief only in one patient Partial relief in 27% with inguinal orchiectomy Benefit reported by 15 patients
24 27
16 53
38 32
34 29
92% with epididymal cyst satisfied 43% with epididymalgia satisfied 14 pts with initial benefit No pain in 93.3% in postvasectomy group No pain in 75% in nonvasectomy group Resolution of symptoms in 32% Excellent results in patients with structural abnormalities 55% chance of improvement in patients with normal findings 70% reported no pain Outcome satisfactory in 27/29; best results in the vasectomy group
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all structures that may be carrying neural fibers are divided while the arteries (testicular, cremasteric, and deferential), lymphatics, and the vas deferens are preserved [50]. After reviewing eight reports on MDSC (204 patients, 2- mo follow-up), Laurence and Levine reported that 83% of patients achieved a pain-free status while 12% improved. The major advantage of MDSC is the possibility of sparing the testicle. Prevention of adhesion with the use of concurrent administration of the inhibitors of adhesion and fibrosis hyaluronic acid and carboxymethylcellulose are reported to be useful to improve the outcome of epididymectomy [44].
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[13] Doble A, Taylor-Robinson D, Thomas BJ, Jalil N, Harris JR, Witherow RO. Acute epididymitis: a microbiological and ultrasonographic study. Br J Urol 1989;63:90–4. [14] Melekos MD, Asbach HW. Epididymitis: aspects concerning etiology and treatment. J Urol 1987;138:83–6. [15] Mittemeyer BT, Lennox KW, Borski AA. Epididymitis: a review of 610 cases. J Urol 1966;95:390–2. [16] Eickhoff JH, Frimodt-Moller N, Walter S, Frimodt-Moller C. A double-blind, randomized, controlled multicentre study to compare the efficacy of ciprofloxacin with pivampicillin as oral therapy for epididymitis in men over 40 years of age. BJU Int 1999;84:827–34. [17] Harnisch JP, Berger RE, Alexander ER, Monda G, Holmes KK. Aetiology of acute epididymitis. Lancet 1977;1:819–21. [18] Robinson AJ, Grant JB, Spencer RC, Potter C, Kinghorn GR. Acute
Conflicts of interest
epididymitis: why patient and consort must be investigated. Br J Urol 1990;66:642–5. [19] Guidelines EAU. EAU Guidelines, edition presented at the 29th EAU
The authors have nothing to disclose.
Annual Congress. Arnhem, The Netherlands: EAU Guidelines Office; 2014.
Appendix A. Supplementary data
[20] Lee CT, Thirumoorthy T, Lim KB, Sng EH. Epidemiology of acute epididymo-orchitis in Singapore. Ann Acad Med Singapore 1989;18: 320–3.
Supplementary material related to this article can be found, in the online version, at http://dx.doi.org/10.1016/j. eursup.2017.01.003.
[21] Pearson RC, Baumber CD, McGhie D, Thambar IV. The relevance of Chlamydia trachomatis in acute epididymitis in young men. Br J Urol 1988;62:72–5. [22] Banyra O, Shulyak A. Acute epididymo-orchitis: staging and treat-
References
ment. Cent European J Urol 2012;65:139–43. [23] Hongo H, Shinojima T, Yazawa S, et al. Development of an algorithm
[1] Nickel JC, Teichman JM, Gregoire M, Clark J, Downey J. Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial
for predicting severe acute epididymitis. J Urol 2014;191:e160. [24] Tae BS, Ham BK, Kim JH, Park JY, Bae JH. Clinical features of mumps
cystitis, and epididymitis in outpatient urological practice: the
orchitis in vaccinated postpubertal males: a single-center series of
Canadian PIE Study. Urology 2005;66:935–40.
62 patients. Korean J Urol 2012;53:865–9.
[2] Collins MM, Stafford RS, O’Leary MP, Barry MJ. How common is prostatitis? A national survey of physician visits. J Urol 1998;159: 1224–8.
[25] Wesselhoeft C. Orchitis in mumps. Boston Med Surg J 1920;183: 425–524. [26] Garthwaite MA, Johnson G, Lloyd S, Eardley I. The implementation
[3] CDC Guidelines. Sexually Transmitted Diseases Treatment Guide-
of European Association of Urology guidelines in the management
lines., Centers for Disease Control and Prevention; 2010 https://
of acute epididymo-orchitis. Ann R Coll Surg Engl 2007;89:799–
www.cdc.gov/std/treatment/2010.
803.
[4] Somekh E, Gorenstein A, Serour F. Acute epididymitis in boys:
[27] Parr NJ, Prasad BR, Hayhurst V, McMillan A, Leen CS, Fowler JW.
evidence of a post-infectious etiology. J Urol 2004;171:391–4,
Suppurative epididymo-orchitis in young ‘‘high risk’’ patients–a
discussion 4.
new problem? Br J Urol 1993;72:949–51.
[5] Ho¨ppner W, Strohmeyer T, Hartmann M, Lopez-Gamarra D,
[28] Drury NE, Dyer JP, Breitenfeldt N, Adamson AS, Harrison GS. Man-
Dreikorn K. Surgical treatment of acute epididymitis and its
agement of acute epididymitis: are European guidelines being
underlying diseases. Eur Urol 1992;22:218–21. [6] Kaver I, Matzkin H, Braf ZF. Epididymo-orchitis: a retrospective study of 121 patients. J Fam Pract 1990;30:548–52. [7] Pilatz A, Hossain H, Kaiser R, et al. Acute epididymitis revisited: impact of molecular diagnostics on etiology and contemporary guideline recommendations. Eur Urol 2015;68:428–35.
followed? Eur Urol 2004;46:522–4, discussion 4–5. [29] Pilatz A, Wagenlehner F, Bschleipfer T, et al. Acute epididymitis in ultrasound: results of a prospective study with baseline and followup investigations in 134 patients. Eur J Radiol 2013;82:e762–8. [30] Yu KJ, Wang TM, Chen HW, Wang HH. The dilemma in the diagnosis of acute scrotum: clinical clues for differentiating between testicular
[8] Nickel JC, Siemens DR, Nickel KR, Downey J. The patient with
torsion and epididymo-orchitis. Chang Gung Med J 2012;35:38–45.
chronic epididymitis: characterization of an enigmatic syndrome.
[31] Street EJPM, Kopa Z, Skerlev M, Wilson JD, Patel R. 2012 (IUSTI/
J Urol 2002;167:1701–4. [9] Strebel RT, Schmidt C, Beatrice J, Sulser T. Chronic scrotal pain syndrome (CSPS): the widespread use of antibiotics is not justified. Andrology 2013;1:155–9. [10] Campbell MF. Gonococcus epididymitis: observations in three thousand cases from the urological service of bellevue hospital. Ann Surg 1927;86:577–90. [11] Berger RE, Alexander ER, Harnisch JP, et al. Etiology, manifestations and therapy of acute epididymitis: prospective study of 50 cases. J Urol 1979;121:750–4.
WHO) guideline on the management of epididymo-orchitis., IUSTI EO Guideline; 2012
http://www.iusti.org/regions/Europe/pdf/
2013/Epididymo-orchitis-2013IUSTI_WHO.pdf. [32] Doehn C, Fornara P, Kausch I, Buttner H, Friedrich HJ, Jocham D. Value of acute-phase proteins in the differential diagnosis of acute scrotum. Eur Urol 2001;39:215–21. [33] Yagil Y, Naroditsky I, Milhem J, et al. Role of Doppler ultrasonography in the triage of acute scrotum in the emergency department. J Ultrasound Med 2010;29:11–21. [34] Altinkilic B, Pilatz A, Weidner W. Detection of normal intratesti-
[12] Berger RE, Kessler D, Holmes KK. Etiology and manifestations of
cular perfusion using color coded duplex sonography obviates need
epididymitis in young men: correlations with sexual orientation.
for scrotal exploration in patients with suspected testicular torsion.
J Infect Dis 1987;155:1341–3.
J Urol 2013;189:1853–8.
Please cite this article in press as: C¸ek M, et al. Acute and Chronic Epididymitis. Eur Urol Suppl (2017), http://dx.doi.org/10.1016/ j.eursup.2017.01.003
EURSUP-740; No. of Pages 8 8
EUROPEAN UROLOGY SUPPLEMENTS XXX (2016) XXX–XXX
[35] Liu CC, Huang SP, Chou YH, et al. Clinical presentation of acute scrotum in young males. Kaohsiung J Med Sci 2007;23:281–6.
[43] Lee JY, Lee TY, Park HY, et al. Efficacy of epididymectomy in treatment of chronic epididymal pain: a comparison of patients
[36] Kalfa N, Veyrac C, Lopez M, et al. Multicenter assessment of ultra-
with and without a history of vasectomy. Urology 2011;77:177–82.
sound of the spermatic cord in children with acute scrotum. J Urol
[44] Chung JH, Moon HS, Choi HY, et al. Inhibition of adhesion and
2007;177:297–301. [37] Moore CA, Lockett BL, Lennox KW, et al. Prednisone in the treatment of acute epididymitis: a cooperative study. J Urol 1971;106: 578–80. [38] Nickel JC. Chronic epididymitis: a practical approach to understanding and managing a difficult urologic enigma. Rev Urol 2003;5:209–15.
fibrosis improves the outcome of epididymectomy as a treatment for chronic epididymitis: a multicenter, randomized controlled, single-blind study. J Urol 2013;189:1730–4. [45] Kulchavenya E, Khomyakov V. Male genital tuberculosis in Siberians. World J Urol 2006;24:74–8. [46] Calleary JG, Masood J, Hill JT. Chronic epididymitis: is epididymectomy a valid surgical treatment? Int J Androl 2009;32:468–72.
[39] Hoag N, Pommerville PJ, Kibsey PC, Cavers DJ, Eddy RJ. Tuberculous
[47] Haidl G, Allam JP, Schuppe HC. Chronic epididymitis: impact on
epididymitis following intravesical Bacillus Calmette-Guerin im-
semen parameters and therapeutic options. Andrologia 2008;40:
munotherapy. Can J Urol 2009;16:4589–91. [40] Shen Y, Liu H, Cheng J, Bu P. Amiodarone-induced epididymitis: a
92–6. [48] Khambati A, Lau S, Gordon A, Jarvi KA. OnabotulinumtoxinA (Botox)
pathologically confirmed case report and review of the literature.
nerve blocks provide durable pain relief for men with chronic
Cardiology 2014;128:349–51.
scrotal pain: a pilot open-label trial. J Sex Med 2014;11:3072–7.
[41] Davatchi F, Shahram F, Chams-Davatchi C, et al. Behcet’s disease in Iran: analysis of 6500 cases. Int J Rheum Dis 2010;13:367–73. [42] West AF, Leung HY, Powell PH. Epididymectomy is an effective treatment for scrotal pain after vasectomy. BJU Int 2000;85: 1097–9.
[49] Hori S, Sengupta A, Shukla CJ, Ingall E, McLoughlin J. Long-term outcome of epididymectomy for the management of chronic epididymal pain. J Urol 2009;182:1407–12. [50] Laurence A, Levine MD. Chronic Scrotal Content Pain AUA Update Series Lesson 37, vol. 31. Linthicum, MD: AUA; 2012.
Please cite this article in press as: C¸ek M, et al. Acute and Chronic Epididymitis. Eur Urol Suppl (2017), http://dx.doi.org/10.1016/ j.eursup.2017.01.003
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Acute and Chronic Epididymitis Mete C¸ek a,*, Laura Sturdza b, Adrian Pilatz b a
Department of Urology, Trakya University, School of Medicine, Edirne, Turkey;
b
Department of Urology, Pediatric Urology and Andrology, Justus Liebig
University Giessen, Germany
Article info
Abstract
Keywords: Acute epididymitis Chronic epididymitis Chronic scrotal pain Sexually-transmitted infections Epididymo-orchitis
Epididymitis is a relatively common clinical condition presenting as acute or chronic forms. Acute epididymitis is the inflammation of epididymitis accompanied by pain and swelling, while chronic epididymitis may present only with pain. Etiological factors may be infectious or noninfectious, for example urinary obstruction, drug induced, or idiopathic. Bacterial ascent through the urogenital tract is the most common etiology in acute epididymitis, with Chlamydia trachomatis being isolated in all adult age groups. Diagnosis is generally based on patient history, symptoms, and clinical findings. Recent data indicate that sexually active patients with acute epididymitis should be screened for sexually-transmitted diseases, regardless of their age. Additional laboratory investigations and imaging may be required for differential diagnosis with other intrascrotal conditions, particularly with testicular torsion. Although no evidence-based recommendations can be given for the antimicrobial treatment of acute epididymitis, >85% of bacterial strains causing acute epididymitis are susceptible to fluoroquinoles and thirdgeneration cephalosporins. Chronic epididymitis has not been investigated as thorough as acute epididymitis; however, the development and use of a symptom index is promising in terms of achieving a widely-accepted standardization of diagnosis and evaluation. A conservative approach may be beneficial; medical treatment employing antibiotics, anti-inflammatory agents, pain medication, and others are also being utilized without any evidence-based data. Spermatic cord block with short-term and long-term acting agents as well as surgical treatment including epididymectomy microdenervation of the spermatic cord are other treatment alternatives in patients with chronic epididymitis. Patient summary: In this article, we provide an update on the definition, epidemiology, etiology, diagnostics, and therapy in terms of acute and chronic epididymitis.
Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Trakya University, School of Medicine, Rekto¨rlu¨g˘u¨, Edirne 22030, Turkey. Tel. +90 532 262 6032. E-mail address: [email protected] (M. C¸ek).
1.
Introduction
The epididymis is a coiled, tubular organ which is attached to the testis. The functions of the epididymis include transport, maturation, and storage of sperm. The epididymis may become the target of various inflammatory conditions which may or may not be associated with
infectious agents. The clinical picture of this inflammation is epididymitis. 2.
Epidemiology
Epididymitis is a common clinical condition with incidence rates ranging from 25 to 65 per 10 000 person-yr (Table 1).
http://dx.doi.org/10.1016/j.eursup.2017.01.003 1569-9056/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Table 1 – Overview on epidemiologic studies investigations epididymitis Author
Koch et al (1980) Collins et al (1998) Bohm et al (2009) Nicholson et al (2010) Nickel et al (2005)
Period
Region
Age (yr)
Incidence/yr and 10 000 men
Comments
1977–1978 1990–1994 2001–2004 2003–2007 2004
US US US UK Canada
All ages 18–50 14–35 15–60 All ages
40 29 37 25 65
Estimation, about 60% follow-up investigations Consultations to general practitioners and urologists Insurance data analysis, only first event Consultations to general practitioners Consultations to urologists; chronic epididymitis?
However, most of the data are derived from coded diagnoses investigating largely different study populations. In this context, acute epididymitis, chronic epididymitis (CE), and recurrent epididymitis are not always strictly separated. Nickel et al [1] reported that more than 80% of all cases are chronic (defined as duration >3 mo). In summary, the reported prevalence includes the following figures: 0.29% of ambulatory office visits in men <50 yr of age [2] and <1% of men presenting to urology outpatient clinics [1]. It is the most common cause of scrotal pain in adults in the outpatients setting, reaching up to 600 000 cases/yr in the US [3]. In children, the incidence of epididymitis was found to be one per 1000 boys in a prospective, population based study [4]. Acute epididymitis can occur at any patient age and largely depends on the study population investigated [5–7]. Two different studies on CE reported the average age of patients as 49 15 yr (age range, 21–83 yr) and 41.1 yr (18–78 yr) [1,8], while the median age of patients with chronic scrotal pain was reported to be 34 yr (age range, 19–52) in another study [9]. This indicates that acute and CE are both an important issue in men within the reproductive ages. 3.
Acute epididymitis
3.1.
Definition
Acute epididymitis is the inflammation of the epididymis accompanied by pain and swelling with symptoms lasting <6 wk. This clinical picture usually develops within a few days and is typically unilateral. Without adequate therapy a further spread to the testis occurs within a couple of days. This is why several authors use the term epididymo-orchitis. 3.2.
Etiology/pathophysiology
Acute epididymitis can be related to different etiologies. The generally accepted route of infection in epididymitis is the ascent of microorganisms from the urethra. Already in 1927, Campbell [10] concluded that gonococcal epididymitis arose as a result of pathogen ascent starting as urethritis leading to epididymitis a couple of weeks later. Another finding was that from patients with indwelling urinary catheters bacterial pathogens could be isolated from the vas deferens and were identical with those isolated from the urine. The hypothesis was confirmed by studies investigating pathogens isolated simultaneously from the urine/ urethra and epididymis showing 84% identicalness [11–14]. Finally, the bacterial ascent model was underlined by
studies reporting an involvement of the prostate or seminal vesicles by biopsy, ultrasound, or measuring prostatespecific antigen changes [6,7,13]. However, the true incidence of bacterial origin in acute epididymitis is unknown. Before the breakthrough of identifying Chlamydia trachomatis as a major pathogen in young patients, studies investigating the etiology reported a high incidence of idiopathic cases with about 50% [15]. Nevertheless, important studies from the 80s and 90s still reported on 30% idiopathic cases [11,13,16–18]. The percentage of idiopathic cases could be clearly decreased to 13% in a recent study by applying modern molecular diagnostics including polymerase chain reaction analysis [7]. The pathogenic spectrum is related to the depth of microbiological investigations performed, as well as the study population investigated. Traditionally patients with epididymitis <35 yr were suspected to have a sexuallytransmitted disease (STD; eg, C. trachomatis) as an underlying cause while patients >35 yr were believed to have epididymitis caused by enteric pathogens (eg, Escherichia coli) [17]. Unfortunately, this cut-off is still present in international guidelines [3,19], whereas recent studies clearly provide evidence that sexually-transmitted infections (STIs) are not restricted to a specific age [7,16]. In addition, a systemic spread of viral pathogens appears a plausible cause of epididymitis, since about 5% of patients report a previous respiratory tract infection within the previous 14 d before the development of acute epididymitis [7]. However, studies on viral pathogens are scarce, but indicate that mumps virus and enterovirus epididymitis represent rare causative entities [4,7]. It is not conclusively clarified, if the epididymitis is a result of a direct viral infection or a postinfectious immunologic epididymal reaction [4,7]. 3.3.
Symptoms and signs
The presenting symptoms are usually pain and swelling [6,12]. In 96% of cases the epididymitis is unilateral [5,16,18,20]. From the first symptoms to medical consultation on average 2–4 d pass by [6,7,11,21]. Typical physical signs include unilateral swelling and tenderness of the involved epididymis. Swelling usually starts at the cauda epididymis before it ascends and involves the whole epididymis and finally reaches the testis [10]. The clinical spectrum of acute epididymitis ranges from mild epididymal tenderness to severe, febrile systemic disease including urosepsis [6,7,22,23]. In a recent
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Table 2 – Clinical and laboratory findings in epididymitis Positive urine culture (>10 000 cfu/ml) Fever >38.5 8C Erythema of the scrotal skin Leukocytosis (white blood count >11 000/mm3) CRP " Urethritis (>4 white blood cells/hpf) Involvement of the adjacent testis hpf = high power field.
series of 237 patients with acute epididymitis, Pilatz et al [7] reported fever, defined as body temperature >38 8C, to be present in 27.0% of cases. Hongo et al [23] reported age over 65 yr, history of diabetes mellitus, and fever >38 8C to be independent variables associated with severe disease in a series of 160 patients with acute epididymitis. Clinical and laboratory findings in epididymitis are summarized in Table 2. Interestingly, only 30% of patients report concomitant dysuria [6,21], while the presence of typical urethritis symptoms is much lower and largely depends on the study population, with prevalence rates from 0% to 73% [6,17,18,21]. Of note, patients suffering C. trachomatis epididymitis are usually asymptomatic in terms of urethral discharge [7]. In patients with mumps epididymo-orchitis, scrotal swelling occurs in about 40% of patients 5–10 d after initial parotitis and patients suffer typically unilateral a painful and enlarged testis [24]. However, large epidemiologic data evaluating several thousand cases in the area before vaccination clearly showed that mumps primarily involves the testis, while the epididymis is only secondarily affected [25]. 3.4.
Diagnostic considerations
3.4.1.
Medical history
A careful history is essential to detect possible comorbidities and risk factors [26,27]. In addition, symptoms of urethritis, history of urethral instrumentation, previous scrotal surgery, previous episodes, and recent sexual activity should be inquired. The sexual history is crucial, since various studies could show that up to 37.5% of men had multiple sexual partners in parallel [21], and up to 66% of men below 35 yr of age reported new sexual contacts within the previous 4 wk [21]. Further, sexual intercourse with professional sex workers as well as homosexual practices have to be considered [12,20]. Despite the importance of the sexual history, it is only inquired in about 50% of patients in the routine setting [26,28]. 3.4.2.
Physical examination
Patients should be examined for systemic signs like tachycardia or fever, which may indicate severe disease. Examination of the scrotum may reveal a tender spermatic cord. The epididymis is tender and swollen; an indurated cauda or the whole epididymis is frequently palpable [7,10]. Testicular swelling may occur in the early
3
stage as well as later on [6,20]. Cremasteric reflex (ipsilateral contraction of the cremasteric muscle resulting in ipsilateral testis elevation) is present in early stages of epididymitis. Prehn’s sign (relief of pain when the testes are elevated) should also be evaluated. Thus, in cases with isolated epididymitis palpation without ultrasound is sufficient to establish the correct diagnosis [16]. Since bacterial ascension is the major etiologic cause, a rectal examination to exclude prostatic abscess formation might be recommended [10]. 3.4.3.
Imaging
Ultrasound is the gold standard for the evaluation of scrotal disease. In virtually all patients with acute epididymitis, an epididymal enlargement associated with epididymal hyperperfusion can be detected [11,29]. Since most epididymitis cases can be diagnosed on the basis of clinical findings [6,16], scrotal ultrasound is not suggested in cases with simple epididymal enlargement [3,16,29]. However, ultrasound is essential in severe cases, persisting disease, or unclear findings when adequate palpation is hindered by pain, scrotal wall induration, or large reactive hydroceles [3]. Specifically, abscess formation and secondary testicular infarction can easily be detected. If a conservative therapy is chosen in severe cases, serial investigations are recommended [29]. 3.4.4.
Microbiological analysis
Since bacterial ascension through the urogenital tract is of major etiologic relevance, diagnostic studies are required to confirm the infectious etiology and to detect the causative pathogen. Urine analysis shows leukocyturia in up to 80% of patients and a positive test on nitrite in 30% of patients [6,16,30]. Current guidelines recommend urine culture and susceptibility testing in all patients with epididymitis [3,19,31]. In addition, STDs should be screened in at least all patients with a sexual history or signs of urethritis suggesting STDs. Even better would be to screen all sexual active patients, since STDs are frequently present in patients who did not report such risk [7]. Depending on the local facilities the urethritis diagnostics on STDs can apply urethral smears or first void urine. Possible procedures include a gram stain of urethral smears to screen for Neisseria gonorrhoeae, cultures, or polymerase chain reaction-based methods to detect N. gonorrhoeae, C. trachomatis, and Mycoplasma species [3,19,31]. Patients might be tested as well for other STDs, depending on the individual risk [3]. However, only 30% of patients under the age of 35 yr receive an adequate diagnostic when presenting with symptoms of urethritis in the clinical routine [26,28]. Currently, no clear recommendations can be given regarding postprostatic massage urine specimens for microbiological investigations. However, microbiological diagnostics on semen samples at the acute infection stage is not recommended, because of pain and the low additional benefit compared with adequate urine diagnostics [18,20]. Invasive procedures (eg, epididymal aspiration) are obsolete because of the risk of obstruction. Only in cases where surgical procedures are required (epididymectomy or
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orchiectomy) an isolation of the pathogen from that specimen should be aimed at in order to optimize antimicrobial therapy in the recovery phase [7,27]. Finally, it is of utmost importance to perform all microbiological investigations before starting any antimicrobial therapy, since afterwards a bacterial pathogen can only seldom be detected [7,20,26].
beneficial to reduce unnecessary scrotal explorations [33]. This concept has to be supported by the local infrastructure. Specifically, any relevant delay (eg, waiting for the radiologist) needs to be avoided to preserve testicular function in case of torsion [33,34]. In addition, investigators have to be experienced in scrotal ultrasound to minimize the risk of misdiagnosis [36].
3.4.5.
3.5.
Laboratory investigations
A systemic inflammation is regularly present in patients depending on the severity of the local findings. While leukocytosis has been described in only 20% of patients in older studies, recent data indicate that leukocytosis is common in about 70% of cases [7]. In addition, measurement of C-reactive protein is helpful for disease confirmation and monitoring [7,32]. In different studies mean C-reactive protein levels were reported to be 60 mg/l [7,32]. When applying a cutoff value of 20 mg/l, sensitivity and specificity have been described to be each 95% to rule out testicular torsion [32]. To date, a specific serum marker to confirm epididymitis is not available. 3.4.6.
Differential diagnosis
Differential diagnostic work up of acute epididymitis includes testicular torsion, torsion of the appendix testis, inguinal hernia, testicular carcinoma, painful varicocele, scrotal abscess, phlegmon, acute orchitis, and testicular trauma. Elimination of testicular torsion is the first step as this condition is a surgical emergency [33]. Although patient’s age, medical history, clinical signs, laboratory, and ultrasound findings normally allow a distinction between different entities (Table 3) [32,34], not uncommonly contrary constellation of findings occur [30,35]. This explains the high rate of surgical exploration in up to 60% in older studies, where ultrasound was not available [5,14]. A pooled analysis of 20 studies published after the year 2000 demonstrated a sensitivity of 90% and a specificity of 97% to detect testicular torsion by ultrasound [34]. Thus, the broad application of ultrasound was
Treatment
Treatment should aim to cure infection while improving symptoms. Thus, antimicrobial therapy is of utmost importance. Historically, bed rest, scrotal elevation, and local cooling were applied, since antimicrobials were not available [10]. Although randomized studies are missing, these recommendations are still widely applied. However, adjuvant corticoid therapy as well as spermatic cord infiltration have been abandoned due to a lack of efficacy and the upcoming availability of nonsteroidal anti-inflammatory drugs for analgesia [11,37]. Patients can safely be managed on an outpatient basis. Hospitalization will be limited to patients with multimorbidity, severe pain, high fever, or when patients are noncompliant [3,7]. When utilizing adequate diagnostics and antimicrobial therapy, surgical therapy is only rarely necessary and includes mainly epididymectomy, orchiectomy, or both [7]. These procedures should be limited to patients with refractory epididymitis and those with secondary testicular infarctions. While some authors suggest drainage of epididymal abscess formation [22], a recent large study showed epididymal abscess formation to resolve completely under conservative therapy [7]. 3.5.1.
Antimicrobial therapy
Antimicrobial therapy has to be chosen upon consideration of the most probable pathogens and epididymal drug penetration. Unfortunately, antimicrobial studies are rare. In those, tetracyclines have demonstrated good results in
Table 3 – Differential diagnosis of acute epididymitis Acute epididymitis Duration of symptoms Pain intensity Age group Swelling
Nausea/vomiting Cremasteric reflex Testicular position
Few d Moderate All ages Epididymal cauda, later on whole epididymis and/or testis Uncommon Present in mild forms Normal
Prehn’s sign Discharge or urinary symptoms Tenderness Fever Pyuria Leukocytosis Perfusion in ultrasound
Relief of pain (= positive) Common Local, then diffuse Possible Common Common Increased in epididymitis
Testicular torsion
Appendix testis torsion
Few h Severe Adolescents, young adults High-riding, transversally oriented testis
Few d Moderate Children Epididymal head
Possible Usually absent Abnormal axis Abnormal elevation Exacerbation of pain (= negative) Rare diffuse No Uncommon Uncommon Absent or decreased intratesticular flow
Uncommon Present Palpable nodule Blue dot sign Rare Local, then diffuse No Uncommon Uncommon Normal or increased epididymal head perfusion
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patients with suspected C. trachomatis involvement [11]. A clear advantage was the medication with fluoroquinolones starting in the 1980s, because of their efficiency against both C. trachomatis and common urinary pathogens [14]. In the only randomized controlled trial ciprofloxacin was clearly superior to pivampicillin with reported clinical failure rates of 20% and 40%, respectively [16]. These data are the basis of the current Centers for Disease Control and Prevention and European association of Urology guidelines’ recommending fluoroquinolones with activity against C. trachomatis as first choice, except in cases with N. gonorrhoeae [3,19]. A recent study confirmed the recommendations reporting that >85% of bacterial strains are still susceptible despite increasing antimicrobial resistance rates worldwide to both fluoroquinolones and thirdgeneration cephalosporins [7]. However, no evidence-based recommendations can be given for how long the antimicrobial therapy should be given. In patients with confirmed STIs, the therapy of sexual partners is mandatory to prevent reinfection and spread of STIs [18,21]. 4.
CE
4.1.
Definition
CE is defined as ‘‘symptoms of discomfort and/or pain in the scrotum, testicle, or epididymis, localized to one or each epididymis on clinical examination’’ [3,9,38]. Centers for Disease Control and Prevention definition requires a period of 6 wk for the duration of symptoms, while others accept a period of 3 mo with symptoms, relating this condition with chronic orchalgia [8]. 4.2.
Etiology/pathophysiology
Various etiological factors have been held responsible for the development of CE. Among these are inflammation, infection, and urinary obstruction [38]. However, the etiology cannot be identified in many patients. Strebel et al [9] suggested that postinfectious alterations/inflammatory reactions rather than ongoing bacterial infections play a major role in the etiology of CE. Granulomatous reaction, particularly tuberculosis, is one of the frequent causes of infectious CE. Intravesical instillations of Bacillus Calmette–Gue´rin can also induce CE [39]. Sarcoidosis, brucellosis, and other causes of granulomatous epididymitis are infrequent. Nickel et al [8] performed a survey to describe the main characteristics of patients with CE which revealed that certain conditions seem to be associated with CE: (1) having more sexual partners, (2) less often usage of STD protection, (3) general self-reported musculoskeletal, neurologic, and infectious and/or inflammatory medical problems, including a history of urinary tract infections, and depression, compared with men without this condition. However, these differences did not reach statistical significance. Of interest, a history of vasectomy did not have a major association with CE in this survey [8].
5
Epididymitis induced by drugs (eg, amiodarone) as well as associated with generalized diseases (eg, Behc¸et’s disease) have also been described in medical literature [40,41]. CE occurring after vasectomy has been described and is suggested to be associated with obstruction as a potential cause of chronic pain [42]. Finally, idiopathic cases are not uncommon. 4.3.
Clinical presentation and classification (symptoms and
signs)
Patients with CE, by definition, have at least 6 wk or longer a history of discomfort or pain in the epididymis. The epididymis may be felt normal or abnormal on physical examination. In addition, patients may experience testicular pain. While an infectious cause can be documented in some patients with CE, there are patients without any signs of infection. Obstruction due to vasectomy and reflux of urine into the ejaculatory ducts are two main causes of noninfectious CE [43,44]. CE has a negative impact on the quality of life, being sometimes associated with depression [8]. Tuberculous epididymitis has a rather subacute onset; swelling of the epididymis may or may not be painful. Systemic symptoms, scrotal thickening, and fistula may accompany tuberculous epididymitis [45]. After evaluating clinical features in 50 patients with chronic epididymitis, Nickel et al [8] have developed a classification for chronic epididymitis, aiming to provide a useful tool for future clinical studies [8] (Table 4). 4.4.
Diagnostic considerations
4.4.1.
Medical history
A thorough history is essential. The location, severity, and frequency of epididymal/scrotal pain as well as potential exacerbating activities/factors should be inquired. Particularly noninfectious epididymitis can be incited by prolonged periods of sitting or vigorous exercise. History of previous urinary tract infection, scrotal surgery (eg, vasectomy), and sexual history should be carefully inquired [8]. 4.4.2.
Chronic Epididymitis Symptom Index
Nickel et al [1] have developed a Chronic Epididymitis Symptom Index to provide a standard for the evaluation of patients with CE as well as guiding/comparing future
Table 4 – Classification of Chronic Epididymitis (CE) [38] 1) Inflammatory CE where the patient expresses pain and discomfort while the epididymis is swollen and indurated. a) Infective (eg, chlamydia) b) Postinfective (eg, after acute bacterial epididymitis) c) Granulomatous (eg, tuberculosis) d) Drug-induced (eg, amiodarone) e) Associated with a known syndrome (eg, Behc¸et’s disease) f) Idiopathic (ie, no identifiable etiology of inflammation) 2) Obstructive CE (eg, following vasectomy) 3) Chronic epididymalgia
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clinical trials. This symptom index has two questions about the severity of symptoms and three questions in the domain of quality of life. Pain scores range between 0 and 15, while quality of life impact scores vary between 0 and 12, resulting in a total score between 0 and 27. Wide acceptance and application of this symptom index may help investigators to achieve standardized evaluation and treatment protocols for the management of CE. The mean symptom score of patients with CE was reported to be 15.5.
one-fourth of these patients receive pain medication [38]. Unfortunately, these treatment modalities have not been compared in randomized, placebo controlled trials, to date. Patient-specific, tailored treatment regimens utilizing combinations of these modalities may be useful. Unresponsive patients may benefit from spermatic cord block with lidocaine. Encouraging results have been obtained with onabotulinum toxin A injections which provide long lasting pain reduction (3–6 mo) [48].
4.4.3.
4.5.3.
Physical examination
Physical examination should include careful examination of the scrotum as well as the lower abdomen and prostate. The presence of any induration on the epididymis and the testis, location of pain, any irregular finding on the spermatic cord, and signs of inflammation should be noted [8]. 4.4.4.
Laboratory tests
Initial laboratory analysis should include a urinalysis and midstream urine sample for culture. Further investigations should be tailored individually, such as STD screening in patients with urethral discharge and two/four glass test in patients with symptoms compatible with chronic pelvic pain syndrome [38,46]. CE may also induce changes in semen parameters which include a decrease in sperm count and motility as well as significant changes in sperm functions. These changes include atypical staining of flagella, disturbed DNA integrity, increased granulocyte elastase, and decreased a-glucosidase [47]. 4.4.5.
Differential diagnosis
Differential diagnosis of CE should be made with hydrocele, tumors of the testis and epididymis, painful varicocele, and chronic pelvis pain syndrome. 4.4.6.
Imaging
Doppler ultrasound imaging of the scrotum may be useful if the physical examination findings of an indurated epididymis require differential diagnosis with an epididymal and/ or testicular tumor as well as suspicion of painful varicocele. 4.5.
Treatment
4.5.1.
Conservative treatment
Patients with mild symptoms can be observed without any intervention. In this case, the patients should be reassured that the condition is benign in nature, and the clinical symptoms may fade away in time. Some patients in this group may benefit from conservative measures like scrotal support and local heat. Patients can be advised to avoid certain activities that seem to aggravate CE symptoms. 4.5.2.
Surgical treatment
Unfortunately, randomized controlled trials comparing surgical treatment (epididymectomy) with other modalities are lacking in this area. Various investigators evaluated the results of epididymectomy in a series of 16 to 53 patients with follow-up periods varying between 1 mo and 7.4 yr. Postoperative pain-free rates are reported to be between 5% and 59% [42,46,49]. Success rates are not strikingly different between postvasectomy or nonvasectomy series, although better results are obtained in the latter group [50]. Based on the published series, Laurence and Levine [50] reported that palpable painful epididymis and tender cystic lesions isolated to the epididymis predict good results after epididymectomy, while normal structural findings on physical examination and on ultrasonography predict unsuccessful results. The outcome of epididymectomy in patients with CE are summarized in Table 5. Microdenervation of the spermatic cord (MDSC) is a surgical treatment modality which is performed in patients not responding to any of the above-mentioned therapies. After receiving successful results with spermatic cord block,
Medical treatment
Due to the lack of evidence-based data for the treatment of CE, various modalities have been employed by clinicians. Among these are antibiotics, anti-inflammatory agents, phytotherapy, anxiolytics, narcotic analgesics, acupuncture, and injection therapy (steroid or anesthetic). Around
Table 5 – Outcomes of epididymectomy in patients with chronic epididymitis Author
Davis (1990) Davis & Noble (1993) Chen & Ball (1991) Padmore et al (1996)
West et al (2000) Hori et al (2009)
Sweeney et al (2008) Calleary et al (2009)
Siu et al (2007) Sweeney et al (1998)
No. patients undergoing epididymectomy
Results
10
Relief only in one patient Partial relief in 27% with inguinal orchiectomy Benefit reported by 15 patients
24 27
16 53
38 32
34 29
92% with epididymal cyst satisfied 43% with epididymalgia satisfied 14 pts with initial benefit No pain in 93.3% in postvasectomy group No pain in 75% in nonvasectomy group Resolution of symptoms in 32% Excellent results in patients with structural abnormalities 55% chance of improvement in patients with normal findings 70% reported no pain Outcome satisfactory in 27/29; best results in the vasectomy group
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all structures that may be carrying neural fibers are divided while the arteries (testicular, cremasteric, and deferential), lymphatics, and the vas deferens are preserved [50]. After reviewing eight reports on MDSC (204 patients, 2- mo follow-up), Laurence and Levine reported that 83% of patients achieved a pain-free status while 12% improved. The major advantage of MDSC is the possibility of sparing the testicle. Prevention of adhesion with the use of concurrent administration of the inhibitors of adhesion and fibrosis hyaluronic acid and carboxymethylcellulose are reported to be useful to improve the outcome of epididymectomy [44].
7
[13] Doble A, Taylor-Robinson D, Thomas BJ, Jalil N, Harris JR, Witherow RO. Acute epididymitis: a microbiological and ultrasonographic study. Br J Urol 1989;63:90–4. [14] Melekos MD, Asbach HW. Epididymitis: aspects concerning etiology and treatment. J Urol 1987;138:83–6. [15] Mittemeyer BT, Lennox KW, Borski AA. Epididymitis: a review of 610 cases. J Urol 1966;95:390–2. [16] Eickhoff JH, Frimodt-Moller N, Walter S, Frimodt-Moller C. A double-blind, randomized, controlled multicentre study to compare the efficacy of ciprofloxacin with pivampicillin as oral therapy for epididymitis in men over 40 years of age. BJU Int 1999;84:827–34. [17] Harnisch JP, Berger RE, Alexander ER, Monda G, Holmes KK. Aetiology of acute epididymitis. Lancet 1977;1:819–21. [18] Robinson AJ, Grant JB, Spencer RC, Potter C, Kinghorn GR. Acute
Conflicts of interest
epididymitis: why patient and consort must be investigated. Br J Urol 1990;66:642–5. [19] Guidelines EAU. EAU Guidelines, edition presented at the 29th EAU
The authors have nothing to disclose.
Annual Congress. Arnhem, The Netherlands: EAU Guidelines Office; 2014.
Appendix A. Supplementary data
[20] Lee CT, Thirumoorthy T, Lim KB, Sng EH. Epidemiology of acute epididymo-orchitis in Singapore. Ann Acad Med Singapore 1989;18: 320–3.
Supplementary material related to this article can be found, in the online version, at http://dx.doi.org/10.1016/j. eursup.2017.01.003.
[21] Pearson RC, Baumber CD, McGhie D, Thambar IV. The relevance of Chlamydia trachomatis in acute epididymitis in young men. Br J Urol 1988;62:72–5. [22] Banyra O, Shulyak A. Acute epididymo-orchitis: staging and treat-
References
ment. Cent European J Urol 2012;65:139–43. [23] Hongo H, Shinojima T, Yazawa S, et al. Development of an algorithm
[1] Nickel JC, Teichman JM, Gregoire M, Clark J, Downey J. Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial
for predicting severe acute epididymitis. J Urol 2014;191:e160. [24] Tae BS, Ham BK, Kim JH, Park JY, Bae JH. Clinical features of mumps
cystitis, and epididymitis in outpatient urological practice: the
orchitis in vaccinated postpubertal males: a single-center series of
Canadian PIE Study. Urology 2005;66:935–40.
62 patients. Korean J Urol 2012;53:865–9.
[2] Collins MM, Stafford RS, O’Leary MP, Barry MJ. How common is prostatitis? A national survey of physician visits. J Urol 1998;159: 1224–8.
[25] Wesselhoeft C. Orchitis in mumps. Boston Med Surg J 1920;183: 425–524. [26] Garthwaite MA, Johnson G, Lloyd S, Eardley I. The implementation
[3] CDC Guidelines. Sexually Transmitted Diseases Treatment Guide-
of European Association of Urology guidelines in the management
lines., Centers for Disease Control and Prevention; 2010 https://
of acute epididymo-orchitis. Ann R Coll Surg Engl 2007;89:799–
www.cdc.gov/std/treatment/2010.
803.
[4] Somekh E, Gorenstein A, Serour F. Acute epididymitis in boys:
[27] Parr NJ, Prasad BR, Hayhurst V, McMillan A, Leen CS, Fowler JW.
evidence of a post-infectious etiology. J Urol 2004;171:391–4,
Suppurative epididymo-orchitis in young ‘‘high risk’’ patients–a
discussion 4.
new problem? Br J Urol 1993;72:949–51.
[5] Ho¨ppner W, Strohmeyer T, Hartmann M, Lopez-Gamarra D,
[28] Drury NE, Dyer JP, Breitenfeldt N, Adamson AS, Harrison GS. Man-
Dreikorn K. Surgical treatment of acute epididymitis and its
agement of acute epididymitis: are European guidelines being
underlying diseases. Eur Urol 1992;22:218–21. [6] Kaver I, Matzkin H, Braf ZF. Epididymo-orchitis: a retrospective study of 121 patients. J Fam Pract 1990;30:548–52. [7] Pilatz A, Hossain H, Kaiser R, et al. Acute epididymitis revisited: impact of molecular diagnostics on etiology and contemporary guideline recommendations. Eur Urol 2015;68:428–35.
followed? Eur Urol 2004;46:522–4, discussion 4–5. [29] Pilatz A, Wagenlehner F, Bschleipfer T, et al. Acute epididymitis in ultrasound: results of a prospective study with baseline and followup investigations in 134 patients. Eur J Radiol 2013;82:e762–8. [30] Yu KJ, Wang TM, Chen HW, Wang HH. The dilemma in the diagnosis of acute scrotum: clinical clues for differentiating between testicular
[8] Nickel JC, Siemens DR, Nickel KR, Downey J. The patient with
torsion and epididymo-orchitis. Chang Gung Med J 2012;35:38–45.
chronic epididymitis: characterization of an enigmatic syndrome.
[31] Street EJPM, Kopa Z, Skerlev M, Wilson JD, Patel R. 2012 (IUSTI/
J Urol 2002;167:1701–4. [9] Strebel RT, Schmidt C, Beatrice J, Sulser T. Chronic scrotal pain syndrome (CSPS): the widespread use of antibiotics is not justified. Andrology 2013;1:155–9. [10] Campbell MF. Gonococcus epididymitis: observations in three thousand cases from the urological service of bellevue hospital. Ann Surg 1927;86:577–90. [11] Berger RE, Alexander ER, Harnisch JP, et al. Etiology, manifestations and therapy of acute epididymitis: prospective study of 50 cases. J Urol 1979;121:750–4.
WHO) guideline on the management of epididymo-orchitis., IUSTI EO Guideline; 2012
http://www.iusti.org/regions/Europe/pdf/
2013/Epididymo-orchitis-2013IUSTI_WHO.pdf. [32] Doehn C, Fornara P, Kausch I, Buttner H, Friedrich HJ, Jocham D. Value of acute-phase proteins in the differential diagnosis of acute scrotum. Eur Urol 2001;39:215–21. [33] Yagil Y, Naroditsky I, Milhem J, et al. Role of Doppler ultrasonography in the triage of acute scrotum in the emergency department. J Ultrasound Med 2010;29:11–21. [34] Altinkilic B, Pilatz A, Weidner W. Detection of normal intratesti-
[12] Berger RE, Kessler D, Holmes KK. Etiology and manifestations of
cular perfusion using color coded duplex sonography obviates need
epididymitis in young men: correlations with sexual orientation.
for scrotal exploration in patients with suspected testicular torsion.
J Infect Dis 1987;155:1341–3.
J Urol 2013;189:1853–8.
Please cite this article in press as: C¸ek M, et al. Acute and Chronic Epididymitis. Eur Urol Suppl (2017), http://dx.doi.org/10.1016/ j.eursup.2017.01.003
EURSUP-740; No. of Pages 8 8
EUROPEAN UROLOGY SUPPLEMENTS XXX (2016) XXX–XXX
[35] Liu CC, Huang SP, Chou YH, et al. Clinical presentation of acute scrotum in young males. Kaohsiung J Med Sci 2007;23:281–6.
[43] Lee JY, Lee TY, Park HY, et al. Efficacy of epididymectomy in treatment of chronic epididymal pain: a comparison of patients
[36] Kalfa N, Veyrac C, Lopez M, et al. Multicenter assessment of ultra-
with and without a history of vasectomy. Urology 2011;77:177–82.
sound of the spermatic cord in children with acute scrotum. J Urol
[44] Chung JH, Moon HS, Choi HY, et al. Inhibition of adhesion and
2007;177:297–301. [37] Moore CA, Lockett BL, Lennox KW, et al. Prednisone in the treatment of acute epididymitis: a cooperative study. J Urol 1971;106: 578–80. [38] Nickel JC. Chronic epididymitis: a practical approach to understanding and managing a difficult urologic enigma. Rev Urol 2003;5:209–15.
fibrosis improves the outcome of epididymectomy as a treatment for chronic epididymitis: a multicenter, randomized controlled, single-blind study. J Urol 2013;189:1730–4. [45] Kulchavenya E, Khomyakov V. Male genital tuberculosis in Siberians. World J Urol 2006;24:74–8. [46] Calleary JG, Masood J, Hill JT. Chronic epididymitis: is epididymectomy a valid surgical treatment? Int J Androl 2009;32:468–72.
[39] Hoag N, Pommerville PJ, Kibsey PC, Cavers DJ, Eddy RJ. Tuberculous
[47] Haidl G, Allam JP, Schuppe HC. Chronic epididymitis: impact on
epididymitis following intravesical Bacillus Calmette-Guerin im-
semen parameters and therapeutic options. Andrologia 2008;40:
munotherapy. Can J Urol 2009;16:4589–91. [40] Shen Y, Liu H, Cheng J, Bu P. Amiodarone-induced epididymitis: a
92–6. [48] Khambati A, Lau S, Gordon A, Jarvi KA. OnabotulinumtoxinA (Botox)
pathologically confirmed case report and review of the literature.
nerve blocks provide durable pain relief for men with chronic
Cardiology 2014;128:349–51.
scrotal pain: a pilot open-label trial. J Sex Med 2014;11:3072–7.
[41] Davatchi F, Shahram F, Chams-Davatchi C, et al. Behcet’s disease in Iran: analysis of 6500 cases. Int J Rheum Dis 2010;13:367–73. [42] West AF, Leung HY, Powell PH. Epididymectomy is an effective treatment for scrotal pain after vasectomy. BJU Int 2000;85: 1097–9.
[49] Hori S, Sengupta A, Shukla CJ, Ingall E, McLoughlin J. Long-term outcome of epididymectomy for the management of chronic epididymal pain. J Urol 2009;182:1407–12. [50] Laurence A, Levine MD. Chronic Scrotal Content Pain AUA Update Series Lesson 37, vol. 31. Linthicum, MD: AUA; 2012.
Please cite this article in press as: C¸ek M, et al. Acute and Chronic Epididymitis. Eur Urol Suppl (2017), http://dx.doi.org/10.1016/ j.eursup.2017.01.003