2016 (IUSTI/WHO) Guideline on the Management of Epididymo-Orchitis
2016 (IUSTI/WHO) guideline on the management of epididymo-orchitis
Authors:
Street EJ1, Justice ED2, Portman MD3, Kopa Z4, , Skerlev M5, Wilson JD6, Patel R7
1. Calderdale and Huddersfield NHS Foundation Trust, UK
2. The Dudley Group NHS Foundation Trust, UK
3. Central and North West London NHS Foundation Trust, UK
4. Semmelweis University, Hungary
5.. Department of Dermatology and Venereology, Zagreb University School of Medicine, Croatia
6. Leeds Teaching Hospitals NHS Trust, UK
7. Solent NHS Trust, University of Southampton, UK
Abstract:
Epididymo-orchitis is a commonly encountered condition with a reported incidence of 2.45 cases per 1000 men in the United Kingdom.(1) The 2016 IUSTI guideline provides up-to-date advice on the management of this condition. It describes the aetiology, clinical features, and potential complications, as well as presenting diagnostic considerations and clear recommendations for management and follow-up. Early diagnosis and management are essential, as serious complications can include abscess formation, testicular infarction and infertility. Recent epidemiological evidence suggests that selection of fluoroquinolone antibiotics with anti-Chlamydial activity is more appropriate in the management of sexually active men in the over 35 years age group.(2)
Keywords:
Epididymitis, Epididymo-orchitis, Europe, treatment, antibiotic
Declarations of interest: None of the authors or editors had any conflicts of interest forthe content of this guideline.
Revision date: 30/06/2020Proposed date for review: 30/06/2018
AETIOLOGY AND TRANSMISSION
Epididymo-orchitis is an inflammatory process of the epididymis +/- testes.(3) This clinical syndrome most often presents with acute onset of pain and swelling. It is caused by eithersexually transmitted pathogens ascending from the urethra or non-sexually transmitteduropathogens spreading from the urinary tract.
Sexually transmitted infections
Chlamydia trachomatis- especially in younger patients
Neisseria gonorrhoeae- especially in younger patients
Gram negative enteric organisms – in men engaging in insertive anal intercourse(4)
Non- sexually transmitted infections
Gram negative enteric organisms- risk factors include obstructive urinary disease, urinarytract surgery or instrumentation.(5)
Mumps (commonest cause of isolated orchitis) - may occur as part of an epidemic, morefrequently in an area with insufficient vaccination programme.(6)
Tuberculosis (TB) - commonly associated with renal TB, but can also be an isolated finding.(7)
Brucellosis - in endemic areas.(8),(9)
Candida
Non-infectious
Amiodarone - symptoms usually resolve on cessation of treatment.(10)
Behçet's disease - associated with more severe disease, occurring in 12-19% of men with Behçet’s disease.(11)
CLINICAL FEATURES
Symptoms: acute onset, usually unilateral scrotal pain +-/ swelling. (12)
Symptoms of urethritis- urethral discharge, dysuria, penile irritation butpatients can be asymptomatic.(13),(14),(15)
Symptoms of urinary tract infection: dysuria, frequency, urgency.
Physical signs: typically unilateral swelling and tenderness of epididymis +/- testes, usually beginning in the tail of the epididymis and spreading to involve the whole ofthe epididymis and testes.
Other signs:
◦ Urethral discharge
◦ Hydrocoele
◦ Erythema +/- oedema of scrotum
◦ Pyrexia
Disease specific symptoms and signs:
Mumps: headache and fever followed by unilateral/bilateral parotid swelling. This is followed 7-10days later by unilateral testicular swelling. Atypically, those affected can presentwith bilateral testicular swelling, epididymitis alone or without systemic symptoms.(16),(17)
Tuberculosis: subacute/more chronic onset of painless/ painful scrotal swelling +/-systemic symptoms +/- scrotal sinus +/- thickened scrotal skin.(7, 18)
Brucellosis: fever, sweats, headache, back pain, and weakness in acute infection.(19)
Complications:
These tend to be more frequently seen with uropathogen associated infection.(20)
◦ Hydrocoele
◦ Abscess and infarction of the testicle
◦ Infertility - there is a poorly understood relationship betweenepididymo-orchitis and infertility.
DIAGNOSIS
Epididymo-orchitis is a clinical diagnosis based on symptoms and signs.The history, eliciting genitourinary symptoms and the risk of STIs (including analintercourse), alongside examination findings and preliminary investigations will suggest themost likely aetiology and guide empiric antibiotics.
Historically sexually transmitted infections have been attributed as the predominant cause for Epididymitis in the <35 age group and enteric pathogens in the >35 age group. Evidence to support this approach is limited; and age and sexual history taking are not sufficient for guiding antibiotic therapy alone.(2)
Differential diagnosis:
Testicular torsion is the main differential diagnosis. This is a surgical emergency.If a young man or adolescent presents with a painful swollen testicle of sudden onset thenthe diagnosis is testicular torsion until proven otherwise.(21) The patient should be promptlyreferred to urologist. Testicular salvage is required within six hours and the likelihood of agood outcome decreases with time.(22),(23) Empiric antibiotics should also be issued in thesecircumstances.
Torsion is more likely if:
The patient is under 20 years (but can occur at any age)
The pain is sudden (within hours)
The pain is severe
Preliminary tests do not show urethritis or likely urinary tract infection.(22),(23)
A colour Doppler ultrasound (duplex) may be helpful in assessing the vascularity of thetestes and therefore may aid in differentiating between epididymo-orchitis and testiculartorsion.(24),(25)Although colour Doppler has high sensitivity for diagnosing epididymo-orchitis, it cannot be used to exclude the condition.(26),(27) If there is suspicion of testicular torsion, arranging an ultrasound should not delay surgical exploration.
Preliminary investigations should include:
Diagnosis of urethritis with microscopy of a gram stained(28)/methylene blue stained(29),(30)urethral smear showing > 5PMNLs per HPF ( 1000x) OR a spun down samplefrom first pass urine gram stained showing >10 PMNLs per HFP ( 1000x).
Urine dipstick – useful only as an adjunct to MSU.(31) A negative dipstick test in menshould not exclude the diagnosis of UTI.(32),(33). The presence of nitrite and leukocyte-esterasesuggests UTI in men with urinary symptoms.(32),(33)
Laboratory investigations:
• Urethral swab for N. gonorrhoea culture
• First pass urine (FPU)/ urethral swab for nucleic acid amplification test (NAAT) forN. gonorrhoeae and C. trachomatis
• Mid-stream urine for microscopy and culture
• CRP and ESR can aid the diagnosis of epididymitis if raised, but surgical referral orantibiotic treatment should not be delayed on the basis of these tests.(34),(35)
All patients with sexually transmitted epididymo-orchitis should be screened for othersexually transmitted infections including blood borne viruses.
MANAGEMENT
Information, explanation and advice should be given to the patient: an explanationof the causes of epididymo-orchitis (both sexually transmitted and non-sexuallytransmitted), the short term course of the infection and the long term implications forthemselves and their partner (if sexually transmitted cause).
General advice: analgesia, rest and scrotal support.
Sexual abstinence should be advised for those with suspected sexually transmitted epididymo-orchitis until treatment is completed by both patient and partner and their symptoms have settled.(4)
Therapy: empiric antibiotics according to the likelihood of a sexually transmitted oruropathogen.
Choose regime based on immediate tests- urethral/FPU smear, urinalysis and taking into account age, sexual history, recent surgery/ catheterisation, any known urinarytract abnormalities and the local prevalence of gonorrhoea and antibiotic resistancepatterns.
Sexually transmitted epididymo-orchitis:
First line choice:
Ceftriaxone 500mg intramuscular injection (36)IIIB PLUS
Doxycycline 100mg twice daily for 10 to 14 days (37),(38) IIIB
OR
Second line choice:
Ofloxacin 200mg twice daily for 14 days(37),(38) IIB OR
Levofloxacin 500mg once daily for 10 days (39) IIIB
Epididymo-orchitis most likely secondary to enteric organisms:
Ofloxacin 200mg twice daily for 14 days(40),(41),(42)IIB OR
Levofloxacin 500mg once daily for 10 days (2),(27),(43)IIIB[R1]
Points to note and consider:
1. Where gonorrhoea is considered unlikely; urethral /FPU microscopy negative forGNID, no risk factors for gonorrhoea identified (absence of all of the following – apurulent urethral discharge, known contact of GC, MSM, black ethnicity)(36)and incountries/ populations where there is known very low gonorrhoea prevalence, omitting Ceftriaxone or using Ofloxacin could be considered.(44) Ofloxacin treats N.gonorrhoeae, C, trachomatis and most uropathogens with good penetration into theprostate. However, it is not first line treatment for N. gonorrhoea due to increasingbacterial resistance to quinolones.(45)
2. In patients where gonorrhoea is considered likely (see risk factors above) Azithromycin should be added to Ceftriaxone and Doxycycline to provide optimal antibiotic cover.(45)
3. Ciprofloxacin does not effectively treat Chlamydia.(46)
4. If epididymitis secondary to gonorrhoea is confirmed, a test of cure is required at 2weeks following completion of gonorrhoea treatment with a positive NAAT; and after 3 days following completion of gonorrhoea treatment with a positive gonorrhoeaculture, particularly if treatment has been with a quinolone.(45) If epididymitis secondary to chlamydia is confirmed, a test of cure is required at 4 week following completion of a treatment course.
Partner notification:
For patients with confirmed or suspected sexually transmitted epididymo-orchitis (N. gonorrhoeae or C. trachomatis) all partners potentially at risk should be notified andevaluated. They should be tested for all STIs and given treatment with antibiotics to coverC. trachomatis (and N. gonorrhoeae if confirmed in the index patient). The duration of look-back for contact tracing would be 6 months for confirmed C. trachomatis epididymo-orchitis and 60 days for confirmed N. gonorrhoeae epididymo-orchitis. In other cases thought to be sexually transmitted infections other than C. trachomatis and N.gonorrhoeae, the duration of look-back is arbitrary, although sixty days is suggested.(47),(48)
Follow up:
- At 3 days if no improvement in symptoms, the patient should be seen for clinicalreview and the diagnosis should be re-assessed.
- At 2 weeks for compliance check, assessment of symptoms and partnernotification. This could be done by telephone but if the patient has persistingsymptoms, arrangements should be made for clinical review.
Further investigations:
All patients with suspected/confirmed sexually transmitted epididymo-orchitis should bescreened for all other STIs including blood borne viruses.
All patients with uropathogen confirmed epididymo-orchitis should be referred to a urologyspecialist for further investigations looking for structural abnormalities /urinary tract obstruction.(49)
In patients where there has not been significant improvement in symptoms/signs aftercompletion of therapy, or there is diagnostic doubt, a scrotal ultrasound should be ordered.
Differential diagnoses to consider in these circumstances include progression to abscess (50), testicular ischaemia/ infarct (51), testicular/epididymal tumour (12). Further referralto urology should also be considered.
Prevention/health promotion:
Patients should be advised that consistent condom use will reduce the risk of acquiringsexually transmitted epididymo-orchitis.(52)
SEARCH STRATEGY
This guideline represents an updated and revised version of the ‘2012 European guideline on the management of epididymo-orchitis’.(53)The guideline for management of epididymo-orchitis was written after a literature search in the Medline, Embase, and Cochrane databases for English-language articles published between 2001 and March 2012. The guideline was updated following a further literature search in the Medline, Embase, and Cochrane databases between March 2012 and February 2016. Current major European National and CDC guidelines were also reviewed.
Grading of Evidence:
Levels of evidence are assigned and recommendations graded as below:
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised controlled trial.
IIa Evidence obtained from at least one well designed study without randomisation.
IIb Evidence obtained from at least one other type of well designed quasi-experimentalstudy.
III Evidence obtained from well designed non-experimental descriptive studies such ascomparative studies, correlation studies, and case control studies.
IV Evidence obtained from expert committee reports or opinions and /or clinicalexperience of respected authorities.
A (Evidence levels Ia, Ib) Requires at least one randomised control trial as part of thebody of literature of overall good quality and consistentlyaddressing the specific recommendation.
B (Evidence IIa, IIb, III) Requires availability of well conducted clinical studies but norandomised clinical trials on the topic of recommendation.
C (Evidence IV) Requires evidence from expert committee reports or opinionsand/or clinical experience of respected authorities. Indicatesabsence of directly applicable studies of good quality.
REFERENCES:
1.Nicholson A, Rait G, Murray-Thomas T, Hughes G, Mercer CH, Cassell J. Management of epididymo-orchitis in primary care: results from a large UK primary care database. Br J Gen Pract. 2010;60(579):e407-22.
2.Pilatz A, Hossain H, Kaiser R, Mankertz A, Schüttler CG, Domann E, et al. Acute epididymitis revisited: impact of molecular diagnostics on etiology and contemporary guideline recommendations. Eur Urol. 2015;68(3):428-35.
3.Tracy CR, Steers WD, Costabile R. Diagnosis and management of epididymitis. Urol Clin North Am. 2008;35(1):101-8; vii.
4.Centers for Disease Control and Prevention. 2015 Sexually Transmitted Infections Treatment Guidelines - Epididymitis. Division of STD Prevention, National Centre for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention. 2015. Available from:
5.Mittemeyer BT, Lennox KW, Borski AA. Epididymitis: a review of 610 cases. J Urol. 1966;95(3):390-2.
6.Gupta RK, Best J, MacMahon E. Mumps and the UK epidemic 2005. BMJ. 2005;330(7500):1132-5.
7.Viswaroop BS, Kekre N, Gopalakrishnan G. Isolated tuberculous epididymitis: a review of forty cases. J Postgrad Med. 2005;51(2):109-11, discussion 11.
8.Akinci E, Bodur H, Cevik MA, Erbay A, Eren SS, Ziraman I, et al. A complication of brucellosis: epididymoorchitis. Int J Infect Dis. 2006;10(2):171-7.
9.Savasci U, Zor M, Karakas A, Aydin E, Kocaaslan R, Oren NC, et al. Brucellar epididymo-orchitis: a retrospective multicenter study of 28 cases and review of the literature. Travel Med Infect Dis. 2014;12(6 Pt A):667-72.
10.Gasparich JP, Mason JT, Greene HL, Berger RE, Krieger JN. Amiodarone-associated epididymitis: drug-related epididymitis in the absence of infection. J Urol. 1985;133(6):971-2.
11.Cho YH, Jung J, Lee KH, Bang D, Lee ES, Lee S. Clinical features of patients with Behçet's disease and epididymitis. J Urol. 2003;170(4 Pt 1):1231-3.
12.Giesler WM, Krieger JN. Epididymitis In Sexually Transmitted Diseases. In: Holmes KK, Sparling PF, Stamm WE, et al. (eds.)Sexually Transmitted Diseases, 4th Edition. McGraw Hill Medical, New York; 2008. p. 1127-1146.
13.Hawkins DA, Taylor-Robinson D, Thomas BJ, Harris JR. Microbiological survey of acute epididymitis. Genitourin Med. 1986;62(5):342-4.
14.Mulcahy FM, Bignell CJ, Rajakumar R, Waugh MA, Hetherington JW, Ewing R, et al. Prevalence of chlamydial infection in acute epididymo-orchitis. Genitourin Med. 1987;63(1):16-8.
15.Watson RA. Gonorrhea and acute epididymitis. Mil Med. 1979;144(12):785-7.
16.Wharton IP, Chaudhry AH, French ME. A case of mumps epididymitis. Lancet. 2006;367(9511):702.
17.Nickel WR, Plumb RT. Mumps orchitis. In: Harrison JH, Gittes RF, Perlmutter AD, Stamey TA, Walsh PC. (eds.)Campbells Urology, 5th edn. Philadelphia: W.B. Saunders Co; 1986. p. 977-988.
18.Ferrie BG, Rundle JS. Tuberculous epididymo-orchitis. A review of 20 cases. Br J Urol. 1983;55(4):437-9.
19.Maloney GE. Brucellosis.2010. Medscape. Available from:
20.Luzzi GA, O'Brien TS. Acute epididymitis. BJU Int. 2001;87(8):747-55.
21.Dudley M. Assume nothing. Medical Protection Society Casebook.2007. 15(3):23. Available from:
22.Williamson RC. Torsion of the testis and allied conditions. Br J Surg. 1976;63(6):465-76.
23.Knight PJ, Vassy LE. The diagnosis and treatment of the acute scrotum in children and adolescents. Ann Surg. 1984;200(5):664-73.
24.Rizvi SA, Ahmad I, Siddiqui MA, Zaheer S, Ahmad K. Role of color Doppler ultrasonography in evaluation of scrotal swellings: pattern of disease in 120 patients with review of literature. Urol J. 2011;8(1):60-5.
25.Dell'Atti L, Fabiani A, Marconi A, Mantovani P, Muzzonigro G. Reliability of echo-color-Doppler in the differential diagnosis of the "acute scrotum". Our experience. Arch Ital Urol Androl. 2005;77(1):66-8.
26.Yu KJ, Wang TM, Chen HW, Wang HH. The dilemma in the diagnosis of acute scrotum: clinical clues for differentiating between testicular torsion and epididymo-orchitis. Chang Gung Med J. 2012;35(1):38-45.
27.Centers for Disease Control and Prevention. 2015 Sexually Transmitted Infections Treatment Guidelines - Epididymitis. Division of STD Prevention, National Centre for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention. 2015. Available from:
28.Swartz SL, Kraus SJ, Herrmann KL, Stargel MD, Brown WJ, Allen SD. Diagnosis and etiology of nongonococcal urethritis. J Infect Dis. 1978;138(4):445-54.
29.Falk L, Fredlund H, Jensen JS. Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis. Sex Transm Infect. 2004;80(4):289-93.
30.Moi H, Danielsson D. Diagnosis of genital Chlamydia trachomatis infection in males by cell culture and antigen detection test. Eur J Clin Microbiol. 1986;5(5):563-8.
31.Schmiemann G, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-Pradier E. The diagnosis of urinary tract infection: a systematic review. Dtsch Arztebl Int. 2010;107(21):361-7.
32.Koeijers JJ, Kessels AG, Nys S, Bartelds A, Donker G, Stobberingh EE, et al. Evaluation of the nitrite and leukocyte esterase activity tests for the diagnosis of acute symptomatic urinary tract infection in men. Clin Infect Dis. 2007;45(7):894-6.
33.Etienne M, Pestel-Caron M, Chavanet P, Caron F. Performance of the urine leukocyte esterase and nitrite dipstick test for the diagnosis of acute prostatitis. Clin Infect Dis. 2008;46(6):951-3; author reply 3.
34.Ciftci AO, Senocak ME, Tanyel FC, Büyükpamukçu N. Clinical predictors for differential diagnosis of acute scrotum. Eur J Pediatr Surg. 2004;14(5):333-8.
35.Doehn C, Fornara P, Kausch I, Büttner H, Friedrich HJ, Jocham D. Value of acute-phase proteins in the differential diagnosis of acute scrotum. Eur Urol. 2001;39(2):215-21.
36.Street E, Joyce A, Wilson J, Clinical Effectiveness Group BiAfSHaH. BASHH UK guideline for the management of epididymo-orchitis, 2010. Int J STD AIDS. 2011;22(7):361-5.
37.Berger RE, Alexander ER, Harnisch JP, Paulsen CA, Monda GD, Ansell J, et al. Etiology, manifestations and therapy of acute epididymitis: prospective study of 50 cases. J Urol. 1979;121(6):750-4.
38.Hoosen AA, O'Farrell N, van den Ende J. Microbiology of acute epididymitis in a developing community. Genitourin Med. 1993;69(5):361-3.
39.Saito I, Suzuki A, Saiko Y, Yokozawa M, Ono K, Miyata K, et al. [Acute nongonococcal epididymitis--pharmacological and therapeutic aspects of levofloxacin]. Hinyokika Kiyo. 1992;38(5):623-8.
40.Melekos MD, Asbach HW. Epididymitis: aspects concerning etiology and treatment. J Urol. 1987;138(1):83-6.
41.Weidner W, Schiefer HG, Garbe C. Acute nongonococcal epididymitis. Aetiological and therapeutic aspects. Drugs. 1987;34 Suppl 1:111-7.
42.Weidner W, Garbe C, Weissbach L, Harbrecht J, Kleinschmidt K, Schiefer HG, et al. [Initial therapy of acute unilateral epididymitis using ofloxacin. I. Clinical and microbiological findings]. Urologe A. 1990;29(5):272-6.
43.European Association of Urology. Urological Infections: Acute Infective Epididymitis. European Association of Urology. 2016. Available from:
44.O'Mahony C, Evans-Jones J. Urological management of epididymo-orchitis: simple, ofloxacin for all! Sex Transm Infect. 2011;87(1):43.
45.Bignell C, Fitzgerald M, Group GD, UK BAfSHaH. UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS. 2011;22(10):541-7.