Clinical evaluation
History should include sexual history, risk of STIs, pre-existing lower urinary tract symptoms, and recent instrumentation.[3]Street EJ, Justice ED, Kopa Z, et al. The 2016 European guideline on the management of epididymo-orchitis. Int J STD AIDS. 2017 Jul;28(8):744-9.
http://www.ncbi.nlm.nih.gov/pubmed/28632112?tool=bestpractice.com
These factors will allow the likely causative agents to be determined and appropriate empirical antibiotic treatment to be instigated prior to the results of diagnostic tests.
Examination may reveal a warm, erythematous, swollen hemiscrotum, with tender enlargement of the epididymis. Diffuse enlargement of the testis will be present in epididymo-orchitis. In cases of urethritis, urethral discharge and/or symptoms of dysuria may be present. In severe cases, the patient may be febrile and systemically ill. A reactive hydrocele may also be present and abscess formation may be evident by fluctuance of the swelling and induration of the overlying scrotal tissue. A digital rectal examination is recommended to assess for benign prostatic enlargement, which may suggest underlying bladder outflow obstruction and increased risk of acute epididymitis, and exclude tenderness of the prostate suggestive of concurrent acute prostatitis.
Tuberculous epididymitis may present as acute epididymitis refractory to conventional treatment.[20]Gómez García I, Gómez Mampaso E, Burgos Revilla J, et al. Tuberculous orchiepididymitis during 1978-2003 period: review of 34 cases and role of 16S rRNA amplification. Urology. 2010 Oct;76(4):776-81.
http://www.ncbi.nlm.nih.gov/pubmed/20350748?tool=bestpractice.com
Acute involvement usually disappears within 2 to 4 weeks, and as the condition evolves and becomes chronic, a hard, painless mass develops. It should be considered if no obvious other cause is determined, even if there is no known history of tuberculosis (TB) exposure.[19]Yadav S, Singh P, Hemal A, et al. Genital tuberculosis: current status of diagnosis and management. Transl Androl Urol. 2017 Apr;6(2):222-33.
http://tau.amegroups.com/article/view/13854/14808
http://www.ncbi.nlm.nih.gov/pubmed/28540230?tool=bestpractice.com
The clinical features of non-infectious epididymitis are the same as those with an infectious cause, but patients may have a history of amiodarone use or symptoms of vasculitis, such as a rash, and will not usually have a high fever or other symptoms of sepsis.
Investigations
Investigations are indicated to determine the underlying cause of epididymitis.
Where available, a urethral swab should be sent for Gram stain of urethral secretions to assess for the the diagnosis of urethritis in both symptomatic and asymptomatic males.[2]Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344968
http://www.ncbi.nlm.nih.gov/pubmed/34292926?tool=bestpractice.com
[3]Street EJ, Justice ED, Kopa Z, et al. The 2016 European guideline on the management of epididymo-orchitis. Int J STD AIDS. 2017 Jul;28(8):744-9.
http://www.ncbi.nlm.nih.gov/pubmed/28632112?tool=bestpractice.com
A urine dipstick test that is positive for leukocytes is suggestive of infection of the lower urogenital tract, and a first-void urine sample should be sent for urine microscopy and culture. Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae on the first-void urine sample has a higher sensitivity compared with culture, and is the preferred test for patients in whom these infections are suspected.[29]Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae - 2014. MMWR Recomm Rep. 2014 Mar 14;63(rr-02):1-19.
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6302a1.htm
http://www.ncbi.nlm.nih.gov/pubmed/24622331?tool=bestpractice.com
[30]Miller JM, Binnicker MJ, Campbell S, et al. Guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2024 update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clin Infect Dis. 2024 Mar 5:ciae104.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae104/7619499
http://www.ncbi.nlm.nih.gov/pubmed/38442248?tool=bestpractice.com
While culture for N gonorrhoeae is a less sensitive, alternative option to NAAT for gonorrhoea, it is the preferred option if antibiotic susceptibility testing is desired (culture for gonorrhoea requires collection of a urethral swab). Mycoplasma genitalium is diagnosed using NAAT where available.[3]Street EJ, Justice ED, Kopa Z, et al. The 2016 European guideline on the management of epididymo-orchitis. Int J STD AIDS. 2017 Jul;28(8):744-9.
http://www.ncbi.nlm.nih.gov/pubmed/28632112?tool=bestpractice.com
[31]Soni S, Fifer H, Al-Shakarchi Y, et al. British association of sexual health and HIV national guideline for the management of infection with Mycoplasma genitalium, 2025. Int J STD AIDS. 2025 Jul 17:9564624251359054.
https://journals.sagepub.com/doi/10.1177/09564624251359054
http://www.ncbi.nlm.nih.gov/pubmed/40673484?tool=bestpractice.com
[32]Jensen JS, Cusini M, Gomberg M, et al. 2021 European guideline on the management of Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol. 2022 May;36(5):641-50.
https://www.doi.org/10.1111/jdv.17972
http://www.ncbi.nlm.nih.gov/pubmed/35182080?tool=bestpractice.com
[33]Gaydos CA. Mycoplasma genitalium: accurate diagnosis is necessary for adequate treatment. J Infect Dis. 2017 Jul 15;216(suppl 2):S406-11.
https://academic.oup.com/jid/article/216/suppl_2/S406/4040965
http://www.ncbi.nlm.nih.gov/pubmed/28838072?tool=bestpractice.com
The International Union Against Sexually Transmitted Infections (IUSTI) recommends testing for M genitalium in men presenting with acute epididymo-orchitis if they are younger than 50 years.[32]Jensen JS, Cusini M, Gomberg M, et al. 2021 European guideline on the management of Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol. 2022 May;36(5):641-50.
https://www.doi.org/10.1111/jdv.17972
http://www.ncbi.nlm.nih.gov/pubmed/35182080?tool=bestpractice.com
Due to the fastidious nature of M genitalium, culture is difficult and antimicrobial resistance testing is limited. Molecular detection of specific resistance-mediating mutations is available in some countries.[31]Soni S, Fifer H, Al-Shakarchi Y, et al. British association of sexual health and HIV national guideline for the management of infection with Mycoplasma genitalium, 2025. Int J STD AIDS. 2025 Jul 17:9564624251359054.
https://journals.sagepub.com/doi/10.1177/09564624251359054
http://www.ncbi.nlm.nih.gov/pubmed/40673484?tool=bestpractice.com
[32]Jensen JS, Cusini M, Gomberg M, et al. 2021 European guideline on the management of Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol. 2022 May;36(5):641-50.
https://www.doi.org/10.1111/jdv.17972
http://www.ncbi.nlm.nih.gov/pubmed/35182080?tool=bestpractice.com
[34]Unemo M, Jensen JS. Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium. Nat Rev Urol. 2017 Mar;14(3):139-52.
http://www.ncbi.nlm.nih.gov/pubmed/28072403?tool=bestpractice.com
IUSTI-Europe recommends testing for macrolide resistance in all confirmed M genitalium cases.[32]Jensen JS, Cusini M, Gomberg M, et al. 2021 European guideline on the management of Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol. 2022 May;36(5):641-50.
https://www.doi.org/10.1111/jdv.17972
http://www.ncbi.nlm.nih.gov/pubmed/35182080?tool=bestpractice.com
All patients with sexually transmitted epididymo-orchitis should be screened for other STIs including syphilis and HIV.[2]Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344968
http://www.ncbi.nlm.nih.gov/pubmed/34292926?tool=bestpractice.com
[4]European Association of Urology. Guidelines on urological infections. Mar 2025 [internet publication].
https://uroweb.org/guidelines/urological-infections
In patients suspected of having TB, three early morning urine samples should be cultured for acid-fast bacilli and sent for NAAT for Mycobacterium tuberculosis DNA.[4]European Association of Urology. Guidelines on urological infections. Mar 2025 [internet publication].
https://uroweb.org/guidelines/urological-infections
[19]Yadav S, Singh P, Hemal A, et al. Genital tuberculosis: current status of diagnosis and management. Transl Androl Urol. 2017 Apr;6(2):222-33.
http://tau.amegroups.com/article/view/13854/14808
http://www.ncbi.nlm.nih.gov/pubmed/28540230?tool=bestpractice.com
Colour duplex ultrasonography is not routinely indicated for patients with suspected epididymitis, but should be done in patients with signs suggestive of abscess formation or possible testicular torsion and infarction.[10]American College of Radiology. ACR appropriateness criteria: acute onset of scrotal pain-without trauma, without antecedent mass. 2024 [internet publication].
https://acsearch.acr.org/docs/69363/Narrative
[35]Ota K, Fukui K, Oba K, et al. The role of ultrasound imaging in adult patients with testicular torsion: a systematic review and meta-analysis. J Med Ultrason (2001). 2019 Jul;46(3):325-34.
https://www.doi.org/10.1007/s10396-019-00937-3
http://www.ncbi.nlm.nih.gov/pubmed/30847624?tool=bestpractice.com
[36]Sparano A, Acampora C, Scaglione M, et al. Using color power Doppler ultrasound imaging to diagnose the acute scrotum. A pictorial essay. Emerg Radiol. 2008 Sep;15(5):289-94.
http://www.ncbi.nlm.nih.gov/pubmed/18351406?tool=bestpractice.com
Urgent surgical exploration may be indicated in cases where testicular torsion cannot be confidently excluded.[2]Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344968
http://www.ncbi.nlm.nih.gov/pubmed/34292926?tool=bestpractice.com
[3]Street EJ, Justice ED, Kopa Z, et al. The 2016 European guideline on the management of epididymo-orchitis. Int J STD AIDS. 2017 Jul;28(8):744-9.
http://www.ncbi.nlm.nih.gov/pubmed/28632112?tool=bestpractice.com
See Testicular torsion.
Non-infectious causes of epididymitis are usually evident from the history of amiodarone use or underlying vasculitis and are confirmed through negative tests for bacterial infection. Idiopathic epididymitis is a diagnosis of exclusion.