The clinical presentation of acute epididymitis is typically of unilateral pain and swelling of the scrotum. The most important differential diagnosis to consider is that of testicular torsion, particularly when the onset of pain is sudden and severe, and initial examination and tests show no evidence of inflammation or infection.
Risk factors
These include unprotected sexual intercourse. A history of anal intercourse may be associated with infection due to enteric organisms.[15]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
Uncommon risk factors include history of mumps[3]Gupta RK, Best J, MacMahon E. Mumps and the UK epidemic 2005. BMJ. 2005 May 14;330(7500):1132-5.
https://www.bmj.com/content/330/7500/1132.long
http://www.ncbi.nlm.nih.gov/pubmed/15891229?tool=bestpractice.com
or risk factors for tuberculosis (TB) (e.g., personal history of prior TB, exposure to a patient with TB, travel to a TB endemic region, or use of intravesical BCG therapy for bladder cancer).[17]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
Infection with enteric organisms is associated with bladder outlet obstruction, urinary tract infection, recent instrumentation of the urinary tract, or systemic illness, particularly immunosuppression.[15]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
Clinical evaluation
A full patient history is of vital importance in determining the likely etiology of acute epididymitis. In particular, a sexual history reviewing the risk of STIs should be sought, along with any history of preexisting lower urinary tract symptoms or recent instrumentation.[26]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 hot, erythematous, swollen hemiscrotum, with tender enlargement of the epididymis. Diffuse enlargement of the testis will be present in epididymo-orchitis. In cases of urethritis, mucopurulent discharge may be present at the urethral meatus and/or symptoms of dysuria 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.[18]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 a history of known exposure is not present.[17]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 noninfectious 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 presence of urethritis in men with symptoms (e.g., mucopurulent urethral discharge and/or dysuria).[26]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.[27]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
[28]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 forN gonorrhoeae is a less sensitive, alternative option to a NAAT for gonorrhea, it is the preferred option if antibiotic susceptibility testing is desired (culture for gonorrhea requires collection of a urethral swab). Mycoplasma genitalium is diagnosed with NAAT (currently only available in some laboratories).[26]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
[29]Soni S, Horner P, Rayment M, et al. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int J STD AIDS. 2019 Sep;30(10):938-50.
https://www.doi.org/10.1177/0956462419825948
http://www.ncbi.nlm.nih.gov/pubmed/31280688?tool=bestpractice.com
[30]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
[31]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 epidiymo-orchitis if they are younger than 50 years.[30]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.[29]Soni S, Horner P, Rayment M, et al. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int J STD AIDS. 2019 Sep;30(10):938-50.
https://www.doi.org/10.1177/0956462419825948
http://www.ncbi.nlm.nih.gov/pubmed/31280688?tool=bestpractice.com
[30]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
[32]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
IUTSI recommends testing for macrolide resistance in all confirmed M genitalium cases.[30]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.[33]European Association of Urology. Guidelines on urological infections. Mar 2022 [internet publication].
https://uroweb.org/guidelines/urological-infections
Three early morning urine samples should be cultured for acid-fast bacilli and sent for NAAT for Mycobacterium tuberculosisDNA/RNA in patients suspected of having TB.[17]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
[33]European Association of Urology. Guidelines on urological infections. Mar 2022 [internet publication].
https://uroweb.org/guidelines/urological-infections
Color 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.[7]American College of Radiology. ACR appropriateness criteria: acute onset of scrotal pain - without trauma, without antecedent mass. 2014 (revised 2018) [internet publication].
https://acsearch.acr.org/docs/69363/Narrative
[34]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
Surgical exploration may be indicated in cases where testicular torsion cannot be confidently excluded.
Noninfectious 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.