Description

Urethritis describes urethral inflammation and can be the result of infectious or non-infectious causes but is primarily a sexually acquired disease.

Urethritis can be diagnosed if any of the following are present:

• Mucopurulent or purulent discharge from urethral meatus.
• Gram stain of urethral smear showing >5 polymorphonuclear (PMN) cells per high power field. This is the preferred test as it is rapid, highly sensitive and specific for both nonspecific urethritis and gonorrhoea in asymptomatic men.¹
• First pass urine (FPU) positive for >10 PMN per high power field. Some advocate the use of positive leukocytes in FPU - but the sensitivity is low.

Classification of male urethritis²

1. Gonococcal urethritis - caused by Neisseria gonorrhoeae.
2. Non-gonococcal urethritis (NGU) - caused by a number of organisms other than N. gonorrhoeae as well as non-infective agents.
3. Persistent or recurrent urethritis - 10-20% of cases treated for NGU.

Causes of non-gonococcal urethritis²

• No identifiable cause in over 50% of patients.
• Chlamydia trachomatis (up to 45% of patients).³
• Mycoplasma genitalium (10-25%).
• Trichomonas vaginalis (1-20%).
• Ureaplasma urealyticum (5-10%).
• Rarer infective causes:
  • Urinary tract infection (fewer than 6%)
  • Adenoviruses (2-4%).
  • Herpes simplex viruses (2-3%).
  • Occasionally, Candida spp., Haemophilus spp., Neisseria meningitidis, E.coli infection.
• Non-infective causes of NGU include:²
  • Trauma (for example, catheterisation).
  • Irritation (from, for example, soap, spermicidal creams and deodorants).
  • Urethral stricture.
  • Other inflammatory conditions (including lichen sclerosus et atrophicus, Stevens-Johnson syndrome, reactive arthritis, Reiter's syndrome).
  • Urinary calculi and foreign body.

Causes of persistent or recurrent urethritis²

Probable multifactorial causes but usually no identifiable cause. However, M. genitalium (20-40% of cases), U. urealyticum (tetracycline-resistant), and T. vaginalis have been implicated.

Epidemiology²

• Urethritis is the most common condition diagnosed and treated in men attending genitourinary medicine (GUM) clinics in the UK. Over 80,000 cases are diagnosed every year.
• Non-gonococcal urethritis (NGU) is more common than gonococcal urethritis.
• Chlamydia is most common in young people aged 15-24. It is the most common sexually transmitted disease in the UK. In 2009 there were 217,570 new cases diagnosed in any clinical setting. This was 7% more than in the previous year.
• Persistent or recurrent urethritis occurs in 10-20% of men treated for NGU.⁴
• The incidence of gonorrhoea in the UK has fallen over the period of a decade, bucking the upward trend for sexually transmitted infections in general. A small increase of 6% was however seen in the UK between 2008-2009, with more than 17,000 new cases diagnosed that year, and a 3% rise reported in England between 2009 and 2010.The highest rates of gonorrhoea are amongst the young and 50% cases of gonorrhoea were diagnosed in under 25 year-olds. Rates vary within sexual groupings - e.g. higher rates are seen in men who have sex with men than in men who are exclusively heterosexual.⁵

Presentation⁶

• May be asymptomatic (90-95% of men with gonorrhoea⁷, 50% of patients with chlamydial infections).⁸
• Urethral discharge - mucopurulent or purulent; with or without blood; more noticeable after holding urine overnight and more common in gonococcal infection⁹. May have gone unnoticed by the patient and be seen only on examination.²
• Urethral pruritus, dysuria or penile discomfort with a risk of sexually transmitted infection (sexually active and has not used a condom or has a recent new sexual partner).²
• Other symptoms associated with the cause, e.g. skin lesions in herpes simplex virus.
• Systemic symptoms if there is involvement of other organs, e.g. conjunctivitis or arthritis.

Examination may be normal or may reveal haematuria and/or lymphadenopathy.

There is currently a national screening programme for chlamydia.¹⁰

Identify high-risk patients^2,11

• Sexually active
• Male
• Unprotected vaginal sex
• Homosexual or bisexual
• More common in cities
• Age <35-40 years
• Recent partner change

Investigations²

Ideally this should be performed in a GUM clinic or primary care clinic which provides sexual health facilities as an enhanced service:

• Check with the local laboratory to see which investigations they provide.
• FPU for nucleic acid amplification testing (NAAT) is the best option to exclude chlamydia in men, as it is as accurate as, but less invasive than, a urethral swab. The sample should be collected at least one hour and preferably two hours after previous voiding.¹²
• The local laboratory may be able to do NAAT on an FPU for gonorrhoea as well but, if not, a urethral smear will be required. Specimens should be sent to the laboratory as soon as possible. If there is likely to be considerable delay getting swabs from primary care to the laboratory, it may be preferable to ask the patient to attend a GUM clinic.
• Pharyngeal and rectal swabs may also be needed.
• A stick test of urine should be performed to exclude urinary tract infection.

Differential diagnosis²

• Physiological discharge
• Candidal balanitis
• Epididymitis, orchitis
• Cystitis
• Acute prostatitis
• Urethral malignancy

Associated diseases^2,13

Patients with urethritis should be counselled and offered testing for HIV, hepatitis B and syphilis.

Approach to a patient with symptoms suggestive of urethritis

• Full history including full sexual history.
• Examination: local - looking for discharge, skin lesions and systemic examination.
• Refer to a GUM clinic, unless providing sexual healthcare as an enhanced service in primary care.
• Arrange an FPU and, if necessary, a urethral smear.
• If a smear is positive - manage as below.
• If a smear is negative and there is no definitive evidence of urethritis then defer treatment and re-examine one week later. Also, check mid-stream urine sample for urinary tract infection.
• Screen for other sexually transmitted infections.
• There is some debate as to whether there should be blind treatment of those with symptoms and at high risk of infection or those unlikely to return for follow-up.

Management^2,14,15

Treatment is the same in HIV-negative and HIV-positive patients. Always use local guidelines where possible:

• Non-gonococcal urethritis (NGU) - azithromycin 1 g as single oral dose is first-line or doxycycline 100 mg bd for seven days.¹
• Gonococcal urethritis - recommended treatment for confirmed, uncomplicated gonococcal infection in adults is ceftriaxone 500 mg IM stat plus azithromycin 1 g orally stat.⁸ Other options are available. See separate article Gonorrhoea for more details.
• Empirical treatment - patients should be encouraged to attend a specialist service. However, in men who cannot or will not access such services, the opportunity should not be missed to provide treatment. Urethritis should be treated as early as possible and should be treated empirically as a presumed chlamydial infection, as this is the most common cause. Doxycycline 100 mg bd for seven days or azithromycin 1 g as single oral dose should thus be prescribed.

Patient education²

• There is the need to explain the diagnosis, treatment, adverse effects and importance of completing the course of antibiotics.
• Discuss methods of prevention, including advice on safe sex, e.g. condom use.
• Stress to the patient that sexual intercourse should be avoided until the infection has cleared up and that partners should be checked out.
• Contact tracing - it is important to maintain patient confidentiality. It is necessary to trace sexual contacts from the previous four weeks and up to six months if asymptomatic (for non-gonococcal urethritis (NGU)). National guidelines on the management of gonorrhoea recommend that male patients with symptomatic urethral infection should notify all sexual partners within the preceding two weeks or their last partner if longer than two weeks.⁸

Further management²

• Patients should be followed up for review at approximately two weeks.
• Take this opportunity to reinforce health education.
• Assess compliance and efficacy.
• Test of cure should be performed for gonorrhoea in all cases, e.g. NAAT after seven days or repeat culture 72 hours after treatment has finished.⁸ It is not routine for chlamydia unless the patient is pregnant, noncompliance is suspected or re-exposure may have occurred.³
• If there are persistent symptoms or persistent urethritis despite being asymptomatic, consider treatment failure, re-infection or infection with an uncommon pathogen, e.g. T. vaginalis. Be aware that symptoms can take two to three weeks to resolve after a completed course of treatment. If the course was not completed, treat with the original course of antibiotics.
• If doxycycline was used initially there is a need to be aware that there are tetracycline-resistant forms of U. urealyticum and an alternative may need to be tried, e.g. metronidazole or erythromycin.
• If there is no laboratory evidence of infection then advise no sexual intercourse for seven days and until the partner completes treatment.
• Exclude non-infective causes of urethritis - e.g. trauma, irritation or other conditions causing the same symptoms, such as prostatitis, malignancy or epididymitis.
• If symptoms have not resolved three weeks after completing a full course of treatment, advise referral to a GUM specialist. If the patient refuses, prescribe azithromycin 500 mg dose once only, then 250 mg for the next four days, plus metronidazole 400 mg to 500 mg twice daily for five days.
• If there is persistent or recurrent NGU, treat with erythromycin or metronidazole.

Complications²

• Epididymitis and/or orchitis.
• Prostatitis.
• Systemic dissemination of gonorrhoea, e.g. conjunctivitis, skin lesions.
• Reactive arthritis.
• Pelvic inflammatory disease (PID) - infection of female partners with the organisms that cause urethritis can cause PID and subsequent complications.
• Reiter's syndrome.
• HIV transmission increased.

Prognosis

If non-gonococcal urethritis (NGU), chlamydia and gonorrhoea remain untreated they may, rarely, remit spontaneously. However, this may take several months and carries the risk of transmission to others if the patient continues to have unprotected sexual intercourse.

Document references

1. Management of non-gonococcal urethritis, British Association for Sexual Health and HIV (2007); updated December 2008
2. Urethritis - male, Prodigy (September 2009)
3. Management of chlamydia trachomatis genital tract infection, British Association for Sexual Health and HIV (2006)
4. Sexually transmitted infections factsheet, Family Planning Association, 2010
5. Health Protection Report, Weekly Report, Volume 5 Number 24, Health Protection Agency, June 2011
6. Plewa M, Male Urethritis in Emergency Medicine, Medscape, Apr 2010
7. Guidance for gonorrhoea testing in England and Wales, British Association for Sexual Health and HIV (2010)
8. Management of Gonorrhoea, British Association for Sexual Health and HIV (2011)
9. Richens J; Main presentations of sexually transmitted infections in men. BMJ. 2004 May 22;328(7450):1251-3.
10. National Chlamydia Screening Programme, NHS
11. Iser P, Read TH, Tabrizi S, et al; Symptoms of non-gonococcal urethritis in heterosexual men: a case control study. Sex Transm Infect. 2005 Apr;81(2):163-5. [abstract]
12. Chlamydia trachomatis UK Testing Guidelines, British Association for Sexual Health and HIV (2010)
13. Brill JR; Diagnosis and treatment of urethritis in men. Am Fam Physician. 2010 Apr 1;81(7):873-8. [abstract]
14. Guidelines on the Management of Urinary and Male Genital Tract Infections, European Association of Urology (2008)
15. Standards for the management of sexually transmitted infections, British Association for Sexual Health and HIV (2010)