Urethritis in Men Symptoms and Treatment

Description

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

Urethritis in men 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 urethritis^[2]

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

Causes of non-gonococcal urethritis^[1]

• The most common organisms implicated are Chlamydia trachomatis and Mycoplasma genitalium. Chlamydia and M. genitalium are more likely to be detected in younger patients with NGU (although this association is not as strong for M. genitalium) and those presenting with a urethral discharge and/or dysuria.
• The two organisms only infrequently co-exist in the same individual with NGU but dual infections have been identified in up to 10% of men in some studies.
• Men with a urethral discharge have a higher bacterial load than those without.
• In 30-80% of the cases with NGU neither C. trachomatis nor M. genitalium is detected. Pathogen-negative NGU is more likely with increasing age and the absence of discharge or urethritis symptoms.
• Trichomonas vaginalis is more common in non-white ethnic groups and appears to be uncommon in the UK. T. vaginalis isolation is greater in men aged over 30 years and may not always be associated with symptoms.
• Ureaplasmas have been inconsistently associated with NGU. Earlier studies did not differentiate between two biovars: Ureaplasma urealyticum (biovar 2) and Ureaplasma parvum (biovar 1). There is increasing evidence that it is only U. urealyticum (biovar 2) which is pathogenic in some men at least but not U. parvum. U. urealyticum may account for 5-10% of cases of acute NGU.
• A urinary tract infection may account for 6.4% of cases, although this is based upon the results of a single study.
• Adenoviruses may account for perhaps 2-4% of symptomatic patients and are often associated with a conjunctivitis.
• Herpes simplex viruses types 1 and 2 are an uncommon cause of NGU (2-3%).
• Epstein Barr virus, Neisseria meningitidis, Haemophilus spp., Candida spp., urethral stricture and foreign bodies have all been reported in a few cases and probably account for a small proportion of NGU.
• The cause of organism-negative NGU (also called idiopathic urethritis) is unclear and has recently been reviewed. Some of these cases are almost certainly non-infective but the tools to be able to differentiate between infective and non-infective cases are not currently available.

Causes of persistent or recurrent urethritis^[2]

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.

Epidemiology^[2]

• 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.
• NGU is more common than gonococcal urethritis.
• Chlamydia is most common in young people aged 15-24 years. 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.
• Gonorrhoea^[3]:
• In 2013, the total number of new cases of gonorrhoea diagnosed in GUM clinics in England was 29,291. This was an increase of 15% compared to those diagnosed in 2012. The prevalence of gonorrhoea has increased gradually over a period of ten years, principally in men.
• There was a disproportionate increase in men who have sex with men (MSM). In 2013, 63% of diagnoses of gonorrhoea occurred in MSM, a 26% increase on the previous year. This was thought to be due to a rise in men coming forward for testing, as well as an increase in sexually unsafe activity.
• The use of new diagnostic techniques - rectal and pharyngeal testing using nucleic acid amplification testing (NAAT) - has also improved detection rates.
• The highest rates of gonorrhoea are amongst the young. In 2013 among heterosexuals diagnosed with gonorrhoea, 56% (8,122/14,647) occurred in those aged 15-24 years.

Presentation

• May be asymptomatic (90-95% of men with gonorrhoea, 50% of patients with chlamydial infections^[4]).
• Urethral discharge - mucopurulent or purulent; with or without blood; more noticeable after holding urine overnight and more common in gonococcal infection^[5]. May have gone unnoticed by the patient and be seen only on examination 
• 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 - eg, skin lesions in herpes simplex virus.
• Systemic symptoms if there is involvement of other organs - eg, conjunctivitis or arthritis.

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

There is currently a national screening programme for chlamydia^[6].

Identify high-risk patients^{[2, 7]}

• Sexually active.
• Male.
• Unprotected vaginal sex.
• Males who have sex with males.
• More common in cities.
• Age <35 years.
• Recent partner change.

Investigations^[2]

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

The diagnosis of urethritis is confirmed by demonstrating an excess of polymorphonuclear leukocytes in the anterior urethra. This is usually assessed using a urethral smear but a first-pass urine test specimen can also be used^[1]. Check with the local laboratory to see which investigations they provide.

• FPU for 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^[8].
• 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.
• NAATs are the test of choice for testing asymptomatic individuals for urethral infection with N. gonorrhoeae^[4].
• Pharyngeal and rectal swabs may also be needed.
• A stick test of urine should be performed to exclude urinary tract infection.

Differential diagnosis^[2]

• Physiological discharge
• Candidal balanitis
• Epididymo-orchitis
• Cystitis
• Acute prostatitis
• Urethral malignancy 

Associated diseases^{[2, 9]}

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

Approach to a patient with potential urethritis symptoms

• 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 MSU 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 urethritis symptoms and at high risk of infection or those unlikely to return for follow-up.

Management^{[2, 10]}

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

Non-gonococcal urethritis (NGU)^[1]

Recommended regimens

• Doxycycline 100 mg twice daily for seven days; or
• Azithromycin 1 g stat; or
• If the patient (or their sexual partner) is known to be M. genitalium-positive: azithromycin 500 mg stat then 250 mg daily for the next four days. Moxifloxacin is emerging as a useful alternative where azithromycin resistance is suspected^[11].

Alternative regimens

• Ofloxacin 200 mg twice daily, or 400 mg once daily, for seven days; or
• Azithromycin 500 mg stat then 250 mg daily for the next four days.

Gonococcal urethritis

Recommended treatment for confirmed, uncomplicated gonococcal infection in adults is ceftriaxone 1 g IM stat^[4]. Other options are available. See the separate Gonorrhoea article 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. Ofloxacin 200 mg twice daily or 400 mg daily for seven days may be offered as an alternative.

Patient education^[2]

• 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 - eg, 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 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^[4].

Further management^[2]

• 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 - eg, NAAT after seven days or repeat culture 72 hours after treatment has finished^[4]. It is not routine for chlamydia unless the patient is pregnant, noncompliance is suspected or re-exposure may have occurred^[12].

Urethritis treatment failure

• If urethritis symptoms persist or recur after treatment is completed, the man should be strongly advised to attend a GUM clinic or other local specialist sexual health service. If this is declined or not possible:
• Check compliance with the initial drug treatment regime.
• Exclude the possibility of re-infection. Check that current partner(s) have been treated appropriately and simultaneously.
• Reconsider the diagnosis.
• If the man has not adhered to treatment or has had sexual intercourse with an untreated partner and has been treated with doxycycline first line, then treat with azithromycin 1 gram as a single dose then 500 mg once daily for the next two days, plus metronidazole 400 mg twice daily for five days.
• Azithromycin should be commenced within two weeks of completing doxycycline.
• If treated with azithromycin regimen first-line, then prescribe moxifloxacin 400 mg once daily for 10 days, plus metronidazole 400 mg twice daily for five days.
• Or alternatively, prescribed doxycycline 100 mg twice daily for seven days, plus metronidazole 400 mg twice daily for five days. This regime should in any case be preferred if M. genitalium detection assays have not been carried out.
• If symptoms persist and the man has adhered to treatment and has not had sex with an untreated partner, consider prescribing azithromycin 500 mg dose once only, then 250 mg for the next four days, plus metronidazole 400-500 mg twice daily for five days.
• If symptoms persist despite a second course of antibiotics then seek specialist advice.

Complications^[2]

• Epididymitis and/or orchitis.
• Prostatitis.
• Systemic dissemination of gonorrhoea - eg, 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.
• HIV transmission is increased.

Prognosis

If 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.