Urethritis

Urethritis is an inflammatory condition that can be infectious or posttraumatic in nature. Infectious causes of urethritis are typically sexually transmitted and categorized as either GU (ie, due to infections with Neisseria gonorrhoeae) or NGU (eg, due to infections with Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, or Trichomonas vaginalis). The presence of Gram-negative intracellular diplococci on urethral smear is suggestive of gonococcal urethritis. Gonococcal infection is typically accompanied by chlamydial infection, which accounts for 15%-40% of NGU cases. It is essential to document chlamydial infections due to the need for partner evaluation and treatment to prevent complications from chlamydial infections, especially in female partners.

There has been a notable increase in the incidence of urethritis associated with Mycoplasma genitalium, now the second most common cause of NGU, although there is currently a lack of US Food and Drug Administration (FDA)–approved tests for diagnostic use. This organism can be sexually transmitted, accounts for 15%-25% of NGU cases in the United States and should be suspected in cases of recurrent or persistent urethritis. ^{[2, 5]}

Haemophilus species are an increasing cause of NGU, particularly in patients who have unprotected oral sex. ^{[6, 7, 8]}  Rare infectious causes of urethritis include lymphogranuloma venereum, herpes simplex virus types 1 and 2, adenovirus, syphilis, mycobacterial infection, Corynebacterium, ^[9]  and bacterial infections that are typically associated with cystitis (usually gram-negative rods) in the presence of urethral stricture. Other rare but reported causes of urethritis include viral, streptococcal, anaerobic, and meningococcal infections. However, in up to 35% of NGU cases, no pathogen is found. ^[10]

Posttraumatic urethritis can occur in 2%-20% of patients practicing intermittent catheterization and following instrumentation or foreign body insertion. Urethritis is 10 times more likely to occur with latex catheters than with silicone catheters.

Urethritis may be associated with other infectious conditions, such as the following:

• Epididymitis
• Orchitis
• Prostatitis
• Proctitis
• Reactive arthritis
• Iritis
• Pneumonia
• Otitis media
• Urinary tract infection

Urethritis may be gonococcal, nongonococcal, or mixed.

Gonococcal urethritis (80% of cases) is caused by Neisseria gonorrhoeae, which is a gram-negative intracellular diplococcus. Gonococcal urethritis has a shorter incubation period than nongonococcal urethritis (NGU), and the onset of dysuria and purulent discharge is abrupt.

NGU, which comprises 50% of urethritis cases, has a longer incubation period than gonococcal urethritis, and the onset of either dysuria or, less commonly, a mucopurulent discharge, is subacute. Patients with NGU are much more likely to be asymptomatic than are patients with gonococcal urethritis.

Commonly identified causes of NGU include the following:

• Chlamydia trachomatis (15-40% of cases)
• Mycoplasma genitalium (15-20% of cases)
• Ureaplasma urealyticum
• Trichomonas vaginalis

The number of fastidious organisms implicated in NGU is increasing and includes several Ureaplasma and Mycoplasma species. T vaginalis is another potential cause of NGU and has a reported high prevalence (20%) among heterosexual men in Africa. ^[11] Haemophilus species, herpes simplex virus, Epstein-Barr virus, and adenovirus can lead to urethritis in patients who practice oral to penile contact. Enteric bacteria have been implicated in patients who practice insertive anal intercourse. In most patients with NGU, the causative organism cannot be identified. 

Rare cases may be related to lymphogranuloma venereum, herpes simplex, syphilis, mycobacteria, or urinary tract infection with urethral stricture. Other rare but reported causes of NGU include anaerobes, adenovirus, cytomegalovirus, and streptococcus.

Urethritis following catheterization occurs in 2-20% of patients practicing intermittent catheterization and is 10 times more likely to occur with latex catheters than with silicone catheters.

Polymicrobial NGU and cases of urethritis due to both gonococcal infection and nongonococcal factors are possible and can explain some treatment failures. This should also be considered in patients with HIV infection.

STDs are an unrecognized epidemic within the United States and pose a serious threat to the overall health and economic well-being of the population. Nearly 20 million new STDs occur each year in the US, with an estimated treatment cost of $16 billion dollars annually. ^[12] Urethritis occurs in 4 million Americans each year. ^[13]

There is currently a resurgence of various STDs that had previously been on the decline. ^[14]  The incidence of GU steadily declined from 2000 to 2009, but then began intermittently rising. The incidence of NGU is on also the rise. The 2020 Centers for Disease Control and Prevention (CDC) STD Surveillance Report demonstrated marked increases in the incidence of syphilis and gonorrhea but a slight decrease in chlamydia, the three most commonly reported STDs. Relative to 2016, the incidence of gonorrhea increased by 45% to 677,769 cases, and syphilis incidence increased by 52% to 133,945. ^[15]

Although reported Chlamydia infections decreased by 1.2%, to 1.6 million cases, the CDC suggests that the decrease represents limited access to health care due to the COVID-19 pandemic rather than a reduction in new infections. The CDC points out that chlamydial infections are usually asymptomatic, so case rates are heavily influenced by screening coverage. ^[15]

Worldwide, approximately 62 million new cases of GU and 89 million new cases of NGU are reported each year.

Urethritis has no racial predilection. However, persons of low socioeconomic class are affected more often than persons of higher socioeconomic class.

Urethritis has no sexual predilection; however, data may be skewed because urethritis is under-recognized in women. Up to 75% of females with the condition can be asymptomatic or may instead present with cystitis, vaginitis, or cervicitis. ^[16]  Men who have sex with men are at a greater risk for urethritis than are heterosexual males or females in general.

Urethritis may occur in any sexually active person, but incidence is highest among people aged 20-24 years.

All patients with uncomplicated urethritis spontaneously recover with or without treatment.

Complications, such as stricture, stenosis, or abscess formation, are quite rare. Concomitant epididymitis or prostatitis is not uncommon. Increasing evidence shows that genital chlamydial infection in males may predispose to infertility. In addition, both Chlamydia and U urealyticum can impair sperm and adversely affect semen parameters. ^{[17, 18, 19]}

Approximately 10%-40% of women with urethritis eventually develop pelvic inflammatory disease (PID), which may subsequently cause infertility and ectopic pregnancy secondary to postinflammatory scar formation in the fallopian tubes. PID can occur even in women with asymptomatic infections.

Children born to mothers with Chlamydia infection may develop conjunctivitis, iritis, otitis media, or pneumonia if exposed to the organism while passing through the birth canal. Performing cesarean delivery in patients with known chlamydial infections and routine treatment of all newborns with anti-chlamydial eyedrops has decreased the incidence of this problem in developed countries.

Disseminated gonococcal infection (DGI) and reactive arthritis develop in fewer than 1% of female patients with urethritis. Reactive arthritis is characterized by NGU, anterior uveitis, and arthritis and is strongly associated with the gene for HLA-B27. Rare but serious complications of DGI include arthritis, meningitis, and endocarditis.

Morbidity due to urethritis in males is less common (1%-2%), typically taking the form of urethral stricture or stenosis due to postinflammatory scar formation. Other potential complications of urethritis in males include prostatitis, acute epididymitis, abscess formation, proctitis, infertility, abnormal semen, DGI, and reactive arthritis.

Mortality rates are minimal in patients with gonococcal urethritis or NGU.

Patient should be told the following about this condition:

• Refrain from sexual intercourse for one week after starting antibiotic therapy and until all partners are adequately treated.
• Avoid urethral irritants such as perfumed soaps, body washes, lotions, or lubricants and vigorous or frequent masturbation or sexual intercourse.
• Limit the number of sexual partners and always use barrier devices, such as condoms, when engaging in intercourse.
• Infections can spread by oral, anal, or vaginal intercourse.
• Return for evaluation if experiencing persistent or recurrent symptoms of urethritis.

Educate at-risk patients on how to prevent disease recurrence and educate patients on risks of other sexually-transmitted infections, including HIV. ^[20]  Instruct patients to avoid the following high-risk behaviors associated with STDs:

• Intercourse at a young age, which with rare exceptions is associated with multiple sex partners and unprotected intercourse
• Intercourse with multiple partners
• Drug use
• Unprotected sex
• Intercourse with partners known to have infections

For patient education information, see the Sexual Health Center and Sexually Transmitted Diseases.