Urethritis overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Seyedmahdi Pahlavani, M.D. [2]

## Overview

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Urethritis is due to inflammation of the urethra. Based on etiology it is classified into two main groups, infectious and non-infectious. Infectious causes are further classified into gonorrheal and non-gonorrheal. Urethritis is an inflammation of the genital tract that is mostly due to infectious causes. Its pathogenesis depends on the causative pathogen. Microscopic findings for gonococcal urethritis include, presence of gram-negative intracellular diplococci (GNID), invaded epithelial cells, vacuoles that contain multiple organisms, and >2 WBC per oil immersion field. Nongonococcal urethritis (NGU) is [[microscopically characterized by signs of inflammation with absence of gram-negative intracellular diplococci. If symptoms are present but no evidence of urethral inflammation is present, Nucleic Acid Amplification Tests (NAATs) for C. trachomatis and N. gonorrhoeae might identify infections.The most potent risk factor for urethritis is unprotected sex, especially among men who have sex with men. Other risk factors include low socioeconomic status, history of sexually transmitted diseases, and multiple sex partners. Urethritis is primarily diagnosed based on symptoms, signs of urethral inflammation and microscopic findings. Symptoms may comprise of dysuria, urethral pruritus, burning, Signs of urethral inflammation include urethral discharge, which can be mucoid, mucopurulent, or purulent. Microscopic findings in gonorrheal urethritis include, identification of gram-negative intracellular diplococci (GNID) or purple intracellular diplococci on methylene blue, or gentian violet stain. Presence of Invaded epithelial cells, vacuoles that contain multiple organisms and >2 WBC per oil immersion field. Nongonococcal urethritis (NGU) is microscopically characterized by signs of inflammation with absence of gram-negative intracellular diplococci. If symptoms are present but no evidence of urethral inflammation is present, Nucleic Acid Amplification Tests (NAATs) for C. trachomatis and N. gonorrhoeae might identify infections.Once the diagnosis is confirmed, the appropriate antibiotic regimen should be initiated to reduce the risk of complications. Doxycycline 100 mg PO bid for 7 days is administered to treat Non-gonococcal Urethritis, as an alternative therapy azithromycin 1 g PO in a single dose or azithromycin 500 mg orally in a single dose; then 250 mg orally daily for 4 days is recommended. For gonococcal urethritis, ceftriaxone 500 mg IM in a single dose (for patients weighing ≥150 kg (300 lbs) ceftriaxone 1 g IM in a single dose), for alternate therapy gentamicin 240 mg PO in a single dose plus azithromycin 2 g PO in a single dose, or cefixime 800 mg PO in a single dose is recommended.

## Historical Perspective

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The first known case of urethritis was described by Albert Neisser, a German doctor, in 1879. In 1904, Ludwig Waelsch described mild non-gonococcal urethritis (NGU). In the 1930s and later, Philip Thygeson and others in the United States confirmed the vertical transmission of nongonococcal urethritis (NGU).

## Classification

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Urethritis is classified into two main groups of infectious and non-infectious based on the etiology. Infectious causes are further classified into gonorrheal and non-gonorrheal.

## Pathophysiology

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Urethritis is an inflammation of the genital tract that is mostly due to infectious causes. Its pathogenesis depends on the causative pathogen. N. gonorrhea is usually transmitted via the genital tract to the human host. Following attachment to host cell, which is mediated by pili, gonococci become engulfed in a process known as parasite-directed endocytosis. This organism will survive inside the vacuoles and replicate. Among non-gonorrheal causes, Chlamydia trachomatis is the most common. The infectious process begins with cell surface attachment and phagocytosis by the host cell. The pathogen survives inside the cell by debilitating the cellular lysosomes and replicating as elementary bodies which is considered as the infective form of the pathogen. Microscopic findings for gonococcal urethritis include, presence of gram-negative intracellular diplococci (GNID), invaded epithelial cells, vacuoles that contain multiple organisms, and >2 WBC per oil immersion field. Nongonococcal urethritis (NGU) is microscopically characterized by signs of inflammation with absence of gram-negative intracellular diplococci.

## Causes

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Urethritis may be caused by either infectious or non-infectious causes. Infectious causes are divided into gonorrheal and non-gonorrheal. Non-gonorrheal pathogens are the most common cause of urethritis; Chlamydia trachomatis is the most common among them.

## Differentiating Urethritis from Other Diseases

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Urethritis must be differentiated from other causes of dysuria and urethral discharge, which include acute cystitis, epididymitis, prostatitis, cervicitis, and vulvovaginitis.

## Epidemiology and Demographics

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Urethritis is the cause of several millions of healthcare visits in the United States. Chlamydia trachomatis is the most common reportable disease in the US. In 2014, a total of 350,062 gonorrhea cases were reported to the CDC in the US. Based on The National Health and Nutrition Examination Survey, the overall prevalence of chlamydia among persons aged 14–39 years was 1.7% during 2007-2012. Urethritis has a very good prognosis with proper treatment. Mortality is very uncommon in patients with gonococcal and non-gonococcal urethritis. Almost two-thirds of chlamydia infections occur among youths aged 15-24 years. The highest prevalence rates of gonococcal urethritis were found in ages 20 to 24 years both in men and women. In 2014, the overall rate of chlamydia infection in the United States among women was 627.2 cases per 100,000 females, over two times the rate among men (278.4 cases per 100,000 males). In 2014, the incidence of gonorrhea in the United States was reported as 120 cases per 100,000 males, while it was reported as 100 cases per 100,000 females.

## Risk Factors

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The most potent risk factor for urethritis is unprotected sex, especially among men who have sex with men. Other risk factors include low socioeconomic status, history of sexually transmitted diseases, and multiple sex partners.

## Screening

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High-risk individuals should be screened for sexually transmitted diseases. The U.S. Preventive Service Task Force (USPSTF) developed recommendations for the screening of for Chlamydia trachomatis and N. gonorrhea.

## Natural History, Complications, and Prognosis

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Urethritis has a good prognosis and most patients are treated with appropriate antibiotics. If left untreated, it can resolve within 3 months in 95% of people with gonococcalurethritis. The symptoms of nongonococcal urethritis generally abate within 3 months in 30-70% of untreated people. Rarely, complications such as epididymitis, prostatitis, urethral stricture, chronic gonorrhea carrier state, may occur.

## Diagnosis

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### Diagnostic Study of Choice

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Urethritis is primarily diagnosed based on symptoms, signs of urethral inflammation and microscopic findings. Symptoms may comprise of dysuria, urethral pruritus, burning, Signs of urethral inflammation include urethral discharge, which can be mucoid, mucopurulent, or purulent. Microscopic findings in gonorrheal urethritis include, identification of gram-negative intracellular diplococci (GNID) or purple intracellular diplococci on methylene blue, or gentian violet stain. Presence of Invaded epithelial cells, vacuoles that contain multiple organisms and >2 WBC per oil immersion field. Nongonococcal urethritis (NGU) is microscopically characterized by signs of inflammation with absence of gram-negative intracellular diplococci. If symptoms are present but no evidence of urethral inflammation is present, Nucleic Acid Amplification Tests (NAATs) for C. trachomatis and N. gonorrhoeae might identify infections.

### History and Symptoms

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A detailed history, particularly with regard to sexual activity, must be taken. Symptoms suggestive for urethritis include dysuria and urethral discharge. History should specifically include, recent sexual activities, number of sex partners, or any new partner, use of condoms, history of prior STDs, and history of recent urethral instrumentation (e.g., urethral catheters).

### Symptoms

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Symptoms suggestive of urethritis include dysuria and urethral discharge.

### Physical Examination

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The most common physical finding in urethritis is urethral discharge. The entire genital area must be examined in order to rule out other possibilities. Patients should be examined for inguinal lymphadenopathy, ulcers, and urethral discharge.

### Laboratory Findings

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Urethritis may be considered on the basis of any of the following, mucoid, mucopurulent, or purulent discharge on examination, Gram stain of urethral secretions demonstrating ≥2 WBC per field, positive leukocyte esterase test on first-void urine or microscopic examination of sediment from a spun first-void urine demonstrating ≥10 WBC per high power field.

### Electrocardiogram

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There are no ECG findings associated with urethritis.

### X-ray

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There are no x-ray findings associated with urethritis.

### Echocardiography and Ultrasound

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There are no echocardiography/ultrasound findings associated with urethritis.

### CT scan

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There are no CT scan findings associated with urethritis.

### MRI

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There are no MRI findings associated with urethritis.

### Other Imaging Findings

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There are no other imaging findings associated with urethritis.

### Other Diagnostic Studies

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There are no additional diagnostic findings for urethritis.

## Treatment

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### Medical Therapy

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Once the diagnosis is confirmed, the appropriate antibiotic regimen should be initiated to reduce the risk of complications. Doxycycline 100 mg PO bid for 7 days is administered to treat Non-gonococcal Urethritis, as an alternative therapy azithromycin 1 g PO in a single dose or azithromycin 500 mg orally in a single dose; then 250 mg orally daily for 4 days is recommended. For gonococcal urethritis, ceftriaxone 500 mg IM in a single dose (for patients weighing ≥150 kg (300 lbs) ceftriaxone 1 g IM in a single dose), for alternate therapy gentamicin 240 mg PO in a single dose plus azithromycin 2 g PO in a single dose, or cefixime 800 mg PO in a single dose is recommended. Metronidazole 2 g PO in a single dose is used for patients with recurrent and persistent urethritis. Following treatment, patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Providers should be alert to the possibility of chronic prostatitis/chronic pelvic pain syndrome in male patients experiencing persistent pain (perineal, penile, or pelvic), discomfort, irritating voiding symptoms, pain during or after ejaculation, or new onset premature ejaculation lasting for >3 months. All sex partners within the preceding 60 days should be referred for evaluation, testing, and empiric treatment with a drug regimen effective against Chlamydia. Clinicians must report both chlamydia and gonorrhea to health departments.

### Interventions

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There are no recommended therapeutic interventions for the management of urethritis.

### Surgery

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Surgical intervention is not recommended for the management of urethritis.

### Primary Prevention

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Effective measures for the primary prevention of urethritis include limiting the number of sex partners and using condoms.

### Secondary Prevention

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In order to prevent transmission to one's partner and decrease the risk of antibiotic resistance, all patients must be instructed on safe sex practices and screening requirements after treatment.

## References

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