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{{Urethritis}}
{{Urethritis}}
{{CMG}}; {{AE}} {{MehdiP}}
{{CMG}}; {{AE}} {{MehdiP}}
==Overview==
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 [[Sex organ|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|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==
==Historical Perspective==
The first known case of urethritis was described by Albert Neisser, a German doctor, in 1879.<ref name="pmid8976858">{{cite journal |vauthors=Oriel JD |title=The history of non-gonococcal urethritis |journal=Genitourin Med |volume=72 |issue=5 |pages=374–9 |year=1996 |pmid=8976858 |pmc=1195709 |doi= |url=}}</ref>
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==
==Classification==
Urethritis can be classified into two main groups:
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.  
* Infectious urethritis- This can be further subdivided into gonococcal and non-gonococcal urethritis.
* Non-infectious urethritis
 
==Pathophysiology==
==Pathophysiology==
The pathogenesis of urethritis varies depending on the underlying pathogen.
Urethritis is an [[inflammation]] of the [[Sex organ|genital tract]] that is mostly due to infectious causes. Its pathogenesis depends on the causative pathogen. ''[[Neisseria gonorrhoeae|N. gonorrhea]]'' is usually transmitted via the [[Sex organ|genital tract]] to the human host. Following attachment to host cell, which is mediated by [[pili]], [[Gonorrhea|''gonococci'']] become engulfed in a process known as parasite-directed [[endocytosis]]. This [[organism]] will survive inside the [[Vacuole|vacuoles]] and replicate. Among non-gonorrheal causes, ''[[Chlamydiae|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 (biology)|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]].
*''[[Neisseria gonorrhoeae]]'' is usually transmitted to the human host via the genital tract.
*Following attachment to host cell, which is mediated by [[Pilus|pili]], gonococci become engulfed in a process known as parasite-directed [[endocytosis]]. The organism can survive inside the [[Vacuole|vacuoles]] and replicate.<ref name="pmid9916098">{{cite journal |vauthors=Scheuerpflug I, Rudel T, Ryll R, Pandit J, Meyer TF |title=Roles of PilC and PilE proteins in pilus-mediated adherence of Neisseria gonorrhoeae and Neisseria meningitidis to human erythrocytes and endothelial and epithelial cells |journal=Infect. Immun. |volume=67 |issue=2 |pages=834–43 |year=1999 |pmid=9916098 |pmc=96394 |doi= |url=}}</ref>
*[[Chlamydia trachomatis]] is the most common of the non-gonorrheal pathogens that cause urethritis.  
**The infectious process begins with cell surface attachment and [[phagocytosis]] by the host cell. This pathogen survives inside the cell by debilitating the cellular [[Lysosome|lysosomes]], and replicating as elementary bodies (the infective form of the pathogen).<ref>Beatty, Wandy L., Richard P. Morrison, and Gerald I. Byrne. "Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis." Microbiological reviews 58.4 (1994): 686-699.</ref><ref>Baron, Samuel. Medical microbiology. Galveston, Tex: University of Texas Medical Branch at Galveston, 1996. Print.</ref>


==Causes==
==Causes==
Urethritis may be caused by either infectious or non-infectious causes. Infectious causes can be further subdivided into ''gonorrheal'' and ''non-gonorrheal.''<ref name="pmid22000844">{{cite journal |vauthors=Al-Sweih NA, Khan S, Rotimi VO |title=The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among men with urethritis in Kuwait |journal=J Infect Public Health |volume=4 |issue=4 |pages=175–9 |year=2011 |pmid=22000844 |doi=10.1016/j.jiph.2011.07.003 |url=}}</ref> Non-gonorrheal pathogens are the most frequent cause of urethritis; [[Chlamydia trachomatis]] is the most common among them.<ref name="kim">{{Cite journal
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|''Chlamydia trachomatis'']] is the most common among them.
| author = [[Kimberly A. Workowski]] & [[Gail A. Bolan]]
 
| title = Sexually transmitted diseases treatment guidelines, 2015
==Differentiating Urethritis from Other Diseases==
| journal = [[MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control]]
Urethritis must be differentiated from other causes of [[dysuria]] and urethral [[discharge]], which include [[acute cystitis]], [[Epididymo-orchitis|epididymitis]], [[prostatitis]], [[cervicitis]], and [[vulvovaginitis]].
| volume = 64
 
| issue = RR-03
==Epidemiology and Demographics==
| pages = 1–137
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 [[Gonorrhea|gonococcal]] and [[non-gonococcal urethritis]]. Almost two-thirds of [[chlamydia]] [[infections]] occur among youths aged 15-24 years. The highest [[prevalence]] rates of [[Gonorrhea|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]].
| year = 2015
 
| month = June
==Risk Factors==
| pmid = 26042815
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.
}}</ref><ref name="pmid22000844">{{cite journal |vauthors=Al-Sweih NA, Khan S, Rotimi VO |title=The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among men with urethritis in Kuwait |journal=J Infect Public Health |volume=4 |issue=4 |pages=175–9 |year=2011 |pmid=22000844 |doi=10.1016/j.jiph.2011.07.003 |url=}}</ref><ref name="pmid20852197">{{cite journal |vauthors=Le Roux MC, Ramoncha MR, Adam A, Hoosen AA |title=Aetiological agents of urethritis in symptomatic South African men attending a family practice |journal=Int J STD AIDS |volume=21 |issue=7 |pages=477–81 |year=2010 |pmid=20852197 |doi=10.1258/ijsa.2010.010066 |url=}}</ref>
==Screening==
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|''Chlamydia trachomatis'']] and [[N. gonorrhea|''N. gonorrhea'']].
==Natural History, Complications, and Prognosis==
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 [[Gonorrhea|gonococcal]]<nowiki/>urethritis. 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==
===Diagnostic Study of Choice===
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]].


==Differential diagnosis of urethritis==
===History and Symptoms===
Urethritis must be differentiated from other causes of [[dysuria]] and urethral [[discharge]], which include [[acute cystitis]],<ref>{{Cite journal
A detailed history, particularly with regard to [[sexual]] activity, must be taken. Symptoms suggestive for urethritis include [[dysuria]] and urethral [[discharge]].
| author = [[Stephen Bent]], [[Brahmajee K. Nallamothu]], [[David L. Simel]], [[Stephan D. Fihn]] & [[Sanjay Saint]]
History should specifically includerecent sexual activities, number of sex partners, or any new partner, use of condoms, history of prior [[STD]]s, and history of recent urethral instrumentation (e.g., urethral [[catheters]]).
| title = Does this woman have an acute uncomplicated urinary tract infection?
| journal = [[JAMA]]
| volume = 287
| issue = 20
| pages = 2701–2710
| year = 2002
| month = May
| pmid = 12020306
}}</ref><ref>{{Cite journal
| author = [[W. E. Stamm]]
| title = Etiology and management of the acute urethral syndrome
| journal = [[Sexually transmitted diseases]]
| volume = 8
| issue = 3
| pages = 235–238
| year = 1981
| month = July-September
| pmid = 7292216
}}</ref><ref>{{Cite journal
| author = [[W. E. Stamm]], [[K. F. Wagner]], [[R. Amsel]], [[E. R. Alexander]], [[M. Turck]], [[G. W. Counts]] & [[K. K. Holmes]]
| title = Causes of the acute urethral syndrome in women
| journal = [[The New England journal of medicine]]
| volume = 303
| issue = 8
| pages = 409–415
| year = 1980
| month = August
| doi = 10.1056/NEJM198008213030801
| pmid = 6993946
}}</ref> [[Epididymo-orchitis|epididymitis]],<ref>{{Cite journal
  | author = [[A. Stewart]], [[S. S. Ubee]] & [[H. Davies]]
| title = Epididymo-orchitis
| journal = [[BMJ (Clinical research ed.)]]
| volume = 342
| pages = d1543
| year = 2011
| month =
| pmid = 21490048
}}</ref> [[prostatitis]],<ref>{{Cite journal
| author = [[Felix Millan-Rodriguez]], [[J. Palou]], [[Anna Bujons-Tur]], [[Mireia Musquera-Felip]], [[Carlota Sevilla-Cecilia]], [[Marc Serrallach-Orejas]], [[Carlos Baez-Angles]] & [[Humberto Villavicencio-Mavrich]]
| title = Acute bacterial prostatitis: two different sub-categories according to a previous manipulation of the lower urinary tract
| journal = [[World journal of urology]]
| volume = 24
| issue = 1
| pages = 45–50
| year = 2006
| month = February
| doi = 10.1007/s00345-005-0040-4
| pmid = 16437219
}}</ref> [[cervicitis]],<ref>{{Cite journal
| author = [[Kimberly A. Workowski]] & [[Gail A. Bolan]]
| title = Sexually transmitted diseases treatment guidelines, 2015
| journal = [[MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control]]
| volume = 64
| issue = RR-03
| pages = 1–137
| year = 2015
| month = June
| pmid = 26042815
}}</ref> and [[vulvovaginitis]].<ref>{{Cite journal
| author = [[Daniel V. Landers]], [[Harold C. Wiesenfeld]], [[R. Phillip Heine]], [[Marijane A. Krohn]] & [[Sharon L. Hillier]]
| title = Predictive value of the clinical diagnosis of lower genital tract infection in women
| journal = [[American journal of obstetrics and gynecology]]
| volume = 190
| issue = 4
| pages = 1004–1010
| year = 2004
| month = April
| doi = 10.1016/j.ajog.2004.02.015
| pmid = 15118630
}}</ref>


==Epidemiology==
===Symptoms===
[[Chlamydia]] and [[gonorrhea]] are the most commonly reported diseases to the US Centers for Disease Control and Prevention ([[CDC]]). Worldwide, there are approximately 78 million cases of [[gonorrhea]] and 131 million cases of [[chlamydia]] annually.<ref name=who> WHO epidemiology http://www.who.int/mediacentre/factsheets/fs110/en/ (2016) Accessed on September 26, 2016</ref><ref name="pmid25254560">{{cite journal |vauthors=Torrone E, Papp J, Weinstock H |title=Prevalence of Chlamydia trachomatis genital infection among persons aged 14-39 years--United States, 2007-2012 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=63 |issue=38 |pages=834–8 |year=2014 |pmid=25254560 |doi= |url=}}</ref>
[[Symptoms]] suggestive of urethritis include [[dysuria]] and [[urethral discharge]].
===Incidence===
*'''[[Chlamydia trachomatis]]''' is the most commonly reported disease in the United States. 1,441,789 [[chlamydia]] infections were reported to the [[CDC]] in 2014, which corresponds to a rate of 456.1 cases per 100,000 individuals.
*'''[[Gonorrhea]]:'''  In 2014, a total of 350,062 cases of [[gonorrhea]] were reported in the United States, and the national [[gonorrhea]] rate increased to 110.7 cases per 100,000 individuals in the United States.<ref name="urlNational Overview - 2014 STD Surveillance">{{cite web |url=http://www.cdc.gov/std/stats14/natoverview.htm |title=National Overview - 2014 STD Surveillance |format= |work= |accessdate=}}</ref>


===Gender===
===Physical Examination===
*'''[[Chlamydia trachomatis]]:''' In 2014, the overall rate of [[chlamydia]] infection in the United States among women (627.2 cases per 100,000 females) was over two times the rate among men (278.4 cases per 100,000 males).<ref name="urlNational Overview - 2014 STD Surveillance">{{cite web |url=http://www.cdc.gov/std/stats14/natoverview.htm |title=National Overview - 2014 STD Surveillance |format= |work= |accessdate=}}</ref>
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 region|inguinal]] [[lymphadenopathy]], [[ulcers]], and [[urethral discharge]].
*'''[[Gonorrhea]]:''' In 2014, the incidence of [[gonorrhea]] in the United States was reported as 120 cases per 100,000 males and 100 cases per 100,000 females.


===Age===
===Laboratory Findings===
*'''[[Chlamydia trachomatis]]:''' Almost two-thirds of [[chlamydia]] infections occur among youths aged 15-24 years.<ref name=abc> Chlamydia CDC Fact Sheet. CDC.http://www.cdc.gov/std/chlamydia/stdfact-chlamydia-detailed.htm#_ENREF_3. Accessed on September 28,2016</ref>
Urethritis may be considered on the basis of any of the following, mucoid, [[mucopurulent]], or [[purulent]] discharge on [[examination]], [[gram staining|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.
*'''[[Gonorrhea]]:''' The highest prevalence rates were observed in individuals between the ages of 20 and 24 years. This was consistent in both men and women.


===Race===
=== Electrocardiogram ===
*'''[[Chlamydia trachomatis]]:''' In 2014, the [[chlamydia]] rate in the African-American population in the United States was 6 times the rate in Caucasians, and the rate among American Indians/Alaska Natives was almost 4 times the rate among Caucasians.<ref name="urlChlamydia - 2014 STD Surveillance">{{cite web |url=http://www.cdc.gov/std/stats14/chlamydia.htm |title=Chlamydia - 2014 STD Surveillance |format= |work= |accessdate=}}</ref>
There are no [[ECG]] findings associated with urethritis.
*'''[[Gonorrhea]]:''' In 2014, the rate of reported [[gonorrhea]] cases remained highest among African-Americans (405.4 cases per 100,000 individuals). The rate among African-Americans was 10.6 times higher than the rate among Caucasians (reported cases of gonorrhea among Caucasians was 38.3 cases per 100,000 individuals). The [[gonorrhea]] rate among American Indians/Alaska Natives was 159.4 cases per 100,000 population, 4.2 times that of Caucasians.<ref name="urlChlamydia - 2014 STD Surveillance">{{cite web |url=http://www.cdc.gov/std/stats14/chlamydia.htm |title=Chlamydia - 2014 STD Surveillance |format= |work= |accessdate=}}</ref>


==Risk Factors==
=== X-ray ===
The most important risk factor in developing urethritis is unprotected sex, especially among men who have sex with men. Other risk factors include:<ref name="pmid6547226">{{cite journal |vauthors=Chacko MR, Lovchik JC |title=Chlamydia trachomatis infection in sexually active adolescents: prevalence and risk factors |journal=Pediatrics |volume=73 |issue=6 |pages=836–40 |year=1984 |pmid=6547226 |doi= |url=}}</ref><ref name="pmid18073009">{{cite journal |vauthors=Van Howe RS |title=Genital ulcerative disease and sexually transmitted urethritis and circumcision: a meta-analysis |journal=Int J STD AIDS |volume=18 |issue=12 |pages=799–809 |year=2007 |pmid=18073009 |doi=10.1258/095646207782717045 |url=}}</ref>
There are no [[x-ray]] findings associated with urethritis.
*Low socioeconomic status
*Prior or current STD
*New or multiple sex partners
*Circumcision


==Screening==
=== Echocardiography and Ultrasound ===
According to the U.S. Preventive Service Task Force ([[USPSTF]]), all sexually active women aged under 25 years and over 25 years with increased risk should undergo screening. Factors that increase risk include:<ref name=cde>US preventive services task forces. Gonorrhea and chlamydia screening (2014) https://www.uspreventiveservicestaskforce.org/Page/Document/ClinicalSummaryFinal/chlamydia-and-gonorrhea-screening Accessed on September 28, 2016</ref>
There are no [[echocardiography]]/[[ultrasound]] findings associated with urethritis.
*Prior history of [[sexually transmitted infection]]
*A new sex partner
*More than one sex partner
*A sex partner who has a [[sexually transmitted infection]]


==Natural History==  
=== CT scan ===
If left untreated, urethritis will resolve within 3 months in 95% of patients. The symptoms of [[non-gonococcal urethritis]] generally abate within 3 months in 30% to 70% of untreated people.<ref>{{cite book |last = Bennett |first = John |title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases |publisher = Elsevier/Saunders |location = Philadelphia, PA |year = 2015 |isbn=9781455748013}}</ref>
There are no [[CT]] [[scan]] findings associated with urethritis.
Prolonged asymptomatic [[Urethra|urethral]] carriage of gonococci occurs in 2% to 3% of newly infected men if left untreated.<ref name="pmid22256336">{{cite journal |vauthors=Detels R, Green AM, Klausner JD, Katzenstein D, Gaydos C, Handsfield H, Pequegnat W, Mayer K, Hartwell TD, Quinn TC |title=The incidence and correlates of symptomatic and asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae infections in selected populations in five countries |journal=Sex Transm Dis |volume=38 |issue=6 |pages=503–9 |year=2011 |pmid=22256336 |pmc=3408314 |doi= |url=}}</ref>


==Complications==
=== MRI ===
Common complications of urethritis include:
There are no [[MRI]] findings associated with urethritis.
*[[Epididymitis|Acute epididymitis]]
*[[Prostatitis]]
**It occurs In 20% to 30% of men with non-gonorrheal urethritis (NGU); however, it is usually asymptomatic and responds to standard therapy.<ref name="pmid165407">{{cite journal |vauthors=Holmes KK, Handsfield HH, Wang SP, Wentworth BB, Turck M, Anderson JB, Alexander ER |title=Etiology of nongonococcal urethritis |journal=N. Engl. J. Med. |volume=292 |issue=23 |pages=1199–205 |year=1975 |pmid=165407 |doi=10.1056/NEJM197506052922301 |url=}}</ref>
*Urethral stricture
**Gonorrhea may cause urethral stricture.
*Oculogenital syndrome
**[[Conjunctivitis]] and non-gonorrheal urethritis (NGU) may be seen in approximately 4% of patients with urethritis.<ref name="pmid6958007">{{cite journal |vauthors=Rönnerstam R, Persson K |title=Chlamydial eye infection in adults |journal=Scand J Infect Dis Suppl |volume=32 |issue= |pages=111–5 |year=1982 |pmid=6958007 |doi= |url=}}</ref>


==History and Symptoms==
=== Other Imaging Findings ===
===History===
There are no other [[imaging]] findings associated with urethritis.
A detailed history must be taken, with  particular emphasis on sexual activity. Specific areas of focus when obtaining a history from the patient include:<ref name="pmid20358658">{{cite journal |vauthors= |title=Information from your family doctor. Urethritis in men |journal=Am Fam Physician |volume=81 |issue=7 |pages=879 |year=2010 |pmid=20358658 |doi= |url=}}</ref>
*Recent sexual activities
*Number of sex partners or any new partner
*Use of condoms
*History of prior [[STD]]s
*History of recent urethral instrumentation (e.g., urethral [[catheters]])


===Symptoms===
=== Other Diagnostic Studies ===
*Symptoms suggestive of urethritis include [[dysuria]] and [[urethral discharge]].
There are no additional [[diagnostic]] findings for urethritis.


==Physical Examination==
==Treatment==
*The most common physical finding in urethritis is [[urethral discharge]]. The entire genital area must be examined in order to rule out other possibilities.<ref name="pmid20353145">{{cite journal |vauthors=Brill JR |title=Diagnosis and treatment of urethritis in men |journal=Am Fam Physician |volume=81 |issue=7 |pages=873–8 |year=2010 |pmid=20353145 |doi= |url=}}</ref>
===Medical Therapy===
*Patients should be examined for [[Inguinal region|inguinal]] [[lymphadenopathy]], [[ulcers]], and [[urethral discharge]].
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|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.


==Laboratory Findings==
===Interventions===
Urethritis may be considered on the basis of any of the following:<ref name="pmid67816">{{cite journal |vauthors=Jacobs NF, Kraus SJ |title=Gonococcal and nongonococcal urethritis in men. Clinical and laboratory differentiation |journal=Ann. Intern. Med. |volume=82 |issue=1 |pages=7–12 |year=1975 |pmid=67816 |doi= |url=}}</ref><ref>{{cite book |last = Bennett |first = John |title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases |publisher = Elsevier/Saunders |location = Philadelphia, PA |year = 2015 |isbn=9781455748013}}</ref><ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=MMWR Recomm Rep |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=}}</ref>
There are no recommended therapeutic interventions for the management of urethritis.
*Mucoid, [[mucopurulent]], or [[purulent]] discharge on examination
*[[Gram staining|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.<ref name="pmid17331273">{{cite journal |vauthors=Horner PJ, Taylor-Robinson D |title=Is there a role for leucocyte esterase testing in non-invasive screening using nucleic acid amplification tests of asymptomatic men? |journal=Int J STD AIDS |volume=18 |issue=2 |pages=73–4 |year=2007 |pmid=17331273 |doi=10.1258/095646207779949718 |url=}}</ref><ref name="pmid12671557">{{cite journal |vauthors=Chernesky M, Jang D, Chong S, Sellors J, Mahony J |title=Impact of urine collection order on the ability of assays to identify Chlamydia trachomatis infections in men |journal=Sex Transm Dis |volume=30 |issue=4 |pages=345–7 |year=2003 |pmid=12671557 |doi= |url=}}</ref>


==Medical Therapy==
===Surgery===
The preferred [[antibiotic]] regimen depends on the [[etiologic]] pathogen.<ref>{{cite book |last = Bennett |first = John |title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases |publisher = Elsevier/Saunders |location = Philadelphia, PA |year = 2015 |isbn=9781455748013}}</ref><ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=MMWR Recomm Rep |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=}}</ref><ref name="pmid20353145">{{cite journal |vauthors=Brill JR |title=Diagnosis and treatment of urethritis in men |journal=Am Fam Physician |volume=81 |issue=7 |pages=873–8 |year=2010 |pmid=20353145 |doi= |url=}}</ref>
Surgical intervention is not recommended for the management of urethritis.
*'''Gonorrheal urethritis:''' [[Ceftriaxone]] 250 mg IM in a single dose  '''PLUS''' [[Azithromycin]] 1 g PO in a single dose
*'''Non-gonorrheal urethritis:''' [[Azithromycin]] 1 g PO in a single dose  '''OR''' [[Doxycycline]] 100 mg PO bid for 7 days


==Primary Prevention==
===Primary Prevention===
Effective measures for the primary prevention of urethritis include:<ref name=primary-prev>LeFevre ML. USPSTF: behavioral counseling interventions to prevent sexually transmitted infections. Ann Intern Med 2014;161:894–901.</ref><ref name=gono-condom>Warner L, Stone KM, Macaluso M, et al. Condom use and risk of gonorrhea and Chlamydia: a systematic review of design and measurement factors assessed in epidemiologic studies. Sex Transm Dis 2006;33:36–51.</ref>
Effective measures for the [[primary prevention]] of urethritis include limiting the number of sex partners and using condoms.
*Educating adolescents about safe sex practices
*Practicing abstinence
*Using condoms
*Limiting the number of sex partners


==Secondary Prevention==
===Secondary Prevention===
In order to prevent transmission to partners and decrease the risk of [[antibiotic resistance]], all patients must be instructed on guidelines for safe sex practice, and have screening tests done following treatment.<ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=MMWR Recomm Rep |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=}}</ref><ref name="pmid20353145">{{cite journal |vauthors=Brill JR |title=Diagnosis and treatment of urethritis in men |journal=Am Fam Physician |volume=81 |issue=7 |pages=873–8 |year=2010 |pmid=20353145 |doi= |url=}}</ref>
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==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Infectious disease]]
[[Category:Primary care]]


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Latest revision as of 16:08, 27 August 2021

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Urethritis Microchapters

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Urethritis from other Diseases

Epidemiology and Demographics

Risk Factors

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Natural History, Complications and Prognosis

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Diagnostic Study of Choice

History and Symptoms

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Laboratory Findings

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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

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

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

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

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 piligonococci 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

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

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

Epidemiology and Demographics

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

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

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

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

Diagnostic Study of Choice

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

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

Symptoms suggestive of urethritis include dysuria and urethral discharge.

Physical Examination

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

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

There are no ECG findings associated with urethritis.

X-ray

There are no x-ray findings associated with urethritis.

Echocardiography and Ultrasound

There are no echocardiography/ultrasound findings associated with urethritis.

CT scan

There are no CT scan findings associated with urethritis.

MRI

There are no MRI findings associated with urethritis.

Other Imaging Findings

There are no other imaging findings associated with urethritis.

Other Diagnostic Studies

There are no additional diagnostic findings for urethritis.

Treatment

Medical Therapy

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

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

Surgery

Surgical intervention is not recommended for the management of urethritis.

Primary Prevention

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

Secondary Prevention

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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