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]

Historical Perspective

The first known case of urethritis was described by Albert Neisser, a German doctor, in 1879.[1]

Classification

Urethritis can be classified into two main groups:

  • Infectious urethritis- This can be further subdivided into gonococcal and non-gonococcal urethritis.
  • Non-infectious urethritis

Pathophysiology

The pathogenesis of urethritis varies depending on the underlying pathogen.

  • Neisseria gonorrhoeae is usually transmitted to the human host via the genital tract.
  • Following attachment to host cell, which is mediated by pili, gonococci become engulfed in a process known as parasite-directed endocytosis. The organism can survive inside the vacuoles and replicate.[2]
  • 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 lysosomes, and replicating as elementary bodies (the infective form of the pathogen).[3][4]

Causes

Urethritis may be caused by either infectious or non-infectious causes. Infectious causes can be further subdivided into gonorrheal and non-gonorrheal.[5] Non-gonorrheal pathogens are the most frequent cause of urethritis; Chlamydia trachomatis is the most common among them.[6][5][7]

Differential diagnosis of urethritis

Urethritis must be differentiated from other causes of dysuria and urethral discharge, which include acute cystitis,[8][9][10] epididymitis,[11] prostatitis,[12] cervicitis,[13] and vulvovaginitis.[14]

Epidemiology

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.[15][16]

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.[17]

Gender

  • 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).[17]
  • 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

  • Chlamydia trachomatis: Almost two-thirds of chlamydia infections occur among youths aged 15-24 years.[18]
  • 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

  • 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.[19]
  • 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.[19]

Risk Factors

The most important risk factor in developing urethritis is unprotected sex, especially among men who have sex with men. Other risk factors include:[20][21]

  • Low socioeconomic status
  • Prior or current STD
  • New or multiple sex partners
  • Circumcision

Screening

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:[22]

Natural History

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.[23] Prolonged asymptomatic urethral carriage of gonococci occurs in 2% to 3% of newly infected men if left untreated.[24]

Complications

Common complications of urethritis include:

  • 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.[25]
  • 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.[26]

History and Symptoms

History

A detailed history must be taken, with particular emphasis on sexual activity. Specific areas of focus when obtaining a history from the patient include:[27]

  • Recent sexual activities
  • Number of sex partners or any new partner
  • Use of condoms
  • History of prior STDs
  • History of recent urethral instrumentation (e.g., urethral catheters)

Symptoms

Physical Examination

Laboratory Findings

Urethritis may be considered on the basis of any of the following:[29][30][31]

Medical Therapy

The preferred antibiotic regimen depends on the etiologic pathogen.[34][31][28]

Primary Prevention

Effective measures for the primary prevention of urethritis include:[35][36]

  • Educating adolescents about safe sex practices
  • Practicing abstinence
  • Using condoms
  • Limiting the number of sex partners

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.[31][28]

References

  1. Oriel JD (1996). "The history of non-gonococcal urethritis". Genitourin Med. 72 (5): 374–9. PMC 1195709. PMID 8976858.
  2. Scheuerpflug I, Rudel T, Ryll R, Pandit J, Meyer TF (1999). "Roles of PilC and PilE proteins in pilus-mediated adherence of Neisseria gonorrhoeae and Neisseria meningitidis to human erythrocytes and endothelial and epithelial cells". Infect. Immun. 67 (2): 834–43. PMC 96394. PMID 9916098.
  3. 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.
  4. Baron, Samuel. Medical microbiology. Galveston, Tex: University of Texas Medical Branch at Galveston, 1996. Print.
  5. 5.0 5.1 Al-Sweih NA, Khan S, Rotimi VO (2011). "The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among men with urethritis in Kuwait". J Infect Public Health. 4 (4): 175–9. doi:10.1016/j.jiph.2011.07.003. PMID 22000844.
  6. Kimberly A. Workowski & Gail A. Bolan (2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. PMID 26042815. Unknown parameter |month= ignored (help)
  7. Le Roux MC, Ramoncha MR, Adam A, Hoosen AA (2010). "Aetiological agents of urethritis in symptomatic South African men attending a family practice". Int J STD AIDS. 21 (7): 477–81. doi:10.1258/ijsa.2010.010066. PMID 20852197.
  8. Stephen Bent, Brahmajee K. Nallamothu, David L. Simel, Stephan D. Fihn & Sanjay Saint (2002). "Does this woman have an acute uncomplicated urinary tract infection?". JAMA. 287 (20): 2701–2710. PMID 12020306. Unknown parameter |month= ignored (help)
  9. W. E. Stamm (1981). "Etiology and management of the acute urethral syndrome". Sexually transmitted diseases. 8 (3): 235–238. PMID 7292216. Unknown parameter |month= ignored (help)
  10. W. E. Stamm, K. F. Wagner, R. Amsel, E. R. Alexander, M. Turck, G. W. Counts & K. K. Holmes (1980). "Causes of the acute urethral syndrome in women". The New England journal of medicine. 303 (8): 409–415. doi:10.1056/NEJM198008213030801. PMID 6993946. Unknown parameter |month= ignored (help)
  11. A. Stewart, S. S. Ubee & H. Davies (2011). "Epididymo-orchitis". BMJ (Clinical research ed.). 342: d1543. PMID 21490048.
  12. Felix Millan-Rodriguez, J. Palou, Anna Bujons-Tur, Mireia Musquera-Felip, Carlota Sevilla-Cecilia, Marc Serrallach-Orejas, Carlos Baez-Angles & Humberto Villavicencio-Mavrich (2006). "Acute bacterial prostatitis: two different sub-categories according to a previous manipulation of the lower urinary tract". World journal of urology. 24 (1): 45–50. doi:10.1007/s00345-005-0040-4. PMID 16437219. Unknown parameter |month= ignored (help)
  13. Kimberly A. Workowski & Gail A. Bolan (2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. PMID 26042815. Unknown parameter |month= ignored (help)
  14. Daniel V. Landers, Harold C. Wiesenfeld, R. Phillip Heine, Marijane A. Krohn & Sharon L. Hillier (2004). "Predictive value of the clinical diagnosis of lower genital tract infection in women". American journal of obstetrics and gynecology. 190 (4): 1004–1010. doi:10.1016/j.ajog.2004.02.015. PMID 15118630. Unknown parameter |month= ignored (help)
  15. WHO epidemiology http://www.who.int/mediacentre/factsheets/fs110/en/ (2016) Accessed on September 26, 2016
  16. Torrone E, Papp J, Weinstock H (2014). "Prevalence of Chlamydia trachomatis genital infection among persons aged 14-39 years--United States, 2007-2012". MMWR Morb. Mortal. Wkly. Rep. 63 (38): 834–8. PMID 25254560.
  17. 17.0 17.1 "National Overview - 2014 STD Surveillance".
  18. Chlamydia CDC Fact Sheet. CDC.http://www.cdc.gov/std/chlamydia/stdfact-chlamydia-detailed.htm#_ENREF_3. Accessed on September 28,2016
  19. 19.0 19.1 "Chlamydia - 2014 STD Surveillance".
  20. Chacko MR, Lovchik JC (1984). "Chlamydia trachomatis infection in sexually active adolescents: prevalence and risk factors". Pediatrics. 73 (6): 836–40. PMID 6547226.
  21. Van Howe RS (2007). "Genital ulcerative disease and sexually transmitted urethritis and circumcision: a meta-analysis". Int J STD AIDS. 18 (12): 799–809. doi:10.1258/095646207782717045. PMID 18073009.
  22. 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
  23. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
  24. Detels R, Green AM, Klausner JD, Katzenstein D, Gaydos C, Handsfield H, Pequegnat W, Mayer K, Hartwell TD, Quinn TC (2011). "The incidence and correlates of symptomatic and asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae infections in selected populations in five countries". Sex Transm Dis. 38 (6): 503–9. PMC 3408314. PMID 22256336.
  25. Holmes KK, Handsfield HH, Wang SP, Wentworth BB, Turck M, Anderson JB, Alexander ER (1975). "Etiology of nongonococcal urethritis". N. Engl. J. Med. 292 (23): 1199–205. doi:10.1056/NEJM197506052922301. PMID 165407.
  26. Rönnerstam R, Persson K (1982). "Chlamydial eye infection in adults". Scand J Infect Dis Suppl. 32: 111–5. PMID 6958007.
  27. "Information from your family doctor. Urethritis in men". Am Fam Physician. 81 (7): 879. 2010. PMID 20358658.
  28. 28.0 28.1 28.2 Brill JR (2010). "Diagnosis and treatment of urethritis in men". Am Fam Physician. 81 (7): 873–8. PMID 20353145.
  29. Jacobs NF, Kraus SJ (1975). "Gonococcal and nongonococcal urethritis in men. Clinical and laboratory differentiation". Ann. Intern. Med. 82 (1): 7–12. PMID 67816.
  30. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
  31. 31.0 31.1 31.2 Workowski KA, Bolan GA (2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR Recomm Rep. 64 (RR-03): 1–137. PMID 26042815.
  32. Horner PJ, Taylor-Robinson D (2007). "Is there a role for leucocyte esterase testing in non-invasive screening using nucleic acid amplification tests of asymptomatic men?". Int J STD AIDS. 18 (2): 73–4. doi:10.1258/095646207779949718. PMID 17331273.
  33. Chernesky M, Jang D, Chong S, Sellors J, Mahony J (2003). "Impact of urine collection order on the ability of assays to identify Chlamydia trachomatis infections in men". Sex Transm Dis. 30 (4): 345–7. PMID 12671557.
  34. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
  35. LeFevre ML. USPSTF: behavioral counseling interventions to prevent sexually transmitted infections. Ann Intern Med 2014;161:894–901.
  36. 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.

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