Is Non-Chlamydial Non-Gonococcal Urethritis Associated with Significant Clinical Complications in Men? A Systematic Review

Abstract

Background: It is estimated that between 50 and 89% of non-gonococcal urethritis is not caused by Chlamydia trachomatis. Associations between non-chlamydial non-gonococcal urethritis (NCNGU) with balanoposthitis, epididymo-orchitis and reactive arthritis have been suggested, but evidence to support these often-theoretical relationships is sparse and further investigation is called for. Concerns over increasing antimicrobial resistance has rendered the need for clarity over this question ever more pressing in recent years. A review of the current evidence on the complications of NCNGU in men is therefore urgently warranted. Objective: This systematic review summarizes and evaluates the available evidence that NCNGU, whether symptomatic or asymptomatic, causes the significant complications that are already well-recognized to be associated with non-gonococcal urethritis. These significant complications are epididymo-orchitis, balanoposthitis, and sexually-acquired reactive arthritis (Reiter's syndrome) including arthritis or conjunctivitis. Summary: We conducted a systematic review and qualitative synthesis using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis framework. Five databases (PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and British Nursing Index) were searched. We included studies that measured clinical outcome after diagnosis of NCNGU in men. Bias was assessed using variations of the Newcastle-Ottawa scale. Data were extracted and entered into a pre-written data abstraction proforma. Seven peer-review studies were included. This included 2 retrospective cohort studies, 1 case series, 2 case reports and 2 cross-sectional studies. The studies described and analyzed 3 types of complication: balanitis, posthitis and/or meatitis; reactive arthritis and/or conjunctivitis; and epididymitis. All studies reported one or more complications. Key Messages: This review identifies an important avenue for future research: while the available evidence suggests that NCNGU has the potential to cause significant complications in men, with the strongest evidence existing for balanitis, posthitis and/or meatitis, the nature and significance of these relationships is far from clear. The findings of this review suggest that prospective, adequately powered research into whether there is a causal link between NCNGU and significant clinical complications in men would be highly worthwhile. The findings of this review raise important questions about the utility of the term NCNGU in research and clinical practice.

A young man with red eye

“…In reactive arthritis, inflammatory arthritis accompanies urethritis and mild, transient conjunctivitis (without excessive mucopurulent discharge) 1011. Chlamydia trachomatis , Mycoplasma genitalium , and adenovirus are causative agents of non-gonococcal urethritis with conjunctivitis 12. In non-gonococcal urethritis, conjunctivitis is usually chronic and without large amounts of mucopurulent discharge—conjunctivitis can develop over weeks or months and might be related to sexual activity or autoinoculation 13…”

Increased infections by herpes simplex virus type 1 and polymicrobials of the genital tract, in the general population of a Spanish middle city

“…En el varón, U. urealyticum fue el segundo microorganismo más frecuente después de N. gonorrhoeae y por delante de C. trachomatis, por lo que obtuvimos que las uretritis más frecuentes en el varón fueron las gonocócicas y que, entre las no gonocócicas, C. trachomatis y U. urealyticum. Estos datos coinciden con los de otros estudios en los que se concluye que, en las uretritis no gonocócicas, aumentan las causadas por microorganismos diferentes de C. trachomatis, aunque este sigue siendo el principal [13]. Así mismo, C. trachomatis también está implicado en proctitis infecciosa, sobre todo en varones homosexuales y mujeres, y en relación con prácticas sexuales sin protección, donde es la cuarta etiología más frecuente en nuestro medio.…”

“…Los microrganismos más prevalentes son C. trachomatis y N. gonorrhoeae, pudiendo encontrase también M. genitalium, U. urealyticum, Haemophilus spp., G. vaginalis, Candida spp. y T. vaginalis [13]. El hecho de que puedan cursar de manera poco sintomática (hasta en el 50% de los casos) aumenta la probabilidad de transmisión [14,15].…”

A Genital Infection-Attenuated Chlamydia muridarum Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge

“…In women, Ct infection can spread from the cervix into the uterus and fallopian tubes, causing inflammation and serious reproductive complications. In contrast, urethral Ct infections in men usually elicit local inflammation and self-limiting urethritis symptoms ( 2 ) and only rarely cause upper genital tract complications ( 3 ). Ct rectal infections are also prevalent in both sexes and are often detected in individuals who do not report high-risk behaviors that are risk factors for other rectal STIs ( 4 , 5 ).…”