Is non-chlamydial non-gonococcal urethritis associated with significant clinical complications in men? A systematic review

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.