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Defining the Urethritis Syndrome in Men Using Patient Reported Symptoms

Jordan, Stephen, J., MD, PhD; Aaron, Kristal, J., DrPH, MSPH; Schwebke, Jane, R., MD; Van Der Pol, Barbara, J., PhD, MPH; Hook, Edward, W., III, MD

Sexually Transmitted Diseases: July 2018 - Volume 45 - Issue 7 - p e40–e42
doi: 10.1097/OLQ.0000000000000790
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To evaluate self-reported symptoms to guide urethritis diagnosis, symptomatic men being evaluated for urethritis were asked about 7 symptoms captured during history taking. Discharge and dysuria were significantly associated with urethritis and, when combined with genital irritation and itching, identified 95% of urethritis cases; odor and urinary frequency performed poorly.

We evaluated the performance of 7 self-reported symptoms in men with and without urethritis. Discharge and dysuria were associated with urethritis. Other symptoms, including urinary frequency and odor were poorly recorded.

From the Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL

Acknowledgments: The authors are grateful to Paula Dixon and Austin Culver for assistance with specimen processing/testing and Drs. Teri Anderson, Laura Bachmann, Dennis Fortenberry, William Geisler, Khalil Ghanem, H. Hunter Handsfield, David Martin, Angela Montgomery, Anne Rompalo, Bradley Stoner, Kimberly Workowski, and Jonathan Zenilman for their responses to the survey.

Conflicts of Interest and Source of Funding: S.J.J. has no conflicts of interest. K.J.A. has no conflicts of interest. J.R.S. has received honoraria, consulting fees, or research support from Cepheid, BD Diagnostics, LabCorp, and Hologic. B.V.D.P. has received honoraria, consulting fees, or research support from the following sponsors: Abbott Molecular Diagnostics, Atlas Genetics, BD Diagnostics, Beckman Coulter, Great Basin, Scientific, Cepheid, Hologic, Rheonix, and Roche Diagnostics. E.W.H. has received honoraria, research support, or consulting fees from Cepheid, BD Diagnostics, Gen-Probe Hologic, and Roche Diagnostics. Reagents and test kits for this study were supplied by Cepheid (Sunnyvale, CA). This work was funded from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health Sexually Transmitted Infection Cooperative Research Center grant U19AI113212 (E.W.H., P.I.).

Correspondence: Stephen J. Jordan: Indiana University, 635 Barnhill Drive, Van Nuys Medical Science Bldg, MS 224E, Indianapolis, Indiana 46202. E-mail: jordansj@iu.edu.

Received for publication August 9, 2017, and accepted January 9, 2018.

Urethritis is the most common genitourinary syndrome in sexually active men younger than 50 years1 with an estimated 2.8 million cases occurring annually in the United States.2 Urethritis is associated with a number of etiological agents3 including Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and Mycoplasma genitalium and causes a wide variety of symptoms, which include discharge, dysuria, localized pruritus, and penile tingling.2,4–7 To collect information on urethral symptoms, health care providers often use standardized data collection forms, driven by the rapid adoption of electronic medical records (EMR).8 A result is that they may be both time consuming and inefficient as they encompass symptoms of both urinary tract infections (eg, frequency, odor, etc) and sexually transmitted infections (STI) (eg, discharge, dysuria, etc).9 To our knowledge, there are no recent data on the relative importance of specific symptoms in predicting urethritis syndrome, which could help “recalibrate” modern syndromic management approaches to urethritis. Given the increasing trend in STI rates10,11 and utilization of health care resources,12 such information could increase clinical efficiency by reducing unnecessary questioning and by shortening screening forms seeking urethritis symptoms. To this end, we evaluated 384 men attending a Birmingham, Alabama, sexually transmitted disease (STD) clinic and used data from the clinic's EMR and urethral Gram stain smears to diagnose symptomatic urethritis. Our primary objective was to test the performance of specific symptoms at accurately predicting urethritis. A secondary outcome was to compare our findings to an expert clinician-ranked survey of urethritis symptoms that predict urethritis to assess the accuracy of clinicians at predicting urethritis by syndromic management.

We enrolled 384 participants of whom 194 (51%) had at least 1 of the 7 potential EMR urethritis symptoms (discharge, dysuria, urinary frequency, genital irritation, genital itching, genital lesions, and odor) captured on the EMR and were included in this study. All participants answered the same 7 questions, none of which were specifically listed when recruiting for the study. Participants were enrolled as part of a larger diagnostic study of nongonococcal urethritis (NGU) in men 19 years or older, which included a detailed symptoms questionnaire and collection of a urethral swab for STI pathogen testing. All procedures were reviewed and approved by the local and National Institutes of Health internal review processes and informed content was obtained for all men before enrollment. Men were 19 to 65 years old and 93% were black. Physical examinations were performed by trained clinicians to determine the presence of urethral discharge, and a urethral swab was obtained from all men for Gram stain testing of urethral secretions. Gram stains were read in blinded fashion by a single expert microscopist (J.R.S.). One hundred thirty-nine (64%) men were diagnosed with symptomatic urethritis based on the presence of self-reported symptoms and either a discharge on physical examination (N = 106) or the presence of 5 or more polymorphonuclear cells per high-power field (PMNs/HPF) by microscopy of a Gram stain smear of urethral secretions (N = 124). Using nucleic acid amplification testing, 33 (17%) participants were positive for NG, 35 (18%) had positive tests for CT, and 19 (10%) had tests positive for both NG and CT. Then, we compared the results to a survey from 13 experienced sexual health clinicians, all leaders in the STI field, who were asked to rank the 7 EMR symptoms in order of importance for predicting urethritis using a linear 1 (most important) to 7 (least important) scale.

As shown in Table 1, in the 194 symptomatic men, urethral discharge was the most common complaint (61%), followed by dysuria (50%), genital irritation and lesions (both 10%), then urinary frequency and genital itching (both 7%), and then odor (1%). One hundred thirty-nine (72%) of the symptomatic men were subsequently diagnosed with documented urethritis. In men with symptomatic urethritis, discharge was the most common symptom (71%), followed by dysuria (59%). All other symptoms were present in 6% or less of men with urethritis. Stratified by gonococcal (GC) urethritis or NGU, discharge was present in 88% of men with GC urethritis and 58% of men with NGU. Dysuria was present in 75% of men with GC urethritis and 47% of men with NGU. The other symptoms were present in 9% or less of men with either GC urethritis or NGU (data not shown). Compared with men without urethritis, discharge or dysuria was significantly associated with a twofold increased risk for urethritis. In contrast, the other symptoms were independently either not associated with urethritis (frequency, itching, or odor) or had an approximately fourfold negative association with urethritis (lesions, irritation). We then used our study findings and the expert survey responses to determine the contribution of each symptom to accurate syndromic diagnosis of urethritis. All 13 surveyed expert clinicians identified either discharge (n = 9, 69%) or dysuria (n = 4, 31%) as the most important symptom predicting urethritis, and identified the other symptom (either dysuria or discharge) as the second most important (data not shown). The mean expert-ranked score and standard deviation for each symptom, from most to least important, were discharge (1.3 ± 0.48), dysuria (1.7 ± 0.48), urinary frequency (3.8 ± 1.14), genital irritation (4.1 ± 0.76), genital itching (mean 4.6 ± 1.12), genital lesions (5.9 ± 1.04), and odor (6.5 ± 0.78).

TABLE 1

TABLE 1

Given the strong association between dysuria or discharge and urethritis and our observation that almost half of men with symptomatic urethritis (n = 67, 48%) complained of more than one symptom (data not shown), we then calculated the proportion of documented urethritis diagnoses that could be identified by taking a stepwise combination approach for the utility of urethritis symptoms. As shown in Table 2, the addition of self-reported dysuria to a discharge complaint captured an additional 22 (16%) men with a clinical diagnosis of urethritis (87% total), compared with discharge alone. The addition of genital irritation added another 6 (4%) men, encompassing 91% of all urethritis diagnoses. The remaining 9% of all clinical diagnoses included the symptoms genital itching, genital lesions, and urinary frequency.

TABLE 2

TABLE 2

In this study, self-reported urethral discharge was the symptom most predictive of urethritis, present in 71% of men with clinical urethritis. Dysuria, the second most prevalent symptom, was reported in 59% of men with urethritis. Only discharge and dysuria were significantly associated with a urethritis diagnosis and appear to increase the risk by twofold. Men with urethritis rarely complained of the remaining 5 symptoms, in which each occurred in 6% or less of men. In fact, only 4% (range, 0–6%) of patients with urethritis complained of frequency, genital irritation, itching, lesions, or odor, which were either not associated with urethritis or were more likely to be associated with a diagnosis other than urethritis. This suggests that these symptoms provide specific information that, excluding discharge or dysuria, support an alternative diagnosis (eg, lesions caused by HPV, etc.).

Our study suggests that discharge and dysuria are clearly the most important symptoms to ask men being evaluated for urethritis. The remaining symptoms of irritation, itching, and lesions appear to be beneficial only when added to discharge and dysuria because, independently, they were not significantly associated with urethritis. Asking about urinary frequency or genital odor, in addition to the mentioned symptoms, identified only 2 additional cases of urethritis, suggesting that there is little utility in adding those symptoms to either the clinical interview or in a symptom survey.

Genital irritation, genital itching, genital lesions, urinary frequency, and urinary odor were relatively infrequent, cumulatively comprising only 13% of urethritis diagnoses in differing proportions. This suggests that men may have difficulty articulating their symptoms perhaps colored by their preconceptions of what symptoms of an STD “should” feel like. Specifically, men may have difficulty differentiating “genital irritation” from “genital itching” and combining them into a broader term may be appropriate. For example, in our study, 4 men admitted to irritation, but specifically identified their symptom as “tingling” (data not shown). As a simplifying strategy, we suggest the use of a broader, more encompassing term, such as “genital discomfort” instead of “genital irritation” and/or “genital itching,” which could identify 95% of urethritis diagnoses, when combined with urethral discharge and dysuria. In contrast, adding urinary frequency or odor to the list of queried symptoms had little impact on the percent of identified urethritis cases (Table 2) and could likely be excluded from urethritis screening.

Our study has several limitations. In this single-center study, the majority of the men in this study were African American, which is representative of our clinic population, and therefore these findings may not be generalizable to other populations. The GC rate was high in our study, and we cannot exclude that our findings may differ in populations with different STI rates and/or etiologies of urethritis (eg, M. genitalium, T. vaginalis, etc), especially outside the United States. We also used a Gram stain cutoff of 5 PMNs/HPF or greater (recommended by the European NGU treatment guidelines)13 to maximize the urethritis diagnosis specificity. It is possible that using the lower cutoff of 2 PMNs/HPF or greater (recommended by the 2015 CDC STD treatment guidelines)4 could have yielded different results. Although the latter cutoff appears to identify more chlamydia diagnoses,13 whether it more accurately reflects urethritis remains unclear. Also, our study only enrolled men who presented to the STD clinic, and we cannot rule out the possibility of a selection bias, given that our study does not include men presenting to other clinics or mildly symptomatic men who did not come in for symptom evaluation.

In conclusion, in sexually active men who present with genitourinary complaints, a history of discharge and/or dysuria should prompt appropriate evaluation and screening for urethritis and could identify up to 87% of the cases. If combined with discharge and/or dysuria, up to 95% of urethritis cases could be identified if genital irritation and/or itching were also present. Excluding discharge and dysuria, however, the other symptoms were not independently associated with a urethritis. Urinary frequency and odor were poor predictors of urethritis and can likely be excluded from symptom queries trying to identify men with symptomatic urethritis. These results could form the basis for an effective standardized EMR-based method for screening sexually active men for symptomatic urethritis.

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