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Journal of American College Health Association Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzch20
Nonspecific Urethritis: Its Current Status Clyde E. Rapp Jr. M.D.
a
a
Division of Adolescent Medicine , Children's Hospital of Philadelphia , Pennsylvania, 19104, USA Published online: 07 Apr 2011.
To cite this article: Clyde E. Rapp Jr. M.D. (1978) Nonspecific Urethritis: Its Current Status, Journal of American College Health Association, 27:2, 87-110, DOI: 10.1080/01644300.1978.10392832 To link to this article: http://dx.doi.org/10.1080/01644300.1978.10392832
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Nonspecific Urethritis: Its Current Status* CLYDE E. RAPP, jr., M.D.1Drexel University
Downloaded by [York University Libraries] at 07:15 29 December 2014
Abstract The etiology, epidemiology, clinical presentation, diagnosis, and treatment o f nonspecific urethritis (NS. U.) is discussed. Chlamydia seems to be responsible for approximately 40-50% o f cases while the etiology o f the remainder remains obscrue. There seems to be reasonably good evidence for venereal transmission as well as for treatment o f the female partner whether symptomatic or asymptomatic. Tetracyline given for 21 days or oxytetracycline given for four days seem to be the most effective first line treatment regimens at this time. Complications which include prostatitis, epididymitis, urethral stricture, and Reiter ’s Syndrome, are discussed. It appears as though there is a reasonable possibility that ReiterS Syndrome is a separate entity (or immunological sequela) rather than a complication. As i s widely known, nonspecific urethritis (N.S.U.) i s a frequent diagnostic problem among students coming to college health centers. Exact incidence figures are not readily available because of inadequate reporting and confusion as t o diagnostic criteria. A study from Great Britain, where reporting procedures are more thorough, stated the N.S.U. was more prevalent than gonococcal urethritis in the year 1968 as well as during the three receding years.l Another study,l from a public health clinic !venereal disease clinic in DeKalb County, Georgia) noted that 30% of the patients coming to the clinic had nongonococcal urethritis while 31% of the patients had gonococcal urethritis. The clinic where the study was performed i s not completely comparable to a college health center because of a relatively high percentage o f black patients attending the clinic. This would tend to inflate the incidence of gonococcal urethritis, since a higher percentage (73%) of the patients with gonococcal urethritis were black, (in the DeKalb County Study), and a higher percentage (71%) o f the N.S.U. patients were white. Personal observations and communications with others in the college health field would suggest that the prevalence of nonspecific urethritis is higher than gonococcal urethritis. Etiology A number o f attempts have been made to isolate a single organism that can be shown t o be the cause o f all cases o f nonspecific urethritis. Chlamydia trachomatis has been the organism most frequently implicated, but it has never been shown to be responsible for all cases in a given series. Oriel recovered Chlamydia in 36% o f 98 men with first attacks of nonspecific urethritis but from none o f 34 controls without urethritis.3 In a very thorough study, Holmes e t at, isolated Chlamydia trachomatis from 42% (or 481113) o f patients with nonspecific (or nongonococcal) urethritis and from only 7% (or 4/58) o f matched controls and 19% (or 13/69) o f *A synopsis presented at the Fifty-Fifth Annual Meeting, American College Health Association, Philadelphia, Pennsylvania, April 20,1977
t Director o f Health Services,
Drexel University; Division of Adolescent Medicine, Children’s Hospital o f Philadelphia, Pennsylvania 19104 VOL. 27, OCTOBER 1978
patients with gonococcal ~ r e t h r i t i s . In ~ addition, seroconversion was demonstrated in 9 o f 17 culture positive, initially seronegative patients with nonspecific urethritis. Their study did not demonstrate any significant difference between patients with nonspecific urethritis and controls when attempts were made to isolate mycoplasma hominis, T-mycoplasma, H. hominis and cytomegalovirus. Therefore, the etiology o f slightly over half o f their cases remains obscure. An attempt to associate herpes simplex type 1 or herpes simplex type 2 with nonspecific urethritis failed t o demonstrate any significant difference between patients and cont r o l ~ . Grimble ~ and Amarasuriya6 found multiple isolates containing varying combinations o f Chlamydia, T-mycoplasma, M. hominis, Trichomonas vaginitis, and cytomegalovirus, as well as negative cultures, in a number o f cases. They f e l t this data suggested that multiple .organisms may be responsible or that the etiology may be noninfectious in some cases or at least caused by organisms that are not identifiable with present techniques. Scott and Rasbridge7 determined that the pattern and degree o f elevation o f IgG, IgA, and IgM in nonspecific and gonococcal urethritis were similar and that this data supported an infectious etiology for nonspecific urethritis. Ureaplasma urealyticum has also been f e l t to be a possible etiological agent for the 40-50% o f cases o f nonspecific urethritis not due t o Chlamydia trachomatis. Bowie found that ureaplasma type organisms were recovered in 35 o f 43 (81%) o f cases o f Chlamydia negative nonspecific urethritis, while he found ureaplasma in only 11 out o f 26 (42%) o f patients with Chlamydia positive nonspecific urethritk8 Twenty-two out o f thirty-eight (or 58%) o f patients without urethritis carried the organism. The ureaplasmacarrier rate i s known to be high,g so this casts some doubts on the possibility o f the pathogenic role o f the ureaplasmas. In summary then, as far as etiology i s concerned, the data o f Holmes et at4 as well as other studies support the fact that a significant percentage of cases are due to Chlamydia trachomatis. However, the etiology o f approximately 50% o f cases remains obscure. Transmission The mechanism o f transmission and recommendations re87
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garding examination and treatment o f consorts are perhaps the hardest questions to answer since l i t t l e work has been done in this area. Grimble and Amarasuriya examined female sexual consorts o f index cases where there was only one consort and determined the following: 28% had nonspecific vaginitis, 11% had Trichomonal infection with or without Candida, 14.5% had vaginitis plus Candida, 29% had Candida present with or without vaginitis and 33.5% had normal flora.6 They suggested a possible etiological relationship between these conditions or that N.S.U. may be secondary to T. vaginitis and Candida, but the study does not compare the organisms isolated in the female consort with those isolated in the male. Nevertheless, the high incidence o f these conditions in female consorts lends support to the practice o f requesting that the sexual consorts o f cases with nonspecific urethritis come in to be evaluated and examined. Holmes et a14 determined that the prevalence o f microimmunofluorescent antibodies against C. trachomatis in culture negative controls and patients with gonococcal urethritis correlated directly with the number o f sexual partners during the preceding six months, strongly supporting venereal transmission and the importance of multiple sexual partners in the spread o f the disease (at least o f the cases secondary to Chlamydia trachomatis). He also found that Chlamydia trachomatis was recovered from the endocervix o f the female sexual partners o f 15 o f 22 patients with N.S.U. secondary to Chalamydia trachomatis and from only 2/24 o f the female consorts o f patients with N.S.U. not secondary to Chlamydia. Rees performed pelvic examinations on 245 female contact o f men with nonspecific urethritis.1° Eighty-seven percent o f those with hypertrophic cervical erosions were Chlamydia positive and 84% o f those with mucopurulent cervical contents were Chlamydria positive. This data would seem to lead strong support to venereal transmission o f cases of nonspecific urethritis secondary to Chlamydia (with obvious implications for treatment o f the female sex partner), but does not speak t o the question o f venereal transmission of cases not secondary to Chlamydia trachomatis. O f related interest were the findings of Mardh e t a/ concerning the role o f Chlamydia in the etiology o f acute salpingitis, again suggesting a female reservoir for those cases of N.S.U. secondary to Chlamydia.” Mardh and his colleagues cultured Chlamydia from 19/53 cervical specimens o f patients with laparoscopically verified acute salpingitis. In six o f seven cases where the cervical culture was positive and where tuba1 material was also cultured, Chlamydia was isolated from the fallopian tubes. The apparent increasing importance o f Chlamydia in the etiology o f salpingitis indicates that there is a good reason to request examination and evaluation o f female consorts o f male index cases, and certainly has certain implications for prophylactic treatment o f sexual consorts (see “Treatment” section.) No mention is made by Mardh and his colleagues concerning the precise symptomatology o f the female patients who were studied. I t should be emphasized that salpingitis is frequently accompanied by very vague symptoms and that the patient with salpingitis does not necessarily spontaneously seek medical attention. This adds t o the importance o f making vigorous efforts to bring contacts in to be examined. In addition, Holmes et a/, as noted earlier, successfully cultured Chlamydia from the cervix o f sexual consorts of index patient^.^ He made no mention o f symptomatology, so that it i s reasonable to assume that they may have been asymptomatic. This coincides with the observation o f others that Chlamydia are capable o f causing clinically unapparent disease.1° In addition, it has also been demonstrated by means o f screening studies that Chlamydia can be recovered from clinically normal cervices.12 A tenable conclusion then, would seem t o be that sexual partners o f 88
patients with nonspecific urethritis should be brought in to be examined, whether symptomatic or not. In conclusion, it would seem that the epidemiology o f nonspecific urethritis has not been thoroughly worked out. The only reasonable solid evidence for venereal transmission seems to be from those cases secondary to Chlamydia. Because we are usually unable t o determine which cases are secondary to Chlamydia and which are not, it i s therefore advisable to bring all sexual consorts of patients with nonspecific urethritis to be examined and treated, even if asymptomatic. History and Symptomatology The male patient with nonspecific urethritis typically presents with a history o f whitish, mucoid discharge and/or burning.13 The usual interval from the time o f last sexual intercourse is at least two weeks, allowing one t o help differentiate N.S.U. from gonococcal urethritis, which usually has an incubation period o f several days to a week. In an excellent review, jacobs e t a / found that dysuria plus discharge occurred in 71% o f their patients with gonococcal urethritis and 38% o f the patients with nonspecific ~ r e t h r i t i s . ’ ~Dysuria alone occurred in only 2% o f cases o f gonococcal urethritis and 15% o f those with N.S.U. Discharge alone occurred in 27% o f patients with gonococcal urethritis and 47% o f patients with N.S.U. Spontaneous and purulent discharge occurred only in patients with gonococcal urethritis and lack of discharge or minimal mucoid discharge was found exclusively in nongonococcal urethritis. Therefore, if one were to define the typical presentation o f nongonococcal urethritis, one would expect to see a patient with minimal mucoid discharge (personal note: this frequently occurs only in the morning in patients with N.S.U.) with a slight possibility of dysuria. The typical patient with gonococcal urethritis would present with purulent discharge (frequently spontaneous) and dysuria. It has been shown that a number o f patients with gonococcal urethritis also are carriers o f Chlamydia trachomatis, and there i s solid evidence that post gonococcal urethritis i s secondary to Chlamydia trachomatis approximately 70% o f the time.15 Therefore, since neither ampicillin, penicillin, or spectinomycin will eradicate Chlamydia, one may often see post gonococcal urethritis secondary to Chlamydia after a patient has been successfully treated for gonococcal urethritis. Thus, a patient may present with a history of a purulent discharge typical o f gonorrhea at one time and one to two weeks later may come in with symptoms typical o f nonspecific urethritis. There i s evidence to suggest that 65% o f those patients who develop post gonococcal urethritis secondary t o Chlamydia are infected with both organisms simultaneousIy.15 Physicians who see nonspecific urethritis frequently have observed that patients may prolong the discharge that began as a symptom o f nonspecific urethritis follows the initial nonspecific urethritis. I have personally observed a traumatic urethritis secondary to “mil king” following prostatitis. This i s particularly likely to occur in a compulsive individual who focuses a great deal o f anxiety on the discharge. Diagnosis If an exudate o f any kind is present, i t should be examined by means o f gram stains. (“Milking” or “stripping” the urethra may be necessary). It i s also important to culture the exudate in oll cases. As noted previously, occasionally a patient with gonorrhea may present with mucoid discharge, and in approximately 2% o f patients with gonococcal urethritis, the culture may be positive while the smear is negative.14 If no intracellular (or extracellular) diplococci are present on the gram strain
J. A .C.H. A .
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URETHRITIS
and only polymorphonuclear leukocytes are identified, then a tentative diagnosis of nonspecific urethritis can be made. The examining physician should be particulary interested in obtaining a reliable culture for gonorrhea in those individuals who have been treated unsuccessfully with one of the regimens (e.g. tetracycline or erythomycin) for nonspecific urethritis. Since these regimens are suboptimal for the treatment of gonorrhea, the patient may actually have gonorrhea which has never been treated properly. In some cases the symptoms may be somewhat attenuated and a positive culture may be easier to obtain if the patient i s off of all antibiotics for two days. It has been stated many times that the gonococcus i s a fastidious organism and the culture must be obtained properly. The most important factor in increasing the yield of positive cultures i s to plate the specimen immediately after obtaining it. The use of plastic “crush tubes” with built-in media has not been as satisfactory a method as immediately plating the material to be cultured on appropriate media directly after obtaining it. Needless to say, the dish should be placed in an incubator with a CO;! atmosphere as soon as possible. One should keep in mind that asymptomatic gonorrhea in men i s a more common, phenomenon than was previously thought to be true,16 so that where the index of suspicion of gonorrhea i s high (based on the type of clinic, and racial and socioeconomic factors). an individual who is symptomatically recovered from nonspecific urethritis should have a culture for gonorrhea. This will uncover those individuals who have received suboptimal treatment for undiagnosed gonorrhea and, therefore, noted a decrease in the amount of discharge. This i s accomplished by inserting a calcium algonate swab 1.O cm into the anterior urethra and then plating the material to be cultured, on appropriate culture media. In all cases of treatment failure, a specimen of discharge should be obtained and immersed in saline. Part of the saline should be examined for trichomonads by the hanging drop method and a second portion combined with a drop o f 10% potassium hydroxide solution and examined for the spores and mycelia of Candida after heat fixation. I t is also recommended that a culture for gonorrhea be done in these cases. Treatment Various regimens have been attempted in the treatment of nonspecific urethritis. The most popular seems to be 500 mgm of tetracycline every six hours for a total of seven days.13 An 80% cure rate has been achieved with this regimen by one group of authors,16 and definite superiority of this regimen over placebo therapy has been demonstrated. Other authors feel that a twenty-one day course of tetrac cline a t 250 mgm four times a day i s the regimen of choice1 . They stress that it i s particularly important to carry out treatment for this long a period of time in women, since it apparently takes longer to eradicate the organism in females. It i s clear from two studies6~17that placebo therapy does result in cure of a reasonable percentage of cases (34% and 20%). One of the aforementioned studies17 evaluated a regimen of 250 mgm of tetracycline four times a day for seven days compared with 500 mgm of tetracycline four times a day for seven days. Fifty-eight percent of the low dose group (with 20% being unresponsive and 22% defaulting) responded to treatment within two weeks. Sixty-one percent of the larger dose group responded in two weeks (with 22% being unresponsive and 17% defaulting). Oxytetracycline was evaluated in the same study and was found to be superior to tetracycline with 68% responsive within two weeks on 250 mgm four times a day for four days and 73% responding to 250 mgm four times a day for 10 days. There were no unresponsive patients although
Y
VOL. 27, OCTOBER 1978
32% defaulted from the four-day regimen and 27% defaulted from the 10-day regimen.) It appears that either a 21-day course of tetracycline (at 250 mgm/da ) or a four-day course of oxytetracycline (at 250 mgm/dayr constitutes adequate first line treatment of nonspecific urethritis. The tetracycline has the advantage of being cheaper and the oxytetracycline has the advantage of being given over a shorter period of time. In cases of treatment failure with tetracycline, it would certainly seem wise to attempt to use oxytetracycline (being sure to rule out reinfectiongonorrhea, or urethritis secondary to candida or trichomonas). If oxytetracycline is used as first line treatment, erythromycin (250 mgm four times a day for 21 days l8 or sulfisoxazole (500 mgm four times a day for 10 days l9 may be tried if oxytetracycline is not effective or as alternate regimens if allergies exist.
1
Complications
’
Complications of N.S.U., with the exception of prostatitis, are extremely rare as well as difficult to document accurately because of vague diagnostic criteria. Prostatitis, which is usually asymptomatic and painless, i s thought to occur in 20% of cases; epididymitis, which i s usually unilateral in the disease, occurs in under 3% of patients, and urethral stricture occurs in 0.5 to 5%.9 The reliability of this last statistic is subject to doubt, because of the possibility of gonorrhea prior to the nonspecific urethritis which may have produced the stricture and thereby predisposing the patient to nonspecific urethritis. Reiter’s syndrome consists of conjunctivitis, urethritis, polyarticular arthritis and mucocutaneous lesions. These usually consist of superficial ulcerations on the palate or buccal mucosa, kerataderma blenorrhagica on the palms and soles (which has an appearance similar to pustular psoriasis), and balanitis circinata, which consists of circular lesions with raised borders, usually found on the glans penis. Only two of the four parts of the clinical syndrome are necessary to make the diagnosis. It has been estimated that 0.8% of patients with N.S.U. develop the complication of Reiter’s syndrome. The levels of a heretofore unknown beta globulin were examined in a group of patients with N.S.U., a group with Reiter’s syndrome, and a group of patients with gonorrhea.*O I t was found that approximately the same percentage of patients with Reiter’s syndrome as N.S.U. patients had elevated levels (while none of the patients with gonorrhea had elevated levels.) This suggests an association between the two, a t least as far as the immunological responses are concerned. However, one study reported that 14/25 patients with N.S.U. were positive for the HL-A27 whereas only 3/41 patients with N.S.U. were positive for the same antigenz1. Obviously the question of whether Reiter’s syndrome i s a separate entity or a complication has not been settled.
I
Summary In summary, nonspecific urethritis is a common disease and the etiology o f all cases i s not known a t this time. It seems quite certain that 40-50% of cases of N.S.U. are caused by Chlamydia trachomatis. The etiology o f the other 50% seems not to be clear. The typical patient presents with a scant mucoid discharge, usually most copious in the morning. The most efficacious treatment regimen seems to be oxytetracycline given for four days or tetracycline given for 21 days, but relapses are common. Complications include prostatitis, urethral stricture, epididymitis, and Reiter’s syndrome. Some evidence seems to suggest that Reiter’s syndrome is not a complication but a separate disease entity. Continued on page 110
89
COLLEGE HEAL T H
positive feelings about self and others and academic standing, while Iswering anxiety levels. It should be noted that athough clients (n = 33) did not see their psychological evaluations as helpful, their perceptions do not account for the extensive professional use of these evaluations in treatment planning. References
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1 . Bloom B: Current issues in the provision of campus community
mental health services./ Amer Coll Health Assoc 18:257-264,1970 2 . Krumboltz JD: An accountability model for counselors. Pers Gu’dj 5 2 : 6 3 9 6 4 6 , 1 9 7 4 3. Warnath CF: College counseling: between the rock and the hard 5 1 : 2 2 9 - 2 3 51~9 7 2 4. Meadows M: Assessment o f college counseling: a follow-up study. / Counsel Psychol, 2 2 : 4 6 3 4 7 0 , 1 9 7 5 5. Frank AC and Kirk BA: Differences in outcomes for users and nonusers of university counseling and psychiatric services; a 5-year accountability study./ Counsel Psychol 3:252-258, 1975
Nonspecific Urethritis (continued) from puge 89
References 1 . Venereal Disease: Extract from the Annual Report o f the Chief Medical Officer o f the Department of Health and Social Security for the Year 1968. Brit/ VenerDis46:76-83,1970 2. Volk J and Krauss SJ: Nongonococcal urethritis. Arch lntern Med 1 3 4 5 11-514,1974 3. Oriel JD, et ul: Genital yeast infections. Br Med / 4:761-769, 1972 4. Holmes K, e t 01: Etiology o f nongonococcal urethritis. New Eng / Med292:1199-1205,1975 5 , Gordon HI, Miller DH, Rawls WE: Viral studies i n patients with nonspecific prostatourethritis. / Urol 108:299, 1972 6. Grimble AS, Amarasuriya KC: Nonspecific urethritis and the tetracyclines. Brit/ Vener Dis 51:198-205, 1975 7 . Scott AJ, Rasbridge MR: Serum immunoglobulin levels In gonococcal and ‘nonspecific urethritis. B r i t / Vener Dls 48:133-136, 1972 8. Bowie WR, Wang SP, Alexander ER, e t ul: Etiology o f nongonococcal urethritis: Evidence for Chlamydia trachomatis and Ureaplasma Urealyticum./ Clin Invest, 59:735-742, 1977 9. McCormack W, Braun P, Lee YH, et 01: The genital mycoplasmas. New Eng J Med 288:78-89., 1973 10. Rees E, Tait IA, Hobson D, et al: Chlamydia in relation to cervical infection and pelvic inflammatory disease, nongonococcal urethrit i s and related infections. Holmes KK, Hobson D (eds), Washington DC, American Society for Microbiology, 1977, pp. 148-152 1 1 . Mardh P, RipaT, Svenson L, Westrom L: Chlamydia trachomatis
170
infection in patients with acute salpingitis. New Eng / Med 296:13771379,1977 12. Schacter J: Chlamydial infections (second of three parts). New Eng J Med 2 9 8 : 4 9 0 4 9 5 , 1 9 7 8 13. Kaufman RE, Wiesner PJ: Nonspecific urethritis. New Eng / Med 291 :1175-1177,1974 14. Jacobs NF, Krauss S J: Gonococcal and nongonococcal urethritis In man. Ann lntern Med 82:7-13,1975 15. Schacter J: Chlamydial infections (first of three parts). New Eng J Med 298:428-435,1978 16. Handsfield H, Lipman T, Harnisch J, Tronca El Holmes K: Asymptomatic gonorrhea in man. 290:117-123, 1974 17. Fowler W: Studies i n nongonococcal urethritis therapy: the long-term value of tetracycline. B r i t / Vener Dis 46:464-468, 1970 18. Blackman HI, Yoneda C, Dawson CR, et ul: Antibiotic susceptability o f Chlamydia trachomatis antimicrobe agents, Chemotherupy 12:673-677,1977 19. Bowie WR, Alexander ER, Floyd JF, etal: Differential response o f Chlamydial and ureaplasma associated urethritis is sulphafurazole (sulfasoxisole) and aminocyclitols, Lancet 2:1276-1278, 1978 20. Csonka GW, Bassett EW, Furness G: Raised levels of an unknown beta globulin in patients with nonspecific urethritis o f Reiter’s disease, Brit/ Vener Dis 50:17-21, 1974 21. Harris JR, Gelstrope K, Doughty RW, Lee D,Martini RS: HLA27 and W-10 in Reiter’s syndrome and nonspecific urethritis, Act0 Derm Vener (Stackh) 55:127-130,1975
/ . A .C.H.A.
Journal of American College Health Association Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzch20
Nonspecific Urethritis: Its Current Status Clyde E. Rapp Jr. M.D.
a
a
Division of Adolescent Medicine , Children's Hospital of Philadelphia , Pennsylvania, 19104, USA Published online: 07 Apr 2011.
To cite this article: Clyde E. Rapp Jr. M.D. (1978) Nonspecific Urethritis: Its Current Status, Journal of American College Health Association, 27:2, 87-110, DOI: 10.1080/01644300.1978.10392832 To link to this article: http://dx.doi.org/10.1080/01644300.1978.10392832
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Nonspecific Urethritis: Its Current Status* CLYDE E. RAPP, jr., M.D.1Drexel University
Downloaded by [York University Libraries] at 07:15 29 December 2014
Abstract The etiology, epidemiology, clinical presentation, diagnosis, and treatment o f nonspecific urethritis (NS. U.) is discussed. Chlamydia seems to be responsible for approximately 40-50% o f cases while the etiology o f the remainder remains obscrue. There seems to be reasonably good evidence for venereal transmission as well as for treatment o f the female partner whether symptomatic or asymptomatic. Tetracyline given for 21 days or oxytetracycline given for four days seem to be the most effective first line treatment regimens at this time. Complications which include prostatitis, epididymitis, urethral stricture, and Reiter ’s Syndrome, are discussed. It appears as though there is a reasonable possibility that ReiterS Syndrome is a separate entity (or immunological sequela) rather than a complication. As i s widely known, nonspecific urethritis (N.S.U.) i s a frequent diagnostic problem among students coming to college health centers. Exact incidence figures are not readily available because of inadequate reporting and confusion as t o diagnostic criteria. A study from Great Britain, where reporting procedures are more thorough, stated the N.S.U. was more prevalent than gonococcal urethritis in the year 1968 as well as during the three receding years.l Another study,l from a public health clinic !venereal disease clinic in DeKalb County, Georgia) noted that 30% of the patients coming to the clinic had nongonococcal urethritis while 31% of the patients had gonococcal urethritis. The clinic where the study was performed i s not completely comparable to a college health center because of a relatively high percentage o f black patients attending the clinic. This would tend to inflate the incidence of gonococcal urethritis, since a higher percentage (73%) of the patients with gonococcal urethritis were black, (in the DeKalb County Study), and a higher percentage (71%) o f the N.S.U. patients were white. Personal observations and communications with others in the college health field would suggest that the prevalence of nonspecific urethritis is higher than gonococcal urethritis. Etiology A number o f attempts have been made to isolate a single organism that can be shown t o be the cause o f all cases o f nonspecific urethritis. Chlamydia trachomatis has been the organism most frequently implicated, but it has never been shown to be responsible for all cases in a given series. Oriel recovered Chlamydia in 36% o f 98 men with first attacks of nonspecific urethritis but from none o f 34 controls without urethritis.3 In a very thorough study, Holmes e t at, isolated Chlamydia trachomatis from 42% (or 481113) o f patients with nonspecific (or nongonococcal) urethritis and from only 7% (or 4/58) o f matched controls and 19% (or 13/69) o f *A synopsis presented at the Fifty-Fifth Annual Meeting, American College Health Association, Philadelphia, Pennsylvania, April 20,1977
t Director o f Health Services,
Drexel University; Division of Adolescent Medicine, Children’s Hospital o f Philadelphia, Pennsylvania 19104 VOL. 27, OCTOBER 1978
patients with gonococcal ~ r e t h r i t i s . In ~ addition, seroconversion was demonstrated in 9 o f 17 culture positive, initially seronegative patients with nonspecific urethritis. Their study did not demonstrate any significant difference between patients with nonspecific urethritis and controls when attempts were made to isolate mycoplasma hominis, T-mycoplasma, H. hominis and cytomegalovirus. Therefore, the etiology o f slightly over half o f their cases remains obscure. An attempt to associate herpes simplex type 1 or herpes simplex type 2 with nonspecific urethritis failed t o demonstrate any significant difference between patients and cont r o l ~ . Grimble ~ and Amarasuriya6 found multiple isolates containing varying combinations o f Chlamydia, T-mycoplasma, M. hominis, Trichomonas vaginitis, and cytomegalovirus, as well as negative cultures, in a number o f cases. They f e l t this data suggested that multiple .organisms may be responsible or that the etiology may be noninfectious in some cases or at least caused by organisms that are not identifiable with present techniques. Scott and Rasbridge7 determined that the pattern and degree o f elevation o f IgG, IgA, and IgM in nonspecific and gonococcal urethritis were similar and that this data supported an infectious etiology for nonspecific urethritis. Ureaplasma urealyticum has also been f e l t to be a possible etiological agent for the 40-50% o f cases o f nonspecific urethritis not due t o Chlamydia trachomatis. Bowie found that ureaplasma type organisms were recovered in 35 o f 43 (81%) o f cases o f Chlamydia negative nonspecific urethritis, while he found ureaplasma in only 11 out o f 26 (42%) o f patients with Chlamydia positive nonspecific urethritk8 Twenty-two out o f thirty-eight (or 58%) o f patients without urethritis carried the organism. The ureaplasmacarrier rate i s known to be high,g so this casts some doubts on the possibility o f the pathogenic role o f the ureaplasmas. In summary then, as far as etiology i s concerned, the data o f Holmes et at4 as well as other studies support the fact that a significant percentage of cases are due to Chlamydia trachomatis. However, the etiology o f approximately 50% o f cases remains obscure. Transmission The mechanism o f transmission and recommendations re87
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garding examination and treatment o f consorts are perhaps the hardest questions to answer since l i t t l e work has been done in this area. Grimble and Amarasuriya examined female sexual consorts o f index cases where there was only one consort and determined the following: 28% had nonspecific vaginitis, 11% had Trichomonal infection with or without Candida, 14.5% had vaginitis plus Candida, 29% had Candida present with or without vaginitis and 33.5% had normal flora.6 They suggested a possible etiological relationship between these conditions or that N.S.U. may be secondary to T. vaginitis and Candida, but the study does not compare the organisms isolated in the female consort with those isolated in the male. Nevertheless, the high incidence o f these conditions in female consorts lends support to the practice o f requesting that the sexual consorts o f cases with nonspecific urethritis come in to be evaluated and examined. Holmes et a14 determined that the prevalence o f microimmunofluorescent antibodies against C. trachomatis in culture negative controls and patients with gonococcal urethritis correlated directly with the number o f sexual partners during the preceding six months, strongly supporting venereal transmission and the importance of multiple sexual partners in the spread o f the disease (at least o f the cases secondary to Chlamydia trachomatis). He also found that Chlamydia trachomatis was recovered from the endocervix o f the female sexual partners o f 15 o f 22 patients with N.S.U. secondary to Chalamydia trachomatis and from only 2/24 o f the female consorts o f patients with N.S.U. not secondary to Chlamydia. Rees performed pelvic examinations on 245 female contact o f men with nonspecific urethritis.1° Eighty-seven percent o f those with hypertrophic cervical erosions were Chlamydia positive and 84% o f those with mucopurulent cervical contents were Chlamydria positive. This data would seem to lead strong support to venereal transmission o f cases of nonspecific urethritis secondary to Chlamydia (with obvious implications for treatment o f the female sex partner), but does not speak t o the question o f venereal transmission of cases not secondary to Chlamydia trachomatis. O f related interest were the findings of Mardh e t a/ concerning the role o f Chlamydia in the etiology o f acute salpingitis, again suggesting a female reservoir for those cases of N.S.U. secondary to Chlamydia.” Mardh and his colleagues cultured Chlamydia from 19/53 cervical specimens o f patients with laparoscopically verified acute salpingitis. In six o f seven cases where the cervical culture was positive and where tuba1 material was also cultured, Chlamydia was isolated from the fallopian tubes. The apparent increasing importance o f Chlamydia in the etiology o f salpingitis indicates that there is a good reason to request examination and evaluation o f female consorts o f male index cases, and certainly has certain implications for prophylactic treatment o f sexual consorts (see “Treatment” section.) No mention is made by Mardh and his colleagues concerning the precise symptomatology o f the female patients who were studied. I t should be emphasized that salpingitis is frequently accompanied by very vague symptoms and that the patient with salpingitis does not necessarily spontaneously seek medical attention. This adds t o the importance o f making vigorous efforts to bring contacts in to be examined. In addition, Holmes et a/, as noted earlier, successfully cultured Chlamydia from the cervix o f sexual consorts of index patient^.^ He made no mention o f symptomatology, so that it i s reasonable to assume that they may have been asymptomatic. This coincides with the observation o f others that Chlamydia are capable o f causing clinically unapparent disease.1° In addition, it has also been demonstrated by means o f screening studies that Chlamydia can be recovered from clinically normal cervices.12 A tenable conclusion then, would seem t o be that sexual partners o f 88
patients with nonspecific urethritis should be brought in to be examined, whether symptomatic or not. In conclusion, it would seem that the epidemiology o f nonspecific urethritis has not been thoroughly worked out. The only reasonable solid evidence for venereal transmission seems to be from those cases secondary to Chlamydia. Because we are usually unable t o determine which cases are secondary to Chlamydia and which are not, it i s therefore advisable to bring all sexual consorts of patients with nonspecific urethritis to be examined and treated, even if asymptomatic. History and Symptomatology The male patient with nonspecific urethritis typically presents with a history o f whitish, mucoid discharge and/or burning.13 The usual interval from the time o f last sexual intercourse is at least two weeks, allowing one t o help differentiate N.S.U. from gonococcal urethritis, which usually has an incubation period o f several days to a week. In an excellent review, jacobs e t a / found that dysuria plus discharge occurred in 71% o f their patients with gonococcal urethritis and 38% o f the patients with nonspecific ~ r e t h r i t i s . ’ ~Dysuria alone occurred in only 2% o f cases o f gonococcal urethritis and 15% o f those with N.S.U. Discharge alone occurred in 27% o f patients with gonococcal urethritis and 47% o f patients with N.S.U. Spontaneous and purulent discharge occurred only in patients with gonococcal urethritis and lack of discharge or minimal mucoid discharge was found exclusively in nongonococcal urethritis. Therefore, if one were to define the typical presentation o f nongonococcal urethritis, one would expect to see a patient with minimal mucoid discharge (personal note: this frequently occurs only in the morning in patients with N.S.U.) with a slight possibility of dysuria. The typical patient with gonococcal urethritis would present with purulent discharge (frequently spontaneous) and dysuria. It has been shown that a number o f patients with gonococcal urethritis also are carriers o f Chlamydia trachomatis, and there i s solid evidence that post gonococcal urethritis i s secondary to Chlamydia trachomatis approximately 70% o f the time.15 Therefore, since neither ampicillin, penicillin, or spectinomycin will eradicate Chlamydia, one may often see post gonococcal urethritis secondary to Chlamydia after a patient has been successfully treated for gonococcal urethritis. Thus, a patient may present with a history of a purulent discharge typical o f gonorrhea at one time and one to two weeks later may come in with symptoms typical o f nonspecific urethritis. There i s evidence to suggest that 65% o f those patients who develop post gonococcal urethritis secondary t o Chlamydia are infected with both organisms simultaneousIy.15 Physicians who see nonspecific urethritis frequently have observed that patients may prolong the discharge that began as a symptom o f nonspecific urethritis follows the initial nonspecific urethritis. I have personally observed a traumatic urethritis secondary to “mil king” following prostatitis. This i s particularly likely to occur in a compulsive individual who focuses a great deal o f anxiety on the discharge. Diagnosis If an exudate o f any kind is present, i t should be examined by means o f gram stains. (“Milking” or “stripping” the urethra may be necessary). It i s also important to culture the exudate in oll cases. As noted previously, occasionally a patient with gonorrhea may present with mucoid discharge, and in approximately 2% o f patients with gonococcal urethritis, the culture may be positive while the smear is negative.14 If no intracellular (or extracellular) diplococci are present on the gram strain
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URETHRITIS
and only polymorphonuclear leukocytes are identified, then a tentative diagnosis of nonspecific urethritis can be made. The examining physician should be particulary interested in obtaining a reliable culture for gonorrhea in those individuals who have been treated unsuccessfully with one of the regimens (e.g. tetracycline or erythomycin) for nonspecific urethritis. Since these regimens are suboptimal for the treatment of gonorrhea, the patient may actually have gonorrhea which has never been treated properly. In some cases the symptoms may be somewhat attenuated and a positive culture may be easier to obtain if the patient i s off of all antibiotics for two days. It has been stated many times that the gonococcus i s a fastidious organism and the culture must be obtained properly. The most important factor in increasing the yield of positive cultures i s to plate the specimen immediately after obtaining it. The use of plastic “crush tubes” with built-in media has not been as satisfactory a method as immediately plating the material to be cultured on appropriate media directly after obtaining it. Needless to say, the dish should be placed in an incubator with a CO;! atmosphere as soon as possible. One should keep in mind that asymptomatic gonorrhea in men i s a more common, phenomenon than was previously thought to be true,16 so that where the index of suspicion of gonorrhea i s high (based on the type of clinic, and racial and socioeconomic factors). an individual who is symptomatically recovered from nonspecific urethritis should have a culture for gonorrhea. This will uncover those individuals who have received suboptimal treatment for undiagnosed gonorrhea and, therefore, noted a decrease in the amount of discharge. This i s accomplished by inserting a calcium algonate swab 1.O cm into the anterior urethra and then plating the material to be cultured, on appropriate culture media. In all cases of treatment failure, a specimen of discharge should be obtained and immersed in saline. Part of the saline should be examined for trichomonads by the hanging drop method and a second portion combined with a drop o f 10% potassium hydroxide solution and examined for the spores and mycelia of Candida after heat fixation. I t is also recommended that a culture for gonorrhea be done in these cases. Treatment Various regimens have been attempted in the treatment of nonspecific urethritis. The most popular seems to be 500 mgm of tetracycline every six hours for a total of seven days.13 An 80% cure rate has been achieved with this regimen by one group of authors,16 and definite superiority of this regimen over placebo therapy has been demonstrated. Other authors feel that a twenty-one day course of tetrac cline a t 250 mgm four times a day i s the regimen of choice1 . They stress that it i s particularly important to carry out treatment for this long a period of time in women, since it apparently takes longer to eradicate the organism in females. It i s clear from two studies6~17that placebo therapy does result in cure of a reasonable percentage of cases (34% and 20%). One of the aforementioned studies17 evaluated a regimen of 250 mgm of tetracycline four times a day for seven days compared with 500 mgm of tetracycline four times a day for seven days. Fifty-eight percent of the low dose group (with 20% being unresponsive and 22% defaulting) responded to treatment within two weeks. Sixty-one percent of the larger dose group responded in two weeks (with 22% being unresponsive and 17% defaulting). Oxytetracycline was evaluated in the same study and was found to be superior to tetracycline with 68% responsive within two weeks on 250 mgm four times a day for four days and 73% responding to 250 mgm four times a day for 10 days. There were no unresponsive patients although
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VOL. 27, OCTOBER 1978
32% defaulted from the four-day regimen and 27% defaulted from the 10-day regimen.) It appears that either a 21-day course of tetracycline (at 250 mgm/da ) or a four-day course of oxytetracycline (at 250 mgm/dayr constitutes adequate first line treatment of nonspecific urethritis. The tetracycline has the advantage of being cheaper and the oxytetracycline has the advantage of being given over a shorter period of time. In cases of treatment failure with tetracycline, it would certainly seem wise to attempt to use oxytetracycline (being sure to rule out reinfectiongonorrhea, or urethritis secondary to candida or trichomonas). If oxytetracycline is used as first line treatment, erythromycin (250 mgm four times a day for 21 days l8 or sulfisoxazole (500 mgm four times a day for 10 days l9 may be tried if oxytetracycline is not effective or as alternate regimens if allergies exist.
1
Complications
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Complications of N.S.U., with the exception of prostatitis, are extremely rare as well as difficult to document accurately because of vague diagnostic criteria. Prostatitis, which is usually asymptomatic and painless, i s thought to occur in 20% of cases; epididymitis, which i s usually unilateral in the disease, occurs in under 3% of patients, and urethral stricture occurs in 0.5 to 5%.9 The reliability of this last statistic is subject to doubt, because of the possibility of gonorrhea prior to the nonspecific urethritis which may have produced the stricture and thereby predisposing the patient to nonspecific urethritis. Reiter’s syndrome consists of conjunctivitis, urethritis, polyarticular arthritis and mucocutaneous lesions. These usually consist of superficial ulcerations on the palate or buccal mucosa, kerataderma blenorrhagica on the palms and soles (which has an appearance similar to pustular psoriasis), and balanitis circinata, which consists of circular lesions with raised borders, usually found on the glans penis. Only two of the four parts of the clinical syndrome are necessary to make the diagnosis. It has been estimated that 0.8% of patients with N.S.U. develop the complication of Reiter’s syndrome. The levels of a heretofore unknown beta globulin were examined in a group of patients with N.S.U., a group with Reiter’s syndrome, and a group of patients with gonorrhea.*O I t was found that approximately the same percentage of patients with Reiter’s syndrome as N.S.U. patients had elevated levels (while none of the patients with gonorrhea had elevated levels.) This suggests an association between the two, a t least as far as the immunological responses are concerned. However, one study reported that 14/25 patients with N.S.U. were positive for the HL-A27 whereas only 3/41 patients with N.S.U. were positive for the same antigenz1. Obviously the question of whether Reiter’s syndrome i s a separate entity or a complication has not been settled.
I
Summary In summary, nonspecific urethritis is a common disease and the etiology o f all cases i s not known a t this time. It seems quite certain that 40-50% of cases of N.S.U. are caused by Chlamydia trachomatis. The etiology o f the other 50% seems not to be clear. The typical patient presents with a scant mucoid discharge, usually most copious in the morning. The most efficacious treatment regimen seems to be oxytetracycline given for four days or tetracycline given for 21 days, but relapses are common. Complications include prostatitis, urethral stricture, epididymitis, and Reiter’s syndrome. Some evidence seems to suggest that Reiter’s syndrome is not a complication but a separate disease entity. Continued on page 110
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COLLEGE HEAL T H
positive feelings about self and others and academic standing, while Iswering anxiety levels. It should be noted that athough clients (n = 33) did not see their psychological evaluations as helpful, their perceptions do not account for the extensive professional use of these evaluations in treatment planning. References
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1 . Bloom B: Current issues in the provision of campus community
mental health services./ Amer Coll Health Assoc 18:257-264,1970 2 . Krumboltz JD: An accountability model for counselors. Pers Gu’dj 5 2 : 6 3 9 6 4 6 , 1 9 7 4 3. Warnath CF: College counseling: between the rock and the hard 5 1 : 2 2 9 - 2 3 51~9 7 2 4. Meadows M: Assessment o f college counseling: a follow-up study. / Counsel Psychol, 2 2 : 4 6 3 4 7 0 , 1 9 7 5 5. Frank AC and Kirk BA: Differences in outcomes for users and nonusers of university counseling and psychiatric services; a 5-year accountability study./ Counsel Psychol 3:252-258, 1975
Nonspecific Urethritis (continued) from puge 89
References 1 . Venereal Disease: Extract from the Annual Report o f the Chief Medical Officer o f the Department of Health and Social Security for the Year 1968. Brit/ VenerDis46:76-83,1970 2. Volk J and Krauss SJ: Nongonococcal urethritis. Arch lntern Med 1 3 4 5 11-514,1974 3. Oriel JD, et ul: Genital yeast infections. Br Med / 4:761-769, 1972 4. Holmes K, e t 01: Etiology o f nongonococcal urethritis. New Eng / Med292:1199-1205,1975 5 , Gordon HI, Miller DH, Rawls WE: Viral studies i n patients with nonspecific prostatourethritis. / Urol 108:299, 1972 6. Grimble AS, Amarasuriya KC: Nonspecific urethritis and the tetracyclines. Brit/ Vener Dis 51:198-205, 1975 7 . Scott AJ, Rasbridge MR: Serum immunoglobulin levels In gonococcal and ‘nonspecific urethritis. B r i t / Vener Dls 48:133-136, 1972 8. Bowie WR, Wang SP, Alexander ER, e t ul: Etiology o f nongonococcal urethritis: Evidence for Chlamydia trachomatis and Ureaplasma Urealyticum./ Clin Invest, 59:735-742, 1977 9. McCormack W, Braun P, Lee YH, et 01: The genital mycoplasmas. New Eng J Med 288:78-89., 1973 10. Rees E, Tait IA, Hobson D, et al: Chlamydia in relation to cervical infection and pelvic inflammatory disease, nongonococcal urethrit i s and related infections. Holmes KK, Hobson D (eds), Washington DC, American Society for Microbiology, 1977, pp. 148-152 1 1 . Mardh P, RipaT, Svenson L, Westrom L: Chlamydia trachomatis
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infection in patients with acute salpingitis. New Eng / Med 296:13771379,1977 12. Schacter J: Chlamydial infections (second of three parts). New Eng J Med 2 9 8 : 4 9 0 4 9 5 , 1 9 7 8 13. Kaufman RE, Wiesner PJ: Nonspecific urethritis. New Eng / Med 291 :1175-1177,1974 14. Jacobs NF, Krauss S J: Gonococcal and nongonococcal urethritis In man. Ann lntern Med 82:7-13,1975 15. Schacter J: Chlamydial infections (first of three parts). New Eng J Med 298:428-435,1978 16. Handsfield H, Lipman T, Harnisch J, Tronca El Holmes K: Asymptomatic gonorrhea in man. 290:117-123, 1974 17. Fowler W: Studies i n nongonococcal urethritis therapy: the long-term value of tetracycline. B r i t / Vener Dis 46:464-468, 1970 18. Blackman HI, Yoneda C, Dawson CR, et ul: Antibiotic susceptability o f Chlamydia trachomatis antimicrobe agents, Chemotherupy 12:673-677,1977 19. Bowie WR, Alexander ER, Floyd JF, etal: Differential response o f Chlamydial and ureaplasma associated urethritis is sulphafurazole (sulfasoxisole) and aminocyclitols, Lancet 2:1276-1278, 1978 20. Csonka GW, Bassett EW, Furness G: Raised levels of an unknown beta globulin in patients with nonspecific urethritis o f Reiter’s disease, Brit/ Vener Dis 50:17-21, 1974 21. Harris JR, Gelstrope K, Doughty RW, Lee D,Martini RS: HLA27 and W-10 in Reiter’s syndrome and nonspecific urethritis, Act0 Derm Vener (Stackh) 55:127-130,1975
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