Dysuria in adolescents

Dysuria is a frequent and often frustrating complaint of young women. Although it is tempting to equate dysuria with a urinary tract infection, special care must be taken in adolescents to rule out a sexually transmitted infection. Even with a careful history, the difficulty differentiating between a urinary tract infection and a sexually transmitted infection often forces physicians to subject patients to invasive exams and laboratory studies. Many young women receive their first pelvic exam when they experience dysuria; it costs the physician time and causes discomfort to the patient. A review of the literature yields more confusion than clarity regarding the reliability of pelvic exams, urine dipstick tests, and microscopic analysis. However, a few conclusions may be drawn from experience with these tests, and newer tests may make the treatment of adolescent girls with dysuria less daunting and more time and cost effective.

Summary points

• Dysuria in adolescent girls can be a symptom either of a urinary tract infection or a sexually transmitted infection

• The incidence of sexually transmitted infections is higher in sexually active adolescent women than in women in other age groups

• The consequences of pelvic inflammatory disease, a complication of untreated cervicitis, include chronic pain, infertility, and an increased risk of ectopic pregnancy

• A pelvic exam may be necessary if pelvic inflammatory disease is suspected but in certain situations a bimanual exam may be sufficient

• The discriminating use of laboratory tests may help physicians avoid invasive exams

• Treatment should be started while awaiting the results of confirmatory tests

METHODS

The references chosen for this article were obtained by searching MEDLINE and MDConsult, as well as being discovered in the course of general reading. Additional information was provided by lectures given by specialists at UCLA in the adolescent medicine and emergency medicine and infectious disease departments.

WHAT PLACES ADOLESCENTS AT RISK OF SEXUALLY TRANSMITTED INFECTIONS?

Fifty-three percent of high school students have had at least one sexual encounter,¹ and 20.8% of 12th grade girls have had more than four sexual partners.² In 1995, just under half of all girls in high school had used condoms,² and the number decreased as girls progressed from 9th to 12th grade.^1,3 The risk factors associated with sexually transmitted infections such as choosing a partner whose health history is not determined, using drugs or alcohol with sexual activity, being young at the time of first consensual sexual encounter, having been incarcerated, having had a new partner within the preceding 2 months, and having a history of a similar infection are often difficult to elicit from an adolescent patient. Even when risky behaviors are controlled for, the incidence of chlamydia is twice as high among women aged 15-19 as among other age groups.² This is probably because susceptible columnar epithelium is present on the exocervix of adolescents; this changes to squamous epithelium as women reach their 20s. The prevalence of chlamydia among teenage women is 13%-26% and the prevalence of gonorrhea is 2%-10%. There is a 10%-40% chance that a teen will contract chlamydia again in the months after the initial diagnosis is made.^2,4

WHAT ARE THE GOALS OF TREATMENT?

The appropriate treatment of a symptomatic infection, whether sexually transmitted or a urinary tract infection, should relieve a woman's discomfort and prevent undesirable complications. Treating a condition that has been transmitted to her by a partner and helping her to contact the partner may prevent future cases of sexually transmitted infection. Most importantly, 10%-40% of untreated gonorrheal or chlamydial infections will progress to pelvic inflammatory disease, a term describing the constellation of endometritis, tubo-ovarian abscess, salpingo-oophoritis, and pelvic peritonitis. Pelvic inflammatory disease is diagnosed in 1 million women annually.⁵ Of these cases, 20% to 30% occur in adolescent girls, and one study found that sexually active adolescent girls have a 1 in 8 chance of contracting pelvic inflammatory disease in comparison with the 1 in 80 chance of contracting the disease that is found among sexually active women in other age groups.³ The morbidity associated with one case of pelvic inflammatory disease is great: there is a 12% risk of infertility, an 18% chance of chronic pelvic pain,⁶ and a sevenfold increase in the risk of ectopic pregnancy. The risk of infertility increases to 25% after two episodes and to >50% after three.⁷ The annual cost of treating these complications is $4 billion to $5 billion.⁸ Preventing the complications of pelvic inflammatory disease requires that sexually transmitted infections be diagnosed early.

ARE THERE SYMPTOMS THAT RELIABLY DIFFERENTIATE BETWEEN SEXUALLY TRANSMITTED INFECTIONS AND URINARY TRACT INFECTIONS?

The cliché that foul vaginal discharge can be treated with a shot of penicillin is an archaic view of sexually transmitted infections. Unfortunately, asymptomatic carriage of a sexually transmitted infection is so prevalent that many experts now recommend that all teens be routinely screened for these infections.⁹ However, studies have been unsuccessful in identifying reliable indicators in women who have symptoms. Sexually transmitted infections can cause dysuria, with or without frequency, either from external lesions or by causing inflammation of the urethra, which is known as acute urethral syndrome.⁷ Two emergency departments retrospectively reviewed presenting symptoms in women of all ages who later tested positive for chlamydia. At Wayne State University in Indiana, of 181 young women who tested positive for chlamydia, 61% complained of abdominal pain, 35% of vaginal discharge, 30% of vaginal bleeding, and 4% of dysuria.¹⁰ Of 233 women who tested positive for chlamydia at Albany Medical College in New York, 18% had “urinary tract infection symptoms” but only 13% had vaginal discharge.¹¹ Many of these women did not initially receive appropriate antibiotic treatment.

Gonorrhea can cause symptoms that are similar to those of chlamydia or can present as proctitis (10%-30% of cases), an abscess of Bartholin's gland with pain and swelling over the labia minora, or as an abscess of Skene's gland with periurethral pain.² Roughly about 25% of adolescent girls with dysuria who are considered to be at high risk of contracting a sexually transmitted infection will have one; at one clinic 60% of women with dysuria had vaginitis.¹² In cases of acute urethral syndrome occurring secondary to candidal or trichomonal vaginitis, dysuria is associated with a vaginal discharge but many women with urinary tract infections also complain of vaginal discharge.^9,12 At least one study found there was no significant difference between symptoms in women who were later proved to have urinary tract infections and in those with sexually transmitted infections; in many cases symptoms included a low-grade fever.¹³ The only historical factors reliably shown to be preferentially associated with urinary tract infection are a history of urinary tract infection, urgency, and gross hematuria.¹² Therefore, history alone can neither lead the physician to a definitive diagnosis nor obviate the need for a pelvic exam.

OF WHAT BENEFIT IS THE EXAMINATION?

This question is composed of two parts: which physical findings help point to a specific diagnosis and, with the advent of sensitive urine tests for gonorrhea and chlamydia, is an external exam and quick swab of the vaginal vault adequate for diagnosis in most cases?

Regardless of whether a speculum exam is performed, an external exam of the genitalia is invaluable. About 10%-12% of those younger than age 20 have genital manifestations of infection with the herpes simplex virus,¹ and 10% of women with this infection will complain of dysuria.¹² Often women deny having urinary frequency and complain of external pain. Patients with herpes might also complain of fever, malaise, headache, and myalgia, especially during their first infection. Viral culture of vesicle fluid has a high sensitivity for diagnosing herpes infection but it takes about 24 hours.¹⁴ A more efficient alternative is to do a Tzanck test of the vesicle base; this yields an immediate result.

The other painful external lesion seen in America is chancroid; it can produce dysuria, vaginal discharge, and dyspareunia. Chancroid is much less common than herpes, occurs predominantly in men, and tends to occur in epidemics. On exam, a red, tender papule or a painful ulcer with ragged edges and foul smelling gray-yellow exudate will be apparent, and a Gram or Giemsa stain or culture of the lesion will confirm the diagnosis.¹⁵

Findings that support the diagnosis of chlamydia during a pelvic exam are vaginal discharge (seen in 66% of women with chlamydia), cervical motion tenderness (31%), vaginal bleeding (19%), and abdominal or adnexal tenderness (16%). These findings lack specificity.¹⁰ Cervical motion tenderness, for example, is a sign of peritoneal irritation and can be found in women with an ectopic pregnancy, appendicitis, and other abdominal conditions. Mucopus has a sensitivity of 11% and a specificity of 95% for diagnosing chlamydia. Friability of the cervix is also a sign of cervicitis having a sensitivity of 13% and a specificity of 94%.¹⁶

Clinics fortunate enough to have urinary tests (ligase chain reaction, for example) available for diagnosing chlamydia and gonorrhea may need to decide if these tests, coupled with a swab of the vaginal vault, are adequate to allow the physician to forgo the speculum exam. A study done at Johns Hopkins University compared the results of a full speculum exam to those of a blind vaginal swab in 686 women aged 12-22.¹⁶ There was no significant difference in the accuracy of the diagnosis of vaginitis between collection methods. Other studies have shown ligase chain reaction, a gene amplification technique, to have a sensitivity of 95%-96% and a specificity of 100% for gonorrhea, and a sensitivity of 88%-96% and a specificity of 100% for chlamydia. Ligase chain reaction performed on urine is approved only as a screening tool for gonorrhea, but it has been used successfully for both gonorrhea and chlamydia in adolescents.^16,17,18

The most pressing reason for a practitioner to perform at least a bimanual exam is to rule out the possibility of pelvic inflammatory disease, which is classically diagnosed by the triad of low abdominal pain, cervical motion tenderness, and adnexal tenderness. Unfortunately, if compared with the gold standard of laparoscopy, the clinical accuracy of these findings reaches only 65%.^3,19 Other indications that can help confirm the diagnosis are that symptoms occur early in the menstrual cycle, douching is performed regularly, and that there is nausea, dysuria, fever, irregular bleeding, dyspareunia, and vaginal discharge. Concentrations of C reactive protein are raised in up to 96% of cases, and their fall to normal limits indicates that treatment has been adequate.²⁰ If the patient has an erythrocyte sedimentation rate >15 mm/hour, temperature >38°C, and an adnexal mass in addition to the standard diagnostic criteria, sensitivity increases to 98%.¹⁹ Magnetic resonance imaging and ultrasound scanning look promising in studies of nonsurgical diagnoses.^6,21

Adolescents with pelvic inflammatory disease can be treated as outpatients if they are reliable, stable, and not infected with HIV, if they will take oral medication, and if a follow-up appointment is arranged for 72 hours later (box). Physicians should, however, maintain a low threshold for admitting women who do not meet these criteria or who have a tubo-ovarian abscess.²² If pelvic inflammatory disease is diagnosed, a cervical culture should be done to ensure that the pathogen is gonorrheal or chlamydial, since other agents may be involved including mycoplasmas, herpes simplex virus, anaerobic bacteria, Escherichia coli, streptococcus species, bacteriodes species, peptostreptococcus, and even actinomyces species in patients who use intrauterine devices.²³

WHICH LABORATORY TESTS HELP?

Initial decisions about treatment need to be made in the context of a quick visit to an office or emergency department, and laboratory tests that can be done quickly are the most useful guides. Results of urine dipstick analyses are sometimes useful. Leukocyte esterase is produced by white blood cells and is a marker of their presence in urine. The presence of this enzyme indicates that there are bacteria in the urine, and this finding is 90%-95% sensitive if the urine contains >100,000 bacteria; it is 70% sensitive for <100,000 bacteria. Unfortunately, both acute urethral syndrome and urinary tract infections can yield positive leukocyte esterase tests, and many substances, including cephalexin and tetracycline, can cause false negatives. The presence of nitrites points toward a probable urinary tract infection but the lack of nitrites cannot rule one out; Staphylococcus saprophyticus, a non-nitrate reducing bacteria, is a common cause of urinary tract infections in adolescents.¹³ Negative tests for nitrites and leukocyte esterase have a negative predictive value of 97.5% for ruling out urinary tract infections but they do not rule out acute urethral syndrome.²⁹ Hematuria, either gross or microscopic, is uncommon in acute urethral syndrome but is common in urinary tract infections, particularly those caused by S saprophyticus.^30,31,32

Pyuria may be identified by microscopic exam in both urinary tract infections and acute urethral syndrome. It is defined by different sources as >5 to >10 white blood cells per high power field. Using the cut off of ≥8 white blood cells per high power field the sensitivity for diagnosing a urinary tract infection is 91% and the specificity is 50%.³² About 50% of urinary tract infections occurring in the lower tract and 90%-95% of those occurring in the upper tract will have Gram stains with >100,000 bacteria/mL.³¹ Identification of a single typical organism has a sensitivity and specificity of >90% for diagnosing a urinary tract infection.²⁴ Unfortunately, patients with acute urethral syndrome may have any number of white blood cells or bacteria present on microscopic exam, although the syndrome is generally associated with a lower white blood cell count and a lower bacterial count than urinary tract infections. In patients with gonorrheal urethritis, the appearance of intracellular gram-negative diplococci on urine microscopy is pathognomonic but is seen in only 50% of women with the disease.¹²

It is not necessary to culture a sample to treat uncomplicated, nonrecurrent cystitis in healthy people provided patients know that they should return in 48 hours if there is no improvement. Urine cultures are required, however, in uncomplicated pyelonephritis occurring in healthy people, although blood cultures are not.²⁵ However, a much higher percentage of urinary tract infections in adolescents may be caused by infection with Staphylococcus saprophyticus than in the general population. Therefore, if an antibiotic that is not effective against gram-positive bacteria is used, a culture may be necessary. The more common reason for doing a culture is to ensure that, if tests for gonorrhea and chlamydia have not been done, the symptoms attributed to a urinary tract infection are not actually related to a sexually transmitted infection.

If vaginitis is suspected, a swab from the vaginal vault should be obtained and slides made for a wet mount. More sensitive methods of detecting trichomonas species include culture and polymerase chain reaction.³³ If taken from the cervix, a cell culture is 100% specific for chlamydia but only 65%-80% sensitive, and it requires 3-5 days to produce results.² Direct immunofluorescence and enzyme immunoassay are sensitive tests for gonorrhea and chlamydia; enzyme immunoassay is technically easier and requires only 4-5 hours to perform. Ligase chain reaction is a sensitive test that can be performed either on a cervical swab or a urine sample. For gonorrhea, an additional helpful test is a Gram stain of the cervical mucus, which will test positive for polymorphonuclear neutrophils with intracellular diplococci in 2 of 3 patients with symptoms.¹⁹

CONCLUSIONS

In an adolescent girl who is at high risk of contracting a sexually transmitted infection and who has dysuria and frequency, it is difficult to rule out a sexually transmitted infection using only results from simple, noninvasive tests. If an external exam rules out lesions such as genital herpes and chancroid, and the results of a potassium hydroxide slide and wet mount are negative and have made the diagnosis of vaginitis unlikely, the question of how extensive a work up is needed remains to be answered. In a woman at a low risk of contracting a sexually transmitted infection treatment of cystitis may be appropriate, if her symptoms include urgency, hematuria, suprapubic pain, a dipstick test that is positive for nitrites, and a finding of >100,000 bacteria/mL on an unspun urine sample. If the diagnosis is less clear, a urine culture and an exam for gonorrhea and chlamydia may be necessary.

As urine ligase chain reaction testing becomes more widely available for the diagnosis of chlamydia and gonorrhea, it will be reasonable to limit the number of full pelvic exams performed. It may be possible to treat a woman for cystitis while awaiting the results of the ligase chain reaction if she is at low risk and has dysuria with or without discharge, no abdominal pain, and the results of the external exam and vaginal wet mount are normal. As long as follow up of these results is ensured and careful discharge instructions are given, many women presenting to clinics and emergency rooms can avoid a speculum exam. If necessary, a bimanual exam to exclude pelvic inflammatory disease may be done instead of a full speculum and bimanual exam since it is more comfortable for the patient, faster for the physician, and does not require a speculum, exam lights, and a gynecological bed.

Pregnant teens with pain or vaginal bleeding generally have both a speculum exam and a bimanual exam, as well as assessment for cervicitis and a urinary tract infection. Localization of pain, estimation of uterine size, and visualization of the os to see if it is open all help in evaluating the risk of an ectopic pregnancy and in managing a possible spontaneous abortion.^34,35 Many texts teach that any woman with low abdominal pain should have a bimanual exam to differentiate between abdominal and pelvic pathology, although no study has directly evaluated the accuracy of this advice.^36,37 Since pelvic inflammatory disease, a ruptured ectopic pregnancy, and many other gynecological disorders can present as generalized abdominal pain, consideration should be given to performing a bimanual exam on teens who are at moderate to high risk of these conditions and who have these symptoms.³⁸

Table 1.

Outpatient treatment of urinary tract infections²⁴,²⁵,²⁶,²⁷,²⁸,³⁶

Diagnosis	First line treatment*	Second line treatment	Percentage of cases resistant to these drugs at UCLA's student health services†
Uncomplicated cystitis	3 days of trimethoprim-sulfamethoxazole double strength twice a day; or 3 days of ciprofloxacin 250 mg two times a day, ofloxicin 200 mg two times a day, or another fluoroquinolone‡	Cephalexin 500 mg orally four times a day for 7-10 days	Trimethoprim-sulfamethoxazole 15%; ciprofloxacin 0%; ampicillin 39%; cephalexin 15% (E coli in 81% of isolates)
Uncomplicated pyelonephritis	Doses as above but increase treatment duration to 14 days for trimethoprimsulfamethoxazole and 7 days for ciprofloxacin (slightly more effective than trimethoprim-sulfamethoxazole)	Doses as above but increase treatment duration to 14 days	As above

^*Single-dose treatment no longer recommended

^†Quinolones are recommended for first line treatment if resistance to trimethoprim-sulfamethoxazole is >10%. They have better bacteriologic resolution and fewer side effects but are more costly. Most studies identify resistance to ciprofloxacin in 5% to 10% of samples

^‡Not recommended for treating patients ≤17 years. Ciprofloxacin and ofloxacin may be effective against Staphylococcus saprophyticus.