Epidemiology

The cause of urethritis varies with the age of the patient, sexual practices, and hygienic standards. Chlamydia infections and gonorrhea are common occurrences in adolescents; fecal contamination or irritation caused by physical or chemical substances is a more usual occurrence in preschool-aged children. Transmission during sexual activity is the usual means of spread of Neisseria gonorrhoeae and Chlamydia trachomatis in teenagers and in sexually abused patients; nonvenereal transmission has been described in prepubertal children. Manifestations after nonvenereal spread has occurred may include urethritis, vaginitis, balanitis, conjunctivitis, and complications of disseminated infection (arthritis, meningitis).

The home and social environments of prepubertal children must be examined to identify fully the pattern of spread and infection in the patient and contacts because complex psychosocial diagnoses and therapies often are involved. Children with gonorrhea and chlamydial infections are concentrated in large urban centers, usually in poor socioeconomic environments.

Although nonvenereal transmission of N. gonorrhoeae is well established, gonococcal infections in children 2 to 10 years of age should be considered evidence of probable sexual abuse. Household contacts have been found to have positive cultures in 27% to 63% of such cases. Prepubertal girls infected with N. gonorrhoeae as a result of sexual abuse outnumber boys by a ratio of at least 3 : 1 and in one report 8 : 1.

Pathophysiology

Infection caused by N. gonorrhoeae usually is localized to the urethra in boys and to the vagina in girls; however, rectal and pharyngeal carriage sometimes occurs in the absence of urethral colonization. Gonococcal virulence factors include pili, the ability to attach to urethral epithelial cells, and production of extracellular proteases that cleave IgA. Initial attachment of gonococci to the surface of columnar epithelial cells is mediated by pili, which are filamentous outer membrane appendages composed of multiple subunits, the most important of which is pilin. Local invasion involves multiple adhesins interacting with host receptors at the mucosal cell level. After attachment occurs, gonococci become internalized in a process known as membrane ruffling. The organisms are able to undergo intracellular replication within phagocytic vacuoles and columnar epithelial cells, which is a successful adaptive response promoting survival.

Chlamydia infections are the most frequent cause of sexually transmitted infection in the United States. Chlamydiae are structurally complex organisms that are obligate intracellular parasites and contain DNA and RNA. Attachment, which is not understood completely, is the first step in the infectious process of the susceptible host cell. It is followed by phagocytosis and then the failure of cellular lysosomes to fuse with the phagosome containing the elementary body, which may be mediated partly by macromolecules in the chlamydial cell envelope. After these two crucial events occur, the elementary bodies undergo biologic changes, and, after approximately 72 hours, they are released from the host cell as new infective elementary bodies ( Fig. 38.1 ).

Schematic description of the growth cycle of Chlamydia trachomatis .

(From Batteiger BE, Jones RB. Chlamydial infections. Infect Dis Clin North Am. 1987;1:55–81.)

Urethritis in younger children also may be caused by the introduction of fecal bacteria or pinworms into the urethra during the early years of toilet training, particularly in girls. Inflammation may be related to bubble baths and other chemical and physical irritants. The entity of idiopathic urethritis is also observed in young boys and girls as a cause of dysuria and hematuria. Edema of the mucosa and the presence of inflammation and red blood cells are common histopathologic features of urethritis that lead to dysuria, hematuria, and microscopic pyuria.

Clinical Presentation

Gonococcal urethritis is characterized by a 2- to 7-day incubation period after sexual intercourse. The onset often is sudden, with dysuria and copious urethral discharge in boys and leukorrhea in girls. The urethral discharge often is thick, profuse, and yellow. The patient usually has no fever. In prepubertal girls, leukorrhea is more prominent as a sign of gonococcal infection (reflecting a vulvovaginitis), and urethritis occurs less commonly. This difference may be related to the method of infection and the different sensitivity of the vaginal epithelial surface to infection in a prepubertal child. Leukorrhea may be minimal in adolescent girls, and dysuria may be absent.

Diagnosis often is made earlier in adolescent boys than in girls, perhaps because of the prominence of urethral discharge in boys and misinterpretation of the significance of leukorrhea in girls. Gonococcal urethritis also may cause asymptomatic pyuria in boys. Occasionally, prepubertal patients have conjunctivitis or balanitis without significant urethritis. Clinical presentations include systemic illness with fever, arthritis, and skin lesions secondary to bacteremia in 3% of untreated individuals with mucosal gonorrhea. These lesions often begin on the extremities as small erythematous macules that progress to circular papules with an area of central necrosis.

The clinical presentation of nongonococcal urethritis may be similar to that described for gonorrhea, but it more commonly has a longer incubation period (often 8 to 14 days after sexual intercourse) and a scanty exudate, which may be clear and intermittent. This condition also is referred to as nonspecific urethritis and may be present in association with or subsequent to gonococcal urethritis. In the latter case, the scant urethral discharge may persist after the patient has been treated for gonorrhea. Asymptomatic urethral colonization with C. trachomatis also is reported in males.

An equivalent syndrome, acute urethral syndrome, has been described in sexually active females. The patient experiences an acute onset of dysuria and increased frequency, and pyuria (≥10 white blood cells/mm ³ of midstream urine) is a common finding. Bacterial cultures of the urine often are sterile or show less than 10 ⁵ bacteria/mL; coliform bacteria, Staphylococcus saprophyticus, and C. trachomatis are the most common causes. Clinical expression of infection with C. trachomatis in adolescent girls is characterized by a yellowish, mucopurulent secretion at the cervical os. However, infection with C. trachomatis may be asymptomatic in both sexes, an important consideration in designing effective strategies for diagnosis and management of sexual contacts.

A patient with urethritis caused by trauma may have hematuria and dysuria without fever. The trauma may be obvious or related to masturbation or introduction of foreign bodies into the urethra. Patients with urethritis secondary to bubble bath or detergent usually have transient dysuria and no systemic signs. Fecal contamination of the urethra may be accompanied by hematuria, dysuria, and pyuria.

Differential Diagnosis

Table 38.1 lists the differential diagnoses for urethritis.

Specific Diagnosis

A standard method for diagnosing gonorrhea in a sexually active male is to obtain urethral discharge by manually stripping the urethra or, if that is unproductive, by gently inserting a swab 2 to 3 cm into the distal urethra. The best culture technique for isolating N. gonorrhoeae, a fastidious organism, is immediate inoculation of this material onto a selective growth medium, such as regular or modified Thayer-Martin agar. Any delay in inoculation of the plates necessitates the use of a transport method with growth media in a carbon dioxide environment that support the gonococcus at ambient temperatures. These media protect the organism from its marked susceptibility to the effects of drying, cold, and overgrowth by other bacteria. Urethral exudate from a male patient should be Gram stained at the same time; typical kidney bean–shaped, gram-negative, intracellular diplococci are presumptively diagnostic, with a sensitivity and specificity approaching 100% ( Fig. 38.2 ).

Gram-stained smear of urethral discharge from a teenage boy with gonorrhea.

Putative gonococcal colonies should be confirmed by oxidase reaction, Gram staining, sugar use tests, rapid enzyme tests, nucleic acid probes, or agglutination reactions with antibodies specific for N. gonorrhoeae . The last four tests are especially important in evaluating sites of infection (e.g., the pharynx) or populations of patients with a low prevalence of gonorrhea.

Sexually active females with urethritis also should undergo urethral culture. Although the Gram stain of cervical secretions is only 66% sensitive in detecting N. gonorrhoeae in adolescent girls, the finding of kidney bean–shaped, intracellular gram-negative diplococci is highly specific and helpful. Vaginal, cervical, and rectal swabs are recommended. Asymptomatic colonization with gonococci seems to occur most commonly in female patients, although it has been described in adolescent boys. Pharyngitis, conjunctivitis, balanitis, and other, less common, manifestations of gonorrhea may coexist with urethritis. Samples obtained from these sites should be handled as described earlier. Blood agar and other specialized media may be indicated to identify nongonococcal causes of urethritis.

Nucleic acid amplification tests (NAATs) are highly sensitive and specific when used on urethral swab (males), endocervical swab, patient-obtained vaginal swabs, and urine specimens. These tests include polymerase chain reaction (PCR), transcription-mediated amplification, and strand displacement assays. Most commercially available products now are approved by the U.S. Food and Drug Administration (FDA) for testing male urethral swab specimens, female endocervical or vaginal swab specimens (collected by provider or patient), male or female urine specimens, or liquid cytology specimens. Use of urine specimens increases the feasibility of initial testing and follow-up of hard-to-access populations such as adolescents. These techniques also permit dual testing of urine for C. trachomatis and N. gonorrhoeae . NAATs are not cleared by the FDA for N. gonorrhoeae or C. trachomatis testing on rectal and pharyngeal swabs. However, some noncommercial laboratories have initiated nucleic amplification testing of rectal and pharyngeal swab specimens after establishing the performance of the test to meet requirements of the Clinical Laboratory Improvement Amendments (CLIA). These tests are superior to culture, and their ease of use (i.e., for urine or self-obtained specimens) renders them extremely attractive.

Gonococcal urethritis in prepubescent boys is diagnosed as described earlier for adolescent boys. Vaginal swabs are most useful in female patients, although vaginal discharge may not be prominent. Endocervical cultures are not recommended for the diagnosis of gonorrhea in prepubescent girls. The yield of vaginal swabs seems to be adequate for most diagnostic purposes; rectal swabs also may be useful in female patients. Showing kidney bean–shaped, gram-negative intracellular diplococci in a prepubescent boy or girl is useful for establishing a presumptive diagnosis and instituting therapy. Confirmation by culture as described for a sexually active male is necessary.

Other infectious causes of urethritis may be diagnosed by specific techniques, including wet mount or nucleic acid amplification for Trichomonas, Gram stain, and culture on Sabouraud dextrose agar for C. albicans, and culture or PCR for herpes simplex virus, used in the patients and their contacts. New culture techniques for Chlamydia, such as the use of microtiter cell monolayers, have increased the recovery rates, decreased the cost, and shortened the turnaround time for the isolation of C. trachomatis . The rigorous transport conditions and the small number of laboratories with cell culture techniques have limited the availability of Chlamydia cultures; however, nonculture methods, including direct immunofluorescence staining of smears with use of monoclonal antibodies, enzyme-linked immunosorbent assay (ELISA) techniques, and NAATs, are available. The use of immunofluorescence and ELISA techniques has been surpassed in sensitivity and ease of use by NAATs.

When documentation of infection is being sought in cases of suspected child abuse, performing cultures is strongly preferred. NAATs can be used as an alternative to culture with vaginal swab specimens or urine specimens from prepubertal girls. Culture remains the preferred method for urethral specimens from boys and extragenital specimens (pharynx and rectum) in boys and girls. When culture is unavailable, some experts support using NAAT if a positive result can be verified by another NAAT. ELISA and fluorescent antibody tests should not be used for testing rectal, vaginal, or urethral specimens from infants and children because of low sensitivity and specificity. A recent multicenter investigation showed NAATs for detection of C. trachomatis and N. gonorrhoeae in children being evaluated for child abuse were superior to culture.

Ureaplasma and other genital Mycoplasma spp. currently can be identified only by culture. This test should be reserved for the evaluation of recurrent cases of urethritis with poor response to treatment. Specimens of urethral and vaginal discharge secondary to fecal contamination and foreign bodies can be examined by conventional diagnostic bacterial techniques.