REVIEW ARTICLE Sexually Transmitted Infections and Increased Risk of Co-infection with Human Immunodeficiency Virus Margaret R.H. Nusbaum, DO, MPH; Robin R. Wallace, MD; Lisa M. Slatt, MEd; Elin C. Kondrad, MD The incidence of trichomoniasis (Trichomonas vaginalis) Clinical Presentation in the United States is estimated at 5 million cases annu- Urethritis, Epididymitis, and Proctitis ally; chlamydia (Chlamydia trachomatis) at 3 million; gon- In men, STIs usually remain confined to the urethra. Symptoms orrhea (Neisseria gonorrhoeae), 650,000; and syphilis (Tre- of urethritis include urethral discharge, dysuria, or urethral ponema pallidum), 70,000. However, most sexually itching. The discharge of nongonococcal urethritis (NGU) is transmitted infections (STIs) are asymptomatic—con- often slight, and may not be apparent without massaging the tributing to underdiagnosis estimated at 50% or more. urethra. Discharge of NGU is usually minimal and gray, white, Diagnosis of an STI signals sexual health risk because an or mucoid rather than yellow. Discharge that is yellow and pre- STI facilitates the transmission and acquisition of other sent in greater volume most often signals infection with N STIs, including human immunodeficiency virus (HIV). gonorrhoeae. In fact, comorbid STIs increase patients’ susceptibility of Epididymitis presents as acute unilateral testicular pain acquiring and transmitting HIV by two- to fivefold. Sev- and swelling. Clinical findings include tenderness of the epi- eral studies have shown that aggressive STI prevention, didymis and ductus deferens, erythema and edema of the testing, and treatment reduces the transmission of HIV. overlying scrotal skin, urethral discharge, and dysuria. Swelling The authors discuss common clinical presentations, and tenderness may be localized or may extend to the entire screening, diagnosis, and treatment for trichomoniasis, epididymis and surrounding areas, making the epididymis less chlamydia, gonorrhea, syphilis, and herpes simplex virus. distinct in the inflammatory mass. Proctitis presents as anorectal or perineal itching, anorectal iagnosis of a sexually transmitted infection (STI) sig- pain, and discharge. Dnals sexual health risk. STIs facilitate the transmission Trichomoniasis tends to be asymptomatic in men, while and acquisition of other STIs, including human immunode- chlamydia and gonorrhea present as acute urethritis or epi- ficiency virus (HIV). Coexisting STIs increase susceptibility of didymitis. In sexually active men, however, C trachomatiscauses acquiring and transmitting HIV by two- to fivefold.1 Studies 30% to 50% of cases of NGU,4 an even higher proportion of post- show that aggressive STI prevention, testing, and treatment gonococcal urethritis, and the majority of cases of epididymitis. reduces transmission of HIV.1 Ureaplasma urealyticum appears to be causative in the remaining Most STIs are asymptomatic, contributing to widespread cases, although the cause is undetermined in approximately one underdiagnosis estimated at 50% or higher.2 In the United third of men who have NGU. Routine screening for U ure- States, the annual incidence of trichomoniasis (Trichomonas alyticum is not recommended as NGU is often associated with vaginalis) is estimated at 5 million; chlamydia (Chlamydia tra- infection from C trachomatis and N gonorrhoeae. chomatis) at 3 million; gonorrhea (Neisseria gonorrhoeae), 650,000, Other urinary tract pathogens, including Escherichia coli and syphilis (Treponema pallidum), 70,000. 3 This article dis- and Pseudomonas aeruginosa, can be causative agents in men cusses the common clinical presentations, screening, diagnosis, who are older, have structural abnormalities of the urethra, and treatment for trichomoniasis, chlamydia, gonorrhea, have recently undergone a urinary tract procedure or manip- syphilis, and herpes simplex virus. ulation, or engage in anal intercourse. Although ascending infection to the epididymis is rare, most cases of epididymitis are caused by STIs. In addition to infectious causes, differential diagnoses should also include trauma, testicular torsion, and tumor. From the Department of Family Medicine in the School of Medicine at the Positive results for leukocyte esterase on urinalysis can University of North Carolina at Chapel Hill. Address correspondence to: Margaret R.H. Nusbaum, DO, MPH, Asso- indicate C trachomatis, N gonorrhoeae, or other urinary tract ciate Professor, Department of Family Medicine, 101 Manning Dr, CB 7595, pathogens. Chlamydia trachomatis or T vaginalis should be sus- Chapel Hill, NC 27514-7595. pected in the absence of gram negative intracellular diplo- E-mail: [email protected] Nusbaum et al • Review Article JAOA • Vol 104 • No 12 • December 2004 • 527 REVIEW ARTICLE cocci on Gram stain. Patients presenting with epididymitis Leukocytosis and elevated erythrocyte sedimentation rate also should be examined and tested for chlamydia and gonorrhea. support a diagnosis of PID. In the case of proctitis, cultures should be taken from the Pelvic inflammatory disease can lead to infertility, ectopic symptomatic area. pregnancy, and chronic pelvic pain. Because PID can poten- In women, urethritis can be a manifestation of C tra- tially cause significant damage to women’s reproductive health, chomatis, herpes simplex virus (HSV), N gonorrhoeae, or T vagi- clinicians should have a low threshold for diagnosis and treat- nalis. As in men, proctitis in women presents as anorectal or ment of PID. perineal itching, or anorectal pain and discharge. Genital Ulcerative Disease Vaginitis and Cervicitis Herpes simplex virus is the most common single cause of Etiologic agents of vaginitis and cervicitis include C trachomatis, genital ulcers in the United States. Herpetic ulcers appear on N gonorrhoeae, HSV, and T vaginalis. More than half of endo- the external genital, urethral, and anorectal areas as well as in cervical infections do not cause sufficient inflammation to the vagina and on the cervix. About 10% of ulcers are the result in clinical signs and symptoms, however. When pre- result of more than one etiologic agent, however. The clinical sent, symptoms can include dysuria, vaginal discharge, dys- features of ulcers can be altered in immunosuppressed indi- pareunia, perineal itching, and pelvic discomfort or pain. Ery- viduals. Differential diagnosis includes syphilis and herpes thema multiforme and swelling of the vulva or labia suggest zoster as well as noninfectious causes such as trauma, con- trichomonal or HSV infection. tact dermatitis, lichen sclerosis, and Behçet’s syndrome. Trichomonal discharge is usually copius, frothy, and The primary lesion of syphilis, the chancre, is usually yellow-green or occasionally gray. The vaginal walls are often painless. It is a solitary ulcer with raised, well-defined bor- erythematous and granular in appearance, while punctate ders and a clean, indurated base. The chancre occurs at the site hemorrhages of the cervix give it the classic “strawberry” of infection and is usually associated with nontender regional appearance. lymphadenopathy and heals spontaneously and without scar- Perineal swelling, cervical vesicles, or venereal (or den- ring in 3 to 6 weeks. driform) ulcers, suggest HSV infection. Alternatively, swelling, Secondary syphilis occurs 4 to 10 weeks after the primary tenderness, and drainage in glandula vestibularis major lesion of syphilis appears—and goes untreated. Symptoms of (ie, Bartholin’s gland) sites suggest gonorrheal infection. A secondary syphilis include myalgia, arthralgia, malaise, low- friable cervix and mucopurulent vaginal discharge can be grade fever, and generalized lymphadenopathy. A nonpruritic, seen with gonorrhea and chlamydia. maculopapular eruption affecting the trunk, limbs, palms, Because chlamydia, gonorrhea, and trichomoniasis, may and soles is present in 10% to 75% of patients. Condylomata present similarly with mucopurulent vaginal discharge, lata, fleshy lesions that may be broad-based, flat, or raised, drainage from the cervix, or a friable cervix, physicians should may be seen in the mucous membranes (eg, anus, external screen for all three—as well as for bacterial vaginosis. Ulcer- genitals, mouth). ative lesions should be tested for HSV. A definitive diagnosis In up to one third of patients with secondary syphilis, of trichomoniasis requires identifying T vaginalis on a Tri- the primary chancre is still present, increasing the likelihood chomonas wet prep test. of transmission to any additional sexual contacts. Left untreated, syphilis becomes latent with no readily Pelvic Inflammatory Disease apparent clinical findings. Without therapy, approximately With the exceptions of T vaginalis and HSV, pathogens in the one third of those infected will develop tertiary syphilis 10 to lower genital tract in women frequently and rapidly ascend to 30 years after the initial infection. The manifestations of tertiary the endometrium and adnex uteri, causing pelvic inflamma- syphilis include gummas, aortitis and other cardiovascular tory disease (PID) and pelvic adhesive disease. Manifestations disease, and neurosyphilis. of PID include endometritis, salpingitis, tuboovarian abscess, and pelvic peritonitis. Suspected Exposure to Sexually Transmitted Infections Physical symptoms of PID include perineal and urethral Patients may initially present to physicians’ offices with con- itching or burning, vaginal discharge and odor, spotting with cerns about STI exposure for numerous reasons. Some patients intercourse, insertional