Gonorrhea

Gonorrhea is caused by Neisseria gonorrhoeae , a gram-negative intracellular diplococcus. It is the most common bacterial STD affecting the anorectum. Anoreceptive transmission, after a 5- to 7-day incubation period, causes proctitis and cystitis. In women, gonorrhea can result from ARI autoinoculation of vaginal gonorrhea into the lower rectum. Asymptomatic gonococcal proctitis occurs frequently and can only be detected by laboratory testing.

When symptoms occur, patients present with severe tenesmus, pruritus, and bloody or mucoid rectal discharge. The initial infection, if untreated, can progress on rare occasions to more advanced disease, such as perihepatitis, meningitis, endocarditis, and probably the most common disseminated form, gonococcal arthritis.

A thick, yellow, mucopurulent discharge with or without proctitis is highly suggestive of gonorrhea. One classic finding is the ability to express the mucopus from the anal crypts by applying gentle external pressure while the anoscope is in place.

In symptomatic men, polymorphonuclear leukocytes with intracellular Gram-negative diplococci seen on Gram stains of urethral specimens are diagnostic. Gram stains of rectal specimens, however, are insufficient for detection of infection.

Although nucleic acid amplification tests (NAATs) have not been approved by the U.S. Food and Drug Administration (FDA) for use on rectal specimens, they are in fact being used with increasing frequency in this clinical context and are more sensitive than cultures. Many laboratories have now established performance criteria for the utilization of NAATs on rectal swab specimens.

Cultures using modified Thayer-Martin agar with antimicrobial susceptibility testing are still the “gold standard” and are recommended in all cases of treatment failures.

Chlamydia trachomatis and Lymphogranuloma venereum

Chlamydia infection is one of the most common STDs in the United States. Approximately 4 million chlamydial infections occur yearly. The incidence in both men and women who practice ARI is rising. Approximately 70% of rectal chlamydia infections are asymptomatic, thereby providing a reservoir for future infections.

Chlamydia proctitis typically occurs within 10 days of penetrating anal sexual contact and may coexist with other STDs, especially gonorrhea. Up to 15% of asymptomatic MSM harbor chlamydia organisms. Fifteen immunotypes are known; serovars D through K are responsible for C. proctitis , and serovars L1, L2, and L3 are responsible for Lymphogranuloma venereum (LGV).

After either ARI or oral-anal intercourse, non-LGV proctitis presents with pain, tenesmus, and fever. Examination reveals erythematous rectal mucosa, but mucosal ulcerations are rare. Inguinal and/or femoral nodes may be enlarged and matted (“buboes”). Patients with LGV also experience pain and tenesmus, but with associated mucosal ulcerations and a more pronounced friability resembling Crohn-related proctitis. The inguinal lymphadenopathy plays an important role in differentiating LGV from Crohn-related proctitis. Untreated disease can progress to ulceration, causing rectovaginal or rectovesical fistulas, abscesses, and, as a late finding, rectal strictures mimicking rectal cancer. Because of similarities between LGV and IBD, LGV should be considered as a differential diagnosis in patients with proctitis or IBD-related symptoms, especially among HIV-positive men. LGV also may exhibit extraintestinal manifestations, including reactive arthritis and hepatitis.

Among MSM infected with rectal gonorrhea or chlamydia, a history of two additional prior rectal infections was associated with an eightfold increased risk of HIV. Therefore, HIV testing should be considered.

Anorectal Chlamydia trachomatis infections can be diagnosed by NAATs even though these tests do not carry an FDA indication for use on rectal swabs. As in the case of anorectal gonococcal infections, an increasing number of laboratories are validating the use of NAATs for C. trachomatis detection on rectal swab specimens. Aptima Combo 2 (Hologic Inc., Marlborough, Mass.) is a transcription-mediated assay that has the advantage of detecting both N. gonorrhoeae and C. trachomatis .

For LGV, chlamydia serology is supportive of the diagnosis when the complement fixation titers are greater than 1:64. Genital lesion swabs or lymph node aspirates can be tested either by culture, direct immunofluorescence, or nucleic acid detection.

Biopsy reveals infectious proctitis with crypt abscesses, infectious granuloma, and giant cells. The presence of granulomas can lead to an erroneous diagnosis of Crohn-related proctitis.

Chancroid

Chancroid is caused by Haemophilus ducreyi, a small gram-negative, nonmotile, non–spore-forming aerobic bacillus. It is characterized by painful adenopathy, multiple perianal abscesses, and tender genital or anorectal ulcers. The presence of painful “kissing ulcers” is typical of this infection. Because of the soft nature of the ulcers, distinguishing them from herpes or syphilis is difficult. Lymphadenopathy (bubo formation) is present in approximately 50% of cases, and sometimes the lymph nodes become suppurative. Chancroid is common in developing countries and facilitates HIV transmission. Effective and early treatment is therefore an important part of any strategy to control the spread of HIV infection. Diagnosis is determined primarily by culture of a specimen obtained by a swab from the base of the genital ulcer. Several different media have been used, but GC agar (Life Technologies [GIBCO], Grand Island, N.Y.) has the highest sensitivity (80%) for the isolation of H. ducreyi . No FDA-approved polymerase chain reaction test for H. ducreyi is available. Testing for herpes simplex virus (HSV) and syphilis should also be performed.

Granuloma Inguinale

Granuloma inguinale is a chronic glaucomatous infection caused by Klebsiella granulomatis , a gram-negative intracellular bacterium. The disease is insidious, with several months passing before red, shiny, hard masses develop on the genitals or around the anorectum. Scarring can lead to stenosis of the anorectum. The bacterium is difficult to culture. Tissue crush preparation or biopsy confirms the diagnosis with the presence of the dark-staining Donovan bodies. No FDA-approved molecular assays exist for K. granulomatis . The differential diagnosis includes carcinoma, secondary syphilis, and amebiasis. This disease is fairly rare in the United States.

Syphilis (“The Great Masquerader”)

The organism that causes syphilis ( Treponema pallidum ) enters the anus during ARI, and anal ulcers usually appear within 2 to 6 weeks but may occur up to 3 months later. In 10% to 20% of cases, the primary lesion, referred to as a chancre, may be hidden within the anal canal. The chancre is usually at the anal verge and typically is painless. In some instances, especially if the lesion becomes secondarily infected, it may cause exquisite pain and be mistaken for an anal fissure. Unlike classic fissures, the lesion may be situated off the midline, peripherally on the anal skin or proximally above the dentate line. Multiple chancres may be present.

When chancres are not treated, the ulcer heals spontaneously in 3 to 4 weeks. This stage is followed “classically” 2 to 10 weeks later by secondary lesions in the guise of a diffuse red maculopapular rash on the palms of the hands and soles of the feet.

Secondary syphilis also may present as a pale brown or pink flat verrucous lesion called condyloma latum, which is a large perianal mass composed of many raised smooth warts, which tend to secrete mucus and are associated with pruritus and a foul odor. These lesions are highly infectious and can coexist with primary chancre. The differential diagnosis includes condyloma acuminatum, which is often more desiccated and keratinized. Spirochetes are usually demonstrated in condyloma latum on modified Steiner silver staining. Both primary and secondary lesions are infectious.

Proctitis in the absence of anogenital lesions, mimicking IBD, has also been reported. Rectal syphilis with painless inguinal adenopathy has been mistaken for lymphoma because both diseases present with rubbery inguinal lymphadenopathy and submucosal rectal irregularities. In contrast, genital ulcers are associated with painful adenopathy. Syphilitic rectal gummas are exceedingly rare and can be confused with malignant growths. Like lymphoma, rectal syphilis is generally accompanied by tenesmus, mucoid discharge, and rectal pain.

In one third of patients, anal syphilis proceeds to a spontaneous cure, with an additional third remaining latent. About a third of the cases will progress to late or tertiary syphilis, which can occur several years after primary or secondary disease. Asymptomatic central nervous system involvement is demonstrated in up to 25% of patients with late or latent syphilis. Because syphilis is a systemic infectious disease, central nervous system involvement (neurosyphilis) can occur at any stage of infection. Ideally, a sample of the cerebrospinal fluid should be obtained for examination. Syphilitic ocular involvement is almost pathognomonic of neurosyphilis and needs to be treated as neurosyphilis.

Because of the variable manifestations of syphilitic ulcers, any ulcer in MSM must be viewed with suspicion. Women with anal ulcers should be questioned regarding ARI. Anoscopy with modified Steiner silver staining of scrapings from the base of the chancre reveals early syphilis. Biopsy may demonstrate spirochetes on a Treponema pallidum immunohistochemical stain. T. pallidum cannot be isolated by culture.

Indirect diagnoses can be based on serologic tests that are defined as treponemal or nontreponemal. Nontreponemal tests include Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin tests, which vary according to disease activity; hence titers can reflect persistent disease or responsiveness to treatment. The VDRL is used predominantly for screening, and false-positive results have been reported with rheumatologic disorders, Epstein-Barr virus, infections, and cancer.

T. pallidum –specific assays usually use the fluorescent treponemal antibody absorption test (FTA-ABS). The FTA-ABS becomes positive earlier than nontreponemal tests and is confirmatory for syphilis.