We thank Radu Clincea, MD, infectious disease consultant, for his assistance with this chapter.
The anorectum is being used with increased frequency for sexual fulfillment. In both sexes this practice has resulted in an increase in the incidence and variety of sexually transmitted diseases (STDs). The lifestyle that is often associated with men who have sex with men (MSM) is a definite risk factor for STDs, although monogamous MSM have no higher risk for STDs than do monogamous heterosexuals.
Anorectal venereal infections also afflict women who practice anal receptive intercourse (ARI). Heterosexual anal intercourse confers a much greater risk of human immunodeficiency virus (HIV) transmission than does vaginal intercourse and is far more common than generally realized; more than 10% to 30% of American women and their male partners engage in the act regularly.
The multiple organisms found in the area, only some of which are pathogenic, often hamper the diagnosis and treatment of STDs.
The rising incidence of infectious proctitides, especially in MSM, warrants consideration of infectious causes when proctitis is diagnosed. The symptoms mimic inflammatory bowel disease (IBD), and thus the history and physical examination should address sexual habits, including ARI, as well as anogenital lesions and lymphadenopathy.
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.
Preferred Clinical Approach
Empiric treatment is started based on clinical suspicion while awaiting definitive culture results. Screening 3 months after treatment is an important part of the management because 35% of patients will experience a recurrence. Treatment of all sexual contacts decreases the recurrence rate.
The Centers for Disease Control and Prevention no longer recommends use of oral cephalosporins for the treatment of gonococcal infections. For uncomplicated gonococcal infections of the rectum, the recommended regimen is a single dose of ceftriaxone, 250 mg intramuscular (IM) plus a single dose of azithromycin, 1 g orally or doxycycline, 100 mg orally twice a day for 7 days. Alternative regimens include a single dose of cefixime, 400 mg orally plus a single dose of azithromycin, 1 g orally or doxycycline, 100 mg orally twice a day for 7 days. Because concomitant chlamydia infections are common, a single dose of azithromycin, 1 g, is added. For patients with documented severe cephalosporin allergies, a single oral dose of azithromycin, 2 g, is to be used. All patients should be followed up with a test of cure 1 week later. With close follow-up and treatment of all sexual partners, a 95% cure rate is a reasonable expectation. Evaluation for other sexually transmitted pathogens, such as syphilis and HIV, is also required because multiple organisms are often present. Guidance by regional public health services regarding the prevalence of emerging resistant strains of gonorrhea help determine therapeutic choices.
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.
Preferred Clinical Approach
Presumptive treatment for both N. gonorrhoeae and C. trachomatis co-infection remains the standard of care. Recommended regimens are a single dose of azithromycin, 1 g orally, or doxycycline, 100 mg orally twice a day for 7 days.
The alternative regimens are erythromycin base, 500 mg orally twice a day for 7 days, or erythromycin ethylsuccinate, 800 mg orally four times a day for 7 days, or levofloxacin, 500 mg orally once daily for 7 days, or ofloxacin, 300 mg orally twice a day for 7 days.
For LGV, the recommended treatment is doxycycline, 100 mg orally twice a day for 21 days, and the alternative regimen is erythromycin base, 500 mg by mouth four times a day for 21 days.
Azithromycin, 1 g orally once weekly for 3 weeks, could also be used based on its antimicrobial susceptibility activity. A test of cure should be performed at least 4 weeks after completion of therapy.
Treatment of the strictures is often complicated because they can be multiple and of varying segments. Many extend to the splenic flexure and must be differentiated from IBD, ischemia, and cancer.
The treatment of symptomatic strictures should initially include a 3-week course of the appropriate antibiotics. Proximal diversion or sphincter-saving excisional surgery may be the only alternative for treatment failures. Asymptomatic strictures require no treatment.
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.
Preferred Clinical Approach
The recommended treatment regimens include azithromycin, 1 g orally (single dose); Doxycycline 100 mg orally twice a day for 7 days; alternative therapy includes: Erythromycin base 500 mg orally four times a day for 7 days or Levofloxacin 500 mg orally once daily for 7 days or Ofloxacin 300 mg orally twice a day for 7 days. Treatment should be started based on clinical suspicion while awaiting culture results. Resolution of the adenopathy lags behind resolution of the ulcers.
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.
Preferred Clinical Approach
Recommended regimens are Azithromycin 1 g orally once per week or 500 mg daily for at least 3 weeks and until all lesions have completely healed. Alternative regimens are all to be prescribed for a minimum of 3 weeks or until all lesions have healed and consist of Doxycycline 100 mg orally twice a day or trimethoprim-sulfamethoxazole, one double-strength tablet (160 mg/800 mg) orally twice a day, or ciprofloxacin, 750 mg orally twice a day, or erythromycin base, 500 mg orally four times a day.
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.
Preferred Clinical Approach
The treatment of primary and secondary syphilis is a single dose of long-acting benzathine penicillin (Bicillin), 2.4 million units IM, regardless of HIV status. For patients with early latent syphilis (defined as evidence of infection acquired during the preceding 12 months), a single dose of benzathine penicillin is still recommended. However, if the latent period is greater than 1 year or is of unknown duration, then the patient is classified as having late latent syphilis and the 2.4 million units injection of benzathine penicillin is repeated every week for 3 consecutive weeks for delivery of a total of 7.2 million units.
By definition, patients with latent syphilis have serologic evidence of infection but are asymptomatic, and the objective of treatment is the prevention of complications.
Tertiary syphilis is defined by the presence of gummas and cardiovascular complications without neurologic involvement. The recommended treatment regimen is the same as for late latent or latent syphilis of undetermined duration. Benzathine penicillin G, 2.4 million units IM, is administered once a week for 3 weeks.
Neurosyphilis is treated with aqueous penicillin G, 18 to 24 million units every 24 hours for 10 to 14 days. An alternative regimen is procaine penicillin, 2.4 million units IM once daily plus probenecid, 500 mg orally four times a day, both for 10 to 14 days.
In nonpregnant patients who are allergic to penicillin, doxycycline 100 mg by mouth twice a day has been used for many years with good results.
Pregnant patients and patients with HIV disease who are allergic to penicillin should always be treated with penicillin after desensitization.
In all patients, a fourfold drop in the rapid plasma reagin titer is needed to document a successful treatment response.