Sexually transmitted anorectal infections have been recognized to have significant clinical and public health implications. They are associated with high-risk behavior and coinfection with human immunodeficiency virus (HIV). In addition to ulcerative genital infections, nonulcerative anorectal infections increase the risk of acquiring HIV.1 Sexually acquired proctitis may be asymptomatic, resulting in continuing transmission of sexually transmitted diseases (STD).2 Since 2003, proctitis caused by lymphogranuloma venereum has emerged as an epidemic involving men who have sex with men (MSM) in the Netherlands, followed by other Western countries.3 Some STD clinics have seen increasing numbers sexually transmitted proctitis in MSM, caused mainly by gonorrhea, chlamydia, syphilis, and herpes simplex virus.4 However, cytomegalovirus (CMV) is not a common cause of proctitis in patients attending STD clinics.5,6
CMV infection of the lower gastrointestinal tract manifests mainly as colitis related to viral reactivation, especially among immunosuppressed or HIV-infected patients.7 Isolated case reports describe CMV proctitis, some of which are associated with primary CMV infection and unprotected anal intercourse (Table 1). However, published reviews of sexually transmitted proctitis and current STD treatment guidelines do not extensively discuss sexually transmitted CMV proctitis.22–24 For example, the 2010 STD guidelines mention that Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and herpes simplex virus (HSV) are the most common causes of sexually transmitted proctitis, and that CMV can be involved in immunosuppressed HIV-infected patients with proctocolitis.24 Treatment recommendations for CMV proctitis are not discussed. In order to bring attention to the role of CMV as a cause of sexually acquired proctitis, and provide management guidelines for this rare STD, a review of published case reports of CMV proctitis and a detailed description of a recently managed case are presented.
Clinically evaluable cases of CMV proctitis were identified through a Medline search of the English language literature, from 1964 until 2011, using keywords “cytomegalovirus proctitis,” “sexually transmitted proctitis,” “sexually transmitted cytomegalovirus,” “venereal cytomegalovirus,” and “venereal proctitis.” Reference lists from relevant articles were reviewed for additional cases. Proctocolitis cases, who may be associated with orally transmitted enteric pathogens, were excluded in order to focus attention on sexually transmitted proctitis.22 The literature search yielded 284 articles, 57 of which were analyzed as potentially relevant. In all, 15 cases of CMV proctitis, confirmed by serological, histopathological, or immunohistochemical testing, were identified from a total of 14 published articles from that time period. Clinical and endoscopic findings, therapeutic interventions, and outcomes were analyzed.
A 24-year old homosexual man with fever and passing blood per rectum was admitted to the hospital in November, 2010. Three weeks before admission, he had unprotected receptive anal sex with a new sexual partner. One week later, he had fever to 102°F, malaise, anorexia, tenesmus, and loose stools mixed with fresh blood. He continued to pass drops of fresh blood and mucus per rectum several times daily.
On admission, his leukocyte count was 8.1 K/μL with 49% lymphocytes and moderate atypical lymphocytes. Aspartate aminotransferase was 182 U/L and alanine aminotransferase was 241 U/L. Fecal leukocytes were abundant. Stool microbiologic studies and tests for gonorrhea and chlamydia were negative. CMV IgM antibody was positive, and Epstein Barr Virus indices for acute infection were negative. As he did not have findings suggestive of herpetic proctitis, such as painful ulcerations, he was not tested for HSV infection. HIV serology and RPR were negative. HIV-1 RNA by polymerase chain reaction was not detected.
Colonoscopy showed erythema and edema of rectal mucosa. Histopathology demonstrated extensive ulceration and inflammation, and large cells with intranuclear and cytoplasmic inclusions (Fig. 1). Immunoperoxidase stain for CMV was positive (Fig. 2). The patient's fever, symptoms, and laboratory abnormalities resolved gradually over several weeks. He received STD risk-reduction counseling. Follow-up HIV serology remained negative.
A detailed summary of 16 cases of CMV proctitis, including the author's case (case 7), is presented in Table 1. There were 10 men (63%) and 6 (37%) women, with a mean age of 43 years (range, 20–86 years). Seven cases (44%), including 2 women, developed CMV proctitis following anal intercourse within several days to 2 weeks. Three cases were associated with acute HIV infection (cases 4, 5, and 11).
Typical endoscopic findings included mucositis and ulcerations. Several cases had polypoid or mass lesions (cases 6, 10, 12). One had fistulas and sinus tracts along the rectal wall (case 13), and another vesicorectal and vesicovaginal fistulas (case 15). Diagnosis was confirmed by serology with CMV rectal tissue culture (case 9), serology with urine and blood cultures (case 8), serology with histopathology (cases 1, 2, 3, 4, 5, and 10), or CMV immunohistochemistry (cases 6, 7, 11, 12, 13, 14, 15, and 16). Histopathological findings included proctitis with ulcerations, and enlarged cells with intracytoplasmic and intranuclear inclusion bodies.
Patients with sexually transmitted CMV proctitis (cases 1–7) typically presented with rectal bleeding, fever, systemic symptoms, lymphocytosis with atypical lymphocytes, and hepatitis. Their mean age was 29 years (range, 20–37). Colonoscopies demonstrated mucositis and ulcers. Two patients from this group (cases 4 and 5) had concurrent acute HIV infection. All cases of sexually transmitted CMV proctitis resolved spontaneously without complications.
Cases without documented anal intercourse (cases 8–16) were older (mean age, 55 years), had multiple comorbidities, such as diabetes mellitus, inflammatory bowel disease and multiorgan failure, and had worse outcome. Three cases (cases 12, 13, and 15) were complicated by fistula formation. Two elderly patients (cases 12 and 16) died because of septicemia and rectal bleeding, respectively. Ganciclovir and valganciclovir were prescribed to 4 older patients with various comorbidities, including cachexia (case 12), diabetes mellitus (case 13), and Crohn disease (case 14).
Primary CMV infection in adults typically causes a mononucleosis-like syndrome with fever, malaise, lymphocytosis with atypical lymphocytes, and abnormal liver function tests.13 Most cases of CMV proctitis were associated with systemic symptoms of CMV infection. Close to half of reported cases, which included both sexes, occurred several days to 2 weeks following anal intercourse consistent with the sexual transmission. Over 90% of MSM test positive for CMV infection, compared to 54% of heterosexual men.25 CMV infection in MSM is characterized by prolonged excretion of CMV in semen, and is associated with unprotected anal intercourse.5 Lang et al. describe a relatively high CMV titer of 7.7 log DNA copies/mL in whole semen, and persistence in semen for up to 14 months, in a patient with CMV mononucleosis.26 CMV- and HIV-coinfected men have increased shedding of CMV in semen (median, 5.78 logs DNA copies/mL; range, 3.0–7.8 log DNA copies/mL) compared to CMV-infected males without HIV infection.27 Use of saliva as a lubricant in anal intercourse may be another mode of transmission.28 On the other hand, reports of CMV proctitis without documented anal intercourse describe older patients (mean age, 55 years compared to 29 years) with comorbidities, local complications such as fistula formation, and less favorable outcome.
Diagnostic testing in reported cases of CMV proctitis included gastrointestinal endoscopy, serological testing, histopathology, and CMV histochemistry. Typical endoscopic findings included rectal mucositis and ulcerations, although polypoid lesions were described in several cases (Table 1). Anoscopy or sigmoidoscopy is recommended by the latest STD guidelines.24 Although viral tissue culture may be available in some settings, histopathology and CMV histochemistry provide more rapid diagnosis.7 Concurrent HIV infection was documented in several cases of CMV proctitis underlying the importance of testing for HIV coinfection. In addition, patients with sexually transmitted proctitis should be evaluated for infection with HSV, N. gonorrhoeae, C. trachomatis, and T. pallidum.24
Although the role of antiviral therapy in primary CMV proctitis has not been defined, it is probably not essential in all cases, as most reported cases resolved spontaneously without complications. Reported cases associated with acute HIV coinfection resolved without antiviral therapy (Table 1). On the other hand, CMV colitis in immunosuppressed or HIV-infected patients may be progressive, is associated with high mortality, and requires antiviral treatment.7
In conclusion, the triad of mononucleosis-like illness with rectal bleeding shortly after unprotected anal intercourse is pathognomonic for sexually transmitted CMV proctitis. CMV should be considered in any case of unexplained proctitis. Suggestive findings on anoscopy or sigmoidoscopy include rectal mucositis and ulceration. CMV serology and biopsy, including CMV histochemistry, are confirmatory. Sexually transmitted CMV proctitis generally resolves spontaneously without antiviral therapy. Management of at-risk patients with CMV proctitis should include HIV testing and STD risk-reduction counseling.
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