Images in HIV/AIDS: HIV-Associated Lymphogranuloma Venereum Proctitis

Dr. Schlecht is a senior fellow in infectious diseases; Dr Panther is assistant professor of medicine in infectious diseases in the department of internal medicine, division of infectious diseases; and Dr Fugelso is clinical instructor in surgery in the department of surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.

A 41-year-old HIV-positive homosexual man with a CD4+ cell count of 666/µL presented with 2 months of diarrhea and cramping. He had had unprotected sexual exposures but denied a history of rectal bleeding, mucous stools, penile or rectal discharge, fevers, chills, or anogenital sores. Treatment with metronidazole was initiated for Blastocystis hominis, according to his stool study results.

Following initial improvement, his cramps and diarrhea recurred and persisted, and painful, bloody bowel movements began. Examination demonstrated anal condylomata and hemorrhoids on anoscopy. On referral to a colorectal surgeon, the patient was found to have shotty, bilateral, and nontender inguinal lymphadenopathy; anoscopy revealed a friable 3-cm mass adhering to his prostate. Biopsy of the mass revealed rectal mucosa with ulceration, granulation tissue, acute and chronic inflammation including numerous plasma cells, and focal granulomas. No viral inclusions, acid-fast bacteria, fungi, or evidence of malignancy were seen (Figures 1 and 2).

Laboratory studies demonstrated negative rapid plasma reagin test results, a negative rectal culture for gonococci, and a positive rectal culture for Chlamydia. Serology performed at the Massachusetts Department of Public Health revealed a Chlamydia trachomatis microimmunofluorescence titer of 1:1024. The patient's clinical condition was thought to probably be lymphogranuloma venereum (LGV) proctitis. He was treated with 21 days of doxycycline and showed resolution of his mass and symptoms 1 month later.

The differential diagnosis of proctitis in men who have sex with men is dominated by the sexually transmitted infections gonorrhea, herpes simplex, chlamydial infection, and syphilis, although enteric pathogens, such as Shigella, Campylobacter, Salmonella, and Entamoeba histolytica, may also cause proctitis and may be transmitted sexually.

In addition, non-sexually transmitted infections, such as those with Escherichia coli, Clostridium difficile, and cytomegalovirus, may also cause a proctitis- or proctocolitis-like syndrome and require evaluation. Of the noninfectious causes of proctitis, the initial presentation of inflammatory bowel disease is indistinguishable from LGV proctitis based on clinical, endoscopic, and histologic grounds. Thorough care must be given to fully evaluate patients for all infectious and noninfectious causes of proctitis.

LGV infection is a sexually transmitted genital ulcer disease caused by the L1, L2, and L3 serovars of C trachomatis. While infection with the D-K serovars causes milder anogenital infections, LGV infection is invasive and more symptomatic. LGV infection typically involves 3 stages:

• Primary stage. Characterized by a small papule or herpetiform lesion at the site of inoculation, which is painless and appears 3 to 30 days after exposure.

• Secondary stage. Beginning 2 to 6 weeks after infection and characterized either by painful lymphadenopathy of the nodes draining the primary lesion (eg, inguinal lymphadenopathy and femoral lymphadenopathy typically follow penile, urethral, and vulvar inoculation) or by an anogenitorectal syndrome in which LGV infection of the cervix or rectum causes proctitis or proctocolitis and inflames the deep pelvic and even the lumbar lymph nodes (Figure 3).

With same-sided inguinal and femoral lymph node involvement, a classic "groove sign" may appear between the 2 lymph node groups. Affected lymph nodes become severely inflamed, then coalesce, necrose, and become abscessed to form a classic bubo. Buboes may drain spontaneously and/or may become loculated abscesses, fistulas, or externally draining sinus tracts. Patients also complain of fever, malaise, headache, and/or myalgia.

• Late or tertiary stage. Developing years after exposure and characterized by a paucity of organisms yet severe inflammation, reactive lymphoid hyperplasia, fibrosis, and scarring that may result in anogenital fistulas, strictures, and/or lymphatic obstruction leading to lymphedema and elephantiasis of the genitalia.1 These complications may require surgical intervention.

LGV infection is rare in the United States, and diagnosis can prove difficult.² The mainstays of laboratory diagnosis include nucleic acid testing and culture of involved mucosa or bubo fluid during the secondary stage of infection. Positive results should be considered for further serovar-specific testing through the regional department of public health. Serologic testing remains nonspecific and plays a strictly supportive role.

Presumptive treatment is indicated while awaiting further results. Oral doxycycline 100 mg given twice daily for 21 days remains the therapy of choice, with oral erythromycin 500 mg 4 times a day for 21 days a viable alternative. Further antibiotic therapy may be necessary depending on resolution of symptoms. Sexual contacts within 60 days of symptom onset should be screened for infection. Asymptomatic contacts should receive prophylaxis with a single 1-g dose of azithromycin or with doxycycline 100 mg twice daily for 1 week; symptomatic persons should undergo evaluation.³

With the recent recognition of an outbreak of LGV in Europe and its spread to the United States, clinicians must remain vigilant against missing LGV infection in patients with proctitis, particularly in men who have sex with men.^4-6

References:

References1. Stamm WE, Jones RB, Batteiger BE. Chlamydia trachomatis (trachoma, perinatal infections, lymphogranuloma venereum, and other genital infections). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Elsevier Churchill-Livingstone; 2004:2239-2255.
2. Centers for Disease Control and Prevention. Lymphogranuloma venereum among men who have sex with menÑNetherlands, 2003-2004. MMWR. 2004;53:985-988.
3. Centers for Disease Control and Prevention; Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006 [published correction appears in MMWR. 2006;55:997]. MMWR. 2006;55(RR-11):1-94.
4. Tinmouth J, Rachlis A, Wesson T, Hsieh E. Lymphogranuloma venereum in North America: case reports and an update for gastroenterologists. Clin Gastroenterol Hepatol. 2006;4:469-473.
5. Van der Bij AK, Spaargaren J, Morre SA, et al. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study. Clin Infect Dis. 2006;42:186-194.
6. Nieuwenhuis RF, Ossewaarde JM, Gotz HM, et al. Resurgence of lymphogranuloma venereum in Western Europe: an outbreak of Chlamydia trachomatis serovar l2 proctitis in the Netherlands among men who have sex with men. Clin Infect Dis. 2004;39:996-1003.