Definition, Etiology, PathogenesisTop
1. Etiologic agent: Chlamydia trachomatis, serovars/genovars L1, L2, and L3. In Europe the majority of lymphogranuloma venereum (LGV) cases are caused by serovars L2b and L2.
2. Pathogenesis: The disease starts at the site of entry of C trachomatis through mucous membranes, predominantly in the genitourinary, perianal, or perirectal area. Later in the disease the infection spreads, causing necroinflammatory lesions in regional lymph nodes and lymphangitis. Abscesses with a tendency to disrupt and ooze may develop.
3. Reservoir and transmission: The infection is predominantly transmitted through sexual contacts.
4. Risk factors: Similar as in other sexually transmitted infections (STIs). Since 2003 LGV has been endemic in Europe among men who have sex with men (MSM), but it is rare in heterosexual individuals. Coinfection with HIV is relatively common.
5. Incubation and contagious period: Week to 4 weeks.
Clinical Features and Natural HistoryTop
There are 3 stages of disease progression:
1) Primary stage: Primary lesion at the site of microbial entry.
2) Secondary stage: Regional lymphadenitis with fistulas and abscesses.
3) Late disease: Fibrosis and irreversible lymphedema.
Pathogen entry in the anogenital area leads to inguinal disease, while inoculation through the rectum, to anorectal syndrome.
1. Inguinal disease:
1) Primary stage: The primary lesion develops in the urogenital area, at the site of inoculation. The lesion is initially a small, painless nodule or papule that disintegrates rapidly forming nontender superficial ulceration with seropurulent discharge. The ulceration quickly resolves, usually within a week (also spontaneously), and often remains unnoticed by the patient. A typical location in men is the coronal sulcus of the penis, glans, foreskin, and frenular area, and in women, cervix of the uterus, posterior vaginal wall, and vulva. In rare cases urethritis or cervicitis may be the initial manifestations of LGV.
2) Secondary stage (regional lymphadenitis): Regional lymph nodes that drain lymph from the primary infection site are usually affected after 2 to 6 weeks from the occurrence of the primary lesion. The disease may be unilateral or, less frequently, bilateral. Inguinal and/or femoral lymph nodes are usually affected in men. The lymph nodes become tender and enlarged and gradually form conglomerates (buboes). Pain may cause walking difficulty. Skin over the affected lymph nodes has features of inflammation. In about one-third of patients lymph node rupture is observed, with formation of fistulas that heal with scarring. The “sign of the groove” may be seen, caused by enlargement of inguinal and femoral lymph nodes localized above and below the inguinal ligament. In countries with low- and middle-income economies, this is the most common manifestation of LGV, prevalent mainly in men, but rare in MSM. In women deep lymph nodes (iliac, perirectal, or lumbosacral) are often involved, which is related to the location of the primary lesion. Involvement of these lymph nodes manifests with hypogastric or lumbosacral pain. At this stage bacteremia may develop, as well as generalized symptoms such as fever, malaise, and arthralgia. Some patients may have manifestations associated with meningoencephalitis or, rarely, with pneumonia or hepatitis.
2. Anorectal disease (anorectal syndrome) develops as a consequence of anal mucositis in persons who have anal sexual contacts. Proctitis due to infection with C trachomatis serovars L1 to L3 is usually more severe than infection with serovars D to K. Presenting symptoms include perianal pruritus and pain, constipation, mucous or mucopurulent anal discharge, and anal bleeding. Proctitis is the most common presenting symptom of LGV in MSM in Europe. In ~25% of patients it is asymptomatic. Anal ulceration and proctocolitis may develop, followed by perirectal lymphadenitis. Abscesses, rectocutaneous fistulas, and perianal lesions (lymphorrhoids) may be present in some patients.
1. Identification of the etiologic agent:
1) Molecular tests: Nucleic acid amplification test (NAAT); the specimens for testing are discharge from the lesion, lesion swab, or aspirate from the affected lymph nodes.
2) Serologic tests should be performed if a NAAT is not available.
3) Biopsy is contraindicated due to the risk of fistula formation.
2. Other tests:
1) Proctoscopy to visualize proctitis.
2) Computed tomography (CT) of the lesser pelvis to visualize intra-abdominal abscesses.
Diagnosis is based on patient history (high-risk sexual behaviors), clinical features, and identification of the etiologic agent.
1. Inguinal LGV: Chancroid, syphilis, inguinal granuloma, inguinal hernia, lymphadenopathy of other etiology (eg, lymphatic malignancy, tuberculosis, tularemia, actinomycosis, infectious mononucleosis, cat-scratch disease).
2. Anorectal LGV: Proctitis of other etiology (eg, bacterial, protozoal, fungal), hemorrhoids, Crohn disease, ulcerative colitis, anal cancer.
1. Preferred treatment: Oral doxycycline 100 mg every 12 hours for 21 days.
2. Alternative treatment: Oral azithromycin 1 g once weekly for 3 weeks or oral erythromycin 400 mg every 6 hours for 21 days.
Every patient with diagnosed LGV should be offered specialist counseling and recommended sexual abstinence until completion of treatment and resolution of symptoms. Asymptomatic patients and contacts should also receive treatment.
1. Pharmacotherapy: Nonsteroidal anti-inflammatory drugs (NSAIDs).
2. Surgical treatment: In the secondary stage, aspiration of bubo contents reduces the risk of spontaneous rupture.
Possible complications include conjunctivitis, arthritis, pneumonia, pericarditis, and meningitis. A rare complication of the primary infection in men is lymphangitis of the dorsal penis.
In some cases permanent complications may develop after years due to fibrosis and obstruction of lymphatic channels. These include lymphedema and elephantiasis of the external genitourinary organs. The lesions are more often found in women, typically on the labia, which are swollen and undergo papillary hyperplasia.
Intestinal wall perforation and peritonitis may develop in severe anorectal disease. Anorectal syndrome may lead to permanent anal stricture, causing difficulty with defecation.
Early in the disease the prognosis is good. In patients with scarring and permanent lesions, the response to treatment is minor. Reinfections and recurrences are possible.
Immunoprophylaxis: None available.
1. Avoiding high-risk sexual contacts, using condoms.
2. Contact investigation: Obtain information about the patient’s sexual contacts from the last 3 months. Try to contact all of them to offer them proper diagnostic workup, treatment, and counseling.
3. Screening for other STIs, including gonorrhea, syphilis, HIV infection, hepatitis B, and hepatitis C.
4. Patient isolation: Not required.
5. Personal protective equipment (PPE) for medical staff: Standard.