para>May be acquired perinatally from the birth canal; congenital transmission is not known to occur.
ETIOLOGY AND PATHOPHYSIOLOGY
- 3 of the 15 known strains of C. trachomatis, (serovars L1, L2, L3) cause LGV. Strains of C. trachomatis that cause urethritis infect only squamocolumnar cells; LGV strains are more invasive, replicate in macrophages, and can spread to lymphatic tissue at the site of infection, leading to systemic illness.
- Tissue damage occurs from lymphatic inflammation and obstruction (1).
RISK FACTORS
- HIV-positive (particularly HIV-positive MSM) (2,3)
- Unprotected intercourse
- Multiple sexual partners
- Anal intercourse (2)
- Residing in tropical or developing countries
- Uncircumcised penis
GENERAL PREVENTION
Condoms may provide some protection against genital " anogenital transmission but have no impact on transmission between other sites (1)[C].
COMMONLY ASSOCIATED CONDITIONS
HIV, gonorrhea, chlamydia (cervicitis, urethritis), hepatitis B, hepatitis C, herpes simplex virus, syphilis
DIAGNOSIS
History, physical examination, and diagnostic exclusion are important factors in the diagnosis of LGV.
HISTORY
Recent unprotected anogenital intercourse (3- to 30-day incubation period), often with MSM (4)
PHYSICAL EXAM
Three stages
- Primary: Superficial painless lesions (papules, vesicles, ulcers, or erosions) that appear primarily on the external genitalia, in the area of inoculation, 3 to 30 days after exposure. These resolve in a few days, leaving no scar.
- Secondary: inguinal syndrome (bubonic stage) or hemorrhagic proctitis (following rectal intercourse)
- Prodrome of fever, chills, headache, myalgias, malaise
- Inguinal syndrome: Regional lymphadenopathy, usually unilateral (may include femoral lymph nodes), develops 2 to 6 weeks after primary stage. Buboes begin as firm, tender, enlarged, matted lymph nodes and eventually involve the overlying skin, causing erythema, adhesions, and severe groin pain. Within 1 to 2 weeks, the buboes may become fluctuant and rupture, relieving the pain but leaving fistulas to drain or involute and form inguinal masses. Drainage patterns in women can affect deep pelvic lymph nodes causing pelvic, abdominal, and lower back pain.
- Proctitis: Anal pruritus and mucoid rectal discharge, multiple discrete superficial ulcerations with irregular borders, rectal pain, and tenesmus (5); discharge and lesions may be seen on anoscopy or endoscopy.
- Tertiary: anogenital stage
- Lymphatic obstruction and scarring may lead to lymphedema of the genitals (elephantiasis); it may produce perianal lymphoid growths resembling hemorrhoids.
- Severe inflammation of genitalia or anorectal canal
- Perirectal abscesses, rectal strictures, or stenosis
- Ischiorectal, rectovaginal, and anal fistulas (1)
DIFFERENTIAL DIAGNOSIS
- Genital herpes
- Chancroid
- Beh §et syndrome
- Abscess
- Syphilis
- Granuloma inguinale (Donovanosis)
- HIV
- Lymphoma
- Malignancy
- Gonococcal and non-LGV chlamydial proctitis
- Inflammatory bowel disease
- Bartonella henselae
DIAGNOSTIC TESTS & INTERPRETATION
- Swabs obtained from infected lesions (at the ulcer base), rectal mucosa, and from aspirates of affected lymphatic tissue (bubo) may be examined by nucleic acid amplification testing (NAAT), culture, or direct immunofluorescence (1,3).
- NAAT is the first line since it has the highest sensitivity (>90%) and specificity (>99%) for detecting C. trachomatis and LGV (6)[A]. NAAT can also be used on a urethral swab or urine sample but this will not detect anorectal disease and should not be used if anorectal disease is suspected.
- Once C. trachomatis is identified by NAAT, a second step (usually PCR) will identify the serogroup.
- Culturing the base of the lesion and bubo aspirates can take 5 to 7 days to result; sensitivity is 75 " 85%.
- Direct immunofluorescence can be performed if NAAT is not available; sensitivity is 75 " 85% (1).
Initial Tests (lab, imaging)
Follow-Up Tests & Special Considerations
- Test for concomitant STIs: HIV, gonorrhea, chlamydia (cervicitis, urethritis), hepatitis B, hepatitis C, herpes simplex virus, syphilis
- NAATs are not approved for extragenital sites, but multiple studies support the validity of testing rectal samples (1,3).
- With cultures, genotyping is necessary to differentiate LGV from other C. trachomatis strains.
- Imaging may be necessary to evaluate for complications or to exclude other diagnoses.
- CT scan can assess for deep lymphatic involvement or abscess formation.
- Barium enema or endoscopy may demonstrate strictures or fistulas.
- Lymphocytosis, monocytosis, and/or macrocytosis can be seen on a complete blood count.
- An elevated erythrocyte sedimentation rate may be present (1).
TREATMENT
Oral antibiotics administered in the ambulatory setting are effective in most uncomplicated cases.
GENERAL MEASURES
Avoid all sexual contact once lesions appear and until test of cure is negative to decrease transmission risk.
MEDICATION
Consider treating empirically for LGV if specific LGV diagnostic testing is not available for patients with a compatible clinical syndrome (e.g., proctocolitis, genital ulcer disease with lymphadenopathy) (3)[A].
First Line
Doxycycline 100 mg PO BID for 21 days (7)[A]. For chronic or relapsing cases (as may be seen with HIV infected individuals): Consider longer course of therapy or alternate antibiotics.
Second Line
- Erythromycin base 500 mg PO 4 times daily for 21 days (3)[A]
- Azithromycin (1 g once weekly for 3 weeks) and the fluoroquinolones may be effective based on their activity against chlamydia, but further studies are needed (3)[A].
General Considerations
Asymptomatic partners who have had sexual contact with an individual diagnosed with LGV within 60 days of symptom onset should be evaluated and treated for chlamydial infection (doxycycline 100 mg PO BID for 7 days or azithromycin 1 g orally as a single dose) (3)[A].
Pregnancy Considerations
ISSUES FOR REFERRAL
Surgical intervention for complications associated with LGV may be warranted after antibiotic treatment has been initiated/completed.
SURGERY/OTHER PROCEDURES
In the bubonic stage, nodes should be aspirated through intact, healthy skin for diagnostic purposes. Surgical intervention may be warranted for fistulas, strictures, and scar revision.
INPATIENT CONSIDERATIONS
Inpatient treatment is rarely necessary.
Admission Criteria/Initial Stabilization
Unable to tolerate oral antibiotics, ambulate, or perform self-care due to pain or other complications
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patients should be observed until symptom-free. Test of cure is recommended 3 to 5 weeks after treatment.
Patient Monitoring
- Fever and buboes usually respond within 1 to 2 days after starting antibiotics. For persistent fever or malaise, monitor closely for complications such as an abscess or superinfection (1).
- Treatment has no effect on existing scar tissue; therefore, monitor for surgical complications.
PATIENT EDUCATION
The patient should be counseled about STIs and safer sex practices. Patients should abstain from intercourse or other sexual contact until treatment is complete with test of cure performed.
PROGNOSIS
- Improved by early treatment
- Complete resolution of symptoms if treated before scarring
- Reinfection/inadequate treatment may result in relapse (8).
COMPLICATIONS
- Scarring, including possible urethral or bowel obstruction, persistent rectovaginal fistula, or gross destruction of the anal canal, anal sphincter, or perineum may occur. Repair of such complications, as well as relief of lymphatic obstruction, such as genital elephantiasis, are the more common surgical indications (1). Mild rectal strictures can occasionally be dilated on an outpatient basis.
- Squamous cell carcinoma has been associated with LGV.
REFERENCES
11 Ceovic R, Gulin SJ. Lymphogranuloma venereum: diagnostic and treatment challenges. Infect Drug Resist. 2015;8:39 " 47.22 Pallawela SN, Sullivan AK, Macdonald N, et al. Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K. Sex Transm Infect. 2014;90(4):269 " 274.33 Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1 " 137.44 R Άnn M, Hughes G, Simms I, et al. Challenges presented by re-emerging sexually transmitted infections in HIV positive men who have sex with men: an observational study of lymphogranuloma venereum in the UK. J AIDS Clin Res. 2014;5(8):1000329.55 Heiligenberg M, Verweij SP, Speksnijder AG, et al. No evidence for LGV transmission among heterosexuals in Amsterdam, the Netherlands. BMC Res Notes. 2014;7:355.66 Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae " 2014. MMWR Recomm Rep. 2014;63(RR-02):1 " 19.77 R Άnn MM, Ward H. The association between lymphogranuloma venereum and HIV among men who have sex with men: systematic review and meta-analysis. BMC Infect Dis. 2011;11:70.88 Kong FY, Hocking JS. Treatment challenges for urogenital and anorectal Chlamydia trachomatis. BMC Infect Dis. 2015;15:293.
ADDITIONAL READING
- Mart -Pastor M, Garc a de Olalla P, Barber ‘ MJ, et al. Epidemiology of infections by HIV, syphilis, gonorrhea and lymphogranuloma venereum in Barcelona City: a population-based incidence study. BMC Public Health. 2015;15:1015.
- Rodriguez-Dominguez M, Gonzalez-Alba JM, Puerta T, et al. High prevalence of co-infections by invasive and non-invasive Chlamydia trachomatis genotypes during the lymphogranuloma venereum outbreak in Spain. PLoS One. 2015;10(5):e0126145.
CODES
ICD10
A55 Chlamydial lymphogranuloma (venereum)
ICD9
099.1 Lymphogranuloma venereum
SNOMED
Lymphogranuloma venereum (disorder)
CLINICAL PEARLS
- Consider high-risk populations when deciding to screen patients: MSM, HIV-positive.
- In MSM presenting with colorectal symptoms (tenesmus, constipation, anal discharge, and weight loss), consider LGV proctocolitis in the differential diagnosis; it can occasionally be misdiagnosed as inflammatory bowel disease (1)[C].
- When LGV is diagnosed, obtain further STI testing.
- Treat partners.