AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Lymphogranuloma venereum (LGV) is a sexually transmitted chlamydial disease that should be a part of the differential diagnosis for any patient presenting with a genital ulcer and/or inguinal lymphadenopathy. Treatment involves the use of antibiotics to clear the infection and to prevent tertiary sequelae. The disease is an important emerging sexually transmitted disease among men who have sex with men.

Pathophysiology

Chlamydia trachomatis, an obligate intracellular organism, is the causative agent, and serotypes L1, L2, and L3 have been associated with infection. While other serotypes of C trachomatis are limited to superficial infection of mucous membranes, serotypes L1, L2, and L3 are more invasive and virulent, tending to result in systemic disease. The organism travels through the lymphatics to multiply within macrophages in regional lymph nodes. Characterization of the rate of transmission or the reservoir of C trachomatis has not been defined clearly, although asymptomatic women are believed to be a source of infection.

LGV occurs in 3 stages, the first of which has an incubation period of anywhere from 3 days to 6 weeks (10-14 d average) and is characterized by a painless genital papule, which usually disappears after a few days. The onset of the second stage occurs 2-6 weeks later and often manifests as unilateral inguinal lymphadenopathy. The third stage may occur years after the initial infection and is termed genitoanorectal syndrome.

Frequency

United States

Only 113 cases were reported to the Centers for Disease Control and Prevention in 1997. The true incidence of the disease is believed to be 400-600 cases per year.

International

LGV is most common in Southeast Asia, Africa, Central America, and the Caribbean. LGV accounts for 2-10% of genital ulcer disease in India and Africa.

Mortality/Morbidity

Complete cure is achieved by early recognition and appropriate antibiotic treatment.

Progression to the third stage of the disease can result in serious and sometimes permanent sequelae such as genital deformity, fistulas, and rectal strictures. Death is rare but may be caused by complete bowel obstruction and perforation resulting from a rectal stricture.

Race

As a cause of rectal strictures, LGV is found more commonly in blacks.

Sex

LGV is significantly more common in men than in women. Men are more likely to present with inguinal lymphadenopathy in the second stage of the disease. Women and homosexual men who engage in receptive anal intercourse are more likely to present with complications of late disease.

Age

Peak range is in individuals aged 15-40 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• The primary stage is characterized by a transient nonpainful lesion that usually remains unnoticed by the patient; therefore, it is rare for a patient to present with the early stage of the disease. Travel and sexual histories are important because LGV often is seen in people who have been sexually active in areas where the disease is endemic.
• Male patients tend to present in the second stage with painful inguinal lymphadenopathy that usually is unilateral. Constitutional symptoms, such as fever, chills, malaise, myalgias, and arthralgias, are common in this stage of the disease. Women may complain of lower abdominal or back pain because they often have involvement of deep pelvic nodes. Systemic spread occasionally can result in arthritis, pneumonitis, hepatitis, or, rarely, perihepatitis.
• The tertiary stage of the disease is termed genitoanorectal syndrome. Women are more likely to present in this stage. Symptoms include fever, pain, tenesmus, pruritus, and purulent or bloody diarrhea. These symptoms are associated with proctocolitis, abscesses, and fistulas.

Physical

• Primary stage
• • The primary lesion is a small painless papule or herpetiform ulcer on the genitalia.
  • The lesion usually heals within a few days; therefore, it is identified in only approximately 10% of patients at initial presentation.
  • When present, lesions are found most typically on the glans penis or vaginal wall.
  • An associated mucopurulent discharge may be present affecting the urethra in men and the cervix in women.
• Secondary stage
• • The most prominent physical finding at the secondary stage is unilateral painful inguinal lymphadenopathy.
  • Bilateral lymphadenopathy occurs in fewer than one third of patients.
  • The nodes most commonly involved are the horizontal group of inguinal nodes; however, the vertical inguinal and femoral nodes also may be affected.
  • A characteristic physical finding, termed the groove sign, occurs in approximately one third of patients. This sign is caused by enlargement of the nodes above and below the inguinal ligament.
  • One third of the inguinal buboes become fluctuant and rupture, while the remaining two thirds involute to form a hard nonsuppurative inguinal mass.
  • A 10:1 predominance of buboes exists in men compared to women who reach this stage of disease.
  • Women often have primary involvement of the rectum, vagina, cervix, or posterior urethra, which drain to the deep iliac or perirectal nodes; therefore, only 20-30% have the classic finding of inguinal lymphadenopathy.
• Tertiary stage
• • Physical findings at the tertiary stage include proctocolitis, perirectal abscess, fistulas, strictures, and hyperplasia of the intestinal and perirectal lymphatics (lymphorrhoids).
  • Chronic infection can result in extensive scarring with ischemia and tissue necrosis.
  • The end result can be esthiomene (elephantiasis of the female genitalia characterized by fibrotic labial thickening) in women or elephantiasis and deformation of the penis in men.

Causes

• The causal organism is C trachomatis, serotypes L1, L2, and L3; L2 is the most common.
• Risk factors include the following:
• • Unprotected sex
  • Anal intercourse
  • Sex with partners in endemic countries
  • Multiple sex partners
• Other diagnostic considerations: Causes of lymphadenopathy include sexually transmitted diseases (STDs), such as chancroid, primary and secondary syphilis, and granuloma inguinale, and nonvenereal diseases, such as cat-scratch disease, infectious mononucleosis, tuberculosis, tularemia, brucellosis, bubonic plague, lymphoma, and metastatic malignancies.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Primary lesion
Genital herpes
Primary syphilis
Chancroid

Genitoanorectal syndrome
Crohn disease
Rectal strictures resulting from carcinoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Diagnosis is hampered by the difficulty in culturing the organism. The best results have been obtained using aspirates from an involved inguinal lymph node and from bacterial typing of the culture after growth. Culture requires growth in cycloheximide-treated McCoy or HeLa cells, and even under these conditions, yields of only 30-50% are reported.
• Serologic tests also are available and produce a strong reaction by complement fixation. Tests typically are positive within 2 weeks of disease onset and have a sensitivity of 80%. The difficulty is in separating the various serotypes of Chlamydia species including those involved in conjunctivitis; however, in the appropriate clinical setting, an antibody titer of 1:64 or greater or a 4-fold increase in titer is supportive of the diagnosis. Other types of chlamydial infections rarely demonstrate a titer of greater than 1:16. Antibody titers do not correlate well with clinical severity of the disease.
• Other testing modalities include microimmunofluorescence and polymerase chain reaction (PCR). The usefulness of these methods is limited by availability.

Other Tests

• Other testing may include screening for coexistence of other STDs.
• As with all STDs, consider concomitant infections and perform screening tests.

Procedures

• Necessary procedures may include aspiration of buboes to speed healing and relieve discomfort.

Histologic Findings

Histologic findings in the lymph nodes show focal accumulations of neutrophils in necrotic foci in the early stages. Lymphocytic hyperplasia and plasma cell infiltration follow. The classic lesion of this disease is the stellate abscess and can be identified in lymph node biopsies in secondary and, occasionally, tertiary stage disease.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Recommended treatment is with doxycycline (100 mg PO bid) or erythromycin (500 mg qid). Continue treatment for 3 weeks, combined with aspiration of the lymph nodes if needed. Incision and drainage may result in nonhealing fistula formation, which can be minimized by draining involved lymph nodes from above the inguinal ligament. Symptomatic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and local heat for pain relief may be useful adjuncts.

Surgical Care

Surgery often is necessary for repair of late complications such as fistulas and strictures.

Consultations

A surgery consult may be necessary for late complications or aspiration of fluctuant nodes.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goal of pharmacotherapy is to reduce morbidity and to prevent complications.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Complications

• Complications usually arise from progression to the third stage of LGV. Scarring and local tissue destruction is the rule, with stricture and fistula formations and deformation of genitalia. Complete bowel obstruction from rectal stricture is possible.
• Systemic spread occasionally can result in arthritis, pneumonitis, hepatitis, or, rarely, perihepatitis.
• Rare systemic complications include pulmonary infection, cardiac involvement, aseptic meningitis, and ocular inflammatory disease.

Prognosis

• Prognosis is excellent if LGV is treated early; however, late complications can cause significant morbidity.

Patient Education

• Instruct patients that infection confers little or no protective immunity. Refer sexual contacts for evaluation and possible treatment. Encourage safe sex.
• For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center. Also, see eMedicine's patient education articles Sexually Transmitted Diseases and Chlamydia.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The diagnosis of LGV should not preclude a thorough search for other STDs (eg, granuloma inguinale, syphilis, chancroid) that may be cured by different treatment modalities. The use of broad-spectrum antibiotics to replace an accurate differential diagnosis and focused treatment should be discouraged.
• The diagnosis of LGV may be missed easily in women and homosexual males because they tend not to present with the classic inguinal lymphadenopathy. Careful diagnostic consideration should be used in these patient populations.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Blank S, Schillinger JA, Harbatkin D. Lymphogranuloma venereum in the industrialised world. Lancet. May 7 2005;365(9471):1607-8. [Medline].
• Bremer V, Meyer T, Marcus U, Hamouda O. Lymphogranuloma venereum emerging in men who have sex with men in Germany. Euro Surveill. Sep 20 2006;11(9):[Medline].
• Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part I. J Am Acad Dermatol. Oct 1999;41(4):511-32. [Medline].
• Burgoyne RA. Lymphogranuloma venereum. Prim Care. Mar 1990;17(1):153-7. [Medline].
• Chen CY, Chi KH, Alexander S, et al. The Molecular Diagnosis of Lymphogranuloma Venereum: Evaluation of a Real-Time Multiplex Polymerase Chain Reaction Test Using Rectal and Urethral Specimens. Sex Transm Dis. Oct 25 2006;[Medline].
• Den Hollander JG, Ossewaarde JM, de Marie S. Anorectal ulcer in HIV patients, don't forget lymphogranuloma venereum!. AIDS. Jul 2 2004;18(10):1484-5. [Medline].
• Gilleece Y, Sullivan A. Management of sexually transmitted infections in HIV positive individuals. Curr Opin Infect Dis. Feb 2005;18(1):43-7. [Medline].
• Hadfield TL, Lamy Y, Wear DJ. Demonstration of Chlamydia trachomatis in inguinal lymphadenitis of lymphogranuloma venereum: a light microscopy, electron microscopy and polymerase chain reaction study. Mod Pathol. Dec 1995;8(9):924-9. [Medline].
• Herida M, de Barbeyrac B, Sednaoui P, et al. Rectal lymphogranuloma venereum surveillance in France 2004-2005. Euro Surveill. Sep 20 2006;11(9):[Medline].
• Joseph AK, Rosen T. Laboratory techniques used in the diagnosis of chancroid, granuloma inguinale, and lymphogranuloma venereum. Dermatol Clin. Jan 1994;12(1):1-8. [Medline].
• Kellock DJ, Barlow R, Suvarna SK, et al. Lymphogranuloma venereum: biopsy, serology, and molecular biology. Genitourin Med. Oct 1997;73(5):399-401. [Medline].
• Klint M, Lofdahl M, Ek C, et al. Lymphogranuloma venereum prevalence in Sweden among men who have sex with men and characterization of Chlamydia trachomatis ompA genotypes. J Clin Microbiol. Nov 2006;44(11):4066-71. [Medline].
• Klotz SA, Drutz DJ, Tam MR, Reed KH. Hemorrhagic proctitis due to lymphogranuloma venereum serogroup L2. Diagnosis by fluorescent monoclonal antibody. N Engl J Med. Jun 30 1983;308(26):1563-5. [Medline].
• Martin DH, Mroczkowski TF. Dermatologic manifestations of sexually transmitted diseases other than HIV. Infect Dis Clin North Am. Sep 1994;8(3):533-82. [Medline].
• Martin IM, Alexander SA, Ison CA, et al. Diagnosis of lymphogranuloma venereum from biopsy samples. Gut. Oct 2006;55(10):1522-3. [Medline].
• Papagrigoriadis S, Rennie JA. Lymphogranuloma venereum as a cause of rectal strictures. Postgrad Med J. Mar 1998;74(869):168-9. [Medline].
• Rosen T, Brown TJ. Cutaneous manifestations of sexually transmitted diseases. Med Clin North Am. Sep 1998;82(5):1081-104, vi. [Medline].
• Simms I, Ward H, Martin I, et al. Lymphogranuloma venereum in Australia. Sex Health. Sep 2006;3(3):131-3. [Medline].
• Sternberg SJ. The penis. Diagn Surg Pathol. 1999;2(3):2039-40.
• Sturm PD, Moodley P, Govender K, et al. Molecular diagnosis of lymphogranuloma venereum in patients with genital ulcer disease. J Clin Microbiol. Jun 2005;43(6):2973-5. [Medline].
• Trager JD. Sexually transmitted diseases causing genital lesions in adolescents. Adolesc Med Clin. Jun 2004;15(2):323-52. [Medline].
• Van de Laar MJ. The emergence of LGV in Western Europe: what do we know, what can we do?. Euro Surveill. Sep 20 2006;11(9):[Medline].
• Weir E. Lymphogranuloma venereum in the differential diagnosis of proctitis. CMAJ. Jan 18 2005;172(2):185. [Medline].
• Workowski KA, Berman SM, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. Aug 4 2006;55(RR-11):1-94. [Medline].

Article Last Updated: Feb 28, 2007