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 an uncommon sexually transmitted disease (STD) caused by Chlamydia trachomatis. This condition is characterized by extremely painful inguinal lymphadenopathy.

Pathophysiology

C trachomatis is an obligate intracellular bacterium. Of the 15 known clinical serotypes, only the L1, L2, and L3 serotypes cause LGV. These serotypes are more virulent and invasive compared to other chlamydial serotypes. Infection occurs after direct contact with the skin or mucous membranes of an infected partner. The organism does not penetrate intact skin. The organism then travels by lymphatics to regional lymph nodes, where they replicate within macrophages and elicit systemic disease. While transmission is predominantly sexual, cases of transmission through laboratory accidents, fomites, and nonsexual contact have been reported.

The L2b serovar may have been identified to play a more important role than previously expected. After the diagnosis of 92 cases of LGV in the Netherlands among men who have had sex with men, Schachter evaluated samples obtained from rectal swabs between 1979 and 1985 from patients infected with HIV in San Francisco and between 2000 and 2005 in Amsterdam. The study revealed the same serotype circulating among patients with HIV and LGV 20-25 years ago. This indicates the L2b serovar has been present and unrecognized for many years.

LGV occurs in 3 stages. The first stage, which is often unrecognized, consists of a rapidly healing, painless genital papule or pustule. The second stage, consisting of painful inguinal lymphadenopathy, occurs 2-6 weeks after the primary lesion. The third stage, which is more common in women, may occur many years after the original infection and is characterized by proctocolitis.

Frequency

United States

Rates of LGV have steadily declined since 1972, with 113 known cases reported in 1997. The true incidence is not known because LGV is not a reported sexually transmitted disease. In November 2004, the CDC began offering assistance to test for LGV in the United States. Between November 2004 and January 2006, LGV was identified in 180 specimens, with 27 specimens identified as being obtained from homosexual males.

International

LGV is an uncommon disease, although it may account for 2-10% of patients with genital ulcer disease in selected areas of India and Africa. The disease is most commonly found in areas of the Caribbean, Central America, Southeast Asia, and Africa. Historically rare in Europe, a cluster of 92 cases was identified in the Netherlands between 2003 and 2004, where fewer than 5 cases are usually reported yearly. In many countries, active surveillance for LGV began in 2004 as a result of the increased number of cases being identified.

Mortality/Morbidity

• With appropriate treatment, the disease is easily eradicated. Death is a rare complication but could possibly result from a small bowel obstruction or perforation secondary to rectal scarring.
• Morbidity is common, especially during the third stage of the disease, and includes such conditions as proctocolitis, perirectal fissures, abscesses, strictures, and rectal stenosis. A chronic inflammatory response may lead to hyperplasia of the intestinal and perirectal lymphatics, causing lymphorrhoids, which are similar to hemorrhoids. Strictures and fistulous tracts may lead to chronic lymphatic obstruction, resulting in elephantiasis, thickening or fibrosis of the labia, and edema or gross distortion of the penis and scrotum. Reports show an association between adenocarcinoma (primarily rectal adenocarcinoma) and chronic untreated LGV.

Race

In North America and Europe, most reported cases of LGV have been identified among white males infected with HIV who acquired the condition after having sex with other men after travel or living in endemic areas, and typically after having multiple anonymous sexual contacts.

Sex

LGV is an STD and probably affects both sexes equally, although it is more commonly reported in men. This predilection may be because early manifestations of LGV are more apparent in men and are thus diagnosed more readily. Men typically present with the acute form of the disease, whereas women often present later, after developing complications from late disease.

• Most cases have been identified among white HIV-positive men who have sex with men presenting with proctitis.

Age

LGV may affect any age but has a peak incidence in the sexually active population aged 15-40 years.

CLINICAL

Section 3 of 10  

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

History

The clinical course of LGV consists of the following stages:

• First stage (primary LGV)
• • This stage occurs 3-30 days after inoculation.
  • Primary LGV begins as a small, painless papule or pustule that may erode to form a small, asymptomatic herpetiform ulcer that usually heals rapidly without scarring.
  • The most common sites of infection for men include the coronal sulcus, prepuce, glans, and scrotum. Rarely, symptoms of urethritis occur.
  • The most common sites of infection in women include the posterior vaginal wall, posterior cervix, fourchette, and vulva.
  • The initial lesion, especially in women, often goes unnoticed by the patient.
• Second stage (secondary LGV)
• • Secondary LGV begins 2-6 weeks after the primary lesion.
  • This second stage consists of painful regional lymphadenopathy (usually in the inguinal and/or femoral lymph nodes).
  • Painful, swollen lymph nodes coalesce to form buboes, which may rupture in as many as one third of patients. Those that do not rupture harden, then slowly resolve.
  • Inguinal lymphadenopathy occurs in only 20-30% of females with LGV; they more typically have involvement of the deep iliac or perirectal nodes and may only present with nonspecific back and/or abdominal pain.
  • This stage is when most men present and are diagnosed; most women are not diagnosed in this stage because of their lack of inguinal lymphadenopathy.
  • Constitutional symptoms associated with the second stage include fever, chills, myalgias, and malaise.
  • Systemic spread may lead to the following conditions:
  • • Arthritis
    • Ocular inflammatory disease
    • Cardiac involvement
    • Pulmonary involvement
    • Aseptic meningitis
    • Hepatitis or perihepatitis
• Third stage (tertiary LGV)
• • Tertiary LGV is termed genitoanorectal syndrome.
  • This condition is more common in women, secondary to their lack of symptoms during the first two stages.
  • Rectal involvement is more common in men who have sex with men and in women who practice anal-receptive intercourse.
  • Tertiary LGV is characterized by proctocolitis.
  • Symptoms include the following conditions:
  • • Malaise
    • Weight loss
    • Bloody purulent discharge
    • Fever
    • Rectal pain
    • Tenesmus

Physical

Large fluctuant buboes or any otherwise unexplained perianal deformity in a young female should suggest a diagnosis of LGV.

• First stage (primary LGV)
• • The initial lesion is usually a small, unnoticed painless papule, shallow ulcer, or herpetiform lesion in the genital area.
  • Initial lesions may be differentiated from the more common herpetic lesions by the lack of pain associated with the lesion. Differentiation from a syphilitic chancre is more problematic and requires serologic testing.
• Second stage (secondary LGV)
• • Secondary LGV is characterized by painful lymph nodes (usually unilateral) known as buboes.
  • Enlargement of the inguinal nodes above and the femoral nodes below the inguinal ligament leads to the classic groove sign, which is observed in one third of affected men.
  • Inguinal lymphadenopathy results from a primary lesion of the anterior vulva, penis, or urethra.
  • Perirectal or pelvic lymphadenopathy results from a primary lesion involving the posterior vulva, vagina, or anus.
  • Affected nodes often coalesce and form abscesses, which can rupture and form sinus tracts.
• Third stage (tertiary LGV)
• • Tertiary LGV most often manifests in women.
  • Patients initially develop proctocolitis.
  • Patients may present with perirectal fistulas, abscesses, strictures, and rectal stenosis.
  • Hyperplasia of intestinal and perirectal lymphatics may form lymphorrhoids, which are similar to hemorrhoids.
  • Patients may develop strictures and fistulous tracts secondary to repeated tissue scarring and repair.
  • Enlargement, thickening, and fibrosis of the labia may occur in women, a condition termed esthiomene.
  • Chronic lymphatic obstruction may lead to elephantiasis of the genitals.
  • Penile and scrotal edema and distortion have been termed saxophone penis.

Causes

The L1, L2, and L3 serovars of C trachomatis cause LGV. Risk factors include residing in or visiting endemic areas, practicing anal-receptive intercourse, eschewing condoms, and working in the commercial sex trade.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Granuloma inguinale
Cancer
Hodgkin disease
Inflammatory proctocolitis
Mycobacterial infection
Fungal infection

WORKUP

Section 5 of 10  

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

Lab Studies

• Diagnosis is based primarily on clinical findings, with increasing evidence supporting the use of nucleic acid amplification tests (NAATs) for confirmation. Serologic testing is problematic because of the difficulty in culturing the organism and cross-reactivity of the many different serotypes.
• Needle aspiration of an involved bubo is the best method to obtain tissue for culture.
• Culture of C trachomatis, while definitive diagnostically, is technically demanding and expensive and yields an isolate only 30% of the time.
• Because of its systemic nature, the disease produces a strong immunologic response that is readily evident on complement fixation testing.
• • Cross-reactivity between various chlamydial infections occurs on complement fixation testing.
  • Chlamydial urethritis, cervicitis, or conjunctivitis rarely produces titers greater than 1:16. LGV titers are usually more than 1:1024.
  • A complement fixation titer greater than 1:64, when coupled with the appropriate clinical scenario, is considered diagnostic of LGV.
  • Immunofluorescent testing with monoclonal antibodies and polymerase chain reaction (PCR) testing are also reported to be effective; however, these tests are not widely available for commercial use.
  • NAATs have shown significant promise in revealing the presence of Chlamydia. Several commercially available NAATS used to identify the presence of Chlamydia in urine demonstrated an increased sensitivity and specificity that ranged from 96-100% and 99.1-100%, respectively.

Procedures

• Needle aspiration of involved buboes may be performed to ease discomfort or to obtain tissue for culture.

Histologic Findings

Histologic findings of lymph node biopsies performed in the second and third stages of the disease typically reveal stellate abscesses.

TREATMENT

Section 6 of 10  

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

Medical Care

The complete treatment of patients with LGV includes appropriate antimicrobial coverage and drainage of infected buboes.

• The recommended medical treatment for LGV involves one of the following antibiotic regimens:
• • Doxycycline 100 mg PO bid for 21 d
  • Erythromycin base 500 mg PO qid for 21 d

Surgical Care

Needle aspiration or incision and drainage of involved inguinal nodes may be required for pain relief and prevention of ulcer formation. Some of the late complications of the third stage of LGV may require surgical repair.

Consultations

Surgical consultation for lymphadenopathy is generally not required unless extensive buboes require further exploration. For tertiary disease, appropriate surgical consultation is indicated.

Activity

No restrictions to physical activities are required; however, patients should abstain from sexual contact until the infection resolves completely.

MEDICATION

Section 7 of 10  

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

The goal of therapy is to eradicate the organism.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Totally eradicate the causative organism or organisms.

FOLLOW-UP

Section 8 of 10  

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

Further Outpatient Care

• For patients who have had incision and drainage of buboes, appropriate outpatient follow-up care may be required to ensure complete healing and to prevent secondary infections.

Deterrence/Prevention

• Patients, especially those traveling to endemic areas, should be counseled about safe-sex practices, including condom use. Advise the patient to refrain from intercourse with high-risk individuals.
• Inform patients that recovery from infection does not confer immunity against future infection.

Complications

• Bubo rupture may lead to fistulas and sinus tracts. This complication typically occurs during the first stage (primary LGV) of infection.
• Proctocolitis may lead to fissures, fistulas, abscess, scarring, and strictures.

Prognosis

• With prompt and appropriate antibiotic therapy, the prognosis is excellent and patients typically make a full recovery.
• Patients must be informed that reinfection and relapses may occur.

Patient Education

• Inform patients how to avoid high-risk sexual activities by using condoms and avoiding sexual intercourse with high-risk sexual partners.
• 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

• Failure to consider the diagnosis
• Failure to screen for HIV, herpes simplex virus (HSV), and syphilis

Special Concerns

• Genital elephantiasis is a medical condition that occurs primarily in tropical environments. Genital elephantiasis is primarily due to filariasis infection. A small number of cases develop secondary to bacterial sexually transmitted infections such as LGV and donovanosis, while other causes include tuberculosis, malignancies, and dermatologic conditions. Although rarely seen in developed countries, this must be considered in patients returning from endemic areas.

REFERENCES

Section 10 of 10

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

• Benson PAS, Hergenroeder AC. Bacterial Sexually Transmitted Infections in Gay, Lesbian, and Bisexual Adolescents: Medical and Public Health Perspectives. Seminars Ped Inf Dis. 2005;16:181-191. [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].
• Burckhardt F. What is the impact of change in diagnostic test method on surveillance data trends in Chlamydia trachomatis infection?. Sex Transm Infect. 2006;82:24-30.
• CDC. Lymphogranuloma venereum among men who have sex with men--Netherlands, 2003-2004. MMWR Morb Mortal Wkly Rep. 2004;53:985-988. [Medline].
• Czelusta A, Yen-Moore A, Van der Straten M, et al. An overview of sexually transmitted diseases. Part III. Sexually transmitted diseases in HIV-infected patients. J Am Acad Dermatol. Sep 2000;43(3):409-32; quiz 433-6. [Medline].
• Fenton KA, Imrie J. Increasing Rates of Sexually Transmitted Disease in Homosexual Men in Western Europe and the United States: Why?. Inf Dis Clin North Am. 2005;19:311-331.
• Gupta S, Ajith C, Kanwar AJ. Genital elephantiasis and sexually transmitted infections - revisited. Int J STD AIDS. 2006;17:157-165.
• Hawkes S, Hart G. The sexual health of travelers. Infect Dis Clin North Am. Jun 1998;12(2):413-30. [Medline].
• Jones, RB, Batteiger, BE. Introduction to Chlamydial Diseases. In: In Mandell, G. Principles and practice of infectious diseases. 5th ed. Churchill-Livingstone;2000: 1989-90.
• Levine, W, Schmid, G. Approach to sexually transmitted diseases and genital tract infections. In: Kelley, W. Textbook of internal medicine, 3d ed. 3rd ed. Lippincott-Raven;1997: 1602-4.
• McDonald LL, Stites PC, Buntin DM. Sexually transmitted diseases update. Dermatol Clin. Apr 1997;15(2):221-32. [Medline].
• Quirk M. LGV: not new disease, but newly detected. Lancet Inf Dis. 2006;6:195.
• Rosen T, Brown TJ. Genital ulcers. Evaluation and treatment. Dermatol Clin. Oct 1998;16(4):673-85, x. [Medline].
• Schachter J. Confirming positive results of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis: all NAATs are not created equal. J Clin Microbiol. 2005;43:1372-1373.

Article Last Updated: May 23, 2006