Dermatologic Manifestations of Lymphogranuloma Venereum 

Updated: May 10, 2018
Author: Jose A Plaza, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

Lymphogranuloma venereum (LGV) is a primarily cutaneous, and sometimes systemic, sexually transmitted disease (STD), which primarily affects lymphatic tissue of the groin. LGV is caused by unique serotypes L1, L2, and L3 of Chlamydia trachomatis. LGV occurs only sporadically in North America, but it is endemic in many parts of the developing world. An outbreak of LGV proctocolitis has been reported among homosexual men in North America and Europe, and many of these individuals were co-infected with HIV.[1, 2, 3, 4, 5, 6, 7, 8, 9]

See the image below.

Lymphogranuloma venereum is caused by the invasive Lymphogranuloma venereum is caused by the invasive serovars L1, L2, or L3 of Chlamydia trachomatis. This young adult experienced the acute onset of tender, enlarged lymph nodes in both groins. Courtesy of Wikimedia Commons (Herbert L. Fred, MD, and Hendrik A. van Dijk, http://cnx.org/content/m14883/latest/).

Pathophysiology

Lymphogranuloma venereum (LGV) is caused by C trachomatis, an obligate intracellular pathogen (ie, the bacterium lives within human cells), and strains L1, L2, and L3 have been associated with infection. LGV is primarily a disease of lymphatic tissue. Because Chlamydia species cannot traverse the intact epithelial barrier, access to lymphatic vessels is gained through microtrauma in the skin or mucous membranes. The pathogen then enters the draining lymph nodes, causing lymphangitis or lymphadenitis. The causal pathologic process involves thrombolymphangitis and perilymphangitis and the consequent spread of the inflammatory reaction from the affected lymph nodes to surrounding tissues.

Etiology

The causal organism of lymphogranuloma venereum (LGV) is C trachomatis, serotypes L1, L2, and L3; L2 is the most common.

Risk factors include the following:

  • Visiting endemic areas

  • Engaging in unprotected sex

  • Engaging in anal intercourse

  • History of multiple sex partners

Epidemiology

Frequency

United States

Lymphogranuloma venereum (LGV) is rare in the United States, and the true incidence is not known.

International

Lymphogranuloma venereum (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.[10]

Race

Lymphogranuloma venereum (LGV) is found more commonly in blacks.

Sex

Lymphogranuloma venereum (LGV) is significantly more common in men than in women.

Age

The peak range for lymphogranuloma venereum (LGV) is in individuals aged 15-40 years.

Prognosis

Prognosis is excellent if lymphogranuloma venereum (LGV) is treated early; however, late complications can cause significant morbidity. Progression to the third phase of LGV can result in serious and permanent sequelae such as genital deformity, fistulas, and rectal strictures, among others. Complete cure is achieved by early recognition of LGV and appropriate antibiotic treatment.

Patient Education

Instruct patients that infection confers little or no protective immunity. Refer sexual contacts for evaluation and possible treatment. Encourage safe sex.

For patient education resources, visit the Sexual Health Center. Also, see the patient education articles Sexually Transmitted Diseases and Chlamydia.

 

Presentation

History

Clinical manifestations of lymphogranuloma venereum (LGV) vary depending on the sex of the patient, his or her sexual practices (vaginal or anal intercourse), and disease stage. Immunosuppression also seems to result in more severe or prolonged symptoms. LGV is a chronic and progressively destructive venereal disease and is divided into primary, secondary, and tertiary stages.

Primary stage

The primary stage of LGV is characterized by transient nonpainful papules, ulcers, or herpetiform erosions that may manifest after an incubation period of 3–12 days. The lesion usually remains unnoticed by the patient. 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. Occasionally patients may have balanitis, balanoposthitis, cervicitis, salpingitis, or parametritis. The primary stage of disease is observed in less than 30% of heterosexual men and less frequently in women.

Secondary stage

The symptoms seen in the secondary stage of LGV result from the spread of inflammation to regional lymphatic tissue. Depending on the entry site, inguinal lymphadenopathy is the classic manifestation of the secondary stage of LGV, and it occurs 2-6 weeks after the onset of primary symptoms. Patients tend to present with painful inguinal lymphadenopathy that usually is unilateral. In one third of patients, the affected lymph node ruptures spontaneously after abscessing and developing areas of necrosis. Extragenital primary manifestations also involve regional lymph nodes with lymphadenopathy and the formation of buboes. Constitutional symptoms, such as fever, chills, malaise, myalgias, and arthralgias, are common in this stage of the disease. Systemic spread occasionally can result in arthritis, pneumonitis, or hepatitis.

Tertiary stage

Given the persistence of the pathogen, LGV reaches the tertiary stage in 25% of untreated patients. The chronic inflammatory reaction can lead to fistulas, strictures, rectal stenoses, and lymphedema. As a result of inguinal lymphadenopathy and chronic lymphedema with sclerosing fibrosis, elephantiasis may occur, affecting the penis or scrotum or the labia majora or clitoris. Additionally, other symptoms include fever, pain, tenesmus, pruritus, and purulent or bloody diarrhea.

Physical Examination

Primary stage of lymphogranuloma venereum (LGV)

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.

Secondary stage of LGV

The most prominent physical finding at the secondary stage is unilateral painful inguinal lymphadenopathy.

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 with 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 of LGV

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.

Complications

Complications usually arise from progression to the third stage of lymphogranuloma venereum (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.

 

DDx

Diagnostic Considerations

The diagnosis of lymphogranuloma venereum (LGV) should not preclude a thorough search for other sexually transmitted diseases (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.

Primary lesion considerations include the following:

  • Genital herpes
  • Primary syphilis
  • Chancroid
  • Genitoanorectal syndrome
  • Rectal strictures resulting from carcinoma

Differential Diagnoses

 

Workup

Laboratory Studies

Lymphogranuloma venereum (LGV) 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 for LGV 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 an LGV 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 for LGV include microimmunofluorescence and polymerase chain reaction (PCR).[11] The usefulness of these methods is limited by availability.[12, 13, 14]

Other Tests

Other testing in lymphogranuloma venereum (LGV) may include screening for coexistence of other sexually transmitted diseases (STDs). As with all STDs, consider concomitant infections and perform screening tests.

Procedures

Necessary procedures for lymphogranuloma venereum (LGV) may include aspiration of buboes to speed healing and relieve discomfort.

Histologic Findings

The histologic features of the initial lymphogranuloma venereum (LGV) genital papule are generally nonspecific (ulceration and granulation tissue in dermis). In the lymph nodes, stellate abscesses with surrounding epithelioid cells and macrophage giant cells represent the characteristic lesion. Special stains do not demonstrate the infecting organism in skin or lymph nodes. Tissue cultures of a skin lesion or lymph node are necessary to demonstrate the infection.

 

Treatment

Medical Care

The treatment of choice for lymphogranuloma venereum (LGV) is doxycycline (100 mg orally bid for 21 d).[15, 16] Although azithromycin is effective against other chlamydial strains and may prove to be effective against infection with LGV serovars, no controlled treatment trials support the use of azithromycin treatment for LGV. 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.

Immunocompromised persons, such as those with HIV infection, should receive the same treatment as immunocompetent persons; however, given the lack of data, patients with HIV infection and other immunocompromising conditions should be followed closely to assess resolution of symptoms.[17]

Surgical Care

Surgery often is necessary for repair of late lymphogranuloma venereum (LGV) complications such as fistulas and strictures.

Consultations

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

 

Medication

Medication Summary

The goal of pharmacotherapy for lymphogranuloma venereum (LGV) is to reduce morbidity and to prevent complications.

Antibiotics

Class Summary

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

Doxycycline (Doryx, Bio-Tab)

Doxycycline inhibits protein synthesis in bacteria by binding to the 30S and possibly the 50S ribosomal subunits.

Erythromycin base (Erythrocin)

Erythromycin base inhibits RNA-dependent protein synthesis, possibly by stimulating the dissociation of peptidyl t-RNA from ribosomes. This inhibits bacterial growth (ie, erythromycin is bacteriostatic, not bacteriocidal). In children, consider age, weight, and severity of infection to determine proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, the dose may be doubled.