eMedicine Specialties > Dermatology > Bacterial Infections

Lymphogranuloma Venereum

Jose Antonio Plaza, MD, Director of Dermatopathology, Department of Pathology, Froedtert Hospital; Assistant Professor, Department of Pathology, Section of Dermatopathology, Medical College of Wisconsin
Victor G Prieto, MD, PhD, Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Updated: Sep 2, 2009

Introduction

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. A recent 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 ]}

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.

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.

Mortality/Morbidity

Progression to the third phase of lymphogranuloma venereum (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.

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.

Clinical

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.

• 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.
• 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.
• 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

• 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.

Causes

• 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

Differential Diagnoses

Catscratch Disease
Chancroid
Granuloma Inguinale (Donovanosis)
Syphilis

Other Problems to Be Considered

Primary lesion
Genital herpes
Primary syphilis
Chancroid

Genitoanorectal syndrome
Crohn disease
Rectal strictures resulting from carcinoma

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). The usefulness of these methods is limited by availability.^{[6,7,8 ]}

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). 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.^{[9 ]}

The New York State Department of Health clinical guideline summary, Lymphogranuloma Venereum (LGV), may be of interest.^{[10 ]}

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.

A clinical guideline summary from the US Preventive Services Task Force, Behavioral counseling to prevent sexually transmitted infections: U.S. Preventive Services Task Force recommendation statement, may be helpful.^{[11 ]}

Medication

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

Antibiotics

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

Doxycycline (Doryx, Bio-Tab)

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

Dosing

Adult

100 mg PO bid for 21 d (full course)

Pediatric

<8 years: Not recommended
>8 years: 4.4 mg/kg PO qd or divided bid on day 1 then 2.2-4.4 mg/kg/d PO qd or divided bid; not to exceed 200 mg/d

Interactions

Antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate can decrease bioavailability; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; monitor prothrombin activity in patients taking both medications concurrently; coadministration of tetracyclines can decrease pharmacologic effectiveness of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Use in last half of pregnancy and in children <8 y may cause permanent dental discoloration; in conjunction with prolonged exposure to sunlight or tanning equipment, can cause photosensitivity reaction; lower dosing in patients with renal impairment and, if therapy is prolonged, consider drug serum level determinations; never administer outdated tetracyclines because degradation products of tetracyclines are highly nephrotoxic and can cause Fanconilike syndrome

Erythromycin base (Erythrocin)

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 bid dosing is desired, half total daily dose may be taken q12h. For more severe infections, dose may be doubled.

Dosing

Adult

500 mg PO qid for 21 d

Pediatric

30-50 mg/kg/d PO divided q6-8h

Interactions

Theophylline, digoxin, carbamazepine, and cyclosporine toxicity may increase when administered concurrently; may potentiate anticoagulant effects of warfarin
May significantly alter metabolism of nonsedating antihistamines and cause serious adverse cardiovascular events; concurrent use of lovastatin and erythromycin may cause rhabdomyolysis in patients who are seriously ill; may increase serum theophylline levels and toxicity; concomitant administration of digoxin may result in elevated serum digoxin levels; coadministration can increase effects of anticoagulants; concurrent use with ergotamine or dihydroergotamine has been associated with acute ergot toxicity; erythromycin may decrease clearance of triazolam and midazolam; erythromycin in patients taking other drugs metabolized by cytochrome P-450 system may be associated with elevations in serum concentrations of those drugs; has demonstrated QTc prolongation in combination with other drugs that prolong the QT interval

Contraindications

Documented hypersensitivity; hepatic impairment

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in liver disease; estolate preparation may cause cholestatic jaundice; GI adverse effects are common; therefore, administer after meals; discontinue if nausea, vomiting, malaise, abdominal colic, and/or fever occur

Follow-up

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.

Prognosis

• Prognosis is excellent if lymphogranuloma venereum (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

Medicolegal Pitfalls

• 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.

References

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Keywords

lymphogranuloma venereum, LGV, Chlamydia trachomatis, C trachomatis, STD, sexually transmitted chlamydial disease, sexually transmitted disease, chlamydia

Contributor Information and Disclosures

Author

Jose Antonio Plaza, MD, Director of Dermatopathology, Department of Pathology, Froedtert Hospital; Assistant Professor, Department of Pathology, Section of Dermatopathology, Medical College of Wisconsin
Jose Antonio Plaza, MD is a member of the following medical societies: American Medical Association and American Society for Clinical Pathology
Disclosure: Nothing to disclose.

Coauthor(s)

Victor G Prieto, MD, PhD, Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center
Victor G Prieto, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Medical Association, American Society for Clinical Pathology, American Society of Dermatopathology, College of American Pathologists, European Society of Pathology, International Society of Dermatopathology, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Medical Editor

Terry L Barrett, MD, Clinical Professor of Dermatology and Pathology, University of Texas Southwestern School of Medicine; Director, ProPath Dermatopathology, Dallas, Texas
Terry L Barrett, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society of Dermatopathology, College of American Pathologists, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory
Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Jennifer D. Lorek, MD, Scott M. Acker, MD, Peter Langenstroer, MD, and Milton W. Datta, MD, to the development and writing of this article.

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