eMedicine Specialties > Emergency Medicine > Infectious Diseases

Lymphogranuloma Venereum

Andrew C Bushnell, MD, FACEP, Department of Surgery, Division of Emergency Medicine, Assistant Professor, University of Vermont College of Medicine

Updated: Aug 17, 2009

Introduction

Background

Lymphogranuloma venereum (LGV) is a sexually transmitted disease that primarily infects the lymphatics.

The disease originally was described in 1833 by Wallace. It was defined as a clinical and pathological entity in 1913 by Durand, Nicolas, and Favre.

LGV synonyms include lymphopathia venerea, tropical bubo, climatic bubo, strumous bubo, poradenitis inguinales, Durand-Nicolas-Favre disease, and lymphogranuloma inguinale.

Pathophysiology

LGV is caused by serovars L1, L2, and L3 of Chlamydia trachomatis. It gains entrance through skin breaks and abrasions, or it crosses the epithelial cells of mucous membranes. The organism travels via the lymphatics to multiply within mononuclear phagocytes in regional lymph nodes.

Transmission is predominantly sexual. However, transmission by fomites, nonsexual personal contact, and laboratory accidents has been documented. The creation of aerosols of this organism has been associated with infection and pulmonary symptoms.

LGV occurs in 3 stages. The majority of LGV infections in the primary and secondary stages may go undetected.

The primary stage is marked by the formation of a painless herpetiform ulceration at the site of inoculation.

The secondary stage is classically described as the inguinal syndrome in men, characterized by painful inguinal lymphadenitis and associated constitutional symptoms.

• Tender inguinal lymphadenopathy, usually unilateral, is the most common clinical manifestation.
• Lymphatic drainage from the penis is through the inguinal lymph nodes; thus, heterosexual men are affected most often in the inguinal lymph nodes.
• Homosexual men and women who are receptive to anal sex may develop perirectal and pelvic lymph node involvement. In women, these nodes may also become involved as a result of lymphatic spread from the cervix and posterior vaginal wall.
• Early in the course of the disease, the nodes appear fleshy and show diffuse reticulosis.
• Later, suppurative granulomatous lymphadenitis and perilymphadenitis occur with matting of the nodes. Frequently, these nodes coalesce to form stellate abscesses.
• Histologically, these abscesses are nearly diagnostic, but the clinical appearance may be similar to those seen in other infections, including catscratch fever and mycobacterial granulomatous infections.

The tertiary stage of LGV occurs years after the initial infection. In this stage, an anogenitorectal syndrome may occur with resultant rectal stricture or elephantiasis of the genitalia.

• This syndrome is found predominantly in women and homosexual men, because of the location of the involved lymphatics.
• This late stage is characterized by proctocolitis, which is caused by hyperplasia of intestinal and perirectal lymphatic tissue.
• This inflammation forms perirectal abscesses, ischiorectal abscesses, rectovaginal fistulas, anal fistulas, and rectal stricture. In very late stages, fibrosis and granulomas are characteristic.
• Chlamydial organisms are scarce at this stage.

Extragenital inoculation sites can produce regional lymphadenopathy. Examples are of mediastinal lymphadenopathy from inhalation of C trachomatis, or submandibular and cervical chain lymphadenopathy following inoculation after oral sex.

Frequency

United States

Sporadic cases occur in North America, Australia, and most of Asia. Most cases in the United States involve recent travel to an endemic area where the patient was sexually active; therefore, obtaining a travel history is important. Historically, the average number of LGV cases in the United States has been fewer than 600 per year.

International

LGV is endemic in East and West Africa, India, Southeast Asia, South America, the Caribbean, and Australia.¹ Since 2003, an increasing epidemic of LGV with the L2 serovar has occurred in men who have sex with men in western Europe.

Mortality/Morbidity

• Given appropriate treatment, patients usually have complete resolution of symptoms.
• Death can occur from tertiary LGV if complete bowel obstruction from rectal stricture leads to perforation; this is rare, however.

Sex

LGV is diagnosed in men up to 6 times more frequently than in women.

Age

LGV infection is most common in the second and third decades when sexual activity is highest.

Clinical

History

• Primary lymphogranuloma venereum (LGV)
  • The primary lesion of LGV occurs after an incubation period of 3-21 days following an exposure.
  • The initial lesion may be a painless papule, shallow erosion, ulcer, or grouping of lesions with a herpetiform appearance.
  • If the primary lesion is in the urethra, symptoms of a nonspecific urethritis may occur.
  • The most common sites of primary infection in men include the coronal sulcus, frenulum, prepuce, penis, urethra, glans, and scrotum.
  • In women, the most common sites of the primary lesion include the posterior vaginal wall, fourchette, posterior lip of the cervix, and vulva.
  • The primary lesion is noticed in one third of affected men but rarely is observed in affected women.
  • Primary lesions of the mouth can result from oral sexual exposure.
• Secondary LGV
  • The secondary stage of LGV occurs after a usual incubation period of 10-30 days, but it may be up to 6 months. This stage is characterized by the formation of enlarged, tender regional lymph nodes known as buboes.
  • Patients may experience constitutional symptoms, which can include fever, headache, malaise, chills, nausea, vomiting, and arthralgias.
• Tertiary LGV
  • This late stage is characterized by proctocolitis.
  • Symptoms include anal pruritus, bloody mucopurulent rectal discharge, fever, rectal pain, tenesmus, constipation, pencil-thin stools, and weight loss.

Physical

Often, the diagnosis is considered initially on the basis of physical findings. Clinical findings of large fluctuant buboes or draining sinuses are suggestive of the diagnosis of LGV. The presence of rectal stricture and/or perineal deformity in a young woman is highly suggestive of LGV.

• Primary LGV
  • The initial lesion may be a painless papule, shallow erosion, ulcer, or herpetiform grouping of lesions.
  • A cordlike lymphangitis of the dorsal penis may develop in primary LGV. This may progress to the formation of a solitary, large, tender lymphoid nodule, or bubonulus. These bubonuli may rupture to form sinuses and/or fistulas.
• Secondary LGV
  • Buboes, which are enlarged, tender regional lymph nodes, may be present.
  • The location of lymph node involvement is related directly to the site of the primary lesion.
    • Inguinal lymphadenopathy occurs if the primary lesion involves the anterior vulva, penis, or urethra.
    • Perirectal and pelvic lymphadenopathy result if the primary lesion involves the posterior vulva, vagina, or anus.
    • Lymphadenitis of the submaxillary and cervical glands occurs if the site of primary inoculation is the mouth.
  • Seventy-five percent of all patients have deep iliac nodal involvement, which seldom suppurates.
  • In the classic presentation of the heterosexual man with inguinal lymph node involvement, a groove depression (groove sign) overlying the inguinal ligament is noted. This is caused by proliferation of inguinal and femoral lymph nodes, which are separated by the inguinal (Poupart) ligament. However, this presentation is seen in only 20% of affected men.
  • Two thirds of patients with inguinal involvement have unilateral inguinal bubo formation with edema and erythema of the overlying skin.
    • Frequently these nodes coalesce to form stellate abscesses.
    • One third of these abscesses rupture; two thirds involute. Prior to a rupture, the skin overlying the buboes may become a dark livid color. After a rupture, pain decreases; however, a discharge may continue for weeks to months with the formation of a fistula or sinus tract.
  • Cutaneous manifestations may accompany infection, including erythema multiforme, scarlatiniform eruption, urticaria, and, in 10% of cases, erythema nodosum.
  • Complications of LGV that may be noted on physical examination include arthritis, conjunctivitis, and hepatomegaly. Pericarditis, pneumonia, and meningoencephalitis rarely occur.
• Tertiary LGV
  • This stage is characterized by proctocolitis.
  • Lymphorrhoids or perianal condylomata may be observed on examination of the rectum. These structures appear similar to hemorrhoids and are the result of an obstruction of lymphatics. They are composed of dilated lymph vessels with perilymphatic inflammation.
  • Rectal examination at this stage also may reveal a granular mucosa and palpable, enlarged lymph nodes under the bowel wall. Stricture usually occurs 2-5 cm above the anocutaneous margin, and digital examination above the stricture may reveal smooth healthy mucosa.
  • In very late stages, fibrosis and granulomas are characteristic.
    • In women, esthiomene (eating away) occurs, which results in hypertrophic, chronic granulomatous enlargement of the vulva and subsequent ulceration. This may not appear for 1-20 years after the primary infection.
    • In men, elephantiasis of the genitalia can occur.

Causes

• The causal organism is C trachomatis, serovars L1, L2, and L3.
• Serovar L2 is the most common cause.
• Risk factors
  • Unprotected sex
  • Anal intercourse
  • Residing in or visiting tropical/developing countries
  • Prostitution

Differential Diagnoses

Catscratch Disease
Chancroid
Syphilis

Other Problems to Be Considered

Inguinal syndrome differential
Incarcerated inguinal hernia
Tularemia
Hodgkin disease
Plague
Genital herpes
Granuloma inguinale
Mycobacterial disease

Anogenitorectal syndrome differential
Rectal stricture from cancer
Trauma
Actinomycosis
Schistosomiasis
Inflammatory proctitis

Esthiomene differential
Filariasis
Mycosis

Workup

Laboratory Studies

• Initial laboratory analysis may reveal mild leukocytosis.
• These nonspecific results do not aid the clinician in the diagnosis of lymphogranuloma venereum (LGV).
• Previously, the Frei test was the only method available to identify a chlamydial infection. Currently, the Frei intradermal test is only of historical interest.
  • The test was based on a positive hypersensitivity to an intradermal standardized antigen, lymphogranuloma venereum, which indicated past or present chlamydial infection. The Frei test would become positive 2-8 weeks after infection.
  • Unfortunately, the Frei antigen is common to all chlamydial species and is not specific to LGV. Commercial manufacturing of Frei antigen was discontinued in 1974.
• Complement fixation (CF) is more sensitive than the Frei skin test, but it has some cross-reactivity with other chlamydial species.
  • CF sensitivity is 80% for LGV.
  • A test titer of 1:16 is strongly suggestive of LGV and a titer of >1:64 indicates active LGV.
  • A 4-fold rise or fall in titer further supports the diagnosis.
• The microimmunofluorescence test for the L-type serovar of C trachomatis is a more sensitive and specific test. A titer greater or equal to 1:512 is diagnostic. Availability of this test is the limiting factor.
• Application of nucleic acid amplification techniques have been used to confirm the diagnosis with much greater certainty. Polymerase chain reaction (PCR) assays have been used for diagnosis recently in several outbreaks. PCR is a far superior test but has limited availability to reference laboratories. Recently, multiplexed real-time PCR assays have been developed for the rapid detection of Chlamydia trachomatis and specific serovars.² As these tests are refined and approved for widespread use, they will speed detection and diagnosis.
• Dermatopathology is not pathognomonic for LGV, and cytology using Giemsa stain or iodine stain fails to provide a high percentage of diagnoses.
• Definitive diagnosis may be made by aspiration of the bubo and growth of the aspirated material in cell culture. C trachomatis can be cultured in as many as 30% of cases.

Imaging Studies

• CT scan may be useful if retroperitoneal adenitis or intraabdominal abscess is suspected, but it is rarely necessary in the ED.
• Lymphography does not outline buboes, but it may demonstrate the extent of lymph node involvement. This rarely is ordered in the ED.
• A barium enema may reveal the characteristic elongated stricture in rectal LGV.

Other Tests

• Venereal Disease Research Laboratory (VDRL) test or rapid plasma reagin (RPR), PCR assays for Haemophilus ducreyi and HSV-2, and HIV antibodies should be considered because patients with LGV may also have contracted other sexually transmitted diseases.

Procedures

• A bubo may be aspirated to speed the healing, but this is not necessary for culture since other diagnostic methods are more sensitive and specific.

Treatment

Emergency Department Care

• Aspiration of fluctuant buboes may prevent spontaneous rupture and reduce morbidity.
• Antibiotics are needed to treat ongoing infection.
• Patients with lymphogranuloma venereum (LGV) have been known to harbor other sexually transmitted diseases.
• Symptomatic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) may be beneficial.
• Local heat may provide some pain relief.

Consultations

• In the acute bubonic stage, consultation with a surgeon may be considered for the aspiration of fluctuant nodes.

Medication

The goal of therapy is to eradicate the pathogen.

Antibiotics

Therapy must cover all likely pathogens in the context of the clinical setting.

Doxycycline (Doryx, Bio-Tab, Vibramycin)

Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Sexual contacts of confirmed cases seen within 30 d of confirmed case diagnosis need to receive a prophylactic regimen of either azithromycin or doxycycline.

Dosing

Adult

100 mg PO bid for 21 d

Pediatric

<8 years: Not recommended
>8 years: 2-5 mg/kg/d PO in 1-2 divided doses; not to exceed 200 mg/d

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can increase hypoprothrombinemic effects of anticoagulants; can decrease effects 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

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Erythromycin (EES, Ery-Tab, Erythrocin)

Inhibits RNA-dependent protein synthesis, possibly by stimulating dissociation of peptidyl tRNA from ribosomes. This inhibits bacterial growth. In children, age, weight, and severity of infection determine proper dosage. When bid dosing desired, half-total daily dose may be taken every 12 h. 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

May increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; lovastatin and simvastatin increase risk of rhabdomyolysis

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 formulation may cause cholestatic jaundice; adverse GI effects common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Sulfisoxazole

Sulfonamide derivative that exerts its bacteriostatic action by antagonizing para-aminobenzoic acid (PABA), an essential component in folic acid synthesis. Microorganisms susceptible to this medication are those that depend on folic acid synthesis for growth and cannot use exogenous folic acid.

Dosing

Adult

500 mg PO qid for 21 d

Pediatric

<2 months: Not recommended
>2 months: 100 mg/kg/d PO divided q6h for 21 d

Interactions

May enhance warfarin's anticoagulant effects, and hemorrhage could occur; may enhance thiopental anesthetic effects; cyclosporine may increase risk of nephrotoxicity; may increase serum hydantoin levels; may worsen methotrexate-induced bone marrow suppression; may increase sulfonylurea concentrations and cause hypoglycemia in diabetic patients; may prolong tolbutamide bioavailability; coadministration with diuretics may increase incidence of thrombocytopenia with purpura; indomethacin may increase free drug concentration; when used concomitantly with methenamine mandelate, may form precipitate in acidic urine; probenecid and salicylates may displace from plasma albumin, resulting in increased free-drug concentrations and potentiating its toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use to treat group A beta-hemolytic streptococcal infections; does not eradicate streptococci or prevent sequelae, such as rheumatic fever and glomerulonephritis

Azithromycin (Zithromax)

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.
Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.
Recent evidence suggests that use of azithromycin for 3 wk is a sufficient course. However, more studies using this regimen need to be completed.
Sexual contacts of confirmed cases seen within 30 d of confirmed case diagnosis need to receive a prophylactic regimen of either azithromycin or doxycycline.

Dosing

Adult

1 g PO qwk for 3 wk
Prophylactic regimen: 1 g PO once

Pediatric

Not established

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; do not administer with pimozide

Precautions

Pregnancy

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

Precautions

Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Follow-up

Deterrence/Prevention

• Infection confers little or no protective immunity against future infection.
• Sexual contacts should be referred for evaluation and possible treatment.
• Encourage the practice of safe sex.

Complications

• Primary lymphogranuloma venereum (LGV)
  • Bubonuli may rupture to form sinuses or fistulas. This may result in long-term complications, including fibrosis and deforming scars at the penile base.
  • In women, cervicitis, perimetritis, or salpingitis may occur.
• Tertiary LGV - Complete bowel obstruction from rectal stricture
• Other complications of LGV include arthritis, conjunctivitis, hepatomegaly and, rarely, pericarditis, pneumonia, and meningoencephalitis.

Prognosis

• Generally, full recovery is expected with appropriate treatment.
• Reinfection/relapse may occur.

Patient Education

For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center and Sexually Transmitted Diseases Center. Also, see eMedicine's patient education articles Sexually Transmitted Diseases, Birth Control Overview, Birth Control FAQs, and Chlamydia.

Miscellaneous

Medicolegal Pitfalls

The diagnosis of LGV is frequently missed in women and homosexual men because the initial lesion may not be readily visible and the associated noninguinal lymphadenitis may not be identified readily. In heterosexual men, the diagnosis frequently is made with the occurrence of the painful inguinal syndrome.

Special Concerns

Recent outbreaks have occurred in the western world involving men who have sex with men (MSM). The association with other sexually transmitted diseases, including HIV, has been large probably due to a decline in safe sex practices, and may also be facilitated by LGV infection.

References

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Keywords

lymphogranuloma venereum, lymphopathia venerea, tropical bubo, climatic bubo, strumous bubo, poradenitis inguinales, Durand-Nicolas-Favre disease, lymphogranuloma inguinale, LGV, sexually transmitted disease, STD, Chlamydia trachomatis, C trachomatis

Contributor Information and Disclosures

Author

Andrew C Bushnell, MD, FACEP, Department of Surgery, Division of Emergency Medicine, Assistant Professor, University of Vermont College of Medicine
Andrew C Bushnell, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Eric M Kardon, MD, FACEP, Attending Emergency Physician, Georgia Emergency Medicine Specialists; Physician, Division of Emergency Medicine, Athens Regional Medical Center
Eric M Kardon, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jeter (Jay) Pritchard Taylor III, MD, Compliance Officer, Attending Physician, Emergency Medicine Residency, Department of Emergency Medicine, Palmetto Health Richland, University of South Carolina; Medical Director, Department of Emergency Medicine, Palmetto Health Baptist
Jeter (Jay) Pritchard Taylor III, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

Clinical guidelines

New York State Department of Health. Lymphogranuloma venereum (LVG). New York (NY): New York State Department of Health; 2007 Aug. 11 p.

Clinical Effectiveness Group, British Association for Sexual Health and HIV (BASHH). National guideline for the management of lymphogranuloma venereum (LVG). London (UK): British Association for Sexual Health and HIV (BASHH); 2006. 14 p.

Herring A, Richens J, LGV Incident Group, Health Protection Agency. Lymphogranuloma venereum (LGV). In: Ross J, Ison C, Carder C, Lewis D, Mercey D, Young H. Sexually transmitted infections: UK national screening and testing guidelines. London (UK): British Association for Sexual Health and HIV (BASHH); 2006 Aug. p. 57-62.

U.S. Preventive Services Task Force. Behavioral counseling to prevent sexually transmitted infections: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008 Oct 7;149(7):491-6, W95. ³

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