Lymphogranuloma venereum overview

# Overview
Lymphogranuloma venereum (LGV), also known as lymphopathia venerea, tropical bubo, climatic bubo, strumous bubo, poradenitis inguinales, Durand-Nicolas-Favre disease, lymphogranuloma inguinale and neekerisankkeri in Finland, is a sexually transmitted disease caused by the invasive serovars L1, L2, or L3 of Chlamydia trachomatis.

# Historical Perspective
LGV was first described by Wallace in 1833 and again by Durand, Nicolas, and Favre in 1913.

# Pathophysiology
Lymphogranuloma venereum (LGV) is caused by serovars L1, L2, or L3 of the bacterium Chlamydia trachomatis. C. trachomatis is an obligate intracellular pathogen transmitted through vaginal, anal, or oral sexual contact. C. trachomatis alternates between two forms: the infectious elementary body (EB) and noninfectious, replicating reticulate body (RB). EBs enter through skin abrasions or microabrasion, or by crossing mucous membranes. EBs produce major out membrane protein (MOMP), which binds to heparan sulfate receptors on epithelial cells and are then phagocytized forming chlamydial inclusions. EBs begin to differentiate into RBs that start replicating. Endocytosis and bacterial replication cause host cell destruction leading to the formation of a papule at the site of inoculation. EBs and RBs then travel through lymphatics to regional lymph nodes, primarily to inguinal lymph nodes. C. trachomatis continues to replicate within monocytes causing lymphadenopathy and eventually the formation of buboes. Associated conditions include coinfection with other sexually transmitted diseases.

# Causes
Chlamydia trachomatis is a Gram-negative, obligate intracellular pathogen causing Lymphogranuloma venereum.

# Classification
Lymphogranuloma venereum (LGV) may be classified into three stages: primary LGV characterized by a self-limited papule, secondary LGV characterized by painful lymphadenopathy, and tertiary LGV (genitoanorectal syndrome) characterized by proctocolitis.

# Differential Diagnosis
Lymphogranuloma venereum (LGV) must be differentiated from other diseases that cause genital ulcers, lymphadenopathy, or proctocolitis including syphilis, Herpes simplex, Behcet's disease, chancroid, donovanosis, fixed drug eruption, psoriasis, chlamydial diseases caused by C. trachomatis serovars D-K, and diseases characterized with colitis. Sexually transmitted diseases characterized as genital ulcer diseases will present with the most similar symptoms to LGV.

# Epidemiology and Demographics
Lymphogranuloma venereum (LGV) is rare in developed countries but the disease has become prevalent in the men who have sex with men (MSM) population. Outbreaks in MSM have occurred in the United Kingdom, Netherlands, Germany and United States. LGV is seen most commonly in white individuals whose ages range from 15 to 40 years. Males typically present and earlier stages than females.

# Risk Factors
Risk factors for developing lymphogranuloma venereum include HIV-positive serostatus, unprotected sexual intercourse (anal intercourse higher risk than vaginal intercourse) and multiple sex partners.

# Natural History, Complications, and Prognosis
After an incubation period of 3 - 30 days for Chlamydia trachomatis, a papule develops at the point of inoculation and may ulcerate. The lesion is self-limited and heals in approximately a week. Lymphadenopathy of the inguinal and femoral lymph nodes develops 2 - 6 weeks after onset the primary lesion. Inguinal lymph nodes may develop into fluctuant, suppurative buboes or nonsuppurative abscesses. Iliac and perirectal lymphadenopathy may also develop in patients with rectal exposure, accompanied by hemorrhagic proctocolitis. Chronic inflammation may lead to perirectal fistulas and/or strictures, as well as sclerosing fibrosis that results in elephantiasis of genitalia, esthiomene in women, and frozen pelvis syndrome. Systemic spread may result in arthritis, hepatitis or perihepatitis, pneumonitis, cardiac involvment (rare), aseptic meningitis (rare), ocular inflammatory disease (rare). Prognosis is poor without treatment. However, spontaneous remission is possible. Death can occur from bowel obstruction or perforation.

# Diagnosis

## History and Symptoms
The most common symptom of primary LGV is a painless papule or ulcer. Secondary LGV is characterized by painful inguinal and/or femoral lymphadenopathy, or Iliac and/or perirectal lymphadenopathy in patients with rectal exposure. Proctolcolits may also develop at this stage. Tertiary LGV symptoms include Lymphatic and rectal fibrosis, genital elephantiasis, esthiomene (chronic ulcerative disease of vulva), edema, tenesmus and rectal discharge. LGV may spread systemically and cause the following symptoms: fever, chills, malaise, myalgia, arthralgia, arthritis, hepatitis or perihepatitis, and pneumonitis.

## Physical Examination
Primary LGV is characterized by a small, nontender papule or ulcer. The primary lesion is typically unnoticed so few patients present at this stage. Majority of patients that do present are male. Secondary LGV is characterized by tender, swollen lymph nodes, typically unilateral, known as buboes. Enlarged inguinal and/or femoral lymph nodes occur after primary lesion of anterior genital area. Enlarged iliac and/or perirectal lymph nodes occure after primary lesion of posterior genital area. 20% of patients present with "groove sign". Buboes may be indurated or draining sinuses. Tertiary LGV is characterized by ] fistulas and/or strictures, ulcerative proctitis, and/or Elephantiasis of gentials. Males may present with "saxophone penis". Females may present with with ulceration and thickening of the vulva.

## Laboratory Findings
Because of limitations in commercially available tests, clinical presentation, in conjunction to laboratory findings, plays an important role in diagnosis. C. trachomatis can be identified from lesion swabs, bubo aspirate, or rectal mucosa swabs (in patients with proctitis) using culture methods, serologic testing, and nucleic acid amplification tests (NAATs). Culture is impractical since it is time consuming and lacks sensitivity. Compliment fixation and immunofluorescence serologic tests are sensitive but only genus specific. NAATs are the most reliable method for detecting C. trachomatis and real-time PCR can detect the LGV-specific serovar.

# Treatment

## Medical Therapy
There is no vaccine against the bacteria. LGV can be treated with three weeks of antibiotics. CDC STD Treatment Guidelines recommend the use of doxycyline, twice a day for 21 days. An alternative treatment is erythromycin base or azithromycin. The health care provider will
determine which is best.

## Surgery
Needle aspiration or incision and drainage of inguinal buboes may be required to prevent ulcer  or sinus formation. Patients with rectal strictures as a complication of LGV may need surgery to prevent bowel obstruction and bowel infarction.

## Primary Prevention
Since there is no vaccine for LGV, methods of primary prevention include: abstaining from sexual activity, limiting number of sexual partners and using a male or female condom. The goal of secondary prevention is to stop the spread of disease. Therefore infected individuals should abstain from sexual intercourse until symptoms reside.