Background
Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by specific serovars of Chlamydia trachomatis (L1, L2, L3). LGV is endemic in certain areas of Africa, Southeast Asia, India, the Caribbean, and South America. It was previously thought to be rare in high income countries, but in the last 10 years has been increasingly recognized in North America, Europe, and the United Kingdom as causing outbreaks of proctitis, particularly among men who have sex with men (MSM). [1, 2, 3, 4, 5, 6]
LGV is a subtype of genital ulcer diseases that include other STIs, such as HSV, syphilis, and chancroid. This condition is characterized by self-limited genital papules or ulcers (often unnoticed by patients) followed by painful inguinal and/or femoral lymphadenopathy, which may be the primary clinical manifestation at presentation. Patients with LGV may also present with rectal ulcerations and symptoms of proctocolitis, especially among patients participating in receptive anal intercourse. In these cases, rectal pain, discharge, and bleeding may be confused with other GI conditions such as colitis. [7] If left untreated, disfiguring ulceration and enlargement of the external genitalia, and subsequent lymphatic obstruction may occur.
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 it replicates within macrophages and causes systemic disease. While transmission is predominantly sexual, cases of transmission through laboratory accidents, fomites, and nonsexual contact have been reported.
The L2b serovar has been identified to play a more important role than previously expected. After the diagnosis of 92 cases of LGV in the Netherlands among MSM, 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. [8] 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 and MSM, may have a delayed presentation and is characterized by proctocolitis.
Epidemiology
Frequency
United States
LGV is historically a rare disease in developed countries, but today is best thought of as a re-emerging STI [6] . Since 2003, sporadic outbreaks of LGV proctitis have been reported among MSM in North America, Europe, and Australia. [9, 10] However, in the United States, a precise understanding of the prevalence is unknown for a combination of reasons: LGV as such is not a nationally notifiable condition - aside from the requirements to report Chlamydia infections; some states will attempt to track cases of LGV based on syndrome reporting, but most laboratories do not have the capabilitiy to either grow or serotype Chlamydia. [11]
No universal surveillance data exist for this disease. Twenty four states still mandate reporting of LGV cases to the Center for Disease Control (CDC), which provides limited data for disease prevalance. Since 1972, rates of LGV had declined, with 113 known cases reported to the CDC in 1997. 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 men who have sex with men. A study published in 2011 reporting LGV surveillance data from multiple sites in the United States found that less than 1% of the samples obtained from rectal swabs of MSM that were positive for C trachomatis tested positive for LGV. [12] Much like in the United Kingdom, increasing reports of clusters of LGV transmission in the United States, particularly among MSM patients, have occurred in recent years. [13]
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. [14] The disease is most commonly found in areas of the Caribbean, Central America, Southeast Asia, and Africa. Since 2003, however, the emergence of documented LGV infections, mostly among MSM, but also in women, has prompted increased surveillance and reporting of this disease in developed countries. [15, 16] Proctitis is reemerging as a presentation of LGV in developing countries. [17]
After a cluster of 92 cases was identified in the Netherlands between 2003 and 2004 (where fewer than 5 cases were reported yearly), [18] many countries have begun active surveillance for LGV, and an increasing number of cases has been identified. Evidence exists that among MSM, LGV is endemic in the United Kingdom; between 2004-2008, LGV was documented in 854 isolates by the National Reference Center there. [19, 20, 21, 22, 23, 24, 25] Evidence supporting the endemicity of LGV in the United Kingdom continues to be published, particularly from the LGV Enhanced Surveillance system which collected data from 2004-2010. [6] Over this 6-year period of data collection, they reported 1370 cases, of which 28 were females, heterosexual males or unknown, with the rest being men who have sex with men. Of note, nearly 80% of the patients with a single episode of LGV were also living with HIV, further complicating the rise in cases is evidence from the United Kingdom that a higher percentage of these cases may be asymptomatic. [26]
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 in Europe and North America have been identified among White, frequently HIV-positive MSM patients presenting with proctitis. [24, 27, 28, 29]
Age
LGV may affect any age but has a peak incidence in the sexually active population aged 15-40 years.
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 eMedicineHealth's Sexual Health Center. Also, see eMedicineHealth's patient education articles Sexually Transmitted Diseases and Chlamydia.
