Lymphogranuloma venereum

Lymphogranuloma venereum
Other names: Climatic bubo,[1] Durand–Nicolas–Favre disease,[1] Poradenitis inguinale,[1] Lymphogranuloma inguinale, Strumous bubo[1]
Lymphogranuloma venereum in a young adult who experienced acute onset of tender, enlarged lymph nodes in both groins.
SpecialtyInfectious disease
SymptomsGenital ulcer, large lymph nodes in the groin[2]
ComplicationsFistulae, anal stricture[3]
Usual onset3 to 12 days post exposure[3]
CausesCertain types of Chlamydia trachomatis[2]
Risk factorsMen who have sex with men, HIV/AIDS[3]
Diagnostic methodCulture, PCR[2]
Differential diagnosisHerpes, syphilis, chancroid, granuloma inguinale, HIV/AIDS[3]
TreatmentDoxycycline, erythromycin[2]
PrognosisFair if treated[3]
FrequencyUncommon[3]

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by certain types of Chlamydia trachomatis.[3] Symptoms may include a small painless genital ulcer and large lymph nodes in the groin on one side.[2][3] Rectal exposure can result in anal pain and discharge.[2] Onset is typically 3 to 12 days after exposure.[3] Complications may include fistulae or anal stricture.[3]

The disease is caused by the serovars L1, L2, and L3 of Chlamydia trachomatis.[2] It is spread by sex, including vaginal, oral, and anal sex.[3] Risk factors include men who have sex with men and HIV/AIDS.[3] The infection primarily involves the lymphatic system.[3] Diagnosis is suspected based on symptoms and confirmed by testing the site of infection by culture or PCR.[2]

The recommended treatment is with 3 weeks of doxycycline; with erythromycin as an alternative.[2] Incision and drainage of large lymph nodes may be required.[2] Sexual contacts within the last 60 days should also be tested and treated.[2] With treatment outcomes are fair.[3]

Lymphogranuloma venereum is uncommon; though is more common in tropical areas of the world.[3] It most commonly occurs in those between the ages of 15 and 40.[3] While it likely occurs equally in both sexes, males are more commonly diagnosed.[3] It was rare in developed nations before 2003, though a number of outbreaks have occurred in Europe and the USA since than.[4] The disease was first described by Wallace in 1833 and again by Durand, Nicolas, and Favre in 1913.[5][6]

Signs and symptoms

The clinical manifestation of LGV depends on the site of entry of the infectious organism (the sex contact site) and the stage of disease progression.

  • Inoculation at the mucous lining of external sex organs (penis and vagina) can lead to the inguinal syndrome named after the formation of buboes or abscesses in the groin (inguinal) region where draining lymph nodes are located. These signs usually appear from 3 days to a month after exposure.
  • The rectal syndrome (Lymphogranuloma venereum proctitis, or LGVP) arises if the infection takes place via the rectal mucosa (through anal sex) and is mainly characterized by proctocolitis or proctitis symptoms.[7]
  • The pharyngeal syndrome is rare. It starts after infection of pharyngeal tissue, and buboes in the neck region can occur.

Primary stage

Lymphogranuloma venereum ulcer

LGV may begin as a self-limited painless genital ulcer that occurs at the contact site 3–12 days after infection. Women rarely notice a primary infection because the initial ulceration where the organism penetrates the mucosal layer is often located out of sight, in the vaginal wall. In men fewer than one-third of those infected notice the first signs of LGV. This primary stage heals in a few days. Erythema nodosum occurs in 10% of cases.

Secondary stage

The secondary stage most often occurs 10–30 days later, but can present up to six months later. The infection spreads to the lymph nodes through lymphatic drainage pathways. The most frequent presenting clinical manifestation of LGV among males whose primary exposure was genital is unilateral (in two-thirds of cases) lymphadenitis and lymphangitis, often with tender inguinal and/or femoral lymphadenopathy because of the drainage pathway for their likely infected areas. Lymphangitis of the dorsal penis may also occur and resembles a string or cord. If the route was anal sex, the infected person may experience lymphadenitis and lymphangitis noted above. They may instead develop proctitis, inflammation limited to the rectum (the distal 10–12 cm) that may be associated with anorectal pain, tenesmus, and rectal discharge, or proctocolitis, inflammation of the colonic mucosa extending to 12 cm above the anus and associated with symptoms of proctitis plus diarrhea or abdominal cramps.

In addition, symptoms may include inflammatory involvement of the perirectal or perianal lymphatic tissues. In females, cervicitis, perimetritis, or salpingitis may occur as well as lymphangitis and lymphadenitis in deeper nodes. Because of lymphatic drainage pathways, some patients develop an abdominal mass which seldom suppurates, and 20–30% develop inguinal lymphadenopathy. Systemic signs which can appear include fever, decreased appetite, and malaise. Diagnosis is more difficult in women and men who have sex with men (MSM) who may not have the inguinal symptoms.

Over the course of the disease, lymph nodes enlarge, as may occur in any infection of the same areas as well. Enlarged nodes are called "buboes". Buboes are commonly painful. Nodes commonly become inflamed, thinning and fixation of the overlying skin. These changes may progress to necrosis, fluctuant and suppurative lymph nodes, abscesses, fistulas, strictures, and sinus tracts. During the infection and when it subsides and healing takes place, fibrosis may occur. This can result in varying degrees of lymphatic obstruction, chronic edema, and strictures. These late stages characterised by fibrosis and edema are also known as the third stage of LGV, and are mainly permanent.

Diagnosis

The diagnosis usually is made serologically (through complement fixation) and by exclusion of other causes of inguinal lymphadenopathy or genital ulcers. Serologic testing has a sensitivity of 80% after two weeks. Serologic testing may not be specific for serotype (has some cross reactivity with other chlamydia species) and can suggest LGV from other forms because of their difference in dilution, 1:64 more likely to be LGV and lower than 1:16 is likely to be other chlamydia forms (emedicine).

For identification of serotypes, culture is often used. Culture is difficult. Requiring a special medium, cycloheximide-treated McCoy or HeLa cells, and yields are still only 30-50%. DFA, or direct fluorescent antibody test, PCR of likely infected areas and pus, are also sometimes used. DFA test for the L-type serovar of C. trachomatis is the most sensitive and specific test, but is not readily available.

If polymerase chain reaction (PCR) tests on infected material are positive, subsequent restriction endonuclease pattern analysis of the amplified outer membrane protein A gene can be done to determine the genotype.

Recently a fast realtime PCR (TaqMan analysis) has been developed to diagnose LGV.[8] With this method an accurate diagnosis is feasible within a day. It has been noted that one type of testing may not be thorough enough.

Treatment

Treatment involves antibiotics and may involve drainage of the buboes or abscesses by needle aspiration or incision. Further supportive measure may need to be taken: dilatation of the rectal stricture, repair of rectovaginal fistulae, or colostomy for rectal obstruction.

Common antibiotic treatments include tetracycline (doxycycline)[9][10] (all tetracyclines, including doxycycline, are contraindicated during pregnancy and in children due to effects on bone development and tooth discoloration), and erythromycin. Azithromycin is also a drug of choice in LGV.

Further recommendations

Sex partners should be examined and tested for urethral or cervical chlamydial infection. After a positive culture for chlamydia, clinical suspicion should be confirmed with testing to distinguish serotype. Antibiotic treatment should be started if they had sexual contact with the patient during the 30 days preceding onset of symptoms. People with a sexually transmitted infection should be tested for other STIs. Antibiotics are not without risks and prophylactic broad antibiotic coverage is not recommended.

Prognosis

Prognosis is highly variable. Spontaneous remission is common. Complete cure can be obtained with proper antibiotic treatments to kill the causative bacteria, such as tetracycline, doxycycline, or erythromycin. Prognosis is more favorable with early treatment. Bacterial superinfections may complicate course. Death can occur from bowel obstruction or perforation, and follicular conjunctivitis due to autoinoculation of infectious discharge can occur.

Long-term complications

Genital elephantiasis or esthiomene, which is the dramatic end-result of lymphatic obstruction, which may occur because of the strictures themselves, or fistulas. This is usually seen in females, may ulcerate and often occurs 1–20 years after primary infection. Fistulas of, but not limited to, the penis, urethra, vagina, uterus, or rectum. Also, surrounding edema often occurs. Rectal or other strictures and scarring. Systemic spread may occur, possible results are arthritis, pneumonitis, hepatitis, or perihepatitis.

Epidemiology

All cases reported in Amsterdam and France and a considerable percentage of LGV infections in the UK and Germany were caused by a newly discovered Chlamydia variant, L2b, a.k.a. the Amsterdam variant. The L2b variant could be traced back and was isolated from anal swabs of men who have sex with men (MSM) who visited the STI city clinic of San Francisco in 1981. This finding suggests that the LGV outbreak among MSM in industrialized countries is a slowly evolving epidemic. The L2b serovar has also been identified in Australia.[11]

References

  1. 1 2 3 4 Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
  2. 1 2 3 4 5 6 7 8 9 10 11 "Lymphogranuloma Venereum (LGV) - 2015 STD Treatment Guidelines". www.cdc.gov. 2019-01-11. Archived from the original on 2021-06-28. Retrieved 24 May 2021.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Rawla, P; Thandra, KC; Limaiem, F (January 2021). "Lymphogranuloma Venereum". PMID 30726047. {{cite journal}}: Cite journal requires |journal= (help)
  4. ↑ Richardson D; Goldmeier D (January 2007). "Lymphogranuloma venereum: an emerging cause of proctitis in men who have sex with men". International Journal of STD & AIDS. 18 (1): 11–4, quiz 15. doi:10.1258/095646207779949916. PMID 17326855. S2CID 36269503.
  5. ↑ Parish, Lawrence C.; Gschnait, Friedrich (2012-12-06). Sexually Transmitted Diseases: A Guide for Clinicians. Springer Science & Business Media. p. 90. ISBN 978-1-4612-3528-6. Archived from the original on 2021-08-28. Retrieved 2021-05-24.
  6. ↑ Durand N.J.; Nicolas J.; Favre M. (January 1913). "Lymphogranulomatose inguinale subaiguë d'origine génitale probable, peut-être vénérienne". Bulletin de la Société des Médecins des Hôpitaux de Paris. 35: 274–288.
  7. ↑ de Vries, Henry J. C.; van der Bij, Akke K.; Fennema, Johan S. A.; Smit, Colette; de Wolf, Frank; Prins, Maria; Coutinho, Roel A.; MorrÉ, Servaas A. (February 2008). "Lymphogranuloma Venereum Proctitis in Men Who Have Sex With Men Is Associated With Anal Enema Use and High-Risk Behavior" (PDF). Sexually Transmitted Diseases. 35 (2): 203–8. doi:10.1097/OLQ.0b013e31815abb08. ISSN 0148-5717. PMID 18091565. S2CID 2065170. Archived (PDF) from the original on 2020-08-03. Retrieved 2019-12-17.
  8. ↑ Schaeffer A; Henrich B (2008). "Rapid detection of Chlamydia trachomatis and typing of the Lymphogranuloma venereum associated L-Serovars by TaqMan PCR". BMC Infectious Diseases. 8: 56. doi:10.1186/1471-2334-8-56. PMC 2387162. PMID 18447917.
  9. ↑ Kapoor S (April 2008). "Re-emergence of lymphogranuloma venereum". Journal of the European Academy of Dermatology and Venereology. 22 (4): 409–16. doi:10.1111/j.1468-3083.2008.02573.x. PMID 18363909. S2CID 10325217.
  10. ↑ McLean CA, Stoner BP, Workowski KA (April 1, 2007). "Treatment of Lymphogranuloma Venereum". Clinical Infectious Diseases. Infectious Diseases Society of America. 44 (Supplement 3, Sexually Transmitted Diseases Treatment Guidelines): S147–S152. doi:10.1086/511427. ISSN 1058-4838. JSTOR 4485305. PMID 17342667.
  11. ↑ Stark D; van Hal S; Hillman R; Harkness J; Marriott D (March 2007). "Lymphogranuloma venereum in Australia: anorectal Chlamydia trachomatis serovar L2b in men who have sex with men". Journal of Clinical Microbiology. 45 (3): 1029–31. doi:10.1128/JCM.02389-06. PMC 1829134. PMID 17251405.
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