Lymphogranuloma venereum
Encyclopedia
Lymphogranuloma venereum (also known as "Climatic bubo," "Durand–Nicolas–Favre disease," "Poradenitis inguinale," and "Strumous bubo") is a sexually transmitted disease
caused by the invasive serovars
L1, L2, L2a or L3 of Chlamydia trachomatis
.
LGV was first described by Wallace in 1833 and again by Durand, Nicolas, and Favre in 1913.
s. The organism travels from the site of inoculation down the lymphatic channels to multiply within mononuclear phagocytes of the lymph nodes it passes.
In developed nations, it was considered rare before 2003. However, a recent outbreak in the Netherlands among gay men has led to an increase of LGV in Europe and the United States. A majority of these patients are HIV co-infected.
Since the 2004 Dutch outbreak many additional cases have been reported, leading to greater surveillance. Soon after the initial Dutch report, national and international health authorities launched warning initiatives and multiple LGV cases were identified in several more European countries (Belgium, France, the UK, Germany, Sweden, Italy and Switzerland) and the US and Canada. 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 MSM
who visited the STI city clinic of San Francisco in 1981. This finding suggests that the recent LGV outbreak among MSM in industrialised countries is a slowly evolving epidemic.
The L2b serovar has also been identified in Australia
.
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 1/3 of those infected notice the first signs of LGV. This primary stage heals in a few days. Erythema nodosum
occurs in 10% of cases.
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, abscess
es, 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 stricture
s. These late stages characterised by fibrosis and edema are also known as the third stage of LGV and are mainly permanent.
, 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.
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.
usually is made serologically
(through complement fixation) and by exclusion of other causes of inguinal lymphadenopathy or genital ulcer
s. Serologic testing has a sensitivity of 80% after 2 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. 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.
l 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 in the patient. Patients with a sexually transmitted disease should be tested for other STDs due to high rates of comorbid infections. Antibiotics are not without risks and prophylaxtic broad antibiotic coverage is not recommended.
Common antibiotic treatments include: tetracycline (doxycycline
) (all tetracyclines, including doxycycline, are contraindicated during pregnancy and in children due to effects on bone development and tooth discoloration), and erythromycin
.
Sexually transmitted disease
Sexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex...
caused by the invasive serovars
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...
L1, L2, L2a or L3 of Chlamydia trachomatis
Chlamydia trachomatis
Chlamydia trachomatis, an obligate intracellular human pathogen, is one of three bacterial species in the genus Chlamydia. C. trachomatis is a Gram-negative bacteria, therefore its cell wall components retain the counter-stain safranin and appear pink under a light microscope.The inclusion bodies...
.
LGV was first described by Wallace in 1833 and again by Durand, Nicolas, and Favre in 1913.
Overview
LGV is primarily an infection of lymphatics and lymph nodes. Chlamydia trachomatis is the bacteria responsible for LGV. It gains entrance through breaks in the skin, or it can cross the epithelial cell layer of mucous membraneMucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s. The organism travels from the site of inoculation down the lymphatic channels to multiply within mononuclear phagocytes of the lymph nodes it passes.
In developed nations, it was considered rare before 2003. However, a recent outbreak in the Netherlands among gay men has led to an increase of LGV in Europe and the United States. A majority of these patients are HIV co-infected.
Since the 2004 Dutch outbreak many additional cases have been reported, leading to greater surveillance. Soon after the initial Dutch report, national and international health authorities launched warning initiatives and multiple LGV cases were identified in several more European countries (Belgium, France, the UK, Germany, Sweden, Italy and Switzerland) and the US and Canada. 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 MSM
Men who have sex with men
Men who have sex with men are male persons who engage in sexual activity with members of the same sex, regardless of how they identify themselves; many men choose not to accept sexual identities of homosexual or bisexual...
who visited the STI city clinic of San Francisco in 1981. This finding suggests that the recent LGV outbreak among MSM in industrialised countries is a slowly evolving epidemic.
The L2b serovar has also been identified in Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
.
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 abscessAbscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
es in the groin (inguinal) region where draining lymph nodes are located. These signs usually appear by 3 days to a month after exposure. - The rectal syndrome arises if the infection takes place via the rectal mucosa (through anal sex) and is mainly characterized by proctocolitisProctocolitisProctocolitis is a general term for inflammation of the rectum and colon.-Etiology:Common etiologic agents of proctocolitis include Chlamydia trachomatis, Neisseria gonorrhoeae, HSV, and Campylobacter species....
symptoms. - The pharyngeal syndrome is rare. It starts after infection of pharyngeal tissue, and buboes in the neck region can occur.
Primary stage
LGV may begin as a self-limited painless genital ulcerGenital ulcer
A Genital ulcer is an ulcer located on the genital area, usually caused by a sexually transmitted disease such as genital herpes, syphilis, chancroid, or thrush. Some other signs of having genital ulcers include enlarged lymph nodes in the groin area, or vesicular lesions, which are small, elevated...
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 1/3 of those infected notice the first signs of LGV. This primary stage heals in a few days. Erythema nodosum
Erythema nodosum
Erythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
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 2/3 of cases) lymphadenitisAdenitis
Adenitis is a general term for an inflammation of a gland or lymph node.-Lymph node adenitis:"Lymph adenitis" or "lymph node adenitis" is caused by bacterial infection in lymph nodes. The infected lymph nodes typically become enlarged, warm and tender. A swelling of lymph nodes due to growth of...
and lymphangitis
Lymphangitis
Lymphangitis is an inflammation of the lymphatic channels that occurs as a result of infection at a site distal to the channel. The most common cause of lymphangitis in humans is Streptococcus pyogenes...
, 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
Proctitis
Proctitis is an inflammation of the anus and the lining of the rectum, affecting only the last 6 inches of the rectum.-Overview:Symptoms are ineffectual straining to empty the bowels, diarrhea, rectal bleeding and possible discharge, a feeling of not having adequately emptied the bowels,...
, inflammation limited to the rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
(the distal 10–12 cm) that may be associated with anorectal pain, tenesmus
Tenesmus
Rectal tenesmus is a feeling of incomplete defecation. It is experienced as an inability or difficulty to empty the bowel at defecation...
, and rectal discharge, or proctocolitis
Proctocolitis
Proctocolitis is a general term for inflammation of the rectum and colon.-Etiology:Common etiologic agents of proctocolitis include Chlamydia trachomatis, Neisseria gonorrhoeae, HSV, and Campylobacter species....
, 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
Cervicitis
Cervicitis is inflammation of the uterine cervix. Cervicitis in women has many features in common with urethritis in men and many cases are caused by sexually transmitted infections...
, perimetritis, or salpingitis
Salpingitis
Salpingitis is an infection and inflammation in the fallopian tubes. It is often used synonymously with Pelvic inflammatory disease , although PID lacks an accurate definition and can refer to several diseases of the female upper genital tract, such as endometritis, oophoritis, myometritis,...
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
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
, fluctuant and suppurative lymph nodes, abscess
Abscess
An abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
es, 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
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, and stricture
Stricture
Stricture may refer to:* esophageal stricture, in medicine* stenosis, in medicine* a feature of the Perl programming language* tenet, in religion* degree of contact, in a consonant...
s. These late stages characterised by fibrosis and edema are also known as the third stage of LGV and are mainly permanent.
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, doxycyclineDoxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
, or erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
. Prognosis is more favorable with early treatment. Bacterial superinfections may complicate course. Death can occur from bowel obstruction
Bowel obstruction
Bowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
or perforation, and follicular conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
due to autoinoculation
Autoinoculation
Autoinoculation is derived from the Latin root words "autos" and "inoculate" that mean "self implanting" or "self infection" or "implanting something from oneself". Autoinoculation can refer to both beneficial medical procedures as well as non-beneficial or harmful natural processes...
of infectious discharge can occur.
Long term complications
Genital elephantiasisElephantiasis
Elephantiasis is a disease that is characterized by the thickening of the skin and underlying tissues, especially in the legs and male genitals. In some cases the disease can cause certain body parts, such as the scrotum, to swell to the size of a softball or basketball. It is caused by...
or esthiomene
Esthiomene
Esthiomene is the characteristic ulcerated state of the vulva, characteristic of lymphogranuloma venereum in the female. The labia may be enlarged, thickened, and fibrotic. It is analogous to elephantiasis....
, 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.
Diagnosis
The diagnosisMedical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
usually is made serologically
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
(through complement fixation) and by exclusion of other causes of inguinal lymphadenopathy or genital ulcer
Genital ulcer
A Genital ulcer is an ulcer located on the genital area, usually caused by a sexually transmitted disease such as genital herpes, syphilis, chancroid, or thrush. Some other signs of having genital ulcers include enlarged lymph nodes in the groin area, or vesicular lesions, which are small, elevated...
s. Serologic testing has a sensitivity of 80% after 2 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
Direct fluorescent antibody
Direct fluorescent antibody is a laboratory test that uses antibodies tagged with fluorescent dye that can be used to detect the presence of microorganisms. This method offers straightforward detection of antigens using fluorescently labeled antigen-specific antibodies...
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
TaqMan
TaqMan probes are hydrolysis probes that are designed to increase the specificity of real-time PCR assays. The method was first reported in 1991 by researchers at Cetus Corporation, and the technology was subsequently developed by Roche Molecular Diagnostics for diagnostic assays and by Applied...
analysis) has been developed to diagnose LGV. 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.
Further recommendations
As with all STIs, sex partners of patients who have LGV should be examined and tested for urethraUrethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
l or cervical
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
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 in the patient. Patients with a sexually transmitted disease should be tested for other STDs due to high rates of comorbid infections. Antibiotics are not without risks and prophylaxtic broad antibiotic coverage is not recommended.
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
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
) (all tetracyclines, including doxycycline, are contraindicated during pregnancy and in children due to effects on bone development and tooth discoloration), and erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
.
External links
- http://www.essti.org/