Lymphogranuloma venerum is a sexually transmitted disease caused by Chlamydia, primarily involving the lymphatics.
LGV is caused by Chlamydia trachomatis biovars L1, L2, and L3
3. INTRODUCTION
Lymphogranuloma venerum is a sexually transmitted disease caused by Chlamydia,
primarily involving the lymphatics
Transmission:
1. Sexual intercourse
2. Nonvenereal transmission is seen in the health care personnel from ruptured buboes and
other infected tissues.
3. Transplacental transmission
4. LGV is caused by Chlamydia trachomatis biovars L1, L2, and L3, of which L2 is
the most common serotype.
Intracellular microorganisms which are filterable organisms, don’t grow in cell-free
media, have a cell wall and contain both RNA and DNA, and are obligate
anaerobes.
Chlamydia trachomatis is a natural human parasite causing infections in the eye
and genitalia.
5.
6. MORPHOLOGY OF CHLAMYDIA
Chlamydia are Gram-negative, obligate intracellular organisms, measuring 0.3–1.0 μm.
The cell wall contains two types of antigens:
(a) A common heat stable, complement fixing group antigen.
(b) A type-specific, heat-labile antigen, which helps to differentiate the serovars by
complement fixation (CF) or neutralization test.
It lack muramic acid and peptidoglycan moiety
7. Inner to the cell wall is trilaminar outer membrane which is cystine-rich and it shows
disulfide linkage which maintains the structural and functional integrity of the outer
membrane. During the conversion of elementary body (EB) to reticulate body (RB), there is
a reduction in disulfide linkage. cystine-rich major outer membrane protein plays an
important role during EB’s attachment to the host cells.
8. PATHOGENESIS
C. Trachomatis cannot penetrate intact skin or mucous membrane, but gains entry
through broken skin and abrasions.
Main mechanism is thrombolymphangitis with perilymphangitis
They travel via lymphatics to multiply within macrophages in the regional lymph
nodes.
After lymphadenitis, areas of necrosis occur within the nodes followed by the
formation of stellate abscesses and they coalesce to form a multiloculated abscess
which ruptures spontaneously leading to fistulae and sinus tracts.
9. Inflammatory process subsides, it fibroses, obstructing the lymphatic
channels, leading to lymphedema, and elephantiasis.
The regional blood supply gets secondarily compromised leading to
ischemia, necrosis, and ulceration of overlying skin and mucous
membrane. These sequences of events are responsible for “esthiomene”
of the external genitalia, rectal strictures, and ulceration.
10. CLINICAL MANIFESTATION
LGV is a chronic disease with a variety of acute and late manifestations.
The clinical course of the disease can be divided into three stages
Primary (site of inoculation)
Secondary (inguinal syndrome)
Tertiary (anogenitorectal syndrome)
11. PRIMARY STAGE
Incubation period is 3–30 days
Primary lesion is a superficial, painless ulcer and it heals without a scar.
Atypical ulcers show no uniformity in number, size, or configuration, they are painful
with irregular edges with necrotic base with granulomatous & slightly infiltrated edges.
12. The coronal sulcus, prepuce, shaft of the penis, urethra, glans, and scrotum are the
common sites in men and the posterior vaginal wall, fourchette, posterior lip of the cervix,
and vulva in women.
Extragenital primary lesions involve mouth, pharynx, or tonsils.
Other manifestations include bubonulus, a chord like lymphangitis of the dorsal aspect of
the penis, and the formation of a large, tender lymphangial nodule.
Local and regional edema can be seen, which can produce phimosis in men and genital
swelling in women.
13. SECONDARY STAGE
(Inguinal Syndrome)
Inguinal syndrome - an inflammatory swelling of inguinal lymph nodes and their
corresponding tributaries and branches also known as bubo
The time from exposure to the appearance of the lesion varies from 2–6 weeks and maybe
as long as 4–6 months.
It is characterized by enlarged and tender regional lymph nodes (bubo). It is unilateral in
two-third of cases.
Predominantly inguinal in males and genitoanorectal in females
The patient feels pain in the groin, with the appearance of swelling that is firm and elastic
in the early stages.
As bubo enlarges, the patient complains of severe pain in the groin and walks with a limp,
bent at the waist in an attempt to limit pain.
14. Enlargement of the femoral lymph nodes is observed. When femoral and inguinal lymph
nodes are enlarged, they are separated by Poupart’s ligament, producing a pathognomonic
groove of LGV called groove sign of Greenblatt.
15. Constitutional symptoms such as fever, chills, sweating, lassitude, anorexia, arthralgia,
myalgia, and malaise often precede or are associated with the onset of bubo.
Deep iliac and perirectal involvement is more common in women presenting with lower
abdominal and back pain
Infection falls on the iliac lymph nodes, producing a tender, firm swelling, occupying the
greater part of the iliac fossa.
Adenitis terminate by softening or suppuration or spontaneous resolution.
16.
17. Suppuration occurs in multiple foci, giving rise to multiple sinuses discharging grayish-
white, thick, and gluey pus.
Healing is very slow and leaves behind contracted scars in the inguinal region.
18. TERTIARY STAGE
Lesions involve the genitalia in association with anorectal changes are known as the genito
anorectal syndrome.
The mechanism of spread to rectal mucosa are –
Anal intercourse
Lymphatic spread from posterior urethra
Direct spread from vaginal secretion
Lymphatic dissemination from cervix or posterior vagina
Fibrosis can lead to lymphatic obstruction manifesting as elephantiasis of genitalia.
More common in women.
Penile and scrotal elephantiasis occurs secondary to chronic bilateral inguinal adenitis.
19. SAXOPHONE PENIS
The penis can be solidified due to elephantiasis called as ramrod penis, and can be
twisted, resembling a saxophone.
The prepuce, penis, scrotum can have destructive ulcers with or without elephantiasis.
Chronic superficial ulcers with irregular, serrated edges and a shiny yellowish-white base
have been observed due to vascular compromise.
Doughy, tender, subcutaneous swellings along the dorsal lymphatic lines of the penis,
called “bubonuli”, can occur without associated lymphangitis.
In males, urethral stricture, prostatitis, seminal vesiculitis, and epididymo-orchitis have
been reported.
20.
21. ESTHIOMENE
In females, genital elephantiasis is more common due to retrograde lymphatic infection.
Chronic edema, sclerosing fibrosis of the subcutaneous tissue, elephantiasis, along with the
chronic genital ulcerations due to a primary infection affecting the lymphatics of these
structures, is known as esthiomene.
Elephantiasis affects the vulva, clitoris, and perianal area. The swelling can be localized to
a part or one side of the labium.
The overlying skin is frequently verrucose or mamillated.
Sequel are Vaginal stenosis and urethral strictures may be produced by localized ring-like
sclerosis of the vaginal and urethral mucosae
22.
23. ANORECTALSYNDROME
oInoculation of the rectal mucosa with Chlamydia may occur directly during receptive anal
intercourse or by lymphatic spread.
oThe earliest symptom are bleeding from anus and purulent anal discharge.
oProctitis, rectal ulceration or rectal stricture can be seen on proctoscopy.
oSevere proctocolitis resembling ulcerative colitis in late neglected case.
oIn the fully developed syndrome, the rectal stricture can be felt by the examining finger,
with nodulation and ulceration of the bowel mucosa distal to the stricture.
oPt with stricture formation complains rectal discharge and bleeding with constipation,
colicky pain and passage of ribbon stools
24. The strictures can be of the following types:
1. Annular stricture with a narrow central or eccentric opening situated 0.5–
2.5 inches from the anal margin.
2. In the tubular type the entire length of the bowel from the pelvirectal
junction downward.
3. In the funnel type, there is a narrowing from below upward which
terminates in an almost impassable stricture just at the upper limit of the
ampullae of the rectum.
25. LGV PROCTITIS
The condition presents with tenesmus, pain, itching, rectal discharge, ulcers, fissures, and
constipation.
Untreated cases can present with anorectal strictures, fistulae and uncommonly, complete
bowel obstruction
26. OCCULAR MANIFESTATION
It can occur at any stage of LGV, produces follicular conjunctivitis, usually unilateral
The course may be chronic and progressive, involving the eyelids, bulb, and cornea resulting
in blindness.
Bilateral conjunctivitis, episcleritis, keratitis, or iritis are allergic manifestations seen in the
inguinal and anorectal syndromes.
27. OTHER EXTRAGENITAL
MANIFESTATIONS
LGV of the cervical and axillary lymph nodes occurs secondary to an inoculatory lesion in
lymphatic drainage areas due to either sexual practices or accidental infection among doctors,
nurses, and laboratory workers handling infectious material.
The oral cavity and pharynx can be affected by autoinoculation or by direct infection.
28. INVESTIGATION
Mild leukocytosis with an increase in monocytes and eosinophils
A more significant polymorphonuclear leukocytosis is found in cases of LGV buboes or
abscesses associated with secondary pyogenic infection.
29. SEROLOGICALTEST
Antibodies can be detected with these tests and a four-fold rise in antibody titers in the is
considered diagnostic of active infection.
The COMPLEMENT FIXATION test performed with LGV antigen is reactive in
increasing titers and becomes positive after 1–3 weeks of infection.
Cross reactions are observed with other chlamydial infections, and antibodies may persist
for many years. Titers of 1:64 or higher are suggestive of infection in patients.
The single L-type immunofluorescence test is more sensitive than CF, but cross-reacts with
other chlamydial infections.
30. The Microimmunofluorescence (micro- IF) test using the antigen type of infecting strain
can detect high titers of type-specific antibodies (IgM > 1:32 and IgG > 1:512) in patients
with the active phase of LGV.
Micro-IF is the most accurate serologic assay which uses formalin-fixed EBs grown in the
yolk sac as antigen.
An immune dotblot technique use a genus-specific lipopolysaccharide antigen.
31. ELISA uses monoclonal antibodies
Radioisotope precipitation (RIP) is more sensitive than micro-IF test,
in which antiglobulin is used to precipitate radioactive-labeled and
soluble chlamydial antibodies.
Immunoperoxidase test is a simple and rapid test for detecting C.
trachomatis specific IgG and IgA antibodies. IgG titer > 1:128 and IgA
> 1:16 are suggestive of active infection
32. ANTIGEN DETECTION
A Rapid assays for antigen detection giving results within 30 min have recently been
developed. It is a rapid method for species and subspecies identification by restriction
fragment length polymorphism (RFLP) analysis of 16S–23S rRNA spacer region.
But none of them discriminate between LGV and Non-LGV biovars, and their
sensitivity is low, which makes their use limited.
33. MOLECULAR TECHNIQUES
NAAT has high sensitivity and specificity.
The samples swabs are taken from the primary lesion or bubonic aspirate.
The test is performed in two steps.
The first step includes NAAT using one of the three methods: PCR, strand displacement
amplification, or transcription-mediated amplification. This step confirms chlamydial
infection
Second step include real-time PCR-based assays and real-time quadruplex PCR based assays.
These tests correctly identify LGV chlamydial strains from non-LGV.
34. HISTOLOGY OF C.
TRACHOMATIS
Stains used are Giemsa-Romanowsky, Warthin-Starry, Grocott methenamine silver or
Macchiavello stains.
In Giemsa stain, elementary bodies stain purple, reticulate bodies blue, cytoplasm grey, and
nucleus pink.
Histopathology of the affected lymph nodes shows multiple stellate abscesses representing
microscopic areas of necrosis surrounded by epithelioid and giant cells.
Definitive diagnosis is possible through isolation of C. trachomatis serotypes L1, L2, and L3
from infected tissues or body fluids. Inoculating the material into mouse brain, yolk sac or cell
culture.
The most common material for isolation appears to be bubo pus aspirate.
35. FREI TEST
Intradermal injection of 0.1 cc antigen into the skin of the volar aspect of one forearm and
a similar quantity of yolk sac material into the skin of the other forearm as control.
It is read at 48 h and a positive reaction is a papule at least 6 mm in diameter, provided
that the papule of control is 5 mm or less in diameter.
Positive 2–8 weeks after infection.
Produces cross-reaction in infections caused by other chlamydial organisms. The test also
tends to remain positive for several years
Commercially manufactured antigen is prepared from the culture of LGV in the yolk sac
of chick embryos was used. Antigen is no longer available commercially.
36.
37. SYPHILLIS LGV CHANCROID DONOVANOSIS
Organism Trepanoma pallidum Chlamydia
trachomatis
Heamophillus
ducrey
Klebseilla
granulomatis
Incubation period 9 – 90 days 3 – 30 days 2 – 5 days 8 – 80 days
Genital ulcer Single Single Multiple Single
Painless Painless Painful Painful
Hard and induration
present
Transient Undermined edges Beefy red ulcers
Lymphadenopathy B/L U/L U/L none
Non tender Tender Tender Pseudo-bubo
Rubbery consistency Bubo is U/L in 2/3rd Enlarged pus filled
Investigation Dark ground
microscopy
NAAT School of fish
appearance
Donovan bodies
38.
39. Vulval or genital elephantiasis with or without ulceration can be due to LGV, donovanosis,
filariasis, and tuberculosis.
In case of the anorectal syndrome, the following differential diagnosis:
Condylomata lata, condylomata acuminata, amebic ulceration of the rectum and anus with or
without stricture, fistula-in-ano, and tuberculosis of the rectum and anus.
40. MANAGEMENT
The main goal of the therapy is to eradicate the organism.
Early and prompt treatment prevents transmission, serious complications, and mutilating
sequels.
The following are the recommendations for the treatment of LGV:
World Health Organization (2016)
1. Doxycycline, 100 mg, orally, BD X 21 days
2. Azithromycin, 1 g, weekly X 3 weeks
41. European Guidelines (2019)
a) Doxycycline, 100 mg, orally, BD X 21 days
b) Erythromycin, 400 mg, orally, QID X 21 days
c) Azithromycin, 1 g, orally, weekly once X 3 weeks
d) Minocycline, 300 mg, loading dose followed by 200 mg, orally, BD X 21 days
e) Rifampicin, 600 mg, orally, OD X 21 days
f) Moxifloxacin, 400 mg, orally, OD X 21 days
42. CDC Guidelines (2015)
1. Doxycycline100 mg orally, BD X 21 days
2. Erythromycin 500 mg orally, QID X 21 days
3. Azithromycin 1 g, orally weekly once X 3 weeks
Children and Pregnancy
In pregnant, lactating women and children below 8 years, erythromycin stearate is preferred
In children (7.5–12.5 mg/kg/dose), QID X 2 weeks
For HIV-positive cases, treatment remains the same but for a longer duration.
43. SURGERY
For buboes hot fomentation is advised.
Fluctuant buboes can be aspirated.
Rectal strictures can be dilated manually with Hegar’s dilators. If not resolved then Ileocolostomy
followed by proctocolectomy is done.
Urethral strictures can be dilated with Lister’s or Clutton’s bougies.
Rectovaginal fistulae, bowel obstruction, gross destruction of anal canal, sphincter, perineum,
esthiomene, and genital elephantiasis are indications for surgery.
44.
45. SYNDROMIC APPROACH
Kit 4 is given to patient in primary stage ( before inguinal stage )
Once the bubos sets in we prescribe Kit 7 to the patient
KIT 7
46. FOLLOW-UP
Patients with acute LGV should be regularly followed upto 3–6 weeks.
Whereas those who require surgical management need to be followed up till their
complaints are dealt with.
47. PARTNER MANAGEMENT
Sexual contacts of LGV patients within the last 60 days before the onset
of symptoms should be examined, tested for Chlamydial infection, and
promptly treated.
Educated about safe sexual practices
Doctors and other healthcare workers must observe universal
precautions such as wearing gloves while examining infected sites.
Editor's Notes
Transplacental transmission is not recorded, but infection can be acquired through an infected birth canal.
EB --- ATTACH TO HOST COLUMNAR CELL ---- UTILIZE HOST RESOURCES------- RB ----- MULTIPLY BY BINARY FISSURE/EXTRUDES OUT ---- EB
Bilateral buboes.
Bilateral inguinal buboes discharging pus.
Antigen for the original Frei test was prepared from the pus obtained from unruptured buboes, diluted with saline, and sterilized by heating.
Herpes – multipe painful vesicles with tender b/l lymphadenopathy
Acc to NACO National STI/RTI Control and Prevention Programme
NACP, Phase-III, India
Kit 4---Tab. Doxycycline 100 mg bd for 15 days and Tab. Azithromycin 1 g stat
Kit 7---- Tab. Doxycycline 100 mg bd for 21 days and Tab. Azithromycin 1 g stat
Kit 7 ---