LYMPHOGRANULOMA VENEREUM

LYMPHOGRANULOMA VENEREUM
Lymphogranuloma venereum (LGV) is a sexually transmitted disease of chlamydial etiology with protean clinical manifestation involving the lymphatic system. It should be considered in the differential diagnosis of benign and malignant lymphadenopathy, genical lesions, protocolitis, and rectal stricture. LGV, along with other causes of genital ulcer disease, is increasingly important as a potential facilitator of human immunodeficiency virus (HIV) transmission.
HISTORY
Disease has a colorful nosologic history including such designations tropical or climatic bubo; third, fourth, fifth, or sixth veneral disease lyphopathia venereal; and Nicolas-Farve disease, but the current is now universally accepted. The first major clinical description in 1913, and inclusion bodies in material from lesions were 10 years later. In 1930, the disease was produced by itracerebral inoculation of monkeys with pus from of LGV¬. In 1940, Rake grew the organisin, then thougt a filterable virus, in the yolk sac of ebryonated eggs. In the and 1970s the organism was successfully grown in tissue culture cycloheximide-treated McCoy cells and micrroimmunofluiscence techniques were developed for speciation and recognition.During the 1980s and 1990s. the study of chlamydial. benefited from the considerable advances in the techniques microbial genetics and diagnostic method with the development of polymerase chain reaction and ligase chain reaction techniques for genus identification. No commercial products are yet available for LGV identification, however.
EPIDEMIOLOGY
LGV probably occurs all over the world, with endemic foci in tropical and subtropical countries, but few, if any, systematic data describe incidence or prevalence. Most surveys are actually reports of proportional morbidity in clinic series, and the results are highly variable: Singapore, <1 percent; Australia, rare with a recommendation to intensify surveillance; Durban, South Africa, 6 percenr, Madagascar, 24 percent in 1994 and 14 percent in l999; Rwanda, 10 percent: Paris, 0 percent; Kuala Lumpur, 0 percent; and Jamaica, about 4 percent over the decade of the 1980s with a decrease to 3 percent by l999. Several studies from Africa found very few cases, but a substantial proportional morbidity (8 percent) was noted in Nigeria during the period 1993 to 1997. In the United States, the number of cases reported yearly declined from a peak in 1934 of 2858 cases to a stable level of 200 to 300 during the l980s, and a subsequent decline to 69 reported cases in 1999 .The chief foci of activity have been the District of Columbia and the southeastern United States, affecting predominantly African Americans of low socioeconomic status. Are specific attack rates are highest in the 20- to 40-year-old group. The disease is spread by direct inoculation from genital fluids, but transmission efficiency is not known. Women may be asymptomatic and culture positive, and may serve as a reservoir for infection, as they do for gonorrhea and other genital chlamydial infections.
ETIOLOGY
The disease is caused by members of the eenus Chlamvdia (previously known as Bedsonia) whose structure, metahol sm. DNA and RNA content, and method of reproduction make them similar to Rickettsia The genus is composed of three species: psitacci, pneumoniae, and trachomatis. The species Chlamydia trachomatis has two major biologic varietes (biovars): trachoma or TRIC organisisms, and LGV organisms. The latter, in turn, are characterized by three major --- varieties (or serovars) L1, 1.2, 1.3, and the more recently recognized L2’. The LGV serovars are distibguished by their preferential infectivity for lymph nodes, intracerebral lethality for mice, and different behavior in cell culture. Experimentally, the LGV serovars produce severe hemorragig procititis in monkeys, while TRIC serovars do not. The two biovars, however, share a major cross-reacting antigen which complicates serologic destination between them. Destinations among types is now actively persued with modern biochemichal and molecular biologic methods, including exploration of mechanisms for immunemediate lysis, use of pooled antibody to distinguish between genital and nongenitial infection, and structural genetic differences.
CLINICAL MANIFESTATIONS
LGV is contracted by direct contact with infectious secretions, almost exclusively through sexual activity. The portal of entry and the initial symptoms are determined by the nature of the sex act; inoculation is usually genital, but it may be rectal or pharyngeal. The incubation period varies from 3 to 30 days if primary lesions occur, but it may be longer if adenopathy is the only manifestation. The period of infectiousness and transmission rates are not clearly defined.
Acute and chronic manifestations characterize both the genital (or inguinal) and rectal syndromes. The primary lesion is a 5- to 8- mm soft, erythematous, painless erosion that heals spontaneously in a few days. Occasionally, a button-like papule may appear that is also transient. Such lesions are reported by a fourth to a third of patients. Secondary inguinal adenopathy begins 1 to 2 weeks after the primary lesion as discrete, movable, tender nodes that later coalesce to from a firm, first-sized, elongated, immovable mass. These may occur above and below Poupart’s ligament,giving rise to the “groove sign . Nodes are bilateral in one-third of cases. Rupture of 1uctuant nodes ma’ lead to chronic sinus formation. Initially, the overlying skin is often slightly reddened and edematous, but it later may become thickened and develop a characteristic purplish hue. Generalized systemic symptoms such as fever, chills, and malaise may be prominent. Meningoencephalitis, hepatosplenomegaly, anthralgia, stiff neck, and headache may also occur. A strong association of LGV and other chlamydial infections has been established, but the relationship of chlamydial treatment to improvement of arthritis is more tenuous. Conjunctivitis with marginal corneal ulceration has been reported In untreated cases, the lymphadenopathy usually subsides spontaneously in 8 to 12 weeks.
Late complications of the male inguinal syndrome are rare. Elephantiasis of the penis and scrotum characterized by infiltrative, ulcerative, and fistular lesions occur in approximately 4 percent of cases LGV may mimic cervical lymphoma, as reported in a homosexual male practicing fellatio and a heterosexual male engaging in cunnilingus. In another report. clinical presentation and computerized tomography of intrapelvic nodes suggested cervical cancer in a 24-year-old woman with LGV.32 and LGV has also been associated with tonsillar infection. In keeping with the diagnostic confusion associated with lymphoproliferative syndromes, LGV has also been mistaken for cat-scratch fever,
The acute rectal syndrome occurs more frequently in women than men. In men, direct inoculation of the anal canal is believed to be the mode of entry, whereas the internal lymphatic drainage of the proximal two-thirds of the vagina has been invoked as the source for women. In both sexes, acute manifestations include rectal pain, tenesmus, and mucosanguineous rectal discharge, with typical findings of proctocolicis on sigmoidoscopy. It is important to distinguish LGV from other forms of inflammatory bowel disease, particularly in homosexual men. The major late manifestation is rectal stricture. In women, late scarring, tictulas, ulceration, and elephantiasis of the perineum. called esthiomene. may require radical surgical intervention.
Various dermatologic conditions have been reported in association with acute manifestations, including erythema nodosum, erythema multiforme, scarlatiniform exanthem, and urticana. In addition, photosensitivity has been reported in as many as 35 percent of patients, occasionally associated with conjunctivitis, joint involvement, and erythema nodosum. Sonck observed a phototsensitivity reaction in 140 of 400 LGV cases studied. This rection was manifest 1 to 2 months after the onset of bubo formation and occurred in 60 percent of the chronic and about 20 percent of subacute cases. Punctiform, red papules appeared on the skin 30 min to 3 h after exposure to sunlight. Accompanying this photosensitivity reaction was conjunctivitis in 19 percent, join involvement in 33 percent, and erythema nodosum in 16 percent of patients. The possible allergic or autoimmune nature of these phenomena is supported by the frequent appearance of biologic false-positive tests for syphilis (estimated at 20 percent of cases), the high incidence of cryoprecipitin and rheumatoid factor, and the high serum levels of IgA and IgG in both acute and chronic syndromes.
As noted, as a cause of genital ulceration LGV may play a role in facilitating transmission of HIV. Because of its lymphatic manifestations and potential effects on the immune system, it may also play a role in the differential diagnosis of acquired immunodeficiency syndrome (AIDS) in one reported case, for example, disseminated Kaposi’s sarcoma mimicked LGV in its initial presentation. The syndrome of angioimmunoblastic lymphadenopathy has been reported in association with LGV, and may. As occurred in one case, lead to progressive immunologic deterioration and rapidly fatal immunoblastic lymphoma.
PATHOLOGY
General, histophatologc changes of LGV are nonspecific. Primary are characterized by an exudates of fibrin, polymorphonuclear , and cellular debris. skin test sites or rectal lesions may contain epithelioid nodules. Plasma cells, and occasional giant cells, but these changes are not diagnostic. Stellate triangular abscesses may be observed in biopsy specimens of lymph nodes and are characteristic, but or pathognomonic,of LGV. The pathology of LGV-induced is characterized by crypt distortion, submucosal fibrosis, hypertrophy.fullicular inflammation, and occasional granuloma information. It may be difficult to ditungish these changes from those associated with crohn’s disease. Although localization of lesion is of considerable help (proximal in chron s disease, distal in LGV). it is likely that LGV is not etiologically associated with Chron’s disease.
DIAGNOSIS
One of the earliest diagnosis techniques, the Frei test, used an intradermal inoculation of killed LGV organisms and specificity are in serious doubt, however. and the test is now of historical interest only, because the antigen is no longer commercially available. The diagnostic accuracy of the clinical diagnosis is variable. In one study from South Africa, diagnostic accuracy as true positives divided by true positives plus false positives plus false positives) was found to be 66 percent in men and 40 percent in women but these figures are based on a small number of cases. In another attempt from South Africa, the diagnostic accuracy was 20 percent.Although algorithmic approaches to genital ulcer disease in many clinical settings, clinical diagnosis alone may dependable.
Definitive diagnosis through isolation of the organism from tissue or body among the four be made by using techniques. Because tissue culture may not be readily available, the clinician must often rely on serologic methods. First developed in the 1980s.the complement fixation test has long been the mainstay of diagnosis of LGV. Chlamydia share the target antigen . although less than 3 percent of the general population has a liter as high as 1:16. 40 to 50 percent of women with uncomplicated TRIC-agent cervical infection had titers of 1:16 to 1:32: similar titers occurred in 15 to 20 percent of men with TRIC-associated urethritis. A titer of 1:64 or greater is, however highly suggestive of LGV. Coupled with a fourfold change in titer (which is not uniformly detected), a high titer greatly increases diagnostic assurance. The microimmunofluorescence test, originally developed as a serelogic test. It responds, similar to the complement fixacition test, to the broadly reactive range of antibodies produced by patients with LGV. Again very high titers of LGV antibody are usual in patients with acute infection. Others tests, including enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay methods, are also available but appear to offer little advantage over the microimmunofluorescence test.
DIFFERENTIAL DIAGNOSIS
In view of the nonspecific nature of signs and symptoms, acute LGV should be considered in the differential diagnosis of syphilis, herpes progenitalis, granulomainguinale, and chancroid as well as in bacterial fungal, or tuberculous skin infection. Adenopathy may require consideration of benign and malignant lymphoproliferative disordesrs (e.g., infectious mononucleosis, Hodgkin’s disease), particularly in the presence of oral and cervical infection. Late manifestations must be distinguished from neoplastic skin disease, filariasis, rectal cancer, inflammatory, bowel disease, and hidradenitis suppurativa.
TREATMENT
Antibiotics are effective in the acute illness but may have little or no effect on late lymphatic pathologic pathology. Standard recommended treatment in doxycycline 100 mg orally twice a day for 21 days. An alternative regimen is erythromycin base 500 mg orally four times a day for 21 days. To avoid formation of fistulous tracts, buboes should be aspirated rather than incised and drained. With treatment, prognosis for avoidance of late complications is excellent.

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