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Lymphogranuloma Venereum: What Does the Clinician Need to Know?

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Lymphogranuloma Venereum: What Does the Clinician Need to Know? CME Genitourinary medicine Lymphogranuloma venereum: and constipation. Systemic symptoms such as fever and malaise can accompany what does the clinician need to know? this stage. Tertiary stage John White MBBS FACh SHM, Locum clinical course of LGV is classically divided Untreated infection may then progress to Consultant in Genitourinary Medicine, Guy’s into three stages. chronic inflammation and destruction of and St Thomas’ NHS Foundation Trust, tissue in the involved areas, including: London Primary stage • chronic proctocolitis mimicking Catherine Ison PhD FRCPath, Director, inflammatory bowel disease (IBD) Sexually Transmitted Bacteria Reference The primary lesion is usually transient fistulae Laboratory, Health Protection Agency Centre and often unnoticed. It may appear at the • strictures for Infections, London site of inoculation as a painless papule, • pustule or ulcer, most likely in the • chronic granulomatous conditions Clin Med 2008;8:327–30 anogenital region. Incubation periods of the external genitalia, including from 3–30 days after sexual contact have lymphoedema and elephantiasis. It has been surprising to see that lym- been observed. Proctitis in homosexual These tertiary sequelae tend not to phogranuloma venereum (LGV), caused men can occur as a primary manifestation reverse with antibiotic therapy alone. by the L-serovars of Chlamydia tracho- of infection following direct inoculation matis, a sexually transmitted infection of the rectal mucosa. Symptoms of proc- Presentation of lymphogranuloma (STI) previously rare in industrialised titis may arise within days of anoreceptive venereum in homosexual men countries, has emerged as a significant sexual exposure. disease among homosexual men over the LGV detected among homosexual men in 1,2 past three years. Following the recogni- Secondary stage the UK has so far largely presented as tion of a large number of cases of LGV overt proctitis (Fig 1), possibly as either a proctitis among homosexual men in the The secondary stage of LGV involves the primary or a secondary manifestation of Netherlands in 2004,3 an epidemic is now subsequent spread of C. trachomatis to disease, in many cases with severe local well established in the UK,2,4 Western regional lymph nodes, which leads to and systemic symptoms. Some cases were Europe and the USA. Thus far, the infec- inflammation and swelling, and the misdiagnosed with ulcerative colitis or tion has been confined almost exclusively entire chain can become matted with Crohn’s disease and long delays occurred to the homosexual male population, considerable periadenitis. Suppuration before LGV was recognised and treated especially those coinfected with HIV,2 and bubo formation can ensue, which appropriately. Endoscopic appearances hepatitis C5 and other STIs, most cases may then ulcerate and discharge pus and histopathological findings from rectal presenting with severe proctitis. from multiple points creating chronic biopsies in LGV show severe inflam- Diagnostic delays have occurred, com- fistulae. Rectal involvement at this stage matory changes in common with IBD monly due to the non-specific nature of may develop in both men and women, (Fig 2), and no pathognomonic features the clinical presentation. Even inguino- presenting as an acute haemorrhagic have yet been described that can be attrib- genital manifestations of LGV such as proctitis with symptoms of mucopuru- utable to LGV. A small number of men buboes and genital ulcers, usually seen in lent discharge, pain, bleeding, tenesmus have presented with inguinogenital regions of the world where LGV is endemic, are beginning to be recognised.2 Prompt antibiotic treatment is effective Fig 1. Endoscopic view of the rectum in a and curative, yet broader awareness 42-year-old HIV-positive homosexual man among a wide range of clinicians is needed with a nine-month history of intermittent to enable appropriate investigation and diarrhoea and constipation associated management and the interruption of with blood, mucus and pain on defecation. onward spread. Rectal biopsy showed severe non-specific inflammation and the patient was treated empirically with steroid suppositories for Clinical presentation possible irritable bowel disease. Following genitourinary medicine review, a rectal swab In contrast to the D-K serovars of C. tra- specimen tested positive for Chlamydia trachomatis, subsequently typed as the L2 chomatis responsible for genital mucosal strain. Symptoms abated completely after disease, the LGV-associated serovars are three weeks’ treatment with doxycycline. lymphotropic and thus capable of regional dissemination and systemic disease. The Clinical Medicine Vol 8 No 3 June 2008 327 © Royal College of Physicians, 2008. All rights reserved. CME Genitourinary medicine Fig 2. Rectal biopsy specimen from an addition, no diagnostic service has been HIV-positive homosexual man with a six- available for genotyping C. trachomatis month history of purulent anal discharge, to identify the L-serovars. bleeding and constipation. Histological features included rectal mucosal ulceration and non-specific inflammatory changes Detection of lymphogranuloma within the lamina propria, including both cryptitis and crypt abscesses. venereum in rectal specimens In October 2004, the Sexually Trans- mitted Bacteria Reference Laboratory (STBRL) at the Health Protection Agency (HPA) Centre for Infections Fig 3. Ruptured inguinal bubo in a established a testing algorithm for the homosexual man who had presented with detection of LGV in rectal specimens. a three-week history of painful bilateral This includes confirmation of the pres- inguinal swellings. Lymphogranuloma ence of C. trachomatis using a real-time venereum-associated Chlamydia trachomatis DNA was isolated from aspirated pus. polymerase chain reaction (RT-PCR) that uses primers different from any commercial assay.11 Residual samples from both NAATs and EIAs or dry swabs can be tested. Any specimens giving a negative result are confirmed using the Qiagen RT-PCR (which is not used extensively in the UK) and a report syndrome including anogenital ulceration responses have been observed in LGV issued. All samples confirmed to contain and buboes (Fig 3). Less common presen- infection with the recommended treat- C. trachomatis-specific DNA are then tations have been described such as ure- ment of oral doxycycline 100 mg bid for tested to determine whether this belongs thritis6 and bubonulus7 (primary stage of three weeks.9,10 to an LGV serovar (L1, L2 or L3), using disease with large tender lymphangial an RT-PCR which detects a deletion in nodule and lymphangitis of dorsal penis). Laboratory diagnosis the pmp gene present only in L-serovars Asymptomatic rectal infections have been of C. trachomatis.12 detected only rarely within a large case- The laboratory diagnosis of LGV requires This test gives a positive result for finding exercise in the UK, suggesting that the detection of C. trachomatis belonging LGV-associated serovars and a negative a large reservoir of ‘silent’ infection is to serovars L1, L2 and L3 from clinical result for other serovars and provides a unlikely.8 samples. Historically, growth in tissue timely result allowing a positive report to culture cells has been the only ‘approved’ be issued. All positive specimens are then Differential diagnosis method. However, this facility is available confirmed using a nested PCR that in very few laboratories in the UK, is tech- amplifies the omp1 gene which is present The differential diagnosis of proctitis nically difficult and has a low sensitivity in single copy, followed by digestion with among homosexual men includes rectal even in the most experienced laborato- restriction endonucleases.13,14 The pat- gonorrhoea, which is usually less severe ries. Alternative methods include direct tern obtained is compared with control clinically and often asymptomatic. immunofluorescence, a test licensed for strains and can be confirmed by DNA Anorectal herpes simplex virus-1 or -2 detection of C. trachomatis from rectal sequencing. infection, especially if a primary infec- swabs from symptomatic patients, but STBRL has now tested over 4,000 speci- tion, can cause severe anorectal pain often again technically demanding and with mens and identified over 600 LGV positive out of proportion to other proctitis symp- low sensitivity. Enzyme immunoassays results in the UK. All LGV positive speci- toms and may also cause regional neuro- (EIAs) and nucleic acid amplification mens were found to belong to the serovar logical symptoms including urinary tests (NAATs) have been widely used but L2 where full genotyping was possible retention and constipation. Non-LGV neither is licensed for use with rectal (S. Alexander; personal communication). rectal C. trachomatis infection caused by specimens. Only 36% of the specimens originally serovars D-K is usually asymptomatic but The lack of an available licensed com- tested positive for C. trachomatis by EIA can occasionally show clinical features of mercial test to detect C. trachomatis in were confirmed compared with 92% of overt proctitis. Syphilis infection is on the rectal specimens may have prevented the those originally tested by NAATs.15 This rise again among homosexual men, and true extent of the outbreak being recog- highlights the lack of specificity of EIA for in its role as ‘the great imitator’ can cause nised. Many microbiologists have been detection of C. trachomatis from rectal clinical proctitis. reluctant to use an unlicensed test as
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