Are serological chlamydia specific markers useful to detect asymptomatic cases of LGV proctitis?
Recent reports on lymphogranuloma venereum (LGV) proctitis in men who have sex with men (MSM) have highlighted that affordable diagnostics for both symptomatic as well as asymptomatic LGV infections are urgently needed. 1,2 LGV responds well to extensive antibiotic treatment but when untreated LGV can cause chronic or irreversible complications because of severe inflammation and invasive infection.3
In a recent interesting study, van der Snoek et al conclude that an elevated Chlamydia trachomatis (CT) IgA antibody response and the age of the infected individual are of possible diagnostic value for early detection of LGV proctitis. 4 Based on their study of 24 MSM with L2 proctitis and 15 MSM with rectal CT (non-LGV) infection, they suggest that the association between LGV L2 and significantly higher titers of IgA and IgG are caused by more invasive and more chronic inflammation of the proctum due to the LGV biovar.
As published previously, and also mentioned in the article of van der Snoek, a considerable number of the patients with LGV proctitis in the present epidemic are asymptomatic.2,4,5 In a retrospective case controlled study we found only 47% of the LGV cases had signs of proctitis (mucous membrane abnormalities) upon proctoscopic examination.2 Unfortunately the manuscript of van der Snoek fails to inform its readers on the patient complaints and/or clinical symptoms found among the included patients. Their recommendation to test IgA levels in high risk populations to exclude LGV might therefore possibly miss a considerable number of asymptomatic cases of LGV proctitis with consequences for both the individual patient and the population at risk.
We previously studied MSM patients with any form of chlamydial proctitis and they were designated into 2 groups based upon mucous membrane abnormalities found during proctoscopic examination.5 In the group of 44 cases with mucous membrane abnormalities 32 had LGV proctitis and 12 had non-LGV chlamydial proctitis. In the group of 30 men without mucous membrane abnormalities, 13 had LGV proctitis and 17 had non-LGV proctitis. In the group with mucous membrane abnormalities IgG serology (C. trachomatis–IgG pELISA, Medac Diagnostika GmbH, Hamburg, Germany) had a high positive predictive value for LGV proctitis (0,94) when a cut-off value of < 1:200 was used. However, in the group without mucous membrane abnormalities both the positive and negative predictive value were low (resp. 0,57 and 0,65). We concluded that IgG species-specific serology could help support the LGV diagnosis when clinical symptoms are present but cannot be used for screenings purposes to detect LGV-infected persons without clinical symptoms.
In a second retrospective case controlled study performed by our group in Amsterdam, proctosopic examination and anal mucosal smears in MSM with receptive anal sex in the previous 6 months were found to be helpful to detect LGV proctitis.2 In that study 87 men with proctitis based on CT serovar L2b men were compared with 2 separate control groups: MSM who had non-LGV Chlamydia proctitis (n = 377) and MSM who reported having receptive anorectal intercourse but who did not have anorectal chlamydia (n = 2677). Apart from HIV seropositivity, either proctitis detected by proctoscopic examination or elevated >10 white blood cells/high-power field detected on an anorectal smear specimen were found to be the only clinically relevant predictors for LGV proctitis in MSM.
In the recently published IUSTI/WHO guideline on STI proctitis it is recommended to perform proctoscopy and anal mucosal smears in all MSM with receptive anal sex in the previous 6 months and to screen for anal chlamydia and gonorrhea.6 In case inflammatory signs and/or >10 leucocytes per high-power field upon microscopic examination of anal mucosal smears are detected presumptive treatment with doxycyclin is advised until the definite diagnosis become available. In case anal chlamydia is found, biovar determination of the chlamydia strain is indicated to confirm potential LGV proctitis.
In the ongoing LGV proctitis epidemic there is a great need for simple and affordable diagnostic procedures to screen the (asymptomatic) population at risk. Additional serological markers are required to evaluate as diagnostic tools for LGV proctitis in larger, well defined and described cohorts. Until those studies are performed the gold standard for LGV diagnostics (both in symptomatic as well as in asymptomatic patients) remains molecular determination of chlamydia biovars.
1. Ward H, Martin I, Macdonald N, Alexander S, Simms I, Fenton K, French P, Dean G, Ison C. Lymphogranuloma venereum in the United kingdom. Clin Infect Dis. 2007 Jan 1;44(1):26-32.
2. Van der Bij AK, Spaargaren J, Morré SA, Fennema HS, Mindel A, Coutinho RA, de Vries HJ. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study. Clin Infect Dis. 2006 Jan 15;42(2):186- 94. Epub 2005 Dec 5.
3. Weir E. Lymphogranuloma venereum in the differential diagnosis of proctitis. CMAJ 2005; 172:185.
4. van der Snoek E, Ossewaarde J, van der Meijden W, Mulder P, Thio B. The use of serologic titers of IgA and IgG in (early) discrimination between rectal infection with non-LGV and LGV serovars of Chlamydia trachomatis. Sex Transm Infect. 2007 Aug;83(4):330-4.
5. Spaargaren J, Fennema HS, Morré SA, de Vries HJ, Coutinho RA. New lymphogranuloma venereum Chlamydia trachomatis variant, Amsterdam. Emerg Infect Dis. 2005 Jul;11(7):1090-2.
6. McMillan A, van Voorst Vader PC, de Vries HJ. The 2007 European Guideline (International Union against Sexually Transmitted Infections/World Health Organization) on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens. Int J STD AIDS. 2007 Aug;18(8):514-20