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Diagnosis of lymphogranuloma venereum from biopsy samples
  1. I M C Martin1,
  2. S A Alexander2,
  3. C A Ison1,
  4. N Macdonald2,
  5. K McCarthy3,
  6. H Ward4
  1. 1Sexually Transmitted Bacteria Reference Laboratory, Health Protection Agency Centre for Infections, London, UK
  2. 2HIV and STI Section, Health Protection Agency Centre for Infections, London, UK, and Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, London, UK
  3. 3Department of Pathology, Cheltenham General Hospital, Cheltenham, UK
  4. 4HIV and STI Section, Health Protection Agency Centre for Infections, London, UK, and Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, London, UK
  1. Correspondence to:
    Dr I Martin
    Sexually Transmitted Bacteria Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5HT, UK; iona.martin{at}hpa.org.uk

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The Health Protection Agency Centre for Infections launched an alert in October 2004 to improve the awareness, diagnosis, and control of lymphogranuloma venereum (LGV), a sexually transmitted chlamydial infection, following a series of outbreaks in Western Europe.1 To date (9/3/2006), 334 cases of LGV have been diagnosed in 334 men. The case definition for a confirmed case of LGV is the presence of C trachomatis specific DNA, using two nucleic acid amplification tests (NAATs) with different primers, of serovars L1, L2, or L3, determined by genotyping (http://www.hpa.org.uk/infections/topics_az/hiv_and_sti/LGV/lgv.htm). All cases of LGV to date in the UK have been in men who have sex with men and typically present with proctitis and/or inguinal lymphadenopathy. Some of the men in the UK diagnosed with LGV reported long duration of symptoms presenting to gastroenterologists and having been wrongly diagnosed with inflammatory bowel disease before referral to genitourinary medicine (GUM).

Initially, the Sexually Transmitted Bacteria Reference Laboratory (STBRL) only accepted swabs, residual or unprocessed NAAT specimens, and enzyme immunoassay samples, which we had previously validated as being suitable for testing. In January 2005 we were approached about accepting a histology specimen from a male patient who in retrospect the clinician suspected as having LGV. Since this date we have processed seven histological specimens, which we now report.

Genomic DNA was extracted from formalin fixed paraffin embedded biopsies using a QIAamp DNA mini kit (Qiagen, Crawley, Sussex). The paraffin was removed by incubating at 56°C and then we proceeded with the manufacturer’s recommended tissue protocol without any modifications. C trachomatis was confirmed to be present in the extracted DNA by two different real time polymerase chain reaction methods, each having different gene targets. These targets are different to other commercially available NAATs. The genotype of the C trachomatis was then determined by the method of Lan and colleagues.2 Since September 2005, all samples positive for C trachomatis were tested for LGV using the real time polymerase chain reaction method of Morre and colleagues.3

Seven biopsies were processed from six patients attending GUM clinics in the UK (table 1).

Table 1

 Biopsy results from six patients attending genitourinary medicine clinics in the UK

Of seven biopsy samples submitted to STBRL in the past nine months for LGV investigation, we have successfully been able to extract DNA from the biopsies and diagnose three cases of LGV in two patients (Nos 3, 4 and 5), two that were not LGV associated (Nos 1 and 7), and two samples were negative for C trachomatis (Nos 2 and 6) (table 1). A rectal biopsy from patient No 5 is shown in fig 1. It is interesting that two patients (Nos 1 and 7) presented with clinical symptoms characteristic of LGV that were determined to be infected with chlamydia, but of a non-LGV associated serovar. Further clinical research is indicated to consider whether these chlamydial infections were causing the severe inflammation of proctitis and inguinal lymphadenopathy, or if these were incidental findings.

Figure 1

 Rectal biopsy of patient No 5. The lymph node architecture is preserved but severely distorted. There is a florid active and chronic inflammatory process within the node and extending into the surrounding soft tissues. This consists of epithelioid granulomata showing severe central necrosis which is geographic in outline. There is a severe acute inflammatory component with microabscess formation. There is also follicular hyperplasia.

A diagnosis of LGV should be taken into consideration by gastroenterologists and histologists in patients presenting with proctitis or inguinal lymphadenopathy, particularly in men who have sex with men. Examination of biopsy tissue may be useful for diagnosing LGV in patients where cases are being re-examined due to the increased awareness of LGV in the UK, or where a swab for C trachomatis testing was not obtained. The algorithm for accepted samples has now been altered to include histological specimens.

Acknowledgments

We would like to thank all of the clinicians for submitting the biopsy samples, for providing information on the patients, and for reviewing this report: Dr Duncan Churchill, Brighton GUM; Dr Zubayr Sulaiman Gloucester GUM; Dr Colm O’Mahony Chester GUM; Dr Ben Goorney, Sexual Health Clinic, Salford; Dr Sarah Schoeman, Leeds GUM; Jamie Hardie, Newham GUM.

References

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Footnotes

  • Conflict of interest: None declared.

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