Lymphogranuloma venereum detected from the pharynx in four London men who have sex with men

INTRODUCTION

In 2003, initial clusters of lymphogranuloma venereum (LGV) cases in men who have sex with men (MSM) were reported in the Netherlands, ¹ followed by a series of outbreaks in several other European cities. LGV has now re-emerged as a hyperendemic sexually transmitted infection (STI) among MSM in the UK and Europe. ²

A large study in MSM from London and Brighton showed an estimated prevalence of LGV of 0.90% in the rectum and only 0.04% in the urethra. ³ The prevalence of pharyngeal Chlamydia trachomatis (CT) in London MSM is low at 1.2%; ⁴ only 12% of these patients reported throat symptoms at the time of their testing. Doxycycline for one week and azithromycin 1 g stat were both effective in clearing non-LGV pharyngeal infection but larger studies are needed to determine efficacy. ⁴ A three-week course of doxycycline is the recommended treatment for LGV ⁵ and has been shown to be effective in treating LGV proctitis. ⁶

CASES

We report four cases of pharyngeal LGV in London MSM (Table 1). The median age at presentation was 30 years (range 25–39 years). All four men had a past history of STIs including HIV (2), syphilis (3) and hepatitis C (2, of which one was diagnosed after LGV infection), LGV (2), non-LGV CT and gonorrhoea. At presentation, two men had no oropharyngeal symptoms or cervical lymphadenopathy (LN), one had severe odynophagia with a large indurated ulcer of the frenulum of the tongue and cervical LN, and one reported a history of severe pharyngitis with unilateral cervical LN 10 days prior which had improved with a one-week course of oral amoxicillin. Three of the men had symptoms of proctitis with concurrent confirmed rectal LGV infection. Typing of the fourth pharyngeal specimen was performed in the patient without concurrent rectal LGV infection (case 2) due to his unusual history at presentation. All four men had LGV-specific DNA detected from CT RNA-positive pharyngeal specimens (pCT) using the Aptima Combo2^® (AC2; Gen-Probe Inc., San Diego, CA, USA) assay. All samples were sent to the UK Sexually Transmitted Bacteria Reference Laboratory (STBRL) for confirmation of LGV infection.

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Table 1

Summary of four cases of pharyngeal LGV detected in London MSM

Case	1	2	3	4
Age (years)	25	32	27	39
Presenting symptoms and signs	Haemorrhagic proctitis with purulent discharge	Asymptomatic at presentation, not examined	3 weeks rectal bleeding and discharge, declined proctoscopy	Purulent proctitis
	No oropharyngeal symptoms, not examined	10 days prior: sore throat, unilateral tender enlarged cervical node resolved after 1 week oral amoxicillin	Mouth ulcer for 7 days, associated severe odynophagia. Large, tender, indurated ulcer on the frenulum of the tongue, cervical lymphadenopathy	No oropharyngeal symptoms, not examined
Results:Pharyngeal	Pharyngeal AC2 CT equivocal (CT-positive on dual assay but not confirmed on single analyte CT TMA assay) – LGV-specific DNA detected	(Self-taken) AC2 CT-positive – LGV-specific DNA detected	AC2 CT-positive – LGV-specific DNA detected	AC2 CT-positive – LGV-specific DNA detected
Rectal	AC2 CT-positiveLGV-specific DNA detected	AC2 CT-positive (self-taken) – not sent for typing as no anorectal symptoms	AC2 CT-positiveLGV-specific DNA detected	AC2 CT-positiveLGV-specific DNA detected
		Oral doxycycline 100 mg bd 7days
Other results			Mouth ulcer HSV–PCR and T. pallidum PCR negative
Treatment	Oral cefixime 400 mg stat, oral doxycycline 100 mg bd for 21 days	Prior oral amoxicillin for 1 week, 10 days before presentation	Initially, empirical treatment for CT with 1 g oral azithromycin, and for primary syphilis with intramuscular	Doxycycline 100 mg bd for 21 days
			benzathine penicillin 2.4 million units.
			Oral doxycycline for 14 days
Time from treatment to negative pharyngeal AC2 CT/GC test	6 weeks	19 weeks	12 weeks	20 weeks

Infection responded to doxycycline for 21 days in two cases, as well as to seven and 14 days treatment in the other cases. Tests of cure (TOCs) performed from six weeks to five months following treatment were negative in all cases. The prolonged time to TOC was due to patient non-attendance. Three patients had new STIs diagnosed at the time of TOC including rectal and urethral LGV (after initial resolution of symptoms) and gonorrhoea, suggestive of re-infection.

DISCUSSION

In addition to unprotected sex, risk factors for LGV include use of enemas, anal sex toys and fisting ^7,8 suggesting that transmission may be predominantly rectal-to-rectal. However, a questionnaire on practice of anal enema use revealed that most men did not share enema equipment, ⁸ suggesting that it may be the process of anal irrigation associated with enema use that facilitates STI transmission, or that other confounding factors exist. Our cases highlight possible transmission via oro-genital or oro-anal contact. Further research into modes of transmission of LGV is required.

In the UK, CT serovar typing is only performed on specimens from patients with clinical syndromes suggestive of LGV, usually men with symptomatic proctitis. However, not all LGV cases are symptomatic – in the Netherlands a cross-sectional study reported neither anoscopic abnormalities nor anal discharge in 40% and 56%, respectively, in MSM with rectal LGV. ⁸ Currently, pharyngeal CT screening in MSM reporting receptive oral intercourse is not routine. In one of the above centres, pCT specimens were routinely being referred to the STBRL as part of a study to confirm pharyngeal CT DNA positivity and perform specific LGV DNA testing on these specimens; 1.8% (2/110) of referred pCT specimens had LGV-specific DNA detected. ⁹

In MSM the oropharynx may act as a reservoir for CT and possibly LGV, and consideration should be given to routine screening at this site for MSM. No nucleic acid amplification tests (NAATs) have Food and Drug Administration approval for diagnosis of pharyngeal CT, and only culture or direct fluorescent antibody testing is recommended; however, these tests are seldom available to most clinics. These cases illustrate that NAATs can be used for detection and typing of pharyngeal CT. A recent study in Finland to examine methods for detecting LGV among MSM, hetero- and bisexual individuals reported one case of pharyngeal LGV DNA detected by polymorphic membrane protein H gene (pmpH) polymerase chain reaction (PCR) on pCT specimens tested with the AC2 assay (prevalence of 2%). ¹⁰ A case-finding study to examine CT-positive specimens from all sites in MSM has been conducted in the UK, and is expected to further elucidate the prevalence of LGV DNA detected from the oropharynx (personal communication, UK HPA LGV Incident Group).

There are no specific guidelines for treating pharyngeal CT or LGV infection but infection responded to standard LGV therapy with doxycycline for three weeks in cases 1 and 4, and to standard treatment for asymptomatic rectal CT with one week of doxycycline in case 2.

We also highlight the difficulty of STI control among MSM with high-risk sexual behaviour as demonstrated by the past history of multiple STIs and early re-infection with LGV and gonorrhoea.