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Case of the Month

March 2012

Frans Radebe NICD/NHLS

A 50-year old man from Mozambique presented with a painless penile ulcer with bilateral, tender, matted inguinal lymphadenopathy that had not ruptured. His testes were normal and there was no visible urethral discharge. Genital samples were collected from the ulcer and urethra for Chlamydia culture and blood taken for syphilis and HIV serology.

Genital swab and urethral cultures were positive for Chlamydia trachomatis and Chlamydia trachomatis IgG titre of 1:256 was observed. Syphilis serology was positive at a titre of 1:2 for RPR. He was treated with doxycycline 100mg twice a day for 21 days HIV ELISA was negative. Bubo pus was aspirated from the patient post-treatment, which was negative for Chlamydia on culture. In line with syndromic management of genital ulcer syndrome, he was treated with Benzathine Penicillin for syphilis

Question 1: Discuss the aetiology and pathogenesis of LGV.

Answer to Q1

Aetiology of and pathogenesis of Lymphogranuloma venereum Lymphogranuloma venereum (LGV) is a genital infection caused by the invasive L-serovars of C.trachomatis. The disease is endemic in many parts of the tropics. LGV occurs in travelers who acquire the infection while visiting or living in an endemic area. It cannot penetrate intact skin but gains entry through minute lacerations and abrasions and is predominantly a disease of the lymphatic tissues. Patients with LGV may present with enlarged, painful inguinal lymph nodes, which may be either unilateral or bilateral. Swelling of both inguinal and femoral lymph nodes may result in the formation of a characteristic “groove-sign”. These inflamed lymph nodes may develop into buboes, which may suppurate and subsequently rupture resulting in the formation of inguinal or femoral ulcers and sinuses. Chronic lymphadenopathy with progressive tissue destruction may follow. Apart from a transient, ‘herpetiform’ primary lesion of the external genitalia or an anal ulcer, the clinical evidence of the primary site of infection is only apparent in 3% of cases at presentation. In women early disease may go unrecognized as a result of primary lesions being situated on the cervix. The vast majority of patients recover from LGV without sequelae, but the persistence of Chlamydia in anogenital tissue may cause a chronic inflammatory response and the development of genital ulcers, fistulas, rectal strictures & genital elephantiasis1-4.

In South Africa, LGV is a minor cause of genital ulcer disease, but occurs more frequently in some distinct rural regions comprising Mpumalanga, KwaZulu-Natal and the Eastern Cape with isolation rates of less than 1%.5-8 The infection is frequently detected among migrant-workers, the majority having acquired their infections from Lesotho, Botswana, Swaziland, Mpumalanga and the Eastern Cape.9 Recently, outbreaks of LGV have been reported among MSM and bisexual men many of who are HIV-infected and practice receptive anal intercourse. 10

Question 2: What laboratory tests are available for diagnosis and subtyping of LGV.

Answer to Q2

LGV is commonly diagnosed by:

  • PCR for C. trachomatis serovars L1, L2, L3
  • Culture isolation of LGV from ulcer, urethral swab or bubo pus
  • A positive high-titre Micro-immunofluorescent Test on blood sample.

Less common methods include:

  • Biopsy and histopathologic examination of infected tissue.
  • A positive Frei test – a chlamydial skin test using antigens cultured in yolk sac of chick embryo. A positive test will show a papule on the arm compared to a negative control without an antigen on the other arm. The test remains positive for life if patient exposed to Chlamydia infection. Not specific for serovars L1-3.
  • Complement Fixation Test

Question 3: Discuss the treatment algorithm for a patient with genital ulcer and lymphadenopathy.

Answer to Q3

Treatment algorithm for Genital ulcer syndrome and antibiotic therapy for LGV

Adapted from the revised GUS flowchart of the Primary Health Care Standard Treatment Guidelines and Essential Drugs List, 2009

Antibiotic therapy for C. trachomatis infections include:

  • Doxycycline 100mg twice a day for 21 days
  • Erythromycin 500mg four times a day for 21 days
  • 1g Azithromycin once weekly for 3 weeks
  • Rifampin and sulphonamides can be used in cases of buboes and fistulas

References

  • Annamuthoda H. Rectal Lymphogranuloma venereum in Jamaica. Ann R coll surg Engl. 1961; 29: 141
  • Abrams AJ. Lymphogranuloma venereum. JAMA 1968; 205: 199
  • Sturm PDT, Moodley P, Govender K et al. Molecular diagnosis of Lymphogranuloma venereum in patients with GUD. J Clin Micro 2005; 42: 2973-2975.
  • Mabey D, Peeling RW. Lymphogranuloma venereum. Sex Transm. Infect. 2002; 78: 90-92.
  • Crewe-Brown HH, Krige FK et al, Genital ulceration in males in Ga-Rankuwa Hosp. Pretoria. S Afr Med J.1982; 62:861-3 Coovadia YM, Kharsany A, Hoosen AA. The microbial aetiology of genital ulcers in black men in Durban, South Africa. Genitourin Med 1985;61:266-9
  • O’Farrell N, Hoosen AA, Coetzee KD, Van Ende J. Genital ulcer disease in men in Durban, South Africa. Genitourin Med 1991; 67:322-6
  • Duncan MO, Bilgeri YR, Fehler HG, Ballard RC. The diagnosis of sexually acquired genital ulcerations in black patients in Johannesburg. S Afr J Sex Trasm Dis. 1981;1:203
  • Dangor Y, Fehler HG, Exposto F, Koornhof HJ. Causes and treatment of sexually acquired genital ulceration in Sothern Africa. S Afr Med J 1989; 76:339-41
  • Nieuwenhuis RF, Osserwaarde JM, Gotz HM et.al. Resurgence of LGV in Western Europe: an outbreak of Chlamydia trachomatis serovars L2 proctitis in the Netherlands among men who have sex with men. Clin Infect Dis 2004; 39: 996-1003.
Outcome of the case:

As illustrated in the figure below, the inguinal lymphadenopathy and ulcer were healing by seven and fourteen days respectively (see figure). They had completely healed after 21 days.

Lesson learnt:

Syndromic management is at the heart of STI treatment and accepts that immediate empiric treatment of the symptoms is needed before a definite test result becomes available. Outside of an experienced clinic setting where symptoms can be correctly identified, STI management is often poor. Although LGV responds well to antibiotic treatment, if mismanaged, LGV may cause chronic or irreversible complications. LGV diagnosis may be delayed as it requires tests that are not routinely performed such as C. trachomatis serovar isolation, nucleic acid amplification tests or serology. Recent outbreaks of LGV in Europe among MSM who are mostly HIV-infected, poses a big threat to public health. There is an urgent need to identify risk factors and strengthen clinical recognition and develop point-of-care diagnostic tests for LGV infection to enhance management.

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