Case courtesy of: Bernadett I. Gosnell, Sonal R. Verma, Virgilio J. Da Conceicao, Nithendra Manickchund, M. Yunus, S. Moosa, Department of Infectious Diseases, Nelson R. Mandela School of Medicine, and King Edward VIII Hospital, Durban
A 46-year-old female patient was seen at KEH VIII hospital.
Presenting complaints: Non-healing ulcers of 4 months duration in the genital region, left infra-mammary region, right lateral tongue and lower lips. She also complained of weight loss, malaise and anorexia. She had no fever, no night sweats, no dysphagia, no odynophagia and no other gastrointestinal symptoms.
Past medical history: She was HIV-seropositive on first-line antiretroviral therapy (TDF/FTC/EFV) for the last seven years. Her most recent CD4 count was 3 cells/µL, viral load 29 056 RNA copies/ mL (4.46 log), suggesting that she had been failing treatment for a while. She was diagnosed with pulmonary tuberculosis four years ago and completed six months of appropriate treatment. She was known to be allergic to trimethoprim/ sulfamethoxazole
Social history: She did not smoke or drink alcohol. She was employed but had been on sick leave for the last two months.
Figure 1: Genital lesions
Figures 2-4: Ulcerative lesions on lip and inframammary region
Question 1: What are the commonest causes of genital ulcer disease in South Africa?
Answer to Q1The majority of genital ulcers are caused by sexually transmitted infections (STIs). Non-infectious aetiologies should be considered once STIs have been ruled out. Of significance, genital ulcer disease (GUD) has been recognised as an important risk factor for not only acquiring HIV infection but also for transmitting HIV. A recent study from Johannesburg (Kularatne R. S. et al) reported that herpes simplex virus is the dominant cause of GUD, responsible for about 60% of all cases. This was followed by Treponema pallidum (3.9%), Chlamydia trachomatis (0.9%), Haemophilus ducreyi (0.5%) and mixed aetiology (0.8%). Of interest, no STI pathogen could be identified in 34.8% (Kularatne, Muller et al. 2018). This study also demonstrated a strong association between HIV seropositivity and GUD.
Question 2: How do genital ulcers impact on HIV disease?
Answer to Q2
HIV-associated immune dysregulation results in many diagnostic and therapeutic challenges. The control of STIs is important as this has long term public health implications. GUD has been recognised as a risk factor for acquisition for HIV. Several studies have demonstrated that GUD is more closely associated with HIV infection compared to other STIs. Several hypothesis have been suggested to explain this observation:
Question 3: How should GUD be investigated once syndromic management fails?
Answer to Q3A good history and clinical examination is very important to establish the cause of GUD. However, diagnostic dilemmas and therapeutic challenges always remain. The following investigations should be considered:
Question 4: How do you confirm the diagnosis of HIV-associated genital ulcer disease?
Answer to Q4This is a diagnosis of exclusion. Suspect this when patients have a low CD4 count and a high viral load or are on ineffective ART.
Question 5: What is the algorithm for management?
Flowchart: Adapted from ”Sexually Transmitted Infections Management Guidelines” 2015, South Africa
Effective antiretroviral therapy in this group of patients is critical for several reasons:
Case updateOur patient had a genital ulcer biopsy, which revealed chronic ulcerated skin with acute inflammatory exudate and granulation tissue. The stroma contained a dense mixed acute and chronic inflammatory cell infiltrate. No granulomas, acid fast bacilli, fungi or viral inclusions were identified.
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