Ms Valencia Kekana, Mr Alex Vezi, Mr Melt Ndlovu & Mr Frans Radebe –NICD/NHLS
A 30-year old woman presented with erythematous vesicular eruptions on the skin of the left forearm and right arm (see figure). Pustules on the back of the scalp and gingivostomatitis was observed. The rash on her left arm started as a small pimple, which then became bigger, very hard, red, painful and itchy for 6 days, after which, pustulation occurred. It spread to the right arm, face, upper back, the tongue, and scalp.
Question 1: What is the likely diagnosis and describe its clinial presentation?
Answer to Q1
The most likely diagnosis in this patient’s case is primary or reactivated herpes simplex virus infection.
Herpes infection may be caused by Herpes simplex 1 (HSV-1) of Herpes simplex-2 (HSV-2). Primary infection usually presents as a gingivostomatitis but may occur at any other sites e.g. face. It is characterised by a group of vesicles, which pustulate and then crust, surrounded by erythema. Reactivation usually presents with cold sores on the lips or nose often following an upper or lower respiratory tract infection. HSV-2 ulcers typically involve the skin around anogenital area, . In advanced HIV infection, ulcers may persist for weeks and be several centimetres in diameter. Mucotaneous ulceration for >1 month is an AIDS defining illness.
HSV-1 is almost always transmitted through skin to skin contact, both sexual or non sexual. Even though some individuals do not have herpetic lesions to show, they still continue to shed the virus and can still infect others. Kissing is the most mode of transmission of oral herpes.
Following primary infection, Herpes simplex latency is established in neural ganglia, most commonly the trigeminal ganglia (HSV-1) and sacral ganglia (HSV-2). Reactivation, characterised by reappearnce of the blistering rash occurs as virus travels down nerve fibres, back to the same area where it first appeared, causing another episode of sores and blisters. Herpes simplex reactivation can be precipitated by illnesses; viral URTI, exposure to bright sunlight, emotional and physical stress, inadequate sleep, and menstruation, amongst other causes. Genital herpes may be reactivated by friction.
In an immunocompetent person, crusting usually occurs within 7 days and heralds the patient no longer infectious.
Question 2: What are the common differential diagnoses?
Answer to Q2
Question 3: How does this infection remain latent?
Answer to Q3
Like all members of the herpesvirus family, HSV-1 and HSV-2 are characterised by establishment of viral latency following primary infection. In some cases, the virus will remain dormant for the lifetime of the individual, whereas in others, reactivation will occcur, which may be clincial or sub-clinical. This is most common in persons who become immunosuppressed, either due to immunosensence as a result of ageing, or more commonly, secondary to HIV, cancer and chemotherapy, or transplantation.
Maintenance of latency is a complex and still incompleletly understood series of events. During latent infection, HSV expresses latency associated transcript (LAT) RNA and small numbers of micro-RNAs (mi-RNAs), which regulates host gene expression and inhibits neuronal cell death. One host-derived neuronal protein, that is deemed to be critical in maintaining the latent state is NSRF (Neuronal Restrictive Silencing Factor) also known as REST (human Repressor Element Silencing Transcription factor). This protein binds to viral DNA inducing histone deacetylation on the gene ICP4, which is important in induction of HSV lytic gene expression. This sequence of events prevents HSV lytic gene transcription and hence viral replication.
Question 4: How would you treat the case?
Answer to Q4
Acyclovir was prescribed for the patient, to which she responded positively, though blood tests for HSV1 and HSV2 were negative. PCR of vesicular fluid was not performed. Serology for syphyllis was also negative as well as PCR for Treponema Pallidum, Lymphagranuloma Venereum negative and Haemophilus ducreyi. HIV testing was offered.
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