Herpes Labialis results from reactivation of latent herpes simplex virus (HSV-1 or HSV-2) harbored in the trigeminal ganglion during times of psychological stress, cutaneous injury or photo exposure. Following reactivation, the virus is anterogradely transported through axonal termini to the skin where the virus is released and replicates causing a clinical outbreak. Botulinum neurotoxin A (BoNTA) is known to inhibit presynaptic neuropeptide and neurotransmitter release. Whether it has the capacity to interfere with viral shedding and delivery into the skin remains unclear. We were interested in determining whether BoNTA could serve as a potential therapeutic or prophylactic treatment approach for frequent and severe HSV recurrences. We describe a clinical case report in which a patient successfully maintained a sustained absence of HSV outbreaks in regions where BoNTA was intradermally administered. BoNTA may offer a novel therapeutic approach for preventing recurrent HSV disease. J Drugs Dermatol. 2018;17(10):1127-1129.

CASE REPORT

A 33-year-old Caucasian female patient presented to the Dermatology clinic with a severe case of eczema herpeticum involving the face and dorsal medial hands complicated by impetigo. She had a longstanding history of atopic dermatitis and a 5-6-year history of monthly labial HSV outbreaks on the left upper lip. Although her atopic dermatitis had been controlled using topical steroids, she continued to experience frequent and regular HSV eruptions.The patient was initially treated for her severe eczema herpeticum and impetigo (Figure 1A) with Keflex 500mg PO TID x 14 days, acyclovir 400mg PO x 7 days, and 2.0% mupirocin ointment topically TID x 10 days. Eight days following initial onset of treatment, this outbreak resolved. The patient was allowed to heal for an additional 7 weeks (Figure 1B) at which time we initiated the off-label use of BoNTA as a prophylactic approach to prevent future HSV outbreaks. The initial treatment with BoNTA involved intradermal injections of 1 unit each of onabotulinumtoxinA (BOTOX) injected at 4 sites on the upper cutaneous lip (Figure 1C), spaced approximately 1cm apart. No adverse effects were observed at the time of injection or one week following. However, a new HSV lesion appeared in the upper right perinasal region, 4 weeks later (not shown). No new lesions appeared for the next 10 weeks. A new outbreak of attenuated eczema herpeticum appeared 8 weeks following the initial BoNTA injection, however the areas of skin injected with BoNTA (peri-oral) were spared (not shown). The patient presented with a new HSV outbreak 4 months after the initial BoNTA injections and it was determined that she be re-treated. The patient was initially treated with standard of care, acyclovir 400mg PO 5x daily for 5 days. One week after completing acyclovir treatment she was then reinjected with 15 units of abobotulinumtoxinA (Dysport). Again, the BoNTA treatment prevented HSV flares at the site of the original outbreaks, however three months later she developed two flares of HSV on the left lower lip (Figure 1D), where she had not been treated. The fulminant upper lip outbreaks were eradicated with repeated BoNTA dosing at four-month intervals for 19 months.

DISCUSSION

According to the World Health Organization, 3.7 billion people under the age of 50 are infected with HSV-1.1 HSV-1 is thought to cause roughly 80% of orolabial cases, and HSV-2 the remaining 20%.2 HSV outbreaks occur when a latent virus becomes reactivated and is delivered to the skin via sensory nerves, and the reactivated virus replicates productively in the skin and forms an ulcerative lesion. HSV reactivation from latency stage can be triggered by various stimuli, including sickness and fever, trauma, emotional stress, sunlight and