Herpes Simplex - Part One

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Andi Marmor, MD, and Lisa Patel, MD review the cutaneous and systemic manifestations of HSV1, when testing is indicated, potential co-infections, and discuss management strategies depending on presentation.

• Transmission of HSV-1 occurs when someone with no prior infection comes in contact with herpetic lesions, mucosal secretions, or skin lesions that contain HSV-1. Transmission can occur when infected body secretions come into contact with a break in the skin. 
• In the acute phase of the infection, the herpes virus replicates at the site of contact. From there, the virus enters the sensory nerve and travels to the ganglion. Typically it establishes latency in the trigeminal nerve ganglion (or sacral ganglion depending on the initial site of infection) and it can then reactivate in any of the branches of that nerve throughout life.
• HSV PCR and viral culture are the two tests used to confirm the diagnosis of  HSV.
• • A viral culture can distinguish between HSV-1 and HSV-2.
  • HSV PCR is typically faster and more sensitive than a viral culture. 
  • Serologic testing has a limited role in acute infection but can be helpful in establishing prior infection in someone who is, for example, undergoing an organ transplant where antiviral prophylaxis might be needed. 
• Primary HSV-1 oral infection usually presents as gingivostomatitis in children. High fevers and malaise are the typical prodromal symptoms which are then followed by the development of painful vesicular lesions. Lesions can affect the entire gingiva and also often involves the buccal mucosa, tongue, and the floor of the mouth. There may also be some sores on the outside of the mouth and around the lips.
• • In coxsackievirus, the majority of the lesions are in the posterior oropharynx whereas with HSV gingivostomatitis, the majority are in the anterior mouth. The distribution of the lesions can help distinguish between the two viruses. 
• Children with gingivostomatitis may require hospitalization for pain control and/or dehydration. 
• For pain management, Andi advises using around the clock NSAIDs and does not recommend using Magic mouthwash.
• • Magic mouthwash is typically a 1:1:1: ratio combination of viscous lidocaine, diphenhydramine, magnesium hydroxide (or aluminum hydroxide) mixed with a flavored syrup. Andi does not recommend because 1) viscous lidocaine is well absorbed through the oral mucosa and can quickly reach a toxic level in young kids and 2) there is not much evidence showing that improves pain control or that helps kids hydrate. 
  • Honey was shown in a recent randomized control trial to both improve pain control and less than the time to healing. 
• Acyclovir, in addition to supportive care measures, is recommended in children with severe symptoms and who present within 72-96 hours of disease onset. A Cochrane review from 2008 showed that it decreased the time to healing and lessened the amount of pain medicine needed. The typical dosing is 15 mg/kg by mouth (maximum single dose 200 mg) five times per day.
• Herpetic whitlow is an infection of the soft tissue of the finger caused by HSV. It is usually localized to the nailfold. These lesions are initially clear-yellow vesicles that then coalesce into a larger blister. Herpetic whitlow is often confused with a bacterial infection like paronychia or a pulp abscess.
• • Unlike a paronychia, the area filled with pus is not tense in the setting of herpetic whitlow.
  • Treatment in most cases is doing nothing. The time that this takes to resolve is two to three weeks. Consider treatment with acyclovir if it is on multiple digits, if the child is systemically ill, or if there is concern for a more widespread infection.
• Herpes gladiatorum is a skin infection that classically occurs on the face, neck, and arms of wrestlers.
• Eczema herpeticum is a widespread HSV infection of the skin in a patient with pre-existing atopic dermatitis. Vesicles and characteristic "punched-out" lesions with hemorrhagic crust appear on areas of pre-existing skin disease. 
• Complications of eczema herpeticum include a superimposed bacterial infection, particularly with Staph. Because of the potential seriousness of this condition, treatment with systemic acyclovir is recommended oftentimes with an anti-staphylococcus medication in addition. 
• • The continued use of topical corticosteroid for the treatment of the underlying eczema is somewhat controversial but a recent paper in Pediatric Dermatology showed that receipt of topical steroids did not prolong hospitalization. 
• The most common secondary reactivation is recurrent herpes labialis or cold sores of the lip - that is a recurrence of HSV that has been lying dormant in the trigeminal ganglion.
• • Triggers for recurrence include immunodeficiency, stress, exposure to sunlight, and fevers. 
  • The lesions are typically present along the vermilion border but they can also be present on the oral mucosa. Most patients have prodromal symptoms including pain, burning, or tingling, 
  • Topical treatments, such as Penciclovir, have shown some benefits. However, given the need for frequent application, some people advocate for the use of oral acyclovir. Oral therapy has been shown to shorten the course of infection when taken during the prodromal period. 
  • Chronic suppressive therapy is recommended if recurrences are happening four or more times a year and there is no predictable prodrome. 
• Herpes keratitis is a corneal infection that is caused by reactivation of herpes virus that has been latent in the trigeminal ganglion. It tends to present as a unilateral, uncomfortable tearing eye with redness and irritation. 
• • On fluorescein exam, you will see dendritic lesions.
  • Patients should be referred to Ophthalmology for a slit lamp exam and for monitoring the integrity of the cornea. 
• Herpes virus can cause peripheral facial nerve palsy. In a peripheral seventh nerve palsy, there is weakness affecting the mouth, eye and forehead. It is the involvement of the forehead musculature that distinguishes it from a central lesion. Patients with a peripheral facial nerve palsy will have weakness raising the eyebrow and wrinkling the forehead.
• Neonatal HSV is classified into three categories: localized skin, eye and mouth (SEM); CNS and disseminated disease. 
• • SEM disease is associated with typical herpes ulcers on the face or on the mucous membranes seizures and encephalopathy.
  • Manifestations of neonatal HSV CNS disease include seizures and encephalopathy
  • Disseminated HSV has a sepsis-like presentation, involving multiple organs. These neonates are critically ill. 
  • Women with a primary genital HSV infection acquired near the time of delivery have the highest risk for transmission. 
• HSV encephalitis is mainly caused by HSV-1, whereas meningitis is more often caused by HSV-2