What Are the Symptoms of Herpes Simplex Keratitis?

Patient Presentation
A 6-year-old female came to clinic for her well child examination. She had recently moved to the area and her mother was concerned because of a “spot” on her eyelid. She had been diagnosed with herpes simplex of the right upper eyelid about 1 year previously. Her mother described it as a vesicular rash that was very painful and she took an oral medication for it. It resolved but the mother was concerned about hyperpigmentation on the right eyelid. She had not seen an eye doctor and had been well except for a left forearm fracture from falling off playground equipment which had resolved with casting. The review of systems was non-contributory.

The pertinent physical exam showed a healthy female with normal vital signs and growth parameters were in the 50-90%. HEENT showed no obvious hyperpigmentation but what might have been a tiny area where the mother pointed it out on the right upper eyelid. Visual acuity was 20/20-30 for both eyes and her visual examination was normal as was the rest of her physical examination.

The diagnosis of a healthy child with a history of herpes of the right upper eyelid. As there was no history of ocular involvement and it had been around a year since the original occurrence, the pediatrician only counseled the mother to monitor closely for recurrences including pain, tingling etc. of the eyelid, any visual problems or any concerns about the eyes. She said, “herpes infections are really common and can be hard to diagnose, but they can also cause real problems in the eyes if not treated right away or properly. Herpes tends to happen again especially in children and therefore if something seems to be happening with her eyes, I want to know about it so I can get you some help.”

Herpes simplex virus (HSV) infections are common with an estimated 50% of the US population being infected by age 30, and with latent infection harboring in the trigeminal nerve in 100% of people by age 60 years. HSV infections can cause a vesicular or pustular skin rash that is painful, burning or pruritic and also flu-like symptoms with fever, chills, headache, and fatigue. HSV can also be asymptomatic.

To laymen, herpes simplex viruses cause “cold sores,” but to health care personnel, herpes causes many systemic infections including eczema herpeticum, folliculitis, herpes gladiatorum, whitlow, encephalitis and ocular HSV. Ocular HSV has many forms including primary or recurrent disease and involvement of all ocular tissues including “…blepharitis, conjunctivitis, epithelial keratitis, stomal keratitis, endothelialitis, iritis, trabeculitis, and retinitis.”

Ocular HSV infection is usually caused by HSV-1 but HSV-2 can cause keratitis. Neonatal primary HSV keratitis is caused by HSV-2 because of antenatal, intrapartum and postpartum exposure. HSV-2 seroprevalence in pregnancy is estimated to be 20-30%. Ocular HSV infections can cause significant complications including being the most common cause of corneal blindness in developed countries, and causing some form of visual disability in 1 million people/year globally. Children have worse outcomes with ocular HSV than adults “…includ[ing] recurrence (50%), corneal scarring (80%) and corneal neovascularization (>30%).” Risk factors for recurrence include trauma, eye surgery, atopic dermatitis, diabetes, and immune compromised status.

Learning Point
HSV is primarily a clinical diagnosis, but viral culture (gold standard) and polymerase chain reaction methods can detect HSV when there is active viral replication. Symptoms of HSV keratitis include burning, tearing, swollen eyelids, decreased visual acuity, and photophobia. However, a significant number of primary infections may not cause symptoms (up to 2/3rds) or not be recognized/reported by the children or adult caregivers. It can also be easily misdiagnosed. Therefore patients with potential HSV infection near the eyes usually are discussed or evaluated with ophthalmology.

Complications are caused by viral infectivity and activity and the immunological response of the host. Therefore treatment is both antiviral and steroid medications. Medications are systemic and/or topical. Antiviral medications current including acyclovir, valacylovir and ganciclovir. Patients are often started on prophylatic antiviral medication and monitored for recurrence. If there is no recurrence after a period of time (~1 year) then prophylaxis is stopped and patients continue to be monitored. For recurrence, patients are treated again with antiviral and/or steroids. Antiviral resistance has been documented particularly in patients with severe disease and taking topical steroids.

Questions for Further Discussion
1. What are the differences between herpetic whitlow and acute paronychia? A review can be found here
2. How are neonates evaluated and treated for potential HSV encephalitis?
3. How are outbreaks of herpes gladitorum contained?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Tsatsos M, MacGregor C, Athanasiadis I, Moschos MM, Hossain P, Anderson D. Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents. Clin Experiment Ophthalmol. 2016;44(9):824-837. doi:10.1111/ceo.12785

Pinninti SG, Kimberlin DW. Neonatal herpes simplex virus infections. Semin Perinatol. 2018;42(3):168-175. doi:10.1053/j.semperi.2018.02.004

Vadoothker S, Andrews L, Jeng BH, Levin MR. Management of Herpes Simplex Virus Keratitis in the Pediatric Population. Pediatr Infect Dis J. 2018;37(9):949-951. doi:10.1097/INF.0000000000002114

Valerio GS, Lin CC. Ocular manifestations of herpes simplex virus. Curr Opin Ophthalmol. 2019;30(6):525-531. doi:10.1097/ICU.0000000000000618

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa