CASE REPORT
Herpes Zoster Stromal Keratitis After Varicella Vaccine Booster in a Pediatric Patient Peter Krall, MD, and Anup Kubal, MD
Purpose: In this study, the case of a healthy pediatric patient who presented with herpes zoster (HZ) stromal keratitis after vaccination with live attenuated varicella vaccine (Varivax) and subsequent booster is described.
Method: This is a retrospective case review. Results: A 6-year-old girl with no medical history presented with HZ ophthalmicus and stromal keratitis. She had received the original Varivax vaccine at 1 year of age and a booster 1 year before presentation. Topical prednisolone acetate was started with subsequent improvement in inflammation and visual acuity. However, the patient was unable to be completely tapered off the steroids because of reactivation. Conclusions: HZ ophthalmicus with stromal keratitis is a rare but potentially damaging manifestation of the varicella zoster virus in the pediatric population. Long-term data regarding reactivation rates in the post-vaccination era are still limited. Close follow-up is needed to ensure resolution of the infiltrates, and reactivation may require long-term steroid therapy. Key Words: herpes zoster ophthalmicus, stromal keratitis, herpes zoster vaccine, Varivax (Cornea 2014;33:988–989)
H
erpes zoster (HZ) ophthalmicus is a reactivation of the latent varicella zoster virus in the ophthalmic division of the trigeminal nerve with potentially devastating ocular complications. Although relatively common among adults, it is rarely found in otherwise healthy children.1,2 Ocular manifestations previously reported include interstitial keratitis, anterior uveitis, and sclerokeratouveitis.3–5 Varivax [varicella virus vaccine live (Oka/Merck); Merck], a live attenuated viral vaccine, became commercially available in the United States in May 1995. Since then, Varivax has been marketed worldwide in 46 countries, with ;55 million doses distributed.6 Here, we present a previously healthy, vaccinated patient with delayed development of stromal keratitis after treatment of HZ ophthalmicus.
CASE REPORT A 6-year-old girl with no medical history and a normal ocular examination 1 year ago was referred for HZ in V1 distribution. On presentation, she had new-onset vesicular rash and left eyelid swelling. The left upper eyelid, forehead, and scalp were affected, and the rash was noted to respect the midline (Fig. 1). There was no history of chickenpox or recent exposure, but she did receive a varicella vaccination (Oka strain) 5 years before presentation (November 30, 2007) and a booster 1 year before (August 9, 2011). The referring pediatrician had made a diagnosis of shingles, and the patient was placed on a 10-day course of acyclovir 200 mg 3 times daily and cimetidine 300 mg 3 times daily, and acetaminophen as needed for pain. On initial examination in our clinic (8 days after the onset of rash), visual acuity measured 20/20 OD and 20/30 OS. The intraocular pressure measured 14 mm Hg OD and 15 mm Hg OS. External examination revealed mild left upper eyelid swelling and almost completely resolved left-sided facial rash in the V1 distribution of the trigeminal nerve. By the time she presented to our clinic, there were no active vesicles, and we were unable to obtain fluid for polymerase chain reaction analysis. There was mild conjunctival injection on the left but no anterior chamber inflammation or corneal findings. The patient returned after 9 days for follow-up (17 days after the onset of rash) with a decrease in vision in the left eye to 20/70. On examination of the left cornea, there were 3 avascular opacities with diffuse borders that appeared to be white blood cells in the superficial stroma (Fig. 2). The right eye was unaffected. The patient was started on topical prednisolone acetate 1% (Pred Forte, Allerga, Irvine, CA) 1 drop 4 times daily OS and continued on oral acyclovir 200 mg 3 times daily. One month later, the stromal opacities had improved somewhat but vision was still 20/60. Amblyopia therapy was initiated by patching the right eye 1 hour per day. Vision improved to 20/40 with improvement of the stromal opacities. The patient was then lost to follow-up, presenting again after 4 months with decreased vision after running out of prednisolone drops, which she was reportedly using 4 times daily until this time. She developed reactivation of the keratitis with a decrease in vision to 20/60. Prednisolone drops were then increased to 8 times daily and gradually tapered to 3 times daily over 5 months. At the last visit, 1 year after the original presentation, the visual acuity had improved to best corrected visual acuity (BSCVA) 20/20 OS, and the slit-lamp examination findings were stable, with only mild subepithelial haze. The steroid continues to be tapered.
DISCUSSION Received for publication March 3, 2014; revision received June 1, 2014; accepted June 2, 2014. Published online ahead of print July 24, 2014. From the Department of Ophthalmology, University of Florida, Gainesville, FL. Supported in part by an unrestricted grant from Research to Prevent Blindness. The authors have no conflicts of interest to disclose. Reprints: Peter Krall, MD, 7651 SW 87th Terrace, Gainesville, FL 32608 (e-mail: pkrall@ufl.edu). Copyright © 2014 by Lippincott Williams & Wilkins
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| www.corneajrnl.com
Complications of the Varivax vaccine are well documented in the literature including a previous report of stromal keratitis that presented 2 weeks after vaccination.7 To the best of our knowledge, this is the first reported case of reactivated HZ ophthalmicus occurring at least 1 year after receiving both the initial vaccination and a booster in a pediatric patient. In the United States, a 1-dose childhood varicella vaccination Cornea Volume 33, Number 9, September 2014
Cornea Volume 33, Number 9, September 2014
FIGURE 1. HZ involving the ophthalmic branch of the trigeminal nerve.
program was initiated in 1995, and a 2-dose schedule was recommended in 2007.8 The number of states with a 2-dose varicella vaccination elementary school entry requirement increased from 4 in 2007 to 36 in 2012, making it the standard of care for pediatric varicella vaccination in the United States.9 The overall incidence of childhood varicella zoster diagnosis has decreased in recent population-based studies;
FIGURE 2. Avascular, stromal opacities with diffuse borders in the central cornea. Ó 2014 Lippincott Williams & Wilkins
Herpes Zoster Ophthalmicus With Stromal Keratitis
however, long-term data regarding reactivation rates are still limited.1 Rates of HZ in adult populations are increasing overall, but this increase began before the introduction of the varicella vaccine in the United States.10,11 Further studies are needed to better understand the impact of vaccination on HZ rates in children. Unfortunately, because of our patient’s late presentation, we were unable to confirm whether reactivation was caused by the wild-type or Oka strain varicella-zoster virus. Both are known to cause reactivated HZ in the vaccinated pediatric population with potentially harmful sequelae.1 The Oka strain cannot be ruled out, given recently published reports of reactivation in immunocompetent children.12 Our patient did not have a history of repeated or chronic infections suggestive of immune deficiency. A normal complete blood count was performed in 2011. She did not follow up for additional testing after being referred to an immunologist. Regardless, it is important to remember that no vaccine is 100% effective, and even with the introduction of the 2-dose regimen, HZ remains a legitimate health concern in both immunocompromised and immunocompetent pediatric populations. In addition, previous reports have indicated rapid resolution of stromal disease with topical steroids7; however, our patient has had a chronic course and has had difficulty tapering off of the steroids with subsequent recurrence of disease. In such cases, close follow-up is essential to ensure complete resolution and to monitor for possible ocular side effects of long-term steroid use. In this age range, induction of amblyopia is still a concern and subsequent patching or atropine therapy should be initiated as needed to ensure normal visual development in the affected eye. REFERENCES 1. Weinmann S, Chun C, Schmid DS, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005–2009. J Infect Dis. 2013;208:1859–1868. 2. Russell ML, Dover DC, Simmonds KA, et al. Shingles in Alberta: before and after publicly funded varicella vaccination. Vaccine. 2013;pii:S0264410X:01249-8. 3. Teran CG, Medows M. Herpes zoster ophthalmicus in a healthy child. BMJ Case Rep. 2013;21:2013. 4. Soeteman M, Willems RP, Busari JO. Herpes zoster ophthalmicus in an otherwise healthy 2-year-old child. BMJ Case Rep. 2012;30:2012. 5. Gandhewar J, Birchall W, Kwartz J. Ophthalmic herpes zoster in an 18-month-old child. J Pediatr Ophthalmol Strabismus. 2005;42:57–58. 6. Galea SA, Sweet A, Beninger P, et al. The safety profile of varicella vaccine: a 10-year review. J Infect Dis. 2008;197(suppl 2):S165–S169. 7. Nagpal A, Vora R, Margolis TP, et al. Interstitial keratitis following varicella vaccination. Arch Ophthalmol. 2009;127:222–229. 8. Marin M, Güris D, Chaves SS, et al. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56:1–40. 9. Lopez AS, Cardemil C, Pabst LJ, et al. Two-dose varicella vaccination coverage among children aged 7 years—six sentinel sites, United States, 2006-2012. MMWR Morb Mortal Wkly Rep. 2014;63:174–177. 10. Rimland D, Moanna A. Increasing incidence of herpes zoster among Veterans. Clin Infect Dis. 2010;50:1000–1005. 11. Hales CM, Harpaz R, Joesoef MR, et al. Examination of links between herpes zoster incidence and childhood varicella vaccination. Ann Intern Med. 2013;159:739–745. 12. Chouliaras G, Spoulou V, Quinlivan M, et al. Vaccine-associated herpes zoster ophthalmicus [correction of opthalmicus] and encephalitis in an immunocompetent child. Pediatrics. 2010;125:e969–e972.
www.corneajrnl.com |
989
Herpes Zoster Stromal Keratitis After Varicella Vaccine Booster in a Pediatric Patient Peter Krall, MD, and Anup Kubal, MD
Purpose: In this study, the case of a healthy pediatric patient who presented with herpes zoster (HZ) stromal keratitis after vaccination with live attenuated varicella vaccine (Varivax) and subsequent booster is described.
Method: This is a retrospective case review. Results: A 6-year-old girl with no medical history presented with HZ ophthalmicus and stromal keratitis. She had received the original Varivax vaccine at 1 year of age and a booster 1 year before presentation. Topical prednisolone acetate was started with subsequent improvement in inflammation and visual acuity. However, the patient was unable to be completely tapered off the steroids because of reactivation. Conclusions: HZ ophthalmicus with stromal keratitis is a rare but potentially damaging manifestation of the varicella zoster virus in the pediatric population. Long-term data regarding reactivation rates in the post-vaccination era are still limited. Close follow-up is needed to ensure resolution of the infiltrates, and reactivation may require long-term steroid therapy. Key Words: herpes zoster ophthalmicus, stromal keratitis, herpes zoster vaccine, Varivax (Cornea 2014;33:988–989)
H
erpes zoster (HZ) ophthalmicus is a reactivation of the latent varicella zoster virus in the ophthalmic division of the trigeminal nerve with potentially devastating ocular complications. Although relatively common among adults, it is rarely found in otherwise healthy children.1,2 Ocular manifestations previously reported include interstitial keratitis, anterior uveitis, and sclerokeratouveitis.3–5 Varivax [varicella virus vaccine live (Oka/Merck); Merck], a live attenuated viral vaccine, became commercially available in the United States in May 1995. Since then, Varivax has been marketed worldwide in 46 countries, with ;55 million doses distributed.6 Here, we present a previously healthy, vaccinated patient with delayed development of stromal keratitis after treatment of HZ ophthalmicus.
CASE REPORT A 6-year-old girl with no medical history and a normal ocular examination 1 year ago was referred for HZ in V1 distribution. On presentation, she had new-onset vesicular rash and left eyelid swelling. The left upper eyelid, forehead, and scalp were affected, and the rash was noted to respect the midline (Fig. 1). There was no history of chickenpox or recent exposure, but she did receive a varicella vaccination (Oka strain) 5 years before presentation (November 30, 2007) and a booster 1 year before (August 9, 2011). The referring pediatrician had made a diagnosis of shingles, and the patient was placed on a 10-day course of acyclovir 200 mg 3 times daily and cimetidine 300 mg 3 times daily, and acetaminophen as needed for pain. On initial examination in our clinic (8 days after the onset of rash), visual acuity measured 20/20 OD and 20/30 OS. The intraocular pressure measured 14 mm Hg OD and 15 mm Hg OS. External examination revealed mild left upper eyelid swelling and almost completely resolved left-sided facial rash in the V1 distribution of the trigeminal nerve. By the time she presented to our clinic, there were no active vesicles, and we were unable to obtain fluid for polymerase chain reaction analysis. There was mild conjunctival injection on the left but no anterior chamber inflammation or corneal findings. The patient returned after 9 days for follow-up (17 days after the onset of rash) with a decrease in vision in the left eye to 20/70. On examination of the left cornea, there were 3 avascular opacities with diffuse borders that appeared to be white blood cells in the superficial stroma (Fig. 2). The right eye was unaffected. The patient was started on topical prednisolone acetate 1% (Pred Forte, Allerga, Irvine, CA) 1 drop 4 times daily OS and continued on oral acyclovir 200 mg 3 times daily. One month later, the stromal opacities had improved somewhat but vision was still 20/60. Amblyopia therapy was initiated by patching the right eye 1 hour per day. Vision improved to 20/40 with improvement of the stromal opacities. The patient was then lost to follow-up, presenting again after 4 months with decreased vision after running out of prednisolone drops, which she was reportedly using 4 times daily until this time. She developed reactivation of the keratitis with a decrease in vision to 20/60. Prednisolone drops were then increased to 8 times daily and gradually tapered to 3 times daily over 5 months. At the last visit, 1 year after the original presentation, the visual acuity had improved to best corrected visual acuity (BSCVA) 20/20 OS, and the slit-lamp examination findings were stable, with only mild subepithelial haze. The steroid continues to be tapered.
DISCUSSION Received for publication March 3, 2014; revision received June 1, 2014; accepted June 2, 2014. Published online ahead of print July 24, 2014. From the Department of Ophthalmology, University of Florida, Gainesville, FL. Supported in part by an unrestricted grant from Research to Prevent Blindness. The authors have no conflicts of interest to disclose. Reprints: Peter Krall, MD, 7651 SW 87th Terrace, Gainesville, FL 32608 (e-mail: pkrall@ufl.edu). Copyright © 2014 by Lippincott Williams & Wilkins
988
| www.corneajrnl.com
Complications of the Varivax vaccine are well documented in the literature including a previous report of stromal keratitis that presented 2 weeks after vaccination.7 To the best of our knowledge, this is the first reported case of reactivated HZ ophthalmicus occurring at least 1 year after receiving both the initial vaccination and a booster in a pediatric patient. In the United States, a 1-dose childhood varicella vaccination Cornea Volume 33, Number 9, September 2014
Cornea Volume 33, Number 9, September 2014
FIGURE 1. HZ involving the ophthalmic branch of the trigeminal nerve.
program was initiated in 1995, and a 2-dose schedule was recommended in 2007.8 The number of states with a 2-dose varicella vaccination elementary school entry requirement increased from 4 in 2007 to 36 in 2012, making it the standard of care for pediatric varicella vaccination in the United States.9 The overall incidence of childhood varicella zoster diagnosis has decreased in recent population-based studies;
FIGURE 2. Avascular, stromal opacities with diffuse borders in the central cornea. Ó 2014 Lippincott Williams & Wilkins
Herpes Zoster Ophthalmicus With Stromal Keratitis
however, long-term data regarding reactivation rates are still limited.1 Rates of HZ in adult populations are increasing overall, but this increase began before the introduction of the varicella vaccine in the United States.10,11 Further studies are needed to better understand the impact of vaccination on HZ rates in children. Unfortunately, because of our patient’s late presentation, we were unable to confirm whether reactivation was caused by the wild-type or Oka strain varicella-zoster virus. Both are known to cause reactivated HZ in the vaccinated pediatric population with potentially harmful sequelae.1 The Oka strain cannot be ruled out, given recently published reports of reactivation in immunocompetent children.12 Our patient did not have a history of repeated or chronic infections suggestive of immune deficiency. A normal complete blood count was performed in 2011. She did not follow up for additional testing after being referred to an immunologist. Regardless, it is important to remember that no vaccine is 100% effective, and even with the introduction of the 2-dose regimen, HZ remains a legitimate health concern in both immunocompromised and immunocompetent pediatric populations. In addition, previous reports have indicated rapid resolution of stromal disease with topical steroids7; however, our patient has had a chronic course and has had difficulty tapering off of the steroids with subsequent recurrence of disease. In such cases, close follow-up is essential to ensure complete resolution and to monitor for possible ocular side effects of long-term steroid use. In this age range, induction of amblyopia is still a concern and subsequent patching or atropine therapy should be initiated as needed to ensure normal visual development in the affected eye. REFERENCES 1. Weinmann S, Chun C, Schmid DS, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005–2009. J Infect Dis. 2013;208:1859–1868. 2. Russell ML, Dover DC, Simmonds KA, et al. Shingles in Alberta: before and after publicly funded varicella vaccination. Vaccine. 2013;pii:S0264410X:01249-8. 3. Teran CG, Medows M. Herpes zoster ophthalmicus in a healthy child. BMJ Case Rep. 2013;21:2013. 4. Soeteman M, Willems RP, Busari JO. Herpes zoster ophthalmicus in an otherwise healthy 2-year-old child. BMJ Case Rep. 2012;30:2012. 5. Gandhewar J, Birchall W, Kwartz J. Ophthalmic herpes zoster in an 18-month-old child. J Pediatr Ophthalmol Strabismus. 2005;42:57–58. 6. Galea SA, Sweet A, Beninger P, et al. The safety profile of varicella vaccine: a 10-year review. J Infect Dis. 2008;197(suppl 2):S165–S169. 7. Nagpal A, Vora R, Margolis TP, et al. Interstitial keratitis following varicella vaccination. Arch Ophthalmol. 2009;127:222–229. 8. Marin M, Güris D, Chaves SS, et al. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56:1–40. 9. Lopez AS, Cardemil C, Pabst LJ, et al. Two-dose varicella vaccination coverage among children aged 7 years—six sentinel sites, United States, 2006-2012. MMWR Morb Mortal Wkly Rep. 2014;63:174–177. 10. Rimland D, Moanna A. Increasing incidence of herpes zoster among Veterans. Clin Infect Dis. 2010;50:1000–1005. 11. Hales CM, Harpaz R, Joesoef MR, et al. Examination of links between herpes zoster incidence and childhood varicella vaccination. Ann Intern Med. 2013;159:739–745. 12. Chouliaras G, Spoulou V, Quinlivan M, et al. Vaccine-associated herpes zoster ophthalmicus [correction of opthalmicus] and encephalitis in an immunocompetent child. Pediatrics. 2010;125:e969–e972.
www.corneajrnl.com |
989
