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Pediatric Viral Conjunctivitis

Robert W. Hered, M.D.
Robert W. Hered, M.D. is Chief, Division of Ophthalmology,
Nemours Children's Clinic - Jacksonville.

Viral conjunctivitis is a common problem facing the primary care physician and the ophthalmologist. Viral conjunctivitis is particularly common in children, and can present diagnostic and management challenges. This paper reviews common forms of viral conjunctivitis, with emphasis on adenoviral and herpes simplex conjunctivitis. Clinical presentations will be reviewed, including pediatric signs and symptoms. The differential diagnosis of pediatric viral conjunctivitis will be discussed, as well as diagnostic tests, infection control, and treatment.



Figure 1: (Top) Molluscum contagiosum involving the eyelid margin causes chronic follicular conjunctivitis.

Figure 2: (Bottom)Conjunctival hemorrhage in epidemic keratoconjunctivitis (EKC).

Viruses were originally identified and classified by the diseases they produce, as in the case of the hepatitis viruses. Viruses are now classified into families based on their nucleic acid genome, their mode of replication, and the size, shape, and substructure of the virus particle. Conjunctivitis is caused by members of many of the virus families, presenting either as an isolated ocular disease or as part of a viral syndrome. Seven families of DNA viruses infect humans, and several of these families cause conjunctivitis. Of particular interest are the adenovirus and herpes families. Molluscum contagiosum causes a follicular conjunctivitis when molluscum skin lesions involve the eyelid margin. (Figure 1) Resolution of the conjunctivitis occurs after excision of the molluscum lesions.1

Among RNA viruses, influenza viral infection will occasionally include a self-limited conjunctivitis. Measles (rubeola), now a rare pediatric illness, usually includes papillary conjunctivitis and keratitis in its presentation. Measles conjunctivitis is associated with superficial punctate keratitis, interstitial keratitis, superficial corneal pannus, and pale avascular spots of the conjunctiva.

Acute hemorrhagic conjunctivitis is caused by certain picornaviridae, with prominent subconjunctival hemorrhages and punctate epithelial keratitis. The most common offending organisms are enterovirus 70 and Coxsackie virus type A24. The condition usually lasts four to seven days. Vision threatening secondary bacterial infection commonly develops in third world cases of acute hemorrhagic conjunctivitis. Conjunctival hemorrhages can also occur in adenoviral conjunctivis, a much more common disease in the United States. (Figure 2)

The frequency of conjunctivitis in systemic pediatric viral disease varies. Conjunctivitis is present in more than half of the cases of measles. With the colds and flu caused by rhinovirus, enterovirus, and influenza virus, less than half of cases are accompanied by a self-limited conjunctivitis. Ten to 30% of respiratory syncitial virus infections are accompanied by conjunctivitis. Only a few cases of conjunctivitis have been reported with erythema infectiosum. Erythema infectiosum, or fifth disease, is caused by human parvovirus B19.2

Ocular infection with the herpes simplex virus is common, and carries a significant risk of vision loss. Primary herpes typically presents as conjunctivitis, often accompanied by eyelid vesicles and enlarged preauricular nodes. In the latent phase, the herpes simplex virus resides in the trigeminal ganglion. When reactivated as secondary herpes, the disease can present again as conjunctivitis, but also as the more serious and symptomatic dendritic, disciform, and necrotizing forms of keratitis. In dendritic keratitis, branching lesions of the anterior cornea may lead to corneal ulceration and scarring. Disciform herpes keratitis involves the corneal stroma, and is the result of immune response to viral antigens. Recurrent herpes simplex is almost always unilateral, and prompt treatment reduces the risk of vision loss. Any recurrent unilateral red eye should raise suspicion of herpes simplex keratitis. Specific topical treatment for herpes simplex conjunctivitis and keratitis is available with topical trifluridine solution or vidarabine ointment. Also, oral acyclovir has recently been shown to be effective in pediatric herpes simplex keratitis.3 Prophylactic oral acyclovir may also reduce the risk of recurrence.4 Corticosteroids play a role in the management of stromal herpes simplex keratitis, but such treatment carries risk and is best managed by an ophthalmologist.

Chickenpox may present with eyelid swelling, eyelid vesicles, and localized conjunctival lesions. Less commonly, superficial punctate keratitis and dendritic keratitis can develop. Oral acyclovir may be beneficial.

Members of the adenovirus family cause a variety of human infections. Over 48 adenovirus types have been found to infect humans. Almost half of these types cause conjunctivitis.5 Adenoviral conjunctivitis can present as an isolated condition, or as part of a viral syndrome. Adenovirus can cause a nonspecific acute follicular conjunctivitis. Epidemic keratoconjunctivitis (EKC) includes characteristic corneal involvement. As the name implies, pharyngoconjunctival fever (PCF), more common in children, presents with the triad of pharyngitis, fever, and conjunctivitis. Mixed presentations have become more common, and additional serotypes have been identified as causes, blurring the clinical distinction between EKC and PCF. While pharyngoconjunctival fever is a self-limited disease, disseminated adenoviral disease, with multiple organ system involvement, has a high mortality rate. An outbreak of adenovirus type 7 in a pediatrics ward produced pneumonia, encephalitis, liver dysfunction, myositis, and gastroenteritis in addition to conjuctivitis.6

The early signs of adenoviral conjunctivitis include unilateral conjunctival injection with enlarged palpebral conjunctival follicles. Discharge is watery, typically with a mild mucoid component. Preauricular lymphadenopathy is most common with epidemic keratoconjunctivitis. Within a few days, the disease often becomes bilateral.

Conjunctival hemorrhages can occur in adenoviral conjunctivitis, more commonly with EKC. Also more common in EKC, diffuse punctate corneal epithelial defects develop, accompanied by photophobia.

 

Pseudomembranes of the palpebral conjunctiva appear later, as do subepithelial corneal infiltrates. (Figures 3, 4) Again, these findings are more characteristic of EKC.


Figure 1: (Left) Pseudomembrane of the palperbral conjunctiva in EKC.
 Figure 2: (Right) Subepithelial corneal infiltrates in EKC.

Adenoviral conjunctivitis in infants can present a diagnostic challenge. The conjunctival lymphoid follicles are absent in infants. Additionally, the conjunctivitis can present with marked lid swelling and fever, mimicking periorbital cellulitis.7 Misdiagnosis may lead to hospitalization and intravenous antibiotics, followed by even greater concern when the eyelid swelling does not respond to antibiotic treatment. Careful examination of the anterior segment, often with the assistance of eyelid retractors, is necessary to make the correct diagnosis. Also, infants are at risk for large, slowly resolving corneal epithelial defects.8

The diagnosis of adenoviral conjunctivitis remains primarily clinical. The slit lamp examination is of great importance, but not always easy in young children. A hand-held slit lamp can be helpful in many cases. The ideal laboratory study would be rapid, accurate, and inexpensive. Such a test does not yet exist. Viral cultures are most helpful epidemiologically because of relatively slow turn-around. Enzyme immunoassay and polymerase chain reaction (PCR) tests are rapid but have been troubled by low sensitivity.9 More recent PCR assays are promising, however.10

Regarding the systemic disease accompanying adenoviral conjunctivitis, pharyngoconjunctival fever is a self-limited illness with an excellent prognosis. The same adenovirus types can cause the rarer but more serious disseminated adenoviral disease. Conjunctivitis can be present in disseminated adenoviral disease, and therefore ophthalmologists may be involved in the care of these children. Disseminated adenoviral disease frequently results in multiple organ failure and death. The condition is more common in immunodeficient children, but has a high mortality rate even in immunocompetent children.11

Of particular importance is the risk of systemic adenoviral infection among premature infants. For example a reported outbreak of adenoviral conjunctivitis involved seven premature infants in a neonatal intensive care unit who had undergone retinopathy of prematurity examinations 4 to 7 days earlier. Three developed deterioration of their respiratory disease as a result.12 In a second reported epidemic, 9 premature infants were significantly affected, with 2 resultant deaths.13 The same adenovirus type that caused conjunctivitis, fever, and pharyngitis in adults caused more serious disease in this vulnerable population.

Controlling the spread of adenoviral conjunctivitis is challenging. The virus typically spreads among persons in close contact, either through direct contact, contact with contaminated materials, or by aerosolized droplets. The usual incubation period is 5 to 12 days. Viral agents may be present in secretions two days before the onset of symptoms. In the case of pharyngoconjunctivial fever, epidemics have been linked to contaminated swimming pools. Adenovirus types 3 and 7 cause swimming pool conjunctivitis. Spread is possibly from fecal excretion of the virus, which can occur for 30 days.14

Controlling the spread of adenoviral conjunctivitis in the hospital and the physician's office is of particular importance. The increased risk that adenoviral infection poses to premature infants and immunodeficient children has already been mentioned. Special care should be taken not to spread adenovirus and other organisms with contaminated instruments in the neonatal intensive care unit. In the ophthalmology office, hand washing, furlough for infected employees, and proper cleaning of surfaces and instruments have been shown to reduce the risk of viral spread.15, 16

As of 2002, there is no proven effective treatment for adenoviral conjunctivitis. Military recruits were vaccinated for adenovirus types 4 and 7 between 1971 and 1996, but the vaccine is currently unavailable.17 Antiviral treatment with trifluridine and apha-2 interferon are ineffective.18 A case report suggests that the antiviral agent cidofovir may be effective, but a more recent pilot study showed no benefit.19,20 Nonsteroidal anti-inflammatory eye drops may offer some symptomatic benefit without the risks of topical corticosteroids.21 Secondary coinfections with bacteria, chlamydia, and acanthamoeba can occur and require specific treatment.22, 23

The use of topical corticosteroids for adenoviral conjunctivitis remains controversial. Topical corticosteroids may be useful in managing subepithelial corneal infiltrates, particularly if they persist and reduce visual acuity. They may also help reduce pseudomembranes. Corticosteroids, however, have been shown to enhance and prolong viral replication and shedding.24 Corticosteroids have also been
implicated in producing chronic adenoviral conjunctivitis.25 Management of childhood adenoviral conjunctivitis with corticosteroids is made particularly difficult by the limitations of a pediatric examination, including the difficulty of measuring intraocular pressure and obtaining a detailed slit-lamp examination. Corticosteroids should be avoided in treating most cases of pediatric adenoviral conjunctivitis.
 

TABLE 1. Differential DiagnosisOf  Childhood Red Eye

 Other infectious causes of conjunctivitis must be ruled out. (Table 1) Typically, the purulent discharge of bacterial conjunctivitis helps make the clinical distinction. Bacterial and chlamydial cultures can be helpful in diagnosing questionable cases. Phlyctenular conjunctivitis can cause patchy nonpurulent conjunctival injection. Oculoglandular syndrome, with its prominent follicular conjunctivitis and preauricular lymphadenopathy, is most commonly caused by the cat scratch disease agent, Bartonella henselae.
  • Normal childhood conjunctival folliculosis (age 4 to adolescence)
  • Allergic conjunctivitis
  • Kawasaki Disease
  • Reiter's Syndrome
  • Iritis
  • Bacterial conjunctivitis
  • Chemical conjunctivitis, medicamentosa
  • Occult trauma, foreign body
  • Dacryostenosis
  • Trichiasis
  • Parinaud's syndrome and bartonella henselae

Among the many noninfectious causes of conjunctival injection in children, several are noteworthy. Healthy young children frequently have prominent conjunctival follicles, making the presence of follicles less helpful diagnostically. Acute allergic conjunctivitis can also present with follicles, and preverbal children will not be able to describe their symptoms. Kawasaki disease may present with fever, adenopathy, iritis and conjunctivitis. Although not yet proven, evidence suggests that Kawasaki disease may be the result of a parvovirus infection. Other causes of conjunctival injection, such as iritis and corneal injury, may be more difficult to sort out in younger children because of examination and history limitations. Excessive photophobia and discomfort should prompt suspicion of these conditions.

REFERENCES

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  2. Scharre JE, Veith J. Conjunctivitis associated with fifth disease in a child: a case report. J Am Optom Assoc. 1996:12:763-766
  3. Schwartz GS, Holland EJ. Oral acyclovir for the management of herpes simplex virus keratitis. Ophthalmology. 2000;107:278-282.
  4. Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000;118:1030-1036.
  5. Uchio E, et al. Acute follicular conjunctivitis caused by adenovirus type 34. Am J Ophthalmol. 1999;128:680-686.
  6. Taketazu SH et al. Outbreak of severe infection due to adenovirus type 7 in a paediatric ward in Japan. J Hosp Infect. 1998;39:207-211.
  7. Ruttum MS, Ogawa G. Adenovirus conjunctivitis mimics preseptal and orbital cellulitis in young children. Pediatr Infect Dis J. 1996;15:266-267.
  8. Dawson CR, Hanna L, Togni B. Adenovirus type 8 infections in the United States. IV. Observations on the pathogenesis of lesions in severe eye disease. Arch Ophthalmol. 1972;87:258-268.
  9. Wiley LA et al. A 5-year evaluation of the adenoclone test for the rapid diagnosis of adenovirus from conjunctival swabs. Cornea. 1996;15:363-367.
  10. Cooper RJ, Yeo AC, Bailey AS, Tullo AB. Adenovirus polymerase chain reaction assay for rapid diagnosis of conjunctivitis. Invest Ophthalmol Vis Sci. 1999;40:90-95.
  11. Munoz FM, Piedra PA, Demmler GJ. Disseminated adenovirus disease in immunocompromised and immunocompetent children. Clin Infect Dis. 1998;27:1194-1200.
  12. Birenbaum E, et al. Adenovirus type 8 conjunctivitis outbreak in a neonatal intensive care unit. Arch Dis Child. 1993;68:610-611.
  13. Finn A, Anday E, Talbot GH. An epidemic of adenovirus 7a infection in a neonatal nursery: course, morbidity, and management. Infect Control Hosp Epidemiol. 1988;9:398-404.
  14. Cherry JD, Pharyngoconjunctival Fever, in Feigin RD, Cherry JD (eds) Textbook of Pediatric Infectious Diseases, Edition 4, W.B. Saunders, Philadelphia, 1998.
  15. Gottsch JD. Surveillance and control of epidemic keratoconjunctivitis. Trans Am Ophthalmol Soc. 1996;94;539-587.
  16. Azar MJ et al. Possible consequences of shaking hands with your patients with epidemic keratoconjunctivitis. Am J Ophthalmol. 1996;121:711-712.
  17. Two fatal cases of adenovirus-related illness in previously healthy young adults—Illinois, 2000. MMWR Morb Mortal Wkly Rep. 2001;50:553-5.
  18. Adams CP, Cohen EJ, Albrecht J, Laibson PR. Interferon treatment of adenoviral conjunctivitis. Am J Ophthalmol. 98;429-432,1984.
  19. Gordon YJ, et al. Treatment of adenoviral conjunctivitis with topical cidofovir. Cornea. 1996;15:546.
  20. Hillencamp J et al. Topical treatment of acute adenoviral keratoconjunctivitis with 0.2% cidofovir and 1% cyclosporine. Arch Ophthalmol. 2001;119:1487-1491.
  21. Gordon YJ, Araullo-Cruz T, Romanowski EG. The effects of topical nonsteroidal anti-inflammatory drugs on adenoviral replication. Arch Ophthalmol. 1998;116:900-905.
  22. Gajdatsy AD, Kosmin A, Barrett GD. Coexistent adenoviral keratoconjuctivis and acanthomoeba keratitis. Clin Exper Ophthalmology. 2000;28:434-436.
  23. Mellman-Rubin TL Kowalski RP, Uhrin M, Gordon YG. Incidence of adenoviral and chlamydial coinfection in acute follicula conjunctivitis. Am J Ophthalmol. 1995;119:652-654.
  24. Romanowski EG, et al. The effects of corticosteroids on adenoviral replication. Arch Ophthalmol. 1996;114:581-5.
  25. Pettitt TH, Holland GN. Chronic keratoconjunctivitis associated with ocular adenovirus infection. Am J Ophthalmol. 1979;88:748-751.
Jacksonville Medicine / August-September 2002

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