Angel Sanchez* was a very typical and pleasant 2-year-old girl. With the exception of two routine ear infections, she was an exceptionally healthy child. However, this week would be a most atypical one for her. It all began when Angel’s grandmother brought her to our university’s pediatric urgent care clinic on Thursday evening. For the past week, Angel had been experiencing swelling in her right eyelid, increasing redness in and discharge from her right eye, and intermittent nighttime fevers. The other eye was not affected, and Angel had not experienced any symptoms of an upper respiratory infection, nor had she been in contact with any sick children. In fact, she was doing quite well, playing and eating normally. Her grandmother was quite proud of the fact that Angel already knew more than 20 words, was washing her own hands, feeding herself, climbing up stairs and jumping around.
Angel had a normal birth history, and her medical history was remarkable only for eczema and the two ear infections. She was up-to-date on all her immunizations. The pediatrician on call made a snap diagnosis of preorbital cellulitis, cultured the conjunctiva, administered a single 600-milligram intravenous dose of ceftriaxone (Rocephin) and discharged her from the clinic with a prescription for amoxicillin/ clavulanate (Augmentin), to be taken twice daily in a 500-mg oral suspension.
The next morning, Angel returned. By now, her right eye was completely swollen shut, and a new vesicular eruption surrounded it. She was admitted to the general pediatric unit and started on intravenous acyclovir (Zovirax). In addition, an ophthalmology consult was called.
When we saw her, Angel’s visual acuity was central, steady and maintained in both eyes. Her right eyelid was swollen shut, and there were several vesicular, pustular lesions along the lids and lateral canthal area (Fig. 1). In addition, she had right preauricular lymphadenopathy. Her pupils were 3 millimeters bilaterally and quickly reactive without an afferent pupillary defect. Extraocular motility was full in both eyes.
The right palpebral and bulbar conjunctiva was mildly injected, with the exception of the superior temporal region of the bulbar conjunctiva, which was markedly injected. In addition, this region had a peculiar additional finding—a fluorescein-staining conjunctival ulceration (Fig. 2). There was no fluorescein staining of the cornea, and the remainder of the examination was completely normal.
Caption: In addition to intermittent nighttime fevers, the patient had a vesicular eruption along her lids
and lateral canthal area (Fig. 1, left). Closer examination revealed a fluorescein-staining conjunctival ulceration (Fig. 2, right).
Angel’s complete blood count was unremarkable, and her previously obtained conjunctival culture ultimately grew no organisms.
Given her age and the classic vesicular eruption, Angel was given a diagnosis of blepharoconjunctivitis secondary to primary herpes simplex virus infection. Herpesvirus culture was taken, and she was started on oral acyclovir, 400 mg every eight hours; trifluridine (Viroptic), 1 percent drops four times daily to the right eye; erythromycin ointment at bedtime to the right eye; and oral cephalexin (Keflex), 300 mg four times daily, to complete her antibiotic course.
Angel remained in the pediatric unit for the weekend. Over the next two days the swelling greatly decreased and the vesicles mostly resolved. She was able to open her eye completely by Sunday and was discharged to her family on Monday morning. One week later, she was doing very well, and she ultimately made a complete recovery. Her herpes-virus culture returned positive.
A Most Peculiar Finding
Ulceration is an uncommon manifestation of conjunctivitis, and it was a most peculiar finding in this case as well. As a generalization, any traumatic or inflammatory process severe enough to disrupt the intracellular adhesive junctions can produce conjunctival ulceration.1
The differential diagnosis includes direct trauma; primary syphilis; ocular pemphigoid; toxic epidermal necrolysis; erythema multiform major; or any cause of membranous, pseudomembranous or granulomatous conjunctivitis (Parinaud’s oculoglandular syndrome).1 Case reports also have implicated drug toxicity—topical gentamicin (Genoptic and others) and subconjunctival steroid injections—and rare autoimmune disorders such as Wegener’s granulomatosis.2 Sectoral injection warrants close examination with fluorescein for accurate diagnosis of conjunctival ulceration.
Primary Ocular HSV
Primary ocular HSV infection typically manifests as a predominantly unilateral blepharoconjunctivitis. While this infection can occur at any age, it classically occurs in young children from the ages of 6 months to 5 years.
The initial ocular manifestation consists of the classic vesicular lesions commonly occurring on the lids and lid margins, and it is often associated with vesicles on the lips. Following a brief incubation period of three to 12 days, an acute follicular conjunctivitis typically develops along with a regional—typically preauricular lymphadenopathy and a mild malaise syndrome.3 Keratitis develops a few days after the conjunctivitis in about 30 percent to 50 percent of cases, and the corneal manifestations may involve a superficial punctate keratitis, microdendrites or frank dendritic ulceration. Stromal involvement is rare.
The keratitis may last several weeks after the acute conjunctivitis has resolved, and the subjective symptoms of this prolonged keratitis are typically modest, given the general hypoesthesia of the cornea during viral infection.3 Patients with severe primary ocular HSV may benefit from oral acyclovir, which may limit the course of the disease.
An extremely rare manifestation of the conjunctivitis is the development of a conjunctival ulceration, as in Angel’s case. The manifestation of punctate, dendritic or geographic ulcerations has been discussed in the literature in association with primary ocular HSV.4
Conjunctival ulceration rarely occurs in recurrent HSV conjunctivitis, although its frequency and importance have not yet been determined.5 The mechanism of this ulceration has not been completely elucidated; however, topical antiviral treatment may be warranted given the report of active viral disease in excised ulcer margins.5
While ocular HSV is most reliably diagnosed via serodiagnostic testing for immunoglobulin M, it is often diagnosed clinically based on presentation. However, HSV may present as an isolated follicular conjunctivitis or an keratoconjunctivitis without the other typical clinical findings. Such variants of HSV infections are commonly misdiagnosed as adenoviral infections and usually treated inappropriately. A careful literature review indicates that conjunctival ulceration has not been reported in cases of adenoviral infection. Thus, such ulceration may represent strong evidence in favor of HSV infection rather than adenoviral infection.4
1 Liesegang, T. J. “Conjunctiva,” in Textbook of Ophthalmology, ed. K. W. Wright (Baltimore: Lippincott Williams & Wilkins, 1997), 665–690.
2 Fortney, A. C. and J. Chodosh. Cornea 2002; 21:623–624.
3 Duke-Elder, S., ed. “Diseases of the Outer Eye,” in System of Ophthalmology (St. Louis: Mosby, 1965), 307–335.
4 Yao, Y. et al. Am J Ophthalmol 1979;118: 670–671.
5 Brown, D. C. et al. Arch Opthalmol 1968; 79:733.
Mr. Shahinpoor is a fourth-year medical student, Dr. Wood is director of pediatric ophthalmology, Dr. Overturf is chief of pediatric infectious diseases and Dr. Mootha is director of cornea and external diseases; all are at the University of New Mexico Health Sciences Center, Albuquerque. Dr. Mootha also is an attending physician with the New Mexico Veterans Administration Healthcare System in Albuquerque.
* Patient name is fictitious.