A 10-year-old boy who has a couple of active cold sores wakes up one morning with a painfully inflamed right eye. His mother takes him to a local clinic, where his eye is examined. The conjunctivae are clearly inflamed, but the cornea looks clear and there are no other remarkable symptoms. A preliminary diagnosis of bacterial or early adenoviral conjunctivitis is made, so the boy is treated with a topical antibiotic preparation (in case his infection is bacterial) and given an eye patch to wear. His mother is told to bring him back after three days for a follow-up examination.

When the boy is reexamined three days later, it is obvious that the condition of his eye has not improved. If anything, the inflammation is even worse than it was before. Moreover, numerous small vesicles (i.e., fluid-filled lesions) have appeared on the conjunctivae and the periocular skin, and vision in the affected eye is blurred. The patient's tears are not tinged with blood, and there are no other remarkable findings.

Question 3.1: What is your preliminary diagnosis?

Had this been a case of bacterial conjunctivitis, the antibiotic treatment probably would have resulted in some improvement. Adenoviral keratoconjunctivitis is possible, but the symptoms are not a particularly good fit. There appears to be some corneal involvement (evidenced by blurred vision), but the tears do not contain blood as they usually would in a case of adenoviral "hemorrhagic conjunctivitis." Also, there is no sign of preauricular lymphadenopathy. The vesicles are not characteristic of adenoviral infection either, but they frequently do appear during herpes simplex infections. (In fact, if the vesicles do not appear, it is nearly impossible to distinguish HSV infections from adenoviral conjunctivitis.) Given the vesicles and apparent involvement of the cornea, the patient most likely has a herpes simplex eye infection that is developing into keratitis. The fact that the boy has active cold sores lends additional support to this diagnosis. Herpes simplex eye infections are almost always caused by HSV-1, rather than HSV-2.

Question 3.2: How is the diagnosis confirmed?

If infection of the cornea has progressed to a sufficient extent, it is possible to observe a dendritic pattern of corneal ulceration after staining with fluorescein (a fluorescent dye). The development of these dendrites is a hallmark of herpes simplex keratitis. However, they are visible in only a minority of primary infections, often becoming apparent only after several recurrences occur (see below). If the vesicles on the conjunctivae and/or periocular skin have not crusted, it is possible to detect the virus in fluid aspirated from the vesicles. This can be done by culturing the virus, or by using fluorescent antibody-based stains and/or DNA-based methods such as PCR.

Test Results:

In this case, the dendritic corneal ulcerations were not yet visible, but HSV-1 was detected in the fluid from the vesicles.

Question 3.3: Is this a dangerous situation?

Yes, HSV infection of the eye is the most frequent cause of corneal blindness in the U.S. (where trachoma and vitamin deficiencies are rare). Treatment should be initiated as soon as HSV infection is suspected (generally based on the appearance of vesicles or failure of the infection to self-resolve in a timely manner).

Question 3.4: How should you treat this case?

Treatment of HSV keratitis typically involves debridement, topical antiviral therapy (acyclovir or one of the newer variations of this drug), and interferon therapy. These measures usually hasten healing but, unfortunately, recurrences are common because antiviral therapy does not eliminate the virus from the area. (Rather, the virus simply goes back into its latent state.) Recurrences of HSV keratitis tend to further damage the cornea, producing increasingly extensive and noticeable dendritic lesions. Because of the likelihood of recurrences and their potential to cause permanent loss of vision, patients with HSV eye infections should be referred to an ophthalmologist as soon as possible.

Question 3.5: How was the boy's eye infected?

In all likelihood, the virus was carried from his mouth to his eye on his fingers, in fluid from one of the cold sores that he was experiencing at the time.

Question 3.6: What other diseases does this agent cause?

HSV-1 is best known for causing oral infections, which usually manifest as cold sores and fever blisters (fluid-filled, itching or painful lesions) that appear at the corners of the mouth or next to the lips. In infants and toddlers, HSV-1 causes Gingivostomatitis, a painful condition in which the lesions develop around and throughout the mouth. Other diseases caused by HSV-1 include: herpes pharyngitis, herpes whitlow (infection of the finger), herpes gladiatorum (infection of the body), and herpes encephalitis. HSV-1 can also cause genital infections, although most cases (at least 85%) of genital herpes are caused by HSV-2.