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Melissa Neuman, MD; Jack Spittler, MD Painful facial blisters, fever, University of Colorado Family Medicine, Denver and [email protected]

DEPARTMENT EDITOR Following Tx for facial blisters, our patient returned Richard P. Usatine, MD University of Texas Health with what appeared to be viral conjunctivitis. Further at San Antonio evaluation revealed a missed tip-off to the proper Dx. The authors reported no potential conflict of interest relevant to this article. a 58-year-old woman with a history of eye, associated blurriness, and decreased vi- hepatitis C, liver cirrhosis, hepatocellular sion. She had been using a warm compress carcinoma, hypothyroidism, and peripheral on the eye and found that it was getting sticky neuropathy presented to our clinic with left and crusted. A gray was seen ear pain and blisters on her lips, nose, and on physical exam, and a fluorescein exam was mouth. On exam, the patient’s left tympanic performed (FIGURE). membrane was opaque, and she had mul- tiple 3- to 5-mm irregularly shaped ulcers on ● WHAT IS YOUR DIAGNOSIS? her right buccal mucosa, gingiva, and lips. She was given a diagnosis of acute otitis media and ● HOW WOULD YOU TREAT THIS prescribed a course of amoxicillin. The physi- PATIENT? cian, who was uncertain about the cause of her gingivostomatitis, took a “shotgun approach” and prescribed a nystatin/diphenhydramine/ lidocaine mouthwash. FIGURE Three weeks later, the patient returned complaining of cloudy urine, dysuria, fever, Fluorescein exam reveals large, dendritic vomiting, and “pink eye.” On exam, her right epithelial defects eye was mildly injected with no drainage. She had normal eye movements and no ophthal-

moplegia. We diagnosed viral (vs allergic) con- IMAGE COURTESY OF: MELISSA NEUMAN, MD, AND JACK SPITTLER, MD junctivitis and pyelonephritis in this patient and advised her to use lubricant eyedrops and an oral antihistamine for the eye. We also started her on cefpodoxime (200 mg bid for 10 days) for pyelonephritis. Three days later, the patient called our clinic and said that her right eye was not im- proving. We prescribed ophthalmic drops, 1 to 2 drops every 6 hours, for presumed bacterial conjunctivitis. Four days later, she returned to our clinic; she had been using the ofloxacin drops and antihistamine but was experiencing worsen- ing symptoms, including itching of her right

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Diagnosis: a mild-to-moderate iritis are signs of endotheliitis.5 The patient was sent to the ❚ Neurotrophic keratopathy. This form clinic, where a slit-lamp examination of the of HSV keratitis is associated with corneal hy- right eye showed 3+ injection, large dendritic poesthesia or complete anesthesia secondary epithelial defects spanning the majority of to damage of the corneal nerves, which can the (with 10% haze), and trace nuclear occur in any form of ocular HSV. Anesthesia sclerosis of the . These findings were con- may lead to nonhealing corneal epithelial de- sistent with a diagnosis of herpes simplex vi- fects.6 These defects, which are generally oval rus (HSV) keratitis, with a likely neurotrophic lesions, do not represent active viral disease component (decreased sensation of the af- and are made worse by antiviral drops. These fected eye compared with that of the other lesions may cause stromal scarring, corneal eye). There was no evidence of secondary perforation, or secondary bacterial infection. infection. Treatment consists of supportive care using artificial tears and prophylactic antibi- otic eye drops, if appropriate; more advanced Discussion ophthalmologic treatments may be needed for The global incidence of HSV keratitis is ap- advanced disease.7 proximately 1.5 million, including 40,000 The symptoms new cases of monocular or Other conditions, including of HSV keratitis blindness each year.1 Primary infection with conjunctivitis, have similar symptoms include eye pain, HSV-1 occurs following direct contact with The differential for redness of the eye includes redness, blurred infected mucosa or skin surfaces and inocula- conditions such as conjunctivitis, , vision, tearing, tion. (Our patient likely transferred the infec- and keratitis. discharge, and tion by touching her eyes after touching her ❚ Conjunctivitis of any form—bacterial, sensitivity to nose or mouth.) The virus remains in sensory viral, allergic, or toxic—involves injection of light. ganglia for the lifetime of the host. Most ocular both the palpebral and bulbar . disease is thought to represent recurrent HSV ❚ Acute angle closure glaucoma can in- (rather than a primary ocular infection).2 It has volve symptoms of headache, malaise, nausea, been proposed that HSV-1 latency may also and vomiting. In addition, the is fixed in occur in the cornea. mid-dilation, and the cornea becomes hazy. The symptoms of HSV keratitis include ❚ Anterior /iritis causes sensitivity eye pain, redness, blurred vision, tearing, dis- to light in both the affected and unaffected charge, and sensitivity to light. eyes, as well as ciliary flush (a red ring around the ). Typically, there is no eye discharge. The 4 diagnostic categories ❚ Bacterial keratitis causes foreign body There are 4 categories of HSV keratitis, based sensation and purulent discharge. This form of on the location of the infection: epithelial, keratitis usually occurs due to improper wear stromal, endotheliitis, and neurotrophic of contact lenses. keratopathy. ❚ Viral keratitis is characterized by pho- ❚ Epithelial. The most common form, tophobia, foreign body sensation, and watery epithelial HSV manifests as dendritic or geo- discharge. A faint branching grey opacity may graphic lesions of the cornea.3 Geographic be seen on penlight exam, and dendrites may lesions occur when a dendrite widens and be seen with fluorescein. assumes an amoeboid shape. ❚ involves severe, boring pain of ❚ Stromal. Stromal involvement accounts the eye in addition to and head- for 20% to 25% of presentations4 and may ache. It is usually associated with systemic in- cause significant anterior chamber inflamma- flammatory disorders. tion. Vision loss can result from permanent ❚ Subconjunctival hemorrhage is as- stromal scarring.5 ymptomatic and occurs following trauma. ❚ Endotheliitis. Keratic precipitates (on ❚ Cellulitis manifests following trauma top of stromal and epithelial edema) and with a deep violet color and marked edema.

574 THE JOURNAL OF FAMILY PRACTICE | SEPTEMBER 2018 | VOL 67, NO 9 Standard Tx: this diagnosis might have prevented the ocular Antiviral medications disease, as the treatment would have been an Topical antiviral therapy is the standard treat- oral antiviral. ment for epithelial HSV keratitis, although oral ❚ If conjunctivitis is refractory to usual antiviral medications are equally effective. management, the patient must be seen to rule A randomized trial found that using an oral out dangerous eye diagnoses such as HSV agent in addition to a topical antiviral did not keratitis, preseptal or , or in the improve outcomes.8 A 2015 systematic review worst case, acute angle closure glaucoma. If found that topical antivirals acyclovir, ganci- there is uncertainty regarding diagnosis, a flu- clovir, , were equally ef- orescein exam is helpful. This simple in-office fective in treatment outcome; 90% of patients exam can facilitate a referral to Ophthalmol- healed within 2 weeks.9 ogy or the emergency department for a slit- Recurrent ocular HSV-1 infections are lamp exam and appropriate therapy. treated in the same way as the initial infection. ❚ Our patient was started on valacyclovir Recurrent infection can be prevented with 1 g bid, trifluridine eyedrops (5×/d), and eryth- daily suppressive therapy. In one study, pa- romycin ophthalmic ointment (3×/d), with tients who took suppressive therapy (acyclovir Ophthalmology follow-up in 1 week. JFP 400 mg bid) for 1 year had 19% recurrence of CORRESPONDENCE ocular infection vs 32% in the placebo group.10 John Spittler, MD, 3055 Roslyn St, Suite 100, Denver, CO ❚ Prompt Tx is key. If the infection is su- 80238; [email protected] It’s always perficial—involving only the outer layer of better to the cornea (epithelium)—the eye should heal consider a REFERENCES without scarring with proper treatment. How- 1. Farooq AV, Shukla D. Herpes simplex epithelial and stromal kera- diagnosis of ever, if the infection is not promptly treated or titis: an epidemiologic update. Surv Ophthalmol. 2012;57:448- primary oral HSV 462. if deeper layers are involved, scarring of the 2. Holland EJ, Mahanti RL, Belongia EA, et al. Ocular involve- infection than cornea may occur. This can lead to vision loss ment in an outbreak of herpes gladiatorum. Am J Ophthalmol. to treat candida 1992;114:680-684. or blindness. 3. Cook SD. Herpes simplex virus in the eye. Br J Ophthalmol. and pain 1992;76:365-366. with a mixed 4. Liesegang TJ. Herpes simplex virus epidemiology and ocular im- A missed opportunity portance. Cornea. 2001;20:1-13. medication for an earlier diagnosis 5. Sekar Babu M, Balammal G, Sangeetha G, et al. A review on viral mouthwash. This case highlights the importance of con- keratitis caused by herpes simplex virus. J Sci. 2011;1:1-10. 6. Hamrah P, Cruzat A, Dastjerdi MH, et al. Corneal sensation ducting a thorough exam to identify findings and subbasal nerve alterations in patients with : an in vivo confocal microscopy study. Ophthalmology. that could shift the diagnosis from a simple 2010;117:1930-1936. allergic, viral, or bacterial conjunctivitis. It is 7. Bonini S, Rama P, Olzi D, et al. . Eye. always better to consider primary oral HSV 2003;17:989-995. 8. Szentmáry N, Módis L, Imre L, et al. Diagnostics and treatment of infection than resort to a “shotgun approach” infectious keratitis. Orv Hetil. 2017;158:1203-1212. of treating candida and pain with an oral mix- 9. Wilhelmus KR. Antiviral treatment and other therapeutic inter- ventions for herpes simplex virus epithelial keratitis. Cochrane ture. In this case, the ulcers and vesicles on Database Syst Rev. 2015;(1):CD002898. the buccal mucosa, gingiva, and lips were a 10. Herpetic Study Group. Acyclovir for the preven- tion of recurrent herpes simplex virus eye disease. N Engl J Med. missed sign of primary HSV infection. Making 1998;339:300-306.

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