Two months ago, Marissa Benton* was annoyed to notice redness in her left eye (Figure 1). She also developed pressure and pain around both eyes, particularly on the left. Despite antibiotics to treat suspected sinusitis, her symptoms gradually worsened. In the past month she also developed vertigo, nausea, otalgia and diminished appetite, as well as progressively worsening vision. Tylenol provided moderate pain relief.
We Get a Look
When we saw Ms. Benton, a 42-year-old Caucasian, she was anxious about her worsening condition. She denied any hearing loss, diplopia, fever, cough, rhinorrhea, otorrhea, tinnitus or vomiting.
Her medical history included fibromyalgia, borderline hypertension, hypothyroidism, celiac disease, nonalcoholic steatohepatitis, polycystic ovarian syndrome, fibroids, asthma and type 2 diabetes mellitus. Her family, social and ocular histories were unremarkable.
On examination, she had a visual acuity of 20/20 bilaterally. We noted that she had photophobia. Her pupillary exam, extraocular movements and IOPs were all within normal limits. A slit-lamp exam revealed faint hazy opacities within the deep stroma (Figure 2) and several vascular loops extending into the cornea in the midstromal layers (Figure 3). She also had moderate ciliary injection and tenderness of the globe. The rest of the examination was unremarkable.
The patient appears to have interstitial keratitis and episcleritis. Interstitial keratitis is an uncommon chronic, non-ulcerative inflammation of the corneal stroma that may be seen in isolation or may be associated with uveitis or episcleritis, as was the case with this patient.
Symptoms include pain, tearing, photophobia and gradual blurring of vision. Interstitial keratitis presents a very interesting differential diagnosis: unusual infections such as brucellosis, chlamydia, Epstein-Barr virus, herpes zoster and simplex, leprosy, Lyme disease, mumps, parasitic infection, rubeola, syphilis and tuberculosis have all been implicated.1 Interstitial keratitis may rarely be seen in association with systemic and autoimmune diseases such as Cogan’s syndrome, lymphoma, polyarteritis nodosa, relapsing polychondritis, rheumatoid arthritis, sarcoidosis and Wegener’s granulomatosis.
Slit-lamp examination, careful history and appropriate serological testing help to determine the diagnosis. The etiology directs the treatment, and corticosteroids may be required. In Ms. Benton’s case, the addition of otalgia and vertigo in the review of systems make the diagnosis.
What's Your Diagnosis
|(Figure 1) Ms. Benton was initially prescribed antibiotics for suspected sinusitis. |
|(Figure 2) At the slit lamp, we noticed faint, hazy opacities within the deep stroma. |
|(Figure 3) Vascular loops extending into the cornea in the midstroma. |
Cogan’s syndrome is a rare, chronic inflammatory disorder commonly affecting young to middle-aged adults. Dr. David Glendenning Cogan described the syndrome in 1945 as “an interstitial keratitis associated with vertigo, tinnitus and usually profound deafness.”2 Since then, chronic interstitial keratitis and vestibuloauditory dysfunction have remained the hallmarks of Cogan’s syndrome. The etiology is unknown, but is believed to be an autoimmune process involving the inner ear and cornea. HLA-B17, HLA-A9, HLA-Bw35 and HLA-Cw4 have been correlated with an increased incidence of the syndrome.
Cogan’s syndrome is a clinical diagnosis based on the clinical findings and exclusion of infectious causes. Most patients initially present with eye symptoms. The classic finding is interstitial keratitis, which causes redness, photophobia, pain and blurred vision. Even though interstitial keratitis is a hallmark finding, it is not essential for diagnosis. Inflammation may involve other areas of the eye and result in conjunctivitis, episcleritis, scleritis or retinal vasculitis. Significant visual impairment may result from posterior scleritis and/or retinitis; therefore, if either is detected, urgent treatment is necessary.3
Autoimmune inner ear disease in Cogan’s syndrome produces vertigo, nausea, ataxia, vomiting, tinnitus and hearing loss. If audiological assessment reveals any hearing loss, prompt referral to otolaryngology is essential as bilateral sensorineural hearing loss may result if treatment is delayed.4
Rheumatologic evaluation is necessary for evidence of systemic vasculitis, which is present in many patients.5 Some systemic associations may include life-threatening aortitis (up to 10 percent), inflammatory bowel disease, pericarditis, abdominal pain, fatigue, weight loss, arthralgia, myalgia, fever, headache and urticaria. Lab studies usually indicate leukocytosis, increased ESR and increased CRP. ESR and CRP may assist in monitoring progression.
Anterior eye disease (including interstitial keratitis) is treated with topical corticosteroids with or without mydriatics for comfort. Topical or oral NSAIDs may help in the management of associated episcleritis and scleritis. Posterior ocular inflammation is treated with systemic corticosteroids.
Hearing loss from Cogan’s syndrome requires systemic corticosteroids (from 1 to 2 mg/kg/day) for two to six months. Audiometry should be obtained at baseline and used to determine the degree of hearing loss. Steroid taper may begin when auditory and vestibular functions are stable. Consider steroid sparing therapy when excessive amounts of steroids would be required to prevent hearing loss or if significant steroid-related side effects result. In these cases, azathioprine, cyclophosphamide, methotrexate and tacrolimus have been used successfully. Acute vestibular dysfunction may be treated with antihistamines or benzodiazepines and bed rest.
Systemic vasculitis associated with Cogan’s is treated with prednisone (usually 1 mg/kg/day) with associated steroid taper. Therapy with cyclosporine and/or cyclophosphamide may also be necessary depending on disease severity.
We treated Ms. Benton with prednisolone 1 percent drops four times a day in the left eye. Lab studies showed leukocytosis in the upper limits of normal, mildly elevated ESR, and nonreactive syphilis serologies. Prompt referrals to otolaryngology and rheumatology were arranged. In the week after our exam she did develop tinnitus, though complete otolaryngology and audiology evaluation showed no hearing loss. MRI of the head was negative. At one week after presentation, the interstitial keratitis and discomfort from episcleritis had totally resolved. She will be followed closely by the otolaryngology team, and oral therapy will be initiated if any hearing loss or worsening symptoms develop.
The acute stage of Cogan’s syndrome may last anywhere from months to years. The chronic stage may last indefinitely.
*Patient name is fictitious.
Ms. Freed is a medical student and Dr. Graff is a resident at the University of Iowa.
1 Whitcup, S. M. and J. A. Smith. “Nonsyphilitic Interstitial Keratitis.” Chapter 90 in Krachmer, J. H. et al. Cornea, 2nd ed., vol. 1 (Philadelphia: Elsevier Mosby, 2005), 1161–1167.
2 Cogan, D. G. Arch Ophthal 1945;33:144–149.
3 Gonclaves, R. M. et al. Ocul Immunol Inflamm 2004;12:149–152.
4 Chynn, E. W. and F. A. Jakobiec. Int Ophthalmol Clin 1996;36:61–72.
5 Cheson, B. D. et al. Am J Med 1976;60:549–555.