Article

A rare disorder appears in your clinic

Cogan syndrome’s symptoms are classically found in the eyes and ears.

A 28-year-old female presented with complaints of photophobia and decreased vision OU. She had received a presumptive diagnosis of uveitis in the past, and a previous uveitis workup was negative. She had been intermittently treated with topical steroids with temporary and moderate resolution of symptoms. At the time of presentation, she was using prednisolone acetate 1% in both eyes twice daily. Past medical history, family medical history and social history were noncontributory.

At the time of initial presentation, visual acuity was 20/40 OD and 20/150 OS. Slit-lamp examination was significant for superficial and deep corneal neovascularization and 1+ anterior chamber cell in the right eye. There was similar superficial and deep corneal neovascularization in the left cornea, along with ghost vessels extending into the visual axis; the anterior chamber was quiet in this eye (Figure 1). The iris, lens, vitreous and fundus exams of both eyes were unremarkable.

Figure 1. External photograph of patient’s left eye. Superficial and deep corneal neovascularization was noted. Moderate corneal haze was present superiorly and laterally. There was a ghost vessel extending vertically through the visual axis.

Upon further questioning, the patient also reported red bumps on her lower extremities and bilateral hearing loss that had been getting worse over the past few months.

THE PLOT THICKENS …

This patient had interstitial keratitis (IK), subjective bilateral hearing loss and erythema nodosum. The examination findings in IK could include active stromal neovascularization, ghost vessels, lipid keratopathy and white cell infiltrates. The two main etiologic categories in the differential diagnosis of IK are inflammatory and infectious. Inflammatory etiologies include granulomatosis with polyangiitis (previously Wegener’s granulomatosis), polyarteritis nodosa, relapsing polychondritis, sarcoidosis, rheumatoid arthritis and Cogan syndrome. Infectious etiologies include syphilis, herpes simplex virus, herpes zoster virus, tuberculosis, chlamydia, leprosy, brucellosis and various parasitic infections.1

Since the differential diagnosis for IK is potentially broad, it is important to use clinical clues to narrow the possibilities. In addition to IK, this patient had recent onset bilateral hearing loss. Therefore, the suspected diagnosis was Cogan syndrome. The patient was referred for urgent otolaryngology evaluation, audiology testing and rheumatology consultation with plans to initiate oral corticosteroid therapy after ruling out infectious causes. Topical prednisolone acetate 1% was increased from BID to QID OU. This patient was unable to return to our clinic for follow-up and instead received care locally in her home state.

COGAN SYNDROME PRIMER

Cogan syndrome is a rare, chronic inflammatory disorder that most commonly affects young to middle-aged adults; as of 2004, fewer than 250 cases were reported in the literature.2 The hallmarks of the disease are chronic interstitial keratitis and vestibulo-auditory dysfunction.3 Although the cause of this syndrome is unknown, the pathophysiology of the disease, which affects the inner ear and eye, appears to be autoimmune in nature. The ocular manifestation of Cogan syndrome can present as a bilateral interstitial keratitis (typical) or any other ocular inflammation (atypical). The inner ear signs may include a bilateral and progressive sensorineural hearing loss, vertigo, ataxia, nausea, vomiting, tinnitus and/or oscillopsia. Cogan syndrome can also cause a systemic vasculitis involving large, medium and small vessels, which may include the aorta and coronary arteries. Fever, fatigue, weight loss, rash, lymphadenopathy, hepatomegaly, hepatitis, splenomegaly, pulmonary nodules, pericarditis and arthritis are also possible.3

Syphilis and relapsing polychondritis can lead to anterior ocular inflammation and hearing loss. Congenital syphilis may present with a profound interstitial keratitis and hearing loss.4 Therefore, in any instance in which these findings are present, serologic testing for syphilis including RPR/VDRL and FTA-ABS should be ordered. Relapsing polychondritis (RP), an autoimmune disease to collagen-containing structures, can lead to various types of ocular inflammation, vestibulo-auditory symptoms (hearing loss, vertigo, ataxia), ear cartilage inflammation, respiratory symptoms, joint pain, nasal inflammation and cardiovascular symptoms.5 The diagnosis of RP is often difficult to make due to the variability in presentation and absence of specific serologic markers, and therefore requires a high index of suspicion.

THE PLAN OF ATTACK

Patients with suspected Cogan syndrome require evaluation by a multidisciplinary team, including ophthalmology, otolaryngology, rheumatology and cardiology. It is best to refer these patients to a tertiary center so that care can be coordinated quickly, since urgent treatment is critical to avoid permanent hearing loss. Ocular inflammation is usually treated initially with topical steroids and mydriatics; oral corticosteroids may be necessary for severe inflammation. Vestibulo-auditory symptoms should be urgently treated with oral prednisone starting at 1-2 mg/kg/day, after ruling out infectious causes.6 Steroid-sparing agents, such as methotrexate or azathioprine, may be considered for long-term maintenance. Such medications are best dosed in conjunction with a rheumatologist or specialist skilled in the management of these agents given their potency and potential side effects.

Early and follow-up audiology testing is important to diagnose and monitor inner ear disease. The workup for our patient paralleled these guidelines as she received urgent specialty referral for oral steroids and her topical steroids were increased by ophthalmology; unfortunately, we do not know how her long-term immunosuppression is currently being managed.

Timely and appropriate therapy can not only improve visual symptoms, but can also prevent potentially irreversible hearing loss. OM

REFERENCES

  1. Schwartz GS, Harrison AR, Holland EJ. Etiology of immune stromal (interstitial) keratitis. Cornea. 1998; 17: 278-281.
  2. Grasland A, Pouchot J., Hachulla E., et al. Typical and atypical Cogan’s syndrome: 32 cases and review of literature. Rheumatology. 2004;43:1007-1015.
  3. Cogan DS. Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Arch Ophthalmol.1945; 33:144-149.
  4. Bouchard CS. Noninfectious keratitis. In: Yanoff M, Duker JS, eds. Ophthalmology. 3rd ed. St. Louis, MO: Elsevier Mosby; 2008:chap 4.17
  5. Sharma A, Gnanapandithan K, Sharma K, Sharma S. Relapsing polychondritis: a review. Clinical Rheumatology. 2013;32:1575-1583.
  6. Tayer-Shifman OE, Ilan O, Tovi H, Tal Y. Cogan’s syndrome — clinical guidelines and novel therapeutic approaches. Clin Rev Allergy Immunol 2014; 47:65.

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