Cogan syndrome (CS), an immune-mediated condition that primarily affects young adults, is associated with ocular inflammation (usually interstitial keratitis) and audiovestibular dysfunction. This syndrome may be accompanied by a systemic vasculitis of large- and medium-sized arteries that may resemble Takayasu arteritis.
The onset of CS is frequently preceded by an upper respiratory tract infection. Because many features of CS can be caused by known pathogens (eg, Treponema pallidum), CS may be the direct consequence of an unidentified pathogen affecting the eyes, ears, and blood vessels. Alternatively, CS may be the indirect consequence of a pathogen that induces an immune response that continues to attack the host long after the pathogen has been eliminated (ie, molecular mimicry). Neither of these theories has been proved.
The most common ocular manifestation of CS is interstitial keratitis, which is characterized by the abrupt onset of photophobia, lacrimation, and eye pain. CS may also be associated with inflammation in other parts of the eye. Scleritis (Figure 42–4), peripheral ulcerative keratitis, episcleritis, anterior uveitis, conjunctivitis, and retinal vascular disease are all possible.
Bilateral scleritis in a patient with Cogan’s syndrome who had suffered the rapid onset of sensorineural hearing loss in both ears.
Patients with CS frequently suffer the acute onset of vertigo, tinnitus, nausea, and vomiting. These symptoms may be enormously disabling. The audiovestibular symptoms may occur before or after the onset of ocular disease, and are often separated in onset by weeks or months. If not treated promptly and aggressively, permanent hearing loss may ensue. Recurrent attacks, which are common, may cause decremental loss of hearing. Ultimately, complete hearing loss occurs in as many as 60% of patients.
The most common manifestation of vasculitis in patients with CS is aortitis. Aortitis may lead to dilatation of the aorta and subsequent incompetence of the aortic valve. Involvement of aortic branches (Figure 42–5) may cause arm or leg claudication. Renal artery stenosis or occlusion of the great vessels may also occur. These manifestations may be accompanied by nonspecific constitutional symptoms, such as malaise, fever, or weight loss as well as arthralgias and frank arthritis.
Large-vessel vasculitis in Cogan syndrome. Femoral artery disease led to lower extremity claudication.
Laboratory findings are nondiagnostic and generally reflect the presence of inflammation. An antibody against a 68-kD antigen has been identified in cases of autoimmune sensorineural hearing loss but is not found in patients with CS. Exclusion of syphilis with fluorescent treponemal antibody testing (ie, FTA-ABS, not just the rapid plasma reagin) is essential.
Gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) studies may demonstrate a hyperintensity in the membranous labyrinth secondary to vessel inflammation in the stria vascularis. This enhancement is not seen in patients with inactive CS and may be useful in identifying the activity of the disease. Brainstem MRI studies are also essential to exclude tumors of the cerebellopontine angle, which may mimic the audiovestibular features of CS. Angiography may be useful to define the involvement of the great vessels (Figure 42–5). Magnetic resonance angiography is useful in evaluating vessel wall thickness and edema as well as the degree of luminal stenosis.
Formal audiometric testing is important early in the evaluation to distinguish conductive hearing loss from sensorineural hearing dysfunction. In CS, audiometry demonstrates sensorineural hearing loss that preferentially affects the low- and high-range frequencies. This may be a useful way to document response to therapy, although subsequent hearing loss is not always due to active disease.
The differential diagnosis of immune-mediated inner ear disease (ie, sensorineural hearing loss with or without vestibular dysfunction) is shown in Table 42–1. Inflammatory eye disease may be caused by a variety of pathogens, including bacterial (eg, Chlamydiae, Neisseriae), spirochetal (eg, Borrelia burgdorferi), viral (eg, herpes simplex, varicella zoster), and mycobacterial (eg, Mycobacterium tuberculosis, M leprae).
Table 42–1. Differential Diagnosis of the Audiovestibular Complications of Cogan Syndrome. ||Download (.pdf)
Table 42–1. Differential Diagnosis of the Audiovestibular Complications of Cogan Syndrome.
|Immune-mediated inner ear disease||Sensorineural hearing loss and vestibular dysfunction in the absence of eye inflammation.|
|Syphilis||Latent and tertiary forms of this disease. Ordering both rapid plasma reagin and FTA-ABS essential.|
|Other infections||Lyme disease, mumps|
|Acoustic neuroma||Performance of brainstem magnetic resonance imaging essential to exclude this tumor.|
|Ménière syndrome||Inner ear disturbances in Ménière syndrome are generally more intermittent, with a waxing/waning character.|
|Systemic vasculitides||Granulomatosis with polyangiitis (formerly Wegener granulomatosis), giant cell arteritis|
|Collagen vascular diseases||Sjögren syndrome|
|Other inflammatory conditions||Sarcoidosis, Susac syndrome|
|Barotrauma||Other etiologies of perilymph fistula formation|
|Medications||Aminoglycosides, loop diuretics, antimalarials|
Some manifestations of CS respond well to symptomatic therapy. In general, the ocular manifestations are more amenable to therapy than the auditory complications. Interstitial keratitis may be treated with topical atropine or glucocorticoids. Sensorineural hearing loss in CS is analogous to rapidly progressive glomerulonephritis in other forms of systemic vasculitis: prompt treatment with immunosuppression is indicated. In addition to glucocorticoids, cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil have all been used. The basis for choosing among these agents is largely empiric. The role for biologic agents, if any, has not been defined. For patients with advanced, irreversible hearing loss, hearing aids and cochlear implants may help. Vestibular retraining may be required for some patients with significant cochlear damage.
The prevention of complications depends directly on the rapid recognition of this diagnosis, and the equally swift institution of therapy. Permanent damage may result early in the course of immune-mediated inner ear disease, and hearing deficits will not respond to therapy if initiated too late. Therefore, a high index of suspicion for this diagnosis must be maintained when evaluating patients with compatible complaints.
Even if the initial event is recognized and responds to therapy, recurrent bouts of sensorineural hearing loss may cause the gradual loss of hearing. Up to 60% of patients experience some degree of permanent hearing loss. Some patients become completely deaf.