Understanding Cogan’s Syndrome

COGAN’S SYNDROME is an extremely rare condition with no single test to identify it and with symptoms that mimic those of many far more common diseases. Its cause remains unknown, as do its specific triggers. But if not diagnosed and treated quickly, it can lead to significant (and sometimes permanent) loss of hearing and degraded vision. It can also manifest with vasculitis, and in extremely severe cases, it can be fatal if the aorta is affected.

Due to its rarity, the actual number of cases is difficult to confirm. The portal for rare diseases and orphan drugs, Orpha. net, reports only approximately 300 cases identified worldwide since the disease was first formally described in 1945, and that was the highest number found (other sources report between 100 cases and 250 cases).¹

What Is Cogan’s Syndrome?

While most diseases are identified by their underlying cause, Cogan’s syndrome is entirely defined by its symptoms: sudden onset of hearing loss, vertigo and inflammation of the eyes with or without vasculitis that cannot be explained by any other possible cause.²

The syndrome is named after ophthalmologist David G. Cogan, a faculty member at Harvard who described the condition in 1945³ as nonsyphilitic “interstitial keratitis associated with vertigo, tinnitus and usually profound deafness.”⁴ However, it is believed the disease was described in a paper written by R.F. Morgan and C.J. Baumgartner in 1934.⁵

Cogan’s syndrome is thought to be an autoimmune disease, possibly even a subset of vasculitis, but disagreement over classification remains. What is known is it is chronic with no cure, although symptoms can often be controlled with treatment, and the severity of symptoms can wane over time.

Interestingly, for a disease that affects so few people, there are two subsets of Cogan’s: Cogan’s syndrome type I as described in this article and atypical Cogan’s syndrome in which either only some symptoms manifest, different symptoms also present or the disease progresses more slowly — over a matter of years rather than months.

The eye inflammation caused by Cogan’s generally presents as bilateral interstitial keratitis or other similar corneal stromal keratitis, but it can also take the form of episcleritis, scleritis, uveitis, papillitis, vitritis or choroiditis.⁵ The hearing issues arise from inflammation and calcification of the canals, the vestibule or the cochlea.⁶

Causes of Cogan’s Syndrome

Although little is presently understood about the causes of Cogan’s syndrome, National Institutes of Health’s (NIH) Genetic and Rare Diseases Information Center reports that current research suggests an unknown autoimmune response causes the body to attack tissues of the eye and ear.⁷ Indeed, the discovery of autoantigen peptides in the eye and ear tissue of patients with Cogan’s strongly suggests an autoimmune response.⁶

Some researchers believe onset of Cogan’s syndrome may be a reaction to a previous infection, but this has yet to be established.³ In fact, currently, no definitive cause or trigger has been identified. And, no genetic cause for Cogan’s has been identified, nor does it seem to run in families.

The disease typically affects younger adults between 20 years and 40 years, and sometimes children.1 Men and women seem equally likely to develop it,⁸ as well as individuals of all ethnicities.²

Symptoms and Progression of Cogan’s Syndrome

Cogan’s syndrome progresses rapidly, with symptoms worsening in a matter of weeks, often before a firm diagnosis has been made. It generally initially presents as hearing loss, inflammation of the eyes or vertigo: 38 percent of patients present with ocular inflammation and 46 percent with auditory symptoms, while just 15 percent have both symptoms at first examination.⁵ However, within five months of an initial exam, 75 percent of patients experience both vision and hearing degradation.

Some portion of hearing loss is almost always permanent, and in two-thirds of patients, the loss is severe.2 In fact, a significant percentage of Cogan’s patients permanently lose 100 percent of their hearing. In most patients, both vision and hearing issues affect both sides. In rare cases, only one ear or one eye will be affected at first, but this almost always progresses to both sides being affected.⁶

According to the American Autoimmune Related Diseases Association, other less-common symptoms that may indicate Cogan’s syndrome are fever, nausea, unexplained weight loss, enlarged lymph nodes or photo sensitivity.

Vasculitis can also occur in Cogan’s syndrome patients and, in severe cases, can include aortitis. But even when the aorta is not involved, significant organ damage can result from the onset of vasculitis, particularly to the kidneys.⁶

Diagnosing and Treating Cogan’s Syndrome

Since there is no diagnostic test for Cogan’s syndrome, a diagnosis is made through a process of elimination. As symptoms and damage can progress quickly, this analysis should be accelerated as much as possible.

If a patient presents with red and inflamed eyes and hearing problems, as well as vasculitis, Cogan’s syndrome can be considered as a possible diagnosis early on. But if a patient presents with only vision or auditory issues, other potential causes will need to be considered initially.

Loren Bartels, MD, FACS, director of the Tampa Bay Hearing and Balance Center and an otolaryngology professor at the University of South Florida who has treated patients with Cogan’s, says due to the quick progression of the disease, it makes sense to reach out to specialists immediately. The best course “is to share the care with an ophthalmic immunologist, as at least three different conditions can present in a similar fashion: Cogan’s, Vogt-Koyanagi-Harada disease and Susac’s syndrome,” explains Dr. Bartels.

The auditory symptoms of Cogan’s are nearly identical to those of Meniere’s disease and are also similar to those of syphilis, Lyme disease and Epstein-Barr virus. Consequently, when a patient presents with these symptoms, these other possible causes should be considered. Syphilis and Lyme disease are both bacterial diseases, and they can be diagnosed (or eliminated) through a blood draw and lab test; syphilis with the rapid plasma reagin test or venereal disease research laboratory test; and Lyme disease with a two-part lab test. Epstein-Barr virus is also diagnosed with a blood test that looks for antibodies made in response to the infection.

While the cause of Meniere’s disease is not fully understood, it is far more common than Cogan’s and, thus, should be eliminated from consideration before making a final diagnosis of Cogan’s. Vision-motion tests such as the video head impulse test are used to test for Meniere’s disease.

Any differences in blood pressure or pulse on the right side versus the left side may indicate vasculitis, as might a noticeable heart murmur. An MRI can help eliminate the possibility of a tumor or other growth, particularly in the ear canals.⁶

Once a diagnosis has been made, the typical treatment is topical and systemic corticosteroids to reduce the inflammation causing the damage in the ears, eyes and circulatory system. The Merck Manual recommends topical prednisolone acetate 1% for treatment of keratitis, episcleritis and anterior uveitis. If the front of the eye is affected, mydriatics (a type of medicine that make the pupil of the eye dilate) may be used to prevent the iris from becoming stuck to the cornea.²

For inflammation causing auditory issues, the recommended treatment is prednisone 1 mg/kg orally daily for at least two months.⁵

For cases that don’t respond to initial treatment or show diminishing response, immunosuppressant drugs may be prescribed to temper the autoimmune response. Infliximab (Remicade, Inflectra) has shown promise for reducing ear damage and also assists with weaning patients from corticosteroids with their long-term side effects.¹

Dr. Bartels points out that while high-dose steroids are commonly prescribed, “it is unclear whether that changes the long-term progression to severe or profound sensory hearing loss.”

He also says that “possibly helpful are immunosuppressive drugs such as methotrexate, cyclophosphamide, cyclosporine or azathioprine, but these would generally be started only if the hearing loss was steroid-responsive.” He notes, however, that these drugs have a significant side-effect risk, which is especially pertinent since this disorder commonly occurs in relatively young individuals of child-bearing age.

When damage to the ear causes permanent hearing loss, cochlear implants have proved effective at restoring some auditory function.¹ “These patients uniformly do well with cochlear implants, but a surgical challenge is common,” Dr. Bartels explains. “The inferior lateral basal turn of the cochlea is commonly ossified (has obstructive new bone formation that plugs the surgical entry area into the inner ear fluid spaces) and requires delicate drilling to get past. Once past that, the cochlear implant typically slides into the inner ear, the cochlear scala tympani, without difficulty. Caution is needed to avoid insertion through the bony spiral lamina and basilar membrane into the cochlear duct or scala vestibuli.”

If one or both corneas are irreversibly damaged, corneal transplants can be considered.

Outside of permanent hearing loss, the gravest risk is from vasculitis, so that needs to be monitored over time — often with liver function tests to track damage. In severe cases, valve implants may be needed in the aorta.

Ongoing Research

With such a small population affected by Cogan’s syndrome, research into its cause and treatments is minimal. Any advances are likely to come via research into other related autoimmune diseases or increases in knowledge about autoimmune disease in general.

One recently canceled study (since not enough subjects volunteered) would have looked at the use of Cacicol20 in promoting the healing of corneal wounds.⁹ And, a 2019 study used intravenous immune globulin to treat a Cogan’s syndrome patient with repeated severe flare-ups through three successful pregnancies.¹⁰

Looking Ahead

While several papers point out that Cogan’s syndrome is likely underdiagnosed and thus underreported, even if the true number of cases were 10 times greater, it would remain a statistical anomaly — one most physicians will never encounter over the course of their careers. Nevertheless, a quick diagnosis and aggressive treatment can have tremendous positive impact on a patient’s quality of life. Given the high probability of permanent hearing loss for any patient who exhibits Cogan’s syndrome, moving rapidly to ascertain the cause of such symptoms should be prioritized so treatment can begin.