What is Cogan Syndrome?
Cogan’s syndrome is a condition in which the body’s own immune system attacks the inner ears and eyes. This causes problems with balance and hearing, as well as eye inflammation, known as interstitial keratitis. The signs of Cogan’s syndrome usually develop over three to 90 days and typically respond well to treatment with steroids.
Professionals believe that the disease is a result of the body’s immune response. Part of this involves the release of specific proteins, called cytokines, such as intercellular cell adhesion molecule-1 (ICAM-1) and IL-1β. The illness was first noted in 1934 by Baumgartner and Morgan, who called it non-syphilitic interstitial keratitis with balance and hearing problems. However, it was Dr. David Cogan who officially recognized it as a specific condition in 1945.
Typically, Cogan’s syndrome is diagnosed after other conditions have been ruled out, including syphilis. Other features of this syndrome can include fever, joint pain and inflammation, headaches, and muscle pain. Some patients might also suffer from problems with their blood vessels, including inflammation of the aorta, the largest artery in the body. Treatment options include steroids and therapies that modify the body’s immune response. Recent advancements suggest that biologic treatments and other therapies that aim to change the body’s immune response may be effective at improving the outlook for people with Cogan’s syndrome.
What Causes Cogan Syndrome?
Initially, it was thought that Cogan syndrome, a rare disease impacting the eyes and ears, might be caused by an infection from a bacteria known as Chlamydia psittaci. This was due to high levels of antibodies (the body’s defense mechanisms) against another type of chlamydia found in some patients who had previously had this infection. However, this theory was not confirmed by other researchers.
Multiple subsequent studies could not find any infection responsible for Cogan syndrome, and using antibiotics as treatment didn’t provide much success. In 1999, a theory was proposed suggesting that Cogan syndrome may be a reaction to certain infections. The idea was that a likely viral infection might trigger a defensive response from the body which mistakenly attacks proteins in the eyes, ears, and other organs.
Currently, Cogan syndrome is believed to be an autoimmune disease, meaning the body’s immune system mistakenly attacks its own healthy cells. However, in the standard methods of diagnosing Cogan syndrome, no specific sign or indicator (biomarker) has been found to confirm this.
Risk Factors and Frequency for Cogan Syndrome
Cogan syndrome is a very uncommon disease, with only about 250 known cases to date. It usually affects young adults of Caucasian descent, typically in their thirties. The average age of diagnosis is 25, but it can appear in anyone between the ages of 5 to 63. Importantly, the disease doesn’t seem to favor any particular gender.
It’s worth noting that this syndrome is extremely rare in countries in the Middle East, with the first case reported in Jordan in 2012. However, the actual number of cases could be higher because many people might be misdiagnosed with idiopathic keratitis (an inflammation of the cornea for which the cause is unknown) and idiopathic hearing loss or deafness (hearing impairment of unknown origin).
Signs and Symptoms of Cogan Syndrome
In 1980, Haynes and his team suggested that Cogan syndrome can be divided into two classes. These are known as “typical” and “atypical” variants of the condition.
The “typical” form of Cogan syndrome is characterized by:
- Interstitial keratitis (IK) – a type of corneal inflammation that doesn’t come from syphilis. IK can cause redness, sensitivity to light, declining vision, eye pain, and watering eyes. It usually starts in the region just beneath the outer layer of the cornea and quickly develops into IK. This condition often results in blood vessels growing into the cornea. The outcome, however, is usually good – despite having scars and “ghost” blood vessels left over after recovery. These symptoms might return years after they were first resolved.
- Inner ear symptoms similar to Ménière disease. These symptoms involve gradually losing the ability to hear and may result in becoming deaf within two years of the eye issues starting. The loss of hearing tends to worsen quickly, often ending in deafness within one to three months. Generally, these ear problems start within two years of the eye issues.
The “atypical” form of Cogan syndrome, on the contrary, features:
- Other eye problems like conjunctivitis, inflammation in various parts of the eye, closed-angle glaucoma, problems with retinal blood vessels, swollen eyes, inflammation of the optic nerve, or swelling of the optic disc.
- Inner ear symptoms that aren’t similar to Ménière disease or show up more than two years before or after the eye symptoms. This version of the condition often involves more systemic, or body-wide, issues.
It’s worth noting that patients with “typical” Cogan syndrome might eventually display characteristics of the “atypical” variant.
Cogan syndrome often comes after an upper respiratory tract infection in about 27% of reported cases. There might be a history of diarrhea, immunization, or dental infections. The symptoms mostly affect the eyes or ears first. Seventy-four percent of patients experience redness in their eyes, 50% experience pain or are sensitive to light and have tearing, and 42% have reduced visual clarity. It’s the vestibular system (part of the inner ear) that is affected first, followed by the cochlear system (also part of the ear) in days or weeks. The symptoms are similar to recurrent Ménière disease, including nausea, vomiting, dizziness, and ringing in the ears.
Various organs are affected in about two-thirds of cases, and one-third of patients have another systemic disorder. Systemic involvement is present in around 30 to 80% of patients. Cardiovascular issues typically involve inflammation of the aorta, which leads to a resulting aortic insufficiency in about 10% of patients and congestive heart failure. Neurologic symptoms are nonspecific, including headaches and comas. Some rare manifestations may include different types of syndromes, facial paralysis, and encephalitis. Musculoskeletal symptoms may also occur, including joint pain, muscle pain, and joint swelling. The rest of the systemic signs are quite rare, such as skin signs, lung involvement, urinalysis abnormalities, and swollen lymph nodes.
Testing for Cogan Syndrome
Diagnosing Cogan syndrome can be challenging as there is no distinct marker for the condition. Doctors often need to rule out other potential diagnoses through extensive testing because Cogan syndrome is identified by the absence of other conditions. Patients may show a range of abnormal lab results such as anemia, increased white blood cell count, increased platelet count, and elevated red blood cell sedimentation rate, which measures inflammation in the body. In addition, during flare-ups of the condition, patients might have low fibrinogen levels and high C-reactive protein, which is also an inflammation marker.
In some instances, patients could test positive for antibodies against certain strains of Chlamydia, though other infection symptoms might not be present. A urine test might show abnormal levels of protein or blood.
Patients may have various antibodies in their blood, such as antinuclear antibodies (ANA), antibodies to smooth muscle, lupus anticoagulants, cryoglobulins, anti-neutrophil cytoplasmic autoantibodies (ANCA), or rheumatoid factor (RF). In some cases, direct antibodies against components of the inner ear and cornea have been observed.
About half of the patients with Cogan syndrome might have antibodies against heat shock protein. Hearing tests often reveal sensorineural hearing loss, which affects all sound frequencies. A patient’s ability to recognize words may improve or worsen, but the initial evaluation usually shows sensory hearing loss with abnormal results on an electronystagmography test, which measures involuntary eye movements.
Treatment Options for Cogan Syndrome
The treatment for Cogan syndrome, a rare disorder characterized by inflammation in the eyes and ears, varies depending on its severity and whether it includes eye disease or inner ear and systemic inflammation. The first line of treatment usually involves a high dosage of corticosteroids, a type of medication that reduces inflammation. If the patient’s condition improves, the dosage of these steroids can be gradually reduced over two to six months. But if the steroids aren’t effective, the patient may need to stop taking them and start using additional immunosuppressive drugs like methotrexate, azathioprine, cyclophosphamide, and cyclosporine A. These have been found to achieve better outcomes.
Interstitial keratitis, an inflammation of the cornea, is tackled with topical steroids, cycloplegics (drugs that paralyze the muscles in your eye), systemic steroids, disease-modifying anti-rheumatic drugs (DMARDs), and biological therapies. Early treatment with systemic corticosteroids can help manage symptoms related to the inner ear and balance. However, steroid eye drops or local atropine (medicine that widens your pupil and relaxes your eye muscles) can be used to treat interstitial keratitis, which usually responds well. For more serious cases of Cogan syndrome, involving large blood vessels inflammation, oral cyclophosphamide may be prescribed. If this doesn’t work, cyclosporine may be an alternative.
Recent developments have highlighted the use of tumor necrosis factors (TNF-a) inhibitory agents, such as infliximab, as another treatment option. Infliximab has been found to be the most effective among these, with 11 out of 12 treated cases achieving clinical remission. Similarly, Rituximab has been used to reduce the need for other medications and avoid cochlear implants or deafness in severe cases. But it isn’t used as the first line of treatment.
For those who didn’t respond to drug therapy for hearing loss, cochlear implants have proven useful. Treatments like Benzodiazepines, antihistamines, or vestibular therapy (exercises designed to minimize dizziness and imbalance) can be used for chronic vestibular dysfunction that occurs in some cases. Lastly, there has been growing interest in stem-cell-based treatment for autoimmune disorders like Cogan syndrome, but more studies are needed to confirm their long-term safety and effectiveness.
What else can Cogan Syndrome be?
Cogan syndrome, a rare condition with hearing and vision issues, can be misdiagnosed because it shares similar symptoms with other diseases. Here are a few that might be considered:
- Susac syndrome: This condition causes damage to the small arteries inside the inner ear, retina, and brain.
- Congenital syphilis: A type of syphilis that is present at birth and can cause specific dental changes, eye inflammation, and hearing loss. A negative test for syphilis is required before Cogan syndrome can be diagnosed.
- Sergent and Christian’s description of inflammation of the blood vessels following ear and eye inflammation, without affecting the inner ear.
- Vogt-Koyanagi-Harada syndrome: A condition causing decreased vision, hearing loss, and inflammation of the brain, eyes, and the covering of the brain. Some of these symptoms can also occur in Cogan syndrome, but unlike Cogan, this condition can cause hair loss and white patches in the hair.
- Polyarteritis nodosa and granulomatosis with polyangiitis: These conditions often affect the ear and eye, and show characteristics not present in Cogan syndrome, such as lung infiltrations, kidney inflammation, nose and throat lesions, and specific blood test results.
- Takayasu arteritis: Another condition that might be considered.
Cogan syndrome is hard to diagnose in its early stages. Additionally, it’s been identified in some cases to co-exist with other autoimmune diseases like rheumatoid arthritis, certain types of kidney inflammation and eye inflammation.
In a study, it was found that four patients with inflammatory bowel disease (IBD) developed Cogan syndrome, eye inflammation and hearing loss after experiencing gastrointestinal symptoms. Another study of 22 patients with both Cogan syndrome and IBD found that half of the patients developed symptoms of Cogan syndrome after their gastrointestinal problems.
Lastly, diseases like syphilis, chlamydia, leprosy, tuberculosis, brucellosis, Lyme disease, herpes, measles, mumps, smallpox, parasitic infections, and autoimmune diseases can cause interstitial keratitis, symptom which is common in Cogan syndrome too.
What to expect with Cogan Syndrome
Cogan syndrome, which affects the ears, eyes, and cardiovascular system, usually has a low success rate for treatment, especially in terms of ear problems. There is no way to reverse the deafness that often comes with this condition. A study done at Mayo clinic showed that out of 60 patients treated between 1940 and 2002, 18% lost hearing in one ear while 52% lost hearing in both ears.
In a positive note, most of these patients had normal or nearly normal vision at their last check-in. However, a separate research in France showed that Cogan syndrome tends to relapse more frequently compared to patients at Mayo Clinic. Around 78% of the patients who were examined over 7.1 years experienced a relapse, compared to 13% and 31% of patients who relapsed after 5 and 10 years respectively.
In terms of treatment, all patients received high doses of steroids. But, the French group used more immunosuppressive drugs compared to the Mayo Clinic group. Interestingly, infliximab was used to treat ten patients in the French study, even though it was only approved in late 1998. An unfortunate side effect reported by a study was a decline in hearing abilities after undergoing cochlear implants. This was due to new bone growth in the ear that positions itself between the implant and neural structures, impacting the effectiveness of the procedure.
Possible Complications When Diagnosed with Cogan Syndrome
Systemic vasculitis is a condition where the blood vessels become inflamed. This can occur in large or medium-sized vessels in 15-21% of reported cases. However, it’s important to note that blood vessels of any size can be affected. Certain life-threatening complications have been noted in about 10% of cases such as aortic insufficiency – a condition where the aortic valve in the heart doesn’t close tightly; aneurysms – a balloon-like bulge in an artery that can rupture and cause serious health problems; and dissection – a condition where the inner layer of your aorta, the large blood vessel branching off the heart, tears. Other heart valves, particularly the mitral valve, may also be affected causing complications.
Apart from affecting blood vessels and potentially the heart, systemic vasculitis can affect other organs like the brain and kidneys. For instance, stroke has been observed in some patients with Cogan syndrome, a rare disorder characterized by recurrent eye and ear inflammation. Neurological symptoms may also occur, such as aphasia (speech impairment) caused by a transient ischemic attack (mini-stroke), hemiplegia (paralysis of one side of the body), and hemiparesis (weakness on one side of the body) due to a cerebral vascular accident (brain stroke).
Summary of Possible Complications From Systemic Vasculitis:
- Aortic insufficiency
- Aneurysms
- Dissection
- Complications to the mitral valve
- Brain disorders such as stroke in Cogan syndrome patients
- Neurological symptoms like aphasia due to transient ischemic attack
- Hemiplegia
- Hemiparesis because of a cerebral vascular accident
Preventing Cogan Syndrome
Cogan syndrome is a rare condition where the body’s immune system attacks its own tissues, affecting the ears and eyes. It tends to cause symptoms such as hearing and balance issues, and an eye condition called non-syphilitic interstitial keratitis. Positive responses to steroid treatments support the theory that this is an autoimmune disorder. Nonetheless, treatment can be tricky because lack of proper treatment for hearing loss might lead to deafness. Hearing loss usually becomes permanent due to repeated episodes of the syndrome.
The primary treatment for this condition is steroids. There are also several different types of drugs that suppress the immune system and have been used as treatment. In severe cases where individuals have major hearing loss that does not respond well to strong medications that suppress the immune system, an operation to implant a device into the ear, known as a cochlear implant, may be considered.
Understanding the illness and its management is crucial for patients and their caretakers. Knowing what to expect in terms of prognosis and treatment outcomes could boost adherence to the treatment regime, leading to better results.