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A rare inflammatory/autoimmune disorder of unknown origin characterized by interstitial keratitis (IK) and audiovestibular dysfunctions.
ORPHA:1467Classification level: Disorder
- Synonym(s): -
- Prevalence: Unknown
- Inheritance: Not applicable
- Age of onset: Childhood, Adolescent, Adult
- ICD-10: H16.3
- OMIM: -
- UMLS: -
- MeSH: D055952
- GARD: 1421
- MedDRA: 10056667
Cogan syndrome (CS) prevalence is unknown. To date, approximately 300 cases have been reported. The disease is primarily described in causasians patients with no gender predilection.
CS mainly affects young adults, with a median age at onset between 20 and 30 years, and occasionally affects children. The syndrome shows a large spectrum of clinical features. Non-syphilitic IK and cochleovestibular symptoms with unilateral or bilateral sensorineural hearing loss, vertigo and tinnitus are typical CS manifestations. The interval between the onset of ocular and audio-vestibular involvement is usually less than 2 years. CS presentation is considered atypical in presence of unusual ocular involvement (such as uveitis, chronic or recurrent conjunctivitis, scleritis, optic disc edema, and retinal vasculitis, with or without IK), audiovestibular symptoms that do not resemble Menière disease, or when the latency between the two organ involvement is more than 2 years A systemic disease expression is reported in at least 1/3 of the patients, especially in atypical cases, with general symptoms such as fever, headaches, weight loss, and/or in presence of signs of organ involvement, mostly cardiovascular (aortitis, aortic insufficiency, congestive heart failure, Raynaud's phenomenon), neurological (peripheral neuropathy, meningitis, hemiparesis or hemiplegia due to a cerebral vascular accident and aphasia due to a transient ischaemic event) and gastrointestinal systems (diarrhea, melena and abdominal pains).
CS is supposed to have an autoimmune etiology, and autoantibodies to inner ear antigens and corneal structures, such as the Cogan peptide are usually present, even if they cannot be considered specific CS serological biomarkers.
The diagnosis is mainly clinical of exclusion of infections (in primis syphilis and Lyme disease) on the good response to corticosteroid treatment. There are no confirmatory diagnostic tests, even if laboratory tests, audiogram, and imaging may be useful for supporting the diagnosis and excluding other potential etiologies.
Differential diagnoses include syphilis, Menière disease, Lyme disease, sarcoidosis, tuberculosis, polyarteritis nodosa, granulomatosis with polyangiitis and Takayasu arteritis.
Management and treatment
Corticosteroids are the cornerstone of CS therapy. Topical glucocorticoids in association with cycloplegics may be considered for the management of isolated, mild eye involvement, while systemic corticosteroids should be considered for more severe eye involvement, hearing impairment, and systemic manifestations. Treatment with high doses of systemic corticosteroids (1-1.5 mg/kg of prednisone daily) are expected to prevent deafness, with a beneficial response usually within 2-3 weeks. However corticosteroids have proven to be of short-term benefit, and they carry a risk of serious side effects, therefore in patients with refractory or steroid-dependent disease, a second line treatment with immunosuppressants should be considered, although conventional immunosuppressive drugs such as methotrexate, cyclophosphamide, azathioprine, or cyclosporin A seem to have a limited efficacy. There are increasing reports of successful response to Infliximab, a tumor necrosis alpha (TNFalpha) blocker. Infliximab showed cochleovestibular symptoms improvement and allowed corticosteroid tapering, with a significantly difference when compared to patients treated with steroids alone or conventional DMARDs. The early use of infliximab as first line therapy in severe cases seems to be even more effective. Cochlear implantation is a valuable rescue surgical strategy in cases of severe sensorineural hearing loss unresponsive to intensive immunosuppressive regimens.
The prognosis is mainly related to the risk of permanent deafness and cardiovascular complications, especially aortic insufficiency. Severe internal organ involvement and cardiovascular complications-related deaths are rare.