Journal of Neuro-Ophthalmology, December 1990, Volume 10, Issue 4

Cogan's syndrome.

Cogan's syndrome is a rare systemic autoimmune disease with preeminent ophthalmological and vestibulocochlear manifestations. Untreated, the disease usually results in profound deafness; eye involvement is usually self-remitting. Ten to twenty percent of patients either develop serious aortic valve disease or vasculitis or both. When given early, immunosuppressive therapy has been shown to be effective in treating all aspects of the disease. Thus, early disease recognition is of great significance. We present a patient with Cogan's syndrome and briefly discuss therapeutic implications.

Journal of CliniCilI Neuro- ophthalmology 10( 4): 261- 263, 1990. Cogan's Syndrome E. Wilder- Smith, M. D., and U. Roelcke, M. D. Cogan's syndrome is a rare systemic autoimmune dis­ease with preeminent ophthalmological and vestibulo­cochlear manifestations. Untreated, the disease usually results in profound deafness; eye involvement is usually self- remitting. Ten to twenty percent of patients either develop serious aortic valve disease or vasculitis or both. When given early, immunosuppressive therapy has been shown to be effective in treating all aspects of the disease. Thus, early disease recognition is of great sig­nificance. We present a patient with Cogan's syndrome and briefly discuss therapeutic implications. Key Words: Cogan's syndrome- Immunosuppressive therapy. From the Department of Neurology, University of Bern, Bern, Switzerland ( E. W.- S.), and the Department of Neurol­ogy, University of Heidelberg, Heidelberg, West Germany ( U. R.) Address correspondence and reprint requests to Dr. E. Wilder- Smith, Universitat Bern, lnselspital, Neurologische KIinik, CH- 3010 Bern, Switzerland. 261 © 1990 Raven Press, Ltd., New York In 1945 Cogan ( 1) first described the syndrome of nonsyphilitic interstitial keratitis associated with vertigo, tinnitus, and usually profound deafness, Since then the systemic autoimmune nature of this rare disease and its broad clinical spectrum has been recognized ( 2,3). CASE REPORT A 20- year- old Caucasian woman of German de­scent was well until 6 weeks prior to admission to our hospitaL She suddenly developed vertigo with increasing bilateral hearing loss accompanied by tinnitus and photophobia. There was no relevant medical or family history. Physical examination revealed profound bilateral hearing loss and bilateral conjunctivitis. An audiogram demonstrated 70 and 40% hear­ing loss on the left and right ear, respectively, Roentgenograms of the skull, sinuses, and inter­nal auditory meatus were normaL A cranial com­puted tomographic scan excluded bilateral acoustic neuromas. Ophthalmological examination could not detect an infectious etiology of the conjunctivitis, A cor­neal biopsy demonstrated follicular lymphocytic conjunctivitis with interstitial keratitis. Laboratory data was remarkable for a leucocyto­sis of lO, 200/ mm3 and an elevated erythrocyte sed­imentation rate ( ESR) of 40/ 72 mm after 1 and 2 h, respectively. Normal values were obtained for C­reactive protein and immunelectrophoresis, hemo­globin, antibodies against smooth muscle, mito­chondria, and double helix DNA. Hepatitis B, VORL, TPHA, FTA- ABS, and TPI were negative, as was antibody screening for herpes simplex vi­rus, cytomegalovirus, Epstein- Barr virus, mumps, measles, enterovirus, mycoplasma, and chlamydia. Coagulation studies included a normal pro- 262 E. WILDER- SMITH AND U. ROELCKE thrombin time, partial thromboplastin time, and thrombin time. Fibrinogen was in the normal range. Cerebrospinal fluid obtained by lumbar punc­ture showed normal cell and protein content. Elec­troencephalogram, electrocardiogram, and ultra­sonography of the abdomen were uneventful. Histological examination of the Vastus lateralis muscle found no evidence of muscle or vessel pa­thology. The common causes of sudden deafness like bacterial and viral infection, ischemic vascular disease, vasomotor disease, Paget's disease, tu­mor, leukemia, and acute allergic reactions could not be detected. Differing etiologies of interstitial keratitis such as tuberculosis, leprosy, and focal virallbacterial infection could also be excluded [ for differential diagnosis, see ( 4)]. Upon administra­tion of prednisone ( 100 mg/ d tapered to 40 mg/ d over a period of 2 months) and azathioprine ( 150 mg/ d), eye symptoms rapidly and completely re­gressed, where as hypakusis persisted. The ESR returned to normal. Because of steroid side effects, azathioprine was replaced with the irnmunosuppressively more ac­tive methotrexate ( 7.5 mg/ week), and prednisone further reduced. As treatment was tapered the pa­tient showing no clinical or laboratory evidence of disease activity. DISCUSSION The etiology of Cogan's syndrome remains ob­scure. Past attempts at etiologic explanations have included such circumstances as small- pox vaccina­tion, upper respiratory infections, Boeck's sarcoid, periarteritis nodosa, drug sensitivity, and general­ized hypersensitivity ( 4). Recent work has demon­strated a defect in the cellular immune system, the humoral system on the whole being unaffected ( 3,5). In 1960 Cody and Williams ( 6) discovered that Cogan's syndrome not only involves the cornea and eighth nerve, but that it is a systemic disease. From the hundred or so cases presented in the literature it is known that profound permanent hearing loss is common ( 2,3). This is thought to be due to direct vestibulocochlear damage caused by the body's own misdirected T cells ( 5). The clas­sical interstitial keratitis as well as the nowadays well- known wide spectrum of ophthalmolog­ical involvement is mostly self- remitting ( 7). Ten percent of the patients dC',; elop grave aortic valve J ( lill Nn/(" disease sometimes necessitating aortic valve replace: nent. A further 10% suffe~ fro~ wi~ e­spread vasculitis ( 2,3). Systemic ~ anife~ tations 10­clude unexplained fever, gastro1Otestinal sy~ p­toms, musculoskeletal involvement, hypertenSIon, lymphadenopathy, splenomegaly, cerebral artery occlusions, and mononeuritis ( 3). Young Cauca­sian adults are primarily affected ( mean age of on­set: 29 years). Between 10 and 20% of those af­fected die due to aortic valve disease and vasculitic involvement. The syndrome is characterized by an acute phase lasting from months to years, and followed by a chronic burntout phase ( 2). Treatment until recently has largely been symp­tomatic. Unsuccessful measures have included an­tibiotics, typhoid vaccine, convalescent plasma, histamine by intravenous infusion, low salt diet, vitamins, and adrenocorticotropin as well as bilat­eral cervical sympathectomy ( 4). Due to the pre­sumed autoimmune nature of the disease several patients have now been treated immunosuppres­sively using either prednisolone alone or in com­bination with azathioprine with encouraging re­sults ( 2,3). There are increasing reports of good hearing improvement if immunosuppressive treat­ment was initiated within 2 weeks of hypoacusis ( 3,8). As a rule, ophthalmological disease rapidly resolves using topical or systemic steroids. Like­wise most other systemic manifestations seem to respond favorably to immunosuppressive therapy ( 3). Our patient presented with typical severe ves­tibulocochlear symptoms and classical interstitial keratitis. With immunosuppressive treatment our patient's eye symptoms rapidly cleared, whereas bilateral significant deafness persisted. We pre­sume that there was no hearing improvement due to late referral of the patient ( 6 weeks after onset of symptoms). The patient, though, was able to con­tinue her language studies with the aid of bilateral hearing aids. In the follow- up ( 3 years), no evi­dence of systemic complications or disease reacti­vation could be found. Except for steroid side ef­fects at the start, therapy was well tolerated and could be successfully tapered. Cogan's syndrome, another recent adage to the long list of probable autoimmune diseases, is a treatable cause of combined eighth nerve and oc­ular damage and often widespread systemic man­ifestations. Complete deafness, aortic valve dis­ease, and vasculitis are not uncommon serious co. mplicatio~ s. Early . immun~ su~ pressive therapy wlth predmsone or 10 combmahon with azathio­prine/ methotrexate is advocated. COGAN'S SYNDROME 263 REFERENCES 1. Cogan DG. Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Arch Ophthalmol 1945; 33: 144- 9. 2. Cheson BD, Bluming AZ, Alroy J. Cogan's syndrome: a systemic vasculitis. Am JMed 1976; 60: 549- 55. 3. Vollertsen RS, McDonald TJ, Younge B. Cogan's syndrome: 18 cases and a review of the literature. Mayo Clin Proc 1986; 61: 344- 61. 4. Roberts J. Cogan's syndrome. Med JAust 1965; 2: 486- 90. 5. Hughes GB, Kinney SE, Barma BP. Autoimmune reactivity in Cogan's syndrome. Otolaryngol Head Neck Surg 1983; 91: 24- 32 6. Cody DT, Williams HL. Cogan's syndrome. Laryngoscope 1960; 70: 447-- 8. 7. Cobo LM, Haynes BF. Early corneal findings in Cogan's syndrome. Ophthalmology 1984; 91: 903- 7. 8. Haynes BF, Pikus A, Kaiser- Kupfer M. Successful treat­ment of sudden hearing loss in Cogan's syndrome with corticosteriods. Arthritis Rheum 1981; 24: 501- 3. I Clin Neuro- ophthalmol, Vol. 10, No, 4, 1990