Ann 0101 Rhinol Lary1l(fol 101:1992
CORNEAL AUTOIMMUNITY IN COGAN'S SYNDROME? REPORT OF TWO CASES MAARTEN H. J. M. MAJOOR, MD UTRECIIT, TIIE NETIIERLANDS
FRANs W. J. ALBERS, MD, PHD
RUTH VAN DER GAAG, PHD
UTREOIT, TIIE NETHERLANDS
AMSTERDAM, TIlE NETHERLANDS
FRITs GMELIG-MEYLING, PHD
EGBERT H. HUIZING, MD, PHD
UTRECIIT, TIlE NETHERLANDS
UTRECIIT, TIIE NETIIERLANDS
Autoimmune reactivity against corneal antigens is described in two patients with Cogan's syndrome, a nonsyphilitic deep interstitial keratitis with vestibuloauditory symptoms. In both cases corneal antibodies were found at the beginning or during an exacerbation of the disease. After administration of high doses of corticosteroids the corneal antibodies diminished. Interstitial keratitis can generally be controlled by local or systemic corticosteroids. The effect of corticosteroid therapy on the audioveslibular symptoms is variable. The possibility of an autoimmune pathogenesis of Cogan's syndrome is discussed. KEY WORDS -
autoimmune disease, Cogan's syndrome, corneal autoimmunity.
INTRODUCTION
ied is still too small to draw significant conclusions from the data. 4, l0
In 1945 the ophthalmologist David Cogan was the first to describe a syndrome of nonsyphilitic deep interstitialkeratitis with vestibuloauditory symptoms. I This disorder is currently known as Cogan's syndrome. More recent reports on this syndrome have indicated involvement of other organ systems and systemic vasculitis.I-'
In Wegener's granulomatosis, polyarteritis nodosa, and rheumatoid arthritis with corneal involvement, a high incidence of circulating antibodies to corneal epithelium has been observed, which suggests an autoimmune cause. I I In this paper two patients with Cogan's syndrome associated with systemic manifestations are presented. During the course of the disease, tests were repeatedly performed to detect the presence ofcirculating antibodies against the cornea. The results support the possibility that autoimmune reactions contribute to the development of Cogan's syndrome.
Although the cause of Cogan's syndrome is still obscure, an immunologic origin has been suggested by several authors. Hughes et a14 frequently found an elevation of the sedimentation rate in the acute stage of the disease. Edstrom and Vahlne 5 described a patient in an acute stage of the syndrome in whom an episode of transient immunologic anergy was accompanied by an increased number ofcirculating T and B lymphocytes and signs of complement consumption. These observations were not confirmed in cases reported later. 4,6,7 Hughes et a1 4 also demonstrated that an inner ear membrane extract could induce lymphocyte migration inhibition in a patient with Cogan's syndrome. Lymphocyte stimulation by eyespecific proteins (5 antigen, outer rod segment, or scleroprotein) was described by Peeters et al.8 Arnold and Gebbers? found antibodies directed against inner ear tissue and corneal epithelium in serum of patients with Cogan's syndrome. There is scattered evidence for human leukocyte antigen allotype associations in Cogan's syndrome, but the number of patients stud-
CASE REPORTS
Case 1. A 21-year-old man developed a mandibular abscess after extraction of a molar. Two days after drainage of the abscess he became very ill with severe headaches, poorly localized discomfort in the neck, lower back pain, and arthralgia, followed by abdominal discomfort 1 week later. He was admitted to the Department of Otorhinolaryngology, University Hospital Utrecht, 4 weeks after his first complaints. Besides the above-described symptoms, he had lost 12 kg in weight and suffered from intermittent fever, anorexia, fatigue, epistaxis, nausea and vomiting, and testicular pain. The patient complained of bilateral hearing loss with tinnitus and fullness in the ears.
From the Departments ofOiorhinolaryngology (Majoor, Albers, Huizing) and Immunology (Gmelig-Meyling), University Hospital Utrecht, and the Department of Ophthalmo-Imrnunology, The Netherlands Ophthalmic Research Institute, Amsterdam (van der Gaag), the Netherlands. REPRINTS - Maarten H. J. M. Majoor, MD, Dept of Otorhinolaryngology, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.
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Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 15, 2015
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Majoor et al, Corneal Autoimmunity in Cogan's Syndrome?
Fig 1. (Case 1) A) Erythema of palm of hand. B) Injected perilimbal vessels and conjunctivitis of both eyes.
An equilibrium loss without vertigo was noticed when he changed position. He furthermore suffered from pain in his eyes, photophobia, and conjunctival redness without diplopia. On physical examination, thrombophlebitis ofboth legs and erythema ofthe palms of the hands and the soles of the feet were found (Fig IA). A loud systolic murmur was heard on abdominal auscultation. There were no neurologic aberrations. Routine otorhinolaryngologic examination revealed no abnormalities and a normal tympanic membrane on both sides. Audiometry showed a slightly sloping sensorineural hearing loss of 30 dB for the right ear and 40 dB for the left ear. Similar losses were measured on speech audiometry, while speech discrimination was found to be normal (Fig 2A). There was no recruitment, tone decay was normal, and Bekesy audiometry was of the cochlear type. The glycerol test was negative and
tympanometry was normal. Electronystagmography did not show spontaneous or positional nystagmus. On caloric examination, both labyrinths responded normally and symmetrically. A rotating chair nystagmogram revealed hypofunction. On ophthalmologic examination, interstitial keratitis with injected perilimbal vessels and conjunctivitis was observed (Fig
IB). Routine laboratory findings showed normal values of blood chemistry and hematology except for an erythrocyte sedimentation rate of 74 mmlh. C-reactive protein value was 14.6. There was increased liver function and normal renal function. Thyroid function was normal except for a high thyroglobulin of 1,000 I-lgIL (normal value is
CORNEAL AUTOIMMUNITY IN COGAN'S SYNDROME? REPORT OF TWO CASES MAARTEN H. J. M. MAJOOR, MD UTRECIIT, TIIE NETIIERLANDS
FRANs W. J. ALBERS, MD, PHD
RUTH VAN DER GAAG, PHD
UTREOIT, TIIE NETHERLANDS
AMSTERDAM, TIlE NETHERLANDS
FRITs GMELIG-MEYLING, PHD
EGBERT H. HUIZING, MD, PHD
UTRECIIT, TIlE NETHERLANDS
UTRECIIT, TIIE NETIIERLANDS
Autoimmune reactivity against corneal antigens is described in two patients with Cogan's syndrome, a nonsyphilitic deep interstitial keratitis with vestibuloauditory symptoms. In both cases corneal antibodies were found at the beginning or during an exacerbation of the disease. After administration of high doses of corticosteroids the corneal antibodies diminished. Interstitial keratitis can generally be controlled by local or systemic corticosteroids. The effect of corticosteroid therapy on the audioveslibular symptoms is variable. The possibility of an autoimmune pathogenesis of Cogan's syndrome is discussed. KEY WORDS -
autoimmune disease, Cogan's syndrome, corneal autoimmunity.
INTRODUCTION
ied is still too small to draw significant conclusions from the data. 4, l0
In 1945 the ophthalmologist David Cogan was the first to describe a syndrome of nonsyphilitic deep interstitialkeratitis with vestibuloauditory symptoms. I This disorder is currently known as Cogan's syndrome. More recent reports on this syndrome have indicated involvement of other organ systems and systemic vasculitis.I-'
In Wegener's granulomatosis, polyarteritis nodosa, and rheumatoid arthritis with corneal involvement, a high incidence of circulating antibodies to corneal epithelium has been observed, which suggests an autoimmune cause. I I In this paper two patients with Cogan's syndrome associated with systemic manifestations are presented. During the course of the disease, tests were repeatedly performed to detect the presence ofcirculating antibodies against the cornea. The results support the possibility that autoimmune reactions contribute to the development of Cogan's syndrome.
Although the cause of Cogan's syndrome is still obscure, an immunologic origin has been suggested by several authors. Hughes et a14 frequently found an elevation of the sedimentation rate in the acute stage of the disease. Edstrom and Vahlne 5 described a patient in an acute stage of the syndrome in whom an episode of transient immunologic anergy was accompanied by an increased number ofcirculating T and B lymphocytes and signs of complement consumption. These observations were not confirmed in cases reported later. 4,6,7 Hughes et a1 4 also demonstrated that an inner ear membrane extract could induce lymphocyte migration inhibition in a patient with Cogan's syndrome. Lymphocyte stimulation by eyespecific proteins (5 antigen, outer rod segment, or scleroprotein) was described by Peeters et al.8 Arnold and Gebbers? found antibodies directed against inner ear tissue and corneal epithelium in serum of patients with Cogan's syndrome. There is scattered evidence for human leukocyte antigen allotype associations in Cogan's syndrome, but the number of patients stud-
CASE REPORTS
Case 1. A 21-year-old man developed a mandibular abscess after extraction of a molar. Two days after drainage of the abscess he became very ill with severe headaches, poorly localized discomfort in the neck, lower back pain, and arthralgia, followed by abdominal discomfort 1 week later. He was admitted to the Department of Otorhinolaryngology, University Hospital Utrecht, 4 weeks after his first complaints. Besides the above-described symptoms, he had lost 12 kg in weight and suffered from intermittent fever, anorexia, fatigue, epistaxis, nausea and vomiting, and testicular pain. The patient complained of bilateral hearing loss with tinnitus and fullness in the ears.
From the Departments ofOiorhinolaryngology (Majoor, Albers, Huizing) and Immunology (Gmelig-Meyling), University Hospital Utrecht, and the Department of Ophthalmo-Imrnunology, The Netherlands Ophthalmic Research Institute, Amsterdam (van der Gaag), the Netherlands. REPRINTS - Maarten H. J. M. Majoor, MD, Dept of Otorhinolaryngology, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.
679
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 15, 2015
680
Majoor et al, Corneal Autoimmunity in Cogan's Syndrome?
Fig 1. (Case 1) A) Erythema of palm of hand. B) Injected perilimbal vessels and conjunctivitis of both eyes.
An equilibrium loss without vertigo was noticed when he changed position. He furthermore suffered from pain in his eyes, photophobia, and conjunctival redness without diplopia. On physical examination, thrombophlebitis ofboth legs and erythema ofthe palms of the hands and the soles of the feet were found (Fig IA). A loud systolic murmur was heard on abdominal auscultation. There were no neurologic aberrations. Routine otorhinolaryngologic examination revealed no abnormalities and a normal tympanic membrane on both sides. Audiometry showed a slightly sloping sensorineural hearing loss of 30 dB for the right ear and 40 dB for the left ear. Similar losses were measured on speech audiometry, while speech discrimination was found to be normal (Fig 2A). There was no recruitment, tone decay was normal, and Bekesy audiometry was of the cochlear type. The glycerol test was negative and
tympanometry was normal. Electronystagmography did not show spontaneous or positional nystagmus. On caloric examination, both labyrinths responded normally and symmetrically. A rotating chair nystagmogram revealed hypofunction. On ophthalmologic examination, interstitial keratitis with injected perilimbal vessels and conjunctivitis was observed (Fig
IB). Routine laboratory findings showed normal values of blood chemistry and hematology except for an erythrocyte sedimentation rate of 74 mmlh. C-reactive protein value was 14.6. There was increased liver function and normal renal function. Thyroid function was normal except for a high thyroglobulin of 1,000 I-lgIL (normal value is
