Article Text

Download PDFPDF

Cogan's syndrome with antineutrophil cytoplasmic autoantibody
  1. M Ikeda1,
  2. H Okazaki2,
  3. S Minota2
  1. 1Health Science Centre, Utsunomiya University, Tochigi, Japan
  2. 2Division of Rheumatology and Clinical Immunology, Jichi Medical School, Tochigi, Japan
  1. Correspondence to:
    Dr M Ikeda, Health Science Centre, Utsunomiya University, Utsunomiya City, Tochigi 321–8505, Japan;

Statistics from

Cogan's syndrome is a rare disease characterised by non-syphilitic interstitial keratitis with vestibuloauditory dysfunction, including loss of hearing, tinnitus, and vertigo.1 We report here a case of Cogan's syndrome positive for antineutrophil cytoplasmic antibody (ANCA). This case is interesting in consideration of the pathogenesis of this syndrome.


In May 1999 a 61 year old man was admitted to our hospital with fever and myalgia localised to the lower part of both legs. He had a history of lung tuberculosis at 22 years old, chronic sinusitis at 30, and bilateral otitis media at 53. On admission, laboratory tests showed a white blood cell count of 11.2×109/l and a CRP level of 63 mg/l. Serum levels of creatine kinase, alanine aminotransferase, and aspartate aminotransferase, and a urinary examination were normal. A serological test was positive for perinuclear ANCA (pANCA) and myeloperoxidase ANCA (MPO-ANCA; 105 EU/ml (normal <10 EU/ml)), but negative for syphilis and cytoplasmic ANCA (cANCA). Electromyographic findings were normal. Although the pathological change of vasculitis was not detected in the biopsied muscle, the presence of microscopic polyangiitis was highly suspected based on the high titre of MPO-ANCA. Prednisolone (30 mg/day) was given at once, and after one month the levels of C reactive protein (CRP) and MPO-ANCA decreased to 5 mg/l and 12 EU/ml, respectively, with clinical improvement.

While receiving continuous prednisolone treatment, in August 2000, the patient suddenly developed severe frontotemporal headache and vertigo. The CRP level increased to 43 mg/l. Two weeks later, complete hearing loss of his left ear developed. Immediate administration of betamethasone (10 mg/day) for three days did not improve his hearing.

In January 2001 myalgia and weight loss developed and continued, and the levels of CRP and MPO-ANCA were raised at 68 mg/l and 46 EU/ml, respectively. In February 2001 redness of both eyes due to keratouveitis suddenly occurred, which improved after treatment with corticosteroid eye drops. Cyclophosphamide (50 mg/day) was also given together with betamethasone (1.5 mg/day), and complete clinical and serological remission was obtained (CRP 5 mg/l, MPO-ANCA 10 EU/ml). A diagnosis of Cogan's syndrome was made based upon the clinical constellation of keratouveitis, sensorineural hearing loss, and suspected systemic vasculitis.


Previously, Cheson et al reviewed 53 cases of Cogan's syndrome2; 10/18 vessel or muscle biopsy specimens showed inflammatory vascular changes, of which four were considered to be diagnostic of polyarteritis in large and medium sized arteries. ANCA is widely used as a useful diagnostic marker for small vessel vasculitis, including Wegener's granulomatosis, microscopic polyangiitis, pauci-immune necrotising crescentic glomerulonephritis, and Churg-Strauss syndrome, although this test is occasionally positive in various other conditions. Recently, it has been reported that the combination of immunoassays for anti-MPO and indirect immunofluorescence for pANCA is highly specific for the diagnosis of systemic vasculitis.3 Until now, five cases of Cogan's syndrome associated with ANCA have been reported, including ours,4–7 and two of them also showed ANCA related glomerulonephritis. In our case, pANCA and MPO-ANCA were positive, and audiovestibular abnormalities and keratouveitis were present, but other manifestations of systemic vasculitis were not noted. We speculate, therefore, that all sizes of arteries may be affected in Cogan's syndrome.

The cause of Cogan's syndrome is still unknown. Interestingly, upper respiratory tract infections have been reported to precede the onset of Cogan's syndrome in 40% of cases,8 suggesting that one of the triggering factors may be upper respiratory infection. Our patient also had a history of upper respiratory infections. The research group in the National Institute of Health found that patients with Cogan's syndrome had significantly high titres of antibodies to Chlamydia trachomatis.9 Ljungstrom et al reported a patient with Cogan's syndrome who had a fourfold increase in serum IgG antibody titre to Chlamydia pneumoniae.10 Furthermore, it has been reported that Chlamydia infections are related to vascular injury, such as arteriosclerosis and vasculitis. A relationship between previous Chlamydia infection and coronary artery disease is supported by seroepidemiological studies. It is suggested that the bacteria adhere to endothelial cells, because Chlamydia pneumoniae is detected in atherosclerotic plaques by both polymerase chain reaction and culture. In our case, the IgG titre to Chlamydia pneumoniae was negative, but the IgA titre was positive (2.23, cut off point 0.9). We suggest that the IgG titre might have been negative in our case because the titre was measured several months after treatment with corticosteroid and cyclophosphamide.

This case suggests a possibility that antinuclear antibodies are related to the pathogenesis of Cogan's syndrome, although further studies are required to confirm this hypothesis.


View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.