Nephrologists are accustomed to managing patients with systemic vasculitis. However, some of the rarer vasculitides may be primarily non-renal in their target organ damage and present with a long prodrome. We would like to briefly discuss one such syndrome that may not be well known to the general nephrological community.
Our patient presented aged 32 when, with no risk factors for coronary atheroma, he sustained a myocardial infarction. Aged 40, he presented with fever, bilateral uveitis and renal impairment (serum creatinine 420 mmol/l). Inflammatory markers and autoimmune profile including ANA, ANCA and anti-GBM antibody were normal. Renal biopsy revealed a diffuse proliferative glomerulonephritis with mesangial hypercellularity, irregular granular deposits of C3 in both the mesangium and capillary loops but no features of vasculitis or crescents. He was treated with a course of antibiotics that coincided with the resolution of his symptoms. His serum creatinine improved to 180 mmol/l and remained stable. Over the next 12 years he developed left hemiparesis; bilateral sensorineural deafness needing a cochlear implant; a second myocardial infarction with ventricular arrhythmia needing coronary stenting and an implantable cardioverter defibrillator.
Aged 52, he presented with bilateral pleural effusion, a widespread scaly erythematous rash and generalized lymphadenopathy. CRP was 64 mg/l (N<10) and the serum creatinine 270 mmol/l. Pleural fluid was haemorrhagic showing only inflammatory cells. Echocardiography revealed severe left ventricular dysfunction. Skin and lymph node biopsy revealed leucocytoclastic vasculitis and dermatopathic lymphadenopathy, respectively.
This clinical presentation was consistent with a diagnosis of Cogan's syndrome (CS). He was commenced on intravenous methyl prednisolone (0.5 g for 3 days), followed by oral prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). Azathioprine was substituted for the cyclophosphamide at 3 months. There was significant clinical improvement returning to his baseline physical function at 6 months although still restricted by his cardiac disease. His serum creatinine had stabilized at 220 mmol/l after 6 months of treatment.
CS is a rare multisystem disease of unknown cause predominantly affecting young adults. Recent studies suggest an autoimmune process directed against the Cogan's peptide, which is homologous to autoantigens such as Connexin 26 and DEP-1/CD148 on the sensory epithelia of inner ear and endothelial cells, as well as other antigens such as Ssa/Ro, laminin, ladinin, kinesin and calcineurin [1,2].
CS comprises the association of inflammatory eye disease and audiovestibular dysfunction. However, firm diagnostic criteria have not been established. The audiovestibular disturbance presents with Meniere's-like illness and progressive sensorineural deafness which is irreversible in 5085% of the patients. The eye signs include interstitial keratitis, scleritis, episcleritis and uveitis [35].
Systemic manifestations are seen in 72% of cases and are usually non-specific but may include lymphadenopathy, hepatosplenomegaly, aortitis, coronary arteritis, pleuritis and pulmonary nodules [3,5]. A systemic vasculitis may occur in
10% of cases usually affecting medium-sized vessels although any sized vessel may be affected [6].
Renal disease is poorly described in the literature. In a review of 78 cases, 14 had abnormal urinalysis, and three had renal impairment. Histopathological findings were available in seven of these patients and were abnormal in five patients. The abnormal findings included glomerulonephritis, renal vasculitis, gross cortical scarring and renal infarction [5].
Corticosteroids are used topically for ocular inflammation and systemically for ear manifestations. Treatment of the cardiovascular manifestations is similar to that of systemic necrotizing vasculitis [7]. Early diagnosis and treatment can significantly reduce morbidity and mortality. Therefore we feel that nephrologists should consider this rare condition in the differential diagnosis of patients presenting with ocularauditory and renal symptoms.
Conflict of interest statement. There is no conflict of interest to be declared by any of the authors.
1 Oxford Kidney Unit Churchill Hospital Oxford OX3 7LJ2 Monklands Hospital Airdrie ML6 0JS
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