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Takayasu’s arteritis and primary biliary cirrhosis (PBC) are two unrelated autoimmune diseases without a so far reported coincidence, probably because they occur at different ages.1,2 As a systemic vasculitis, Takayasu’s arteritis affects predominantly the aorta and its branches in female patients before the age of 40 years. The clinical manifestations are variable and severe anatomical lesions can lead to life threatening ischaemia. We report an unusual case, where, after the initial diagnosis of a coincident severe Takayasu’s arteritis with PBC, subsequent immunosuppressive treatment led to a striking clinical improvement of vasculitic symptoms in an elderly woman.
A 70 year old woman was referred to our hospital with generalised weakness and disseminated painful cutaneous, erythematous nodules on the extensor sites of both lower legs. A rheumatic disorder had been suspected since 1960 because of remittent nausea, attacks of fulminant headaches, and an erythema nodosum. Clinical examination showed a diminished bilateral radial and an absent carotid pulse as well as hypotensive blood pressure on both arms (85/60 and 90/60 mm Hg). No focal neurological and no pathological musculoskeletal findings were present.
In laboratory analysis, a raised erythrocyte sedimentation rate of 52 mm within the first hour as well as a C reactive protein of 14 mg/l (normal <8) were detected. Liver enzymes and measures of cholestasis were moderately raised. Antinuclear antibodies were positive at a titre of 1/1280, with a dense granular nucleoplasmic pattern and cytoplasmic staining suggesting antimitochondrial antibodies (AMA). AMA were confirmed in immunofluorescence on rat kidney cells at a positive titre of 1/32, and in AMA-M2 enzyme linked immunosorbent assay (ELISA; >500 U/ml, normal <10).
In Doppler sonography, occlusion of both common carotid arteries (CCA) and of both internal carotid arteries (ICA) as well as of the left subclavian artery was detected. The filiforme external carotid arteries showed an antegrade flow on the right and a retrograde flow on the left side. Along the right subclavian artery, examination showed a post-stenotic signal. Perfusion of the brain was ensured by two hypertrophic vertebral arteries with a suspected stenosis on the right side. These severe anatomical changes were confirmed by digital subtraction angiography (fig 1A). Ultrasound examination of the abdomen showed no signs of involvement of abdominal vessels, but a chronic alteration of liver tissue.
Despite the age of our patient, Takayasu’s arteritis was diagnosed with the assumption of a disease duration of four decades. Moreover, the remittent attacks of headaches and nausea, the skin involvement, and raised inflammatory parameters were consistent with an active vasculitis. A coincident PBC was supported by high positive AMA, raised measures of cholestasis, and morphological liver changes.3 Therefore, a therapeutic approach with corticosteroids (initially 50 mg a day) in combination with a cyclophosphamide bolus (700 mg) was justified. Immediately, a clear improvement of the overall condition and the skin lesions was accompanied by a normalisation of the inflammatory parameters. However, to our surprise, the headaches and the nausea improved also. Two months after the start of treatment, a minimal perfusion of the right CCA and right ICA was noted in magnetic resonance angiography. The treatment was continued with methotrexate in combination with low dose steroids. Additionally, low dose aspirin, a well tolerated calcium antagonist, and ursodesoxycholic acid completed the drug treatment. One year later, a follow up colour coded Doppler sonography showed reduced antegrade flow in the right CCA (20 cm/s) (fig 1B) as well as in the right ICA (40 cm/s), and retrograde flow in the right external carotid artery (70 cm/s). Over a follow up period of 3 years, the clinical, vascular, and laboratory findings remained stable.
The supra-aortic vessel occlusions in this case were consistent with a giant cell vasculitis. After consideration of the patient’s history, Takayasu’s arteritis was diagnosed, but it was not possible to exclude Horton’s disease, considering the clinical manifestations. The improvement in headaches, especially, could argue for giant cell arteritis, but conversely, the anatomical changes were more typical of Takayasu’s arteritis.
Regression of vessel occlusions remains rare in Takayasu’s arteritis as well as in giant cell arteritis. On the other hand, it is not always possible to exclude a persistent active giant cell vasculitis of the aortic wall or even of its branches using conventional techniques. The presented case reflects this situation by an unexpected improvement of cerebral perfusion and eventually of the neurological symptoms after immunosuppressive treatment. However, despite the encouraging outcome in our case, adequate treatment in Takayasu’s vasculitis remains a problem. Remarkably, immunosuppressive treatment can be effective even in longlasting and occlusive situations of giant cell vasculitis. A coincidence of different systemic forms of vasculitis with PBC has been reported previously and, therefore, in suspicious cases an autoimmune liver disease should be excluded.4–7
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