Takayasu's arteritis is an autoimmune disease that affects mainly young women (1). Primary biliary cirrhosis (PBC), also an autoimmune disease, is seen mainly in middle-aged women (2). Complication of Takayasu's arteritis by PBC has rarely been reported (3–5). We report a woman with Takayasu's arteritis who developed PBC at a time when the disease activity of Takayasu's arteritis was minimal. This patient had been taking prednisolone (PSL) for 18 years, but it did not prevent the development of PBC.

In March 1977, when the patient was 17 years old, she developed fever, cough, general arthralgia, and rash. She did not have any family history of autoimmune diseases. At that time, she was treated with corticosteroid hormone (dosage unknown) under a diagnosis of rheumatic fever. In May 1977, she was hospitalized due to fever and general fatigue and was treated with antibiotics and prednisolone (PSL) at 30 mg/day. She was discharged in June 1977. PSL was tapered to 10 mg/day but was increased again to 30 mg/day in August 1978 due to fever. On December 19, 1980, she was admitted to our clinic, Department of Medicine (II), due to fever and general fatigue. At the time of that admission, she was taking PSL at 10 mg/day. Vascular bruit was heard at her neck, and her right radial artery pulse was weak. Angiography revealed stenosis of the right subclavian artery, and she was diagnosed as having Takayasu's arteritis. PSL was increased to 40 mg/day, and the fever disappeared. She was discharged on May 21, 1981, and thereafter observed regularly. Follow-up digital subtraction angiography on July 4, 1986, showed stenosis and wall irregularity in the bilateral subclavian and common carotid arteries (Fig. 1A). Mild stenosis was observed in the bilateral renal arteries, and prominent stenosis and wall irregularity were seen in the superior mesenteric arteries (Fig. 1B). She remained symptom free with no signs of inflammation until she developed itching in August 1998. Laboratory tests at that time showed elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (γGTP), and total cholesterol (TC). She tested positive for anti-mitochondria antibody (AMA) and for both immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-pyruvate dehydrogenase (PDH). AMA was measured by immunofluorescence (Fluoro AID-1 test, MBL, Tokyo) and anti-PDH (M2) was measured by ELISA assay using recombinant M2 antigen (MESACUP-2 test, MBL, Tokyo). These data suggested that she had developed PBC.

The patient was admitted to our Department of Medicine (III) on June 11, 1999. On physical examination, the patient's blood pressure was 174/64 mm/Hg in the left arm and 150/62 mm/Hg in the right arm. Vascular bruit was heard bilaterally in the neck and in the left subclavian area, epigastrium, and right femoral area. Laboratory data showed her white blood cell count at 9,540/mm³, hemoglobin at 13.4 g/dl, platelet count at 38.4×10⁴/mm³, total protein at 7.9 g/dl, total bilirubin (T Bil) at 1.9 mg/dl, direct bilirubin (D Bil) at 0.9 mg/dl, AST at 129 IU/l, ALT at 183 IU/l, lactate dehydrogenase (LDH) at 575 IU/l, ALP at 1,491 IU/l, γGTP at 1,425 IU/l, leucine amino peptidase at 574 IU/l, chorine esterase (ChE) at 229 IU/l, blood urea nitrogen (BUN) at 13 mg/dl, creatinine (Cr) at 0.7 mg/dl, TC at 421 mg/dl, triglyceride (TG) at 325 mg/dl, NH₃ at 85 μg/dl, cholic acid at 12.0 nmol/ml, serum copper at 115 μg/dl, IgG at 1,325 mg/dl, IgA at 420 mg/dl, IgM at 474 mg/dl, rheumatoid factor at 11.7 IU/ml, C-reactive protein at 0.3 mg/dl, erythrocyte sedimentation rate at 73 mm/h, thrombotest over 150%, and hepaplastin test at 153%. Hepatitis B surface antigen and anti-hepatitis C antibody were negative. Anti-nuclear antibody was negative, anti-smooth muscle antibody was negative, AMA was positive at ×640 serum dilution, and both IgG and IgM anti-PDH antibodies were positive. Analysis of human leukocyte antigens showed A2, A31, B62, B51, DR1, DR2, and DQ1 types.

Ophthalmologic examination revealed no sign of Sjögren's syndrome, and her optic fundi were normal. Laparoscopy and liver biopsy were performed on June 18. Histological diagnosis was chronic non-suppurative destructive cholangitis involving epitheloid granuloma formation with plasma cell infiltration (Fig. 2). These findings were compatible with PBC at Scheuer's stage I (6). Ursodeoxycholic acid (UDCA) was started on June 21 at a dose of 300 mg/day to avoid gastrointestinal symptoms and increased to 600 mg/day on July 13. Serum ALT, ALP, T. Bil was 109 IU/l, 855 IU/l, 0.9 mg/dl at one year after the start of UDCA respectively, and 127 IU/l, 733 IU/l, 1.7 mg/dl at three years. The level of itching was not altered much by UDCA. Follow-up liver biopsy has not been performed.

Many autoimmune diseases such as Sjögren's syndrome (7, 8), systemic sclerosis (7, 9), rheumatoid arthritis (9), polymyositis (5), systemic lupus erythematosus (8, 10, 11), chronic thyroiditis (5), and Graves disease (12) are reported as complications of PBC. Only a few reports from Japan have documented the complication of Takayasu's arteritis by PBC (3–5). The present patient developed Takayasu's arteritis first and was treated with high-dose PSL followed by a maintenance dosage regimen (10 mg/day). She developed PBC 18 years later. When she developed PBC, she had no inflammatory signs, and so Takayasu's arteritis was thought to be burnt out. According to our experience, an amount of PSL adequate to suppress Takayasu's arteritis does not necessarily prevent the development of PBC.

In the treatment of PBC, corticosteroids might ameliorate liver dysfunction to some extent though such treatment can induce various side effects including osteoporosis (13). Therefore, PSL has not been used widely in PBC despite its being an autoimmune disease (2). When life threatening symptoms such as massive pericardial effusions due to SLE develop, however, physicians must prescribe a corticosteroid (8, 10, 11). In previous reports, other steroid-requiring autoimmune diseases were described as having developed after or simultaneously with PBC (8, 11). Harada et al (5) reported a case of Takayasu's arteritis that developed 29 years before the complication of PBC, but their patient was not given steroids for arteritis. The history of our case is interesting because the patient developed PBC during the maintenance PSL therapy for Takayasu's arteritis.

HLA-B52, B39.2 and DR2 are reported to be related to Takayasu's Arteritis (14, 15), and HLA-DR2 (16), DR-8 (17) and DRB1＊08, DRB1＊0402 (18) are reported to be related to PBC. Among the previously reported cases with coexistence of both diseases, one patient showed none of these HLA types (5), and another had HLA-B52 and DR2 but not DR-8 (3). The present patient had DR-2 but not B52 or DR-8. Further reports involving HLA analysis are needed to clarify which HLAs are linked to Takayasu's arteritis complicated by PBC.