Haruyo Iwadate

Clinical features of liver dysfunction in collagen diseases

Aim:  Liver dysfunction is not rare in patients with collagen disease. We sought to elucidate the clinical features of liver dysfunction in the presence of collagen disease.

Plasma osteopontin is correlated with bone resorption markers in rheumatoid arthritis patients

To assess whether any form of osteopontin (OPN) is correlated with bone resorption markers or treatment effects in rheumatoid arthritis (RA).

Thrombin-cleaved Osteopontin Is Increased in Urine of Patients with Rheumatoid Arthritis

Objective. To measure concentrations of the thrombin-cleaved isoform of osteopontin (OPN) in urine and plasma of patients with rheumatoid arthritis (RA), and to assess whether levels of thrombin-cleaved OPN are associated with measures of RA. Methods. Subjects comprised 70 patients with RA, 20 patients with osteoarthritis (OA), and 46 healthy controls. RA disease activity was evaluated by tender joint count, swollen joint count, patient’s global assessment of disease activity, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF), as well as 28-joint count Disease Activity Score (DAS28). OPN levels in plasma and urine were measured by ELISA. Results. Median levels of thrombin-cleaved OPN in urine (U-half) were significantly higher in RA patients (143.5 pmol/mmol Cr) than in healthy controls (67.9 pmol/mmol Cr) or OA patients (69.8 pmol/mmol Cr). Thrombin-cleaved OPN was not detected in plasma. U-half levels correlated significantly with levels of CRP (r = 0.26, p = 0.03), ESR (r = 0.26, p = 0.03), and RF (r = 0.28, p = 0.03). Median U-half levels were significantly higher in patients with stage III (249.9 pmol/mmol Cr) and IV (251.6 pmol/mmol Cr) disease than in patients with stage I (98.6 pmol/mmol Cr) disease. Conclusion. Our results suggest that urine levels of the thrombin-cleaved isoform of OPN may reflect the severity of active inflammatory arthritis in patients with RA.

Ultrasonographic evaluation of synovial effusion and synovial proliferation pattern in the knee joints of patients with rheumatoid arthritis

Abstract In the present study, 49 knee joints of 26 patients with rheumatoid arthritis and 17 knee joints of 17 healthy subjects were ultrasonographically examined. Lateral, superior, and medial aspects of the patella were scanned using an ultrasonograph with a 7.5-MHz annular array transducer to evaluate the thickness of synovial effusion and the synovial proliferation pattern. The overall mean thickness of synovial effusion (mean of all three sites) in the knee joints was 4.9 ± 3.4 mm for rheumatoid arthritis patients and 1.4 ± 0.5 mm for healthy subjects. In rheumatoid arthritis patients, the mean thickness of synovial effusion at the superior aspect of the patella (6.5 ± 4.1 mm) was significantly greater than that at the lateral aspect (4.5 ± 4.8 mm) (P < 0.05) and the medial aspect (4.0 ± 3.1 mm) (P < 0.01). Patients with the villonodular pattern of synovial proliferation had a shorter duration of disease than those with uniform thickening or an overlapping pattern.

Biliary hamartomas (von Meyenburg complex) complicated with microscopic polyangiitis

Vasculitis syndrome accompanied by multiple liver lesions is uncommon. Biliary hamartomas, also called von Meyenburg complexes (VMCs), are small benign liver malformations that pathologically contain cystic dilated bile ducts surrounded by abundant fibrous stroma [1]. VMCs are considered to be congenital bile duct malformations. To date, there have been no reports of any cases of VMC complicated with systemic vasculitis syndrome. Here, we report an extremely rare case of VMC complicated with microscopic polyangiitis (MPA). A 59-year-old man was referred to our hospital with general fatigue, appetite loss, high fever, and numbness of the distal extremities in August 2010. He had been hospitalized in another hospital and had several examinations. Blood tests showed a high white blood cell count (WBC), elevated C-reactive protein (CRP) levels, and elevation of hepatobiliary enzymes. Abdominal CT showed multiple small hypodense lesions scattered in both lobes of the liver, which were suspected to be multiple liver metastases or microabscesses. Although two antibiotics (meropenem and clindamycin) were administered, all symptoms remained. After the detection of high myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) levels (185 EU) in his serum, he was transferred to our hospital for further treatment. His height was 168 cm and his body weight was 65 kg. On examination his body temperature was 37.7 C and his blood pressure was 134/89 mmHg. Physical examination revealed peripheral edema on both lower legs, and neurological examination revealed polyneuropathy on the distal extremities. A blood test showed elevated hepatobiliary enzymes and high levels of WBC and CRP. Laboratory values were as follows: WBC 33000/lL (normal 3800–9800/ lL); red blood cells (RBC) 375 9 10/lL (normal 440–540 9 10/lL); hemoglobin 11.2 g/dL (normal 14–17 g/dL); platelet count 42.6 9 10/lL (normal 15.5–36.5 9 10/lL); CRP 17.91 mg/dL (normal \0.2 mg/dL); asparate aminotransferase (AST) 119 IU/L (normal 10–35 IU/L); alanine aminotransferase (ALT) 73 IU/L (12–33 IU/L); alkaline phosphatase (ALP) 1215 IU/L (115–359 IU/L); c-glutamyl transpeptidase (c-GTP) 148 IU/L (normal 10–47 IU/L); total bilirubin 2.6 mg/dL (normal \1.1 mg/dL). Negative results were obtained for HBs antigen and HCV antibody. His blood urea nitrogen was slightly elevated (23 mg/dL, normal 9–21 mg/dL), and his serum creatinine level was within normal limits (0.57 mg/dL, normal 0.6–1.2 mg/dL). Urine test was positive for protein (?2) and blood (?3). The urine sedimentation test was positive for RBC casts (0–1/10), WBC casts (0–1/10), and granulocyte casts (0–1/10) per high-power field. Anti-nuclear antibody was negative (1:80, normal \1:160), but MPO-ANCA levels were elevated to 402 EU (normal \10 EU). Chest CT showed bilateral ground-glass opacities in both lower lungs. Abdominal enhanced CT showed multiple small hypodense lesions scattered in both lobes of the liver (Fig. 1). Abdominal ultrasonography (AUS) showed multiple small high-echoic lesions in the liver. MRCP demonstrated multiple small hyperintense nodules that were scattered throughout the liver but did not communicate with the biliary tree (Fig. 2). His clinical symptoms—lung shadows and high MPO-ANCA levels—led S. Sato (&) H. Watanabe T. Asano R. Saito H. Iwadate H. Kobayashi H. Ohira Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan e-mail: shuzo@fmu.ac.jp

A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corticosteroid and low-dose methotrexate.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid‐induced diabetes mellitus who was taking corticosteroid and low‐dose methotrexate.

Ultrasonographic evaluation of knee joint synovitis in two patients with palindromic rheumatism.

Abstract The aim was to evaluate synovial proliferation ultrasonographically in order to identify the period of conversion from palindromic rheumatism to the early-stage of rheumatoid arthritis. Two patients, a 35-year-old man and a 44-year-old man, had been suffering from episodic attacks and remission of oligoarthralgia for 15 years and 6 years, respectively. Both patients were negative for rheumatoid factors, and exhibited slightly elevated levels of C-reactive protein and erythrocyte sedimentation rate at the times of the attacks. Radiograms of the affected joints showed no erosion of the bones in either patient. Ultrasonographic examination revealed both synovial effusion and synovial proliferation in the 35-year-old patient, suggesting conversion from palindromic rheumatism to rheumatoid arthritis, whereas only synovial effusion was found in the 44-year-old patient, suggesting the persistence of palindromic rheumatism. Ultrasonographic evaluations of synovial proliferation in the knee joints provide data that can be used to identify the period of conversion from palindromic rheumatism to the early-stage of rheumatoid arthritis.

Anti‐carbonic anhydrase III autoantibodies in vasculitis syndrome

To identify autoantibodies useful in the diagnosis of primary vasculitides.

Membranous nephropathy associated with primary biliary cirrhosis and acute meningitis.

A 40-year-old man with acute meningitis, nephrotic syndrome, elevated antinuclear antibody (2560×), and liver dysfunction was referred to our hospital. He was antimitochondrial antibody positive, and renal and liver biopsy findings revealed membranous nephropathy (MN) and primary biliary cirrhosis (PBC), respectively. This extremely rare MN accompanied by PBC was detected while the patient was undergoing treatment for acute meningitis.

Effect of Sepimostat Mesilate on the Development of Glomerulonephritis in NZB/W F1 Mice

Objective: To determine whether sepimostat mesilate inhibits activation of the complement pathways, and to evaluate the effectiveness of sepimostat mesilate on the development of glomerulonephritis in NZB/W F1 mice. Methods: We used the Wielisa complement functional kit to assess the inhibitory effect of sepimostat mesilate on activation of the complement pathways. Groups of 10 NZB/NZW mice (age 18-22 weeks) were given sepimostat mesilate (200 μg/dose) or glucose (control) five times a week for 5 weeks after onset of proteinuria. Results: Sepimostat mesilate dose-dependently inhibited the activity of all complement pathways. Administration of sepimostat mesilate after disease onset lowered the levels of blood urea nitrogen (243.2 ± 63.1 versus 120.9 ± 22.1 μg/dl; p<0.0001), C4d (0.244 ± 0.083 versus 0.153 ± 0.059 ng/dl; p=0.011), and delayed the development of proteinuria (0.822 ± 0.116 versus 0.470 ± 0.093 mg/mouse/day; p=0.046) at the end of treatment (22 weeks of age). After discontinuation of administration, blood urea nitrogen, C4d level, and proteinuria rapidly became elevated with no difference between the groups. Eventually, mortality was similar between treated and untreated mice. Conclusions: Sepimostat mesilate could be a therapeutic option for lupus nephritis.