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

AIM: To assess whether any form of osteopontin (OPN) is correlated with bone resorption markers or treatment effects in rheumatoid arthritis (RA). METHOD: Subjects comprised 119 patients with RA. RA disease activity was evaluated by Disease Activity Score (DAS) 28, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), rheumatoid factor (RF) and matrix metalloproteinase (MMP)-3. OPN levels in plasma and urine were measured by enzyme-linked immunosorbent assay (ELISA). Levels of tartrate-resistant acid phosphatase (TRACP) 5b in serum and C-terminal telopeptide of type 1 collagen (CTX)-1 in urine were measured by ELISA. Patients were divided into responder and nonresponder groups, and OPN levels were compared at baseline and after treatment. RESULTS: Levels of full-length OPN in plasma (P-fOPN) were significantly correlated with levels of TRACP 5b (r = 0.44, P < 0.001), urine CTX-1 (r = 0.26, P = 0.004) and MMP-3 (r = 0.34, P < 0.001). Levels of TRACP 5b were significantly correlated with age (r = 0.25, P = 0.007), but levels of P-fOPN were not. After treatment, plasma OPN levels were significantly decreased in responders (P = 0.003). Levels of full-length or thrombin-cleaved forms of OPN in urine were not correlated with TRACP 5b or CTX-1. CONCLUSION: Our results suggest that plasma OPN may reflect inflammatory bone destruction in RA patients.

Anti-carbonic anhydrase III autoantibodies in vasculitis syndrome.

AIM: To identify autoantibodies useful in the diagnosis of primary vasculitides. METHODS: The presence of antibodies against proteins in the lysate of mouse blood vessels was examined by two-dimensional electrophoresis followed by Western blotting for the pooled serum sample from patients with various forms of vasculitis: polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), Wegener's granulomatosis (WG) and Takayasu's arteritis (TA). Autoantigenicity in patients with vasculitides was examined by Western blotting and enzyme-linked immunosorbent assay (ELISA). Clinicopathological correlations between the positivity of the autoantibodies and clinical status of patients with the vasculitis were examined. RESULTS: The autoantigen detected in the lysate of pooled sera from patients with vasculitides was identified by mass spectrometry as carbonic anhydrase III (CAIII). ELISA showed significantly higher prevalence of anti-CAIII antibodies in MPA patients (MPA, 11/23 [47.8%]; healthy controls, 2/32 [6.3%]; P < 0.001). Further, anti-CAIII antibody-positive MPA patients had higher vasculitis activity scores compared to anti-CAIII antibody-negative patients, and a weak and not significant negative correlation was observed between anti-CAIII antibody levels and myeloperoxidase - anti-nuclear cytoplasmic antibody (MPO-ANCA) levels. No significant differences were found in anti-CAIII autoantibody levels between MPA and the other primary vasculitides. CONCLUSION: We found significantly high prevalence of anti-CAIII antibody levels in sera from MPA patients. Although the number of samples available in this study is small and anti-CAIII autoantibodies display weak specificity for MPA, anti-CAIII antibodies may be useful for diagnosing MPA in patients who have no ANCA, as well as for assessing disease activity.

Liver dysfunction in patients with systemic lupus erythematosus.

OBJECTIVE: We aimed to define the clinical features of liver dysfunction in patients with systemic lupus erythematosus (SLE). METHODS: The frequency and causes of liver dysfunction were examined in 206 patients with SLE. RESULTS: Liver dysfunction was evident in 123 (59.7%) of the 206 patients. Liver dysfunction in patients with SLE can be drug-induced (30.9%) or caused by SLE itself (28.5%), fatty liver (17.9%), autoimmune hepatitis (AIH) (4.9%), primary biliary cirrhosis (2.4%), cholangitis (1.6%), alcohol (1.6%) or viral hepatitis (0.8%), and it tends to be mild except when caused by AIH. Values for aminotransferase were significantly increased when AIH was the cause, whereas alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GTP) were significantly increased when AIH or drugs were the cause. The liver was already dysfunctional at the time of SLE onset in 56 (45.5%) of 123 patients with liver dysfunction. Neurological involvement was more common among patients with than without liver dysfunction, whereas SLE activity and prognosis did not significantly differ between the two groups. CONCLUSION: Liver dysfunction in the presence of SLE can be caused by many factors, but when extant at the time of SLE onset, either SLE itself or drugs can be the cause. Autoimmune hepatitis should be considered when liver dysfunction is relatively severe.

Serum L-ficolin levels in patients with systemic lupus erythematosus.

OBJECTIVE: L-ficolin plays an important role in innate immunity and is involved in apoptosis. The objective of this study was to investigate the relationship between serum L-ficolin levels and clinical manifestations in patients with systemic lupus erythematosus (SLE). METHODS: Serum L-ficolin levels were determined by enzyme-linked immunosorbent assay in 66 SLE patients and 50 healthy controls. RESULTS: Median serum L-ficolin levels were 5.0 and 8.7 µg/ml in SLE patients and controls, respectively (p = 0.0001). There were no significant differences in serum L-ficolin levels between the active disease group [SLE Disease Activity Index (SLEDAI) >6] and the inactive disease group (SLEDAI <5). Decreased serum L-ficolin levels were associated with thrombocytopenia (median of with vs. without thrombocytopenia 3.4 vs. 5.3 µg/ml, p = 0.008). There were no correlations between serum L-ficolin levels and SLEDAI, serum C3, or serum C4 levels. CONCLUSION: The association between L-ficolin and thrombocytopenia suggests a pathogenic role for L-ficolin in thrombocytopenia in SLE.

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.

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. METHODS: We analyzed the frequency and causes of liver dysfunction in 607 patients (rheumatoid arthritis [RA], n = 220; systemic lupus erythematosus [SLE], n = 164; systemic sclerosis [SSc], n = 47; Sjögren's syndrome [SjS], n = 44; Behçet's disease, n = 43; polymyositis/dermatomyositis [PM/DM], n = 27; vasculitis syndrome, n = 25; mixed connective tissue disease [MCTD], n = 21; and adult-onset Still's disease [AOSD], n = 16). RESULTS: Liver dysfunction was observed in 238 (39.2%) of 607 patients showing collagen disease. Patients with AOSD (81.3%), PM/DM (51.9%) and vasculitis syndrome (48.0%) frequently displayed liver dysfunction. Liver dysfunction in collagen diseases results from many causes; drug-induced liver injury (26.1%), fatty liver (7.6%), viral hepatitis (1.3%), autoimmune hepatitis (4.2%), primary biliary cirrhosis (15.9%) and the collagen disease itself (15.5%). Conversely, primary biliary cirrhosis was a leading cause in SSc (76.1%) and SjS (70.0%). Liver dysfunction in collagen disease tended to be mild. In addition, alanine aminotransferase levels correlated positively with ferritin levels in AOSD (R = 0.708, P < 0.05). Moreover, alkaline phosphatase levels correlated positively with C reactive protein levels in vasculitis syndrome (R = 0.833, P < 0.05). CONCLUSION: Liver dysfunction in the presence of collagen disease has various causes, and dysfunction associated with collagen disease reflects the activity of the collagen disease itself.

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.

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.

Therapy-related myelodysplastic syndrome following cyclophosphamide pulse and/or methotrexate therapy in a patient with systemic lupus erythematosus.

A 27-year-old woman exhibited progressive pancytopenia during cyclophosphamide pulse therapy for lupus nephritis and low-dose methotrexate therapy for severe arthralgia. Bone marrow aspiration revealed highly abnormal cell morphology, indicating therapy-related myelodysplastic syndrome. Pancytopenia and bone marrow cell morphology improved 3 months after discontinuation of cyclophosphamide. It is necessary to promptly examine bone marrow cell morphology and chromosomal aberration in cases with connective tissue diseases complicated by sudden cytopenia during immunosuppressive therapy with chemotherapeutic agents.

Doppler sonographic analysis of synovial vascularization in a patient with rheumatoid arthritis treated with leukocytapheresis.

Synovial vascularization in metacarpophalangeal joints of a patient with rheumatoid arthritis treated with leukocytapheresis (LCAP) was evaluated by Doppler sonography. After the treatment with LCAP, evaluation with American College of Rheumatology core set showed improvement, and the levels of C-reactive protein and serum amyloid A protein decreased. Power Doppler sonography demonstrated a reduction of color flow signals of the joints, and spectral Doppler sonography demonstrated an increase in vascular resistant, indicating a reduction of vessel's permeability. This is the first report evaluating a synovial vascularization and blood flow of the joints by Doppler sonography before and after LCAP therapy. Doppler sonography might be one of the useful methods for evaluating the therapeutic response of LCAP.

Endosonographic diagnosis and follow-up of phlegmonous gastritis.

We report a case of phlegmonous gastritis in a 36-year-old man presenting with anorexia, epigastralgia, and high fever. Endoscopy showed an edematous lesion suggesting a submucosal lesion. Endosonography revealed thickening of the gastric wall, mainly involving the submucosa, with a few anechoic areas. The separation between the submucosa and the muscularis propria was unclear. The patient was treated with antibiotics and endoscopic mucosal resection. Culture of the aspirated pus from the lesion revealed Streptococcus pyogenes. Follow-up endosonography performed 1 week later showed significant improvement.

A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy.

We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.

A case of primary biliary cirrhosis complicated by Behçet's disease and palmoplantar pustulosis.

A 46-year-old woman was diagnosed with palmoplantar pustulosis (PPP) at the Department of Dermatology, Fukushima Medical University Hospital in 2000, and was treated with ointment. However, because liver dysfunction developed in 2003, she was referred to our department, where primary biliary cirrhosis (PBC) was also diagnosed on the basis of clinical findings. One year later, at the age of 49, she developed manifestations of Behçet's disease (BD), including erythema nodosum in the lower extremities. Because she had a history of uveitis, recurrent oral ulceration was present, and the HLA typing was positive for B51, BD was additionally diagnosed. Liver function normalized within three months of the start of treatment with ursodesoxycholic acid (UDCA). This is the first case of PBC associated with BD and PPP.

Usefulness of complement split product, Bb, as a clinical marker for disease activity of lupus nephritis.

To evaluate the usefulness of Bb, a split product of complement factor B, as a clinical marker for disease activity of lupus nephritis, we measured the Bb concentration of sera from 42 patients with lupus nephritis. Serum Bb levels were significantly higher in patients with active nephritis (active nephritis group, n= 30) than in patients with nephritis in remission (remission group, n=12) (14.3+/-8.3 versus 7.4+/-5.9 microg/ml; p = 0.012). In contrast, there was no significant difference in serum C3 levels between active nephritis group and remission group (42.5+/-20.9 versus 44.7+/-15.9 mg/dl ; p = 0.77). In the comparison of Bb levels between active nephritis group and remission group, the sensitivity was 66.6%, specificity was 83.3%, and the positive and negative likelihood ratios were 3.95% and 0.41%, respectively. The present results suggest that serum Bb level is a useful clinical marker for disease activity in lupus nephritis.

Anti-ribosomal P antibodies are associated with nephritis, vascular thrombosis and lymphocytopenia in patients with systemic lupus erythematosus.

In the present study, anti-ribosomal P antibody in sera of patients with systemic lupus erythematosus was assayed using an enzyme-linked immunosorbent assay, and its association with clinical symptoms of the patients was analyzed. The presence of anti-ribosomal P antibody was associated with increased frequency of lupus nephritis in the presence of anti-DNA antibody, and was associated with increased frequency of vascular thrombosis in the presence of anti-beta2 glycoprotein I antibody and/or lupus anticoagulant. The level of anti-ribosomal P antibody correlated inversely with the peripheral lymphocyte counts.

HLA-B52-positive vasculo-Behçet disease: usefulness of magnetic resonance angiography, ultrasound study, and computed tomographic angiography for the early evaluation of multiarterial lesions.

We report a case of HLA-B52-positive Behçet disease accompanied by multiarterial lesions. A 24-year-old woman was suffering from sporadic high fever and recurrent oral and genital ulcers, and laboratory data revealed severe inflammation. A diagnosis of Behçet disease was made. Magnetic resonance angiography, ultrasound study, and computed tomographic angiography demonstrated multiarterial lesions that had caused no symptoms. These noninvasive examinations were extremely useful in evaluating asymptomatic early vascular lesions.

Hepatocellular carcinoma associated with Wilson's disease.

A 23-year-old man was admitted to our department due to hemorrhage from gastric varices. He had been diagnosed as having Wilson's disease at the age of 17. Abdominal ultrasonography and computed tomography (CT) showed portal thrombosis and a large mass occupying most of the right lobe in the liver. The tumor was diagnosed as hepatocellular carcinoma (HCC) by image views and tumor markers. He died 3 months after the diagnosis, and an autopsy was performed. Histologic examination of the tumor showed moderately to poorly differentiated HCC. The nontumorous lesion of the liver revealed cirrhosis. HBX-DNA sequence was not detected in the liver. Hepatic cirrhosis is a well-recognized complication of Wilson's disease, but HCC is extremely rare. We describe the clinical findings of this patient and discuss the relationship of the development of HCC with a review of the relevant literature.