Risk Factors for Low Bone Mineral Density in Korean Patients with Systemic Lupus Erythematosus

OBJECTIVE: To determine the degree and risk factors for decreased bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE). METHODS: One hundred and one patients with SLE and 57 age- and gender- matched healthy controls were enrolled in this study. The BMD was measured by dual energy X-ray absorptiometry (DXA). The laboratory findings and clinical variables evaluated in the SLE patients consisted of disease duration, SLE disease activity index (SLEDAI), and medications, including mean and cumulative dose of glucocorticoid. At the time of the clinical and laboratory assessment, the levels of serum osteocalcin, serum FSH/LH, urine deoxypyridinoline (DPD), and serum cytokines, such as IL-6 and soluble receptor activator of NF-kB ligand (RANKL), were determined in SLE patients using a enzyme-linked immunosorbent assay. RESULTS: The BMD T score decreased in patients with SLE compared to the healthy controls (-1.11 versus -0.41, p=0.001 at lumbar spine, -0.84 versus -0.01, p<0.001 at femur neck, -1.20 versus -0.45, p<0.001 at total hip, respectively). Osteoporosis and osteopenia was present in 16.8% and 46.5% of patients, respectively. Multiple regression analysis revealed a low BMD in the lumbar spine to be associated with increased FSH, low BMI and cumulative glucocorticoid dose. A low BMD in the hip and femur neck was associated with increased FSH, low BMI, and duration of glucocorticoid. On the other hand, the levels of osteocalcin, deoxypyridinoline (DPD), IL-6, and soluble RANKL were similar in patients with a low BMD and those with normal BMD. CONCLUSION: Osteoporosis and osteopenia are more common in young Korean SLE patients than in control subjects. Elevated FSH, low BMI, and the use of glucocorticoid are independent risk factors linked to a decreased BMD in Korean patients with SLE.

Expression and Function of Calcineurin in Inflammatory Arthritis

BACKGROUND: Calcineurin plays a crucial role in T cell activation, cell growth, apoptosis, and angiogenesis, and its over-expression has been implicated in the pathogenesis of cardiomyopathy and stroke. However, the expression and function of calcineurin in the pathologic lesion of chronic inflammatory diseases, like rheumatoid synovium, remain to be defined. This study was aimed to determine the role of calcineurin in inflammatory arthritis and investigate the expression and function of calcineurin in the rheumatoid synovium and synoviocytes, the actual site of chronic inflammation. METHODS: Immunohistochemical staining using specific antibody to calcineurin was perfomed in the synovium of rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients were isolated from RA and OA patients, and cultured with IL-1beta and TNF-alpha in the presence or absence of cyclosporin A, a calcineurin inhibitor. The calcineurin expression was assessed by phosphatase assay and Western blotting analysis. IL-6, -10, -17, matrix metalloproteinase (MMP)-1, -2, -3, and -9 released into the culture supernatants were measured by ELISA. After transfection with GFP-Cabin 1 gene into synoviocytes, the levels of IL-6 and MMPs were measured by ELISA. RESULTS: Calcineurin was highly expressed in the lining layer of synovium and cultured synoviocytes of RA patients. The elevated calcineurin activity in the rheumatoid synoviocytes was triggered by proinflammatory cytokines such as IL-1beta and TNF-alpha. In contrast, IL-10, an anti-inflammatory cytokine, failed to increase the calcineurin activity. The targeted inhibition of calcineurin by the over-expression of Cabin 1, a natural calcineurin antagonist, inhibited the production of IL-6 and MMP-2 by rheumatoid synoviocytes in a similar manner to the calcineurin inhibitor, cyclosporin A. CONCLUSION: These data suggest that abnormal activation of calcineurin in the synoviocytes may contribute to the pathogenesis of chronic arthritis, and thus provide a potential target for controlling inflammatory arthritis.

A Case of Patient with Coincident Lung Cancer and Rheumatoid Arthritis Treated with Docetaxel-Cisplatin Chemotherapy / 대한류마티스학회지

A 54-year-old male was admitted due to lung cancer and polyarthralgia involving wrist, hand, shoulder, and ankle joints. Five months ago, he had been diagnosed as adenocarcinoma of the lung, and treated with three cycles of chemotherapy using gemcitabine and cisplatin. In the course of chemotherapy, he had complained symmetrical polyarthralgia of hand and shoulder joints, resembling rheumatoid arthritis (RA). After treatment with chemotherapeutic agents, he still had severe polyarthritis refractory to anti-rheumatic drugs, including prednisolone, hydroxychloroquine, and methotrexate, and thus referred to our hospital. We changed the previous anti-cancer regimens to cisplatin plus docetaxel, a semisyntheic taxane molecule, which is known to suppress experimental polyarthritis. With additional three cycles of cisplatin plus docetaxel, RA disease activity as well as polyarthralgia was nearly completely resolved, and the extent of lung cancer was not aggravated. Although RA patients have an increased risk of malignancy, the outbreak of RA was very rare in lung cancer patients. Here we report a case of coincident lung cancer and rheumatoid arthritis, which was successfully treated by docetaxel plus cisplatin chemotherapy.

Effect and Mechanism of Arginine-rich Anti-vascular Endothelial Growth Factor Hexapeptide, RRKRRR, on the Regulation of Rheumatoid Inflammation / 대한류마티스학회지

OBJECTIVE: Vascular endothelial growth factor (VEGF) has been suggested to play a critical role in the pathogenesis of rheumatoid arthritis (RA). It has been demonstrated that synthetic arginine-rich hexapeptide, RRKRRR, shows significant inhibition of VEGF-induced angiogenesis, and also retarded the growth and metastasis of colon carcinoma cell by blocking the interaction between VEGF and its receptor. In this study, we investigated whether anti-VEGF RRKRRR peptide (dRK6) could regulate the activation of mononuclear cells of RA patients and suppress collagen-induced arthritis (CIA) in mice. METHODS: Synovial fluid mononuclear cells (SFMC) or synoviocytes from RA patients were cultured in the presence of VEGF, and the levels of TNF-alpha and IL-6 were determined in the culture supernatants by ELISA. Blocking experiments were performed by adding dRK6 to thecells stimulated with VEGF. Additionally, the in vivo effect of dRK6 on the development of arthritis was tested in collagen induced arthritis (CIA) in DBA/1 mice. T cell responses to type II collagen (CII) and IgG antibodies to CII were examined in draining lymph node cells and sera of the mice, respectively. RESUTLS: dRK6 showed concentration-dependent inhibitory activity for the VEGF binding to its receptor on human vascular endothelial cells. The treatment of dRK6 completely abrogated the VEGF-induced productions of TNF-alpha and IL-6 by RA SFMC or synoviocytes. Moreover, a subcutaneous injection of dRK6 resulted in a dose-dependent decrease in the severity and incidence of CIA in mice. In these mice, the T cell responses to type II collagen (CII) in lymph node cells and circulating IgG antibodies to CII were also dose-dependently inhibited by the peptides. CONCLUSION: We observed firstly that anti-VEGF dRK6 blocked the VEGF-induced production of pro-inflammatory cytokine from RA SFMC and synoviocytes, and suppressed the ongoing paw inflammation in mice. These data suggest that dRK6 may be an effective strategy in the treatment of RA, and could be applied to modulate various chronic VEGF-dependent inflammatory diseases.

Influence of Serum TRAIL Concentrations on Disease Activity in RA Patients / 대한류마티스학회지

OBJECTIVE: TNF-alpha related apoptosis inducing ligand (TRAIL) is a member of TNF superfamily that promotes apoptosis by binding to the transmembrane receptors. The effects of TRAIL in patients with rhematoid arthritis (RA) are still debatable. This study was performed to evaluate the effects of TRAIL on RA by measuring serum concentration of TRAIL in patients with RA and assessing relationships between the TRAIL concentration and various clinical parameters of RA. METHODS: A total of 105 patients with RA, 34 patients with osteoarthritis (OA), and 35 age- and gender-matched healthy controls were enrolled in this study. Data from the RA patients included subject's age, duration of disease, daily steroid doses, ESR, CRP, rheumatoid factor, leukocyte count, lymphocyte count, tender joint count, swollen joint count, and serum TRAIL concentration. Serum TRAIL concentration was measured by enzyme immunoassay (EIA) method. The serum concentration of TRAIL in RA patients was compared to those of OA patients and healthy controls. Relationships of TRAIL concentration with various clinical parameters were evaluated. RESULTS: Serum concentration of TRAIL in patients with RA was significantly decreased compared to that in healthy controls (RA: 42.60+/-26.39 pg/mL, control: 57.21+/-19.49 pg/mL, p=0.029). Serum concentration of TRAIL in patients with OA (50.79+/-15.92 pg/mL) was not different from that in normal controls (p=0.115). There were no significant differences in serum TRAIL concentration between patients with RA and those with OA (p=0.360). In patients with RA, serum TRAIL concentration showed no difference between high- and normal ESR subgroups, as well as high- and normal CRP subgroups. Serum TRAIL concentration correlated significantly with ESR (r=0.406, p<0.001). However, other clinical parameters, such as subject's age, duration of disease, daily steroid doses, CRP, leukocyte count, lymphocyte count, tender joint count, swollen joint count revealed no significant correlation with serum TRAIL concentration. CONCLUSION: Serum concentrations of TRAIL in RA patients were significantly lower than those in healthy controls, suggesting that apoptotic ability is decreased in the patients with RA. Serum TRAIL concentration does not seem to reflect disease activity of RA.

Decreased Protein S Activity Related to the Disease Activity of Behcet's Disease / 대한류마티스학회지

OBJECTIVE: To see whether the active inflammation in Behcet's disease (BD) can cause thrombotic disorders by decreasing the protein S activity (PSA), we evaluated the relationship between PSA decrease and disease activity of BD. METHODS: We included 122 patients with BD whose PSAs were measured between August 1998 and April 2005. In 51 BD patients, the PSA was measured again when there were changes in the number of items of "The Behcet's Disease Current Activity Form (BDCAF)". RESULTS: Thrombosis rate was 2.5% (3/122), and the PSA was low in all 3 of the patients. The incidence of low PSA in total 122 BD patients was 27% (33/122). The incidence of low PSA in active BD patients was 33.7% (31/92), and it was significantly more frequent in active BD patients than in inactive patients, 6.7% (2/30) (chi2-test, p value=0.0038). The decrease of PSA had good correlation with the number of BDCAF items (r=-0.351, p=0.012). CONCLUSION: The PSA decrease is related to the disease activity of BD. PSA could be not only the risk factor for thrombotic disorder but also the activity marker for the BD and other inflammatory diseases.

A Case of Adult-onset Still's Disease associated with Congestive Heart Failure / 대한류마티스학회지

Adult onset Still's disease (AOSD) is a multi-systemic inflammatory disorder characterized by several distinguished manifestations including high spiking fever, evanescent salmon-colored skin rash, arthralgia/arthritis, hepato-splenomegaly, lymphadenopathy, sore throat, serositis, and leukocytosis. The frequently noticed cardiopulmonary manifestation is pleuritis, pneumonitis, and pericarditis. Diffuse myocardial dysfunction is uncommon in AOSD, but it may be the cause of life-threatening heart failure. We have experienced a case of AOSD with acute heart failure in 20-year-old female complained of high fever and skin rash. On echocardiogram, the wall motion of left ventricle was globally decreased with a marked diminished ejection fraction (<25%). Two weeks after treatment with high dose steroid and intravenous immunoglobulin, her symptoms and cardiac function on echocardiogram was completely resolved. To our knowledge, this is the first case of AOSD with acute heart failure reported in Korea.

A Case of Lipoma Arborescens of Knee Presenting as Hemarthrosis / 대한류마티스학회지

This report describes a patient with lipoma arborescens presenting as hemarthrosis of a knee with intraosseous lesions. A 44-year old woman complained of pain and swelling of left knee. Arthrocentesis resulted in bloody effusion. Magnetic resonance images showed villous projecting frondlike fatty soft tissue proliferation in the suprapatellar pouch and ovoid intraosseous lesions in proximal tibia. The soft tissue mass was removed through arthroscopic synovectomy and the biopsy of the mass confirmed the diagnosis. The intraosseous lesions were not considered as a cause of hemarthrosis. We failed to find the exact cause of hemarthrosis. The patient remained asymptomatic after removal of the mass for 10 months. As far as we know, this is the first report of hemarthrosis associated with lipoma arborescens in korea.

A Case of Acute Pachymeningitis Misdiagnosed as Subdural Hematoma in a Patient with Polyarteritis Nodosa / 대한류마티스학회지

The pathymeningitis is a very rare neurologic manifestation of PAN. We report a case of pathymeningitis misdiagnosed as subdural hematoma by brain CT in a patient with PAN. A 45-year old man who diagnosed as PAN through arteriography and skin biopsy in the ischemic finger 6 months ago. He complained of sudden headache, nausea, and diplopia 3 days before admission. In emergency room, noncontrast brain CT findings suggested small amount of subdural hematoma. But subsequent MRI findings revealed pachymeningitis of bilateral paratentoria and falx. He was treated with high-dose steroid and cyclophosphamide pulse therapy. Thereafter, his symptoms were gradually resolved. As far as we know, this is the first report of a case of pachymeningitis complicating PAN in Korea.

A case of systemic lupus erythematosus presented with refractory serositis and nephritis during pregnancy / 대한내과학회지

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies and immune complex depositions, has been known that it could be aggravated during pregnancy. We report a case who developed massive pericardial effusion, pleural effusion, and proteinuria during the second trimester of pregnancy. This patient had a history of leukopenia for several years and showed several features of SLE before pregnancy, however, no specific diagnosis was made before pregnancy. High dose oral glucocorticoid with intravenous immunoglobulin administration was done, but serositis and nephritis did not improve. The induced abortion and the use of immunosuppresive agent resulted in remission. We emphasize the importance of the early diagnosis and management of SLE before pregnancy in the patients with the features of autoimmune disease such as leukopenia, skin lesion and Raynaud phenomenon for successful outcome.

Ultrasound Imaging Supplements the Plain Radiography in the Evaluation of the Knee Osteoarthritis / 대한류마티스학회지

OBJECTIVE: Ultrasonography (USG) of joints has a unique position for the diagnosis of joint diseases. Bone surface, cartilage, periarticular soft tissue and their pathologic changes can be assessed by USG. This study was aimed to compare the radiographic and ultrasonographic findings in osteoarthritis (OA) of the knee joint and to evaluate the usefulness of each modality to evaluate the disease early and determine the severity of the arthritis. METHODS: Fifty osteoarthritis patients classified by the American College of Rheumatology (ACR) clinical criteria from December 2002 to April 2003 were included in the study. Routine radiography (standing anteroposterior, lateral, skyline view) and systemic USG examination of both knee were performed. We compared the incidence of the radiographic and ultrasonographic abnormality related to the pathologic change of the knee OA and suggesting the severity of the OA which would help to decide the therapeutic modality. RESULTS: In patient with knee OA, plain radiography showed abnormal findings in 37/50 (74%) patients, but USG showed at least five abnormal findings in all 50 patients. The abnormal findings detected only by plain radiography were subchondral sclerosis and subchondral cyst (14% and 4% each). But, the thinning of cartilage (94%), Baker's cyst (94%), cartilage degeneration (54%), meniscal protrusion (44%), meniscal tear (34%), meniscal cyst (32%), and the pannus (22%) were detected only by USG. Among the findings shared by both method, joint space narrowing was detected better by plain radiography than USG, but fluid accumulation, spur, meniscal calcification and osteochondroma were detected more frequently by USG. CONCLUSION: USG is more sensitive to find the pathologic changes related to the knee OA and to diagnose OA than the plain radiography. But each of the plain radiography and USG have their own unique value for the evaluation of OA in the knee. So the USG supplements the plain radiography in the examination of the knee OA.

Influence of Low Dose Corticosteroid Therapy on Bone Turnover in Patients with Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: This study was performed to evaluate the influence of low dose corticosteroid (CS) on bone turnover and osteoporosis in patients with rheumatoid arthritis (RA). METHODS: Bone mineral density (BMD), erythrocyte sedimentation rate, C-reactive protein, serum osteocalcin, and urinary deoxypyridinoline were measured in 63 patients with RA. According to daily prednisolone dose, patients were divided into low dose DI (5.0 gm) groups. Then we analyzed each groups in relation to several indicators. RESULTS: Most RA patients had low BMD. BMD of DI and DII groups were low without significant difference. Urinary excretion of deoxypyridinoline was high in DI and DII group while serum osteocalcin level was normal in both groups. It suggested patients with RA have an imbalance between bone absorption and bone formation contributing the development of osteoporosis, even though low dose steroid therapy. CONCLUSION: Patients with low dose CS had significantly high urinary deoxypyridinoline excretion, normal serum osteocalcin, and low BMD, as well as patients with medium dose CS. Even though low dose CS use, intensive prevention and treatment for generalized osteoporosis are recommended in patients with RA.

Developing the Hardtack Test to Screen and Monitor the Sjogren's Syndrome in Korea / 대한류마티스학회지

OBJECTIVE: To investigate the usefulness of the Hardtack test to screen the Sjogren's syndrome compared with non-stimulated whole salivary flow (NSWSF) and Schirmer-1 test. METHODS: Fifty patients with RA and other connective tissue disease who had complained sicca symptoms (7 males and 43 females) and twenty healthy participant, were undergone the Hardtack test, NSWSF, and Schirmer-1 test. The Hardtrack test were compared with NSWSF and Schirmer-1 test for the screening of Sjogren's syndrome. And the relationship between the tests were evaluated. RESULTS: 1) The time of dissolution of the hardtack was 88.7sec (Max: 136, Min: 44) in healthy group, and 321 sec (Ma: 900, Min: 92) in patient group (p<0.001). 2) NSWSF was 0.6 ml/min (Max: 1.32, Min: 0.14) in healthy group, and 0.28 ml/min (Max: 0.8, Min: 0.01) in patient group (p<0.001). 3) The lacrimal flow in Schirmer-1 test was 22.0 mm (Max: 30, Min: 8) in healthy groups and 5.26 mm (Max: 21, Min: 0) in patient group (p<0.001). 4) The correlation coefficient between the hardtack test and NSWSF was 0.56 (p<0.001). The correlation coefficient between the hardtack test and Schirmer-1 test was 0.51 (p<0.001). NSWSF was correlated with Shirmer-1 test but not significantly (r=0.254, p=0.075). In the hardtack test, the best balance between sensitivity and specificity was seen with a cut-off value of 120 seconds. CONCLUSION: The Hardtack test is useful screening test to discriminate between subjects with normal and reduced salivary flow. The Hardtack test is easy to perform, inexpensive, imposes minimal discomfort on the subject with xerostomia and correlated well with the NSWSF and the Schirmer-1 test. So it can also be used as to monitor the Sjogren's syndrome before the salivary flow measurement or Schirmer-1 test.

A Case Of Rheumatoid Arthritis Accompanied By Severe Eosinophilia / 대한류마티스학회지

Wegener's granulomatosis (WG) is a syndrome characterized by necrotizing granulomatosis lesions in the upper and lower respiratory tracts, glomerulonephritis, and generalized vasculitis involving both arteries and veins. This syndrome usually affects the upper and lower respiratory tract and the kidneys. Some patients with WG have cardiac involvement such as pericarditis, myocarditis, valvulitis, arrhthymia, coronary arteritis, and rarely cardiomyopathy. Ocular manifestations include keratitis, conjuntivitis, scleritis, retro-orbital granuloma with proptosis. Uncommonly, blindness may occur due to retinal vasculitis and optic neuritis. We report a 45-year-old female patient with WG who had sinusitis and lung nodules. She complained of sudden chest pain. Electocardiography and nuclear myocardial perfusion study suggested transient myocardial ischemia. During the active course of the disease, she complained of severe pain in the right eye-ball with decreased visual acuity. Subsequently, she developed monocular blindness probably due to retinal vasculitis.

A Case of Idiopathic Hypereosinophilic Syndrome Manifested by Massive Pericardial Effusion

Idiopathic hypereosinophilic syndrome is a state of marked eosinophilia of unknown cause accompanied by multiple organ involvement. Any organ may be involved including bone marrow, heart, lung, gastrointestinal tract, liver, kidney and the nervous system. The common cardiac manifestations of hypereosinophlic syndrome are myocarditis, endocardial fibrosis, formation of mural thrombi, valvular hearat disease, restrictive cardiomyopathy and congestive heart failure. We report a case of a 61-year-old man with idiopathic hypereosinophilic syndrome manifested by myocarditis and severe pericardial effusion on transthoracicechocardiography that was successfully treated by pericardiocentesis and on-going steroid therapy.

A case of overlap syndrome of systemic sclerosis/ systemic lupus erythematosus/Sjogren's syndrome / 대한류마티스학회지

Overlap syndrome is a combination of major features of more than one rheumatic disease present in the same patient and often defined by a specific serologic test. Overlap syndrome consistent with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) has been reported in a few cases. Overlap syndrome with SSc and SLE combined with Sjogren's syndrome (SS) is rarely reported worldwide. In Korea, this is the first case report. A 33 year-old female visited our rheumatology clinic complaining of Raynaud' s phenomenon. She was diagnosed as SSc 6 years ago. Clinical and laboratory finding revealed that she has affected by SLE. She also complained dry mouth and dry eye. Finally, she was diagnosed as overlap syndrome consistent with SSc and SLE combined with SS. The authors report a case of overlap syndrome consistent with SSc, SLE, and SS with relevant literatures.

Isolated Splenic Infarction in a Patient with Systemic Lupus Erythematosus / 대한류마티스학회지

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disease caused by various autoantibodies and immune complexes. Splenic involvement in SLE includes hypersplenism, splenic atrophy, and splenic infarction, which has rarely been reported. We report a case of SLE with isolated splenic infarction. A 20-year-old female patient was admitted complaining of general weakness, malar rash, and easy fatigue. She was diagnosed as having SLE with thrombocytopenia and received steroid treatment. On the 7th hospital day, she complained of severe left upper abdominal pain with sudden-onset. While abdominal ultrasonography showed only mild splenomegaly, abdominal CT and 99mTc-RBC splenic scintigraphy revealed segmental splenic infarction. She had no evidence of additional thrombotic event or hemorrhage. After administration of high dose steroid, abdominal pain subsided and splenic infarction was resolved.

A Case of Coronary Artery Dissection After Blunt Chest Trauma Presented as Acute Myocardial Infarction

Coronary artery dissection after blunt chest trauma is very rare conditon, and this can result in a serious acute myocardial infarction. We report a case of a 54-year old male who was presented with an anterior myocardial infarction after traffic accident, with steering wheel injury. His coronary angiography revealed a discrete eccentric 85% stenosis of proximal left anterior descending coronary artery with dissection and intravascular ultrasound showed a dissecting flap from the distal left main coronary artery to proximal left anterior descending coronary artery. He was successfully treated by percutaneous transluminal coronary angioplasty with stent.