OBJECTIVE: We investigated the long-term outcomes of autologous peripheral blood stem cell transplantation (PBSCT) to treat refractory rheumatic diseases. METHODS: Patients who underwent PBSCT for refractory rheumatic diseases at our institution between 2002 and 2005 were assessed for outcomes including treatment response, adverse events, damage accrual, and survival at 6 months and last follow-up. RESULTS: Eleven patients, including six with systemic lupus erythematosus (SLE), four with systemic sclerosis (SSc), and one with Still's disease were treated with PBSCT. In SLE patients, two showed complete response, two partial response, and two expired. One patient who expired responded completely two months after transplantation but discontinued treatment by choice and expired at six months due to an SLE flare. Long-term, two patients went into remission without organ damage, one patient went into remission with organ damage, and one had low disease activity with organ damage. Of the four patients with SSc, two showed a complete response, one a partial response, and there was one transplantation-related death at six months. At the last record notation, two remained in remission without relapse and one was lost to follow-up. The Still's disease patient partially responded at six months and was in remission at the last record notation. CONCLUSION: The ten-year survival rate was 70% with a 40% recurrence rate and 20% treatment-related mortality rate.
Follow-Up Studies ; Humans ; Lost to Follow-Up ; Lupus Erythematosus, Systemic ; Mortality ; Peripheral Blood Stem Cell Transplantation* ; Recurrence ; Rheumatic Diseases* ; Scleroderma, Systemic ; Survival Rate

OBJECTIVE: We compared the Disease Activity Score 28 (DAS28) using C-reactive protein (DAS28-CRP) with DAS28 using erythrocyte sedimentation rate (DAS28-ESR) in assessing rheumatoid arthritis (RA) activity and determining European League Against Rheumatism (EULAR) response criteria. METHODS: We searched the PubMed, EMBASE, and Cochrane databases and performed a meta-analysis to examine comparisons between DAS28-CRP and DAS28-ESR by RA activity and EULAR response criteria. RESULTS: A total of ten studies were included in this meta-analysis. Significantly more patients were classified as having remission or low disease activity when using DAS28-CRP than when using DAS28-ESR (odds ratio [OR]=1.869, 95% confidence interval [CI]=1.180 to 2.959, p=0.008; OR=1.411, 95% CI=1.256 to 1.586, p=7.0×10⁻⁸), whereas fewer patients were classified as having high disease activity when using DAS28-CRP than when using DAS28-ESR (OR=0.534, 95% CI=0.388 to 0.734, p=1.1×10⁻⁴). More patients were classified as having good response with criteria were based on DAS28-CRP than with DAS28-ESR (OR=1.390, 95% CI=1.183 to 1.632, p=6.10×10⁻⁵). CONCLUSION: Our meta-analysis demonstrates that DAS28-CRP underestimates disease activity and overestimates response by the EULAR response criteria compared to DAS28-ESR.
Arthritis, Rheumatoid* ; Blood Sedimentation* ; C-Reactive Protein* ; Erythrocytes* ; Humans ; Rheumatic Diseases

Wegener's granulomatosis (WG) is highly correlated with cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Patients with rheumatoid arthritis (RA) rarely contract WG. Although several concurrent cases have been reported overseas, there are no known cases in Korea. Here we report a unique case of RA with atypical WG testing positive for perinuclear ANCA (p-ANCA) and negative for anti-myeloperoxidase (MPO) antibodies. The 62-yr-old female patient presented with multiple joint pain and showed typical blood test results for RA, i.e., an elevated erythrocyte sedimentation rate and C-reactive protein concentration, and positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. RA was clear based on a total score of 10 when applying the classification criteria developed by the American College of Rheumatology/European League Against Rheumatism (2010). In an autoimmune target test, speckled and skeleton patterns were observed. In an ANCA test, p-ANCA was observed (titer, 1:2,560), and tests for anti-proteinase 3 (PR3) and anti-MPO antibodies were negative. After admission, multiple nodules were detected on a chest X-ray and a computed tomography scan. We suspected that she had rheumatic nodules or vasculitis and performed an open lung biopsy. We detected necrotic granulomatous vasculitis, classified as WG, thus leading to WG diagnosis. In conclusion, WG was diagnosed in an RA patient who was negative for c-ANCA (negative PR3) and positive for p-ANCA (negative anti-MPO), and this peculiar finding is likely to improve diagnosis in cases of RA with atypical WG.
Antibodies ; Antibodies, Antineutrophil Cytoplasmic ; Arthralgia ; Arthritis, Rheumatoid* ; Biopsy ; Blood Sedimentation ; C-Reactive Protein ; Classification ; Cytoplasm ; Diagnosis ; Female ; Hematologic Tests ; Humans ; Korea ; Lung ; Rheumatic Diseases ; Rheumatic Nodule ; Rheumatoid Factor ; Skeleton ; Thorax ; Vasculitis ; Wegener Granulomatosis*

Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic inflammatory disorder, which principally attacks the small joints. Several autoantibodies, such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody, are known to be associated with RA. Anti-proliferating cell nuclear antigen (PCNA) antibodies are mainly observed in patients with systemic lupus erythematosus (SLE). Indeed, a high titer of these antibodies is considered highly suggestive of SLE; however, anti-PCNA antibodies also appear in other autoimmune diseases. Two previous reports described RA patients with low titers of anti-PCNA antibodies, respectively. In this report, we describe a case of an RA patient exhibiting a high titer (>1:2,560) of anti-PCNA antibodies. The 56-yr-old female patient, with no underlying disease or medication history, presented with multiple joint pain and morning stiffness that had begun 6 months prior. The erythrocyte sedimentation rate (ESR) and RF were elevated (102 mm/hr and 77 IU/mL, respectively), and C-reactive protein (CRP) was 0.8 mg/dL. While the test for anti-CCP antibodies was negative, an anti-PCNA pattern (>1:2,560) and a homogeneous pattern (1:320) were detected by autoimmune target (AIT) test. The presence of anti-PCNA antibodies was subsequently confirmed using the double immunodiffusion method. The anti-dsDNA test was also positive (1:160). X-ray imaging showed soft tissue swelling of multiple joints of both hands and wrists. According to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, the patient was classified as having RA. This is the first case to describe high titers anti-PCNA antibodies associated with RA.
Antibodies* ; Arthralgia ; Arthritis, Rheumatoid* ; Autoantibodies ; Autoimmune Diseases ; Blood Sedimentation ; C-Reactive Protein ; Classification ; Female ; Hand ; Humans ; Immunodiffusion ; Joints ; Lupus Erythematosus, Systemic ; Proliferating Cell Nuclear Antigen ; Rheumatic Diseases ; Rheumatoid Factor ; Wrist

OBJECTIVETo establish the migraine rheumatism stasis syndrome animal model.

METHODThe rat migraine rheumatism stasis syndrome animal model was established through rheumatism stimulation with manual climate box, 5-HT reduction caused by reserpine and local cerebral vasospasm. General vital signs (activity, weight, eye gum, hair, feeding, excrement), head scratch frequency and image collection were observed to analyze the changes in biological signs of stasis syndrome (tongue image RGB), thrombin and serotonin of model rats.

RESULTThe reserpine group and the reserpine plus rheumatism model group showed significant reduction in blood coagulation time, pain threshold and 5-HT content in blood and brain (P < 0.01); the reserpine plus rheumatism model group showed an increase in eye gum and decreases in activity, feeding, with thin sloppy stool. According to the tough RGB values, the control group showed light red toughs, the reserpine group showed dark purple toughs, the reserpine plus rheumatism model group showed gray toughs, with notable differences in tough RGB values in all three group.

CONCLUSIONThe rheumatism stimulation with manual climate box, 5-HT reduction caused by reserpine and local cerebral vasospasm can be used to induce the migraine rheumatism stasis syndrome animal model, but its modeling assessment method and process shall be further improved.

Animals ; Blood Circulation ; Diagnosis, Differential ; Disease Models, Animal ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Migraine Disorders ; diagnosis ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Rheumatic Diseases ; diagnosis ; physiopathology

This new classification system redefines the current paradigm of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS), by focusing on the features of the disease at earlier stages. The new classification criteria of RA was devised to facilitate early diagnosis. They include the use of positive anti-cyclic citrullinated peptide antibody test and the presence of the increased level of acute phase reactants such as erythrocyte sedimentation rate and c-reactive protein. As compared to the old criteria in which only plain radiography was used to determine the joint damage, ultrasound can be regarded as a valuable tool for examining the extent of synovitis in the new criteria. In terms of SLE, immunologic criteria were intensified in the new classification criteria. They include hypocomplementemia as a single criterion and the presence of anti beta2GPI antibody is considered to meet the antiphopholipid antibody criterion. The new concept of neuropsychiatric lupus is applied as well. The most recent classification criteria for AS were provided by Assessment of Spondyloarthritis International Society. They cover the whole spectrum of axial spondyloarthritis (SpA) and peripheral SpA and use magnetic resonance imaging as an important tool to assess early sacroiliac changes. In addition, they emphasize the presence of HLA-B27 gene as an important criterion. In order to prevent the undesirable organ damages, it is crucial to diagnose rheumatic diseases at early stages according to these new classification criteria and to start an early aggressive treatment. The accurate diagnosis and early targeted therapies will contribute to the improved quality of life and increased overall survival of the patients with rheumatic diseases.
Acute-Phase Proteins ; Arthritis, Rheumatoid ; Blood Sedimentation ; C-Reactive Protein ; Early Diagnosis ; HLA-B27 Antigen ; Humans ; Joints ; Korea ; Lupus Erythematosus, Systemic ; Magnetic Resonance Imaging ; Quality of Life ; Rare Diseases ; Rheumatic Diseases ; Spondylitis, Ankylosing ; Synovitis

Arthritis is caused by various diseases including rheumatoid arthritis (RA), osteoarthritis, gout and trauma, and joint involvement also occurs in some autoimmune diseases, such as systemic lupus erythematosus and Sjogren's syndrome. Some laboratory tests provide useful information in both diagnosis and prognosis. RF and anti-CCP (cyclic citrullinated peptide) antibody are detected in approximately 70-80% of patients with RA, and often associated with a worse prognosis (e.g., bony erosion and joint deformity). Acute phase reactants, such as erythrocyte sedimentation rate and C-reactive protein, parallel the activity of RA, and their persistent elevation are also associated with a poor prognosis. Crystal examination in synovial fluid is essential to confirm the diagnosis of gout and pseudogout, and the synovial fluid culture is also important in septic arthritis. Anti-nuclear antibody helps to distinguish non-immune arthritis from systemic rheumatic diseases. However, arthritis cannot be diagnosed only with laboratory findings, and physician should consider comprehensive physical examination, clinical findings, and imaging findings as well as laboratory findings. In this topic review, laboratory tests useful for diagnosis of arthritis will be discussed and summarized.
Acute-Phase Proteins ; Arthritis ; Arthritis, Infectious ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Blood Sedimentation ; C-Reactive Protein ; Chondrocalcinosis ; Gout ; Humans ; Joints ; Lupus Erythematosus, Systemic ; Osteoarthritis ; Physical Examination ; Prognosis ; Rheumatic Diseases ; Sjogren's Syndrome ; Synovial Fluid

OBJECTIVETo identify the candidate auto-antigen of rheumatic heart disease as a molecular marker for this disease.

METHODSThe total RNA of the heart tissue of patients with rheumatic heart disease was extracted and reverse-transcribed into long cDNA to construct the phage expression library. The library was screened using the serum from patients with active rheumatic fever, and the positive clone was identified and analyzed by bioinformatics and expressed in vitro. The expressed products were evaluated with Western blotting and its cross-reactivity was assessed.

RESULTSThe phage expression library of the heart tissue of patients with rheumatic heart disease was constructed, with the titer of the primary library of 3.3×10(6) pfu/ml, recombinant rate of 99%, and 81% of the inserted segments were larger than 1 kb. An auto-antigen RHDAG1 was identified by screening, which was homologous to keratin 18. RHDAG1 was detected in the serum of patients with active rheumatic fever and of those with rheumatic heart disease, but not in the serum of healthy subjects.

CONCLUSIONPhage display library can be an effective strategy to screen the auto-antigens of rheumatic heart disease. The auto-antigen RHDAG1 can be a candidate molecular biomarker of rheumatic heart disease and/or rheumatic fever.

Autoantibodies ; blood ; immunology ; Autoantigens ; immunology ; isolation & purification ; Autoimmune Diseases ; blood ; immunology ; Humans ; Peptide Library ; Rheumatic Heart Disease ; immunology

BACKGROUND: We assessed the efficacy of serial interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in patients receiving immunosuppressive agents for treatment of rheumatic diseases in Korea. METHODS: Of 276 patients who underwent consecutive screening with one of two IGRAs [QuantiFERON-TB Gold or QuantiFERON-TB Gold In-Tube], 66 patients were evaluated by the serial IGRA for detection of LTBI during therapy with immunosuppressive agents. Information on clinical diagnosis, medication, previous TB, blood cell count, tuberculin skin test, and interferon-gamma (IFN-gamma) level measured by IGRA was collected. RESULTS: Of the 66 patients, the initial IGRA was positive in 24.2%, negative in 65.2%, and indeterminate in 10.6%. Forty-six patients (69.7%) showed consistent IGRA results during follow-up, and 13 patients (19.7%) had consistently positive results. IGRA conversion rate was 12.1% (8/66) and reversion rate was 4.5% (3/66). Conversion of IGRA results was only observed in ankylosing spondylitis patients, and the median interval between the two tests in patients with conversion was 8.5 months. The mean IFN-gamma level in the group of patients with consistently positive IGRA results was higher than that in the group with inconsistently positive results, although this trend was not statistically significant (P=0.293). Indeterminate results were observed most frequently in patients with systemic lupus erythematosus. CONCLUSIONS: In patients receiving immunosuppressive agents, both IGRA conversions and reversions were observed. Serial IGRA testing may not be needed in patients with a positive initial IGRA result showing high IFN-gamma levels, because of high consistency in the test results.
Adult ; Blood Cell Count ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents/*therapeutic use ; Interferon-gamma/*analysis ; *Interferon-gamma Release Tests ; Latent Tuberculosis/complications/*diagnosis/metabolism ; Lupus Erythematosus, Systemic/complications/diagnosis/metabolism ; Male ; Middle Aged ; Rheumatic Diseases/complications/diagnosis/drug therapy ; Spondylitis, Ankylosing/complications/diagnosis/metabolism ; Tuberculin Test

OBJECTIVE: To determine the mechanism of protective effect of noninvasive limb ischemic preconditioning (NIPC) on myocardium of patients with rheumatic heart disease undergoing heart valve surgery under cardiopulmonary bypass (CPB). METHODS: A total of 32 patients with rheumatic heart disease undergoing heart valve surgeries under CPB were randomly divided into 2 groups: a control group(n=16)and an NIPC group(n=16).Tourniguet was used for each patient in the NIPC group around both the upper extremities in turn, inflated for 8 min and deflated for 5 min for 3 cycles. After the anesthesia, the remaining procedures were the same as in the control group. Blood samples were collected from the central vein after the induction of anesthesia (T(1)), 5 min before aortic clamp (T(2)),30 min after aortic opening (T(3)), 6 h after the operation (T(4)), and 24 h after the operation (T(5)) to measure the concentration of cardiac troponin I and creatine kinase MB in the plasma and CGRP and ET-1 in the serum. Pathologic change of the right auricle of the heart tissue during the superior vena cave intubation and extubation was detected. RESULTS: The content of cardiac troponin I and creatine kinase MB at T(4) and T(5) in the 2 groups was higher than that of other time points in the same group, and it reached the peak at T(5). Comparison of the content of cardiac troponin I and creatine kinase MB at T(4) and T(5) in the 2 groups showed significant difference, and that of the NIPC group was lower than the control group(P<0.05).CGRP and ET-1 contents reached the peak at T(2) in the NIPC group and at T(3) in the control group, but the peak of CGRP in the NIPC group was higher than that in the control group(P<0.01).The peak of ET-1 content in the NIPC group was lower than that in the control group(P<0.01). After the CPB, myocardial and mitochondrion impairment was lighter in the NIPC group than in the control group. CONCLUSION Noninvasive limb ischemic preconditioning can protect the myocardium through increasing CGRP, inhibiting ET-1, and advancing the peak of CGRP and ET-1.
Adult ; Arm ; blood supply ; Calcitonin Gene-Related Peptide ; metabolism ; Cardiopulmonary Bypass ; Female ; Granulins ; Heart Valve Diseases ; surgery ; Heart Valve Prosthesis Implantation ; methods ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Ischemic Preconditioning ; methods ; Male ; Middle Aged ; Mitral Valve ; surgery ; Myocardial Reperfusion Injury ; prevention & control ; Rheumatic Heart Disease ; surgery