TNF Inhibitor Use during the Perioperative Period / 대한류마티스학회지

Tumor necrosis factor (TNF) inhibitors are now established as therapeutic agents for treating active rheumatoid arthritis (RA) that is resistant to conventional drug treatment. However, TNF Inhibitors decrease resistance to infection, including unusual infections such as tuberculosis, and they have been shown to impair wound healing in an experimental setting. To date, there is limited data on patients with RA regarding their infections or the complications of surgery performed while taking TNF inhibitors and there is no professional consensus about this. This problem emphasizes a need for awareness and communication between patients, the rheumatologist and the surgeon when treating patients with RA. We reviewed the effects of TNF inhibitors on the incidence of surgical site infection (SSI) and the risk factors for SSIs after performing elective surgery in patients with RA. TNF inhibitors should not be used during the perioperative period until conclusive evidence to the contrary is available.

A Case of Interstitial Pneumonitis in a Patient with Rheumatoid Arthritis Treated with Leflunomide / 결핵및호흡기질환

Leflunomide, a disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis has been available in Korea since 2003. Leflunomide-associated interstitial pneumonitis has been appearing recently. A 25-year-old woman with a 12-month history of seronegative rheumatoid arthritis (RA) presented with acute respiratory insufficiency. She developed fever, dyspnea, and non-productive cough. Her medication history included methotrexate (15 mg/week. commencing 1 year prior) and leflunomide (20 mg/day, no loading dose, commencing 4 months prior). She was diagnosed with leflunomide-associated interstitial pneumonitis based on history, physical examination, laboratory and radiologic findings. She recovered quickly after leflunomide was withdrawn and steroids and cholestyramine were initiated quickly. We report a case of leflunomide-associated interstitial pneumonitis treated successfully with intravenous high-dose steroid and cholestyramine.

Recent Advance in Rheumatoid Arthritis

ARheumatoid arthritis is a systemic, inflammatory, autoimmune disorder of unknown origins. Enhanced understanding of molecular pathogenesis has enabled the development of new biologic treatment that focuses on selective parts of immune system. Combined genetic and environmental factors in association with the risk of rheumatoid arthritis have received increased attention. Research undertaken on the longitudinal disease process and molecular pathology of joint inflammation has contributed to the development of new therapeutic strategies that promote early use of disease-modifying anti-rheumatic drugs (DMARDs) with tight disease control and measurable treatment outcome. Such approach can be beneficial for control of inflammatory activity and joint destruction. We need to find out how to tailor the best individualized treatment in accordance with different cases.

Recent Advance in Rheumatoid Arthritis

ARheumatoid arthritis is a systemic, inflammatory, autoimmune disorder of unknown origins. Enhanced understanding of molecular pathogenesis has enabled the development of new biologic treatment that focuses on selective parts of immune system. Combined genetic and environmental factors in association with the risk of rheumatoid arthritis have received increased attention. Research undertaken on the longitudinal disease process and molecular pathology of joint inflammation has contributed to the development of new therapeutic strategies that promote early use of disease-modifying anti-rheumatic drugs (DMARDs) with tight disease control and measurable treatment outcome. Such approach can be beneficial for control of inflammatory activity and joint destruction. We need to find out how to tailor the best individualized treatment in accordance with different cases.

Comparison of the Clinical Manifestations, Brain MRI and Prognosis between NeuroBehcet's Disease and Neuropsychiatric Lupus

BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) shows some similarities to neuroBehcet's disease (NBD) in that both conditions have some analogous clinical features and they are both pathologically associated cerebral vasculopathy. This study compared the clinical manifestations, brain MRI findings and prognosis of NPSLE and NBD patients. METHODS: Forty three patients with NPSLE (n = 25) or NBD (n = 18), who were monitored at a single center, were enrolled in this study. We retrospectively analyzed the clinical and brain MRI data. The neuropsychiatric manifestations were classified in both groups according to the new American College of Rheumatology nomenclature for NPSLE. RESULTS: The diffuse symptoms that included mood disorders, psychosis, confusion, cognitive dysfunctions, generalized seizures and headaches other than migraine or cluster headaches were more commonly observed in the NPSLE patients, while the frequency of focal diseases such as cranial neuropathy tended to be higher in the NBD patients. The brain MRI revealed that the NBD patients had more abnormalities in the brain stem than did the NPSLE patients. Most of the patients improved, at least partially, after being treated with glucocorticoid and/or immune suppressants. However, the disease course differed significantly between the two groups. There were more episodic cases in the NPSLE group of patients, while there were more remittent cases in the NBD group of patients. CONCLUSION: NPSLE had a tendency to cause diffuse neuropsychiatric manifestations, and it has a different predilection of brain lesions compared with NBD. The NBD patients showed a poorer outcome than did the NPSLE patients, suggesting that different therapeutic strategies for the two diseases need to be considered.

Myelodysplastic Syndrome with Erythroid Aplasia following Pure Red Cell Aplasia

Myelodysplastic syndrome (MDS) with erythroid aplasia is a very rare disorder that has not been clearly defined. We experienced a case of pure red cell aplasia (PRCA), which evolved to MDS with erythroid aplasia. A 59-year-old male with transfusion-dependent PRCA was referred to our hospital for an evaluation of newly developed thrombocytopenia. Two years ago, PRCA was diagnosed by the laboratory findings and a bone marrow examination, which showed no evidence of any myelodysplastic features and thymoma. Upon admission, the bone marrow findings showed marked hypercellularity. with numerous dysplastic features in the three lineages including erythroid hypoplasia. These findings were compatible with a diagnosis of MDS with red cell aplasia. It is very interesting that the PRCA evolved to MDS with red cell aplasia, which strongly suggests an autoimmune mechanism for the development of MDS.

Reciprocal Activation of Fibroblast-like Synoviocyte and Type II Collagen-reactive T cell in Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: To investigate the interaction between type II collagen (CII)-reactive T cell and fibroblast-like synoviocyte in rheumatoid arthritis (RA). METHODS: Peripheral blood T cells from RA patients were cultured with bovine CII and analyzed by flow cytometry. After co-culture with CII-reactive T cells and fibroblast-like synoviocytes (FLS), the expression of cytokines (IL-15 and TNF-alpha from FLS, IFN-gamma and IL-17 from CII-reactive T cells) were determined by ELISA and RT-PCR. RESULTS: CII-reactive T cells expressed CD69, one of the early activation markers, and produced significant amount of IFN-gamma, and proliferated. IL-15 and TNF-alpha expression from FLS were significantly elevated when co-culture with CII-reactive T cells and inhibited by physical interruption of cell-to-cell contact or anti-CD40 antibody. IFN-gamma and IL-17 expression from CII-reactive T cells were also significantly elevated when co-culture with FLS and inhibited by anti-IL-15 monoclonal antibody. CONCLUSIONS: CII-reactive T cells can activate FLS to secret proinflammatoy cytokines and interactions between these two cells drive further activation of each other. These data suggest that CII-reactive T cell may play a important role in pathogenesis of RA.

Vascular Endothelial Growth Factor Stimulates Productions of Tumor Necrosis Factor-alpha and Interleukin-6 from Mononuclear Cells and Synoviocytes of Rheumatoid Arthritis Patients / 대한류마티스학회지

OBJECTIVE: Vascular endothelial growth factor (VEGF), an angiogenic factor, has been suggested to play a critical role in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated whether VEGF would directly regulate the activation of mononuclear cells of RA patients. MEHTODS: Mononuclear cells and/or synoviocytes of 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. The TNF-alpha-or IL-6-producing cells were also assessed by flow cytometry analysis. Blocking experiments were performed by adding anti-VEGF receptor (anti-Flt-1) mAb to the cells, stimulated with VEGF. RESULTS: VEGF directly increased the productions of TNF-alpha and IL-6 from peripheral blood mononuclear cells (PBMC) from healthy controls. Treatment of PBMC with anti-VEGF receptor (anti-Flt-1) mAb blocked the VEGF-induced productions of TNF-alpha and IL-6, suggesting that VEGF activates the PBMC via a receptor (Flt-1) coupling event. Synovial fluid mononuclear cells (SFMC) of RA patients showed a greater response to VEGF stimulation than the PBMC of healthy controls. The major cell types responding to VEGF were monocytes and synoviocytes. In addition, dexamethasone completely abrogated VEGF- stimulated productions of TNF-alpha and IL-6 from adherent cells, isolated from SFMC. CONCLUSION: Our data suggest that VEGF may directly activate RA monocytes and synoviocytes to produce TNF-alpha and IL-6.

Tuberculosis in Patients with Systemic Lupus Erythematosus: Single Center Retrospective Study / 대한류마티스학회지

OBJECTIVE: To compare the incidence and clinical characteristics of tuberculosis (tbc) between patients with systemic lupus erythematosus (SLE) and kidney transplantation (KT) recipients. METHODS: Six hundreds and twenty-two patients who were diagnosed as SLE from 1990 to 2001 in Kang-Nam St. Mary's hospital were reviewed, retrospectively. As a control group, 347 kidney transplant recipients in the same center were evaluated. The extent of tbc was categorized into two groups: (1) limited disease (2) extensive disease. Cumulative steroid dosage and disease activity index including SLEDAI, serum complement levels, and anti-dsDNA titers were compared between the two groups. RESULTS: The cumulative incidence rate of tbc was similar in both groups (37 cases and 5.7% in SLE versus 17 cases and 4.9% in KT). Mean interval from SLE diagnosis or KT to tbc development was not different between the two groups. The most common site of tbc was lung/pleura, and the others included lymph nodes (2 cases), knee joint (1), bone marrow (1), central nervous system (1), kidney (1), colon (1), liver (1), and skin (1) in SLE. In contrast, most of tbc (16/17) developed exclusively in the lung and pleura in KT recipients. Cumulative doses of prednisolone 1 or 6 months before tbc diagnosis were not different between the two groups. Interestingly, extensive disease tended to be more frequent in SLE patients than in KT recipients although immuno-suppressants such as cyclosporine and azathioprine were more frequently administered in KT recipients. There were no differences in disease activity index including SLEDAI, complement levels, and anti-ds DNA titers at the time of tbc diagnosis as well as in the cumulative doses of steroid between extensive and limited diseases of tbc in SLE. CONCLUSION: The cumulative incidence rate of tbc was higher in SLE patients than in general population. The patterns of tbc tended to be more extensive in SLE compared to KT recipients in whom a stronger immuno-suppression was required, suggesting that immune dysfunction implicated by SLE itself may play an important role in determining the incidence and patterns of tbc infection.