Predicting Imaging Remission in Rheumatoid Arthritis: a Case-control Ultrasound Study

Background@#To elucidate the achievement rates of imaging remission and to examine the characteristics associated with imaging remission status among patients with rheumatoid arthritis (RA) who have attained clinical remission. @*Methods@#Ninety-seven patients with RA patients who had attained clinical remission, defined by DAS28-ESR < 2.6 were enrolled. Power Doppler ultrasonography (PDUS) was performed on 16 joints and 2 tendons, including the first to third metacarpophalangeal, second and third proximal interphalangeal, radiocarpal (RC), second and third metatarsophalangeal joints, and extensor carpi ulnaris tendons. They were graded based on a dichotomous assessment. The clinical and laboratory data of patients who had attained imaging remission were compared to those of patients who had attained only clinical remission. @*Results@#The imaging remission rate was 51.5% in patients who had attained clinical remission. Forty-seven patients (48.5%) were PDUS positive. Power Doppler was detected most frequently in the right RC joint (n = 40). PDUS positive patients had higher evaluator global assessment (EGA) scores (P < 0.001) than PDUS negative patients. PDUS positive patients also had higher clinical disease activity index and simplified clinical disease activity index scores than PDUS negative patients. Patients who had attained imaging remission had lower pain scores and used nonsteroidal anti-inflammatory drugs less frequently. Patients who had attained imaging remission had higher rheumatoid factor (RF) and anti-cyclic citrullinated peptide levels. A low EGA score was found to be a predictor of imaging remission achievement among patients who had attained clinical remission. @*Conclusion@#Only 51.5% of the patients with RA who had attained clinical remission were also in imaging remission. Patients who had attained imaging remission had lower EGA scores and higher RF levels than patients who had attained only clinical remission.

Comparing Effectiveness Rituximab (Mabthera®) to Other Second-line Biologics for Rheumatoid Arthritis Treatment in Patients Refractory to or Intolerant of First-line Anti-tumor Necrosis Factor Agent: An Observational Study

OBJECTIVE: Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. METHODS: Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. RESULTS: Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34, −1.63±0.30 vs. n=31, −2.05±0.34) and standard population set analysis (n=31, −1.51±0.29 vs. n=24, −2.21±0.34). Similarly, the change in DAS28 at 12 months did not reach statistical significance (−1.82±0.35 in the rituximab vs. −2.34±0.44 in the alternative anti-TNF agents, p=0.2390). Furthermore, the incidences of adverse events were similar between two groups (23.5% for rituximab group vs. 25.8% for alternative anti-TNF agents group, p=0.7851). CONCLUSION: Despite the limitations of our study, switching to rituximab or alternative anti-TNF agents after failure of the initial TNF antagonist showed no significant therapeutic difference in DAS28 reduction.

Hypocomplementemic Urticarial Vasculitis Syndrome with Membranous Nephropathy: Case Report

Urticarial vasculitis is a rare disorder that principally manifests with recurrent urticarial, sometimes hemorrhagic, skin lesions and/or angioedema. Its clinical presentation is not always limited to cutaneous lesions and it can potentially affect other organs, such as the joints, lungs, kidneys, and eyes. Systemic involvement can either be present at the onset of disease or develop over time. In cases with systemic manifestations, urticarial vasculitis is more likely to be associated with a low complement level. We present the case of a teenage boy with hypocomplementemic urticarial vasculitis syndrome (HUVS) that occurred shortly following swine-origin influenza A virus infection in 2009. Afterwards, HUVS was systemically complicated with myositis and membranous nephropathy that developed several months and about 2 years after its onset, respectively. A combination of glucocorticoid and immunosuppressive agents has been used to effectively control disease activity.

A Case of Palmoplantar Pustulosis Present in the Daughter of a SAPHO Syndrome Patient

SAPHO syndrome is a rare inflammatory, pseudoinfectious disease. Initially it was an acronym for Syndrome Acne Pustulosis Hyperostosis Osteitis, and the meaning of S was later changed to synovitis. It occurs predominantly in children and adults and is not common over 60 years. The most common clinical presentation is osteoarticular involvement at the anterior chest wall and skin manifestations may be evident, but it could occur years earlier or develop later. We report on two cases of mother and daughter. A 51-year-old female was diagnosed with SAPHO syndrome with costochondritis and palmoplantar pustulosis. Five years later, her 31-year-old daughter presented with similar skin manifestations of the hand and foot.

The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints

This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 mug ml-1) or IL-1beta (0.1 ng ml-1) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1beta. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1beta-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1beta. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1beta in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.

A Case of Myotonic Dystrophy with Electrolyte Imbalance

Type 1 myotonic dystrophy (DM1) is an autosomal-dominant inherited disorder with a multisystem involvement, caused by an abnormal expansion of the CTG sequence of the dystrophic myotonia protein kinase (DMPK) gene. DM1 is a variable multisystem disorder with muscular and nonmuscular abnormalities. Increasingly, endocrine abnormalities, such as gonadal, pancreatic, and adrenal dysfunction are being reported. But, Electrolytes imbalance is a very rare condition in patients with DM1 yet. Herein we present a 42-yr-old Korean male of DM1 with abnormally elevated serum sodium and potassium. The patient had minimum volume of maximally concentrated urine without water loss. It was only cured by normal saline hydration. The cause of hypernatremia was considered by primary hypodipsia. Hyperkalemic conditions such as renal failure, pseudohyperkalemia, cortisol deficiency and hyperkalemic periodic paralysis were excluded. Further endocrine evaluation suggested selective hyperreninemic hypoaldosteronism as a cause of hyperkalemia.

A Case of Overlap Syndrome of Rheumatoid Arthritis and Polymyositis with the Involvement of Upper Pharyngeal Muscles

An overlap syndrome is a combination of major features of more than one connective tissue diseases which is presented in the same patient. An overlap syndrome of rheumatoid arthritis (RA) and polymyositis (PM) which involved the upper pharyngeal muscle has not been reported in Korea. Herein, we report a rare case of a patient with a long-history RA presenting proximal muscle weakness and swallowing difficulty, who was successfully treated with a high-dose of corticosteroid, azathioprine and tacrolimus.

A Case of Behcet's Disease Associated with Myelofibrosis

Behcet's disease (BD) is a systemic vasculitis of unknown etiology that is rarely observed in association with leukemia and other hematologic disorders. We recently encountered a patient who presented with BD associated with myelofibrosis that was not attributable to other underlying causes. The patient was a 49-year-old man with a 3-year history of probable BD diagnosed by clinical findings; he was admitted because of anemia and splenomegaly. Bone marrow examination revealed myelofibrosis. After steroid therapy, the patient's symptoms of BD improved, and his hemoglobin level recovered. Therefore, we believe that the patient had BD with bone marrow involvement.

A Case of Development of Vitiligo Followed by TNF-alpha Antagonist Treatment for Rheumatoid Arthritis

As the usage of biologics for rheumatic diseases increases, such as rheumatoid arthritis and ankylosing spondylitis, various cutaneous adverse events are also being increasingly reported. We experienced a case of development of vitiligo during a TNF-alpha antagonist therapy in a 22-year-old woman with rheumatoid arthritis. The patient was presented with vitiligo lesions on the dorsum of both hands after 1 month of treatment with etanercept. Vitiligo improved with topical tacrolimus ointment and excimer laser treatment without the discontinuation of etanercept. No clearly defined mechanism for vitiligo induced by TNF-alpha antagonist exits. However, considering that vitiligo is an autoimmune disorder, the development of this skin lesion in association with the TNF-alpha antagonist could be explained by a paradoxical induction of the autoimmune process.

Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve beta-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients.

Synergy between adiponectin and interleukin-1beta on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1beta regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1beta, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1beta to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1beta each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1beta did not synergistically support the degradation of IkappaB-alpha or the nuclear translocation of NF-kappaB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-kappaB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1beta may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.

Imatinib Mesylate is Effective for Patients Not Only with Chronic Myeloid Leukemia, but Also Rheumatoid Arthritis / 대한내과학회지

Synovial tissue proliferation and inflammation are regarded as possible causes of rheumatoid arthritis. Activation of tyrosine kinase by numerous cytokines and BCR-ABL translocation contribute to synovial tissue inflammation and the development of rheumatoid arthritis, respectively. Imatinib is a tyrosine kinase-blocking agent that is widely used for treating chronic myeloid leukemia. We found several interesting case reports of patients with refractory rheumatoid arthritis who entered remission after initiating imatinib therapy. However, only one case report on treating rheumatoid arthritis with imatinib was found in Korea. Here, we describe the case of a 50-year-old man who showed clinical remission of rheumatoid arthritis and chronic myeloid leukemia after receiving 3 months of imatinib therapy.

A case of relapsing polychondritis and pyoderma gangrenosum in a patient with Down's syndrome / 대한내과학회지

Relapsing polychondritis (RP) is a rare multisystem disorder of unknown etiology that affects cartilaginous tissues, such as the auricular, nasal, and laryngotracheal cartilages. It may be accompanied by a wide spectrum of skin lesions, including erythema nodosum, erythema multiforme, and panniculitis. Pyoderma gangrenosum is a rare chronic cutaneous disease that usually presents as a painful nodule or pustule and progressively forms an enlarging ulcer. It may be associated with inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythromatosus, leukemia, and myeloproliferative disorders. Pyoderma gangrenosum is rarely associated with RP. RP and pyoderma gangrenosum have been reported in a patient with myelodysplastic syndrome (MDS), and the appearance of skin lesions in MDS may herald its progression to acute myeloid leukemia. Here, we report the first case of RP coexisting with pyoderma gangrenosum in a patient with Down's syndrome.

The Effect of Repeated Intraarticular Bleeding in the Synovium and Articular Cartilage: An Animal Model / 대한정형외과학회잡지

PURPOSE: We designed this study to demonstrate the pathophysiology of hemophilic arthropathy (HA) by creating an animal model for determining the effect of repeated intraarticular bleeding in the synovium and articular cartilage. MATERIALS AND METHODS: 20 normal male New Zealand white rabbits were used for this study. We injected 1 ml of autologous blood from the ear vein of the rabbits into the right knee joint three timeds a week for 18 weeks, and we injected 1 ml of normal saline into the left knee joint three times a week for 18 weeks as a control group. We examined the pathologic changes by microscopy and plain X-ray, and we determined the mRNA expression of proinflammatory cytokines in the synovium of the HA by performing real time RT-PCR at the 11th week and 18th week after starting blood-injection. We also examined the GAG and the PGE2 production in cultured chondrocytes that were extracted from the HA knees. RESULTS: At the 11th week, after blood injection there were no remarkable gross changes in the HA knees and the control knee joints. At the 18th weeks, the experimental knee joints (HA knees) showed grossly swelling and degenerative changes by X-ray. The infiltration of inflammatory cells and the synovial proliferation in the HA knee joints were compared with that in the control knee joints by microscopic examination. The expressions of the mRNA of TNF-alpha, IL-1, MMP-1 and MMP-3 in the HA synovium were increased, as determined by real time RT- PCR, as compared with that in the control knee. In the cultured chondrocytes, the GAG production was decreased and the PGE2 was increased, but the MMP-1 and MMP-3 were not changed, as determined by ELISA. CONCLUSION: Our results showed that the GAG production of chondrocytes of the HA knees was decreased and there was increased PGE2, so that the cartilage degeneration by intra-articular bleeding was caused by the decreased metabolism of chondrocytes rather than by increased catabolism of the chondrocytes. We suggest that HA was associated with synovitis and cartilage degeneration, but decreased cartilage metabolism was the major mechanism of HA.

A case of aseptic meningoencephalitis in adult-onset Still's disease / 대한내과학회지

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology, affecting mainly young adults,characterized by a high spiking quotidian fever, arthralgia or arthritis, evanescent salmon-colored maculopapular rash. It affects almost all organs, but neurological manifestations of AOSD are rare and could be responsible for a delay in diagnosis. We describe a case of AOSD who developed aseptic meningoencephalitis without any infectious cause. A 23-year-old woman was admitted because of high quotidian fever, arthralgia, maculopalpular rashes, leukocytosis with increased ferritin. During treatment by prednisolone, she suddenly developed status epilepticus. The brain image, electroencephalogram, and cerebrospinal fluid analysis did not show any abnormality including evidence of infection. After methyprednisolne pulse therapy, her clinical symptoms and laboratory tests including ferritin dramatically improved, and she could be discharged. To our knowledge, this is the first reported case of aseptic meningoencephalitis in a patient with AOSD in Korea.

A case of relapsing polychondritis with ankylosing spondylitis / 대한내과학회지

Relapsing polychondritis is a rare condition of unknown etiology in which recurrent episodes of inflammation are followed by the destruction of cartilaginous structures, which predominantly include the nose, ears, and tracheobronchial tree. Although many autoimmune disorders, such as systemic vasculitis, rheumatoid arthritis, lupus erythematosus, Sjogren's syndrome, and Behcet's disease, are commonly found in patients with relapsing polychondritis, ankylosing spondylitis is rarely associated with this disease. We report a case of relapsing polychondritis with ankylosing spondylitis in the same patient.

Perioperative Medication Management in Arthritic Patients / 대한류마티스학회지

As elderly population is growing rapidly, the number of patients with arthritis is also increasing. Because of the prolonged lifetime, arthritic patients become to have more chances to undergo surgical procedures. Many of these patients chronically receive medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, and various disease-modifying anti-rheumatic disease (DMARDs) including biologic agents. Decisions regarding withholding or modifying the regimens of these medications may be critical in the perioperative period to optimize surgical outcome. Consultation with a rheumatologist is recommended, but the surgeon also should be aware of these medications. This review article suggests a balanced perioperative medication management to minimize potential surgical complications and maintain disease control in arthritic patients.

Coptis chinensis Extract Inhibits the Production of Inflammatory Mediators and Delayed Type Hypersensitivity in Mice

BACKGROUND: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. METHODS: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 (PGE(2)), interleukin (IL)-2 and IFN-gamma were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. RESULTS: The CCE at 100 microgram/ml significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-gamma) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. CONCLUSION: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.

Coptis chinensis Extract Inhibits the Production of Inflammatory Mediators and Delayed Type Hypersensitivity in Mice

BACKGROUND: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. METHODS: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 (PGE(2)), interleukin (IL)-2 and IFN-gamma were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. RESULTS: The CCE at 100 microgram/ml significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-gamma) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. CONCLUSION: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.

Development of juvenile rheumatoid arthritis in a patient with multiple sclerosis / 대한내과학회지

Multiple sclerosis (MS) is an immune-mediated, inflammatory demyelinating disease of the central nervous system. The coexistence of multiple sclerosis and rheumatoid arthritis is very rare. This rare association is interesting due to the overlapping pathophysiological similarities of T-cells and tumor necrosis factor-alpha (TNF-alpha) in both diseases. We report a case of a Korean 10 year old girl with multiple sclerosis, who after 3 years developed a clinical and serological manifestation of juvenile rheumatoid arthritis.