Park Yb

Clinical characteristics and outcomes of Takayasu's arteritis: analysis of 108 patients using standardized criteria for diagnosis, activity assessment, and angiographic classification

Objectives: To investigate the clinical characteristics and outcomes of Takayasus arteritis (TA) using standardized criteria for diagnosis, disease activity, and angiographic classification, and to identify the predictive factors for remission, angiographic progression, and mortality in patients with TA. Methods: One hundred and eight patients who fulfilled the 1990 American College of Rheumatology (ACR) classification criteria for TA were studied. Their clinical features, laboratory findings, angiographic findings, and clinical outcomes were evaluated retrospectively. The disease activities were assessed using the National Institutes of Health (NIH) criteria for active disease, and the angiographic types were classified using the International TA Conference in Tokyo 1994 angiographic classification. Results: Angiographic classification showed that type I was the most common, followed by types V and IV. Ninety‐one patients had active disease at diagnosis, and remission was achieved in 81.3% of them. Among those who experienced remission and those who had stable disease at diagnosis, 28.6% experienced a relapse. A low erythrocyte sedimentation rate (ESR) at diagnosis and treatment with glucocorticoid were found to be independent predictors for remission, and the stable disease activity at diagnosis was an independent predictor for the quiescence of vascular lesions on follow‐up angiography. Survival rates were 92.9% at the fifth year and 87.2% at the tenth year, and the presence of two or more complications was a risk factor for mortality. Conclusions: These findings could provide useful information on the clinical features, angiographic findings, and outcomes in TA, particularly on the assessment of patients at risk of a poor outcome.

Osteopontin might be involved in bone remodelling rather than in inflammation in ankylosing spondylitis

OBJECTIVES To determine whether osteopontin (OPN) is increased in patients with AS and to investigate its relationship to inflammatory disease activity and bone remodelling process. METHODS This cross-sectional study included 30 patients with AS and 23 age- and sex-matched healthy controls. We assessed clinical characteristics and laboratory parameters including the ESR, CRP, lipid profiles, the Bath AS disease activity index (BASDAI) and the Bath AS radiographic index (BASRI). To evaluate bone metabolism, we tested ALP, OCN and C-telopeptide of type I collagen (CTX-I). Plasma levels of OPN, TNF-alpha and IL-6 were measured by ELISA, and mRNA expression in peripheral blood mononuclear cells (PBMCs) was performed by RT-PCR. Changes in OPN level were also evaluated in eight patients after the treatment with a TNF-alpha blocker. RESULTS Patients with AS had significantly higher plasma OPN, TNF-alpha and IL-6 levels and more mRNA expression than healthy controls. Plasma OPN levels were correlated with serum ALP, OCN and CTX-I levels, but not with ESR, CRP, lipid profiles, BASDAI or BASRI. Treatment with a TNF-alpha blocker did not alter OPN levels, although it reduced the disease activity. CONCLUSIONS Patients with AS had higher levels of OPN compared with controls. The plasma OPN level was correlated with serum ALP, OCN and CTX-I levels, but not with disease activity in AS. OPN might be involved in bone remodelling rather than in inflammation in AS.

Risk of ovarian failure and pregnancy outcome in patients with lupus nephritis treated with intravenous cyclophosphamide pulse therapy

This study was designed to investigate the risk of ovarian failure and the pregnancy outcomes in women treated with intravenous cyclophosphamide (IVCYC) pulse therapy for lupus nephritis. Sixty-seven women with proliferative lupus nephritis were studied. The clinical and laboratory data, SLEDAI and damage indices at IVCYC initiation, doses and numbers of IVCYC pulses, pregnancy and fetal outcomes were evaluated. During a follow-up of 74.4 + 20.6 months, amenorrhea occurred in 25 (37.3%) and was sustained permanently in 10 patients (14.9%). Thirteen women became pregnant with a total of 19 pregnancies. Seventeen pregnancies ended without complications and all babies were born healthy without any congenital anomalies or perinatal illnesses. Two pregnancies were terminated by induced abortion but no congenital anomaly was noted in these cases. Logistic regression analysis showed that old age, high damage index at the initiation of IVCYC pulse therapy and high cumulative dosage of IVCYC were the independent risk factors of ovarian failure, and that the presence of amenorrhea, regardless of its duration, was the risk factor of pregnancy failure. Pregnancy was possible with a favorable outcome after the withdrawal of IVCYC pulse therapy, unless amenorrhea develops.

Adiponectin mitigates the severity of arthritis in mice with collagen‐induced arthritis

Objective: Adiponectin (AD) is considered an inflammation modulator. In this study, we investigated the effect of AD on rheumatoid arthritis (RA) using a collagen‐induced arthritis (CIA) mouse model and RA synovial fibroblasts (RASF). Methods: Fifteen DBA/1 mice were divided into three groups. All mice, except the control group, were injected with type II collagen. AD was intra‐articularly injected in the left hind legs after arthritis development (the AD‐treated group). The severity of the arthritis was measured using an arthritis score and paw thickness. A histopathological assessment of joint sections was performed by haematoxylin/eosin (H&E) staining. Tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, and matrix metalloproteinase (MMP)‐3 expression was evaluated by immunohistochemical staining in the CIA mice. Synovial tissue was obtained from four RA patients during total joint replacement. RASF cultures were established from this tissue. RASF were pretreated with AD and stimulated by TNFα or IL‐1β. TNFα, IL‐1β, IL‐6, and MMP‐3 production was measured by enzyme‐linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT‐PCR). RASF proliferation was evaluated using the MTT assay. Results: AD significantly mitigated the severity of the arthritis and histopathological findings indicative of RA in CIA mice. TNFα, IL‐1β, and MMP‐3 expression decreased, but IL‐6 expression in AD‐treated joint tissues increased. Moreover, AD reduced TNFα, IL‐1β, and MMP‐3 expression in stimulated RASF and increased IL‐6 expression in IL‐1β‐stimulated RASF. AD significantly inhibited IL‐1β‐induced RASF proliferation, despite increased IL‐6 expression. Conclusion: These data suggest that AD may play an anti‐inflammatory role in the pathophysiology of RA.

Serum leptin levels correlate with interleukin‐6 levels and disease activity in patients with ankylosing spondylitis

Objective: To determine whether serum leptin levels are elevated in men with ankylosing spondylitis (AS) and whether the levels correlate with serum cytokine profiles and disease activity of AS. Methods: Forty‐two male patients with newly diagnosed AS were enrolled. Their Bath AS Disease Activity Index (BASDAI), body mass index (BMI), and acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) levels, were assessed. Serum leptin levels were determined using radioimmunoassay (RIA) and serum cytokine profiles, including tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, and interferon (IFN)‐γ, were determined using enzyme‐linked immunosorbent assay (ELISA). These results were compared with those from 42 age‐matched healthy men. After a follow‐up period of 31.0±20.1 months, clinical and biochemical variables were reassessed in the men with AS. Results: At baseline, patients with AS had significantly elevated serum levels of leptin, leptin adjusted for BMI (leptin/BMI), TNFα, and IL‐6, but not IFN‐γ, as compared to the controls. Serum leptin/BMI levels correlated well with IL‐6 levels, and both leptin/BMI and IL‐6 levels correlated well with BASDAI and CRP levels in patients with AS. The changes in leptin/BMI and IL‐6 levels between the baseline and follow‐up measurements correlated well with one another (p<0.05) and both correlated well with the changes in BASDAI (p<0.05). Conclusion: Serum leptin/BMI levels were increased and significantly associated with IL‐6 levels and disease activity in men with AS, suggesting a possible role for leptin in the inflammatory reactions of AS.

Relationship of serum TWEAK level to cytokine level, disease activity, and response to anti‐TNF treatment in patients with rheumatoid arthritis

Objectives: To determine the serum concentration of tumour necrosis factor (TNF)‐related weak inducer of apoptosis (TWEAK) in patients with rheumatoid arthritis (RA) and to investigate the relationship between TWEAK level and disease activity, proinflammatory cytokine levels, and response to anti‐TNF treatment. Methods: Serum samples from 40 patients with RA, 40 patients with ankylosing spondylitis (AS), and 40 healthy subjects were collected. Serum samples from 26 patients with RA who received etanercept treatment were also collected in the 12th week of etanercept therapy. Serum TWEAK, TNFα, and interleukin (IL)‐6 levels were determined by enzyme‐linked immunosorbent assay (ELISA), and disease activity of RA was assessed according to the 28‐joint count Disease Activity Score (DAS28). Results: Patients with RA had significantly higher serum levels of TWEAK, TNFα, and IL‐6 compared with controls (p<0.05). Patients with AS also had significantly higher serum levels of TNFα and IL‐6 (p<0.05), but their serum TWEAK levels were not different from those of the controls. In patients with RA, serum TWEAK levels correlated with DAS28 (r2 = 0.452, p = 0.012) and TNFα levels (r2 = 0.653, p<0.001) but not with IL‐6 levels. Among RA patients who were treated with etanercept, responders showed a significant decrease in serum TWEAK levels at the 12th week of treatment, whereas TWEAK levels in nonresponders were not different from their baseline levels. Conclusions: Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short‐term response to etanercept treatment.

The role of (18) F-fluorodeoxyglucose-positron emission tomography in the assessment of disease activity in patients with takayasu arteritis.

OBJECTIVE The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. METHODS We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. RESULTS At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. CONCLUSION (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.

Relationship of bone morphogenetic proteins to disease activity and radiographic damage in patients with ankylosing spondylitis.

Objectives: To determine serum concentrations of bone morphogenetic proteins (BMPs) in patients with ankylosing spondylitis (AS) and to investigate their relationship to disease activity, spinal dysmobility, and spinal damage. Methods: Serum samples from 40 AS patients, 40 rheumatoid arthritis (RA) patients, and 40 healthy subjects were obtained, and serum BMP‐2, ‐4, and ‐7 levels were determined by enzyme‐linked immunosorbent assay (ELISA). Clinical measurements for AS patients included the Bath AS Disease Activity Index (BASDAI), Metrology Index (BASMI), and Radiographic Index (BASRI), and those for RA patients included the disease activity score (DAS) 28 and Larsen scores. Sample collections and clinical assessments were performed at baseline and after a mean follow‐up of 51.7±19.7 months. Results: At baseline, both AS and RA patients demonstrated significantly elevated serum BMP‐2 and BMP‐7 levels compared with healthy controls (p<0.05). In AS patients, baseline BMP‐2 levels correlated well with BASDAI (p<0.05), and BMP‐7 levels correlated with BASRI‐spine (p<0.05). However, no BMP levels showed significant correlation with DAS28 and Larsen scores in RA patients. The changes in BMP‐7 levels from baseline to after the follow‐up period showed a significant correlation with the changes of BASRI‐spine, but the changes in other BMPs did not show any significant relationship to the changes in clinical parameters. Conclusion: Overproduction of BMP‐2 and BMP‐7 was noted in AS patients, and serum BMP‐7 levels reflected radiographic damage observed in AS.

The efficacy of brain F-fluorodeoxyglucose positron emission tomography in neuropsychiatric lupus patients with normal brain magnetic resonance imaging findings

Brain involvement in systemic lupus erythematosus (SLE) is a significant source of morbidity and mortality. Therefore, the early detection and treatment of brain involvement in SLE is of utmost importance; however, a confirmative diagnostic tool for neuropsychiatric SLE is yet to be developed. In this study, we investigated the efficacy of 18F-FDG-PET for detection of brain involvement in patients with SLE with normal magnetic resonance imaging (MRI) findings. Twenty patients with SLE, who presented with neuropsychiatric symptoms despite normal brain MRI findings and who underwent brain 18F-FDG-PET, were enrolled. The most common neuropsychiatric manifestation was headache (45%), followed by seizure (20%) and mood disorder (20%). 18F-FDG-PET revealed significant glucose metabolic abnormalities in 15 of 20 patients (75%). The temporal (55%) and the occipital (55%) lobes were the most susceptible brain regions, followed by the frontal lobe (50%). However, neuropsychiatric symptoms were not geographically correlated to 18F-FDG-PET findings. Two patients with abnormal 18F-FDG-PET findings underwent follow-up brain 18F-FDG-PET after remission, which showed complete resolution of abnormal glucose metabolism. Our data suggest that 18F-FDG-PET may be an additional diagnostic modality complementary to MRI, when MRI is unable to provide evidence of brain involvement in patients with SLE.

Delta neutrophil index as a marker for differential diagnosis between flare and infection in febrile systemic lupus erythematosus patients

* These authors contributed equally to this work. Fever is a common symptom of systemic lupus erythematosus (SLE), and because of this it is difficult to discriminate between SLE flare and infection. The delta neutrophil index (DNI), automatically determined by the ADVIA 2120 electronic cell analyzer, has been reported to reflect the fraction of circulating immature granulocytes and to be associated with the presence of infection. In this study, we investigated the utility of DNI in discriminating infections from SLE flares in febrile SLE patients. In total, 111 episodes in 92 febrile SLE patients were reviewed. The infection group showed significantly higher white blood cell counts, neutrophil counts, C-reactive protein and procalcitonin than the SLE flare group. Complement (C)3 and C4 levels were decreased significantly in the SLE flare group. Patients in the SLE flare group had significantly lower DNI than those in both infection groups, with or without bacteremia. In a multivariate logistic regression analysis, only DNI was a significant independent factor for the presence of infection (odds ratio (OR): 18.9). When we selected a DNI value of 2.8% as the cutoff for infection, SLE patients with DNI ≥ 2.8% were found to be at higher risk for infection than those with DNI < 2.8% (relative risk 8.48-fold). Our data suggest that DNI may be a marker to differentiate infections from SLE flares in febrile SLE patients.