Infection is one of the serious complications seen in the management of RA patients. The acute inflammatory marker C-reactive protein (CRP) is elevated both during infection and during high disease activity of RA, and this often poses a problem when distinguishing the two. The soluble CD14 subtype, presepsin has been reported to be a novel effective marker for the diagnosis of sepsis but has not been evaluated in RA patients.
Objectives
To evaluate the use of presepsin in RA patients during an infectious event.
Methods
25 RA patients with infections, 21 RA patients with high disease activity, 23 healthy controls (HC) were enrolled in this study. RA patients in whom the pathogens were identified (22 bacterias, 2 viruses, and 1 M. tuberculosis) were designated as the infection RA group (iRA), high disease activity RA patients without infection were designated as the flare RA group (fRA). Presepsin was measured using a chemiluminescent enzyme immunoassay. CRP and procalcitonin (PCT) were also measured. RA disease activity was evaluated using DAS28-CRP. Levels of respective measurements at both pre- and post-treatment were analyzed using the Wilcoxon signed-rank test, and comparisons of levels within each group were analyzed using the Mann-Whitney's U-test. Additionally, Spearman's rank correlation coefficient was used to analyze the correlation of levels of presepsin, CRP, and PCT in iRA and correlation of presepsin, DAS28-CRP, and CRP in fRA. Further, AUC was obtained from the ROC analysis. Treatment for iRA included antibiotics, antivirals, and treatment for fRA included corticosteroids, DMARDs, and biologics.
Results
In fRA, average level of CRP was 2.4±2.1mg/dl, DAS28-CRP was 4.2±1.31. At pre-treatment, levels of presepsin in iRA (2088.4±4243.7pg/ml) was significantly higher compared to in fRA (319.3±321.8pg/ml, p<0.01). Both levels were significantly higher compared to those in HC (136±57.0pg/ml). In iRA, presepsin level correlated with CRP (r=0.65, p<0.01) and PCT (r=0.48, p<0.05). In fRA, presepsin level did not correlate with CRP or DAS28-CRP. After treatment, levels of prepsin (p<0.001), CRP (p<0.001), and PCT (p<0.001) were significant decreased in iRA. On the other hand, in fRA, CRP (p<0.001) and DAS28-CRP (p<0.001) were significantly decreased after treatment, however presepsin level showed no significant change (p=0.37). Furthermore, presepsin levels in fRA with low disase activity after treatment were significantly higher compared to those in HC (p<0.01). ROC analysis of iRA showed that AUC levels for presepsin was 0.817, indicating the efficacy of presepsin for diagnosis of infection in RA.
Conclusions
Presepsin is an effective diagnostic marker for infection in RA patients.
References
Y. Yaegashi, et al., J Infect Chemother 2005;11:234-238 T. Shozushima, et al., J Infect Chemother 2011;17:764-769
A 72-year-old man presented with persistent oligoarthritis and positive results for rheumatoid factor and was suspected of having rheumatoid arthritis (RA). However, the musculoskeletal ultrasonography (MSUS) findings were not consistent with those of typical RA. He had undergone surgery for carpal tunnel syndrome, which allowed both histopathological and microbiological examinations to be performed. A synovial tissue culture was positive for Sporothrix schenckii, and he was diagnosed with sporotrichal tenosynovitis. He received anti-fungal therapy, and the sporotrichal tenosynovitis resolved. This case suggests that MSUS is a useful modality, and sporotrichal tenosynovitis, though rare, should be considered in the differential diagnosis of RA.
Conclusion: Using Fine-Gray proportional hazard regression, we demonstrated that RF positivity was related to a higher discontinuation rate of TNFi therapy due to ineffectiveness in bio-naïve RA patients.
Infection is a critical complication that occurs during the management of RA patients. High levels of serum C-reactive protein (CRP), is not easily distinguishable between the exacerbations of RA from infections. PTX3 is a novel biomarker which responds to local inflammation. The following study evaluates the diagnostic use of PTX3 in RA patients with high levels of CRP.
Objectives
To evaluate the diagnostic use of PTX3 in RA patients with high levels of CRP.
Methods
18 RA patients with infections (infection RA: iRA), 20 with high disease activity of RA (flare RA: fRA) and 23 healthy controls (HC) were enrolled in this study. Patients whom pathogens were identified were designated as iRA (15 bacterial, 2 viral and 1 mycosis). We measured PTX3, CRP, procalcitonin (PCT) and neutrophil CD64 (nCD64), pre- and post-treatments (iRA and fRA) and at any time (HC). PTX3 levels were measured using an enzyme-linked immunoabsorbent assay (ELISA). mCD64 was measured by a quantitative flow cytometry using fluorescene microbeads. Levels of respective measurements at both pre- and post-treatment were analyzed using the Wilcoxon signed-rank test, and comparisons of levels within each group were analyzed using the Mann-Whitney9s U-test.
Results
At pre-treatment, levels of PTX3 in iRA (15.1±20.7 ng/ml) are significantly higher compared with those in fRA (3.6±4.2 ng/ml). Both levels for iRA and fRA were significantly higher compared with those in HC (0.89±0.91 ng/ml). Additionally, levels of PCT (0.048±0.042 ng/ml) and nCD64 (1488±470 molecules per cell) at pre-treatment in fRA were <0.5 ng/ml and <2,000 molecules per cell, respectively. After treatment, levels of PTX3 (p<0.01), CRP (p<0.01), PCT (p<0.01), nCD64 (p<0.01) were significantly decreased in iRA. In fRA, CRP (p<0.01), PCT (p<0.01), nCD64 (p=0.02) were significantly decreased after treatment, but PTX3 levels were not (p=0.13).
Conclusions
Plasma PTX3 levels may be a helpful tool in distinguishing worsening of RA from complications due to infection.
To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers.The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year.The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P < 0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P < 0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P < 0.001). The safety issues were comparable between the two groups.This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.
Lupus nephritis (LN) is one of the most serious clinical manifestations of systemic lupus erythematosus (SLE). Recently, we have reported that the expression levels of CD64 on monocyte (mCD64), a high-affinity receptor for IgG (FcgRI), correlate with the disease activity of SLE (Lupus 2015;24:1076–80). However, the relation between lupus nephritis (LN) and mCD64 expression is yet to be elucidated. The aim of this study is to investigate whether or not mCD64 expression level correlates with the activity of LN.
Methods
We quantitatively measured the mCD64 expression levels by flow cytometry in eight SLE patients with biopsy proven LN before and after treatment. All patients fulfilled the 1997 American College of Rheumatology classification criteria for SLE. The mCD64 expression levels of the individual patients were measured both at active (presence of proteinuria >0.5 g/day and/or active urinary sediment) and inactive phase (absence of proteinuria and active urinary sediment). The changes were analysed statistically (Wilcoxon signed-rank test).
Results
The mean±SD of mCD64 expression levels before and after treatment were 42 463±15 466 and 19 190±1696 molecules/cell, respectively (p<0.01, Wilcoxon signed-rank test). The mCD64 expression levels in active LN was significantly higher than in inactive LN.
Conclusions
The mCD64 expression level correlates with the activity of LN, although a larger scale study is needed to confirm the results.
Hemophagocytic lymphohistiocytosis associated with autoimmune diseases is seen in patients with systemic juvenile idiopathic arthritis, adult-onset Still's disease, and systemic lupus erythematosus, whereas it is rarely seen in patients with dermatomyositis. In addition, central nervous system involvement with dermatomyositis is rare. To the best of our knowledge, this is the first case of hemophagocytic lymphohistiocytosis complicated by leukoencephalopathy in a patient with dermatomyositis accompanied with peripheral T-cell lymphoma. A 17-year-old Asian male adolescent with dermatomyositis and hemophagocytic lymphohistiocytosis that were controlled with corticosteroid therapy presented to our hospital with high fever and altered consciousness. Brain magnetic resonance imaging revealed multiple cerebral lesions. We diagnosed the central nervous system lesions as leukoencephalopathy secondary to dermatomyositis and hemophagocytic lymphohistiocytosis. Because corticosteroid and cyclophosphamide pulse therapy was ineffective, he was treated with a modified hemophagocytic lymphohistiocytosis-2004 protocol, which resulted in the disappearance of the lesions of his central nervous system. Our findings suggest that the hemophagocytic lymphohistiocytosis-2004 protocol including etoposide should be initiated immediately in patients with hemophagocytic lymphohistiocytosis who respond poorly to treatment for the underlying disease. Moreover, irrespective of the underlying disease, patients with hemophagocytic lymphohistiocytosis with central nervous system lesions might require bone marrow transplantation.
RA patients are prone to ulnar deviation and swan-neck deformity even early after onset of the disease. Limitation of finger joint range of motion due to hand-finger deformation brings restriction to ADL in the workplace as well as in the home. Patients and caretakers of patients are often burdened by these limitations; however, RA hand-finger deformation experience equipment have not been developed to experience these limitations. We have developed a novel RA hand-finger deformation experience equipment with opened fingertips (RSE; RA hand/finger simulation equipment).
Objectives
To assess the utilisation of RSE in healthy volunteers (HV) to experience RA hand-finger dysfunction using DASH (Disabilities of the Arm, Shoulder and Hand), STEF (Simple Test for Evaluating Hand Function), and Purdue Pegboard.
Methods
We developed the following equipment: Type U to imitate extension limitation of metacarpophalangeal (MCP) joints seen in ulnar deviation; Type B which imitates flexion deformity of the distal interphalangeal (DIP) joints by seen in boutonniere deformity; and Type S which imitates flexion limitation of proximal interphalangeal (PIP) and interphalangeal (IP) joints by reversing the upper and lower ends of the Oval-8 Finger Splint (Fukui Co. Ltd, Japan). Types U and S were fitted on HV (index to pinky). RSE was evaluated using DASH, STEF and Purdue Pegboard in hand-finger function evaluation. Twenty-four RA patients with hand-finger deformation and Forty-one HV were included in this study to evaluate the equipment.
Results
Mean ±SD ages for RA patients was 67.4±8.0 years (95.8% female) and 38.2±17.7 for HV (63.4% female), respectively. Total hand-finger deformities for RA patients were 23 hands for ulnar deviation, 66 fingers for swan-neck deformity, and 33 fingers for boutonniere deformity. Randomization for RA patients was as follows: 13 DASH, 5 (10 hands) STEF, and 6 Purdue Pegboard. 10 HV were assigned to DASH, 10 to Purdue Pegboard, and 14 (28 hands) to STEF. HV were evaluated with RSE and without RSE. For DASH, STEF, and Purdue Pegboard, RA patients showed significant functional loss compared to HV. Significant function loss in RA patients was also observed with the RSE. However, no differences were seen between the RA group and the HV with RSE group (figure 1).
Conclusions
We developed the RSE, which allows for one to experience the decrease in function with RA hand-finger deformity. Our study showed that RSE use can indeed allow this experience. By using RSE, health care workers, patient caretakers and early RA patients can experience joint limitation of RA for educational purposes, personalised rehab programs, and development of self-help tools.
