甲氨蝶呤治疗银屑病关节炎的护理

回顾性总结38例应用甲氨蝶呤治疗银屑病关节炎的护理经验,认为在护理该类患者时,护理重点是使病人保持心态平和,采用科学的治疗方法,坚持长期治疗的信心和健康的生活方式,药物的正确的使用和副作用的监测观察是服用药物提高疗效的保证。     

Effect of Vitamin D on Peripheral Blood Mononuclear Cells from Patients with Psoriasis Vulgaris and Psoriatic Arthritis

BackgroundPsoriasis, a chronic skin disease with or without joint inflammation, has increased circulating proinflammatory cytokine levels. Vitamin D is involved in calcium homeostasis, bone formation, osteoclastogenesis and osteoclast activity, as well as regulation of immune response. We aimed to study osteoclast differentiation and cytokine secretion of peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris and psoriatic arthritis, in response to 1,25(OH)₂D₃.MethodsSerum levels of bone turnover markers were measured by ELISA in patients with psoriasis vulgaris and psoriatic arthritis, and healthy controls. PBMCs were isolated and cultured with or without RANKL/M-CSF and 1,25(OH)₂D₃. Osteoclast differentiation and cytokine secretion were assessed.ResultsPsoriatic arthritis patients had lower osteocalcin, as well as higher C-telopeptide of type I collagen and cathepsin K serum levels compared with psoriasis vulgaris patients and controls. RANKL/M-CSF-stimulated PBMCs from psoriatic arthritis patients produced higher proinflammatory cytokine levels and had a differential secretion profile in response to 1,25(OH)₂D₃, compared with psoriasis vulgaris and control PBMCs.ConclusionsOur data confirmed altered bone turnover in psoriatic arthritis patients, and demonstrated increased osteoclastogenic potential and proinflammatory cytokine secretion capacity of these PBMCs compared with psoriasis vulgaris and controls. 1,25(OH)₂D₃ abrogated these effects.     

血清抗角蛋白抗体谱测定对类风湿关节炎骨侵蚀的预测价值

目的：探讨血清抗角蛋白抗体谱对类风湿关节炎预后的判断价值。方法：选择早期、活动性类风湿关节炎患者82例（病程≤6个月）,分为病例组（抗角蛋白抗体谱阳性组,n=39）和对照组（抗角蛋白抗体谱阴性组,n=43）,均给予相同的治疗方案,在治疗前、治疗后12个月、治疗后24个月分别记录全部患者的关节肿胀数、关节压痛数、晨僵时间和红细胞沉降率的变化,通过治疗前及治疗后24个月分别记录手足X线正位片、Sharp评分和DAS28评分标准进行评价。结果：治疗12个月后病例组临床指标的改善较对照组差（P〈0.01）;24个月后病例组X线分期变化情况进展明显大于对照组（P〈0.01）。结论：抗角蛋白抗体阳性谱患者的临床指标和影像学变化情况较抗角蛋白抗体谱阴性患者对治疗的反应较差,更易发生关节破坏。     

A Comparison of Disease Burden in Rheumatoid Arthritis,Psoriatic Arthritis and Axial Spondyloarthritis

Objective

The main objective of this study was to compare disease burden in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA).

Methods

In this cross-sectional study, all the RA (1093), PsA (365) and ax-SpA (333) patients who visited the out-patient clinic of the Hospital of Southern Norway Trust during the year 2013 were included; the RA patients all had a RA diagnosis verified by the treating rheumatologist, the PsA patients all fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria and the ax-SpA patients all fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for ax-SpA. Patient-reported health status, demographic variables, medications, and composite scores of disease activity were assessed. The main analyses were performed using General Linear Models adjusted for age, sex and multiple comparisons. Correlation analyses were performed using Spearman’s rho.

Results

The reported pain, joint pain, patient’s global assessment and fatigue were similar in PsA and ax-SpA, but significantly lower in RA. The 28-joint Disease Activity Score (DAS28) (0.3±0.1, p = 0.003), Clinical Disease Activity Index (CDAI) (1.0±0.4, p = 0.028) and Routine Assessment of Patient Index Data 3 (RAPID3) (0.4±0.1, p = 0.004) were all significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation with DAS28 (rho = 0.521, p<0.001) and CDAI (rho = 0.768, p<0.001) in RA and PsA, and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (rho = 0.902, p<0.001) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.865, p<0.001) in ax-SpA and PsA.

Conclusion

In conclusion, patient- reported outcome measures were similar in our population of PsA and ax-SpA patients, but significantly lower for the RA patients. Composite disease activity measures were lower in RA than in PsA and ax-SpA, but the magnitude of these differences was small and probably not of clinical significance. Our study indicates that disease burden in RA, PsA and ax-SpA may be more similar than previously demonstrated.     

Age-Related Differences in Collagen-Induced Arthritis: Clinical and Imaging Correlations

Arthritis is among the most common chronic diseases in both children and adults. Although intraarticular inflammation is the feature common among all patients with chronic arthritis there are, in addition to age at onset, clinical characteristics that further distinguish the disease in pediatric and adult populations. In this study, we aimed to demonstrate the utility of microCT (µCT) and ultrasonography in characterizing pathologic age-related differences in a collagen-induced arthritis (CIA) rat model. Juvenile (35 d old) and young adult (91 d old) male Wistar rats were immunized with bovine type II collagen and incomplete Freund adjuvant to induce polyarthritis. Naïve male Wistar rats served as controls. All paws were scored on a scale of 0 (normal paw) to 4 (disuse of paw). Rats were euthanized at 14 d after the onset of arthritis and the hindpaws imaged by µCT and ultrasonography. Young adult rats had more severe signs of arthritis than did their juvenile counterparts. Imaging demonstrated that young adult CIA rats exhibited more widespread and severe skeletal lesions of the phalanges, metatarsals, and tarsal bones, whereas juvenile CIA rats had more localized and less proliferative and osteolytic damage that was confined predominantly to the phalanges and metatarsals. This report demonstrates the utility of imaging modalities to compare juvenile and young adult rats with CIA and provides evidence that disease characteristics and progression differ between the 2 age groups. Our observations indicate that the CIA model could help discern age-related pathologic processes in inflammatory joint diseases.Abbreviations: μCT, microCT, CIA, collagen-induced arthritisArthritis is among the most common diseases in both children and adults. In children, growth, hormonal changes, and neuroimmune responsiveness and plasticity might confer influences on arthritic processes not seen in adults. Age-dependent outcomes have been demonstrated by using animal models of osteoarthritis;^5,6,11 however, there is limited information about how pathogenic processes vary among different age groups with experimental inflammatory arthritis in general^7,10 and in the collagen-induced arthritis (CIA) model of arthritis in particular.⁸ Studying and comparing features of the CIA model in growing compared with mature rats can be undertaken in ways that are not possible in humans and could help to understand age-related pathologic differences in children and adults with inflammatory joint diseases. Therefore, we undertook to compare clinical and imaging features of CIA in juvenile (growing) compared with young adult (mature) rats.In some animal models, collagen immunization results in a monophasic, polyarticular, inflammatory arthritis that is mediated by an autoimmune response¹⁴ and that is histopathologically similar to rheumatoid arthritis.^3,9,13 CIA predominantly affects the peripheral appendicular joints and is characterized by intense synovitis and pannus formation, with consequent erosions of cartilage and subchondral bone.^12,15Here we report that juvenile and young adult rats differ in their clinical responses to collagen immunization and that, according to findings from microCT (µCT) and ultrasonography, juvenile and young adult rats differ in their responses to collagen immunization with regard to disease pathology.     

Soluble Biomarkers of Cartilage and Bone Metabolism in Early Proof of Concept Trials in Psoriatic Arthritis: Effects of Adalimumab Versus Placebo

Background

There is growing interest in soluble biomarkers that could be used on the group level for screening purposes in small proof of principle studies during early drug development. We investigated early changes in serum levels of several candidate biomarkers involved in cartilage and bone metabolism following the initiation of adalimumab as a prototypic active treatment in psoriatic arthritis (PsA) compared to placebo.

Materials and Methods

Twenty-four PsA patients were randomized to receive either adalimumab 40 mg s.c. every other week or placebo for 4 weeks, followed by an open label extension phase. Serum samples were obtained at baseline and after 4 and 12 weeks of treatment and analyzed for levels of CPII and PINP (synthesis of type II and type I procollagen), melanoma inhibitory activity (MIA) (chondrocyte anabolism), matrix metalloproteinase (MMP)-3, C2C and cartilage oligomeric matrix protein (COMP) (type II collagen degradation), osteocalcin (OC) (bone formation), NTX-I and ICTP (both type I collagen degradation).

Results

After 4 weeks, there was a significant decrease in serum MMP-3 levels in adalimumab-treated patients (P<0.005), while no change was observed in the placebo group. A significant increase in serum MIA was noted after adalimumab therapy (P<0.005) but not after placebo treatment. After 12 weeks, there was a marked reduction in serum MMP-3 in both groups (P<0.005), whereas other markers did not show significant changes compared to baseline.

Conclusion

MMP-3 and MIA could serve as soluble biomarkers associated with inflammation as well as joint remodelling and destruction and may, together with clinical evaluation and in combination with other biomarkers, assist in distinguishing between effective and ineffective therapy in small, proof-of-principle studies of short duration in PsA.

Trial Registration

Current Controlled Trials ISRCTN23328456     

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis:A Systematic Review

Psoriasis(Ps)and psoriatic arthritis(Ps A)are genetically complex diseases with strong genetic evidence.Recently,susceptibility genes for Ps and Ps A have been identified within the late cornified envelop(LCE)gene cluster,especially the cluster 3(LCE3)genes.It is noteworthy that the deletion of LCE3B and LCE3C(LCE3C_LCE3B-del)is significantly associated with these two diseases.Gene-gene interactions between LCE3 genes and other genes are associated with Ps and Ps A.LCE3 genes also have pleiotropic effect on some autoimmune diseases,such as rheumatoid arthritis,atopic dermatitis and systemic lupus erythematosus.Further studies need to focus on the potential function of LCE3 genes in the pathogenesis of Ps and Ps A in the future.     

Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10^-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors.     

Crossreactive Autoantibodies Directed against Cutaneous and Joint Antigens Are Present in Psoriatic Arthritis

Background

Psoriatic arthritis (PsA) is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA.

Methods

We used pooled IgG immunoglobulins derived from 30 patients with PsA to screen a random peptide library in order to identify disease relevant autoantigen peptides.

Results

Among the selected peptides, one was recognised by nearly all the patients’ sera. The identified peptide (PsA peptide: TNRRGRGSPGAL) shows sequence similarities with skin autoantigens, such as fibrillin 3, a constituent of actin microfibrils, desmocollin 3, a constituent of the desmosomes and keratin 78, a component of epithelial cytoskeleton. Interestingly the PsA peptide shares homology with the nebulin-related anchoring protein (N-RAP), a protein localized in the enthesis (point of insertion of a tendon or ligament to the bone), which represents the first affected site during early PsA. Antibodies affinity purified against the PsA peptide recognize fibrillin, desmocollin, keratin and N-RAP. Moreover antibodies directed against the PsA peptide are detectable in 85% of PsA patients. Such antibodies are not present in healthy donors and are present in 13/100 patients with seroposive rheumatoid arthritis (RA). In seronegative RA these antibodies are detectable only in 3/100 patients.

Conclusions

Our results indicate that PsA is characterized by the presence of serum autoantibodies crossreacting with an epitope shared by skin and joint antigens.     

Adipokines and the Right Ventricle: The MESA-RV Study

Objective

Obesity is associated with changes in both right (RV) and left (LV) ventricular morphology, but the biological basis of this finding is not well established. We examined whether adipokine levels were associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.

Methods

We examined relationships of leptin, resistin, TNF-α, and adiponectin with RV morphology and function (from cardiac MRI) in participants (n = 1,267) free of clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25^th and 75^th] and generalized additive models [GAM]) were used to examine the independent association of each adipokine with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF).

Results

Higher leptin levels were associated with significantly lower levels of RV mass, RVEDV, RVESV and stroke volume, but not RVEF, after adjustment for age, gender, race, height and weight. These associations were somewhat attenuated but still significant after adjustment for traditional risk factors and covariates, and were completely attenuated when correcting for the respective LV measures. There were no significant interactions of age, gender, or race/ethnicity on the relationship between the four adipokines and RV structure or function.

Conclusions

Leptin levels are associated with favorable RV morphology in a multi-ethnic population free of cardiovascular disease, however these associations may be explained by a yet to be understood bi-ventricular process as this association was no longer present after adjustment for LV values. These findings complement the associations previously shown between adipokines and LV structure and function in both healthy and diseased patients. The mechanisms linking adipokines to healthy cardiovascular function require further investigation.     

不稳定心绞痛患者超敏C 反应蛋白水平与病变血管支数的关系

目的:探讨超敏c反应蛋白(hs-CRP)水平对于不稳定心绞痛(UA)患者多支血管病变的诊断价值。方法:回顾性选取不稳定心绞痛患者据其动脉造影结果分为单支病变组、多支病变组均行超敏c反应蛋白检测并比较两组的差异,在阳性结果基础上行ROC曲线分析。结果:1.单支病变组、多支病变组hs-CRP存在显著差异;2.ROC曲线下面积>0.5。结论:针对于不稳定心绞痛患者其超敏c反应蛋白水平与病变血管支数关系密切,对于临床诊断有一定价值。     

枸橼酸托法替布片联合仙灵骨葆胶囊对类风湿性关节炎合并骨质疏松患者血清炎症细胞因子、骨强度及骨代谢水平影响

摘要 目的：探讨枸橼酸托法替布片联合仙灵骨葆胶囊对类风湿性关节炎（RA）合并骨质疏松患者血清炎症细胞因子、骨强度及骨代谢水平影响。方法：纳入2021年8月至2022年8月期间徐州医科大学附属连云港医院诊治的80例RA合并骨质疏松患者。根据随机数字表法将患者分为对照组（雷公藤多苷片联合仙灵骨葆胶囊治疗）和实验组（枸橼酸托法替布片联合仙灵骨葆胶囊治疗）,各为40例。对比两组疗效、炎症细胞因子、骨强度及骨代谢指标,观察两组不良反应发生率。结果：实验组的临床总有效率高于对照组（P<0.05）。实验组治疗后巨噬细胞集落刺激因子（M-CSF）、白细胞介素-1β（IL-1β）、环氧合酶-2（COX-2）低于对照组同期（P<0.05）。实验组治疗后横截面积（CSA）、横截面转动惯量（CSMI）、截面系数（Z）、皮质厚度（CT）高于对照组同期（P<0.05）。实验组治疗后骨钙素N端中分子（N-MID）、总Ⅰ型胶原氨基端延长肽（T-PINP）、骨钙素（BGP）、Ⅰ型胶原羧基端前肽（PICP）高于对照组同期,β-胶原降解产物（β-CTX）低于对照组同期（P<0.05）。两组治疗后腰椎骨密度和股骨颈骨密度较治疗前升高,且实验组高于对照组同期（P<0.05）。两组治疗后血沉（ESR）、C反应蛋白（CRP）、类风湿关节炎患者病情（DAS28）评分下降,且实验组低于对照组同期（P<0.05）。两组不良反应发生率组间对比无统计学差异（P>0.05）。结论：枸橼酸托法替布片联合仙灵骨葆胶囊应用于RA合并骨质疏松患者,可有效调节骨代谢水平,增强骨强度,降低血清炎症细胞因子水平。     

The Risk of Metabolic Syndrome in Patients with Rheumatoid Arthritis: A Meta-Analysis of Observational Studies

Background

Observational studies suggest an association between the incidence of rheumatoid arthritis (RA) and the prevalence of metabolic syndrome (MetS). However, the relationship between RA and MetS is controversial and research in this area is currently lacking.

Objective

The aim of this study was to assess whether the prevalence of MetS was higher in a group of RA patients compared to subjects without RA.

Design

A PubMed database search was conducted during April 2013 to identify observational studies of RA and risk of MetS. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments, and the method used to control for potential confounding factors. A random-effects model was used for the risk estimates.

Results

Our meta-analysis of four cross-sectional controlled studies plus eight case-control studies involving a total of 2283 cases and 4403 controls identified a significant association between RA and risk of MetS, with an overall OR of 1.24 (95% CI, 1.03-1.50).

Conclusion

This meta-analysis provides further evidence supporting patients with RA have a higher prevalence of MetS than subjects without RA. In addition, the geographic region of the population and the criteria used for MetS diagnosis could influence the association. However, these observations would need to be evaluated using prospective, randomized studies.