Serum 25-hydroxy vitamin D levels in Egyptian patients with rheumatoid arthritis: Association with disease activity,functional disability and radiological damage

Aim of the workThe aim of this study was to examine vitamin D (VD) levels and its associations with disease activity, functional disability and radiological damage in Egyptian patients with RA.Patients and methodsThis study included 150 RA patients and 150 matched controls. All participants were not receiving VD supplements. Serum 25(OH)-D levels were measured in all participants. Serum 25(OH)-D levels at 30 and 20 ng/ml were the cut-off values for VD insufficiency and deficiency, respectively. Associations of 25(OH)-D levels with disease activity score associated with C-reactive protein (DAS-28-CRP), functional disability assessed by the Health Assessment Questionnaire (HAQ) and radiological damage as assessed by the modified Larsen method were considered.ResultsLow VD levels were frequent in RA patients (22 ± 9.2 ng/ml) compared to the control (28.7 ± 9.6 ng/ml) (p < 0.001); 42.7% had VD levels <20 ng/ml and was <30 ng/ml in 80.7%. RA patients with VD deficiency were older, more frequently females and had higher swollen joint count (SJC), tender joint count, visual analogue scale for pain and DAS28-CRP. Only SJC and DAS28-CRP remained significant following the multivariate analysis (p = 0.029, p = 0.007 respectively), while rheumatoid factor, anti-cyclic citrullinated peptide antibodies, medications used, HAQ and radiologic score had no association with VD levels.ConclusionsVitamin D insufficiency and deficiency are common among Egyptian RA patients and are associated with decreased sun exposure. VD deficiency was related to older age, female gender, swollen joint count and disease activity. Vitamin D levels had no relation with RA functional disability and radiological damage.     

类风湿关节炎患者血清25羟基维生素D水平变化及其临床意义

目的 观察类风湿关节炎(RA)患者血清中25羟基维生素D[25(OH)D]水平变化,并探讨其临床意义.方法 收集130例RA患者及80名健康对照者的血清,酶联免疫法测定其25(OH)D浓度,比较RA患者25(OH)D水平的变化;同时运用双能X线吸收仪(DXA)测定RA患者骨密度,双手X线Sharp评分(SHS)评定患者骨侵蚀及狭窄程度并详细记录RA患者临床、实验室及影像学资料,计算疾病活动性.采用t检验或单因素方差分析,组间比较采用x2检验,相关性采用Pearson相关分析,危险因素分析采用多元线性回归分析和Logistic回归分析进行统计学分析.结果 ①RA患者血清25(OH)D水平较健康对照组明显降低[(17±6) ng/ml与(23±6) ng/ml,t=-6.624,P＜0.01],且RA患者25(OH)D不足者明显多于健康对照组(98.5％与87.5％,x2=26.291,P＜0.01);②25(OH)D水平分别与RA患者晨僵时间、关节压痛数(TJC)、关节肿胀数(SJC)、红细胞沉降率(ESR)、C反应蛋白(CRP)、生活质量(HAQ)评分等呈负相关(r=-0.370,-0.307,-0.243,-0.369,-0.175,-0.381,P均＜0.05);③根据DAS28评分,稳定或轻度活动组明显高于中度活动组和重度活动组的RA患者血清25(OH)D水平(P均＜0.05);线性回归分析进一步提示RA患者血清25(OH)D水平减低是疾病活动性的危险因素(b=-0.46,P=0.029);④25(OH)D水平与RA患者骨侵蚀度无相关性(P＞0.05);⑤根据骨密度分为RA骨量正常组、骨量减少组及骨质疏松组,3组间的25(OH)D水平呈依次下降趋势且相互间比较差异均有统计学意义(P＜0.05),经Logistic回归分析,RA患者血清25(OH)D是其骨质疏松的保护因素(OR=0.898,95％CI 0.830～0.972,P=0.008).结论 RA患者血清25(OH)D水平显著低下,与RA疾病活动性、骨质疏松相关;25(OH)D水平减低是RA疾病活动以及高发骨质疏松症的危险因素.     

Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis

Rheumatoid arthritis (RA) is commonly associated with decreased bone mineral density (BMD) due to numerous factors. BsmI polymorphism of the vitamin D receptor (VDR) gene has been implicated in the pathogenesis of osteoporosis. Vitamin D has several immunomodulatory effects and thus may play a role in the course of arthritis. However, little data is available on the possible relationship between RA and VDR gene polymorphisms. In this study, the frequency of BsmI polymorphism genotypes were compared with that found in other countries. In this study, 64 RA patients and 40 healthy controls were tested for VDR gene BsmI polymorphism genotypes. Frequencies of B and b alleles were associated with markers of bone metabolism and RA. Among control subjects, the frequency of the BB genotype is relatively high (27.5%). In RA with secondary osteopenia/osteoporosis the BB genotype was more rare, the bb was more common than in control subjects. Markers of bone metabolism were associated with the B allele. RA patients carrying the B allele had lower BMD and increased bone loss over 1 year. The B allele was also correlated with increased osteoclast and osteoblast function, as determined by the assessment of biochemical markers of bone metabolism. Rheumatoid factor titer, which is an independent marker for disease progression in RA, was higher in bb patients. Our data suggest, that the imbalance in B and b allele expression may be involved in the pathogenesis of RA-associated osteoporosis. The possible involvement of vitamin D and VDR gene polymorphisms in the development and progression of RA needs further elucidation.Financial support: ETT 314/96 and ETT 60/2001 grants from the Medical Research Council of Hungary (Z.S.), and FKFP 18/2000 grant from the Research and Development in Highest Education Council (Z.S.).     

Serum osteocalcin as an index of bone turnover in active rheumatoid arthritis and in active psoriatic arthritis

Summary Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05±1.27 ng/ml vs 4.83±0.88 ng/ml;p<0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.     

Clinical implications of milk fat globule-epidermal growth factor 8 (MFG-E8) and vitamin D levels in patients with rheumatoid arthritis and primary knee osteoarthritis

Aimof the work to determine serum levels of vitamin D and Milk fat globule-epidermal growth factor 8 (MFG-E8) in rheumatoid arthritis (RA) and primary knee osteoarthritis (OA) compared to healthy controls and their possible associations. Patients and methods: The study included 30 RA and 30 primary knee OA patients as well as 25 control. The  disease activity was measured by disease activity score 28 (DAS28) in RA. The functional status was estimated by Western Ontario and McMaster Universities index (WOMAC index) in OA. While the assessment of pain was measured by the visual analog scale (VAS) in both RA and OA. Serum vitamin D and MFG-E8 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: The mean age of RA patients was 41.1 ± 9.2 years; 25 females and 5 males (F:M 5:1) and a disease duration of 6.9 ± 4.6 years. The mean age of OA patients was 48.7 ± 8.3 years; 28 females and 2 males (F:M 14:1) and disease duration was 5.4 ± 3.3 years. The mean vitamin D was significantly lower in RA (9.7 ± 5.04 ng/ml) than OA (16.4 ± 4 ng/ml) and controls (17.7 ± 3.4 ng/ml), p < 0.0001. The mean MFG-E8 serum level was significantly lower in RA and OA patients (4.9 ± 2.4 ng/mland 5.3 ± 1.2 ng/ml) than in controls (9.1 ± 3 ng/ml), p < 0.0001.Vitamin D significantly correlated with MFG-E8 (r = 0.6, p = 0.002) in RA and both inversely correlated with DAS28 (r = -0.66, p < 0.0001 and r = -0.58, p < 0.0001 respectively). Vitamin D (9.7 ng/ml) and MFG-E8 (4.9 ng/ml) significantly predicted RA (p < 0.0001) at specificity (100%) and sensitivity (66.7%). MFG-E8 at cut-off 5.3 ng/ml significantly predicted OA at specificity of 88% and sensitivity 86.7%.Conclusion: An association between low serum vitamin D and MFG-E8 levels with RA and the disease activity has been determined. Low MFG-E8 was associated with OA.     

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目的探讨类风湿关节炎(RA)患者中贫血的发生率、严重程度及其与RA病情活动及治疗间的关系。方法对2002-07-2004-04在北京大学人民医院风湿免疫科住院的239例类风湿关节炎患者进行回顾性分析。结果(1)RA患者中贫血的发生率为51.4%,伴发贫血的程度为轻、中度的贫血;(2)RA贫血组患者和RA不伴发贫血组患者在病程、晨僵、血沉、C反应蛋白、双手X线分级方面的差异有显著性。(3)RA贫血患者和RA不伴发贫血患者在白细胞计数及血小板计数方面差异有显著性。(4)RA贫血患者住院前后的Hb水平存在显著性差异。结论(1)贫血是RA最常见的关节外表现之一,伴发贫血程度为轻、中度贫血。(2)RA伴发的贫血与病情活动性相关,病情活动性越高,贫血程度越重;并且贫血程度越重者,关节破坏越重,病情预后差。(3)RA贫血患者的血红蛋白水平可以随着抗风湿治疗后RA病情的好转而上升。     

Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease

AIM: To determine serum vitamin D levels and colonic vitamin D receptor(VDR) expression in inflammatory bowel disease(IBD) and non-IBD patients and correlate these with histopathology.METHODS: Puerto Rican IBD(n = 10) and non-IBD(n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis(active/inactive), and scored for the degree of inflammation present(0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale.RESULTS: The IBD cohort was significantly younger(40.40 ± 5.27, P 0.05) than the non-IBD cohort(56.70 ± 1.64) with a higher prevalence of vitamin D deficiency(40% vs 20%, respectively) and insufficiency(70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients(1.95 ± 0.25) than in normalappearing mucosa from control patients(0.25 ± 0.08, P 0.01) and from IBD patients(0.65 ± 0.36, P 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients(r =-0.44, P 0.05) and from IBD patients with Crohn's disease(r =-0.69, P 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients(r = 0.38, P 0.05) and with patient age(r = 0.54, P 0.01). CONCLUSION: Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients.     

Malnutrition in rheumatoid arthritis

Summary A nutrition study was conducted in thirty-eight hospitalized rheumatoid arthritis (RA) patients. Twenty-seven (71.1%) had a high likelihood of malnutrition (LOM). Laboratory and anthropometric data suggest that multiple vitamin, calory, and protein deficiencies are present. Age, female sex and a poor grip strength correlated with some indices of malnutrition. Fifteen of 18 patients with a high LOM had a bad outcome whereas 3 of 7 patients with a low LOM had a bad outcome. Malnutrition per se may be a contributing factor to increased morbidity and mortality in RA.     

Prevalence of decreased bone mass in rheumatoid arthritis. Relation to anti-inflammatory treatment

Summary The bone mineral content (BMC) in both forearms (highly correlated to total body calcium) was measured by photon absorptiometry in a representative sample of rheumatoid arthritis outpatients comprising 129 patients treated with either gold salts (n=29), penicillamine (n=61), prednisone (n=24), or other anti-RA drugs (n=15). The mean BMC value was 84% of normal (p<0.001) with the lowest mean value in the group treated with prednisone (73% of normal). The patients as a group had hypocalcaemia (p<0.001), raised serum alkaline phosphatase (p<0.001), and normal urinary excretion rates of calcium and hydroxyproline. These results indicate that RA patients have disturbances in their calcium and bone metabolism.     

Palmar erythema in rheumatoid arthritis

Summary Palmar erythema (liver palms) was seen in 32/100 consecutive patients with classical rheumatoid arthritis and in 10/100 patients with various other internal diseases (p<0.001). Age of the patients, sex, duration of disease, titer of rheumatoid factor, stage of disease, erythrocyte sedimentation rate and frequency of volar tenosynovitis of the hands did not differ between patients with and those without palmar erythema. Ulnar deviation of the fingers was less common and the hemoglobin content of the blood was higher in patients with palmar erythema.     

Bone mineral loss,bone histomorphometry and vitamin D metabolism in patients with rheumatoid arthritis on long-term glucocorticoid treatment

Summary Long-term glucocorticoid treatment might interfere with the vitamin D metabolism. The serum concentrations of 25-OHD were significantly reduced whereas the circulating levels of 1,25-(OH)₂D were normal in 50 patients with rheumatoid arthritis on long-term treatment with small doses of prednisone. The bone mineral content of the forearm was significantly reduced, but the degree of bone loss did not correlate with duration of treatment or dose of prednisone given. Quantitative bone histomorphometry was performed in 18 patients. Apart from a significant correlation between serum 25-OHD and the fractional trabecular bone volume, no relationships were observed between bone histomorphometry and vitamin D metabolites or serum iPTH. The results indicate that the bone loss was due to a decreased osteoblastic activity rather than to an impaired vitamin D metabolism.     

肌少症维生素D缺乏在类风湿关节炎合并糖皮质激素诱发骨质疏松中的临床研究

目的:探讨肌少症和维生素D缺乏在RA患者合并糖皮质激素诱发骨质疏松(GIOP)患者中的临床意义。方法:选2017年1月至2018年12月我院311例RA患者和158名正常健康者,并详细记录RA患者临床、实验室指标及糖皮质激素(GC)使用情况。以生物电阻抗法测四肢骨骼肌质量,化学发光法测血清25羟维生素D水平,双能X线骨密度吸收仪测腰椎和髋部骨密度(BMD)。采用χ^2检验、非参数检验、多元Logistic回归进行统计分析。结果:①RA患者OP发生率33.4%(104/311)高于对照组12.7%(20/158)(χ^2=23.267,P<0.01);311例RA患者GC使用率为56.6%(176/311),其中GIOP发生率40.9%(72/176)。RA患者中肌少症发生率61.7%(192/311)高于对照组9.0%(14/156)(χ^2=117.310,P<0.01)。RA患者维生素D缺乏发生率为81.7%(254/311)高于对照组38.0%(60/158)(χ^2=90.415,P<0.01)。②在不考虑是否使用GC的情况下,无肌少症RA患者OP发生率17.6%(21/119)低于肌少症患者OP发生率43.2%(83/192)(χ^2=21.601,P<0.01)。在未服用GC的RA中,无肌少症患者OP发生率9.8%(6/61)低于肌少症患者OP发生率35.1%(26/74)(χ^2=11.834,P<0.01);在使用GC的RA中,无肌少症RA患者OP发生率25.9%(15/58)低于肌少症患者OP发生率48.3%(57/118)(χ^2=8.103,P<0.01)。③不考虑是否存在维生素D缺乏情况下,未服用GC患者OP发生率23.7%(32/135)低于服用GC患者GIOP发生率40.9%(72/176)(χ^2=10.161,P<0.01)。在维生素D不缺乏RA中,未服用GC患者OP发生率21.4%(6/28)与服用GC患者GIOP发生率31.0%(9/29)差异无统计学意义(χ^2=0.678,P>0.05);在维生素D缺乏的RA中,未服用GC患者OP发生率24.3%(24/107)低于服用GC患者GIOP发生率42.9%(63/147)(χ^2=9.3702,P<0.01)。④在服用GC的RA中,与不发生GIOP组比,发生GIOP组患者的年龄(t=5.313,P<0.01)和Sharp评分(Z=2.999,P<0.01)更高、病程(Z=2.141,P<0.05)和GC使用时间(Z=2.460,P<0.05)更长,而ESR(Z=2.262,P<0.05)、CRP(Z=2.551,P<0.05)和BMI(t=2.425,P<0.05)更低,X线分期构成比更差(χ^2=12.484,P<0.01)。⑤多元Logistic回归显示:女性[OR(95%CI)=14.240(3.878,52.288),P<0.01]、年龄[OR(95%CI)=1.079(1.042,1.118),P<0.01]、肌少症[OR(95%CI)=1.079(1.192,5.120),P<0.05]是RA患者发生GIOP的危险因素。结论:RA患者服用GC比例约60%,GIOP发生率高达40.9%,与肌少症和维生素D缺乏密切相关。     

Protrusio acetabuli in juvenile rheumatoid arthritis

Summary Acetabular protrusion (PA) as measured by a line crossing method was studied in 73 patients with juvenile rheumatoid arthritis (JRA) and its frequency found to be 12% (9/73), presenting bilaterally in 5 cases and unilaterally in 4. All patients had some other forms of radiological damage and the presence of PA was predominantly observed in the JRA group with greater age at onset (8 vs 4.2 years; p<0.001) and lower frequency of extraarticular manifestations (22% vs 72%; p<0.01). There was no correlation with type of JRA onset, course of disease, sex, disease duration, seropositivity for rheumatoid factor, and prior steroid intake.     

IgG and IgM rheumatoid factor in active seronegative nodular rheumatoid arthritis and in children with benign rheumatoid nodules

Summary Rheumatoid nodules in rheumatoid arthritis are usually associated with high levels of IgM rheumatoid factors and aggressive disease. IgM, IgG, and C3 have been identified in tissue sections of rheumatoid nodules, suggesting pathogenetic importance. The role of IgM and IgG rheumatoid factors in sero-negative RA is poorly understood. Seven patients with active seronegative RA and rheumatoid nodules and 10 seronegative children with the syndrome of benign rheumatoid nodules were studied for the presence of IgG and IgM rheumatoid factors by radioimmunoassay and for complement-fixing IgM rheumatoid factor by haemolytic assay. Elevated titres of hidden complement fixing IgM rheumatoid factor were found in 60 % of the patients with benign rheumatoid nodules studied but in none of the patients with active seronegative nodular RA. Serum IgG and IgM rheumatoid factor levels by radioimmunoassay and circulating immune complex levels in both groups were not significantly different from normal controls. These data suggest IgG and IgM rheumatoid factors do not participate in the pathogenesis of active seronegative rheumatoid arthritis with rheumatoid nodules.     

Food allergy in patients with rheumatoid arthritis

Summary Three hundred patients of the Swiss Rheumatoid Arthritis Patient Union were asked by questionnaire whether they had any adverse reaction from food. Of the 159 replies 52 gave a positive history. Thirty-five patients could be further evaluated. Six patients, who gave the mose typical history of allergy, were investigated clinically, with laboratory tests and technetium-scintigramme after food challenge. There was no sign of an immunologic reaction in any of the measured parameters. The other patients were interviewed a second time with an extensive allergological questionnaire. None of the food intolerances could be substantiated.     

Experimental animal models resembling rheumatoid arthritis

Summary The experimental animal models of arthritis which in certain aspects share similarities to human rheumatoid arthritis are reviewed. Various methods have been applied to induce in animals experimental models of arthritis which would provide important insights into the aetiopathogenetic mechanisms of human RA. Immunological methods and infectious agents induced the most interesting models. The histology of the synovial tissue, regardless of the inducing mechanisms, is similar to the lesions of RA. Yet, none of these experimental models of arthritis reflects all the articular and systemic features, the immunological profile and the genetic factors which characterize the human disease. The animal models of arthritis reported here and the development of new ones may ultimately offer the information necessary for the understanding of the mechanisms involved in the aetiopathogenesis of human rheumatoid disease.     

Methotrexate in refractory rheumatoid arthritis

Summary Fourteen patients with severe rheumatoid arthritis refractory to hydroxychloroquine, gold-thioglucose, D-penicillamine and azathioprine completed a 6-month open study with oral methotrexate (2.5 to 5 mg every 12 hours, three doses weekly). Twelve of them were followed up for 12 months. Compared with pretreatment values, there was a significant reduction in duration of morning stiffness (p<0.01), in the number of tender or painful joints (p<0.02), number of swollen joints (p<0.01), visual analog scale, patient's assessment of joint discomfort and overall well-being (p 0.01) after 2, 6 and 12 months. Likewise there was an improvement in the erythrocyte sedimentation rate (p<0.001) C-reactive protein (p<0.01) and the levels of IgG, IgM and IgA (p<0.01). Two patients were withdrawn from the study, one for severe diarrhoea and one because of a depression. Adverse reactions during methotrexate therapy included nausea (5/16) and transaminase elevation (4/16). We conclude that this pilot study provides evidence that a weekly low dose of methotrexate is effective in the short-term treatment for patients with rheumatoid arthritis, refractory to hydroxychloroquine, auriothioglucose, D-penicillamine and azathioprine.     

Bone metabolism in patients with rheumatoid arthritis

Summary Bone metabolism in patients with rheumatoid arthritis is reviewed. Two different entities are recognised: 1) a localised periarticular bone loss, due to inflammatory processes and 2) a generalised increased bone turnover, ultimately leading to a loss of axial bone mass. The mechanism of this loss of axial bone is not completely understood; probably immobilisation is the most important factor. The influence of certain drugs is discussed.     

HLA- DR typing in 58 cases of rheumatoid arthritis

Summary The results of a previous study led us to believe that the association of HLA-DR₄ and rheumatoid arthritis could be of particular interest in our region. In this work we typed 58 caucasoid patients in the Marseilles area by microlymphocytotoxicity assay in B-cells. HLA-DR₄ was found to be at the same level as that observed by the authors in the 8^th Workshop of histocompatibility (1980) (X²: 32.36, P (0.001) and very high in the seropositive patients (61.5 per cent). No correlation with sex was observed. We again found a low frequency of HLA-DR₄ (15.8 per cent) in our controls.     

Juvenile rheumatoid arthritis: Clinical characteristics in 100 Thai patients

Summary The clinical characteristic of 100 patients diagnosed for JRA at the Department of Pediatrics, Ramathibodi Hospital, Bangkok, Thailand during 1968–1984 are reported. There were 64 male and 36 female patients with a respective ratio of 1.71. In ninety-one percent the age of onset was over the age of five, the most common type being polyarticular onset (77%) followed by pauciarticular onset (13%) and systemic onset (10%). Twenty percent had a positive rheumatoid factor and 4% had cardiac complications. Over half of the patients (58%) responded to salicylate and other supportive treatment. The overall remission was 36 percent with a mean follow-up of 3.8 years. The highest remission rate was found in the polyarticular type of onset (43%) followed by systemic onset (33%) and pauciarticular onset (23%). Only 11 percent of the patients responded poorly to the treatment. As opposed to Western reports differences occurred in the type of onset, sex, and eye complications.