exudates and Arthritis--Rheumatoid

The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations.. A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations.. The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)).. Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests additional association with a PADI2 gene. The study thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to RA development in multiple populations of Asian descent.

Topics: Adult; Arthritis, Rheumatoid; Asian People; Autoantibodies; Case-Control Studies; China; Enzyme-Linked Immunosorbent Assay; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Hydrolases; Malaysia; Male; Middle Aged; Polymorphism, Single Nucleotide; Protein-Arginine Deiminase Type 2; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent.. A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated.. In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA.. The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.

Topics: Adult; Arthritis, Rheumatoid; Autoantibodies; Case-Control Studies; Citrulline; Epitopes; Female; HLA-DRB1 Chains; Humans; Malaysia; Male; Middle Aged; Smoking

Methotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (N

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Malaysia; Metabolic Networks and Pathways; Methotrexate; Polymorphism, Single Nucleotide

Patients with rheumatoid arthritis (RA) experience a higher prevalence of periodontitis. This study aimed to examine the variation of periodontitis experienced with different serotypes suffered by RA patients and to examine the relationship between the different medications taken for RA that may influence this relationship. Two hundred and sixty RA and control participants underwent standardized periodontal examinations. Medical, serological and radiological (Sharp/van der Heijde) records were assessed. Functional status was assessed using the administered Health Assessment Questionnaire. Moreover, disease parameters, including disease activity (DAS28-ESR) and anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) seropositivity were evaluated. Periodontitis was higher in RA (71.54%) compared with controls (54.62%). The stage of periodontitis experienced by ACPA-positive participants were higher than APCA-negative participants. The probing pocket depth and recession experienced by RF-positive participants were higher than those who were RF-negative. RA participants on methotrexate had lower clinical attachment loss and lower periodontal probing depth compared with participants on a combination methotrexate and other disease-modifying antirheumatic drugs. Participants taking corticosteroids had lower gingival index scores. The association between seropositivity and the type of medications taken with periodontal health parameters in this group of patients suggests that both seropositivity and medications taken are important modifiers in the relationship between periodontitis and RA.

Topics: Anti-Citrullinated Protein Antibodies; Antirheumatic Agents; Arthritis, Rheumatoid; Case-Control Studies; Female; Humans; Malaysia; Male; Methotrexate; Middle Aged; Osteoarthritis; Periodontitis; Serogroup

Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder characterised by symmetrical polyarthritis which leads to damage of joints if untreated. Early diagnosis and treatment of RA to achieve tight control of the disease will improve outcome and prevent disability.. We aimed to examine the delays in the diagnosis of RA in patients presenting to the Rheumatology Unit, Sarawak General Hospital (SGH).. Data on demographics and various delays were collected from the medical records from January 2015 until March 2018. Patient delay is defined as from the time onset of symptom to the first primary care presentation. Primary care delay is defined as from the first primary care presentation to referral to rheumatology. Rheumatology delay is defined as from rheumatology referral to appointment at the rheumatology clinic. Disease modifying anti-rheumatic drugs (DMARDS) delay is defined as from the rheumatology clinic appointment to starting DMARDS. Total delay is from symptom onset to starting DMARDS.. There were 84 new patients diagnosed with rheumatoid arthritis, out of which 66 were females (78.6%). The mean age was 54.1±12.0 years. Only 19 patients (22.6%) were treated with DMARDS within 12 weeks of symptom onset. The median time for patient delay was four weeks (Interquartile range (IQR) 2-20 weeks), while the median time primary care delay was 11 weeks (IQR 4-24 weeks). The median time for rheumatology delay was zero weeks (IQR 0- 1 week) and the DMARDS delay was zero week (IQR 0). The median time from symptom onset to DMARDS initiation was 23.5 weeks (IQR 13.25-51 weeks).. The delays in the diagnosis of rheumatoid arthritis were mainly from the patient and primary care.

Topics: Aged; Arthritis, Rheumatoid; Delayed Diagnosis; Female; Hospitals; Humans; Malaysia; Male; Medical Audit; Middle Aged

Fatigue is an important yet infrequently evaluated component in patients with rheumatoid arthritis (RA) and may have a major impact on quality of life.. To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients.. A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities).. A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P < .02).. Fatigue was associated with functional disability and has a significant impact on HRQoL in RA. Fatigue assessment should be considered in routine clinical practice for RA patients.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Blood Sedimentation; Cross-Sectional Studies; Disability Evaluation; Fatigue; Female; Humans; Malaysia; Male; Middle Aged; Pain Measurement; Predictive Value of Tests; Quality of Life; Surveys and Questionnaires

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of the joints with the involvement of other systems. Previous studies have demonstrated its association with chronic periodontitis (CP), a chronic inflammatory disease of tooth-supporting tissues. Positive rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) in RA patients have been found to be associated with CP. The aim of this study is to determine the prevalence of CP in RA patients, and to investigate the association of ACPA, RF status and RA disease activity with CP and non-CP RA patients.. A comparative cross-sectional study involving 98 RA patients was conducted at Hospital Universiti Sains Malaysia, Kubang Kerian, Malaysia. Clinical oral examination was carried out to determine the CP status of RA patients. RF, ACPA and erythrocyte sedimentation rate (ESR) were measured, and the 28-joint Disease Activity Score (DAS-28) was assessed.. Forty-five patients (45.9%) were found to have CP (95% CI: 0.36-0.56). No significant difference was observed in the prevalence of positive RF (p=0.989) or ACPA (p=0.431) in CP and non-CP RA patients. There was also no significant association between active RA disease (DAS-28 score ≥3.2) and RF positivity in CP (p=0.927) and non-CP (p=0.431) RA patients as well as ACPA positivity in CP (p=0.780) and non-CP (p=0.611) RA patients.. In our cohort of RA patients, we did not find significant associations between elevated RF, ACPA, or active RA disease with the presence of CP. There were also no significant associations between elevated RF or ACPA with active RA disease.

Topics: Adult; Aged; Aged, 80 and over; Anti-Citrullinated Protein Antibodies; Arthritis, Rheumatoid; Chronic Periodontitis; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Middle Aged; Rheumatoid Factor

Vitamin D. One hundred RA patients and 50 healthy controls, sex- and age-matched, were recruited. Disease Activity Score of 28 joints and Health Assessment Questionnaire scores were assessed. Baseline serum 25(OH)D. Vitamin D deficiency (<50 nmol/L) was found in 63% of RA patients and 76% of healthy controls. Chinese RA patients and healthy controls had significantly more sufficient 25(OH)D. Vitamin D deficiency is prevalent in Malaysian RA patients. This study suggests that vitamin D is not associated with disease activity or serum IL-6 levels but it may have a role in functional disability in RA patients.

Topics: Adult; Arthritis, Rheumatoid; Biomarkers; Calcifediol; Case-Control Studies; Cross-Sectional Studies; Disability Evaluation; Female; Humans; Interleukin-6; Malaysia; Male; Middle Aged; Prevalence; Prospective Studies; Vitamin D Deficiency

Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body. RA can lead to destruction of bone and cartilage which may cause severe disability and it is characterized by the presence of serum rheumatoid factor (RF). The anti-cyclic citrullinate peptide (anti-CCP) antibody is another serum biomarker used in RA diagnosis with higher sensitivity and specificity.In this cross-sectional study with retrospective record review, 159 established RA patients from Hospital Universiti Sains Malaysia (HUSM) were recruited. Enzyme-linked immunosorbent assays (ELISAs) for serum RF and anti-CCP were performed. Our goal was to evaluate the significance of anti-CCP antibody in predicting the disease activity and progression in terms of radiological and extra-articular manifestations upon diagnosis.Of the 159 RA patients included in this study, mean age was 48.3 years old and majority (n = 134; 84.3%) were female. A total of 83 (52.2%) and 99 (62.3%) patients had anti-CCP antibody and RF, respectively. Mean Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (ESR) (DAS28-ESR) score for all patients was 4.74 (medium and high disease activity). Fifty-eight (36.5%) patients had radiological defects and 49 (30.8%) patients had extra-articular involvement manifested by rheumatoid nodule, pulmonary involvement, and anemia.In terms of anti-CCP antibody association with clinical and laboratory parameters, a significant co-occurrence of RF and anti-CCP antibody (P = .002) was observed. Anti-CCP antibody was significantly associated with radiological defects in which majority of patients with such defects (n = 40/58; 68.9%) were positive for anti-CCP antibody (P = .001). However, there was no significant difference between mean and classes of disease activity score and extra-articular manifestations between different anti-CCP antibody groups. In addition, extra-articular manifestations were not associated with high disease activity upon RA diagnosisThere was a significant association between anti-CCP antibody positivity and positive RF. Radiological defects were the sole clinical parameter significantly associated with anti-CCP antibody positivity, indicating that patients positive for anti-CCP antibody should be routinely monitored for radiological defects and their onset.

Topics: Adult; Age Factors; Age of Onset; Anti-Citrullinated Protein Antibodies; Arthritis, Rheumatoid; Biomarkers; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Malaysia; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Rheumatoid Factor; Severity of Illness Index; Sex Factors

To determine the prevalence, correlates and independent predictors of self-reported depression, anxiety and stress in Rheumatoid arthritis (RA) patients in Hospital Melaka.. This was a cross-sectional survey using convenient sampling of 192 RA patients who attended the Rheumatology Clinic outpatient appointment, Hospital Melaka from June 2013 to December 2013. Depression, Anxiety and Stress Scale (DASS21) questionnaire was used to evaluate symptoms of depression, anxiety and stress. RA disease activity was assessed using the DAS28-ESR formula. Functional status was assessed via the Health Assessment Questionnaire Disability Index (HAQ-DI).. Out of 189 completed questionnaires, 46%(n=86) patients reported psychological distress symptoms, and 25%(n=48) experienced more than one negative emotional states. The prevalence of depression, anxiety and stress among our patients were 23.3%(n=44), 42.3%(n=80) and 20.1%(n=38) respectively. There were significant positive correlations (p<0.05) between these psychological symptoms with disease activity, number of tender joints, general health, pain and HAQ score. Age was inversely correlated with depression, anxiety and stress. Higher number of swollen joints correlated positively with depression but not with anxiety and stress. HAQ was the only independent predictor for depression (Odds Ratio [OR]=2.07; 95%CI: 1.19 to 3.61) and anxiety (OR=1.81; 95%CI: 1.1 to 3.0) whilst pain was found to be independent predictor for stress (OR=1.04; 95%CI: 1.0 to 1.1).. The incidence of depression and anxiety in our Malaysian sample of RA patient was comparable to that observed in Caucasian populations. Functional status was an independent predictor of depression and anxiety, whereas pain was an independent predictor of stress.

Topics: Anxiety; Arthritis, Rheumatoid; Cholestyramine Resin; Cross-Sectional Studies; Depression; Female; Humans; Malaysia; Male; Middle Aged; Prevalence; Self Report; Severity of Illness Index; Stress, Psychological

Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women.. A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae.. Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD.. In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.

Topics: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Bone Density; Cross-Sectional Studies; Female; Humans; Malaysia; Middle Aged; Vitamin D; Vitamin D-Binding Protein

Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate 'bioavailable' levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls.. A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys. Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.. In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.

Topics: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Asian People; Biomarkers; Body Mass Index; Bone Density; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Malaysia; Menopause; Middle Aged; Severity of Illness Index; Vitamin D; Vitamin D-Binding Protein

To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Cross-Sectional Studies; Disability Evaluation; Female; Humans; Malaysia; Male; Medication Adherence; Middle Aged; Patient Reported Outcome Measures; Practice Patterns, Physicians'; Remission Induction; Retrospective Studies; Risk Factors; Severity of Illness Index; Time Factors; Treatment Failure

The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p < 0.001). Overall, 16.9% achieved DAS28 remission at 6 months. A third (35.6%) of patients reported adverse events, three commonest being infections (46.5%), allergy (22.9%) and laboratory abnormalities (12.9%). 3.7% of our patients had tuberculosis. Biologic DMARDs were effective in treating RA in real-world practice in Malaysia, despite a lower remission rate compared to developed countries. Except for higher rates of tuberculosis, the AEs were similar to the published reports.

Topics: Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Drug Therapy, Combination; Female; Humans; Hypersensitivity; Infections; Malaysia; Male; Methotrexate; Middle Aged; Retrospective Studies; Rituximab; Treatment Outcome; Tumor Necrosis Factor-alpha

Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects.. A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fibα563-583, Fibα580-600, Fibβ36-52, Fibβ62-81a, Fibβ62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%.. Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibβ62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [P. Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.

Topics: Adolescent; Adult; Aged; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Case-Control Studies; Female; Filaggrin Proteins; Humans; Malaysia; Male; Middle Aged; Peptides, Cyclic; Sweden; Young Adult

Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke.. Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case-control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI.. Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2).. This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene-environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.

Topics: Adult; Alleles; Antibodies; Arthritis, Rheumatoid; Case-Control Studies; Dust; Epitopes; Female; Gene-Environment Interaction; HLA-DRB1 Chains; Humans; Malaysia; Middle Aged; Occupational Diseases; Occupational Exposure; Peptides, Cyclic; Risk Factors; Textile Industry; Textiles

The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.

Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Cohort Studies; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Folic Acid; Humans; Malaysia; Male; Methotrexate; Middle Aged; Surveys and Questionnaires; Treatment Outcome; Vitamin B Complex

Silica exposure has been associated with an increased risk of developing rheumatoid arthritis (RA), especially among smokers. In this study, we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of RA in the Malaysian population.. In total, 149 cases and 213 matched controls, all men, were included between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched on sex, age and residential area. Silica exposure was defined as exposure to stone dust, rock drilling or stone crushing, and smoking status was categorized as ever/never cigarette smoking.. An increased risk of anti-citrullinated protein antibody (ACPA)-positive RA (OR = 2.4, 95 % CI 1.0-5.6) was observed among those exposed to silica. Ever-smokers exposed to silica had a particularly high risk of developing ACPA-positive RA (OR = 7.5, 95 % CI 2.3-24.2), compared with never-smokers not exposed to silica. No association was found regarding ACPA-negative RA.. Our data demonstrate that exposure to both silica and cigarette smoke comprise risks for developing RA in the Malaysian genetic context. The findings expand a link between environmental lung exposures and ACPA-positive RA to Asian populations.

Topics: Adult; Arthritis, Rheumatoid; Asian People; Autoantibodies; Case-Control Studies; Environmental Exposure; Humans; Malaysia; Male; Middle Aged; Peptides, Cyclic; Risk Factors; Silicon Dioxide

The prognostic significance of rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) in rheumatoid arthritis (RA) remains contentious due to the conflicting lines of evidence. This study aims to determine the association between RF isotypes and anti-CCP with disease severity in RA patients from three ethnic groups.. A total of 147 RA patients from three different ethnic groups (Malays, Chinese, and Indians) who fulfilled the 1987 American College of Rheumatology (ACR) revised criteria for RA were recruited into this study. The seroprevalence of RF isotypes immunoglobulin (Ig)A, IgG, and IgM, as well as anti-CCP was determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Multinomial regression analysis was performed to assess the independent effects of autoantibody status on the development of deforming and erosive RA and the presence of extra-articular manifestations (EAM).. In Chinese patients, we found a significant association (p < 0.05) between IgG RF and anti-CCP and the presence of erosive disease, as well as IgM RF and IgG RF with the presence of joint deformities. In Indian patients, IgM RF was associated with deforming disease, whereas none of the antibodies were associated with disease severity in Malay patients. Multinomial regression analysis revealed that IgG RF was the most important predictor variable for erosive disease in Chinese patients, and IgM RF the only predictor variable associated with deforming disease in both Chinese and Indian RA patients.. There is variability in the phenotypic association of RF isotypes and anti-CCP in relation to disease severity of RA in the three ethnic groups. RF, in particular, IgG and IgM, may be better prognosticators of severe disease in Chinese and Indian patients.

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; China; Cross-Sectional Studies; Female; Humans; India; Malaysia; Male; Middle Aged; Peptides, Cyclic; Prognosis; Rheumatoid Factor; Seroepidemiologic Studies; Severity of Illness Index

We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.

Topics: Arthritis, Rheumatoid; Autoantibodies; Case-Control Studies; China; Dose-Response Relationship, Drug; Female; Humans; India; Malaysia; Male; Middle Aged; Peptides, Cyclic; Risk Assessment; Smoking; Surveys and Questionnaires; Time-to-Treatment

To determine the prevalence of sexual dysfunction (FSD) among women with rheumatoid arthritis attending the Rheumatology Clinic in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and Hospital Putrajaya, Malaysia, and to determine its associations with potential clinical and disease activity factors.. This was a cross-sectional study involving women with rheumatoid arthritis between the ages of 20 and 60 years. A validated Malay Version Female Sexual Function Index (MVFSFI) was administered to diagnose FSD. Sociodemographic and disease activity profiles were obtained and those who had and did not have FSD were compared.. Among 63 respondents, 51 patients were included in the analysis for FSD. The prevalence of FSD in women with rheumatoid arthritis attending UKMMC and Hospital Putrajaya Rheumatology Clinic was 29.4%. Erythrocyte sedimentation rate (ESR) and Disease Activity Score in 28 joints (DAS28-ESR) correlates with MVFSFI score with r=-0.364 (P=0.009) and r=-0.268 (P=0.057), respectively. Sociodemographic factors that correlate with MVFSFI score were: patient's age (r=0.520, P<0.001); duration of marriage (r=-0.355, P=0.001); husband's age (r=-0.460, P=0.001); age of oldest child (r=-0.449, P=0.001); and age of youngest child (r=-0.627, P<0.001).. We found in this study that the prevalence of FSD in rheumatoid arthritis in our centers was 29.4%. Age and family dynamics appear to be more important predictors compared to disease activity.

Topics: Adult; Aging; Arthritis, Rheumatoid; Cross-Sectional Studies; Culture; Disability Evaluation; Family Relations; Female; Humans; Logistic Models; Malaysia; Middle Aged; Prevalence; Quality of Life; Severity of Illness Index; Sexual Dysfunction, Physiological

The aim of our study is to describe the impact of tight control strategy on the care of RA patients in Sarawak General Hospital. We performed a prospective study of all patients with a diagnosis of RA who received treatment at the Rheumatology Clinic in Sarawak General Hospital over a 1-year period. Systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS 28-ESR <2.6) were carried out in the clinic over the 1-year period. Disease activity and treatment regimes of all 142 patients were collected for at baseline and 1 year later for statistical analysis. Our patients have a significantly lower DAS 28 with a mean of 2.99 ± 0.95 compared with baseline of 4.31 ± 1.34 (p < 0.000). More patients were in remission 1 year later compared to baseline (36.6% vs 11.3%). Tight control strategy has a positive impact on the care of RA patients in our centre. By optimising the care of RA through tight control strategy, RA can be better controlled in our centre.

Topics: Activities of Daily Living; Adult; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Malaysia; Male; Middle Aged; Prospective Studies; Remission Induction; Retrospective Studies; Rheumatology; Severity of Illness Index; Time Factors; Treatment Outcome

The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti-cyclic citrullinated peptides (anti-CCP) in Malaysian rheumatoid arthritis (RA) patients.. In this cross-sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme-linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second-generation anti-CCP were performed and the prevalence of each auto-antibody was compared in the three ethnic groups.. The anti-CCP was the most prevalent auto-antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti-CCP-RF IgM combination provided the best test sensitivity. Seroprevalence of anti-CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti-CCP did not increase or decrease with advancing age, age at onset and disease duration.. When used alone, anti-CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti-CCP assay, step-wise serum testing with IgM RF followed by anti-CCP may provide a more economically sensible option to optimize test sensitivity for RA.

Topics: Adolescent; Adult; Antibodies, Anti-Idiotypic; Arthritis, Rheumatoid; Autoantibodies; China; Female; Humans; Immunoglobulin Isotypes; India; Malaysia; Male; Middle Aged; Peptides, Cyclic; Rheumatoid Factor; Seroepidemiologic Studies; Young Adult

The aim of this study was to evaluate the left ventricular (LV) diastolic dysfunction in rheumatoid arthritis (RA) patients without clinically evident cardiovascular manifestations and to estimate whether there is any correlation between RA disease severity and disability and LV diastolic dysfunction.. The study was a cross-sectional study involving 53 patients (47 female and 6 male) with RA without clinically evident heart disease and 53 healthy subjects (47 female and 6 male) who served as a control group. Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects.. Of 17 cardiac parameters assessed, only two were abnormal. None of the specific cardiac diastolic dysfunction parameters were significantly different in RA patients compared to the control group. There was no significant correlation between diastolic function values in RA patients and value of Disease Activity Score 28 (DAS-28) and value of Health Assessment Questionnaires Disability Index (HAQDI). Atrial (A) wave velocity was greater in RA patients compared to the control group (0.71 [0.58-0.83] vs. 0.61 [0.51-0.71]; P < 0.04). However, interventricular relaxation time (IVRT) ([73.08 ± 9.92 vs. 70.74 ± 9.02], P = 0.207), lower E/A ratio (1.27 [1.02-1.56] vs. 1.42 [1.20-1.68], P = 0.102), diastolic dysfunction parameters according to Redfield Classification (25 [47.2%] vs. 27 [50.9%] P = 0.56), diastolic dysfunction using E/A (P = 0.321) and tissue doppler imaging (E/E') (P = 0.148) were not different.. Prevalence of diastolic dysfunction in the rheumatoid arthritis group (47.2%) was not different from controls (50.9%). LV diastolic function had no significant correlation with RA disease severity and duration of disease.

Topics: Arthritis, Rheumatoid; China; Comorbidity; Cross-Sectional Studies; Diastole; Disability Evaluation; Echocardiography; Female; Health Status; Hemodynamics; Humans; India; Malaysia; Male; Middle Aged; Severity of Illness Index; Ventricular Dysfunction, Left

Rheumatoid arthritis (RA) patients who have active disease with longer disease duration have been reported to have increased risk of cardiovascular events compared to the normal population.. The primary aim of our study is to ascertain the prevalence of significant asymptomatic coronary artery disease (CAD) in Asian RA patients who are in remission using multi-detector computed tomography (MDCT). The secondary aims of our study are the usage of pulse wave velocity and the biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-senstivity C-reactive protein (hs-CRP) to detect subclinical atherosclerosis in RA patients.. We performed a comparative cross-sectional study of 47 RA patients who were in remission with a control group of non-RA patients with a history of atypical chest pain in Sarawak General Hospital from November 2008 to February 2009. All patients underwent 64-slice MDCT, assessment of arterial stiffness using the SphygmoCor test and blood analysis for NT-proBNP and hsCRP.. There were 94 patients in our study with a mean age of 50 +/- 8.8 years. The RA and control patients in each group were matched in terms of traditional CV risk factors. Our RA patients had a median disease duration of 3 years (IQR 5.5). MDCT showed evidence of CAD in nine (19.1%) RA patients and three (6.4%) control patients (P = 0.06). There was no significant association between pulse wave velocity (PWV) and presence of CAD in our RA group. There was no significant correlation between PWV with levels of proBNP or hsCRP in our RA patients.. In our current pilot study with the limitation of small sample size, RA was not associated with an increased risk of CAD in our RA patients who were in remission. Larger studies of CAD in Asian RA patients are needed to confirm our current finding.

Topics: Adult; Arteries; Arthritis, Rheumatoid; Asian People; Asymptomatic Diseases; Biomarkers; C-Reactive Protein; Case-Control Studies; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Elasticity; Female; Humans; Malaysia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prevalence; Remission Induction; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Ultrasonography

Rheumatoid factors (RF) are currently used in the diagnosis of rheumatoid arthritis (RA). Several other autoantibodies found in RA are directed to epitopes in citrullinated proteins such as anti-cyclic citrullinated and recently anti-modified citrullinated vimentin (MCV).. In this study we determined the sensitivity and specificity of anti-MCV in comparison with anti-cyclic citrullinated peptide (CCP) antibodies and RF in RA patients and in a control group using the American College of Rheumatology (ACR) criteria as the gold standard.. A cross sectional study was conducted from January to December 2008 on 100 patients with RA and 153 patients with arthritis or arthralgia but not fulfilling ACR criteria for RA. Serum from each subject was tested for anti-MCV, anti-CCP antibodies and immunoglobulin G (IgG) RF by enzyme-linked immunosorbent assay. Sensitivity and specificity of the tests were evaluated using the ACR criteria as the gold standard.. The sensitivity of RF was 85% with 74.5% specificity. For anti-CCP antibodies the sensitivity was 71% and the specificity was 94.8%. The sensitivity of anti-MCV antibodies was 80% with 59.5% specificity. The area under the curve for RF was 0.759, for anti-CCP antibodies was 0.866 and for anti-MCV antibodies was 0.681, while for at least one positive test it was 0.691.. Anti-CCP antibodies have higher diagnostic specificity and positive predictive value than RF and anti-MCV antibodies. RF has the highest sensitivity when compared to anti-CCP and anti-MCV antibodies. Thus anti-MCV antibody is not a better marker when compared to RF or anti-MCV antibody in the diagnosis of RA patients.

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Case-Control Studies; Citrulline; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Malaysia; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Rheumatoid Factor; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Vimentin

Rheumatoid arthritis (RA) is a systemic disease of unknown cause. A variety of pulmonary disorders have been described in association with RA. Among the most common are interstitial lung disease (ILD) and bronchiectasis.. This study aims to determine the characteristics of RA patients with lung disease in relation to clinical characteristics, pulmonary function test (PFT) and high resolution computed tomography (HRCT) thorax.. This is a 6-months cross-sectional study involving 63 consecutive RA patients in an outpatient rheumatology clinic. Patients had a mean disease duration of 5 years and above. Disease activity and severity was assessed by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Articular Damage (RAAD) score. Full pulmonary function test (PFT) and HRCT of thorax were performed.. The prevalence of RA-ILD is 44% and 67% of patients are asymptomatic. There was significant higher proportion (68%) in patients of Chinese ethnicity who have ILD. Diffusion capacity of carbon monoxide was abnormal in all patients and forced expiratory flow (FEF)(25-75%) was low in 16%. Restrictive pattern was 66.7% by PFT. The most common HRCT findings were reticulation (46%) followed by ground glass opacities (38.1%) and bronchiectasis (28.6%). There was no association between ILD and male gender, duration of the disease, smoking, rheumatoid factor, extra-articular manifestations, disease activity or severity.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Asian People; Bronchiectasis; Carbon Monoxide; Cross-Sectional Studies; Disability Evaluation; Female; Follow-Up Studies; Forced Expiratory Flow Rates; Humans; Lung Diseases, Interstitial; Malaysia; Male; Middle Aged; Prevalence; Sex Distribution; Surveys and Questionnaires; Tomography, X-Ray Computed

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Health Surveys; Humans; Malaysia; Multicenter Studies as Topic

The objectives of this study are to provide data regarding the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in Malaysian rheumatoid arthritis (RA) patients and to correlate the levels of anti-CCP antibody with the Disease Activity Score (DAS).. We studied the prevalence of anti-CCP antibodies in 51 RA patients attending our clinic and 29 controls. We also looked for correlation between anti-CCP antibody levels with the DAS and parameters such as duration of disease, rheumatoid factor (RF) and disease-modifying anti rheumatic drug (DMARD) usage.. None of the controls demonstrated anti-CCP antibodies. Forty-one out of 51 patients (80.4%) were positive for anti-CCP antibodies. Sensitivity and specificity were 80.4% and 100% respectively in this study. Anti-CCP levels correlated significantly with rheumatoid factor, but no correlation was observed with the other parameters.. Anti-CCP antibody is prevalent in Malaysian RA patients at 80.4% and more sensitive than RF in our cohort of established RA patients. Even though the anti-CCP levels correlated with RF, it did not show correlation with DAS.

Topics: Adult; Aged, 80 and over; Antirheumatic Agents; Arthritis, Rheumatoid; Autoantibodies; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Middle Aged; Peptides, Cyclic; Rheumatoid Factor; Seroepidemiologic Studies; Severity of Illness Index; Young Adult

The aim of our study is to describe the pattern, clinical features, treatment regimes, and disease activity among the patients treated for rheumatoid arthritis (RA) in the Sarawak General Hospital. We performed a cross-sectional study of all patients with a diagnosis of RA who received treatment at the General Medical Clinic and the Rheumatology Clinic in Sarawak General Hospital over a 1-year period from 1st June 2006 to 31st May 2007. Demographic data, clinical features, and disease activity of all 154 patients were collected for statistical analysis. Rheumatoid arthritis afflicts all the major racial groups in Sarawak including the native population. Our patients have a mean disease duration of 5.4 years (SD 5.69) and a mean duration of delay in diagnosis RA and initiation of disease-modifying antirheumatic drug (DMARD) treatment of 42.9 months (SD 60.1). They have a low rate of interstitial lung disease (6.5%) and rheumatoid nodules (4.5%). Rheumatoid factor was positive in 65.5% of our patients. They have a mean Disease Activity Score (DAS) 28 score of 4.28 (SD 1.33). Only 12.5% of our patients are in remission with DAS 28 < 2.6 and 30.9% of our patients are having high disease activity with DAS 28 > 5.1. Despite the high usage of DMARDs in Sarawak (>80%), our patients have severe disease with high disease activity indices. This is most likely due to delay in diagnosis and initiating DMARDs in RA patients in Sarawak.

Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Hospitals, General; Humans; Malaysia; Male; Middle Aged; Practice Patterns, Physicians'; Severity of Illness Index

To assess the relationship between the HLA-DRB1 genes with disease severity as assessed by radiological erosions in Malaysian patients with rheumatoid arthritis (RA).. In this cross-sectional study, we studied 61 RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1 genotyping was performed by sequence specific primer (SSP) - PCR. Radiological grading and erosive score of the hands and wrists was calculated according to the Larsen-Dale method. Demographic data and treatment given to the patients were obtained from their case records.. Fifty-six females and five males were studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE) in 31%. The median delay in starting DMARDs was 24 months. The presence of rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated with a worse erosive score. Patients who possessed the SE had a higher erosive scores, compared to those who did not (p = 0.05). Concurrently, a delay in starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348). However, after adjustment for the delay in starting DMARD, SE was no longer significantly associated with the erosive score.. In these patients, the delay in starting DMARDs had a greater influence on the erosive score than SE alone. Whilst we cannot discount the contribution of the SE presence, we would advocate early usage of DMARDs in every RA patient to reduce joint erosions and future disability.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Cross-Sectional Studies; Female; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Malaysia; Male; Middle Aged; Radiography

In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: -1087G>A), rs1800871 (position: -824C>T) and rs1800872 (position: -597C>A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P>0.05). However, a significant difference was observed in allele frequencies of -824CT, -824TT, -597CA, and -597AA between the RA patients and healthy volunteers (P=0.04). The -1087A/-824T/-597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P=0.012) or two (P=0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA.

Topics: Alleles; Arthritis, Rheumatoid; Case-Control Studies; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Interleukin-10; Malaysia; Male; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Sequence Analysis, DNA

Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Although numerous studies reported the association of human leukocyte antigen (HLA)-DRB1*04 and RA, other genes, e.g. cytokines genes, may contribute towards disease susceptibility. Interleukin-18 (IL-18) is a proinflammatory cytokine postulated to play a role in the acute and chronic inflammatory phases of RA. The IL-18 protein expression seems to be regulated by two single-nucleotide polymorphisms (SNPs) located at positions -607 and -137 in the promoter region of the gene. It is postulated that specific alleles may be associated with susceptibility to the development of RA. In the present study, we described the IL-18 gene promoter region genotypes and combined genotypes (-607/-137) in 106 RA patients and 273 unrelated healthy controls to evaluate the contributions of these alleles to RA predisposition in Chinese, Malays, and Indians. The genotyping were performed using sequence-specific polymerase chain reactions. Rheumatoid factors were assayed by enzyme-linked immunosorbent assay. Biodata were obtained through chart review. The controls had significantly higher frequency of AA genotype at position -607 when compared to RA patients. No significant differences were observed in the distribution of either allelic or genotypic frequencies at position -137. There was no association between the genotypes and the presence of rheumatoid factors. This study did not find evidence of a genetic susceptibility factor but demonstrated the novel finding that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. This protection may be mediated through inhibition of cyclic (Adenosine 3', 5'-cyclic monophosphate) AMP-responsive element (CRE)-binding protein by the disruption of the CRE consensus sequence.

Topics: Adult; Arthritis, Rheumatoid; Case-Control Studies; China; Female; Gene Frequency; Genotype; Humans; India; Interleukin-18; Malaysia; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Rheumatoid Factor

Worldwide population studies have generally agreed that rheumatoid arthritis (RA) is associated with a group of HLA-DRB1 alleles which share a common amino acid sequence at residues 70-74. This represents the first study to investigate the association of HLA-DRB1 genes with susceptibility to RA amongst Malay, Chinese and Indian ethnic groups in Malaysia. One hundred and thirty three RA patients and one hundred and sixty seven healthy controls were recruited. The HLA-DRB1 alleles were studied using the Phototyping method. The subtypes of HLA-DR4 were detected by "high resolution" PCR-SSP DRB1*04 typing techniques. The prevalence of HLA-DRB1*0405 was significantly higher in Malay patients with RA than in healthy controls (28.9 vs. 8.3%, p = 0.0016, OR = 4.48, 95% CI = 1.26-16.69). Similarly, DRB1*0405 was more common in Chinese RA patients than in controls (30.0 vs. 6.7%, p = 0.0029, OR = 6.00, 95% CI = 1.67-23.48). In addition, DRB1*0901 was a predisposing factor (32.0 vs. 6.7%,p = 0.0015, OR = 6.59, 95% CI = 1.85-25.64) and *0301/04 had a protective role (4.0vs. 25.0%, p = 0.00562, OR = 0.13, 95% CI = 0.02-0.62) in Malaysian Chinese RA. RA in Indians was associated with DRB1*1001 (51.1 vs. 8.5%,p = 0.00002, OR = 11.24, 95% CI = 3.13-44.18). DRB1*0701 (13.3 vs. 42.6%,p = 0.0022, OR = 2.73, 95% CI = 1.40-5.37) may have a protective effect. Therefore, in the Malaysian population, RA is primarily associated with the QRRAA motif, and we suggest that genetic factors play a crucial role in the pathogenesis of RA, compared to environmental factors.

Topics: Alleles; Arthritis, Rheumatoid; Asian People; Gene Frequency; Genetic Predisposition to Disease; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Malaysia; Odds Ratio; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational

Seventy consecutive patients with definite or classical RA attending a University Hospital Rheumatology Clinic in Malaysia, were compared with an age, sex, disease duration matched group of RA patients seen in a British University Hospital. There were no differences in measures of disease activity, overall functional status or serological status in the two groups. However significant differences were seen in both the articular and extra-articular manifestations of the disease in the two countries. British patients had more severe disease in the feet, and a higher prevalence of nodules, vasculitis and pulmonary fibrosis. The Malaysian population had fewer erosions, more frequent involvement of the wrists and cervical spine, and a much higher incidence of secondary sicca syndrome. Radiographic changes were generally milder in Malaysian patients. Possible reasons for these differences in the expression of RA in the two countries are discussed.

Topics: Adolescent; Adult; Age Factors; Arthritis, Rheumatoid; Female; Humans; Malaysia; Middle Aged; Prevalence; Radiography; Sex Factors; Time Factors; United Kingdom

Topics: Adolescent; Adult; Age Factors; Aged; Arthritis, Rheumatoid; China; Climate; Female; gamma-Globulins; Gout; Humans; India; Latex Fixation Tests; Lupus Erythematosus, Systemic; Malaysia; Male; Middle Aged; Racial Groups; Rheumatoid Factor; Rheumatoid Nodule; Serum Albumin