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Fulltext Intra- and Inter-observer Variability in Different Methods of Measuring Carpal Collapse

Agrawal S, Chabra T, Pandey S, Bhardwaj P

Malays Orthop J, 2019 Mar;13(1):20-24.
PMID: 31001379 DOI: 10.5704/MOJ.1903.003

Introduction: Carpal collapse of wrist occurs in disorders like rheumatoid arthritis and Kienbock's disease. Three techniques have been described to measure carpal collapse. First, the carpal height ratio (CHR), measured by dividing carpal height by 3rd metacarpal length. Second, the revised carpal height ratio (RCH ratio), measured by dividing carpal height by length of capitate. Third, capitate radius distance (CR index), measured by shortest distance between distal edge of radius and the proximal edge of capitate. The index publications describe good reliability of all these but which method out of the three is best in terms of intra- and inter-observer variability is not known. The purpose of this study was to find out which method had the least inter- and intra-observer variability for determining carpal collapse. Materials and Methods: Fifty normal wrist postero-anterior radiographs were studied by three assessors who measured CHR, RCH ratio and CR index separately. The measurements were repeated after one month by all the three observers. The results were then statistically analysed. Results: The p-value was <0.001 in all the three assessors in CR index meaning that the intra-observer variability was least in CR index. For the inter-observer variability intra class coefficient of 0.9 indicated that the CR index has the least variability. Conclusion: CR index is the most reproducible method to measure carpal collapse. The method which provides accurate measurement of carpal collapse will allow better staging of carpal disorders.

Study site: Grande Hospital, Nepal

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Early results of total knee replacements: "a clinical and radiological evaluation"

Dhillon KS, Jamal A, Bhupinderjeet S

Med J Malaysia, 1993 Dec;48(4):427-35.
PMID: 8183167

From March 1986 to June 1992, 100 primary total knee arthroplasties were done in 69 patients. The demographic data and complications were analysed in these 69 patients. The first 50 knees with a minimal follow-up of one year (range 1-6 years) were analysed in more detail according to the International Knee Society Rating System. Detailed radiological evaluation was also carried out to assess positioning of the components. There were 79 knees with osteoarthritis, 20 knees with rheumatoid arthritis and one with Systemic Lupus Erythromatosus (SLE). The knee score was poor in all knees pre-operatively. Post-operatively 78% had good to excellent score and the other 22% had fair knee score. However the functional score remained poor in 50% of the knees. Ideal tibio-femoral alignment was obtained in 68% of the knees. Twenty four percent of the knees had 0.4 degrees of varus and eight percent had 10-12 degrees valgus. Complication rate was low with 1% of infection (one knee). Overall early results were satisfactory.
Study site; University Hospital Kuala Lumpur (University Malaya Medical Centre)

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Recognizing rheumatoid arthritis: oncoprotein survivin opens new possibilities: a population-based case-control study

Chun-Lai T, Murad S, Erlandsson MC, Hussein H, Sulaiman W, Dhaliwal JS, et al.

Medicine (Baltimore), 2015 Jan;94(4):e468.
PMID: 25634192 DOI: 10.1097/MD.0000000000000468

Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/genetics
Fulltext An unusual case of shortness of breath

Wan Muhammad Hatta SF, Kandaswamy L, Gherman-Ciolac C, Mann J, Buch HN

Endocrinol Diabetes Metab Case Rep, 2018;2018.
PMID: 30087779 DOI: 10.1530/EDM-18-0074

Myopathy is a well-known complication of hypercortisolism and commonly involves proximal lower-limb girdle. We report a rare case of Cushing's syndrome in a 60-year-old female presenting with significant respiratory muscle weakness and respiratory failure. She had history of rheumatoid arthritis, primary biliary cirrhosis and primary hypothyroidism and presented with weight gain and increasing shortness of breath. Investigations confirmed a restrictive defect with impaired gas transfer but with no significant parenchymatous pulmonary disease. Respiratory muscle test confirmed weakness of respiratory muscles and diaphragm. Biochemical and radiological investigations confirmed hypercortisolaemia secondary to a left adrenal tumour. Following adrenalectomy her respiratory symptoms improved along with an objective improvement in the respiratory muscle strength, diaphragmatic movement and pulmonary function test.
Learning points: Cushing's syndrome can present in many ways, a high index of suspicion is required for its diagnosis, as often patients present with only few of the pathognomonic symptoms and signs of the syndrome.Proximal lower-limb girdle myopathy is common in Cushing's syndrome. Less often long-term exposure of excess glucocorticoid production can also affect other muscles including respiratory muscle and the diaphragm leading to progressive shortness of breath and even acute respiratory failure.Treatment of Cushing's myopathy involves treating the underlying cause that is hypercortisolism. Various medications have been suggested to hinder the development of GC-induced myopathy, but their effects are poorly analysed.

Matched MeSH terms: Arthritis, Rheumatoid
Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease

Sharma JN, Buchanan WW

Exp. Toxicol. Pathol., 1994 Dec;46(6):421-33.
PMID: 7703672 DOI: 10.1016/S0940-2993(11)80053-9

Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokine and cytokine mediators of inflammation, e.g., PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF, derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.

Matched MeSH terms: Arthritis, Rheumatoid/metabolism*
Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy

Alam J, Jantan I, Bukhari SNA

Biomed Pharmacother, 2017 Aug;92:615-633.
PMID: 28582758 DOI: 10.1016/j.biopha.2017.05.055

An autoimmune disease is defined as a clinical syndrome resulted from an instigation of both T cell and B cell or individually, in the absence of any present infection or any sort of distinguishable cause. Clonal deletion of auto reactive cells remains the central canon of immunology for decades, keeping the role of T cell and B cell aside, which are actually the guards to recognize the entry of foreign body. According to NIH, 23.5 million Americans are all together affected by these diseases. They are rare, but with the exception of RA. Rheumatoid arthritis is chronic and systemic autoimmune response to the multiple joints with unknown ethology, progressive disability, systemic complications, early death and high socioeconomic costs. Its ancient disease with an old history found in North American tribes since 1500 BCE, but its etiology is yet to be explored. Current conventional and biological therapies used for RA are not fulfilling the need of the patients but give only partial responses. There is a lack of consistent and liable biomarkers of prognosis therapeutic response, and toxicity. Rheumatoid arthritis is characterized by hyperplasic synovium, production of cytokines, chemokines, autoantibodies like rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA), osteoclastogensis, angiogenesis and systemic consequences like cardiovascular, pulmonary, psychological, and skeletal disorders. Cytokines, a diverse group of polypeptides, play critical role in the pathogenesis of RA. Their involvement in autoimmune diseases is a rapidly growing area of biological and clinical research. Among the proinflammatory cytokines, IL-1α/β and TNF-α trigger the intracellular molecular signalling pathway responsible for the pathogenesis of RA that leads to the activation of mesenchymal cell, recruitment of innate and adaptive immune system cells, activation of synoviocytes which in term activates various mediators including tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8), resulting in inflamed synovium, increase angiogenesis and decrease lymphangiogensis. Their current pharmacotherapy should focus on their three phases of progression i.e. prearthritis phase, transition phase and clinical phase. In this way we will be able to find a way to keep the balance between the pro and anti-inflammatory cytokines that is believe to be the dogma of pathogenesis of RA. For this we need to explore new agents, whether from synthetic or natural source to find the answers for unresolved etiology of autoimmune diseases and to provide a quality of life to the patients suffering from these diseases specifically RA.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/etiology*; Arthritis, Rheumatoid/metabolism
Relation of Doppler ultrasound synovitis versus clinical synovitis with changes in native complement component levels in rheumatoid arthritis patients treated with biologic disease-modifying anti-rheumatic drugs

Montoro Alvarez M, Chong OY, Janta I, González C, López-Longo J, Monteagudo I, et al.

Clin Exp Rheumatol, 2015 Mar-Apr;33(2):141-5.
PMID: 25665178

The complement system plays a fundamental role in mediating the activity of rheumatoid arthritis (RA). Biologic therapy can reduce native complement component levels and its activation. We aimed to study the relation of Doppler ultrasound (US) synovitis versus clinical synovitis with changes in native complement component levels in RA patients on biologic therapy.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/immunology; Arthritis, Rheumatoid/ultrasonography
Casticin from Vitex species: a short review on its anticancer and anti-inflammatory properties

Chan EWC, Wong SK, Chan HT

J Integr Med, 2018 05;16(3):147-152.
PMID: 29559215 DOI: 10.1016/j.joim.2018.03.001

This short review provides an update of the anticancer and anti-inflammatory properties of casticin from Vitex species. Casticin is a polymethylflavone with three rings, an orthocatechol moiety, a double bond, two hydroxyl groups and four methoxyl groups. Casticin has been isolated from various tissues of plants in the Vitex genus: fruits and leaves of V. trifolia, aerial parts and seeds of V. agnus-castus and leaves of V. negundo. Studies have reported the antiproliferative and apoptotic activities of casticin from Vitex species. The compound is effective against many cancer cell lines via different molecular mechanisms. Studies have also affirmed the anti-inflammatory properties of casticin, with several molecular mechanisms identified. Other pharmacological properties include anti-asthmatic, tracheospasmolytic, analgesic, antihyperprolactinemia, immunomodulatory, opioidergic, oestrogenic, anti-angiogenic, antiglioma, lung injury protection, rheumatoid arthritis amelioration and liver fibrosis attenuation activities. Clinical trials and commercial use of the casticin-rich fruit extract of V. agnus-castus among women with premenstrual syndrome were briefly discussed.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Association of Immunoglobulin G abnormalities in diseases: a mini review

Foong, Audrey Kow Siew, Nuha Fahimah Binti Wan Zahidi, Chau, Ling Tham

Life Sciences, Medicine and Biomedicine, 2018;2(1):24-39.
MyJurnal

Immunoglobulins are antibodies that play important roles in preserving our immune system. They have the ability to initiate humoral responses and remove antigen from the body. Out of the five major isotypes of immunoglobulins, IgG are most abundantly found in human serum. Abnormalities – deficiency or elevation in the level of IgG are found to be associated to the occurrence of several autoimmune diseases. These may include rheumatoid arthritis, Crohn’s disease, Mikulicz’s disease, Kuttner’s tumour and Hashimoto’s thyroiditis. Apart from autoimmune diseases, IgG has been found to play a role in initiating anaphylaxis, a severe and life threatening form of allergy and lately it has been discovered in cases of dengue virus infection too. It is important to acknowledge the roles of IgG on diseases especially subclass IgG4 which the elevation has been tied to numerous diseases such as Kuttner’s tumour and Hashimoto’s thyroiditis hence termed IgG4-related diseases. In addition, the roles of IgG in anaphylaxis are of importance, too, as IgG has been used in allergy immunotherapy. Hence, this review is a mini compilation of effects of IgG abnormalities based on their subclasses. Hopefully it will provide insightful understanding on the development of diagnostic and therapeutic courses for the aforementioned IgG abnormalities in the future.

Matched MeSH terms: Arthritis, Rheumatoid
Anti-CCP antibodies: A better diagnostic tool for rheumatoid arthritis

Dollah R, Yaacob A, Ismail AH, Che Hussin CM

International Medical Journal (Tokyo), 2011;18(1):53-57.

Objective: The assay for anti-cyclic citrullinated peptide (anti-CCP) antibody is a recent test of interest due to low diagnostic specificity of rheumatoid factor in the diagnosis of rheumatoid arthritis. To determine the sensitivity and specificity of anti-CCP antibodies in rheumatoid arthritis patients using American College of Rheumatology (ACR) criteria as a gold standard.
Design: A cross sectional study was conducted from January 2008 to December 2008 on 100 patients with rheumatoid arthritis and 153 patients with arthritis or arthralgia but not fulfilling ACR criteria for rheumatoid arthritis.
Materials and Methods: Serum from each subject was tested for anti-CCP antibodies and IgM rheumatoid factor (IgM RF) by an enzyme linked immunosorbent assay (ELISA). Sensitivity and specificity of the tests were evaluated using the ACR criteria as the gold standard. Data was analyzed using SPSS version 12.0 software. The association between the two categorical variables were tested using chi-square test. The differences between the two groups were tested using independent t-test. Results: The sensitivity of anti-CCP antibodies was 71% with 94.8% of specificity. For rheumatoid factor the sensitivity was 85% and the specificity was 74.5%. Positive predictive value for anti-CCP antibodies was 89.9% whereas for rheumatoid factor it was 68.5%. The sensitivity of ACR criteria with inclusion of anti- CCP antibodies was 100% and specificity of 94.8% (95%CI: 91.3%, 98.2%).
Conclusion: Anti-CCP antibody has a higher diagnostic accuracy compared to the RF. Anti-CCP antibody is a useful laboratory marker to support the diagnosis of rheumatoid arthritis and to differentiate patients with rheumatoid arthritis from rheumatoid arthritis-like symptoms. Therefore, it is suggested that anti-CCP antibodies should be included as another laboratory supportive criterium besides RF test in ACR criteria in the diagnosis of RA.
Study site: family medicine clinic, rheumatology clinic and immunology laboratory of Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, Kelantan, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
IL-23/IL-17 axis in the pathogenesis and treatment of systemic lupus erythematosus and rheumatoid arthritis

Farah Izati A, Wong KK, Che Maraina CH

Malays J Pathol, 2020 Dec;42(3):333-347.
PMID: 33361714

Interleukin-23 (IL-23) and IL-17 are the gatekeepers of CD4+ T helper 17 (Th17) cells where IL-23 is required for the development and expansion of Th17 cells that subsequently produce IL-17 to promote inflammation. Owing to such pro-inflammatory properties, the IL-23/IL-17 axis has emerged as an important mechanism in the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In recent years, therapeutic antibodies targeting IL-23 (e.g. ustekinumab, tildrakizumab, guselkumab) or IL-17 (e.g. brodalumab, secukinumab, ixekizumab) have been approved for the treatment of various autoimmune diseases. In this review, we describe the pathogenic mechanisms of IL-23/IL-17 axis in SLE and RA, as well as summarising the findings from phase II and III clinical trials of anti-IL-23/IL-17 therapeutic antibodies in SLE and RA patients. In particular, phase II study has demonstrated that the anti-IL-23 antibody (ustekinumab) confers enhanced treatment outcomes in SLE patients, while anti-IL-17 antibodies (secukinumab and ixekizumab) have shown improved clinical benefits for RA patients in phase II/III studies. Our review highlights the emerging importance of targeting the IL-23/IL-17 axis in SLE and RA patients.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy; Arthritis, Rheumatoid/immunology*
Fulltext One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study

Lim CH, Lin CH, Chen DY, Chen YM, Chao WC, Liao TL, et al.

PLoS One, 2016;11(11):e0166339.
PMID: 27832150 DOI: 10.1371/journal.pone.0166339

OBJECTIVE: To investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012.
METHODS: We used the 2003-2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008-2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. We used propensity score matching (1:6) for age, sex, and the year of the drug index date to re-select the TNFi group and the non-TNFi controls. After adjusting for potential confounders, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to examine the 1-year TB risk in the TNFi group compared with the non-TNFi controls. Subgroup analyses according to the year of treatment initiation and specific TNFi therapy were conducted to assess the trend of 1-year TB risk in TNFi users from 2008 to 2012.
RESULTS: This study identified 5,349 TNFi-treated RA patients and 32,064 matched non-TNFi-treated controls. The 1-year incidence rates of TB were 1,513 per 105 years among the TNFi group and 235 per 105 years among the non-TNFi controls (incidence rate ratio, 6.44; 95% CI, 4.69-8.33). After adjusting for age, gender, disease duration, comoridities, history of TB, and concomitant medications, TNFi users had an increased 1-year TB risk (HR, 7.19; 95% CI, 4.18-12.34) compared with the non-TNFi-treated controls. The 1-year TB risk in TNFi users increased from 2008 to 2011 and deceased in 2012 when the Food and Drug Administration in Taiwan announced the Risk Management Plan for patients scheduled to receive TNFi therapy.
CONCLUSION: This study showed that the 1-year TB risk in RA patients starting TNFi therapy was significantly higher than that in non-TNFi controls in Taiwan from 2008 to 2012.

Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/drug therapy*
Ten-year fracture risk by FRAX and osteoporotic fractures in patients with systemic autoimmune diseases

Lai EL, Huang WN, Chen HH, Hsu CY, Chen DY, Hsieh TY, et al.

Lupus, 2019 Jul;28(8):945-953.
PMID: 31177913 DOI: 10.1177/0961203319855122

The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients' 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.

Matched MeSH terms: Arthritis, Rheumatoid/complications*
Fulltext The risk of tuberculosis disease in rheumatoid arthritis patients on biologics and targeted therapy: A 15-year real world experience in Taiwan

Lim CH, Chen HH, Chen YH, Chen DY, Huang WN, Tsai JJ, et al.

PLoS One, 2017;12(6):e0178035.
PMID: 28570568 DOI: 10.1371/journal.pone.0178035

The objective of this study is to determine the risk of tuberculosis (TB) disease in biologics users among rheumatoid arthritis (RA) patients in Taiwan from 2000 to 2015. This retrospective cohort study enrolled adult RA patients initiated on first biologics at Taichung Veterans General Hospital. TB risks were determined as hazard ratio (HR) with 95% confidence interval (CI) using cox regression. A total of 951 patients were recruited; etanercept (n = 443), adalimumab (n = 332), abatacept (n = 74), golimumab (n = 60), tocilizumab (n = 31) and tofacitinib (n = 11). Twenty-four TB cases were identified; 13 in etanercept and 11 in adalimumab group with the TB incidence rate of 889.3/ 100,000 and 1055.6/ 100,000 patient-years respectively. There was no significant difference in TB risk between adalimumab and etanercept users with an incidence rate ratio of 1.27 (p = 0.556 by Poisson model). Significant 2-year TB risk factors included elderly patient >65 year-old (HR: 2.72, 95% CI: 1.06-6.99, p = 0.037), history of TB (HR: 6.24, 95% CI: 1.77-22.00, p = 0.004) and daily glucocorticoid use ≥5mg (HR:5.01, 95% CI: 1.46-17.21, p = 0.010). Sulfasalazine treatment appeared to be protective (HR: 0.32, 95% CI: 0.11-0.97, p = 0.043). Risk management plan (RMP) for TB before initiation of biologics commenced in 2012. The 2-year TB risks after RMP was compared with that before 2012 (HR:0.67, 95% CI: 0.30-1.49, p = 0.323). Elderly RA patients with a history of previous TB infection and concomitant moderate dose glucocorticoid were at higher risk of TB disease. Concurrent sulfasalazine treatment appeared to be a protective factor against TB disease.

Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/therapy
Self-reported symptoms of depression, anxiety and stress among patients with Rheumatoid Arthritis in a Malaysian rheumatology centre - prevalence and correlates

Ruhaila AR, Chong HC

Med J Malaysia, 2018 08;73(4):226-232.
PMID: 30121685 MyJurnal

OBJECTIVE: To determine the prevalence, correlates and independent predictors of self-reported depression, anxiety and stress in Rheumatoid arthritis (RA) patients in Hospital Melaka.
METHODS: 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).
RESULTS: 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).
CONCLUSION: 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.

Matched MeSH terms: Arthritis, Rheumatoid/complications; Arthritis, Rheumatoid/psychology*
Fulltext Analytical and diagnostic performance of an automated anti-CCP assay

Pavai S, Sargunan S, Zain AA, Chow SK

Malays J Pathol, 2011 Dec;33(2):101-6.
PMID: 22299210 MyJurnal

Aim: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the diagnostic and analytical performances of the automated anti-CCP assay.
Materials and Method: Sera from 80 patients with established RA, 65 from other rheumatic diseases (non-RA) and 55 from healthy controls were studied using second generation anti-CCP. Rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP fi ndings. Serum pools were used to determine the precision and linearity.
Results: At a cut-off of 7.4 U/ml for anti-CCP, the sensitivity and specificity for RA were 65% and 98% respectively. RF had a sensitivity of 58% and a lower specifi city of 93 % than anti-CCP. Conclusion: The high specificity of the assay suggests that anti-CCP is useful in the diagnosis of rheumatoid arthritis and in our cohort of study population anti-CCP exhibits a better diagnostic value than RF. A considerable proportion (28%) of RF-negative RA patients were anti-CCP positive. Based on analytical performance of the assay, we conclude that full automation and high throughput features of AxSYM makes it an ideal platform for routine testing of anti-CCP.
Study site: Rheumatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid/blood; Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/immunology
Fulltext Role of radiosynovectomy in the treatment of rheumatoid arthritis and hemophilic arthropathies

Das B

Biomed Imaging Interv J, 2007 Oct;3(4):e45.
PMID: 21614297 DOI: 10.2349/biij.3.4.e45

Radiosynovectomy is a novel method of treatment for several acute and chronic inflammatory joint disorders. A small amount of a beta-emitting radionuclide is injected into the affected joint delivering a radiation dose of 70 to 100 Gy to the synovia. The proliferative tissue is destroyed, secretion of fluid and accumulation of inflammation causing cellular compounds stops and the joint surfaces become fibrosed, providing long term symptom relief. The radionuclides are injected in colloidal form so that they remain in the synovium and are not transported by lymphatic vessels causing radiation exposure to other organs. Complete reduction of knee joint swelling has been seen in above 40% and pain relief in 88% of patients. Wrist, elbow, shoulder, ankle and hip joints showed significant improvement in 50-60% and restoration of normal function and long term pain relief has been achieved in about 70% of small finger joints. In hemophilic arthropathies complete cessation of bleeding in about 60% and improved mobility in 75% of patients has been reported.

Matched MeSH terms: Arthritis, Rheumatoid
To compare ESR and CRP as predictors of disease activity in rheumatoid arthritis patients in Hospital Seremban. [Abstract]

Gun SC, Loh YL, Das Gupta E

APLAR Journal of Rheumatology, 2006;9 Suppl 1:A185.

Background: Rheumatoid arthritis (RA) is an inflammatory disease. Predictors of disease activity include presence of joint inflammation, blood investigations such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). ESR is said to be imprecise as it is affected by aging, female sex, obesity, pregnancy, anaemia and polycythaemia. But it is inexpensive and easy to perform. CRP is produced as an acute phase reactant by the liver in response to interleukin 6 and other cytokines. CRP is more specific but costs more than ESR. Both tests are done in the rheumatology clinic of Hospital Seremban. Objective: To compare the usefulness of ESR and CRP as a predictor of disease activity in rheumatoid arthritis (RA) patients. Method: This was a retrospective study. The medical records of 248 RA patients who attended the rheumatology clinic, Hospital Seremban between 1 January 2004 and 31 Dec 2004 were reviewed. The following data were obtained: joint swelling and tenderness, other clinical features which indicate inflammation secondary to infection or trauma and inflammation of soft tissue, ESR, CRP, FBC and UFEME. Results: Data was analysed and the results showed that a total number of 248 patients were seen. There were 13 defaulters. Of the 248 patients there were 929 patients' visits. Of the total number of patients' visits where patients clinically had active disease, 80.2% had raised ESR while 88.8% had raised CRP. As for visits where patients had quiescent disease clinically, 57.3% had normal ESR and 36.5% had normal CRP. Conclusion: CRP is more sensitive but less specific than ESR. This suggests that we still should use both tests as they complement each other. ESR can serve as a countercheck for CRP and vice versa.

Matched MeSH terms: Arthritis, Rheumatoid
The effects of TNF α antagonist therapy on bone metabolism in rheumatoid arthritis: a systematic review

Sakthiswary R, Das S

Curr Drug Targets, 2013 Dec;14(13):1552-7.
PMID: 23848441

Osteoporosis is a common complication observed in rheumatoid arthritis (RA). Accelerated bone loss is always a matter of concern. The pathogenesis of RA may be important for better understanding of the bone loss. The mechanism involved in the bone loss in RA is not well understood although cytokines such as interleukin 1 and tumour necrosis factor α (TNF α) have been strongly implicated. TNF α antagonists have revolutionised the treatment of RA in the recent years. Beyond the control of disease activity in RA, accumulating evidence suggests that this form of therapy may provide beneficial effects to the bone metabolism and remodeling. An extensive search of the literature was performed in the Medline, Scopus and EBSCO databases to evaluate the documented research on the effects of TNF α antagonists in RA on bone mineral density and bone turnover markers. The available data based on our systematic review, depict a significant association between TNF α antagonists treatment and suppression of bone resorption.

Matched MeSH terms: Arthritis, Rheumatoid/complications; Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/metabolism; Arthritis, Rheumatoid/pathology
Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count

Kamarudin TA, Othman F, Mohd Ramli ES, Md Isa N, Das S

EXCLI J, 2012;11:226-36.
PMID: 27366139

Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 µg collagen. All rats with established CIA, with arthritis scores exceeding 1, were orally treated with betamethasone (0.5 mg/ml/kg body weight), curcumin (110 mg/ml/kg body weight) or olive oil (1.0 ml/kg body weight) daily, for two weeks. One remaining group was kept as normal control. Treatment with 110 mg/ml/kg curcumin showed significant mean differences in the average white blood cell (WBC) count (p<0.05), cell infiltration, bone and cartilage erosion scores (p<0.05) compared to the olive oil treated group. Pannus formation scores showed that curcumin supplementation successfully suppressed the pannus formation process that occurred in the articular cartilage of the CIA joints. The mean difference for histological scores for the curcumin group was insignificant compared to the betamethasone treated group. It is concluded that supplementation of curcumin has protective effect on the histopathological and degenerative changes in the joints of CIA rats which was at par with betamethasone.

Matched MeSH terms: Arthritis, Rheumatoid

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