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Fulltext Nocardiosis in a patient with rheumatoid arthritis treated with rituximab and a summary of reported cases

Ngiu CS, Said MS, Periyasamy P, Low SF

BMJ Case Rep, 2010;2010.
PMID: 22778377 DOI: 10.1136/bcr.11.2009.2421

Rituximab is a B-cell-depleting monoclonal anti-CD20 antibody. It is widely used in haematology and rheumatology. However, usage of rituximab in immunosupressed patient has been associated with various opportunistic infections. The authors reported a case of refractory rheumatoid arthritis treated with rituximab, which later presented with non-resolving pneumonia with pulmonary nodule. Percutaneous computer tomogram guided lung biopsy was arranged to confirm the suspicion of tuberculosis, but did not yield conclusive results. Later, she presented left-chest abscess and underwent incision and drainage. The pus culture and sensitivity confirmed pulmonary nocardiosis with chest wall dissemination. She was treated with 2-week course of trimethoprim sulfamethoxazole and responded. The authors also reviewed published cases of nocardiosis post-rituximab.

Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/drug therapy
Fulltext Corticosteroids causing severe growth suppression in juvenile rheumatoid arthritis

Lyn PCW

Med J Malaysia, 1984 Dec;39(4):300-5.
PMID: 6544938

Two children with Juvenile Rheumatoid Arthritis (JRA) and severe growth suppression from corticosteroid therapy are described. Prolonged 'tailing-off' of steroids occurred during outpatients follow-up and this may be related to the high turnover of doctors involved. Suggestions for improving such follow-ups and caution against the continuous use of steroids are made.
Study site: Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Immunomodulation by melatonin: its significance for seasonally occurring diseases

Srinivasan V, Spence DW, Trakht I, Pandi-Perumal SR, Cardinali DP, Maestroni GJ

Neuroimmunomodulation, 2008;15(2):93-101.
PMID: 18679047 DOI: 10.1159/000148191

Melatonin is not only synthesized by the pineal gland but also in many other organs and tissues of the body, particularly by lymphoid organs such as the bone marrow, thymus and lymphocytes. Melatonin participates in various functions of the body, among which its immunomodulatory role has assumed considerable significance in recent years. Melatonin has been shown to be involved in the regulation of both cellular and humoral immunity. Melatonin not only stimulates the production of natural killer cells, monocytes and leukocytes, but also alters the balance of T helper (Th)-1 and Th-2 cells mainly towards Th-1 responses and increases the production of relevant cytokines such as interleukin (IL)-2, IL-6, IL-12 and interferon-gamma. The regulatory function of melatonin on immune mechanisms is seasonally dependent. This fact may in part account for the cyclic pattern of symptom expression shown by certain infectious diseases, which become more pronounced at particular times of the year. Moreover, melatonin-induced seasonal changes in immune function have also been implicated in the pathogenesis of seasonal affective disorder and rheumatoid arthritis. The clinical significance of the seasonally changing immunomodulatory role of melatonin is discussed in this review.

Matched MeSH terms: Arthritis, Rheumatoid/immunology
Clinical and economic implications of upper gastrointestinal adverse events in Asian rheumatological patients on long-term non-steroidal anti-inflammatory drugs

Pok LSL, Shabaruddin FH, Dahlui M, Sockalingam S, Mohamed Said MS, Rosman A, et al.

Int J Rheum Dis, 2018 May;21(5):943-951.
PMID: 29314744 DOI: 10.1111/1756-185X.13256

AIM: To determine the incidence and direct costs of NSAID-induced upper GI adverse events in Malaysian rheumatology patients.
METHODS: A retrospective, multi-centre, cohort study of rheumatology patients on long-term NSAIDs was conducted. Clinical data of patients treated between 2010 and 2013 were collected for a 24-month follow-up period. The costs of managing upper GI adverse events were based on patient level resource use data.
RESULTS: Six hundred and thirty-four patients met the inclusion criteria: mean age 53.4 years, 89.9% female, diagnosis of rheumatoid arthritis (RA; 59.3%), osteoarthritis (OA; 10.3%) and both RA and OA (30.3%). Three hundred and seventy-one (58.5%) patients were prescribed non-selective NSAIDs and 263 (41.5%) had cyclo-oxygenase-2 inhibitors. Eighty-four upper GI adverse events occurred, translating into a risk of 13.2% and an incidence rate of 66.2 per 1000 person-years. GI adverse events comprised: dyspepsia n = 78 (12.3%), peptic ulcer disease (PUD) n = 5 (0.79%) and upper GI bleeding (UGIB) n = 1 (0.16%). The total direct healthcare cost of managing adverse events was Malaysian Ringgit (MR) 37 352 (US dollars [USD] 11 419) with a mean cost of MR 446.81 ± 534.56 (USD 136.60 ± 163.42) per patient, consisting mainly of GI pharmacotherapy (33.8%), oesophagoduodenoscopies (23.1%) and outpatient clinic visits (18.2%). Mean cost per patient by GI events were: dyspepsia, MR 408.98 ± 513.29 (USD125.03 ± 156.92); PUD, MR 805.93 ± 578.80 (USD 246.39 ± 176.95); UGIB, MR 1601.94 (USD 489.74, n = 1).
CONCLUSION: The economic burden of GI adverse events due to long-term NSAIDs use in Malaysian patients with chronic rheumatic diseases is modest.
Study site: Rheumatology clinics, Hospital Putrajaya, Hospital Selayang, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Optimization of Aceclofenac Proniosomes by Using Different Carriers, Part 1: Development and Characterization

Sammour RMF, Taher M, Chatterjee B, Shahiwala A, Mahmood S

Pharmaceutics, 2019 Jul 18;11(7).
PMID: 31323799 DOI: 10.3390/pharmaceutics11070350

In the contemporary medical model world, the proniosomal system has been serving as a new drug delivery system that is considered to significantly enhance the bioavailability of drugs with low water solubility. The application of this system can improve the bioavailability of aceclofenac that is used for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The present study is intended to develop an optimized proniosomal aceclofenac formula by the use of different carriers. Aceclofenac proniosomes have been prepared by slurry method, and different carriers such as maltodextrin, mannitol, and glucose were tried. Prepared proniosomes characterized by differential scanning calorimetry (DSC) analysis and Fourier transform infrared (FTIR) analysis revealed the compatibility of the drug chosen with the ingredient added, powder X-ray diffractometry (XRD) confirmed the amorphous phase of the prepared proniosomes, and finally, the surfactant layer was observed by scanning electron microscopy (SEM). Aceclofenac physical state transformations were confirmed with all formulas but maltodextrin proniosomes exhibited solubility more than other formulations. HPLC method has been used to analyze the niosomes derived from proniosomes in terms of their entrapment capability and drug content. The obtained results revealed that aceclofenac proniosomes can be successfully prepared by using different carriers.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA)--positive rheumatoid arthritis in three Asian ethnic groups

Too CL, Padyukov L, Dhaliwal JS, Lundström E, Yahya A, Muhamad NA, et al.

PLoS One, 2011;6(6):e21069.
PMID: 21698259 DOI: 10.1371/journal.pone.0021069

BACKGROUND: To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.
METHODS: 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.
RESULTS: The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.
CONCLUSION: The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Ultrastructural changes of the articular cartilage in some arthropathies with special reference to chondrocyte cell death

Kapitonova MY, Mansor O

Malays J Pathol, 2003 Jun;25(1):15-27.
PMID: 16196374

OBJECTIVE: To determine in situ using TEM the balance of apoptosis and necrosis in the articular cartilage of patients with inflammatory (rheumatoid arthritis and seronegative spondyloarthritis) and degenerative (osteoarthritis) joint diseases and to establish possible correlation between the cell death rate and the matrix vesicles formation.
METHODS: Cartilage samples of the knee joint were obtained from patients with rheumatoid arthritis (RA, 18 cases), osteoarthritis (OA, 22 cases), Reiter's disease (RD, 9 cases), peripheral form of the ankylosing spondyloarthritis (AS, 6 cases) and psoriatic arthritis (PA, 6 cases) during arthroscopy or knee surgery. Normal samples taken from autopsy cases without a history of joint diseases were used as control. Samples were processed for TEM with subsequent semi-quantitative estimation of the cell death rate in the superficial, middle and deep zone of non-calcified articular cartilage, and computer-aided ultramorphometric evaluation of the matrix vesicles of different types.
RESULTS: Both apoptotic and necrotic cell death could be identified in the cartilage of patients with inflammatory joint diseases, including seronegative spondyloarthritides and degenerative arthropathies. Apoptosis dominated over necrosis in all examined arthritides, including RA patients in which necrosis of the chondrocyte was the most frequent among arthropathies, while the highest apoptotic cell death rate was discovered in OA in which it correlated with the volume and numeric density of the matrix vesicles. These data provide evidence that apoptosis may contribute to the cartilage breakdown not only in RA and OA but also in the seronegative spondyloarthritides, which had a significantly higher apoptotic rate than the normal cartilage.

Matched MeSH terms: Arthritis, Rheumatoid
Nanomaterials for Nanotheranostics: Tuning Their Properties According to Disease Needs

Wong XY, Sena-Torralba A, Álvarez-Diduk R, Muthoosamy K, Merkoçi A

ACS Nano, 2020 03 24;14(3):2585-2627.
PMID: 32031781 DOI: 10.1021/acsnano.9b08133

Nanotheranostics is one of the biggest scientific breakthroughs in nanomedicine. Most of the currently available diagnosis and therapies are invasive, time-consuming, and associated with severe toxic side effects. Nanotheranostics, on the other hand, has the potential to bridge this gap by harnessing the capabilities of nanotechnology and nanomaterials for combined therapeutics and diagnostics with markedly enhanced efficacy. However, nanomaterial applications in nanotheranostics are still in its infancy. This is due to the fact that each disease has a particular microenvironment with well-defined characteristics, which promotes deeper selection criteria of nanomaterials to meet the disease needs. In this review, we have outlined how nanomaterials are designed and tailored for nanotheranostics of cancer and other diseases such as neurodegenerative, autoimmune (particularly on rheumatoid arthritis), and cardiovascular diseases. The penetrability and retention of a nanomaterial in the biological system, the therapeutic strategy used, and the imaging mode selected are some of the aspects discussed for each disease. The specific properties of the nanomaterials in terms of feasibility, physicochemical challenges, progress in clinical trials, its toxicity, and their future application on translational medicine are addressed. Our review meticulously and critically examines the applications of nanotheranostics with various nanomaterials, including graphene, across several diseases, offering a broader perspective of this emerging field.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*
Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Boesenbergia rotunda (L.) Mansf. inhibits CFA-induced rheumatoid arthritis in rats

Voon FL, Sulaiman MR, Akhtar MN, Idris MF, Akira A, Perimal EK, et al.

Eur J Pharmacol, 2017 Jan 05;794:127-134.
PMID: 27845065 DOI: 10.1016/j.ejphar.2016.11.009

Boesenbergia rotunda (L.) Mansf. had been traditionally used as herbs to treat pain and rheumatism. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) is a compound isolated from Boesenbergia rotunda (L.) Mansf.. Previous study had shown the potential of cardamonin in inhibiting the release of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. Thus, the possible therapeutic effect of cardamonin in the rheumatoid arthritis (RA) joints is postulated. This study was performed to investigate the anti-arthritic properties of cardamonin in rat model of induced RA, particularly on the inflammatory and pain response of RA. Rheumatoid arthritis paw inflammation was induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA) in Sprague Dawley rats. Using four doses of cardamonin (0.625, 1.25, 2.5, and 5.0mg/kg), anti-arthritic activity was evaluated through the paw edema, mechanical allodynia and thermal hyperalgesia responses. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma level of TNF-α, IL-1β, and IL-6. Histological slides were prepared from the harvested rat paws to observe the arthritic changes in the joints. Behavioral, biochemical, and histological studies showed that cardamonin demonstrated significant inhibition on RA-induced inflammatory and pain responses as well as progression of joint destruction in rats. ELISA results showed that there was significant inhibition in TNF-α, IL-1β, and IL-6 levels in plasma of the cardamonin-treated RA rats. Overall, cardamonin possesses potential anti-arthritic properties in CFA-induced RA rat model.

Matched MeSH terms: Arthritis, Rheumatoid/blood; Arthritis, Rheumatoid/chemically induced*; Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/pathology
Fulltext Morsellized Allograft and Acetabular Reconstruction Cage: Follow â€“ up of 2 to 9 years

Abbas, A.A., Merican, A.M., Mohamad, J.A.

Malays Orthop J, 2007;1(1):5-7.
MyJurnal

We report the outcome of 32 patients who underwent total hip replacement (THR) augmented with morsellized fresh frozen femoral head allografts and acetabular reconstruction cages. Nine patients underwent primary THR and 23 patients underwent revision THR. Follow-up ranged from two to 9 years. Two most common indications for the procedures as reported in literature were rheumatoid arthritis and aseptic loosening of the hip. All but one patient achieved good outcome with radiographs showing full incorporation of bone grafts and no evidence of loosening of the implants. Morsellized bone grafting used with acetabular reinforcement devices is valuable for addressing severe acetabular deficiencies.

Matched MeSH terms: Arthritis, Rheumatoid
Pomegranate use to attenuate bone loss in major musculoskeletal diseases: an evidence-based review

Shuid AN, Mohamed IN

Curr Drug Targets, 2013 Dec;14(13):1565-78.
PMID: 24200293

This review explores the effects of pomegranate on the pathogenesis of bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. A systematic review of the literature was conducted to identify the relevant studies on pomegranate and osteoporosis/osteoarthritis/rheumatoid arthritis. A comprehensive search was conducted in Medline and CINAHL for relevant studies published between the years 1946 to 2012. The main inclusion criteria were research articles published in English, studies had to report the association or effect of pomegranate and these bone and joint diseases: osteoporosis, osteoarthritis or rheumatoid arthritis. The literature search identified 35 potentially relevant articles, whereby 8 met the inclusion criteria. Two animal studies, two combinations of animal and in vitro studies, three in vitro studies and one human study were included in this review. All the studies reported positive effects of pomegranate extract or juice on osteoporosis, osteoarthritis and rheumatoid arthritis. This evidence-based review highlighted the potential of pomegranate extract being used for treating bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. Further studies are required to identify the active ingredients and molecular mechanisms before controlled human observational studies are conducted to provide stronger evidence.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*
Subclinical atherosclerosis among rheumatoid arthritis patients without overt cardiovascular risk factors

Sahari NS, Shaharir SS, Ismail MR, Rajalingham S, Mohamed Said MS

Mod Rheumatol, 2014 Nov;24(6):920-5.
PMID: 24645724 DOI: 10.3109/14397595.2014.891497

OBJECTIVE: To determine the associated factors of subclinical atherosclerosis measured with carotid intima media thickness (CIMT) among rheumatoid arthritis (RA) patients without any overt traditional cardiovascular (CV) risk factors.
METHODS: Forty RA patients with matched age and gender healthy controls were recruited. Carotid ultrasound was performed to all subjects. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex reference values. Univariate and multivariate analyses were performed to determine the association between the sociodemographics and disease characteristics of RA with thickened CIMT.
RESULTS: Abnormally thickened CIMT were observed in 11 RA patients (27.5%) and in 4 control subjects (10%), p = 0.04. It was highly prevalent among RA patients with active disease (54.5% vs 17.2%), p = 0.02. Patients with thickened CIMT also tend to have erosive disease, p = 0.06. Seropositive rheumatoid factor (RF) patients also had significantly higher CIMT values as compared with sero-negative patients, p = 0.03. Multivariable logistic regression analysis revealed that active disease was independently associated with thickened CIMT.
CONCLUSIONS: RA patients are at risk for subclinical atherosclerosis despite absence of traditional CV risk co morbidities and active disease was the independent factor associated with it.
KEYWORDS: Atherosclerosis; Carotid intima media thickness; Disease activity; Rheumatoid arthritis
Study site: Rheumatology Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/ultrasonography
Fulltext Anti-cyclic citrullinated peptide antibody is a good indicator for the diagnosis of rheumatoid arthritis

Abdul Wahab A, Mohammad M, Rahman MM, Mohamed Said MS

Pak J Med Sci, 2013 May;29(3):773-7.
PMID: 24353626

Objectives: Anti-cyclic citrullinated peptide (CCP) antibody has recently been used in the classification
of rheumatoid arthritis (RA). This antibody is more specific than rheumatoid factor (RF) for the diagnosis of RA. The study objectives were to determine the sensitivity, specificity, positive and negative predictive values of anti-CCP in RA diagnosis.
Methodology: Eighty RA patients and 80 non-RA individuals were included in the study. Blood was collected from both arms of study subjects and tested for anti-CCP and RF antibodies. Relevant clinical information and laboratory profiles of the RA patients were evaluated using patients’ medical records and Integrated Laboratory Management System (ILMS), respectively.
Results: The sensitivity and specificity of anti-CCP were 35% and 100% respectively. The positive and
negative predictive values were 100% and 61%, respectively. Positive anti-CCP was found significantly
associated with multiple joint pain (p < 0.001) and hand’s joints pain (p=0.01), symmetrical joints
involvement (p=0.015) and high CRP value (p < 0.001). Anti-CCP was also found to have positive association with RF (p < 0.001).
Conclusion: Anti-CCP is highly specific for the diagnosis of RA. High positive predictive value should be taken into consideration for effective treatment.
KEY WORD: Rheumatoid arthritis, anti-CCP, Rheumatoid factor, Sensitivity, Specificity, Positive predictive value, Negative predictive value.
Study site: Rheumatology Unit, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Sexual dysfunction and its determinants in Malaysian women with rheumatoid arthritis

Shahar MA, Hussein H, Sidi H, Shah SA, Mohamed Said MS

Int J Rheum Dis, 2012 Oct;15(5):468-77.
PMID: 23083037 DOI: 10.1111/j.1756-185X.2012.01753.x

AIM: 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.
METHOD: 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.
RESULTS: 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).
CONCLUSION: 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.
Study site: Rheumatology Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) and Hospital Putrajaya, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/ethnology
Fulltext Salivary and serum levels of Ca and Zn in periodontitis with or without rheumatoid arthritis

Jazli Aziz, Zamri Radzi, Rathna Devi Vaithilingam, Mohammad Tariqur Rahman

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):32-32.
MyJurnal

Introduction: While sharing a common causal link, both rheumatoid arthritis (RA) and periodontitis (PD) manifest similar inflammatory responses. With the progression of severity, both diseases result in bone loss. Hence, Ca and Zn, as structural components of the bones, are expected to be altered in saliva and serum in PD and RA respectively. Zinc and calcium concentrations have been studied previously in patients with PD or RA, with PD patients exhibiting increased salivary Ca and decreased Zn concentrations in serum, while RA patients have been reported to express low plasma concentrations of both Zn and Ca. The aim of this study is to evaluate the saliva and serum levels of Ca and Zn in PD patients with or without RA. Methods: Serum and saliva samples were collected from 82 patients from the Faculty of Dentistry, University of Malaya and the University Malaya Medical Centre rheumatoid clinic. Patients were grouped according to their periodontal health and RA status (healthy n=21; PD n=21; RA n=21; RAPD n=19). Results: Zinc concentration in serum was significantly higher (p

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Effect of Atorvastatin on the Disease Activity and Severity of Rheumatoid Arthritis: Double-Blind Randomized Controlled Trial

Mowla K, Rajai E, Ghorbani A, Dargahi-Malamir M, Bahadoram M, Mohammadi S

J Clin Diagn Res, 2016 May;10(5):OC32-6.
PMID: 27437268 DOI: 10.7860/JCDR/2016/16538.7814

INTRODUCTION:
HMG-CoA (3-hydroxy-3- methylglutary lcoenzyme A) reductase inhibitors (statins) have anti-inflammatory properties which may be particularly useful in rheumatoid arthritis to suppress disease activity and inflammatory factors.

AIM:
The purpose of this clinical trial was to determine anti-inflammatory properties of statins in rheumatoid arthritis.

MATERIALS AND METHODS:
Eighty Iranian patients with rheumatoid arthritis, aged between 19 to 75 years were recruited to take part in this randomized, double-blind placebo-controlled trial. Subjects were randomly allocated to two groups to take atorvastatin or placebo 40 mg daily as an adjunct to current disease-modifying anti-rheumatic drugs (DMARDs) treatment. Disease Activity Score-28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) & tender joint count (TJC) were assessed before and after three months intervention.

RESULTS:
Analysis was based on intention to treat. DAS28 significantly declined in the atorvastatin group in comparison with placebo (p< 0.001). SJC, TJC, CRP and ESR also were significantly dropped in the atorvastatin group in comparison with placebo.

CONCLUSION:
It can be concluded that atorvastatin can suppress RA activity and inflmmatory factors in RA patients for high to moderate grade of inflmmation.

KEYWORDS:
Anti-inflammatory agents; Erythrocyte sedimentation rate; HMG-CoA; Swollen joint count; Tender joint count

Matched MeSH terms: Arthritis, Rheumatoid
Diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis

Syed Mohamed Suhail SM, Nur Atiqah I, Nur Salimi Zakirah ZA, Lailatul Syazwani Z, Batis WW, Md Monoto EM, et al.

Malays J Pathol, 2019 Dec;41(3):259-265.
PMID: 31901910

INTRODUCTION: Rheumatoid arthritis is diagnosed based on the 2010 Rheumatoid Arthritis Classification Criteria whereby rheumatoid factor and anti-citrullinated protein antibody are the serological markers included in these criteria. Anti-RA33 antibody has the potential to provide additional diagnostic value in rheumatoid arthritis. The aim of this study is to determine the diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis.
MATERIAL AND METHODS: Thirtyfour patients with rheumatoid arthritis and 34 non-rheumatoid arthritis individuals were included in this cross-sectional study. Anti-RA33 antibody and rheumatoid factor were performed on all samples.
RESULTS: The sensitivity, specificity, positive and negative predictive value for anti-RA33 antibody and rheumatoid factor were 41.1%, 97.1%, 93.3%, 62.3% and 64.7%, 79.4%, 75.9%, 69.2% respectively. The overall sensitivity and specificity if either anti-RA33 antibody or rheumatoid factor are positive were 79.4% and 76.47% respectively.
CONCLUSION: Anti-RA33 antibody showed good specificity and positive predictive value and could be considered as a potential serological marker for rheumatoid arthritis diagnosis.

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/diagnosis*
Fulltext Effects of Methotrexate Therapy on the Levels of Gonadotropic Hormones in Rheumatoid Arthritis Patients of Reproductive Age

Kyaw MT, Sakthiswary R, Ani Amelia Z, Rahana AR, Munirah MM

Cureus, 2020 Apr 11;12(4):e7632.
PMID: 32399364 DOI: 10.7759/cureus.7632

BACKGROUND: Methotrexate (MTX), which is the anchor drug in rheumatoid arthritis (RA), targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve. The purpose of this study was to determine the effects of MTX therapy on gonadotropic hormones, i.e. follicular stimulating hormone (FSH) and luteinizing hormone (LH) in female RA patients of reproductive age.
MATERIALS AND METHODS: This is a cross-sectional study conducted at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC), from January 2018 to July 2018. Women with RA aged between 15 and 49 years who were on MTX therapy for at least six months, were consecutively recruited. All subjects were interviewed to gather information on their menstrual history and menopausal symptoms. The medical records were reviewed to obtain further data on the disease characteristics and RA treatment. The RA disease activity was determined using the DAS 28 scoring system. All subjects were tested for their serum FSH and LH levels.
RESULTS: A total of 40 patients were included in this study. The median dose of MTX used by the subjects was 12.5 mg weekly. The mean cumulative MTX dose was 1664.92 ± 738.61 mg. More than half (53.1%) of the subjects reported menopausal symptoms especially hot flushes. We found that FSH levels had a significant positive correlation with cumulative MTX dose [(r = 0.86), p < 0.001] and the duration of MTX therapy [(r = 0.84), p < 0.001]. Besides, there was a significant relationship between disease activity based on DAS 28 and FSH levels (p < 0.01). Age, body mass index, disease duration, and weekly MTX dose showed no associations with the FSH levels. On multivariate analysis, DAS 28 was found to be the only parameter that remained significant [β = 1.74 (95% CI 1.17-2.31), p < 0.001]. The LH levels, on the other hand, were not associated with MTX therapy or disease activity.
CONCLUSION: Higher levels of FSH, which is an indicator of diminished ovarian reserve, have a significant positive relationship with disease activity, cumulative dose, and duration of MTX therapy in RA.

Matched MeSH terms: Arthritis, Rheumatoid
Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-negative rheumatoid arthritis in Asian populations: evidence from the Malaysian MyEIRA case-control study

Yahya A, Bengtsson C, Lai TC, Larsson PT, Mustafa AN, Abdullah NA, et al.

Mod Rheumatol, 2012 Aug;22(4):524-31.
PMID: 22006120 DOI: 10.1007/s10165-011-0544-2

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.

Matched MeSH terms: Arthritis, Rheumatoid/ethnology; Arthritis, Rheumatoid/etiology*; Arthritis, Rheumatoid/immunology
Fulltext Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case-control study

Too CL, Muhamad NA, Ilar A, Padyukov L, Alfredsson L, Klareskog L, et al.

Ann Rheum Dis, 2016 06;75(6):997-1002.
PMID: 26681695 DOI: 10.1136/annrheumdis-2015-208278

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Matched MeSH terms: Arthritis, Rheumatoid/etiology*; Arthritis, Rheumatoid/genetics

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