AIM: The main objective of this study is to elucidate the role of immunoglobulin A (IgA) rheumatoid factor (RF) in predicting the clinical response to tumour necrosis factor α inhibitors (TNFi) among patients with rheumatoid arthritis (RA).
METHOD: We recruited all patients with RA who were ever on TNFi for a minimum duration of 3 months at our centre. Based on the European League Against Rheumatism response criteria, subjects were further divided into responders and non-responders. Age-matched RA patients who were on conventional disease-modifying anti-rheumatic drugs and in remission were enrolled as controls. Subjects were tested for quantitative values of IgA, IgM, IgG RF and anti-citrulinated cyclic peptides (CCP). Further, all subjects were assessed for the disease activity score that includes 28 joints (DAS28) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI).
RESULTS: A total of 31 subjects with RA who had received TNFi and 15 controls were enrolled in this study. There was a trend for the non-responders (n = 10) to have higher levels of all isotypes of RF and anti-CCP. However, only the IgA RF and anti-CCP levels were significantly higher in the non-responder group compared to the responders and controls (P = 0.001, P = 0.034, respectively). On multivariate analysis, only the IgA RF remained significant (OR 0.989; 95% CI 0.980-0.999; P = 0.026).
CONCLUSION: IgA RF is potentially a novel predictor of response to TNFi in RA patients. Testing for pretreatment IgA RF levels could be a reasonable consideration before commencement of TNFi.
Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
OBJECTIVE:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and glucocorticoid is the mainstay of treatment in SLE. The reported incidence of steroid-induced diabetes mellitus (SDM) ranged between 1-53%. We sought to investigate the prevalence and associated factors of SDM in patients with SLE.
METHODOLOGY:
A total of 100 SLE patients attending the Nephrology/SLE and Rheumatology Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) who received corticosteroid treatment were recruited. The diagnosis of diabetes mellitus was based on the 2010 American Diabetes Association's criteria. Prevalent cases of SDM were also included. Statistical analysis was performed to determine the factors associated with SDM.
RESULTS:
Thirteen of them (13%) developed SDM, with the median onset of diagnosis from commencement of glucocorticoid treatment being 8 years (range 0.5-21 years). Although only seven Indians were recruited into the study, three of them (42.9%) had SDM compared to Malays (9.3%) and Chinese (12.8%) (P ≤ 0.05). Univariate and multivariate analysis showed that higher numbers of system or organ involvement in SLE, abdominal obesity, hypertriglyceridemia and daily prednisolone of ≥ 1 mg/kg/day were the important associated factors of SDM (P ≤ 0.05). Meanwhile, hydroxychloroquine (HCQ) use was associated with reduced SDM prevalence (P < 0.05).
CONCLUSION:
The prevalence of SDM among SLE patients was 13% and Indians were more prone to develop SDM compared to other races. Higher numbers of system involvement, abdominal obesity, hypertriglyceridemia and the use of oral prednisolone of ≥ 1 mg/kg/day were associated with SDM, while HCQ use potentially protects against SDM.
AIM: To evaluate the clinical and antibody profile of systemic sclerosis (SSc) in a Malaysian cohort.
METHODS: Consecutive patients with SSc in University Malaya Medical Centre from March to November 2012 were included in this study. In addition to clinical characterization, all subjects underwent autoantibody testing using Euroline immunoblot assay. The association between clinical features and autoantibody profile was evaluated.
RESULTS: There were 31, predominantly Chinese (45.2%), subjects. Limited cutaneous disease was the most common subtype (71%). Raynaud's phenomenon was the most commonly observed feature (83.9%). Nine (29%) had esophageal dysmotility symptoms and 23 (74.2%), including all patients with diffuse SSc, had symptoms of gastro-esophageal reflux disease (GERD). Restrictive pattern on pulmonary function test and evidence of lung fibrosis were seen in more than 70% of patients. Echocardiographic evidence of pulmonary arterial hypertension was seen in 58.1%. Telangiectasia, calcinosis, digital ulcers, digital pulp loss or pitting were seen more commonly in the diffuse subtype. The two most prevalent autoantibodies were anti-Scl-70 and anti-Ro-52. The presence of anti-Scl-70 was significantly associated with restrictive lung disease (P = 0.05). Anti-Ro-52 was associated with control subjects with other autoimmune diseases (P = 0.043). The presence of anti-PM-Scl-75 was associated with overlap syndrome (P = 0.032). Patients with anticentromere antibodies were more likely to have vasculitic rash (P = 0.012).
CONCLUSION: In Malaysia, SSc most commonly affects the Chinese. Limited cutaneous is more common than diffuse subtype. Features of CREST (calcinosis, Reynaud disease, esophageal dysmotility, sclerodactyly, telangiectasia) are more commonly observed in the diffuse cutaneous subgroup. Anti-Scl-70 and anti-Ro-52 antibodies are promising biomarkers for pulmonary involvement in SSc.
KEYWORDS: Malaysia; autoantibodies; clinical profile; systemic sclerosis
Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC33 (2,6-bis[2,5-dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti-inflammatory activity has been synthesized and the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) were evaluated in vitro.
The aims of this study were to translate and examine the psychometric properties of the Malaysian version of the Osteoporosis Health Belief Scale (OHBS-M) among type 2 diabetes patients (T2DM) and to assess the correlation between osteoporosis knowledge, health belief and self-efficacy scales, as well as assess the osteoporosis risk in the sample population using quantitative ultrasound measurement (QUS).
We report a 29-year-old Malay man who had pulmonary manifestations as an initial presentation for systemic lupus erythematosus. He had prolonged hospitalization and was treated with intensive care therapy with immunosuppressants.
The modified Rodnan skin score is widely accepted as a validated tool to assess skin involvement in systemic sclerosis, which is a hallmark of this heterogeneous disease. Ultrasonography is increasingly being utilized in the study of other rheumatic diseases. The utility of ultrasonography to measure skin thickness in systemic sclerosis has been explored since three decades ago. The aim of this review was to examine the validity of ultrasonography as an outcome measure of skin involvement in systemic sclerosis. Original articles in English, published before December 2010, pertaining to the use of B mode ultrasound assessing skin involvement in systemic sclerosis were reviewed. Data were extracted with a focus on criterion and construct validity, reproducibility and responsiveness to change. Seventeen papers were analyzed. Skin thickness was most commonly studied, although skin echogenicity has also been examined. There was heterogeneity with regards to subjects, definitions used and sites imaged. Although there was limited information regarding reliability, when reported, the results showed excellent reproducibility. There was also a lack of construct and criterion validity and evidence for sensitivity to change. Ultrasound has potential as an outcome measure in systemic sclerosis. However, more work needs to be done in order to prove that it is a feasible outcome measure with proven validity.
Mycophenolate is an immunosuppressive agent which has been used in systemic lupus erythematosus (SLE) patients who have failed conventional therapy. However, the use of mycophenolate sodium in extra-renal SLE involvement has yet to be established. This study aimed to assess the efficacy of mycophenolate sodium in extra-renal SLE.
BACKGROUND: The ethiopathogenesis of increased apoptosis of lymphocytes in systemic lupus erythematosus (SLE) is still incompletely understood but anti-C1q autoantibodies have been shown to induce apoptosis in lymphocytes from healthy donors and certain cell lines.
AIM: This study was undertaken to investigate the relationship between peripheral lymphocyte apoptosis and serum levels of anti-C1q autoantibodies in SLE patients.
METHODS: The sera of 124 patients with SLE involving 62 active SLE and 62 inactive SLE, fulfilling America College of Rheumatology (ACR) classification criteria for SLE (1997) were incubated with peripheral blood lymphocytes of healthy donors. The results were compared with 124 sex- and age-matched normal controls. Apoptotic lymphocytes (AL) were detected by flow cytometry using annexin V and propidium iodide binding. Anti-C1q autoantibodies were detected by an enzyme-linked immunoassay kit for all SLE patients.
RESULTS: Results demonstrated that the percentage of AL in the peripheral blood of active SLE patients was significantly higher (n = 62, 34.95 ± 12.78%) than that of the inactive SLE patients (n = 62, 30.69 ± 10.13%, P = 0.042, 95%CI = 0.16-8.36) and normal controls (n = 124, 27.92 ± 10.22%, P = 0.001, 95%CI = 3.33-10.73). The percentage of AL significantly correlated with serum levels of anti-C1q autoantibodies in the active SLE patients (r = 0.263, P = 0.039) but not in the inactive SLE patients (r = 0.170, P = 0.185).
CONCLUSION: The results of this study suggest that increased serum levels of anti-C1q autoantibodies are responsible for apoptosis and may play a pathogenic role in SLE patients, especially in active disease.
KEYWORDS: anti-C1q; apoptosis; flowcytometry; systemic lupus erythematosus
Study site: Medical outpatient clinic and medical wards, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia
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
AIM: To determine if baseline vitamin D levels would influence the gain in bone mineral density (BMD) in female systemic lupus erythematosus (SLE) patients on corticosteroids (CS) taking bone-active medication.
METHOD: Premenopausal SLE patients participating in a trial assessing the efficacy of calcium alone, calcitriol and calcium, and alendronate and calcium, on BMD in patients on CS, were studied. Patients were randomly allocated to the treatment groups at the start of the study and followed up for 2 years. Serum 25-hydroxy vitamin D [25(OH)D] was measured at baseline.
RESULTS: Thirty-eight patients were studied. One (2%) patient had osteoporosis, nine (24%) had osteopenia and all others had normal BMD. The mean baseline 25(OH)D levels were 21.6 ± 4.6 ng/mL (± 1 SD). Twelve (32%) patients had vitamin D deficiency [25(OH)D < 20 ng/mL]. There was a significant negative correlation between SLEDAI scores and 25(OH)D levels, that is, patients with high SLEDAI scores had significantly lower 25(OH)D levels (P = 0.033). Left femoral neck BMD was significantly lower in the deficient compared to insufficient group (P = 0.042). There was a trend toward better BMD gain at 2 years in the vitamin D insufficient compared to the deficient group, which did not reach statistical significance.
CONCLUSION: This study showed that in female SLE patients, low vitamin D levels are associated with higher disease activity and suggests that patients who have higher vitamin D levels have a better BMD response during treatment with bone-active agents.
We report a 57-year-old woman with a 20-year history of hepatitis B presenting with progressive proximal lower limb weakness for the previous 1 month. Previous medical history included a pericardial and pleural effusion, of which no cause was found and pulmonary tuberculosis which has been adequately treated. Examination revealed multiple telangiactasia over face and nail beds and bilateral proximal lower limb weakness of power 4/5. Biochemical investigation revealed a raised erythrocyte sedimentation rate of 36 mm/h, elevated creatinine kinase levels (14,363 IU/L) and raised liver enzymes (alanine aminotransferase 445 IU/L, aspartate aminotransferase 606 IU/L) with high hepatitis B virus DNA (1,021,158 copies/mL). Nerve conduction tests and muscle biopsy were consistent with polymyositis. She received entacavir for hepatitis B treatment. Despite treatment with entacavir for 10 weeks, her weakness persisted and prednisolone was added. Upon commencement of prednisolone, her symptoms and biochemical profiles returned to normal.
AIM: The objectives of this study were to investigate the frequency of thickened carotid intima media thickness (CIMT) and atherosclerosis among lupus nephritis (LN) patients and to study their associated risk factors.
METHOD: In this cross-sectional study, carotid ultrasonography was performed on consecutive LN patients to determine CIMT and presence of carotid plaques. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex from the 'Carotid Atherosclerosis Progression Study'. The association between thickened CIMT with traditional cardiovascular risk factors and lupus characteristics were examined. A total of 83 patients with the mean age of 33.6 ± 10 years were recruited.
RESULTS: Fourteen patients (16.9%) had thickened CIMT and three (3.6%) had carotid plaques. On univariate analysis, traditional risk factors significantly associated with thickened CIMT (P < 0.05) were patient's current age, diabetes mellitus and waist circumference. Meanwhile, a lower serum C4 levels and higher serum C-reactive protein levels were the lupus-specific factors associated with thickened CIMT (P < 0.05, P < 0.05 and P < 0.01, respectively). In logistic regression analysis, the independent predictors of thickened CIMT were age of diagnosis, lower serum C4 levels and waist circumference (P < 0.05).
CONCLUSION: More lupus specific factors were independently associated with thickened CIMT, suggesting that a multi-targeted approach of treatment addressing both the lupus and traditional cardiovascular risks are very important. Larger prospective studies of these special risk factors are indicated.
Introduction: 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.
Objectives: 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.
Method: 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.
Conclusions: 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.
Key words: high resolution computed tomography, interstitial lung disease, lung function test, rheumatoid arthritis.
Study site: Rheumatology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
AIM: To measure the level of anti-nucleosome antibodies in systemic lupus erythematosus (SLE) patients, to determine the sensitivity and the specificity of these antibodies in the diagnosis of the disease and to evaluate the relationship between the levels of anti-nucleosome antibodies, anti-dsDNA (double-stranded DNA) and SLE disease activity.
METHODS: A cross-sectional study was conducted. All patients attended either a medical specialist clinic or were admitted to the medical wards of Hospital Universiti Sains Malaysia with the diagnosis of SLE (n = 90), other connective tissue diseases (n = 45) or were normal controls (n = 90) within the period from July 2004 until September 2005. They were tested for anti-nucleosome antibodies by enzyme-linked immunosorbent assay and anti-DNA antibodies by immunofluorescence. SLE disease activity was evaluated by SLE disease activity index (SLEDAI) score.
RESULTS: Out of 90 SLE patients, anti-nucleosome antibodies were positive in 47 (52.2%) patients, whereas these antibodies were positive in three (6.7%) patients with other connective tissue diseases. Anti-dsDNA antibodies were positive in 33 (36.7%) SLE patients, whereas these antibodies were positive in four (8.9%) patients with other connective tissue diseases. Anti-nucleosome antibodies were positive in 40 (97.6%) patients with active SLE, whereas these antibodies were positive in seven (14.3%) patients with inactive SLE. Anti-nucleosome antibodies had a stronger correlation than anti-dsDNA antibodies with SLEDAI score. There was a significant association between anti-nucleosome antibodies and disease activity.
CONCLUSION: Anti-nucleosome antibodies test is highly sensitive and specific for the diagnosis of SLE, especially when the anti-dsDNA antibodies are absent. They are additional disease activity markers in the assessment of SLE disease activity.
AIM: The aim of this study was to ascertain the management of gout by doctors in Malaysia.
METHODS: A cross-sectional questionnaire survey was carried out among doctors attending rheumatology post-graduate courses, where gout was not a lecture topic.
RESULTS: A total of 128 questionnaires were analyzed, of which the majority (67: 52.3%) were general practitioners. In the treatment of acute gout, 68.0% use non-selective non-steroidal anti-inflammatory drugs (NSAIDs), 53.9% use selective COX-2 inhibitors (coxibs), 66.4% use colchicine and 10.2% use allopurinol (ALLO). In the treatment of chronic gout, 36.7% use NSAIDs, 44.5% use coxibs, 19.5% use colchicine and 93% use ALLO. In both acute and chronic gout, corticosteroids (CS) are not used by over 90% of respondents. Fifty percent would stop ALLO during an acute attack. 95.3% do not start ALLO during an acute attack; 87.5% would start ALLO after the attack, with a median of 14 days afterwards. Once ALLO was started, 54.7% would continue indefinitely. Regarding target urate levels while on treatment, 10.9% would be satisfied with a high normal range, 21.9% middle of the range, 18.0% low normal range and 45.3% anywhere within the normal range. Fifteen percent would treat asymptomatic hyperuricemia.
CONCLUSIONS: In Malaysia, anti-inflammatory agents are most commonly used for the treatment of acute and chronic gout, with corticosteroid usage at a low level. However, there are areas of concern regarding the diagnosis of gout and the usage of ALLO which are not consistent with current guidelines
AIM: 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).
METHOD: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Comment on: Shahrir M, Shahdan M, Shahid M, Sulaiman W, Mokhtar AM, Othman M, et al. Multicentre survey of rheumatoid arthritis patients from ministry of health rheumatology centers in malaysia. Int J Rheum Dis. 2008;11(3):287-92. doi:10.1111/j.1756-185X.2008.00379.x;