Antinuclear antibodies in primary osteoarthritis of the knee

Objective: Although osteoarthritis (OA) is widely accepted as a degenerative disease, autoimmune processes are believed to be involved in the pathogenesis. There are limited studies in this area and most of them focused on antibodies against chondrocyte membrane. In an attempt to address the paucity of evidence in this regard, we explored the clinical significance of antinuclear antibody (ANA) in primary osteoarthritis of the knee (OAK). Method: We studied 106 patients with primary osteoarthritis of at least 1 knee and 63 healthy controls from two tertiary centres in Malaysia from September 2005 to May 2012. All subjects were tested for ANA by immunofluorescence testing, and a titer of 1:40 and above was considered positive. Besides, the radiographs of bilateral knees were evaluated for grading, tibiofemoral compartment involvement and total knee replacement (TKR) implants. We compared the clinical characteristics between the ANA positive and ANA negative OAK cases. Results: The incidence of ANA positivity among the cases (39.4 %) was higher than the controls (27 %) but this difference was statistically insignificant (p=0.754). ANA positive cases showed significantly higher incidence of bilateral and Grade IV OAK with higher frequency of TKR. In the multiple regression analysis, bilateral OAK (p< 0.0001; odds ratio 9.00), Grade IV OAK (p<0.001, odds ratio 3.44) and TKR (p=0.009; odds ratio 2.97) remained associated with ANA positivity. Conclusions: ANA test is a potential prognostic tool in primary OAK and its positivity is associated with the clinical outcomes of bilateral, Grade IV OAK and TKR

Case Review of Sarcoidosis Resembling Sjogren's Syndrome

We would like to report a case of a 29-year-old male patient who presented with multiple lymphadenopathy and vague symptoms of low grade fever, cough, weight loss, rashes, vomiting, dry eyes and dry mouth. Physical examination revealed submandibular lymphadenopathy, vasculitic rashes over both lower limbs, and parotid gland enlargement. Blood investigations showed mild anemia with leukocytosis, predominantly eosinophilia and high erythrocyte sedimentation rate and C-reactive protein. Computed tomography of the neck, thorax and abdomen showed bilateral submandibular, submental adenopathy, mediastinal and para-aortic lymphadenopathy with generalized reticulonodular densities in both lower lobes. There were hepatomegaly and bilateral enlarged kidneys with renal cyst. Histopathological examination from the cervical lymph node later revealed non-caseating granuloma, consistent of sarcoidosis. Patient responded well to prednisolone 50 mg daily with subsequent reduction in the size of cervical lymphadenopathy and parotid swelling

A Study of Intima Media Thickness and Their Cardiovascular Risk Factors in Patients with Psoriatic Arthritis

Introduction: Psoriatic Arthritis (PsA) is an inflammatory arthritis associated with Psoriasis. Its recognition as an inflammatory disease distinct from Rheumatoid Arthritis has put forward for consideration several questions regarding its specific CVS mortality and morbidity (9, 11, 16, 26). Carotid intima media thickness is a useful surrogate and sensitive marker to determine atherosclerosis even in its subclinical stages (6, 14, 22, 27, 32). Objective: Prevalence of carotid intima media thickness in patients with Psoriatic arthritis is unknown in Asian population. We aim to identify the presence of subclinical atherosclerosis in patients with psoriatic arthritis and disease activity association and its predictors in a series of patients with PsA attended to the rheumatology clinic, tertiary hospitals. Methods: A total of 63 patients with PsA who fulfilled the CASPAR criteria were recruited from UKM Medical Centre and Hospital Putrajaya. Common carotid intima media thickness (IMT) was measured in both right and left carotid artery by using high resolution B-mode ultrasound. This was a cross sectional study first done in Malaysia for PsA patients. Results: The positive IMT (IMT >1.00 mm) among PsA was observed in 10 out of 63 patients (15.9 %) regardless of background cardiovascular risk. The mean±SD of IMT was 0.725 ±0.260 mm for this study. Variables significantly associated with positive IMT (p<0.05) included age at the time of study (p=0.005), waist circumference (p=0.001), Hypertension (p=0.007), Diabetes (p=0.002) and Metabolic syndrome (p=0.001) and not associated with gender, ethnicity, duration of PsA disease, pattern of PsA, disease activity and severity. Above all, only age had positive IMT independent predictor (p=0.032), with OR 1.116; 95 % CI (1.010–1.234). Conclusions: There was a significant association between CVS risk and positive Intima Media Thickness in Psoriatic Arthritis patients. Otherwise, there was no association in disease activity, disease severity and DMARDS therapy with positive Intima Media Thickness in Psoriatic Arthritis patients. The study was approved by Research and Ethics Committee of the faculty of medicine, Universiti Kebangsaan Malaysia with project code FF-114-2008 and by Community Research Center (CRC) of National Institutes of Health (NIH) for the case study in Hospital Putrajaya with the project code NMRR-08- 970-2125

Damage in the Multiethnic Malaysian Systemic Lupus Erythematosus (SLE) Cohort: Comparison with Other Cohorts Worldwide.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and despite the improvement in the survival in the past few decades, the morbidity due to disease damage remains significant. The objectives of this study were to investigate the disease damagepattern and determine the associated factors of damage in the multi-ethnic Malaysian SLE patients. We consecutively 424SLE patients who attended a consistent follow-up at the National University of Malaysia Medical Centre and Putrajaya Hospital were recruited. Disease damage was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index (SDI) scores. Information on their demographics and disease characteristics were obtained from the clinical record. Univariate analysis was performed and the best model of independent predictors of disease damage was determined by multivariate logistic regression analysis. A total of 182 patients (42.9%) had disease damage (SDI ≥1). A significantly higher number of Indian patients had disease/organ damage and they predominantly developed steroid-induced diabetes mellitus (SDM). Patients with corticosteroid-induced osteoporosis (CIOP) were more likely to be Malayswhile majority of patients who developed malignancy were Chinese (p<0.05). In the univariate and multivariate analyses, disease damage was significantly associated with age, Indian ethnicity, lower mean cumulative C3 level, neuropsychiatry lupus (NPSLE), and antiphospholipid syndrome (APLS). Patients who had ever and early treatment with hydroxychloroquine(HCQ)were less likely to develop disease damage while more patients who had received oral prednisolone ≥1mg/kg daily over 2 weeks had disease damage (p<0.05). In conclusion, there were inter-ethnic differences in the damage pattern and risks among SLE patients

Sera of patients with systemic lupus erythematosus cross-neutralizes dengue viruses

Dengue is the most prevalent mosquito-borne disease in Southeast Asia, where the incidence of systemic lupus erythematosus (SLE) is approximately 30 to 53 per 100,000. Severe dengue, however, is rarely reported among individuals with SLE. Here, whether sera of patients with SLE cross-neutralize dengue virus (DENV) was investigated. Serum samples were obtained from individuals with SLE who were dengue IgG and IgM serology negative. Neutralization assays were performed against the three major DENV serotypes. Of the dengue serology negative sera of individuals with SLE, 60%, 61% and 52% of the sera at 1/320 dilution showed more than 50% inhibition against dengue type-1 virus (DENV-1), DENV-2 and DENV-3, respectively. The neutralizing capacity of the sera was significantly greater against DENV-1 (P < 0.001) and DENV-3 (P < 0.01) than against DENV-2 (P < 0.05). Neutralization against the DENV correlated with dengue-specific IgG serum titers below the cut-off point for dengue positivity. Depletion of total IgG from the sera of patients with SLE resulted in significant decreases of up to 80% in DENV inhibition, suggesting that IgG plays an important role. However, some of the SLE sera was still able to neutralize DENV, even with IgG titers <0.1 OD absorbance. Our findings suggest that sera of patients with SLE contain IgG, and possibly other type of antibodies, that can cross-neutralize DENV, which may explain the rarity of severe dengue in individuals with SLE. Further studies, are needed to further substantiate this finding and to elucidate the specific neutralizing epitopes recognized by the sera of individuals with SLE

Clinical and economic implications of upper gastrointestinal adverse events in Asian rheumatological patients on long-term non-steroidal anti-inflammatory drugs

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