Sakthiswary Rajalingham

Antagonizing IL-6 in ankylosing spondylitis: a short review.

Ankylosing spondylitis (AS) is a chronic inflammatory disorder with predilection for the axial skeleton, leading to progressive restricted mobility and deformity of the spine. The fundamental mechanism involves autoimmunity orchestrated by T cells. Similar to other rheumatic diseases, the complex interplay of cytokines such as tumour necrosis factor alpha, interleukin-6 (IL 6) and interleukin-10 (IL 10) has been implicated in the pathogenesis of the disease. Despite extensive research over the past decades, the treatment options for AS, are limited. Non steroidal antiinflammatory drugs are the first line of therapy, whereas anti TNF drugs are administered for refractory cases which fail to respond to the treatment. There have been conflicting views on the correlation of IL 6 with disease activity in AS. As such, the debate on the role of anti IL6 in AS is still ongoing. Anti IL 6 such as tocilizumab and siltuximab have proven efficacy based on the large randomized controlled trials. The Food and Drug Administration (FDA) has approved these drugs for treating rheumatoid arthritis and systemic juvenile idiopathic arthritis. Researchers have adventurously experimented anti IL 6 therapy in AS but the conclusions made were not consolidated into international guidelines or consensus statement for clinical practice. In the present review, we explore the role of anti IL6 in the treatment of AS based on the cumulative evidence over recent years.

Chronic necrotizing pulmonary aspergillosis presenting as bilateral pleural effusion: a case report.

IntroductionChronic necrotizing pulmonary aspergillosis is an uncommon subacute form of Aspergillus infection. It typically occurs in immunocompromised individuals and in those with underlying lung disease. This interesting case highlights the occurrence of this entity of aspergillosis in an immunocompetent middle-aged woman with atypical radiological findings. To the best of our knowledge this is the first case report of chronic necrotizing pulmonary aspergillosis presenting with pleural effusion.Case presentationOur patient was a 64-year-old Malay woman with a background history of epilepsy but no other comorbidities. She was a lifelong non-smoker. She presented to our facility with a six-month history of productive cough and three episodes of hemoptysis. An initial chest radiograph showed bilateral pleural effusion with bibasal consolidation. Bronchoscopy revealed a white-coated endobronchial tree and bronchoalveolar lavage culture grew Aspergillus niger. A diagnosis of chronic necrotizing pulmonary aspergillosis was made based on the clinical presentation and microbiological results. She responded well to treatment with oral itraconazole.ConclusionsThe radiological findings in chronic necrotizing pulmonary aspergillosis can be very diverse. This case illustrates that this condition can be a rare cause of bilateral pleural effusion.

Subclinical atherosclerosis among rheumatoid arthritis patients without overt cardiovascular risk factors.

Abstract 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.

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.

Etanercept in the treatment of recalcitrant enteropathic arthritis: a case report

IntroductionEnteropathic arthritis is one of the recognized extraintestinal manifestations of inflammatory bowel disease and affects up to 25% of patients. The treatment options for refractory disease were rather limited and ineffective until the arrival of biologic therapy in the last few years. The use of etanercept was unique for this disease.Case presentationIn this case report, a 58-year-old Malay woman with a 17-year history of ulcerative colitis had persistent left knee effusion and synovitis for seven years, despite remission of the primary disease. She had had multiple courses of systemic and intra-articular steroid that caused significant systemic side effects such as impaired fasting glucose, hypertension, cataract, and weight gain. She also had a total left knee replacement for secondary osteoarthritis. But the left knee synovitis and effusion recurred a month after the total knee replacement, and she was subjected to a total synovectomy the following year. In view of failure of remission despite multiple immunosuppressants (100 mg of azathioprine daily, 1 g of sulfasalazine twice a day, 10 mg of prednisolone daily, and 10 mg of methotrexate weekly), 25 mg of subcutaneous etanercept twice weekly was started. After 5 weeks of treatment, complete resolution of left knee effusion and normalization of the inflammatory markers were shown. This continued up to 12 months of follow-up while our patient was on etanercept and 10 mg of methotrexate weekly. No relapse or serious side effects were noted.ConclusionsThis case demonstrates the efficacy of etanercept in recalcitrant enteropathic arthritis with no relapse of the underlying colitis while on treatment. The usage of this tumor necrosis factor inhibitor was unique in this case of rheumatology and gastroenterology.

Role of hormonal fluctuations in temporomandibular disorder pain: facts to ponder.

To the Editor: I commend Srikandarajah and Gilron for critiquing the pain assessment approach used in the current research literature. Pain assessment scores are a valuable source of quality outcome data on analgesia efficacy [7]. It was disappointing to find that only 39% of trials included movement-evoked pain (MEP) as a quality measure [5]. Assessment of acute pain intensity at rest (RAP) after surgery is important to allow the patient to rest and sleep, but MEP during mobilization, deep breathing, and coughing is more important to determine whether analgesia is adequate for recovery of function, reducing risks of cardiopulmonary and thrombembolic complications and hospital stay [2]. Adequate postoperative analgesia is a basic human right; its management is essential to reduce morbidity and mortality [7]. Pain assessment is a fundamental quality tool that assists the diagnosis of a patient’s pain, selecting of appropriate analgesic modality and evaluating and modifying therapy to the patient’s response [1]. It is a subjective individual phenomenon, and measurement relies primarily on the patient’s perception [3]. The wide variation in pain amongst individuals leads to large variability in pain score of patients after similar surgery [4]. Clinically with no absolute reference standard for the measurement of pain, individuals vary in the subjective rating that they indicate, which may not reflect their capacity to mobilize, deep breathe or cough. At our institution, Royal Melbourne Hospital, our service has tried to bring some objectivity to pain measurement by observing each patient’s capacity to perform a task relevant to the surgical procedure. The degree of restriction was categorized accordingly as nil, mild, or severe. Severe restriction alerted us to inadequate analgesia and the need to initiate improvements to our regimen. In 2007, the Victorian Quality Council launched the Acute Pain Measurement Toolkit incorporating the Functional Activity Scale (FAS). The FAS score is a simple categorical score, used to assess whether the patient can undertake the appropriate activity at their current level of pain control (A = no limitation; B = mild limitation, with the patient able to undertake the activity and experiencing mild to moderate pain; C = significant limitation, with the patient unable to complete the activity because of pain) [6]. Unfortunately, this tool has not been validated; but to improve our pain assessment, it is time to explore how best to develop a framework within which to work to appreciate our patients’ experience of postoperative pain. Pain assessment tools are used to evaluate the efficacy of the analgesic regimen, to ensure that patients experience safe, effective, and individualized pain management [1]. Pain assessment is required to adequately capture the complexity of the pain experience postoperatively. Surgical trials need a standardized approach to pain assessment that can assist us to translate the scientific evidence found into improvements in our clinical practice.

THU0266 Effects of Various Immunosuppressants in the Disease Damage Among Patients with Systemic Lupus Erythematosus (SLE)

Background Various factors have been implicated in the disease damage in SLE. Objectives To investigate disease damage among SLE patients and to determine their association with patient exposure to the various immunosuppressive treatment. Methods A total of 220 SLE patients from the Universiti Kebangsaan Malaysia Medical Centre and Putrajaya Hospital were recruited. Information on the sociodemographic background, lupus characteristics and treatment were obtained from the medical records. Patients were stratified by the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology cumulative disease damage index (SDI ≥ 1= damage). Results Overall, 35% (78/220) patients had disease damage. Those who had ever received hydroxychloroquine (HCQ) were less likely to develop disease damage (37.5% vs 89.3%, p<0.001). Early HCQ treatment (≤3 months from the onset of diagnosis) and receipt of a loading dose of HCQ (6.5mg/kg daily) were less likely to be associated with disease damage [23.2% vs 67.1% and 28 % vs 54%, p<0.001 respectively]. In the HCQ treated group of patients, those with disease damage had a significantly lower cumulative HCQ [189.3 ± 192.2 g vs 314.1 ± 339.4 g, p<0.01]. Those who had a longer duration of corticosteroid treatment tended to develop disease damage (5.1 ± 4.8 years vs 3.8 ± 3.1 years, p=0.057) and more patients who received high dose prednisolone (≥ 1mg/kg daily) developed disease damage (52.2% vs 35.3%, p=0.04). Cyclophosphamide and cyclosporin A use were also associated with disease damage, 78.7% vs 31.7% and 85% vs 41%, p<0.001 respectively. After adjustment of age and major organ involvement of SLE (renal and NPSLE), in the regression analysis, presence of treatment with HCQ (OR 0.12, CI 95% 0.02-0.61, p=0.01) and early treatment with HCQ (≤ 3 months before the onset of SLE) protected against disease damage (OR0.32, CI 95% 0.11-0.91, p=0.03). Cyclophosphamide was an independent risk for disease damage (OR 11.5 CI 95% 3.5-35.6, p=<0.01). These data suggest that the use of cytotoxic agents such as cyclophosphamide and cyclosporine A were probably associated with more severe disease manifestations such as severe lupus nephritis. Conclusions Cyclophosphamide use increased the risk of disease damage whilst early treatment with HCQ protected against disease damage. A larger prospective study is needed to further delineate the contribution of the immunosuppressive treatment towards disease damage among SLE. References M. Petri et al. Predictors of Organ Damage in SLE: The Hopkins Lupus Cohort Arthritis Rheum. 2012 Dec;64(12):4021-8. Disclosure of Interest None Declared

AB0244 Retrospective study on effects of ramadhan month fasting on rheumatoid arthritis patients

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease which affects about 0.5% of adults in Malaysia. Objectives This study aimed to explore the overall effect of Ramadhan fasting onto RA disease activity and identify drug modification, drug side effects and diet changes occurring in Ramadhan. The study was approved by the Ethics Committee of UKMMC. Methods A retrospective case control study was done involving 71 patients who had appointments at the Rheumatology Clinic in UKMMC before Ramadhan and 2 months after Ramadhan, in 2010 and 2011. The fasting cohort (39 patients) and non fasting cohort (32 patients) were compared for RA disease activity (DAS28), intake of medication, side effects and diet before and during Ramadhan. Results In the fasting cohort, the mean for DAS28 before Ramadhan was higher than that after Ramadhan but this was not significant (p>0.05). Clinical symptoms of morning stiffness and fatigue were found in fewer patients after Ramadhan but this was not significant (p>0.05). There was a significant reduction in morning stiffness (x2=13.380, p=0.001) and in functional class (Z=-2.548, p=0.011) after Ramadhan, in the fasting cohort in 2010. The fasting cohort also showed asignificant reduction in the intake of high calorie food (Z=-2.295, p=0.022) in Ramadhan. There was an improvement in medication compliance among the patients, although this was not significant (p<0.05). Conclusions In conclusion, fasting lowers the mean of DAS28 in rheumatoid arthritis patients although this is statistically not significant. During fasting, changes in diet and medication intake do not significantly affect RA disease activity and do not cause significant side effects to fasting patients. Disclosure of Interest None Declared

Smoking bans and the reduction in heart diseases: The emerging scenario

We congratulate the authors for publishing the interesting article ‘Reassessing the evidence relating smoking bans to heart disease’ (Lee and Fry, 2011). This article is one of the first ever published meta-analyses which scrutinized and reassessed the accuracy of the available data on reduction in coronary events with smoking bans. Whilst the deleterious effects of smoking is well proven, this article highlighted that the reduction in acute myocardial infarction (AMI) with smoking bans is rather modest; ranging between 3% and 8%. The reduction of AMI may also vary from age to age. We feel that the Health stakeholders worldwide should concentrate on other forms of lifestyle modification in order to address the increasing burden of coronary artery disease. The authors meticulously analyzed 24 studies. All these studies hailed from the American and European continents. As medical practitioners from Asia, we would like to express our concern and disappointment on the lack of published data from this area in comparison to other regions of the world. Genetic predisposition varies from country to country and its influence on susceptibility to develop coronary artery disease is indisputable. Consumption of cigarettes is increasing more rapidly in developing countries compared to developed countries. Interestingly, in some parts of Asia, 70% of individuals are smokers (Taha and Ball, 1985). Hence, we see the need for further meta-analyses which includes data from more of the seven continents of the world. It would be interesting to evaluate the post smoking ban reduction in other conditions related to smoking such as stroke, lung malignancy and peripheral vascular disease. Intriguingly, a theoretical calculation of the effect of smoking bans in Gujarat estimated that 17,000 additional heart attacks were averted and 438,000 life years (LY) were gained. The paper assumed that a complete ban on smoking in public places would reduce acute myocardial infarction rates by 17%. In the light of these observations, banning smoking in public places may be cost-effective when key variables were varied in the sensitivity analyses. The cost-effectiveness ratio ranged from

Rheumatoid Arthritis: Refractory to Infliximab, a Tumor Necrosis Factor Inhibitor

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