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Antagonizing IL-6 in ankylosing spondylitis: a short review

Rajalingham S, Das S

Inflamm Allergy Drug Targets, 2012 Aug 1;11(4):262-5.
PMID: 22452603

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

Rajalingham S, Anshar FM

J Med Case Rep, 2012;6:62.
PMID: 22333492 DOI: 10.1186/1752-1947-6-62

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

Das S, Rajalingham S

Pain, 2012 Jan;153(1):250-251.
PMID: 22119339 DOI: 10.1016/j.pain.2011.10.039
Fulltext Personal Protective Equipment (PPE) and Its Use in COVID-19: Important Facts

Das S, Rajalingham S

Indian J Surg, 2020 May 28.
PMID: 32837060 DOI: 10.1007/s12262-020-02411-8
Fulltext An increasingly notorious mimicker of testicular tumours; crossing borders

Periyasamy P, Subramaniam SR, Rajalingham S

BMJ Case Rep, 2011;2011.
PMID: 22675021 DOI: 10.1136/bcr.09.2011.4816

Data from the WHO state that up to 85% of cases of human schistosomiasis are from Africa. The common sites of this parasitic infection are the intestine and bladder. Testicular schistosomiasis is extremely rare but the number of reported cases worldwide has doubled over the past decade. The authors report a case of testicular schistosomiasis of a Myanmar immigrant in Malaysia who presented with a 6-month history of progressively enlarging left testicular swelling. His biochemical markers and cultures were not suggestive of an ongoing infection. Hence, a testicular malignancy was strongly suspected, for which, he underwent a left orchidectomy. Our clinical suspicion was proven wrong when the histopathology of the removed left testis revealed schistosomal eggs with granulamatous tissue formation. Subsequently, the patient was treated with praziquantel.
Fulltext Rheumatoid arthritis: refractory to infliximab, a tumor necrosis factor inhibitor

Solehan HM, Said MS, Shaharir S, Rajalingham S

J Clin Med Res, 2011 Oct;3(5):270-4.
PMID: 22383918 DOI: 10.4021/jocmr630w

Rheumatoid arthritis is one of the commonest autoimmune diseases. It is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis. If left untreated, it leads to joint destruction and thus deformity and disability.In the recent years, advances in molecular biology have led to a variety of new treatment approaches to rheumatoid arthritis and other systemic inflammatory diseases associated with autoimmunity. Anti tumor necrosis factor (TNF) agents are emerging in the frontline management of rheumatoid arthritis (RA) in the current era of biological treatment. We presented a 46-year-old Chinese female with a history of seropositive RA for the past 22 years refractory and intolerant to multiple medications including sulphasalazine (SSZ), leflunomide, hydroxychloroquine (HCQ) and methotrexate (MTX), thus infliximab, a tumor necrosis factor (TNF) inhibitor was initiated. However, despite receiving 6 cycles of infliximab therapy, she still complained of persistent disabled multiple joint pain and swelling. This report will discuss about rheumatoid arthritis, which is refractory to infliximab (a TNF inhibitor) and its alternative.
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
Fulltext Etanercept in the treatment of recalcitrant enteropathic arthritis: a case report

Mohamed Said MS, Shaharir S, Rajalingham S, Abdullah SA, Bin Hassanudin A, Soon NC, et al.

J Med Case Rep, 2012;6:10.
PMID: 22236863 DOI: 10.1186/1752-1947-6-10

Enteropathic 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.
Fulltext Dermatomyositis masquerading musculoskeletal tuberculosis

Rajalingham S, Said MS, Shaharir SS, AbAziz A, Periyasamy P, Anshar FM

BMJ Case Rep, 2011;2011.
PMID: 22675098 DOI: 10.1136/bcr.08.2011.4675

Dermatomyositis is a rare rheumatic disease which predominantly affects the muscles and skin requiring a protracted course of immunosuppressants which may predispose the patients to opportunistic infections. A 49-year-old lady was diagnosed to have dermatomyositis in August 2010 based on history, significantly raised creatine kinase level and muscle biopsy findings. She had recurrent admissions due to fever, myalgia and muscle weakness. She had spiking temperature despite high dose steroids, broad-spectrum antibiotics and antifungal agents. This prompted extensive investigation which leads us to the additional diagnosis of disseminated tuberculosis involving the lungs, muscles and bones. This case demonstrates the challenge in controlling the disease activity of dermatomyositis with immunosuppressants in the setting of disseminated tuberculosis.
Fulltext Burden of Systemic Lupus Erythematosus on Work Productivity and Daily Living Activity: A Cross-Sectional Study Among Malaysian Multi-Ethnic Cohort

Abu Bakar F, Sazliyana Shaharir S, Mohd R, Mohamed Said MS, Rajalingham S, Wei Yen K

Arch Rheumatol, 2020 Jun;35(2):205-213.
PMID: 32851369 DOI: 10.46497/ArchRheumatol.2020.7405

Objectives: This study aims to assess the self-reported work productivity and activity daily living (ADL) impairment among Malaysian patients with systemic lupus erythematosus (SLE) and to examine their associated factors.
Patients and methods: This cross-sectional study included 167 SLE patients (21 males, 146 females; mean age 38.2±9.8 years; range, 20 to 60 years) recruited from the outpatient Rheumatology and Nephrology clinics. Face-to-face interviews were conducted to record patients' socio- demographics (age, sex, ethnicity, marital status, and occupation) and SLE disease characteristics (system involvement, age onset, and presence of organ damage). Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K). Short form 36 (SF-36) was used to determine health-related quality of life (HRQoL) while Work Productivity and Activity Impairment (WPAI) questionnaire was used to assess the four domains of absenteeism, presenteeism, overall work productivity, and non-work related ADL impairment. Univariate analyses and multivariable regression analysis examined the association of demographic variables, SLE disease characteristics, and activity with reduced HRQoL and WPAI scores.
Results: The majority of the patients were Malays (59.3%), followed by Chinese (34.7%) and Indian (3.6%) patients. More than two-thirds of the patients reported some degree of impairment in their work productivity and ADL due to the disease. The absenteeism rate was 10.4% in the past one week and their indirect costs were 2,875.17 Malaysian ringgits (US $701.22) in the past seven days. Significant predictors of higher work productivity and ADL impairment scores were higher disease activity, more frequent SLE flares, lupus nephritis, and hematological involvement of SLE. Patients with higher work productivity and ADL impairment scores were also strongly associated with poor QoL. No ethnic disparities of work productivity and ADL impairment were found.
Conclusion: Systemic lupus erythematosus significantly affected the overall productivity in work and non-work related activity in our Malaysian multi-ethnic cohort and both impairments were significantly associated with poor QoL.
Fulltext Damage in the multiethnic Malaysian systemic lupus erythematosus (SLE) cohort: Comparison with other cohorts worldwide

Shaharir SS, Hussein H, Rajalingham S, Mohamed Said MS, Abdul Gafor AH, Mohd R, et al.

PLoS One, 2016;11(11):e0166270.
PMID: 27846298 DOI: 10.1371/journal.pone.0166270

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.
Serum and urine interleukin-17A levels as biomarkers of disease activity in systemic lupus erythematosus

Nordin F, Shaharir SS, Abdul Wahab A, Mustafar R, Abdul Gafor AH, Mohamed Said MS, et al.

Int J Rheum Dis, 2019 Aug;22(8):1419-1426.
PMID: 31179646 DOI: 10.1111/1756-185X.13615

OBJECTIVES: This study examined the correlations of both serum and urine interleukin-17A (IL-17A) levels with disease activity in systemic lupus erythematosus (SLE). This study was also aimed at determining their sensitivity and specificity as biomarkers of disease activity in SLE.
METHODS: A cross-sectional study was performed involving SLE patients (n = 120 patients) from Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Serum and urinary IL-17A levels were determined by immunoassay while disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) and British Isles Lupus Assessment Group's 2004 index (BILAG 2004) scores. The correlations between serum and urinary IL-17A levels with total SLEDAI-2K and BILAG 2004 scores were determined using bivariate correlation analyses. Receiver operating characteristic curves were calculated to determine their sensitivity and specificity as disease activity biomarkers.
RESULTS: Both serum and urinary IL-17A levels correlated with total scores of BILAG 2004, BILAG renal, BILAG mucocutaneous, and SLEDAI-2K (P
Fulltext Risk factors for symptomatic Avascular Necrosis (AVN) in a multi-ethnic Systemic Lupus Erythematosus (SLE) cohort

Shaharir SS, Chua SH, Mohd R, Mustafar R, Noh MM, Shahril NS, et al.

PLoS One, 2021;16(3):e0248845.
PMID: 33739994 DOI: 10.1371/journal.pone.0248845

Avascular necrosis of bone (AVN) is increasingly being recognized as a complication of SLE and causes significant disability due to pain and mobility limitations. We studied the prevalence and factors associated with avascular necrosis (AVN) in a multiethnic SLE cohort. SLE patients who visited the outpatient clinic from October 2017 to April 2019 were considered eligible. Their medical records were reviewed to identify patients who developed symptomatic AVN, as confirmed by either magnetic resonance imaging or plain radiography. Subsequently, their SLE disease characteristics and treatment were compared with the characteristics of patients who did not have AVN. Multivariable logistic regression analyses were performed to determine the independent factors associated with AVN among the multiethnic SLE cohort. A total of 390 patients were recruited, and the majority of them were females (92.6%); the patients were predominantly of Malay ethnicity (59.5%), followed by Chinese (35.9%) and Indian (4.6%). The prevalence of symptomatic AVN was 14.1%, and the mean age of AVN diagnosis was 37.6 ± 14.4 years. Both univariate and multivariable logistic regression analyses revealed that a longer disease duration, high LDL-C (low density lipoprotein cholesterol), positive anti-cardiolipin (aCL) IgG and anti-dsDNA results, a history of an oral prednisolone dose of more than 30 mg daily for at least 4 weeks and osteoporotic fractures were significantly associated with AVN. On the other hand, hydroxychloroquin (HCQ), mycophenolate mofetil (MMF) and bisphosphonate use were associated with a lower risk of AVN. No associations with ethnicity were found. In conclusion, several modifiable risk factors were found to be associated with AVN, and these factors may be used to identify patients who are at high risk of developing such complications. The potential protective effects of HCQ, MMF and bisphosphonates warrant additional studies.
Fulltext The Effects of Annatto Tocotrienol Supplementation on Cartilage and Subchondral Bone in an Animal Model of Osteoarthritis Induced by Monosodium Iodoacetate

Chin KY, Wong SK, Japar Sidik FZ, Abdul Hamid J, Abas NH, Mohd Ramli ES, et al.

Int J Environ Res Public Health, 2019 08 13;16(16).
PMID: 31412648 DOI: 10.3390/ijerph16162897

Osteoarthritis is a degenerative joint disease which primarily affects the articular cartilage and subchondral bones. Since there is an underlying localized inflammatory component in the pathogenesis of osteoarthritis, compounds like tocotrienol with anti-inflammatory properties may be able to retard its progression. This study aimed to determine the effects of oral tocotrienol supplementation on the articular cartilage and subchondral bone in a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). Thirty male Sprague-Dawley rats (three-month-old) were randomized into five groups. Four groups were induced with osteoarthritis (single injection of MIA at week 0) and another served as the sham group. Three of the four groups with osteoarthritis were supplemented with annatto tocotrienol at 50, 100 and 150 mg/kg/day orally for five weeks. At week 5, all rats were sacrificed, and their tibial-femoral joints were harvested for analysis. The results indicated that the groups which received annatto tocotrienol at 100 and 150 mg/kg/day had lower histological scores and cartilage remodeling markers. Annatto tocotrienol at 150 mg/kg/day significantly lowered the osteocalcin levels and osteoclast surface of subchondral bone. In conclusion, annatto tocotrienol may potentially retard the progression of osteoarthritis. Future studies to confirm its mechanism of joint protection should be performed.

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