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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.
Predictors of thickened carotid intima media thickness among well controlled lupus nephritis patients in a Malaysian tertiary centre

Shaharir SS, Mohamed Said MS, Kong NC

Reumatismo, 2012;64(6):341-9.
PMID: 23285477 DOI: 10.4081/reumatismo.2012.341

OBJECTIVES: To investigate the prevalence of thickened carotid intima media thickness (CIMT) and its associated risk factors in patients with lupus nephritis (LN) who were in remission.
METHODS: This was a cross sectional study in which consecutive LN patients who were in remission and attending our Nephrology/SLE Clinic were included. Their demographic profile, traditional cardiovascular risk factors and treatment medications were evaluated by clinical interview and review of medical records. Carotid intima media thickness (CIMT) was measured using B Mode carotid ultrasonography. CIMT was considered to be abnormally thickened if it exceeded the 75th percentile matched for age-and sex-matched normal controls. The associated factors for thickened CIMT were examined.
RESULTS: A total of 39 patients with a mean remission duration of 29 ± 24.3 months and on a mean prednisolone dose of 9.10 ± 7.83 mg daily completed the study. Six patients (15.4%) had thickened CIMT. On univariate analysis, male gender, patient age, older age at diagnosis, higher serum CRP levels, greater proteinuria and higher mean cumulative azathioprine dose were associated with thickened CIMT (P<0.05). Lower mean cumulative doses of cyclosporine A (CyA) and mycophenolic acid (MPA) (P<0.05) each were associated with thickened CIMT. Using regression analysis, the associated factors of CIMT were older age at diagnosis and proteinuria.
CONCLUSIONS: Lupus factors particularly age at diagnosis and proteinuria were the associated factors of thickened CIMT. Larger prospective trials are indicated to confirm our findings.
Fulltext Disseminated tuberculosis masquerading primary myelodysplastic syndrome

Shaharir SS, Tumian NR, Yu Lin AB, Abdul Wahid SF

J Infect Dev Ctries, 2013 Mar;7(3):286-8.
PMID: 23493009 DOI: 10.3855/jidc.2691

Tuberculosis is notoriously known to be a great mimicker of other diseases and may cause various haematologic abnormalities, especially with marrow involvement. A 61-year-old man who presented with right empyema and pancytopenia was diagnosed to have disseminated tuberculosis supported by the presence of caseating granuloma with Langhan's giant cells in the marrow and demonstration of acid-fast bacilli in the pleural fluid. Trilineage dysplasia from marrow aspirate was initially attributed to be reactive to the infection. A cytogenetic study was repeated after he showed poor response to a year of anti-tuberculosis treatment. The underlying primary myelodysplastic syndrome was unmasked when his cytogenetics showed trisomy 8. This case report has demonstrated the various haematological manifestations of tuberculosis and highlighted the importance of cytogenetic study in differentiating between primary and secondary myelodysplastic marrow changes.
Posterior reversible encephalopathy syndrome in systemic lupus erythematosus: pooled analysis of the literature reviews and report of six new cases

Shaharir SS, Remli R, Marwan AA, Said MS, Kong NCT

Lupus, 2013 Apr;22(5):492-6.
PMID: 23435619 DOI: 10.1177/0961203313478303

INTRODUCTION:Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder which is increasingly recognized to occur in systemic lupus erythematosus (SLE).
OBJECTIVE: The purpose of this study was to identify the characteristics of SLE patients with PRES and the associated factors of the poor outcome among them.
METHODS: We investigated SLE patients who developed PRES between 2005-2011 at the Universiti Kebangsaan Malaysia Medical Centre. A comprehensive literature search was done to find all published cases of PRES in SLE. Pooled analysis was conducted to identify the factors associated with poor outcome.
RESULTS: There were 103 cases of PRES in SLE published in the literature but only 87 cases were included in the analysis in view of incomplete individual data in the remaining cases. The majority of the cases were Asians (74.2%), female (95.4%) with mean age of 26.3 ± 8.8 years. PRES was highly associated with active disease (97.5%), hypertension (91.7%) and renal involvement (85.1%). We found that 79 patients had a full recovery (90.8%) with a mean onset of full clinical recovery in 5.6 ± 4.1 days. On univariate analysis and logistic regression analysis the predictors of poor outcome, defined as incomplete clinical recovery or death, were intracranial hemorrhage, odds ratio (OR) 14 (1.1-187.2), p=0.04 and brainstem involvement in PRES, OR 10.9 (1.3-90.6), p=0.003.
CONCLUSION: Intracranial hemorrhage and brainstem involvement were the two important predictors of poor outcome of PRES. Larger prospective studies are needed to further delineate the risk of poor outcome among them.
A descriptive study of the factors associated with damage in Malaysian patients with lupus nephritis

Shaharir SS, Ghafor AH, Said MS, Kong NC

Lupus, 2014 Apr;23(4):436-42.
PMID: 24399814 DOI: 10.1177/0961203313518624

INTRODUCTION: Renal involvement is the most common serious complication in patients with systemic lupus erythematosus (SLE).
OBJECTIVE: The objective of this article is to investigate and determine the associated factors of disease damage among lupus nephritis (LN) patients.
METHODS: Medical records of LN patients who attended regular follow-up for at least one year in the Nephrology/SLE Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), were reviewed. Their Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index scores were noted. Univariate analysis and multivariable regression analysis were performed to determine the independent factors of disease damage in LN.
RESULTS: A total of 150 patients were included and their follow-up duration ranged from one to 20 years. Sixty (40%) LN patients had disease damage (SDI ≥1). In the univariate analysis, it was associated with age, longer disease duration, antiphospholipid syndrome (APS), higher maximum daily oral prednisolone dose (mg/day), lower mean C3 and C4, higher chronicity index and global sclerosis on renal biopsies (p < 0.05). Patients who received early (≤3 months after the SLE diagnosis) hydroxychloroquine (HCQ), optimum HCQ dose at 6.5 mg/kg/day and achieved early complete remission (CR) were less likely to have disease damage (p < 0.05). After adjustment for age, gender, disease duration and severity, multivariable regression analysis revealed that a higher maximum daily dose of oral prednisolone was independently associated with disease damage while early HCQ and CR were associated with lower disease damage.
CONCLUSION: Higher maximum daily prednisolone dose predicted disease damage whereas treatment with early HCQ and early CR had a protective role against disease damage.
KEYWORDS: Antiphospholipid syndrome; lupus nephritis; systemic lupus erythematosus

Study site: Nephrology/SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
Fulltext Interleukin-23 and its correlation with disease activity, joint damage, and functional disability in rheumatoid arthritis

Dalila AS, Mohd Said MS, Shaharir SS, Asrul AW, Low SF, Shamsul AS, et al.

Kaohsiung J. Med. Sci., 2014 Jul;30(7):337-42.
PMID: 24924839 DOI: 10.1016/j.kjms.2014.02.010

The purpose of this study was to compare the serum interleukin (IL)-23 levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of IL-23 levels with disease activity, joint damage and functional disability in RA. Serum samples were obtained from 45 patients with RA and 45 healthy controls. The enzyme-linked immunosorbent assay method was used for quantitative analysis of IL-23. All the RA patients were assessed for disease activity based on the 28-joint disease activity score, joint damage based on modified Sharp score, and functional ability using the Health Assessment Questionnaire-Disability Index. The mean serum IL-23 level was much higher among the RA patients (24.50 ± 13.98 pg/mL) compared to the controls (5.98 ± 3.40 pg/mL; p < 0.01). There was a significant positive relationship between IL-23 levels and disease activity and questionnaire scores (p = 0.003 and 0.020, respectively). On logistic regression analysis, IL-23 levels were significantly higher in patients with moderate to high disease activity (p = 0.008, odds ratio = 1.073, 95% confidence interval = 1.019-1.130) and patients with significant functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval = 1.021-1.153). RA patients have significantly higher levels of serum IL-23. The IL-23 levels correlate well with disease activity and functional disability but not with radiographic joint damage.

Study site: Rheumatology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
Fulltext IgA rheumatoid factor as a serological predictor of poor response to tumour necrosis factor α inhibitors in rheumatoid arthritis

Sakthiswary R, Shaharir SS, Mohd Said MS, Asrul AW, Shahril NS

Int J Rheum Dis, 2014 Nov;17(8):872-7.
PMID: 25292482 DOI: 10.1111/1756-185X.12443

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
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
Persistent hypertension in lupus nephritis and the associated risk factors

Shaharir SS, Mustafar R, Mohd R, Mohd Said MS, Gafor HA

Clin Rheumatol, 2015 Jan;34(1):93-7.
PMID: 25373448 DOI: 10.1007/s10067-014-2802-0

Arterial hypertension (HPT) burden up to two third of systemic lupus erythematosus (SLE) patients and contributes to accelerated atherosclerosis and cardiovascular (CV) risk. We aim to determine the prevalence of HPT among lupus nephritis (LN) patients who were in complete remission (CR) for a minimum of 6 months, with estimated glomerular filtration rate (eGFR) of >60 mL/min/1.73 m(2). This is a cross-sectional study of 64 LN patients who attended Nephrology/SLE Clinic at The National University of Malaysia Medical Centre (UKMMC). Persistent hypertension (blood pressure (BP) ≥140/90 mmHg for at least two occasions), CR for a minimum of 6 months and eGFR of >60 mL/min/1.73 m(2) were identified. Univariate and multivariate analyses were performed to determine the demographic and disease characteristics associated with HPT. Thirty-four of them (53.1 %) were hypertensive. Persistent HPT was associated with disease duration, acute kidney injury and high BP at the onset of LN, longer duration interval to achieve CR, number of relapses and cyclosporine A (CyA) use. There were no associations between histological classes, nephrotic range proteinuria, body mass index and waist circumference with HPT. Factors independently associated with HPT were disease duration OR 1.06 [95 %CI (0.91-1.24)], longer duration interval to achieve CR OR 1.104 [95 %CI (1.02-1.19)], number of relapses OR 2.53 [95 % CI (1.01-6.3)] and CyA use OR 5.3 [95 % CI (1.14-23.9)]. The prevalence of HPT among LN is high despite in remission. Aggressive treatment is important to achieve early CR and to prevent relapses.
Study site: Nephrology/SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Steroid-induced diabetes mellitus in systemic lupus erythematosus patients: analysis from a Malaysian multi-ethnic lupus cohort

Shaharir SS, Gafor AH, Said MS, Kong NC

Int J Rheum Dis, 2015 Jun;18(5):541-7.
PMID: 25294584 DOI: 10.1111/1756-185X.12474

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.

© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

KEYWORDS:
SLE drug treatment; clinical aspects; systemic lupus erythematous
Juvenile spondyloarthropathy: an important clinical lesson to remember

Sridharan R, Ngiu CS, Shaharir SS, Said MS

BMJ Case Rep, 2015;2015.
PMID: 26677159 DOI: 10.1136/bcr-2015-213220

Spondyloarthropathy (SpA) is a group of inflammatory conditions that include spondylitis, sacroiliitis, asymmetrical peripheral arthritis and enthesitis. This condition is known as juvenile SpA when the diagnosis is made in patients up to 16 years of age. Enthesitis is a highly specific feature that occurs more often in juvenile SpA than in the adult form. In contrast to adult onset SpA, the initial manifestation of juvenile SpA rarely presents as inflammatory back pain. Peripheral arthritis is the more common presenting feature. We report a case of a 12-year-old boy who presented with a 1-year history of progressive low back pain, gluteal pain and thigh pain. There were no clinical symptoms of arthropathy of the distal extremities. MRI of the whole spine was performed twice, which, unfortunately, was unyielding. Finally, MRI of the sacroiliac joints revealed asymmetric sacroiliitis as well as enthesitis of the hips and pelvis. Further laboratory data showed negative rheumatoid factor and positive human leucocyte antigen (HLA) B27. A diagnosis of juvenile SpA with sacroiliitis and enthesitis was made. The imaging characteristics of juvenile SpA are highlighted.
The spectrum of nasal involvement in systemic lupus erythematosus and its association with the disease activity

Kusyairi KA, Gendeh BS, Sakthiswary R, Shaharir SS, Haizlene AH, Yusof KH

Lupus, 2016 Apr;25(5):520-4.
PMID: 26657735 DOI: 10.1177/0961203315622279

The purpose of this study was to determine the spectrum of nasal involvement in systemic lupus erythematosus (SLE) and its association with the disease activity of SLE based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This was a cross-sectional and observational study involving 73 stable SLE patients. All subjects were evaluated for the SLEDAI scores and had nasal endoscopic examination. The most commonly reported symptom was nasal congestion (31.5%) followed by nasal itchiness (26.0%), runny nose (20.5%) and nasal dryness (19.2%). Almost half (42.9%) of the subjects had nasal mucosal abnormalities, which included mucositis, crusting, ulceration, bifid middle turbinate, septal spur, Jacobson's organ, deviated nasal septum, bilateral inferior turbinate hypertrophy, everted uncinate process, nasopharynx cleft and torus palatinus. The median SLEDAI score for subjects with nasal symptoms was significantly higher than subjects without nasal symptoms (p
Fulltext The clinical significance of interleukin-1 receptor antagonist +2018 polymorphism in rheumatoid arthritis

Ismail E, Nofal OK, Sakthiswary R, Shaharir SS, Sridharan R

PLoS One, 2016;11(4):e0153752.
PMID: 27105431 DOI: 10.1371/journal.pone.0153752

OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA.
METHODS: Polymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS).
RESULTS: The frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05.
CONCLUSIONS: C/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA.
Study site: Outpatient clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
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.
Fulltext Serum matrix metalloproteinase-3 predicts radiographic joint damage and functional disability in rheumatoid arthritis

Sakthiswary R, Omimah KJN, Endom I, Shaharir SS, Sridharan R

Medicine & Health, 2016;11(2):209-217.
MyJurnal

The search for novel biomarkers has taken centre stage in the past decades of research in Rheumatoid Arthritis (RA). The purpose of the present study was to determine the correlation of serum matrix metalloproteinase-3 (MMP-3) with disease activity, joint damage and functional disability in patients with RA. We consecutively recruited RA patients who were under follow-up at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Information on the RA disease characteristics were obtained from the medical records and all RA patients were
assessed for DAS28 (disease activity score based on 28 joints) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI). The hand radiographs of the RA patients were assessed for joint damage using the Modified Sharp Score (MSS). Serum MMP-3 levels from RA patients and healthy controls were measured using the ELISA method. We recruited a total of 77 RA patients and 18 healthy controls. The serum MMP-3 levels were significantly higher among the RA patients (p<0.05). There were significant correlations between the serum MMP3 levels and MSS (r =0.327) and HAQ-DI (r=0.256), both p<0.05. The mean serum MMP levels in RA patients with radiographic joint erosions was significantly higher than in patients without erosions (p<0.05). Likewise, the subjects with significant functional impairment i.e HAQ-DI ≥1; had significantly higher mean MMP-3 levels compared to RA patients without significant disability (p<0.05). Using multivariate analysis, HAQ-DI remained the independent predictor of serum MMP-3 in RA patients. Serum MMP-3 is a potential biomarker and predictor of radiographic joint damage and functional disability in RA.
Keywords: acquired joint deformity, matrix metalloproteinases, rheumatoid arthritis
Factors associated with increased white matter hyperintense lesion (WMHI) load in patients with systemic lupus erythematosus (SLE)

Shaharir SS, Osman SS, Md Rani SA, Sakthiswary R, Said MSM

Lupus, 2018 Jan;27(1):25-32.
PMID: 28467290 DOI: 10.1177/0961203317707062

Introduction White matter hyperintense (WMHI) lesions are the most common finding in magnetic resonance imaging (MRI) of the brain in patients with systemic lupus erythematosus (SLE). Objective The objective of this article is to determine the clinical factors associated with an increase in WMHI lesion load among SLE patients. Method A total of 83 SLE patients with MRI of the brain from National University of Malaysia Medical Centre were included. The WMHI lesion load was determined using the Scheltens score and Fazekas scale, and their distribution was divided into the deep white matter (DWMHI) and periventricular (PVH) regions. The clinical correlates of WMHI lesions were initially determined using univariate analyses and subsequently multivariable regression analyses were performed to determine the independent factors of increased WMHI lesion load. Results MRI of the brain of 46 patients who had WMHI lesions were compared with 37 patients with normal MRI. We found significant association between the presence of WMHI lesions and age, presence of cerebral infarcts, positive antiphospholipid antibody (aPL), active disease, neuropsychiatric lupus (NPSLE) and disease damage. Age, SLEDAI scores, cerebral infarcts and disease damage were significantly associated with higher DWMHI and PVH Scheltens scores. Meanwhile, patients with active lupus nephritis (LN), lower serum albumin and more severe proteinuria were associated with larger Fazekas WMHI lesions. Multivariable regression analysis revealed that the independent factors associated with presence of WMHI lesions were positive aPL and SLEDAI scores ( p
Non-tuberculous mycobacterium bacteraemia in a pregnant systemic lupus erythematosus (SLE) patient: a case review and pooled case analysis

Shaharir SS, Sulaiman Sahari N, Mohamed Fuad Z, Zukiman WZHW, Mohd Yusof NH, Sulong A, et al.

Clin Rheumatol, 2018 Mar;37(3):837-847.
PMID: 28971307 DOI: 10.1007/s10067-017-3855-7

Non-tuberculous mycobacteria (NTM) are recognized as an important cause of human diseases and infections. It is commonly known to cause infections of the skin, soft tissue infections, and pulmonary infection as well as bacteraemia. We report a challenging case of severe mycobacterium abscessus bacteraemia in a pregnant lady with active systemic lupus erythematous (SLE). A comprehensive literature review of NTM infection among SLE patients was also performed, and pooled analysis of the reported cases, including our case, was done to determine the clinical characteristics and factors associated with poor outcome of NTM infection.
Photoprotection awareness and practices among patients with systemic lupus erythematosus and its association with disease activity and severity

Abdul Kadir WD, Jamil A, Shaharir SS, Md Nor N, Abdul Gafor AH

Lupus, 2018 Jul;27(8):1287-1295.
PMID: 29665756 DOI: 10.1177/0961203318770016

Objective The objective of this paper is to determine photoprotection awareness, knowledge, practices, and its relationship with disease activity and damage in patients with systemic lupus erythematosus (SLE).
Methods A cross-sectional study was performed. Data were acquired from in-person interviews and medical records.
Results A total of 199 (89.6%) females and 23 (10.4%) males were recruited. Median age was 39.00 (interquartile range (IQR) 18) years, disease duration 12.12 (IQR 8) years, Fitzpatrick skin phototype III 119 (53.6%) and IV 81 (36.5%). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) was 2.95 (IQR 4) while Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-ACR DI) was 1.20 (IQR 2). The majority 205 (92.3%) were aware of sun exposure effects on SLE. Photoprotection methods were shade seeking 209 (94.1%), sun avoidance 212 (95.5%), long pants 168 (75.7%), long sleeves 155 (69.8%), sunscreen 116 (52.3%), sunglasses 114 (51.4%) and head cover 103 (46.4%). Significantly higher photoprotection practice scores (PPS) were observed in females, Malays, and individuals with higher education level and internet accessibility. PPS were not significantly correlated with SLICC-ACR DI and SLEDAI-2 K. Independent predictors for good photoprotection practice (GPP) were ethnicity (OR = 3.66, 95% CI 1.78-7.53), awareness (OR = 3.77, 95% CI 1.09-13.08) and cutaneous involvement (OR = 2.43, 95% CI 1.11-5.28). Photoprotection methods and GPP were not predictors for disease activity or damage.
Conclusion Photoprotection awareness and knowledge was good. Shade seeking and sun avoidance were the common photoprotection methods practised. The use of sunscreen requires improvement. Photoprotection awareness and cutaneous manifestation were predictors for GPP. Neither photoprotection methods nor GPP were associated with disease activity or damage.
Study site: Nephrology, Rheumatology and Dermatology clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia: A 6-months open-label, randomized controlled trial

Mukri MNA, Kong WY, Mustafar R, Shaharir SS, Shah SA, Abdul Gafor AH, et al.

EXCLI J, 2018;17:563-575.
PMID: 30108461 DOI: 10.17179/excli2018-1256

Introduction: Hyperuricemia is associated with chronic kidney disease (CKD) progression and poor cardiovascular outcomes. We studied the effect of febuxostat on estimated glomerular filtration rate (eGFR), proteinuria and monitored the safety profile of the medication.
Material and Methods: This is a prospective open-label, randomized study in CKD stage 3 and 4 patients with diabetic nephropathy and asymptomatic hyperuricemia. Patients were randomized into febuxostat 40 mg daily and no treatment group using block randomization method and were followed up for 6 months. Their usual care for diabetes mellitus, hypertension and dyslipidemia were continued in the study. Blood and urine investigations were monitored at baseline, 3 months and 6 months.
Results: The eGFR in febuxostat group was stabilized at 6 months with no significant reduction [26.2 (IQR 14.30) at baseline to 26.3 (IQR 15.2) ml/min/1.73 m2]. Whereas, there was a significant reduction of the eGFR in no treatment group from 28.2 (IQR 17.9) to 27.6 (IQR 19.3) ml/min/1.73 m2 (p value < 0.01). We found the HbA1c (glycosylated hemoglobin) was significantly increased in febuxostat group from 7.2 ± 0.5 % at baseline to 7.6 ± 1.4 at 6 months (p value 0.04) but no significant change of HbA1c in the no treatment group. Proteinuria level was unchanged in both groups. The commonest adverse event was joint pain.
Conclusions: Febuxostat was able to preserve eGFR in CKD patients with diabetic nephropathy and this effect was beyond glycemic control. Increment of HbA1c level in febuxostat group needs further larger trials.
Study site: Chronic kidney disease clinic, Hospital Canselor Tuanku Muhriz, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Systemic lupus erythematosus among male patients in Malaysia: how are we different from other geographical regions?

Shaharir SS, Kadir WDA, Nordin F, Bakar FA, Ting MWH, Jamil A, et al.

Lupus, 2019 Jan;28(1):137-144.
PMID: 30458692 DOI: 10.1177/0961203318812676

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease which predominantly affects females. The disease characteristics in male SLE patients are reported to be distinct and may vary across ethnicities and geographical regions.
OBJECTIVE: To determine and compare the clinical phenotype and organ damage between male and female patients with SLE in Malaysia.
METHODOLOGY: This was a cross-sectional study involving SLE patients from Universiti Kebangsaan Malaysia Medical Centre from June 2016 until June 2017. Information on their socio-demographics and disease characteristics were obtained from the clinical records. Disease damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI) scores. The disease characteristics, autoantibody profiles and organ damage were compared between male and female patients, and multivariable analysis using male sex as dependent variable was then performed.
RESULTS: A total of 418 patients were recruited and a total of 59 (14.1%) patients were male. Male patients presented with lower SLE ACR criteria at initial presentation but a significantly higher number of them had renal involvement (lupus nephritis) (78.0% versus 63.8%, p = 0.04). Male patients had less musculoskeletal involvement (45.8% versus 63.0%, p = 0.02) and tended to have lesser mucocutaneous involvement. Immunologic profile revealed that a lower number of male patients had positive anti-Ro antibody (22.7% versus 44.7%, p = 0.04) and they tended to have positive lupus anticoagulant antibody (27.6% versus 14.3%, p = 0.06). Presence of organ damage (SDI score ≥ 1) was significantly higher among males (55.9% versus 39.6%, p = 0.02) with higher renal damage (25.4% versus 9.2%, p = 0.004) and cardiovascular event of ischaemic heart disease or stroke (20.3% versus 7.0%, p = 0.004). They were also inclined to develop damage much earlier as compared to female patients, 3 (interquartile range (IQR) 7.5) versus 5 (IQR 7) years, p = 0.08. The occurrence of disease damage was independently associated with male gender with odds ratio of 1.9 (95% confidence interval 1.1-3.5), p = 0.02.
CONCLUSION: Male patients with SLE have more severe disease with renal damage and cardiovascular event.

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