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Characteristics and outcome of autoimmune liver disease in Asian children

Lee WS, Lum SH, Lim CB, Chong SY, Khoh KM, Ng RT, et al.

Hepatol Int, 2015 Apr;9(2):292-302.
PMID: 25788179 DOI: 10.1007/s12072-014-9558-0

BACKGROUND: Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population.

METHODS: Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia.

RESULTS: At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012].

CONCLUSIONS: Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications
Characteristics of Malaysian systemic lupus erythematosus (SLE) patients seen in a public and private hospital. [Abstract]

Yeap SS, Das Gupta E, Gun SC

Int J Rheum Dis, 2010;13:121.
DOI: 10.1111/j.1756-185X.2010.01502.x

BACKGROUND: In Malaysia, patients have a choice of attending a public (fully subsidised bygovernment) hospital (PUBH) or a private (fee-paying) hospital (PRIH) for their healthcare.The aim of this study was to, firstly, provide an overview of the characteristics of MalaysianSLE patients attending rheumatology clinics, and secondly, to ascertain if there were any dif-ferences between patients attending PUBH and PRIH.
METHODS:A standardised questionnaire was administered to all SLE patients attendingrheumatology clinics in a PRIH in Selangor state and a PUBH in Negeri Sembilan state dur-ing the months of September to December 2009.
RESULTS:One hundred and thirty patients were included in the study. There were 55(42.3%) patients from PRIH and 75 (57.7%) from PUBH. 93.8% were female. 61.5% wereChinese, 29.2% Malay and 7.7% Indians. The majority of patients completed secondaryschooling (46.9%) with significantly less PUBH patients going onto higher education(P = 0.001). 53.8% were in fulltime employment with 37.7% housewives/unemployed.There were significantly more unemployed patients in PUBH (45.3%) versus PRIH (27.2%)(P = 0.05). 33.8% of patients were single, 60.8% married and 3.8% divorced. Average ageat SLE diagnosis was 29.8510.17 years. At diagnosis, the most common presenting symp-tom was related to the mucocutaneous system 70.8%, followed by joints 55.3%, haemato-logical 46.9% and renal 23.1%. Significantly more patients had renal involvement atdiagnosis in PUBH (33.3%) versus PRIH (9.1%) (P = 0.001). At the time of survey, therewere 12 (9.2%) patients in remission. Of those still symptomatic, 48.5% related to themucocutaneous system, 32.3% joints, 27.7% haematological, 22.3% renal, with significantlymore current renal disease in PUBH (30.7%) versus PRIH (10.9%) (P = 0.008). The mostfrequently prescribed drug was prednisolone in 83.1% of patients, followed by hydroxychlo-roquine 68.5% and azathioprine 23.1%. Only 64.8% of patients on prednisolone were onbone protective agents. More patients in PRIH were on prednisolone (90.9%) versus PUBH(77.3%) (P = 0.04), but more patients were on activated vitamin D in PUBH (72%) versusPRIH (29.1%) (P < 0.001).
CONCLUSION:The demographics and clinical characteristics of SLE patients attending PUBHand PRIH are significantly different. This has important implications when considering edu-cational and treatment strategies

Matched MeSH terms: Lupus Erythematosus, Systemic
Childhood cerebral lupus in an Oriental population

Haji Muhammad Ismail Hussain I, Loh WF, Sofiah A

Brain Dev, 1999 Jun;21(4):229-35.
PMID: 10392744

In a cross-sectional study of 24 Oriental children with systemic lupus erythematosus (SLE) with a mean age of 11.25 years, 75% were found to have clinical and neurophysiological evidence of cerebral lupus. Seizures were the most common manifestation affecting 11 (61%) of the cases, followed by psychosis in five (27.7%), encephalopathy in five (27.7%), headaches in five (27.7%), personality changes in four (22.2%), stroke in three (16.6%), movement disorders in three (16.6%) and myelitis in one child (5.5%). Four children had cerebral lupus as the presenting manifestation of SLE. Twenty-one children had an electroencephalogram (EEG) of which 11 were normal. Abnormalities detected in the rest included focal sharps, slowing of background and electrodecremental changes. There was a poor correlation of EEG with the clinical presentation. Sixteen children with cerebral lupus had a computed tomogram (CT) of which three were normal. The commonest abnormality was cerebral atrophy with or without infarcts. Only four of the cases had lupus anticoagulant but compliment was reduced in 13. Sixteen of the cases also had renal involvement. Treatment was generally with steroids with only two patients receiving cyclophosphamide for cerebral relapse. Eight children (44%) made a full recovery. Learning disability was the most frequent sequelae affecting one-third of children seen at a 1-year follow up. Four (22%) had epilepsy, two (11%) had motor deficits and one child had optic atrophy. One child died of cerebral haemorrhage during a hypertensive crisis.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications*; Lupus Erythematosus, Systemic/epidemiology*
Fulltext Childhood-Onset Systemic Lupus Erythematosus: Southeast Asian Perspectives

Tang SP, Lim SC, Arkachaisri T

J Clin Med, 2021 Feb 03;10(4).
PMID: 33546120 DOI: 10.3390/jcm10040559

Childhood onset systemic lupus erythematosus is a rare disease that is more common amongst Southeast Asian children compared to the West. It is typified by a peripubertal onset and a female preponderance, which increases with advancing age. Organs commonly involved at diagnosis include haematological, renal, and mucocutaneous. Fever, malar rash, and cutaneous vasculitis are common. Lupus nephritis is typically proliferative especially Class IV and contributes to both disease activity and damage. Antinuclear antibody and anti-dsDNA positivity are both prevalent in this region. Disease activity is higher than Western cohorts at onset but responds to therapy reducing to low disease activity by six months. However, organ damage occurs early and continues to accumulate over the time, a consequence of both active disease (neurological and renal systems) and steroid-related complications especially in the eye (cataract and glaucoma) and musculoskeletal systems (avascular necrosis). Infections remain the leading cause of death and mortality in this region is highly variable contributed by the heterogeneity in social economic status, healthcare access, and availability of paediatric rheumatology expertise in the region.

Matched MeSH terms: Lupus Erythematosus, Systemic
Chronic intestinal pseudo-obstruction: a rare first manifestation of systemic lupus erythematosus

Khairullah S, Jasmin R, Yahya F, Cheah TE, Ng CT, Sockalingam S

Lupus, 2013 Aug;22(9):957-60.
PMID: 23761180 DOI: 10.1177/0961203313492873

Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome of ineffective intestinal motility characterised by clinical and radiological evidence of intestinal obstruction with no identifiable mechanical lesion. CIPO can either be idiopathic or secondary to a systemic disease, like systemic lupus erythematosus (SLE). Fewer than 30 cases of CIPO secondary to SLE have been reported so far. Here we describe a case of SLE with the initial presentation of CIPO. In SLE-related CIPO, treatment includes a combination of high-dose intravenous corticosteroids, immunosuppressants and supportive care. With awareness of this condition, unnecessary surgical intervention and repeated invasive procedures could be avoided. Early initiation of treatment would avoid complications and bring about resolution of symptoms.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications*; Lupus Erythematosus, Systemic/diagnosis; Lupus Erythematosus, Systemic/therapy
Class II HLA-DR antigen and DQA, DQB and DPB allele frequencies in Malay patients with systemic lupus erythematosus

Azizah MR, Ainol SS, Kuak SH, Kong NCT, Normaznah Y, Rahim MN

International Medical Journal (Tokyo), 2001;8(2):125-130.

Objective: The frequency of the HLA class II antigens (HLA DR, DQ and DP) were determined among Malay patients with systemic lupus erythematosus (SLE) to ascertain the role they play in disease susceptibility. Study design: Fifty-six Malay SLE patients on follow-up at the SLE Clinic of the National University of Malaysia Hospital, Kuala Lumpur were enrolled into the study. Controls were taken from healthy unrelated individuals, ethnically-matched. Materials and Methods: Five ml of anticoagulated blood was taken from each patient and control and DNA extracted. The HLADR, DQ and DP antigen/allele frequencies were determined by the technique of modified PCR-RFLP and statistical analysis done by Chi-square and Fischers exact test. Relative risk was determined by the odds ratio and significant p values were corrected for the number of antigens/alleles tested. Results: We found that the DR2 antigen was significantly increased among the patients (85.7%) as compared to controls (61%)(p corr=0.03, RR=3.83). As for HLA-DQA1, the allele most commonly found among the patients was *0102 (57 vs 49.2%). HLA-DQA1* 0601 was slightly decreased among the patients but this finding was insignificant. Both HLA-DQB1*0501 and 0601 were found to be increased among the patients even after correction of multiple comparisons made (p=0.0036, RR=4.56 and p=0.0048, RR=6.0, respectively). However, HLA-DQB1*0503 and 0301 was slightly decreased in the sle patients though not statistically significant. The frequency of HLA-DQB1*0201 was insignificantly increased among the patients. Limited studies on the DPB1 locus shows the uncertain role of this antigen in contributing to disease susceptibility. However, our analysis of the HLA-DPB1*0901 showed a slight increase among the patients as compared to controls but failed to remain significant after being corrected with number of comparisons made. All other HLA-DPB1 alleles exhibited similar frequencies between sle patients and controls. Conclusion: From this study we suggest that HLA DR2, DQB1*0501 and *0601 may be important genetic factors in conferring disease susceptibility in the Malay SLE population of Malaysia.

Matched MeSH terms: Lupus Erythematosus, Systemic*
Clinical and electrophysiological characteristics of symmetric polyneuropathy in a cohort of systemic lupus erythematosus patients

Jasmin R, Sockalingam S, Ramanaidu LP, Goh KJ

Lupus, 2015 Mar;24(3):248-55.
PMID: 25253567 DOI: 10.1177/0961203314552115

OBJECTIVE: Peripheral neuropathy in systemic lupus erythematosus (SLE) is heterogeneous and its commonest pattern is symmetrical polyneuropathy. The aim of this study was to describe the prevalence, clinical and electrophysiological features, disease associations and effects on function and quality of life of polyneuropathy in SLE patients, defined using combined clinical and electrophysiological diagnostic criteria.
METHODS: Consecutive SLE patients seen at the University of Malaya Medical Centre were included. Patients with medication and other disorders known to cause neuropathy were excluded. Demographic, clinical and laboratory data were obtained using a pre-defined questionnaire. Function and health-related quality of life was assessed using the modified Rankin scale and the SF-36 scores. Nerve conduction studies (NCS) were carried out in both upper and lower limbs. Polyneuropathy was defined as the presence of bilateral clinical symptoms and/or signs and bilateral abnormal NCS parameters.
RESULTS: Of 150 patients, 23 (15.3%) had polyneuropathy. SLE-related polyneuropathy was mainly characterized by sensory symptoms of numbness/tingling and pain with mild signs of absent ankle reflexes and reduced pain sensation. Function was minimally affected and there were no differences in quality of life scores. NCS abnormalities suggested mild length-dependent axonal neuropathy, primarily in the distal lower limbs. Compared to those without polyneuropathy, SLE-related polyneuropathy patients were significantly older but had no other significant demographic or disease associations.
CONCLUSIONS: SLE-related polyneuropathy is a chronic, axonal and predominantly sensory neuropathy, associated with older age. Its underlying pathogenetic mechanisms are unknown, although a possibility could be an increased susceptibility of peripheral nerves in SLE patients to effects of aging.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications*; Lupus Erythematosus, Systemic/epidemiology; Lupus Erythematosus, Systemic/physiopathology
Clinical experience in using CD20 monoclonal antibody in treating severe systemic lupus erythematosus

Mohd Shahrir MS, Abdul Halim AG, Soehardy Z, Kong NCT

APLAR Journal of Rheumatology, 2007;10(2):112-116.
DOI: 10.1111/j.1479-8077.2007.00270.x

Background and method: This clinical experience involved the treatment of resistant systemic lupus erythematosus (SLE) patients with CD20 monoclonal antibody. Five patients failed conventional therapy, two developed complications and one needed rituximab as an emergency measure. Four patients had lupus nephritis, three had autoimmune hemolytic anemia, two had immune thrombocytopenia and one had lupoid hepatitis. The patients were aged 14-49 years, (mean 28.63). Three were Malays, two Chinese, two Indian and one Turkish; six were females. Mean disease duration was 63.25 months and mean total rituximab dose received was 2812.50 mL. Results: Hemoglobin levels improved from 9.3 ± 5.7 to 13.1 ± 8.6 g/dL for two SLE patients with autoimmune hemolytic anemia after 34 weeks (P = 0.180). Platelet counts improved from 25 ± 17 to 198 ± 97 × 10 9/high powered field from 0 to 10 weeks for three SLE patients with immune thrombocytopenia (P = 0.109). In the lupus nephritis patients on rituximab, serum albumin improved from 24.5 ± 23.2 to 37.5 ± 31.8 mmol/L (n = 3) from week 0 to week 17 (P = 0.100). Urine protein creatinine ratio improved from 0.55 ± 0.23 to 0.08 ± 0.03 g/mmol creatinine (P = 0.068) from week 0 to week 13. C3 and C4 improved from 90.8 ± 36.5 to 120.7 ± 37.9 (P = 0.07) and 21.6 ± 10.1-27.3 ± 16.2 mg/dL (P = 0.27), respectively, and Systemic Lupus Erythematosus Activity Disease Index was reduced from 17.9 ± 11.2 to 6.3 ± 6.8 (P = 0.375) after 8 weeks. Two patients developed drug reactions to rituximab. Conclusion: All of the patients responded to rituximab on top of their conventional therapy. © 2007 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.

Matched MeSH terms: Lupus Erythematosus, Systemic*
Clinical features, disease activity and outcomes of Malaysian children with paediatric systemic lupus erythematosus: A cohort from a tertiary centre

Lim SC, Chan EWL, Tang SP

Lupus, 2020 Aug;29(9):1106-1114.
PMID: 32631203 DOI: 10.1177/0961203320939185

BACKGROUND: Paediatric systemic lupus erythematosus is a rare autoimmune disease with a wide spectrum of clinical presentation in different populations. We present a cohort of paediatric systemic lupus erythematosus in Malaysia where the disease features and outcomes are still largely unknown.
METHODS: A retrospective review of all paediatric systemic lupus erythematosus patients with at least 6 months follow-up at Selayang Hospital from 2004 to 2016. Epidemiological, clinical and outcome data were collected and analysed.
RESULTS: A total of 141 paediatric systemic lupus erythematosus patients, 87.9% females, were followed up for a median 6.3 years (interquartile range 3.6-9.0). The median age at diagnosis was 10.8 years (interquartile range 9.0-12.0 years), positive family history of systemic lupus erythematosus was present in 12.1% and the majority (61.7%) were of Malay ethnicity. Common presentations included fever (87.2%), vasculitic rash (72.3%) and lethargy (69.5%). At diagnosis, leukopenia (51.1%), thrombocytopenia (41.8%) and cutaneous lupus (56%) predominate with significant renal involvement (39.7%). Renal (45.4%), liver (26%) and the central nervous system (17%) were important major organs involved during the course of the disease. At diagnosis, almost all (99.3%) patients had high disease activity (mean Systemic Lupus Erythematosus Disease Activity Index score 20.1 ± 9.6). The majority (62.4%) achieved remission or low disease activity after 6 months, maintained over the next 10 years. Damage occurred early (39.1% at 1 year) and increased with time. Ocular damage was the most common side effect (29%) and was predominantly corticosteroid related (93%). Growth retardation was significant (38.2%) with no gonadal failure or secondary malignancies. End-stage renal disease occurred in 3.1% patients whereas 53.1% had sustained renal remission. Overall mortality was 1.4%.
CONCLUSION: Despite high disease activity at diagnosis, the majority had good sustained response to treatment with low overall mortality. However, there was progressive accrual of organ damage, highlighting the need for further research and refinements into therapies for paediatric systemic lupus erythematosus.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications*; Lupus Erythematosus, Systemic/pathology*; Lupus Erythematosus, Systemic/physiopathology*
Coexistence of antiphospholipid antibodies and cephalalgia

Islam MA, Alam F, Gan SH, Cavestro C, Wong KK

Cephalalgia, 2018 03;38(3):568-580.
PMID: 28952322 DOI: 10.1177/0333102417694881

Background The occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear. Aim The aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals.
Methods A comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence.
Results Cohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology
Fulltext Combined protein- and nucleic acid-level effects of rs1143679 (R77H), a lupus-predisposing variant within ITGAM

Maiti AK, Kim-Howard X, Motghare P, Pradhan V, Chua KH, Sun C, et al.

Hum Mol Genet, 2014 Aug 1;23(15):4161-76.
PMID: 24608226 DOI: 10.1093/hmg/ddu106

Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.

Matched MeSH terms: Lupus Erythematosus, Systemic/ethnology; Lupus Erythematosus, Systemic/genetics*; Lupus Erythematosus, Systemic/metabolism; Lupus Erythematosus, Systemic/pathology
Complement components 2 and 7 (C2 and C7) gene polymorphisms are not major risk factors for SLE susceptibility in the Malaysian population

Lian LH, Ching AS, Chong ZY, Chua KH

Rheumatol Int, 2012 Nov;32(11):3665-8.
PMID: 21881993 DOI: 10.1007/s00296-011-2070-0

There have been numerous studies linking complement components and the pathogenesis of systemic lupus erythematosus (SLE). This is due to their numerous roles in modulating immune responses in the human body. This study examined the association of C2 and C7 genetic polymorphisms with the susceptibility to SLE based on two separate cohorts of patient and control samples from Malaysia. The 28-bp deletion in the C2 exon-intron junction and single nucleotide polymorphism in the 3'untranslated region in the C7 genes were detected based on direct polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. A total of 150 patient and 150 healthy control samples were screened, but there was no association detected between either genes. All individuals presented with null deletion in C2 genes, while the C allele and CC genotypes were most commonly scored. These overall results suggest a lack of strong association with the C2 and C7 gene polymorphisms to the susceptibility of SLE in the Malaysian population.

Matched MeSH terms: Lupus Erythematosus, Systemic/genetics*
Fulltext Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci

Molineros JE, Yang W, Zhou XJ, Sun C, Okada Y, Zhang H, et al.

Hum Mol Genet, 2017 03 15;26(6):1205-1216.
PMID: 28108556 DOI: 10.1093/hmg/ddx026

We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and to perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci. All five loci passed genome-wide significance: MYNN (rs10936599, Pmeta = 1.92 × 10-13, OR = 1.14), ATG16L2 (rs11235604, Pmeta = 8.87 × 10 -12, OR = 0.78), CCL22 (rs223881, Pmeta = 5.87 × 10-16, OR = 0.87), ANKS1A (rs2762340, Pmeta = 4.93 × 10-15, OR = 0.87) and RNASEH2C (rs1308020, Pmeta = 2.96 × 10-19, OR = 0.84) and co-located with annotated gene regulatory elements. The novel loci share genetic signatures with other reported SLE loci, including effects on gene expression, transcription factor binding, and epigenetic characteristics. Most (56%) of the correlated (r2 > 0.8) SNPs from the 82 SLE loci were implicated in differential expression (9.81 × 10-198

Matched MeSH terms: Lupus Erythematosus, Systemic/genetics*; Lupus Erythematosus, Systemic/epidemiology; Lupus Erythematosus, Systemic/pathology
Coronary artery bypass graft surgery in a young female with systemic lupus erythematosus and its operative challenges: A case report

Gurpreet S, Vendargon SJ, Syed Rasul SH

Med J Malaysia, 2019 12;74(6):549-550.
PMID: 31929487

We understand that autoimmune disorders such as Systemic Lupus Erythematosus increases the likelihood of developing coronary heart disease. However, its implications on patients undergoing cardiac surgery is not well understood. Here we present a female patient with SLE who developed coronary artery disease at a young age and underwent coronary artery bypass graft surgery. As SLE is associated with vasculitis, we wanted to understand regarding the choice of conduit as well as its long term patency. Also whether percutaneous angioplasty has a role to play in patients with SLE.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications*
Fulltext Cutaneous tuberculosis mimicking cellulitis in an immunosuppressed patient

Chin PW, Koh CK, Wong KT

Singapore Med J, 1999 Jan;40(1):44-5.
PMID: 10361486

A 28-year-old lady suffering from systemic lupus erythomatosus (SLE) with diffuse proliferative glomerulonephritis (DPGN) and who was on oral cyclophosphamide and prednisolone presented with left lower limb 'cellulitis'. The 'cellulitis' of the left lower limb failed to respond to usual antibiotics which prompted evaluation of the clinical diagnosis. The diagnosis is made based on the presence of granulomas, multinucleated giant cells and acid fast bacilli on the skin biopsy.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications
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.

Matched MeSH terms: Lupus Erythematosus, Systemic/drug therapy; Lupus Erythematosus, Systemic/epidemiology; Lupus Erythematosus, Systemic/physiopathology*
Danazol in the treatment of systemic lupus erythematosus: a qualitative systematic review

Letchumanan P, Thumboo J

Semin Arthritis Rheum, 2011 Feb;40(4):298-306.
PMID: 20541792 DOI: 10.1016/j.semarthrit.2010.03.005

OBJECTIVES: To review and summarize published information on the use, effectiveness, and adverse effects of danazol in patients with systemic lupus erythematosus (SLE).
METHODS: A MEDLINE search from January 1950 to July 2009 was conducted using 2 search strategies retrieving 51 and 62 references, respectively. We also searched 2 standard reference textbooks and bibliographies of the 38 articles selected.
RESULTS: Of the 38 articles selected, there were 19 case series/reports with a total of 153 patients, including 2 prospective trials of 7 and 16 patients, respectively, and 1 randomized controlled trial of 40 patients. Danazol has been used successfully in the treatment of hematologic manifestations of SLE such as thrombocytopenia, Evan's syndrome, autoimmune hemolytic anemia, and a case of red cell aplasia. Thirteen patients responded to danazol after failing splenectomy. There is limited information on the use of danazol in nonhematologic manifestations of SLE. Adverse effects were generally tolerable but high doses may produce undesirable side effects for female patients.
CONCLUSIONS: Danazol is a useful drug in the treatment of SLE patients, especially in patients with refractory thrombocytopenia, autoimmune hemolytic anemia, and premenstrual flares, and in some mild nonhematologic manifestations of SLE. It appears to be relatively well tolerated, safe, and efficacious.

Matched MeSH terms: Lupus Erythematosus, Systemic/drug therapy*
Degraded microarchitecture by low trabecular bone score is associated with prevalent vertebral fractures in patients with systemic lupus erythematosus

Lai EL, Huang WN, Chen HH, Chen JP, Chen DY, Hsieh TY, et al.

Arch Osteoporos, 2020 03 27;15(1):54.
PMID: 32221755 DOI: 10.1007/s11657-020-00726-3

PURPOSE: Recently, trabecular bone score (TBS) has emerged as an important supplementary assessment tool in osteoporosis diagnosis and management. The high incidence of fragility fracture within the non-osteoporotic range of bone mineral density (BMD), among systemic lupus erythematosus (SLE) patients, highlights the crucial role of bone microarchitecture in osteoporosis. This study aimed to evaluate whether TBS identified existing vertebral fractures (VF) more accurately than BMD in SLE patients.
METHODS: This study enrolled 147 SLE patients from the Asia Pacific Lupus Collaboration (APLC) cohort, who had BMD and TBS assessed from January 2018 until December 2018. Twenty-eight patients sustaining VF and risk factors associated with increased fracture occurrence were evaluated. Independent risk factors and diagnostic accuracy of VF were analyzed by logistic regression and ROC curve, respectively.
RESULT: The prevalence of vertebral fracture among SLE patients was 19%. BMD, T-score, TBS, and TBS T-score were significantly lower in the vertebral fracture group. TBS exhibited higher positive predictive value and negative predictive value than L spine and left femur BMD for vertebral fractures. Moreover, TBS had a higher diagnostic accuracy than densitometric measurements (area under curve, 0.811 vs. 0.737 and 0.605).
CONCLUSION: Degraded microarchitecture by TBS was associated with prevalent vertebral fractures in SLE patients. Our result suggests that TBS can be a complementary tool for assessing vertebral fracture prevalence in this population.

Matched MeSH terms: Lupus Erythematosus, Systemic/complications; Lupus Erythematosus, Systemic/physiopathology
Demographic, clinical and immunological features of 134 Malaysian patients with systemic lupus erythematosus

Azizah MR, Ainol SS, Kong NCT, Normaznah Y, Rahim MN

International Medical Journal (Tokyo), 2001;8(1):45-50.

Objective: SLE is an autoimmune disease which affects multiple organ system. Clinical and immunological expression of the disease have been widely studied and variations occur in different ethnic groups. Here in this study, we have analyzed the clinical manifestations and immunological features of Malaysian patients with Systemic lupus erythematosus (SLE) and compared them with SLE population from some of the Asian countries. Study design: A total of 134 Malaysian patients attending the SLE Clinic of The National University Hospital of Malaysia, Kuala Lumpur and who satisfy the revised ACR (American College of Rheumatology) criteria for the classification of SLE were enrolled into the study. Data on the demography, clinical and immunological features were obtained from medical records. Materials and Methods: The female to male ratio in the study cohort was 10:1 and consisted of the Malay, Chinese and Indian races. Past clinical and immunological features were entered into a prepared questionnaire. At study entry patients were seen by a rheumatologist for assessment of present clinical condition and blood obtained for immunological tests (Antinuclear, antids DNA, antiSm, antiU1RNP, antiSSA(Ro), antiSSB(La), anticardiolipin (IgG and IgM) antibodies and complements C3 and C4). Chi-square, Fisher's exact test and Mann Whitney U Test were used to analyze data. Results: Clinical features expressed at disease presentation in order of frequency was mucocutaneous (72%), followed by musculoskeletal (58%) and renal involvement (45%) which was also similar during the course of the disease (90%, 72% and 64% respectively). A high prevalence of antiSSB (La) antibodies was found (48%). Conclusion: This study provides the literature on the clinical and immunological features of Malaysian SLE patients and further shows the different spectrum of disease profile when compared to other ethnic groups. The roles of racial and genetic factors are suggested.

Matched MeSH terms: Lupus Erythematosus, Systemic*
Fulltext Detection of anti-cell membrane DNA antibodies by indirect immunoflouresencence technique in systemic lupus erythematosus

Faten Nurul Amira Awing Kechik, Maha Abdullah, Masriana Hassan, Masita Arip, Hasni Mahayidin

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):28-28.
MyJurnal

Introduction: Systemic lupus erythematosus (SLE) has a broad spectrum of clinical presentations. The diagnosis of SLE remains a challenge and largely depends on the presence of several serum autoantibodies including anti-nuclear antibody (ANA), anti-double-stranded DNA antibody (anti-dsDNA) and anti-Smith antibody (anti-Sm). ANA, a highly sensitive but not specific marker is used for SLE screening Anti-dsDNA and anti-Sm are SLE-specific biomarkers but has lower sensitivity of 80% and 30% for SLE, respectively. However, it is noted that there are SLE patients who are persistently negative for SLE-specific autoantibodies. Anti-dsDNA and anti-Sm were reported to be negative in up to 51.2% and 62.4% of SLE, respectively. This limitation can lead to misdiagnosis and halter proper treatment to SLE patients. Previous studies have suggested that cell membrane DNA (cmDNA) can act as a specific target for the autoantibodies in SLE patients. Autoantibodies towards cmDNA (anti-cmDNA) were reported to have promis-ing value as a reliable biomarker for SLE. In this study, we would like to determine the usefulness of anti-cmDNA in diagnosing SLE as compared to the standard SLE-specific autoantibodies. Methods: Serum samples from 83 SLE patients, 86 other connective tissue diseases and 61 healthy subjects were included in this study. The other connec-tive tissue diseases include samples from 10 Sjogren’s syndrome, 56 rheumatoid arthritis, 12 scleroderma and eight mixed connected tissues disease (MCTD) patients. All samples were analysed by indirect immunofluorescence (IIF) technique using Raji cells as substrate to detect the presence of anti-cmDNA. Anti-cmDNA was reported as positive if there was presence of a fluorescent ring, either continuous or punctate. Sera from SLE patients were also tested for anti-dsDNA and anti-Sm antibodies by using enzyme-immunoassays. Results: Anti-cmDNA positivity was highest in SLE (55.4%) than in other connective tissue diseases (9.3%) and healthy subjects (0%). Anti-cmDNA was 100% spe-cific at differentiating SLE from healthy subjects and 90.7% specific at differentiating SLE from other connective tissue diseases. There was no difference in the sensitivity (55.4%) of anti-cmDNA at differentiating SLE from both groups. Anti-cmDNA were present in 46 SLE samples negative for standard SLE-specific autoantibodies. It was detected in 11 (42.3%) of anti-dsDNA, 23 (63.9%) of anti-Sm and 8 (12.9%) of both anti-Sm and anti-dsDNA negative samples. Conclusion: The high specificity of anti-cmDNA detection using IIF method makes it an excellent diagnostic tool for SLE. Anti-cmDNA is potentially a very useful biomarker for SLE with negative anti-dsDNA or/and anti-Sm antibodies.

Matched MeSH terms: Lupus Erythematosus, Systemic

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