Cerebral toxoplasmosis is a rare complication of systemic lupus erythematosus (SLE). An 18 year old male student, newly diagnosed to have SLE, developed neurological symptoms two days after completing intravenous methylprednisolone. Computed tomography (CT) scan showed features consistent with a diagnosis of probable cerebral toxoplasmosis. He responded dramatically to antitoxoplasma therapy. To our knowledge, this is the first case report in the literature that presents a newly diagnosed SLE patient who rapidly developed cerebral toxoplasmosis following administration of intravenous methylprednisolone. Our case illustrates that this drug is potentially fatal and the importance of differentiating cerebral infection from neuropsychiatric lupus.
A 24-year-old lady presented with four days history of fever, non-pruritic rash, ankle pain and swelling. She had consumed herbal supplement five days before the onset of symptoms. Examinations revealed erythematous maculo-papular lesions of varying sizes on sun exposed areas. Patient was suspected to have Drug Induced Lupus Erythematosus (DILE) and subsequently symptoms subsided rapidly on withholding the herbal medication.
OBJECTIVE: To validate the Medical Outcomes Study Family and Marital Functioning Measures (FMM and MFM) in a multi-ethnic, urban Asian population in Singapore.
METHODS: English speaking Chinese, Malay or Indian SLE patients (n=120) completed a self-administered questionnaire containing the FFM and MFM at baseline, after 2 weeks and after 6 months. Lupus activity, disease-related damage and quality of life were assessed using the British Isles Lupus Assessment Group (BILAG), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and SF-36 Health Survey respectively. Scale psychometric properties were assessed through factor analysis, Cronbach's alpha, quantifying test-retest differences and known-groups construct validity.
RESULTS: Factor analysis of scores obtained at baseline and after 6 months identified 3 factors corresponding to the FFM (1 factor) and the MFM (2 factors). Both scales showed acceptable internal consistency, with Cronbach's alpha of 0.95 for the FFM and 0.70 for the MFM. Mean (s.d.) test-retest differences were -0.31 (3.82) points for the FFM and -0.70 (4.26) points for the MFM. Eleven out of 13 a priori hypotheses relating both the FFM and MFM to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales.
CONCLUSION: The FFM and MFM are valid and reliable measures of family and marital functioning in a multi-ethnic cohort of Asian SLE patients in Singapore.
The aim of this study was to investigate the incidence of IgG anticardiolipin antibody (ACL) and IgG anti-beta(2) glycoprotein I antibody (anti-beta2GPI) positivity in patients with primary or secondary antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE), to assess the association between IgG ACL and anti-beta2GPI, and the relationship between the presence of ACL and anti-beta2GPI with the clinical manifestations of APS. IgG ACL and IgG anti-beta2GPI levels were measured in 51 SLE patients, 20 patients with SLE and APS (secondary APS) and 11 primary APS patients using commercially available ELISA kits. Relationships between laboratory data and clinical manifestations of the patients were examined. The incidence of IgG ACL positivity was significantly higher in primary (36.4%) and secondary (40%) APS than in SLE (13.7%) patients (P = 0.02). The incidence of IgG anti-beta2GPI positivity was significantly higher in primary (54.5%) and secondary (35%) APS than in SLE (7.8%) patients (P = 0.0006). Mean levels of IgG ACL and anti-beta2GPI were significantly higher in the primary and secondary APS than in the SLE patients (P = 0.002 for both). A significant relationship was found between IgG ACL and IgG anti-beta2GPI (P = 0.01, R(2) = 0.56). There was a significant correlation between the presence of IgG ACL and a history of thrombosis in the combined primary and secondary APS group, but not in SLE patients. In conclusion, in this study IgG ACL and IgG anti-beta2GPI are closely related and mean levels of IgG ACL and IgG anti-beta2GPI are higher in patients with either primary or secondary APS than in SLE patients.
Study site: Rheumatology Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
BACKGROUND: Studies have shown that certain genes within the major histocompatibility complex predispose to systemic lupus erythematosus (SLE) and may influence clinical and autoantibody expression. Thus, we studied the frequency of HLA-DR, -DQA, -DQB and -DPB alleles in ethnic Malays with SLE to determine the role of these genes in determining disease susceptibility and their association with clinical and immunological manifestations.
METHODS: Fifty-six Malay SLE patients were enrolled into the study. Demographic, clinical and immunological findings were obtained from medical records. HLA-DR, DQ and DP typing were done using modified PCR-RELP. Controls were from ethnically-matched healthy individuals.
RESULTS: We found a strongly significant association of the DR2 and DQB1 *0501 and DQB1*0601 (pcorr = 0.03, rr = 3.83, pcorr = 0.0036, rr = 4.56 and pcorr = 0.0048 and rr = 6.0, respectively). There was also a weak increase of DQB1*0.201 and DPB1*0.0901 with a weak decrease of DQA1*0601 and DQB1*0503 and *0301 which were not significant after corrections for multiple comparisons were made. There was a significant positive association of DR2 and DQB1*0501 with renal involvement and DR8 with alopecia. A nonsignificant increase of DQB1*0503 in patients with photosensitivity was noted. Significant autoantibody associations were also found: DQB1*0601 with anti-Sm/RNP, DR2 with antiSSA (Ro)/SSB (La), and DR2, DQB1*0501 and *0601 with antibodies to ds DNA. There was no specific DR, DQ or DP associations with age of disease onset (below 30 years or those at or above 30 years).
CONCLUSION: Our data suggests the role of the HLA class II genes in conferring SLE susceptibility and in clinical and autoantibody expression.
Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgammaR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcgammaRIIA) occurs in two allelic forms. The allele FcgammaRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgammaRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcgammaRIIA-H131 has a higher capacity for hIgG2 compared to FcgammaRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcgammaRIIA using a novel polymerase chain reaction-allele specific primer (PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (chi2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcgammaRIIA-H131 in the ethnic groups studied.
Antibodies to the ribosomal P protein are specific for SLE but their prevalence varies in different ethnic groups. In a group of Chinese SLE patients from Malaysia who have a high prevalence of this antibody, we have found an increased frequency of an uncharacterized HLA-DRB gene allele, DR16X, in patients who are positive for anti-P antibodies compared to antibody negative patients (31.3% vs 3.2%, P < 0.01, Pcorr not significant, relative risk = 13.6). DR16X has only been found in south east Asian populations and may be a genetic factor which influences the high prevalence of anti-P antibodies in Chinese.
One hundred and seventy patients with systemic lupus erythematosus (SLE) were studied for the prevalence of antibodies to the small RNA-associated proteins Ro/SSA, La/SSB, Sm, U1RNP and Sm. The relationship of these autoantibodies to different races, sexes and clinical manifestations of SLE was evaluated. Passive immunodiffusion was employed using human spleen extract as antigen source for Ro and rabbit thymus extract for La, Sm and U1RNP. We found the prevalence of antibodies to be as follows: anti-Ro/SSA, 36%; anti-La/SSB, 8%; anti-Sm, 15% ; anti-U1RNP, 21%. Except for a low prevalence of anti-La, the prevalence of these antibodies was similar to that in Western studies, The prevalence of anti-Ro/SSA is similar to that reported in the Western studies, but lower than that reported in the Oriental patients from Singapore and Hong Kong. Linkages of anti-Ro with anti-La antibodies were usual; however, although anti-Sm antibodies were usually associated with anti-U1RNP, they were more frequently associated with anti-Ro antibodies. The Malay patients had a high prevalence of anti U1RNP compared to other races. No gender difference was detected. Anti-Sm antibody was associated with serositis and anti-U1RNP antibodies with Raynaud's phenomenon. No association was found between the presence of skin renal or cerebral manifestations and any specific antibodies or combination of antibodies.
Background: Malignancies are among the leading causes of death in Systemic Lupus Erythematosus (SLE)
patients with studies reporting a higher prevalence of malignancy in SLE patients compared to the general population.
We wanted to determine the frequency of cancer in a cohort of SLE patients and identify its associated risk factors.
Methods: Cross-sectional study involving SLE patients attending the nephrology outpatient clinic, Universiti
Kebangsaan Malaysia Medical Centre between January and June 2014. Results: We recruited 228 patients (207 female,
21 male), aged 40.48 ± 12.86 years with mean SLE duration of 11.65 ± 6.46 years. Majority (87%) had lupus nephritis
and were in remission with a median SLEDAI score 2 (0, 14). Majority (89%) were on corticosteroid with either a
steroid sparing agent like mycophenolate mofetil (15.4%), azathioprine (36.8%) or ciclosporin (15.4%). One hundred
and sixty (70.2%) patients were either receiving or had received intravenous cyclophosphamide with median dose
of 5,173.6 ± 3,242.4 mg. Seven female patients were diagnosed with cancer during the course of their SLE with 56
(34-78) years being median age at malignancy and SLE duration of 4 (0-12) years. Majority (5/7) had lupus nephritis
and all patients a median dose of prednisolone 10 (2.5, 10) mg with 10 (4-24) years of steroids. Two patients had a
family history of cancer with majority developing cancer after the diagnosis of SLE. Two patients received intravenous
cyclophosphamide prior to the development of cancer for their SLE compared to overall cohort of 160. Three patients
had colorectal cancer, 2 had cervical cancer, 1 had breast cancer, and one patient had germ cell tumour and one thyroid
cancer. All patients had their cancer successful treated with no signs of recurrence. Conclusion: We found a lower
occurrence of cancer in our SLE patients as compared with the reported literature.
To compare the clinical presentation, response to therapy and outcome of thrombotic thrombocytopenic purpura (TTP) in an inception cohort of patients with and without SLE.
BACKGROUND: Systemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). Recently, meeting a definition of a lupus low disease activity state (LLDAS), analogous to low disease activity in rheumatoid arthritis, was preliminarily validated as associated with protection from damage accrual. The LLDAS definition has not been previously evaluated for association with patient-reported outcomes. The objective of this study was to determine whether LLDAS is associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of patients with SLE.
METHODS: HR-QoL was measured using the Medical Outcomes Study 36-item short form health survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using the SLE disease activity index (SLEDAI-2 K), physician global assessment (PGA) and LLDAS.
RESULTS: Significant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level and damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p
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
We reported a case of a young female patient presented with sepsis and diagnosed with melioidosis and systemic lupus erythematosus (SLE) within the same admission. She presented with 1-week history of productive cough, progressive dyspnoea together with prolonged fever, arthralgia, rashes and oral ulcers. She had septicemic shock, respiratory failure requiring intubation and ventilation in intensive care unit and subsequently developed acute renal failure requiring haemodialysis. Antibiotics and immunosuppressive treatment including low-dose intravenous cyclophosphamide were commenced. She had a remarkable recovery and was discharged after 6 weeks. There was no evidence of active SLE or relapse of melioidosis during clinic follow-ups.
Systemic lupus erythematosus (SLE) is one of the commonest systemic autoimmune diseases that can present with variable clinical manifestations. Intravenous Immunoglobulin (IVIG) has been used as a salvage therapy for severe lupus with encouraging results though there is yet randomised trial to support the usage. This report highlights the efficacy and safety of high dose IVIG in SLE patients with multi-organ involvement particularly lupus nephritis. We also reviewed the literature on the usage of IVIG for lupus nephritis. However, more studies are needed to further clarify the optimal therapeutic dosage and regime for IVIG and to identify the group of patients who might benefit the most from this expensive therapy.
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.
Systemic lupus erythematosus (SLE) is a debilitating and chronic autoimmune disease which strikes insidiously. The disease currently has a prevalence of 43/ 100 000 individuals in Malaysia. The presentation of the disease is varied resulting in delay in diagnosis and onset of complications prior to management. The disease commonly presents as joint pain and cutaneous manifestations. Neuropsychiatric presentation accounts for 24% of symptoms during onset of illness. This case report highlights that we encountered a patient who presented with neuropsychiatric manifestations, whereby the patient was managed for the psychiatric symptoms prior to the organic diagnosis being made.
Systemic lupus erythematosus (SLE) is a common autoimmune disease that we see in our daily clinical practice. It can involve almost every organs in the body. Cardiac manifestations of SLE include pericarditis, myocarditis, heart block, coronary artery disease and others. Here, we report a case of SLE with an uncommon presentation of massive pericardial effusion as initial presentation. Here we also highlight that massive pericardial effusion can also be associated with other complications of SLE such as heart failure and lupus nephritis.
Joint involvement is common in systemic lupus erythematosus (SLE) patients, however, screening for joint specific autoantibodies in patients is not routinely performed. This may be due to the lack of known antigens and available tissue. The rat musculoskeletal tissue may be a suitable source of antigen to detect arthritic autoantibodies.
Method: We tested plasma of SLE patients, with arthritis (N=9) and without arthritis (N=7) as well as plasma from normal individuals (N=7) on fresh sectioned tissue from rat plantar hind paw using indirect immunofluorescence method.
Results: Binding of autoantibodies to striation in skeletal muscle cells in the tissue was clearly demonstrable in all samples from SLE with arthritis but not on slides incubated with plasma from normal or SLE without arthritis.
Conclusion: Thus, rat plantar tissue may be suitable for detecting autoantibodies from SLE patients that may be involved in the pathogenesis of lupus arthritis.
A 33-year old Malay woman with undiagnosed systemic lupus erythematosus (SLE) and other comorbids presented with acute glomerularnephritis, hypertensive emergency and later acute confusional state. Cranial MRI revealed features consistent with posterior reversible encephalopathy syndrome (PRES).