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)
The clinical outcome of bacteraemic patients is influenced by many factors. It is vital to know one's own local hospital epidemiological data so as to provide optimal care to the affected patients. This was a prospective, observational study carried out in the said patient population over a period of four months in the year 2005. One hundred and ninety one patients presented with bacteraemia over the study period. Fifty-two (27%) of the patients died. Mechanical ventilation, inappropriate empirical antibiotic usage, Chinese ethnicity and low serum albumin levels independently affected prognosis. These factors should alert physicians to those patients who require more intensive monitoring and care.
KEY WORDS:
Bacteraemia, Blood Culture Positive, Outcome, Risk factors, Kuala Lumpur, Malaysia
Systemic Lupus Erythematosus (SLE) is a disease with multiorgan involvement and multiple autoantibody production including antineutrophil cytoplasmic antibodies (ANCA). Despite its reported prevalence in more than one third of SLE patients, the role of ANCA in the pathogenesis or otherwise in SLE remains unresolved. 131 SLE patients had been previously studied for various serologic parameters of disease activity. Their cumulative organ involvement in the course of their disease had also been determined and the Lupus Activity Index (LAI) calculated. Their stored sera were then screened for the presence of ANCA by two methods viz Indirect immunofluorescence (IIF) and also enzyme-linked immunosorbent assay (ELISA). ANCA was present in 24.8% of these SLE patients. The atypical ANCA pattern was predominant and accounted for an overall of 20.6%. Anti-MPO and anti-PR3 were detected in 1.5% of patients respectively. No association was found between ANCA positivity and disease activity. There was also no association of ANCA with specific organ involvement. Despite the high prevalence of ANCA especially the atypical variant in SLE, they probably represent only one of the wide repertoire of autoantibodies found in this disease. Routine testing for ANCA in lupus patients is therefore not recommended.
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.
The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.
Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
An analysis of the clinical and serological features of 12 male and 122 female patients with SLE was done to determine whether sex related differences exist. We found a lower incidence of mucocutaneous symptoms and arthritis but an increased incidence of discoid lesions, pleuritis and pericarditis in males at disease onset. During the disease course, there was a lower incidence of arthritis, a similar prevalence of mucocutaneous symptoms but an increased incidence of pleuritis in males with a trend towards renal involvement. These findings were however not statistically significant except for the higher incidence of thrombosis among males. Serologically, both groups showed similar frequencies of autoantibodies and hypocomplementaemia. Although the study was small, it was shown that several sex-related differences in the clinical and serological features exist in Malaysian SLE patients.
Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), 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
Cerebral lupus (CL) is a common cause of morbidity and mortality in patients with SLE. The brain CTs of 27 consecutive adult patients with SLE and various neurological presentations were reviewed. The median age and duration of neurological symptoms at the time of the brain CT were 30 years (range = 14-51 years) and six days (range = 1 day-22 years), respectively. Eleven patients (41%) had normal CTs. The abnormalities in the remaining patients could be divided into six categories: (a) cerebral atrophy alone (two patients); (b) calcification alone (three patients); (c) infarct(s) alone (five patients); (d) cerebral atrophy and calcification (three patients); (e) cerebral atrophy and infarct(s) (one patient) and (f) cerebral atrophy, calcification and infarct(s) (two patients). Altogether eight patients (30%) (age range = 17-47 years) had intracerebral calcification: the globus pallidus was involved in all, putamen in two, head of the caudate nucleus in one, thalamus in one, centrum semiovale in two and cerebellum in three patients. Two patients had extensive calcifications of most of the basal ganglia, centrum semiovale and cerebellum. There was no relationship between the presence/degree of calcification and age of patients/duration or type of neurological presentation. The pathogenesis of cerebral calcification in CL is unknown. Cerebral lupus must now be included in the differential diagnosis of intracerebral calcification.
A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.
Two-hundred and sixty-five patients with asymptomatic proteinuria and/or haematuria were studied at the Department of Medicine, Universiti Kebangsaan Malaysia and Department of Nephrology, General Hospital Kuala Lumpur. They represented 25.4% of all the renal biopsies performed during the period 1980-88. All the three races were affected with 71.3% occurring between the ages of 20-39 years and 41.1% were detected during routine medical examination. Excluding those patients with lupus nephritis, IgA nephropathy was the commonest histological diagnosis (51.7%). The presence of severe and advanced histological changes in a significant number of biopsies emphasises the need for more effective screening and early referral of this group of patients.
The aim of this study was to assess the bone mineral density (BMD) of premenopausal patients with systemic lupus erythematosus (SLE) on corticosteroids (CS) and to determine the influence of CS and other risk factors on BMD. A total of 98 premenopausal patients with SLE were recruited from outpatient clinics in two teaching hospitals. Risk factors for osteoporosis were determined, and BMD was measured using dual-energy x-ray absorptiometry. The mean age of the patients was 30.05 +/- 7.54 years. The mean dose of prednisolone at time of BMD measurement was 18.38 +/- 10.85 mg daily. Median duration of CS use was 2.5 years (range 0-20). Median cumulative dose of CS was 9.04 g (range 0.28-890.0). Six patients (6.1%) had osteoporosis, 41 (41.9%) had osteopenia and 51 (52.0%) had normal BMD. Lumbar spine T score correlated with cumulative CS dose (P = 0.019). Duration of CS intake correlated with femoral neck T score (P = 0.04) and trochanter T score (P = 0.008). There was no correlation between BMD and race, SLE Disease Activity Index score, smoking and self-reported calcium intake or exercise. Only 52% of these patients had normal BMD. The duration and cumulative dose of CS intake was significantly correlated to BMD, but not the other commonly assessed risk factors. These findings suggest that premenopausal patients with SLE on CS should have their BMD measured at regular intervals to fully assess their osteoporosis risk.
Study site: outpatient clinics in two teaching hospitals
Prehemodialysis and hemodialysis patients are at an increased risk of hepatitis B infection and have an impaired immune response to hepatitis B vaccines. We evaluated the immune response to the new adjuvant of hepatitis B vaccine AS04 (HBV-AS04) in this population. We measured antibody persistence for up to 42 months, and the anamnestic response and safety of booster doses in patients who were no longer seroprotected. The primary vaccination study showed that HBV-AS04 elicited an earlier antibody response and higher antibody titers than four double doses of standard hepatitis B vaccine. Seroprotection rates were significantly higher in HBV-AS04 recipients throughout the study. The decline in seroprotection over time was significantly less in the HBV-AS04 group with significantly fewer primed patients requiring a booster dose over the follow-up period. Solicited/unsolicited adverse events were rare following booster administration. Fifty-seven patients experienced a serious adverse event during the follow-up; none of which was vaccine related. When HBV-AS04 was used as the priming immunogen, the need for a booster dose occurred at a longer time compared to double doses of standard hepatitis B vaccine. Hence, in this population, the HBV-AS04 was immunogenic, safe, and well-tolerated both as a booster dose after HBV-AS04 or standard hepatitis B vaccine priming.
A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.
Microalbuminuria is the earliest indicator of diabetic kidney disease and generalised vascular endothelial dysfunction. The Microalbuminuria Prevalence (MAP) Study was carried out to assess the prevalence of macroalbuminuria, microalbuminuria and normoalbuminuria in Asian hypertensive patients with type 2 diabetes on usual care. This paper presents a subanalysis of data from patients in Malaysia. In 733 analysed patients, the prevalence of macroalbuminuria and microalbuminuria was 15.7% and 39.7%, respectively. The high prevalence of diabetic nephropathy in these high-risk patients is a cause for concern, and the Malaysian Health Care system should be prepared for a pandemic of end-stage renal disease due to diabetic nephropathy.
Study site: six medical centres in Kuala Lumpur, Kota Bharu,
Kuching and Kota Kinabalu
Angiotensin-converting enzyme (ACE) gene polymorphism, especially the deletion/deletion (DD) genotype, is associated with the disease progression of immunoglobulin A (IgA) nephropathy patients in various studies from both Asia Pacific and European populations. However, recent studies within the same populations were unable to reproduce the same results. Hence, we had studied the distribution of the DD genotype, the association between ACE gene polymorphism and the disease progression, and the factors (other than ACE gene polymorphism) which were involved in the disease progression of our local patients.