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To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

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Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.

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Our objective was to investigate the serum levels of interferon-inducible protein-10 (IP-10) in systemic lupus erythematosus (SLE) and their correlation with disease activity and organ manifestations. Serum IP-10 levels were assessed in 464 SLE patients and 50 healthy donors. Disease activity was assessed by the revised SLE Activity Measure, and the concomitant active organ manifestations, anti-ds DNA antibody titres, complement levels and erythrocyte sedimentation rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP-10 in SLE patients and controls was determined by in vitro cultures stimulated with mitogen or lipopolysaccharide. Elevated serum IP-10 levels were observed in SLE patients, which were significantly higher in the presence of active haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced spontaneous IP-10 production in vitro. Serial IP-10 levels correlated with longitudinal change in SLE activity, even at low levels where anti-dsDNA antibody and complement levels remain unchanged. These data demonstrate that IP-10 levels are increased in SLE and serum IP-10 may represent a more sensitive marker for monitoring disease activity than standard serological tests.

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INTRODUCTION: Fibromyalgia syndrome (FMS) is a common but controversial condition. There appears to be different levels of belief of its existence and awareness. We set out to explore the variations of perceptions and awareness of this condition among rheumatologists from Malaysia and Singapore. METHODS: 48 rheumatologists from Malaysia (28) and Singapore (20) were approached to participate in this survey by answering a specific questionnaire regarding their belief in FMS. 23 respondents from Malaysia and 20 from Singapore completed the questionnaire. RESULTS: 91 percent of Malaysian rheumatologists and 95 percent of the Singaporean believe that FMS is a distinct clinical entity and that this condition is considered an illness rather than a disease. 87 percent and 90 percent of rheumatologists from Malaysia and Singapore, respectively, believe that FMS is a mixture of medical and psychological illness. However, not many of those in the university setting include FMS in their undergraduate teaching. 87 percent and 80 percent of the respondents from Malaysia and Singapore, respectively, also ordered blood tests to exclude other serious pathologies, and 100 percent of the respondents from both countries also prescribed some form of drugs to their FMS patients. CONCLUSION: This study confirmed that there was a variation of perceptions and knowledge of FMS among rheumatologists from Malaysia and Singapore. The majority of rheumatologists recognise that FMS is a distinct clinical entity, and is diagnosed by excluding other well-defined clinical diseases through a combination of clinical evaluation and screening tests.

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Symptomatic myocarditis in systemic lupus erythematosus (SLE) is uncommon. We describe the clinical characteristics, management and outcomes of 11 SLE patients without any atherosclerotic risk factors, who presented with acute lupus myocarditis (ALM). All patients were female, 46% Chinese with mean age of 27 +/- 10 years at diagnosis of SLE. ALM was one of the initial manifestations of SLE in eight (73%) patients. The median duration from onset ALM to initiation of treatment was two weeks (range: 0.3-8). All had clinical feature of left ventricle dysfunction. The most common electrocardiographic feature was nonspecific ST/T wave changes (91%). Common echocardiographic findings included segmental wall motion abnormalities (81%) and decreased left ventricular ejection fraction (81%). Median SLE disease activity index at presentation was 16 (range: 4-30). All patients received high dose corticosteroids and 64% received intravenous pulse cyclophosphamide. There were two deaths (18%) from infections. The remaining nine survivors had no recurrence of ALM nor suffer any SLE-related damage (median SLICC damage score of 0), up to a median follow-up of four years (range: 2.5-10.1). Repeat echocardiography after six months or later showed normal LVEF in eight patients (89%). Early immunosuppressive therapy in ALM, with high dose corticosteroids and pulse intravenous cyclophosphamide, results in good cardiac outcome.

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OBJECTIVES: Anti-tumour necrosis factor (anti-TNF) therapy is effective in the treatment of ankylosing spondylitis (AS), but guidelines are needed because of the cost. The primary aim of this study was to evaluate the proportion of patients with AS who meet the criteria for anti-TNF therapy as well as to explore the relationship between disease activity, health status and quality of life in patients with AS who would potentially meet the criteria compared with those who would not. METHODS: All patients with a confirmed diagnosis of AS were identified via a search through the clinic correspondence database and sent postal questionnaires. Data captured included demographics, disease activity, aspects of functional impairment, activity limitation and quality of life using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain scores (using a visual analogue scale), the Bath Ankylosing Spondylitis Functional Index (BASFI), Health Assessment Questionnaire (HAQ), short-form 36 (SF-36) and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. The unpaired Student's t-test, chi(2) test and Mann-Whitney U-test were performed for comparisons of groups where appropriate. RESULTS: Out of 325 mailed questionnaires, 246 (76%) were returned. The mean age of the patients who replied to the questionnaire was 52 yr (+/-12 yr) and 25% (62) were females. Mean BASDAI was 49 (+/-24) and 64% had a BASDAI > or = 40. There were significant differences between the groups with a BASDAI above and below 40 in pain by VAS, functional ability (BASFI, HAQ), health status (SF-36) and quality of life (ASQoL). Almost two-thirds (64%) of patients would meet the criteria for anti-TNF therapy under recommended guidelines. CONCLUSION: Patients with AS demonstrated poor functional status and poor quality of life. There is a large unmet need for effective therapy in AS, with almost two-thirds of patients meeting the proposed criteria for biological therapy. Patients with a BASDAI > or = 40 had a worse functional status and quality of life than those who have a BASDAI of <40. These results indicate that the need for effective intervention for AS is a priority area.

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OBJECTIVES: Systemic lupus erythematosus (SLE), a chronic illness with an unpredictable and variable course, profoundly affects the quality of life (QOL). General health questionnaires are used to assess QOL in SLE, but a disease-specific instrument could offer enhanced responsiveness and content validity. We detail the steps we took to develop and validate a new SLE-specific QOL instrument, SLEQOL. METHODS: Rheumatology professionals nominated items that they felt were important determinants of QOL of SLE patients. One hundred SLE patients were asked to assess the importance and frequency of occurrence of these items and to suggest those that had not been listed. Item reduction was performed using Rasch model and factor analyses to create a new questionnaire in English. This final questionnaire was administered to a cohort of 275 patients to study its psychometric properties. RESULTS: Fifty-one items covering a wide range of QOL concerns were identified. The patients' responses led to the elimination of 11. The new questionnaire of 40 items was found to have Cronbach's alpha of 0.95 and to consist of eight domains covering physical, mental and social QOL issues. It has good test-retest reliability, poor to fair cross-sectional correlation with the SF-36, with poor correlation with lupus activity or damage indices. The SLEQOL was more responsive to change than the SF-36. CONCLUSIONS: We have developed a new 40-item SLEQOL in English and showed that it is valid for use in SLE patients in Singapore. It offers better content validity and responsiveness to change than the SF-36.

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OBJECTIVES: To study serum levels of transforming growth factor beta-1 (TGFbeta1) and the expression of TGFbeta1 in in vitro peripheral blood mononuclear cell (PBMC) cultures in oriental ankylosing spondylitis (AS) patients, and to determine their association with codon 10 and 25 TGFB1 gene polymorphisms. METHODS: Serum levels of TGFbeta1 were measured by enzyme-linked immunosorbent assay (ELISA). The ability of PBMCs to synthesize TGFbeta1 and other cytokines was assessed by in vitro cultures stimulated with mitogen. Genomic DNA was extracted from PBMCs of AS patients (n=72) or unrelated healthy controls (n=96). The codon 10 and 25 polymorphisms in the TGFB1 gene were analysed using standard polymerase chain reaction-based methods. RESULTS: AS patients had significantly higher serum TGFbeta1 levels than controls (P<0.001). There was no difference in the distribution of codon 10 and 25 TGFB1 genotypes between AS patients and controls. Incubation of AS and control PBMC with phytohaemagglutinin (PHA) led to upregulation of TGFbeta1, interleukin-10, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) assessed by ELISA. Importantly, PHA-induced TGFbeta1 production was significantly enhanced in AS patients compared with normal controls whereas the production of the pro-inflammatory cytokines TNFalpha and IFNgamma was reduced. CONCLUSIONS: Our results show that AS patients express significantly higher levels of serum TGFbeta1 independent of the codon 10 and 25 genotype. Activation of AS PBMCs led to enhanced TGFbeta1 production accompanied by reduction of TNFalpha and IFNgamma while the converse was observed in normal controls.

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Behçet's disease is an idiopathic multi-systemic, inflammatory disorder that may affect major organs, including the central nervous system. It is a clinical diagnosis, and a history of recurrent oral and genital ulcers should be elicited, especially in cases of unexplained uveitis with atypical neurological symptoms. We describe the rapid neurological recovery and neuroimaging changes following high-dose systemic corticosteroids in a 44-year-old man with recurrent oral ulcers, panuveitis, and acute neuro-Behçet's, presenting with meningoencephalitis. Early diagnosis with the aid of appropriate neuroimaging and immunosuppressive therapy prevented long-term neurological complications. Appropriate neuroimaging can facilitate early diagnosis and treatment, and provide prognostic information on neuro-Behçet's.

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INTRODUCTION: Relapsing polychondritis (RPC) has been described mainly in Caucasian populations. Reports from other ethnic groups are few. OBJECTIVES: To describe the clinical characteristics, management and outcome of RPC patients seen in an Oriental population in Singapore. METHODS: The case records of RPC patients treated in our department from 1989 to 2001 were reviewed. Only 12 fulfilled the McAdam-Michet-Damiani-Levine diagnostic criteria and these were studied. RESULTS: The female-to-male ratio in our series was 3:1. There were 10 ethnic Chinese and two Malay patients. The age of onset of symptoms ranges from three to 65 years, with a mean of 34 years. A diagnosis was made from two weeks to three years after onset, with a median of 4.5 months. There were 10 patients with pinna, nine articular, eight ocular, six laryngotracheal, five inner ear, four nasal and one cardiac involvement. Five presented with fever. None of them had cutaneous, renal or central nervous system involvement. Ten had raised ESR at presentation. One patient developed discoid lupus erythematosus two years later. All 12 patients received prednisolone with eight of them requiring additional immunosuppressants. Two patients had resistant disease failing to respond adequately to various immunosuppressants together with prednisolone. There was no mortality amongst the nine patients who had remained on follow-up at the time of this report. Five of the six patients with laryngotracheal involvement had tracheostomy and one of them had airway stenting as well. CONCLUSION: Our series suggests that although the clinical manifestations of RPC are similar in the Oriental and the Caucasian populations, Oriental patients may have less cutaneous, renal or nervous system involvement and more serious airway complications.

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We describe a middle-aged lady with systemic lupus erythematosus who presented with chronic left knee monoarthritis without constitutional symptoms. The histology of synovial tissue taken at arthroscopy showed acute inflammation and Erysipelothrix rhusiopathiae, identified with some difficulty, was isolated from the enrichment broth only. Blood cultures were negative. Her history revealed significant exposure to pond fish. She responded well to intravenous penicillin and remains well 12 months later.

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INTRODUCTION: Pulmonary hypertension (PHT) associated with systemic lupus erythematosus (SLE) has a grave prognosis. Continuous prostacyclin infusion significantly reduces pulmonary arterial pressure (PAP) and may improve survival in patients with primary and secondary PHT. We report our experience with intermittent epoprostenol (EPO) infusion in SLE patients with PHT. CLINICAL CHARACTERISTICS: We reviewed patients with SLE associated PHT who were treated with intermittent EPO infusions in 1998. All 3 patients had severe PHT, with maximum systolic PAP (PASP) of 58, 96 and 67 mm Hg, respectively, when measured using Doppler echocardiography, and were in New York Heart Association functional class III. TREATMENT: All patients were given 6 infusions of EPO monthly via peripheral venous access without significant side effects. OUTCOME: The PASP of all patients remained stable during the therapy. The therapeutic response as measured by patient symptoms and PASP was variable. No patient had significant reduction of PASP during the 6-month treatment period. Two patients developed rebound elevation of PASP after cessation of treatment, while the PASP of the other patient remained stable for 10 months. CONCLUSION: Although intermittent EPO infusion did not substantially reduce PASP, it prevented further rise in PAP during the treatment period, suggesting that this regimen may benefit a subset of SLE patients with PHT.

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Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have provided new methods for evaluating early rheumatoid arthritis (RA). Their diagnostic properties in terms of detecting primary pathology of RA (i.e., erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed. High-resolution US plays a significant role in therapeutic and diagnostic procedures. MRI also assists in the understanding of RA pathogenesis and joint mechanics.

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We sought to test our clinical impression that using a low dose methylprednisolone pulse (MEP; < or = 1500 mg over 3 days) in treating flares of systemic lupus erythematosus (SLE) was effective and associated with fewer serious infections. We retrospectively studied SLE patients who received MEP between 1989 and 2000. A 'low dose' group of 26 patients who had received 1-1.5 g and a 'high dose' group of 29 patients who received 3-5 g of MEP were identified. SLEDAI scores and prednisolone doses were recorded at the time of MEP pulses and 6 months later. All serious infections (requiring admission and i.v. antibiotics) occurring during this 6 month period and their outcomes were recorded. Both groups had similar demographic data, initial SLEDAI scores, i.v. cyclophosphamide use, and SLE organ involvement. Despite high- and low-dose MEP being efficacious in controlling disease activity (lowering of SLEDAI scores and subsequent prednisolone dose) there were only nine episodes of serious infection in seven patients in the low-dose group compared with 20 episodes in 17 patients from the high-dose group (P = 0.04). In both groups a majority of infections (75 and 77% in the high- and low-dose groups) occurred in the first month after MEP. Those with a low serum albumin (< 20 g/l) had an increased risk of mortality (OR 44, 90% CI 6.19-312.98) and a trend towards greater numbers of infections. Low-dose MEP was effective in controlling SLE flares and associated with fewer serious infections than traditional high-dose MEP.

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We describe a case of Mycobacterium haemophilum in an immunocompromised patient with systemic lupus erythematosus (SLE). Mycobacterium haemophilum is a recently described pathogen which has not been previously described either in SLE patients or patients on Mycophenolate Mofetil. Mycobacterium haemophilum can be difficult to diagnose, as it may not have the granulomas characteristic of atypical mycobacterial infections. Combination therapy with at least two drugs for several months is required and the outcome depends on the patient's underlying immunocompromised state. Our report highlights the need for early diagnosis and treatment of Mycobacterium haemophilum in immunocompromised patients with SLE.

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Medium-sized artery aneurysms are rare in patients with systemic lupus erythematosus (SLE). We report on a 21-year-old Chinese man with SLE and secondary antiphospholipid syndrome (APS) who presented with acute abdominal pain due to a ruptured right hepatic artery aneurysm. He was also found to have aneurysms of the left hepatic artery and splenic artery on autopsy. There have been only eight cases of hepatic artery aneurysm and one case of splenic artery aneurysm associated with SLE in the English literature. Abdominal aneurysm must be suspected in SLE patients presenting with acute abdominal pain, haemoperitoneum or occult bleeding.

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AIMS: To study the demographic and clinical features as well as outcomes of tetanus patients at the Sarawak General Hospital, Kuching from 1990 to 1999. METHODS: All cases of tetanus from January 1990 to September 1999 were identified from the computer record at the hospital and these were then restrospectively reviewed. RESULTS: A total of 22 cases of tetanus was seen at the Sarawak General Hospital in the ten-year period with a mean of 2.2 cases per year. There were 15 male (68.2%) and 7 female (31.8%) patients. Most cases occurred in the age group 60-69. Eighteen patients (81.8%) had a reasonably identifiable injury prior to the onset; all had their wounds debrided. Body stiffness, trismus and dysphagia were the three commonest presenting complaints. Twenty-one patients (95.5%) were admitted to the intensive care unit (ICU), with an average length of ICU stay of 21.4 days. Nineteen patients (86.4%) required mechanical ventilation for a varying period of time in the ICU. All patients (100%) had tracheostomy performed and intravenous diazepam infusion as part of their management. Twenty patients (90.9%) received intravenous crystalline penicillin as the treatment antibiotics. Twenty-one patients (95.5%) received intramuscular human antitetanus immunoglobulin. There were four deaths, accounting for a mortality of 18.2%. CONCLUSION: In general, tetanus remains in Sarawak an important disease with substantial mortality and morbidity that primarily affects unvaccinated or inadequately vaccinated individuals. It is, however, highly preventable through both routine vaccination and appropriate wound management. Our case series show comparable pattern and outcome with other case series reported in the literatures.

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