Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

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.

Discordant assessment of lupus activity between patients and their physicians: the Singapore experience.

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.

Enhanced expression of interferon-inducible protein-10 correlates with disease activity and clinical manifestations in systemic lupus erythematosus.

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.

The reliability, validity and sensitivity to change of the Chinese version of SF-36 in oriental patients with rheumatoid arthritis.

OBJECTIVE: To assess the reliability, validity and sensitivity to change of a Chinese version of the 36-item Short-Form Health Survey (SF-36) in Chinese-speaking patients with rheumatoid arthritis (RA) in Singapore. METHODS: The psychometric properties of the Chinese Hong Kong standard version of the SF-36 were assessed in 401 RA patients. The construct validity of the Chinese SF-36 was assessed by comparison with the American College of Rheumatology (ACR) functional status, a validated Chinese Health Assessment Questionnaire (C-HAQ) and markers of RA activity and severity. RESULTS: The overall Cronbach's coefficient alpha was 0.921, reflecting excellent internal consistency. The instrument showed reasonable test-retest reliability except in the social functioning (SF) subscale. There was a significant ceiling effect in the role physical (RP), SF and role emotional (RE) subscales and a floor effect in the RP and RE subscales. Physical function (PF) and SF were strongly correlated with C-HAQ and patient's assessment of RA activity [Pearson's correlation coefficient (r) ranging from -0.41 to -0.53] and moderately correlated with ACR functional status (r = -0.35 and -0.3, respectively). Weak correlations were also found between the Chinese SF-36 and markers of RA activity, deformed joint count and radiographic damage. PF and SF were the subscales most responsive to change in quality of life (QOL). CONCLUSION: The Chinese SF-36 showed reasonable reliability, criterion validity and responsiveness with limitations in certain subscales. Overall, the physical domains and PF in particular may be the most ideal psychometric measures of QOL in RA.

Development and preliminary validation of a systemic lupus erythematosus-specific quality-of-life instrument (SLEQOL).

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.

Transforming growth factor beta-1 and gene polymorphisms in oriental ankylosing spondylitis.

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.

Primary meningococcal arthritis and endogenous endophthalmitis: a case report.

INTRODUCTION: Arthritis and endophthalmitis are both recognised complications of meningococcal infection. They may occur in the presence or absence of meningitis or meningococcaemia. Primary meningococcal arthritis (PMA) and endophthalmitis are important diagnoses to recognise as delayed treatment would result in permanent joint and eye damage. We report the first patient with both PMA and meningococcal endophthalmitis and present a review of the literature. CLINICAL PICTURE: An afebrile, non-toxic, 54-year-old female presented with arthritis and a painful red left eye following an episode of diarrhoea. An initial diagnosis of reactive arthritis with uveitis was made. However, subsequent microbiological investigations isolated Neisseria meningitides thus confirming the final diagnosis. TREATMENT: Antibiotics were instituted. OUTCOME: There was complete resolution of the arthritis but her left eye vision had deteriorated to just perception of light. CONCLUSION: The presentations of PMA and meningococcal endophthalmitis are often confusing. This should be considered in the differential diagnosis of reactive arthritis and acute dermatitis-arthritis syndrome.

Abdominal crisis in a young man with systemic lupus erythematosus.

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.

Cyclophosphamide type I hypersensitivity in systemic lupus erythematosus.

Cyclophosphamide is an important immunosuppressive agent in the treatment of many rheumatic diseases. Urticaria and anaphylaxis to intravenous cyclophosphamide (i.v. CYC) have been reported in patients with haematological and solid organ malignancies. This is the first report in the rheumatology literature of a type I hypersensitivity reaction following monthly i.v. CYC. An 18-year-old girl with systemic lupus erythematosus (SLE) developed generalized urticaria (without concomitant angioedema or anaphylaxis) following i.v. CYC. She had previously developed life-threatening angioedema following a respiratory tract infection. She successfully completed regular pulse i.v. CYC with pre-medication with anti-histamine. In the absence of a severe type I hypersensitivity reaction and other suitable immunosuppressive agents, i.v. CYC may be safely continued with pre-medication and careful monitoring during each infusion.

Prophylactic treatment of dens evaginatus using mineral trioxide aggregate.

Two case reports with dens evaginatus are presented. Each patient had one tooth affected. There was a prominent tubercle on the occlusal surface of the mandibular second premolar. Under local anesthesia and rubber dam isolation a partial pulpotomy was conducted and mineral trioxide aggregate was placed. After 6 months the teeth were removed as part of planned orthodontic treatment. Histological examination of these teeth showed an apparent continuous dentin bridge formation in both teeth, and the pulps were free of inflammation. These cases show that mineral trioxide aggregate can be used as an alternative to existing materials in the proplylactic treatment of dens evaginatus.

New disease modifying agents in adult rheumatoid arthritis.

In recent years, new disease modifying agents including leflunomide and tumour necrosis factor (TNF) antagonists have been used to treat patients with rheumatoid arthritis (RA). Leflunomide prevents proliferation of activated lymphocytes by inhibiting dihydroorotate dehydrogenase, a critical step in de novo pyrimidine synthesis. Leflunomide has been shown to be as effective as sulfasalazine and methotrexate (MTX) in placebo-controlled trials. It also improves physical function, quality of life measures and retards radiographic progression. TNF antagonists include infliximab and etanercept. Infliximab is a chimeric TNF monoclonal antibody. Repeated infusions of low dose infliximab (1 mg/kg) are ineffective if given alone. Addition of MTX to infliximab has been shown to prolong the duration of clinical response. Etanercept is a human TNF receptor p75 Fc fusion protein. In active RA patients with suboptimal response to MTX, additional clinical benefit was obtained by the addition of infliximab or etanercept to MTX. The main side effect of etanercept is injection site reaction. However, the long-term effect of TNF antagonists in the development of infection, malignancy and autoimmune disease remains unknown.

A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992.

OBJECTIVE: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively. METHODS: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors. RESULTS: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively). CONCLUSION: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

Epidemiology of cutaneous lupus erythematosus in a tertiary referral centre in Singapore.

The aim of this retrospective study was to investigate the epidemiology, yield of investigations and proportion of patients who develop systemic lupus erythematosus (SLE) among the subsets of cutaneous lupus erythematosus (LE) in the Singapore Asian population. One hundred and twenty-five patients were diagnosed with cutaneous LE on clinico-pathological correlation, of which 73 had discoid lupus erythematosus (DLE), eight had subacute cutaneous LE (SCLE), 22 had acute LE lesions and the remainder had other less common forms of cutaneous LE. Histology was consistent with LE in 94.4% and suggestive in 4.8%. Direct immunofluorescence was positive in 61% of DLE, 86% of SCLE and 80% of acute LE cases. Antinuclear antibody (ANA) was present in the majority of acute LE (85%) and SCLE (88%) but only in 25% of DLE. Eight patients (11%) presenting with DLE had definite SLE at first presentation and two (2.7%) subsequently several months later. Of these patients, six had only mucocutaneous and serological criteria but two had major organ involvement. Five SCLE patients (63%) fulfilled the criteria for SLE, including two with major organ involvement.

Musculoskeletal responses to high- and low-intensity resistance training in early postmenopausal women.

PURPOSE: The purpose of this study was to compare the effects of a high-load (80%, 1-repetition maximum (RM), 8 reps) and a high-repetition (40%, 1-RM, 16 reps) resistance training protocol on muscular strength and bone mineral density (BMD) in early postmenopausal, estrogen-deficient women. The 6-month programs were matched initially for training volume (3 sets, 3 d x wk(-1)) for 12 exercises selected to specifically load the spine and hip. METHODS: Subjects included 25 women (41-60 yr) who were matched by spine BMD then randomly assigned to either the high-load (HL, N = 10), high-repetition (HR, N = 7), or control (C, N = 8) groups. Dietary calcium intakes were supplemented to approximately 1500 mg x d(-1). Total body, spine, and hip BMD (DXA, Lunar Model DPX-IQ), upper and lower body muscular strength, and biochemical markers of bone turnover were measured at baseline and after 6 months of training. RESULTS: There were no group differences in the baseline measures. Both training groups showed similar increases in biceps (20%) and rectus femoris (28-33%) cross-sectional areas, in lower body strength (approximately 30%) and in hip strength (37-40%). HL showed greater improvements in upper body strength (HL 25%, HR 16%). Neither training group experienced significant increases in spine or hip BMD, although the HL total body BMD tended to decrease (-1.1%+/-0.4, P = 0.054) after training. Osteocalcin tended to increase (P = 0.08) in all groups after training, and the % change in osteocalcin was positively related to % changes in the total hip (r = 0.41, P = 0.048) and the trochanter (r = 0.42, P = 0.04) BMD. CONCLUSION: The high-load and high-repetition resistance training protocols were both effective in improving muscular strength and size in postmenopausal women, indicating low-intensity resistance training can be beneficial for the muscular fitness in women for whom high-intensity exercise is contraindicated.

Nocardiosis in patients with systemic lupus erythematosus. The Singapore Lupus Study Group.

Nocardia, a gram positive variably acid-fast aerobic bacterium is an opportunistic pathogen in immunocompromised hosts. We present 5 cases of nocardiosis in patients with systemic lupus erythematosus. We emphasize the clinical features, radiologic findings, and antibiotic sensitivity. Lung involvement was the predominant manifestation; others include brain abscess, retinitis, thyroiditis, and diaphragmatic infiltration. We describe the first cases of pulmonary nocardiosis presenting as pneumothorax and the use of fine needle aspiration cytology in diagnosing nocardial thyroiditis.

Mineral trioxide aggregate (MTA) as a root end filling material in apical surgery--a case report.

Many root end filling materials for apical surgeries have been identified either for scientific evaluation or clinical usage but none meets the requirements of an ideal root end filling material. Recently a new cement, Mineral Trioxide Aggregate (MTA) was researched as a potential root end filling material and showed promising results. This paper reports the significant findings of research done on MTA as a root end filling material and presents a clinical case where apical surgery was performed using MTA as retrograde filling.

Temporomandibular disorders in rheumatoid arthritis.

OBJECTIVE: To determine the frequency and character of temporomandibular disorders (TMD) in Oriental patients with rheumatoid arthritis (RA) and to investigate the relationship between TMD and RA in a tertiary referral center. METHODS: Symptoms and signs related to TMD were investigated in 80 patients (67 female, 13 male) who fulfilled the American College of Rheumatology 1987 revised criteria for RA. Diagnoses of TMD including muscle, disk displacement, or temporomandibular joint (TMJ) disorders were made based on clinical assessment. TMJ disorder was then correlated with the clinical, laboratory, and radiological features of RA. RESULTS: The mean age of the study population was 49.7 years and the mean duration of RA was 86.9 months. Eleven patients (13.8%) had active RA at the time of TMD assessment. About 76% of the study population had seropositive disease and 62% had peripheral joint erosions. Osteoarthrosis of the TMJ was the most common TMD in this Oriental population. Joint sounds on opening (35%), joint sounds on moving sideways or forward (27.5%), and pain in jaw joints (23.7%) were common TMD symptoms. Deviated mouth opening (45%) and coarse crepitus (15-21.3%) were most prevalent on examination. CONCLUSION: Patients with RA who had prolonged disease duration of RA and active peripheral joints tended to have osteoarthrosis of the TMJ. Presence of rheumatoid factor or peripheral joint erosions was not associated with TMJ osteoarthrosis.