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Background: IL-6 plays an important role in B cell hyperactivity and immunopathology of systemic lupus erythematosus (SLE), and may have a direct role in mediating tissue damage [1]. Elevated levels of serum circulating immune complexes (CICs) have been described in SLE but the relationship with disease activity in our multi-ethnic Asian patients remains unclear. Objectives: To determine the correlation between disease activity and the levels of CICs, serum and urine IL-6 in a Singapore cohort of multi-ethnic Asian SLE patients. Methods: Serum levels of CICs, IL-6 and urine IL-6 were measured in 88 SLE patients using CIC-C1q and high sensitivity IL-6 ELISAs. All patients fulfilled the 1997 revised American College of Rheumatology (ACR) classification criteria. Clinical and laboratory manifestations, therapy, disease activity and damage at the time of sample collection was collated. Disease activity was scored with the SLE Activity Measure-revised (SLAM-R) and damage with the ACR/Systemic Lupus International Collaborating Clinic SLE damage index (SDI). The correlation between disease activity score and CICs, serum and urine IL-6 were assessed using Spearman’s correlation. Receiver operator characteristic (ROC) curve analysis was performed to assess the performance of the individual biomarkers in discriminating SLE disease activity. Results: The cohort of 88 patients were predominantly female (n = 78, 89.6%), with a mean age of 40 years±13.1. The majority were of Chinese ethnicity (n = 73, 83%), 13% were Malay (n = 11) and 4 individuals were of other races. The mean disease duration was 98.4 months ± 86.4. The mean scores of SLAM-R and SDI were 2.9 ± 2.2 and 0.9 ± 0.9 respectively. SLE disease manifestations at the time of sample collection included mucocutaneous involvement (5.7%) and active urine sediment (28.7%). 77% had hypocomplementaemia and 70.1% had elevated titres of anti-dsDNA antibody. The majority were on corticosteroids (75.9%) and hydroxycholoroquine (65.5%). Immunosuppressive drugs included azathioprine in 37.9%, mycophenolate in 6.9%, intravenous pulse cyclophosphamide in 6.9% and cyclosporin in 1 patient. There was significant positive correlation between SLAM-R and serum CICs (R = 0.4121, p Conclusion: Our study observed significant correlation between levels of serum circulating immune complexes, serum and urine IL-6 with SLE disease activity in our multi-ethnic Asian patient cohort. ROC curve analysis suggests that serum CICs and urine IL-6 may serve as sensitive biomarkers to identify SLE patients at risk of flares. Reference: [1] Tackey E, et al. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 2004;13(5):339-43. Disclosure of Interests: None declared

Aim We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM-1 (vascular) and sICAM-1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. Methods Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. Results Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. Conclusion Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis.

Gastrointestinal (GI) symptoms are common in patients with systemic lupus erythematosus (SLE) and may be due to the disease itself, side-effects of medications, or non-SLE causes. However, GI manifestations of lupus attract far less attention than the other major organ involvements, are infrequently reviewed and rarely documented in published lupus databases or cohort studies including those from countries in Asia. According to three reports from two countries in Asia, the cumulative prevalence of SLE GI manifestations range from 3.8% to 18%. In this review, we focus on three major GI manifestations in patients from Asian countries: lupus enteritis, intestinal pseudo-obstruction, and protein-losing gastroenteropathy, for which early recognition improves outcome and reduces morbidity and mortality.

To examine the clinical manifestations, intensity of oral anticoagulation and outcomes in the prevention of recurrent thromboses in patients with antiphospholipid syndrome (APS) in a tertiary rheumatology centre in Singapore. Retrospective case review of consecutive patients with APS attending a rheumatology clinic from 1st January 2004 to 31st December 2005. There were 59 (44%) patients with definite APS and 75 (56%) with probable APS. Systemic lupus erythematosus (SLE) was the most common cause of secondary APS. Hypertension and hyperlipidaemia were the most common cardiovascular comorbidities. The most common manifestations were haematological (thrombocytopaenia and haemolytic anaemia), neurological (seizure, headache) and pulmonary hypertension. Among those with definite APS, there were similar proportions with arterial and venous thromboses. Recurrent thromboses occurred in 14 (23.7%) patient with definite APS receiving warfarin, comprising 14 (73.7%) episodes of arterial and 5 (26.3%) episodes of venous thromboses. Recurrent arterial thromboses occurred at international normalized ratio (INR) of 3 in 3 (21.4%) episodes, respectively. Recurrent venous thromboses occurred at INR 3 in 1 (20.0%) episode, respectively. Twenty-eight episodes of bleeding occurred in 21 (35.6%) patients, the majority (78.6%) being minor bleeding. Two-thirds of all major bleeds occurred at INR ≥ 3. Venous and arterial thromboses were equally common in our patients with definite APS, although recurrent thromboses were more common in the arterial circulation. Target INR > 3 was associated with lower rates of recurrent arterial thromboses but higher rates of major and recurrent bleeding. Target INR ≥ 2 appeared to be sufficient to prevent recurrent venous thromboses.

Background:Blomia tropicalis is an important domestic dust mite in the tropics and subtropics. This study describes cDNA cloning of the group 4 allergen of B. tropicalis, and the evaluation of the sensitization of this allergen in atopic populations from 2 geographic regions. Methods: cDNA cloning was carried out using the Smart RACE cDNA amplification kit. The full-length Blo t 4 cDNA was isolated by cDNA library screening, 5′ and 3′ rapid amplification of cDNA ends and long-distance PCR. Sequence analysis was performed with a combination of the Clustal W, CGC and Blast program packages. The cDNA was expressed in Pichia pastoris yeast. The skin prick test was used to evaluate the sensitization profile of recombinant Blo t 4, crude dust mite allergen extracts and major B. tropicalis recombinant allergen Blo t 5. Results: The cloned Blo t 4 had a molecular weight of 56 kDa and had 68% amino acid homology with group 4 allergens of Dermatophagoides pteronyssinus and 65% with those of Euroglyphus maynei. A sensitization profile to the expressed recombinant Blo t 4 allergen (28%) showed an unusually higher frequency than to the major allergen Blo t 5 (22%) in allergic subjects from Chengdu, PR China. In comparison, the subjects from Singapore showed very low sensitization to Blo t 4 (4%) compared with Blo t 5 (84%). Conclusions: Group 4 allergens of B. tropicalis may be an important dust mite allergen in certain distinct populations.

This study surveyed the prescription patterns of adrenaline auto-injectors (AAs) in Singapore to examine the frequency, triggers, and demographic pattern of anaphylaxis requiring such prescriptions. A 6-year retrospective review of 417 consecutive patients prescribed AAs in Singapore from January 1999 to December 2004, as identified from hospital pharmacy records. There were 417 patients identified, consisting of 295 (70.7%) Singaporeans with the remaining being non-Singaporean residents. Based on population census, the frequency of AA prescriptions was estimated at 1 per 10,000 Singaporeans. Demographic factors associated with AA prescriptions were male gender (OR = 1.361; p = 0.002); minority ethnic groups, which included Eurasians, Caucasians, Koreans, and Japanese (OR = 15.873; p < 0.001); and children

Objective We have previously validated the English version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) in our patients with lupus. Many of our Chinese patients are not fluent in English and therefore a Chinese version (SLEQOL-C) has been adapted for their use. Methods Two independent translators translated the SLEQOL into Chinese. A consensus version was derived from both sets of translations. Back translation of this version was performed by another 2 independent translators who had neither been involved in the forward translation nor encountered the SLEQOL. The final version, SLEQOL-C, was finalized after rectifying the discrepancies revealed by the back translation. Linguistic validity was tested in open interviews with bilingual patients with lupus. The SLEQOL-C and SLEQOL were administered to patients to determine whether they displayed differential item functioning (DIF). Results In general, most of the items in English could be expressed in Chinese precisely, although a few instructions had to be altered slightly to make them more idiomatic. The forward and back translations of the SLEQOL were accomplished without major difficulties. A total of 638 patients were interviewed (62.8% with the SLEQOL and 37.2% with the SLEQOL-C). Using DIF analysis, there was no detectable test bias due to language use after controlling for repeated observations, age, sex, and ethnicity. Conclusion The SLEQOL-C has semantic, idiomatic, and conceptual equivalence to the SLEQOL. The rigorous process of cross-cultural translation provides some measure of quality in the content validity.

The management of systemic lupus erythematosus (SLE) has improved in the past 50 years, but there is still a 3–5-fold increased mortality compared to the general population, with major organ failure due to active disease, infection and cardiovascular disease as the major challenges for the coming decade. Research advances at cellular, molecular and genetic levels enhance our understanding of the immunopathogenic mechanisms of SLE, leading to the development of drugs targeting specific sites of immune dysregulation – with therapies directed at cytokines, B- and T-cells, and their interactions showing promise. Advances are expected in the field of haematopoietic stem cell transplant (HSCT) as a therapeutic option for a subset of patients. Furthermore, some non-traditional immunomodulating therapies like statins, leflunomide and tacrolimus may prove useful as alternative or adjunct treatment in some patients. A better understanding of how current immunosuppressants act at the cellular and molecular level should guide the re-evaluation of the indications, doses and duration of therapy in clinical trials using these agents, many of which have not been subjected to proper double-blinded placebo-controlled studies. Research on triggers of SLE onset and flare of activity continues to yield information helpful in prevention. The evidence on the impact of psychosocial and economic factors on the outcome of SLE is overwhelming and the rheumatology community should enlist the assistance of other healthcare professionals, patient advocates and local health authorities to address these issues pertinent to good patient care and outcome.

CD38 is a type II transmembrane glycoprotein found in myriad mammalian tissues and cell types. It is known for its involvement in the metabolism of cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate, two nucleotides with calcium mobilizing activity independent of inositol trisphosphate. CD38 itself has been shown to have clinical significance in certain diseases with possible utilization in diagnostic and prognostic applications. Previous studies on several autoimmune diseases have shown the usefulness of recombinant CD38 protein expressed from Escherichia coli and Pichia pastoris in the detection of autoantibodies to CD38 via Western blot and ELISA. In this study, we produced a 6 x His-tagged GST-CD38 fusion protein using a recombinant baculovirus/insect cell expression technique that was purified as a soluble protein. The fusion protein was purified to homogeneity by affinity and gel filtration chromatography steps. It has an apparent molecular mass of 56 kDa on SDS-PAGE gel stained with Coomassie blue and was recognized on Western blots by antibodies against human CD38 as well as the polyhistidine tag. Peptide mass fingerprinting analysis confirmed the identity of human CD38 in the fusion protein.

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.

ummary Background The importance of assessing health-related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis-specific or general health instruments have not been delineated. Objective We analysed the psychometric properties of a disease-specific instrument, the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) and the general health instrument, the Medical Outcome Short-Form 36 (SF-36) as they are employed in combination in patients with persistent AR in clinical practice. Method We analysed the data collected from a prospective study of 43 newly diagnosed patients with persistent AR and 44 controls. We interviewed the patients four times, at baseline, weeks 4, 8 and 10. Results The RQLQ and SF-36 have good discriminative property, internal consistency, and test–retest reliability. The RQLQ is superior to the SF-36 as an evaluative instrument because more of its domains respond to change, the magnitude of change was greater, and the response was faster. The SF-36 is more susceptible to floor and ceiling effects. Both instruments are unsuitable for mildly symptomatic patients based on Rasch model analysis. Each questionnaire assesses a distinct and significant portion of the total HRQL of persistent AR. Conclusion The SF-36 and RQLQ are good for discriminating rhinitis patients from controls, but the former is poor for detecting changes in QOL. Both are inappropriate for mildly symptomatic patients. Each instrument measures non-overlapping halves of the measurable HRQL. For an assessment of the HRQL in persistent AR that is complete and responsive both instruments should be employed together.

Severe acute respiratory syndrome (SARS) is caused by a novel and highly infectious virus named SARS coronavirus (SARS-CoV). Among the serological tests currently available for the detection of SARS-CoV, a whole-virus-based immunofluorescence assay (IFA) was considered one of the most sensitive assays and served as a “gold standard” during the SARS epidemic in Singapore in 2003. However, the need to manipulate live SARS-CoV in the traditional IFA limits its wide application due to the requirement for a biosafety level 3 laboratory and the risk of laboratory infection. Previously, we have identified two immunodominant epitopes, named N195 and Sc, in the two major structural proteins, the N and S proteins, of SARS-CoV (Q. He, K. H. Chong, H. H. Chng, B. Leung, A. E. Ling, T. Wei, S. W. Chan, E. E. Ooi, and J. Kwang, Clin. Diagn. Lab. Immunol., 11:417-422, 2004; L. Lu, I. Manopo, B. P. Leung, H. H. Chng, A. E. Ling, L. L. Chee, E. E. Ooi, S. W. Chan, and J. Kwang, J. Clin. Microbiol. 42:1570-1576, 2004). In the present study, the N195-Sc fusion protein was highly expressed in insect (Sf9) cells infected with a recombinant baculovirus bearing the hybrid gene under the control of a polyhedrin promoter. An IFA based on Sf9 cells producing the fusion protein was standardized with 23 serum samples from patients with SARS, 20 serum samples from patients with autoimmune diseases, and 43 serum samples from healthy blood donors. The detection rates were comparable to those obtained with a commercial SARS-CoV IFA kit (EUROIMMUN, Gross Groenau, Germany) and a conventional IFA performed at the Singapore General Hospital. Our data showed that the newly developed IFA could detect SARS-CoV in 22 of the 23 SARS-CoV-positive serum samples and gave no false-positive results when the sera from patients with autoimmune diseases and healthy individuals were tested. The detection rate was identical to those of the two whole-virus-based IFAs. Thus, the novel N-S fusion antigen-based IFA could be an attractive alternative to present whole-virus-based IFAs for the diagnosis of SARS-CoV infection.

Toxic epidermal necrolysis (TEN) is a severe, immune-mediated, mucocutaneous reaction resulting in extensive keratinocyte apoptosis. High-dose human intravenous immunoglobulins (IVIG) have been proposed as an effective treatment for TEN. Retrospective data from 8 patients with TEN and 4 patients with Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap treated with high-dose IVIG were analysed. The total dose of IVIG administered was 2 g/kg body weight, with the exception of 2 patients who received a total dose of 1.5 g/kg body weight. Their mean age was 49.9+/-18.8 years (range, 19 to 70 years). The mean time from the first sign of skin lesion or mucosal or epidermal detachment to commencement of IVIG was 8.7+/-5.5 days (range, 3 to 22 days). Of the 11 patients who survived, the mean time to objective response was 3.6+/-1.9 days (range, 2 to 8 days). The length of stay (LOS) in hospital was 20.4+/-8.0 days (range, 10 to 37 days). The survival rate was 91.6%. One patient developed permanent mucocutaneous sequelae following TEN. There were no adverse reactions to IVIG. We conclude that high-dose IVIG may be a safe and effective therapy for Asian patients with TEN.

Objective To determine the clinical features of our systemic lupus erythematosus (SLE) patients presenting with pulmonary hemorrhage (PH). Methods We reviewed the records of all SLE patients who had PH between 1994 and 2001, a total of 22. Results All patients had radiographic infiltrates. The mean drop in hemoglobin was 3.2 ±1.1 g/dL, hemoptysis occurred in 50%, the Dlco was increased in 10 of 11 patients (91%), and 11 of 14 patients who underwent bronchoscopy had positive findings. All received high-dose prednisolone and most also were given pulse methylprednisolone (MEP) and cyclophosphamide. All patients required care in the intensive/monitored care unit, 14 were intubated, 11 had plasmapheresis, and 8 died as a result of PH (mortality rate, 36%). SLEDAI and SLAM were able to indicate active disease in SLE patients with PH (median SLEDAI, 19 [interquartile range, 10 to 24] and mean SLAM, 16.1 ± 5.8). There was a statistically significant increase in the SLEDAI from 1 month prior to PH to the time of PH ( P = .014), indicating that the patients were having a significant disease flare. The median SLEDAI and SLAM scores of patients who died were slightly higher than that of survivors. Conclusion PH in SLE patients occurred in those with severe, multiorgan involvement, with high SLEDAI scores. A high degree of suspicion should be maintained in lupus patients with active disease and unexplained infiltrates on chest radiographs and dropping red cell indices, even in the absence of hemoptysis. Early aggressive management with high-dose steroids and intravenous pulses of cyclophosphamide is advocated and may explain recent trends of improved survival. Plasmapheresis may be useful for the acutely ill patient who does not respond to the above measures but does not clearly lead to improved survival.

To identify a major antigenic determinant for use in the development of a rapid serological diagnostic test for severe acute respiratory syndrome (SARS) coronavirus infection and to study the immune response during SARS coronavirus infection in humans, we cloned the full length and six truncated fragments of the nucleocapsid gene, expressed them, and purified them as glutathione S -transferase-tagged recombinant proteins. The reactivities of the recombinant proteins to a panel of antibodies containing 33 SARS coronavirus-positive sera and 66 negative sera and to antibodies against other animal coronaviruses were screened. A truncated 195-amino-acid fragment from the C terminus of the nucleocapsid protein (N195) was identified that had a strong ability to detect antibodies against SARS coronavirus. No cross-reaction was found between the N195 protein and antibodies against chicken, pig, and canine coronaviruses. The N195 protein was used to develop a Western blot assay to detect antibodies against SARS coronavirus in 274 clinically blinded samples. The specificity and sensitivity of this test were 98.3 and 90.9%, respectively. The correlation between our Western blotting assay and an immunofluorescence assay (IFA) was also analyzed. The results of our Western blot assay and IFA for the detection of SARS coronavirus-positive sera were the same. Thus, the N195 protein was identified as a suitable protein to be used as an antigen in Western blot and other possible assays for the detection of SARS coronavirus infection.

Introduction: Septic arthritis (SA) damages synovial joints and causes considerable morbidity and mortality. We wanted to explore the patterns of presentation, risk factors, causative organisms and outcome of SA in Singapore. In particular, we were interested to see if increasing numbers of drug-resistant organisms were changing the presentation and outcome of SA. Materials and methods: Patients with SA were identified using the computerized discharge diagnosis records. We retrospectively reviewed the case records of 107 patients with SA admitted from January 1995 to June 2000 to the Tan Tock Seng Hospital, Singapore. Results: Amongst the patients studied, 42% were above 60 years of age, 51.4% experienced fever and 47% demonstrated an elevated eythrocyte sedimentation rate. The knee joint was the commonest joint involved (64.5%). Pre-existent joint disease was present in 27.1% and prosthetic joints in 11.2%. Skin infection preceded SA in 19.6% of individuals and large numbers had coexistent medical diseases (43%) with diabetes (29%) and chronic cardiovascular disease. Staphylococcus aureus was the leading causative organism (51.7% of synovial fluid cultures) and 22.6% of these were methicillin-resistant Staphylococcus aureus (MRSA). Seven patients died (6.5%) and 62.3% had incomplete recovery. Using logistic regression, Staphylococcus aureus bacteraemia, isolation of Staphylococcus aureus from the synovial fluid and previous history of SA were shown to be independent risk factors for poorer outcome. Conclusion: Septic arthritis remains an important cause of morbidity and mortality. We have identified clinical factors that may predict poorer outcomes in patients with SA.

Background Drug allergies are unpredictable immunologic adverse effects, usually immunoglobulin E-mediated immediate hypersensitivity or T-cell-mediated delayed hypersensitivity. There is a paucity of accurate prospective data on drug allergy in hospitalized patients. Objective To describe the incidence, manifestations, and outcome of drug allergy in hospitalized patients. Methods All newly developed cases, confirmed or suspected, of drug allergy in inpatients using a network-based electronic notification system. Each notification was evaluated by an allergist-immunologist during the same admission. Results From December 1, 1997 to December 31, 1999, 366 cases were reported from a total of 90,910 admissions. After review, only 210 cases were verified to have drug allergy. Antimicrobials and anti-epileptic drugs comprised 75% of the drug allergies reported. Cutaneous eruptions were the most common clinical presentation (95.7%), with maculopapular rash being the most common morphology. Systemic manifestations occurred in 30%, of which hepatitis was the most common. Serious adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and generalized exfoliative dermatitis occurred in 11 (5.2%) patients. There was no case of anaphylaxis attributable to drug allergy. After adjusting for underreporting, the incidence of drug allergy in our hospitalized patients was 4.20 per 1,000 (95% confidence interval [CI] 2.93 to 5.46), drug allergy developing during the course of inpatient treatment 2.07 per 1,000 (95% CI 1.45 to 2.69), and mortality attributable to drug allergy 0.09 per 1,000 (95% CI 0.06 to 0.12) hospitalizations. Conclusions A network-based, allergist-immunologist-verified, surveillance system enables more accurate labeling of drug allergy. The incidence of drug allergy and mortality in hospitalized patients is low.

We sought to test our clinical impression that using a low dose methylprednisolone pulse (MEP; µ1500 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.

Background: Primary antiphospholipid syndrome (PAPS) is a thrombotic condition which characteristically includes ocular vaso-occlusive pathology. Case: We present the case of a 47-year-old woman with PAPS presenting with retinal vascular leakage. Observations: Vascular leakage was an incidental finding on fundoscopy in a myopic Chinese woman, and initially this was diagnosed as diabetic retinopathy. However, a glucose tolerance test was negative. Subsequently, signs of retinal vaso-occlusion developed. Previous subclinical cerebral thrombosis, mild thrombocytopaenia and positive tests for antiphospholipid antibodies were consistent with the diagnosis of PAPS. Anticoagulation therapy with warfarin prevented further thrombotic episodes. Conclusion: The possibility of PAPS should be considered in patients presenting with retinal vascular disease without obvious vascular risk factors.

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.

*Allergy/Immunology, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio yDepartment of Dermatology, Medical University of Graz, Graz, Austria zDepartment of Internal Medicine, Division of Immunology/Allergy, University of Cincinnati, Cincinnati, Ohio xDepartment of Rheumatology, Allergy, and Immunology Tan Tock Seng Hospital, Singapore jj Faculty of Medicine ABC, Sao Paulo, Brazil {Department of Dermatology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan Department of Dermatology and Allergy, Allergie-Centrum-Charite, Charite e Universitatsmedizin Berlin, Germany **Department of Medicine, Division of Allergy/Immunology, National Jewish Health, Denver, Colorado yyDepartment of Medicine, Division of Rheumatology, Allergy, and Immunology, University of San Diego, San Diego, California

We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990–1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.

We describe a 35-year-old Chinese woman with Behcet disease complicated by recurrent gastrointestinal flares. During admission for acute lower abdominal pain, a computed tomographic scan of the abdomen showed thrombosis of the left ovarian vein. She was treated with increased immunosuppressant and oral anticoagulant. Although she was not compliant to oral anticoagulant with her international normalized ratio frequently subtherapeutic, her symptoms abated and the thrombosis resolved. There has been only 1 reported case of a patient with Behcet disease presenting with postpartum ovarian vein thrombosis and pulmonary embolism and no reported case of Behcet disease with ovarian vein thrombosis occurring outside pregnancy and the puerperium. Ovarian vein thrombosis is a rare cause of abdominal pain that should be considered in patients with Behcet disease.

Background Dapsone 100 mg/pyrimethamine 12.5 mg (Maloprim; Beacons Chemicals Pte Ltd, Singapore) is routinely prescribed for antimalarial chemoprophylaxis in military servicemen in Singapore who are not glucose-6-phosphate dehydrogenase-deficient. Methods We report a series of three male National Servicemen with hypersensitivity syndrome from Maloprim. Results The three patients were diagnosed with hypersensitivity syndrome based on the presence of features of a drug hypersensitivity syndrome including fever, lymphadenopathy, maculopapular exanthema, hepatitis, and definite exposure to weekly Maloprim alone. A mild Coombs positive hemolytic anemia was also observed in one patient. All the clinical, hematologic, and biochemical derangements normalized within 3 months of tapering regimens of moderate-dose prednisolone. Conclusions Drug hypersensitivity syndromes can occur even on low-dose, weekly drug regimens. Hypersensitivity syndrome from weekly Maloprim is potentially reversible when recognized and treated early.

We report the case of a diabetic Chinese male with no previous history of recurrent infections. His course was at first notable for relapsing Salmonella blockley infections, following which he developed repeated soft-tissue infections and Cryptococcus neoformans pneumonia. He was diagnosed as having chronic granulomatous disease and was treated with gamma interferon. During the latter stages of his illness he developed Mycobacterium flavescens infection in soft tissues, joints, bones and lung. This is the first report of disseminated M. flavescens infection.

Serious infection is a common problem in immunosuppressed patients with systemic lupus erythematosus (SLE). Melioidosis is caused by the Gram-negative bacterium Burkholderia pseudomallei and may present as an acute fulminant pneumonia or septicaemia that is often fatal. The organism is endemic in much of South-east Asia but is being increasingly reported from other parts of the world, including India, Northern Australia and North and South America. In addition to occurring in people who come into contact with contaminated soil or water in endemic areas, the infection is more common in immunosuppressed patients and must be recognised early and treated with appropriate antibiotics. Importantly, it can activate many years after the initial exposure, causing diagnostic confusion. We present the cases of three patients with SLE who were admitted with fever and in whom Burkholderia pseudomallei was isolated from blood cultures. Following treatment with intravenous ceftazidime all patients made a good recovery. These cases demonstrate the importance of considering this infectious organism in patients from endemic areas with unexplained fever. They also illustrate how successful outcomes can be achieved in a frequently fatal disease if an early diagnosis is made and appropriate antibiotics are started promptly.

Blomia tropicalis is an important domestic dust mite in the tropics and subtropics. This study describes cDNA cloning of the group 4 allergen of B. tropicalis, and the evaluation of the sensitization of this allergen in atopic populations from 2 geographic regions.cDNA cloning was carried out using the Smart RACE cDNA amplification kit. The full-length Blo t 4 cDNA was isolated by cDNA library screening, 5' and 3' rapid amplification of cDNA ends and long-distance PCR. Sequence analysis was performed with a combination of the Clustal W, CGC and Blast program packages. The cDNA was expressed in Pichia pastoris yeast. The skin prick test was used to evaluate the sensitization profile of recombinant Blo t 4, crude dust mite allergen extracts and major B. tropicalis recombinant allergen Blo t 5.The cloned Blo t 4 had a molecular weight of 56 kDa and had 68% amino acid homology with group 4 allergens of Dermatophagoides pteronyssinus and 65% with those of Euroglyphus maynei. A sensitization profile to the expressed recombinant Blo t 4 allergen (28%) showed an unusually higher frequency than to the major allergen Blo t 5 (22%) in allergic subjects from Chengdu, PR China. In comparison, the subjects from Singapore showed very low sensitization to Blo t 4 (4%) compared with Blo t 5 (84%).Group 4 allergens of B. tropicalis may be an important dust mite allergen in certain distinct populations.

Introduction: The aim of this study was to ascertain the outcomes of chronic hepatitis B (CHB) infection following immunosuppressive therapy in 38 consecutive oriental patients with systemic rheumatic diseases. Materials and Methods: This is a retrospective consecutive, non-comparative study. Results: The majority of patients were female (26, 68.4%), predominantly Chinese (92.1%), with a mean age 54 ± 14 years (range, 16 to 87). The mean duration of rheumatic disease was 9 ± 11 years (range, 0.1 to 48), with rheumatoid arthritis (52.6%) and systemic lupus erythematosus (23.7%) being the most common. The mean duration of CHB infection was 6 ± 5 years (range, 0.1 to 17), with the majority diagnosed during pre-methotrexate screening (50.0%) and asymptomatic transaminitis following initiation of immunosuppressive therapy (23.7%). Upon diagnosis of rheumatic disease, all patients had normal alanine aminotransferase (ALT). Of these, 18.2% were positive for hepatitis B e antigen (HBeAg) and 78.1% were positive for anti-HBe antibody. Twenty (52.6%) developed ALT elevation, which was more than twice the upper limit of normal in 12 patients. ALT normalised spontaneously in 12 patients without hepatic decompensation or change in therapy. Seven (18.4%) patients received lamivudine for 18 ± 22 months (range, 2 to 61). Two patients developed YMDD mutation subsequently treated with adefovir (1) and adefovir/lamivudine (1). There were 3 (7.9%) hepatitis B virus (HBV)-unrelated deaths [infection (2), genitourinary malignancy (1)], and 1 from HBV-reactivation complicated by septicaemia. None have developed hepatocellular carcinoma. Conclusion: Elevated ALT occurred in 52.6% of patients, with only 18.4% requiring anti-viral therapy for HBV reactivation. HBV-related mortality was low. With the appropriate precautionary measures, prednisolone and immunosuppressants (except methotrexate and leflunomide) may be used safely in patients where clinically indicated. Key words: Ankylosing spondylitis, Lamivudine, Rheumatoid arthritis, Spondyloarthropathies

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.

Patients with systemic lupus erythematosus (SLE) frequently have gastrointestinal (GI) symptoms. These are usually self-limiting and related to treatment side-effects or concurrent illness. However, abdominal pain may be due to bowel ischaemia which can lead to infarction and perforation. The likelihood of these serious events is increased in individuals with pain severe enough to require assessment in hospital or a SLEDAI score > 5. This paper describes a group of patients with active SLE and GI symptoms severe enough to require admission to hospital using a retrospectivereview of 52 SLE patients admitted to hospital with acute abdominal symptoms. The results showed that abdominal pain (87%), vomiting (82%) and diarrhoea (67%) had been present for a mean of 4.4 + 6.5 days and SLEDAI score was ≥4 in 83% of patients. CT scanning showed evidence of serositis and bowel involvementin 63% of patients who underwent this investigation.Intravenous(iv) fluids were used in 87%, parenteral steroids in 90% and iv cyclophosphamidein 31%. Most (n 51) were discharged well. Recurrence of GI symptoms occurred in 12 patients. The conclusions are that active SLE may manifest as an acute gastrointestinal syndrome. Early diagnosis, bowel rest, supportive medical therapy and treatment with corticosteroids and/or immunosupressives can result in a good outcome.

Background Gastrointestinal symptoms occur commonly in SLE, but vasculitis of the bowel or SLE related gut disease (lupus gut) have previously been described to be of low incidence. These reports have usually been based on cases admitted with acute abdomen, associated with high mortality. Our experience in Singapore suggests that a milder form of this entity may manifest as acute gastrointestinal symptoms. Objectives To study the clinical characteristics, management and outcome of SLE patients admitted with acute gastrointestinal symptoms and treated as lupus gut after exclusion of infection or other aetiology. Methods The case notes of 20 SLE patients admitted for acute gastrointestinal symptoms and treated as lupus gut were reviewed. All patients satisfied the ACR criteria. We defined lupus gut as patients presenting with abdominal pain, vomiting and/or diarrhoea with raised double stranded DNA or hypocomplementemia and whose gastrointestinal symptoms responded to parenteral corticosteroids, increased oral corticosteroids or immunosuppressants. SLEDAI scores were also performed for disease activity. Results All our patients were females and most were Chinese (95%). The mean age at presentation was 35.7 (13–56 years) and mean duration of SLE to their admission for lupus gut was 6.7 years (1–15 years). Most patients presented with abdominal pain (90%), diarrhoea (75%) and vomiting (70%). Abdominal tenderness was a frequent finding (70%) and 25% were febrile. Double stranded DNA was raised in all 17 patients who had this investigation performed and 75% had hypocomplementemia. Blood and stool cultures were carried out in 55% and 60% of patients respectively and all were negative. The mean SLEDAI score was 5.3 (0–12). Intravenous drip was commenced in 75% of patients with resting of gut and 80% received intravenous hydrocortisone. Intravenous methylprednisolone was administered to 5 patients (25%), 4 of whom had not responded to initial intravenous hydrocortisone. The majority (75%) had a good outcome with resolution of their abdominal symptoms, discharged well from hospital including 1 patient who underwent a laparotomy and was found to have patchy ischmic small bowel. Lupus gut recurred in 4 (20%) patients on subsequent follow up (mean follow up 31.4 months) and all 4 again responded to similar therapy. Three patients died within 4 months of their admission, 2 of whom had developed active nephrits 1 month prior to their death. Conclusion Our study suggests that SLE related gut disease may occur in milder forms more commonly than previously described. Symptoms are associated with markers of active disease and respond to conventional treatment for SLE and resting of gut. References Sultan SM, Ioannou Y, Isenberg DA. A review of gastrointestinal manifestations of systemic lupus erythematosus. Rheumatology 1999;38:917–32 Zizic TM, Classen JN, Stevens MB. Acute abdominal complications of systemic lupus erythematosus and polyarteritis nodosa. Am J Med. 1982;73:525–31 Medina F, Ayala A, Jara LJ, et al. Acute abdomen in systemic lupus erythematosus: the importance of early laparotomy. Am J Med. 1997;103:100–5

Background There is little data on work disability in Asian patients with SLE. Loss of work ability contributes to loss in productivity, increase in health care cost and also loss of self esteem which in turn can lead to anxiety and depression. Objectives To determine the employment status, prevalence of work disability in a cohort of Asian SLE patients and to identify its predictors. Methods We established our SLE registry in 2001. This follows about 1000 patients who are followed up according to a standard protocol by trained staff rheumatologists or trainees at regular 4-12 months. A cross-sectional questionnaire study was performed to evaluate the employment status of consecutive patients with SLE. The following parameters were collected: demographic, socioeconomic data, employment status including their history of having modified their job or having changed their job(s) and disease characteristics. Work disability was defined as failure to work due to SLE activity and its related complications. Results 323 patients were surveyed (mean age 45.5±12.1years, 92.4% women, 90% of Chinese descent, mean SLE duration 15.8±11.1years). Majority were married (65.8%) and 82.8% earned below the median Singapore income of $5000 per month (2010 census) More than half the patients (55.3%) did not have health insurance. There were 62 patients who were not in the workforce at time of questionnaire (30 housewives, 31 student, 1 retiree) and hence were excluded. Of the 261 who were in the workforce, 78((29.9%) lost their working ability. 52 of these patients (67.1%) reported they stopped work earlier than they had wanted to. The self reported causes of inability to work were fatigue (43.9%) and joint pains or aches (36.8%). A significant number of patients who were work disabled also modified their work or had to change jobs. Of the 78 patients who were unable to work, 47/78 (60%) modified their jobs by doing lighter duties (36.4%), or doing fewer hours or going part time (41.9%). Thirty one patients (39.7%) also changed jobs prior to stopping work with 60.5% of patients having changed 2 jobs. Conclusions Work disability is an important problem among SLE patients. The unemployment rate is high compared to the national unemployment rate of 2.2%. Majority of the the patients who were work disabled experienced a period of work instability before they stopped work. Disclosure of Interest None Declared

Background Various generic quality-of-life QoL (QoL) scales such as MOS 36-Item Short-Form Health Survey (SF-36) and disease-specific ones such as systemic lupus erythematosus QoL (SLEQOL) have been used to study the QoL of lupus patients. Most of the studies are cross-sectional and, consequently, information about the responsiveness of such instruments is scant. Objectives We studied the responsiveness of SLEQOL and SF-36 in lupus patient as they receive new drug treatment. Methods We selected patients from our prospective SLE registry who were prescribed new medications. We studied the differences in the QoL at study visits just before and just after the introduction of azathioprine, oral cyclophosphamide, intravenous cyclophosphamide, danazol, cyclosporine A, mycophenolate or hydroxychloroquine in an intention-to-treat manner. We collected clinical data and scores from SF-36, SLEQOL, Rheumatology Attitudes Index (RAI), SLE Disease Activity Index (SLEDAI) and revised Systemic Lupus Activity Measure (SLAM-R). Results There were 216 SLE patients (with 194 females) with 303 new drug initiations. The mean age was 36.23 ± 11.78 years. The mean age of diagnosis was 27.65 ± 10.34 years. Using SLEQOL, we found that the use of IV cyclophosphamide, mycophenolate and azathioprine is associated with significant improvements in QoL, in contrast to oral cyclophosphamide, cyclosporin A, danazol and hydroxychloroquine. IV cyclophosphamide is associated with improvement in the physical functioning, activities and self-image domains of SLEQOL, mycophenolate in the treatment and self-image domains and azathioprine in the activities and mood domains. SF-36 reflected QoL change with the use of IV cyclophosphamide (general health domain) and mycophenolate (physical functioning and role physical). Conclusions SLEQOL is responsive to the changes in QoL of SLE patients as they receive new medications. It distinguishes the differential effects on QoL of the various drugs. Different domains of the SLEQOL and SF-36 improved with the various medications. SLEQOL may be useful as an outcome measure in SLE clinical trials. Disclosure of Interest None Declared

Background Severe acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls.

A 31-year-old man with dysgammaglobulinemia Type I (deficient IgG, IgA, and elevated IgM) and persistent cryptosporidiosis was treated over a 13-week period with oral bovine transfer factor from calves immunized with cryptosporidia. Spiramycin was added toward the end of the treatment period. This patient failed to show clinical response although there was a decrease in the stool oocyst count from the value just prior to therapy. Bovine transfer factor alone and in combination with spiramycin failed to eradicate the infection in this man with well-documented stable cryptospridiosis.