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.

Major gastrointestinal manifestations in lupus patients in Asia: lupus enteritis, intestinal pseudo-obstruction, and protein-losing gastroenteropathy.

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.

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.

Insect venom hypersensitivity: experience in a clinical immunology/allergy service in Singapore.

INTRODUCTION: To study the profile of patients with allergy to the venom of insect stings. METHODS: 31 consecutive cases referred to our clinical immunology/allergy outpatient service from June 1, 1998 to June 30, 2002 were reviewed. RESULTS: These patients comprised 3.5 percent of 889 cases referred during the study period. Their mean age was 28.8 +/- 10.5 (range 19-57) years and the majority were males (90.3 percent). Of these, 20 (64.5 percent) were Chinese, four (12.9 percent) were Malays and seven (22.6 percent) were of other races. 19 patients (61.3 percent) were men from the uniformed services including 12 (63.2 percent) full-time National Servicemen. 71 percent (22 patients) were stung for the first time. Urticaria (22 cases, 71.0 percent), dyspnoea (13, 41.9 percent), angioedema (12, 38.7 percent) and syncope (ten, 32.3 percent) were the most common manifestations of insect allergy. Anaphylaxis occurred in 22 (71.0 percent) cases, constituting 30.1 percent of all cases of anaphylaxis referred to our service during the study period. Although the causative insect was identified as honeybee (12, 38.7 percent), ant (four, 12.9 percent), wasp (three, 9.7 percent), and fire ant (two, 6.5 percent) by the majority of patients, ten (32.2 percent) patients were unable to identify the causative insect. The two patients stung by fire ants were Americans working in Singapore who had been stung while in the United States. Among those with anaphylaxis, honeybee, wasp and fire ant venom, for which specific immunotherapy is available, were identified as the cause in 40.9 percent, 4.5 percent, and 4.5 percent, respectively. CONCLUSION: Insect venom hypersensitivity made up 3.5 percent of allergy/immunology referrals and 32.8 percent of cases of anaphylaxis referred to our institution. The majority were military servicemen who developed allergic reactions during the course of duty. The inability to identify the causative insect in 50 percent with sting anaphylaxis limits the role of specific immunotherapy in our patients.

Anaphylaxis in adults referred to a clinical immunology/allergy centre in Singapore.

INTRODUCTION: To study the clinical features and causes of anaphylaxis in consecutive adult patients referred to a clinical immunology/allergy centre in Singapore. METHODS: A retrospective review of 67 consecutive adults with anaphylaxis who presented from July 1, 1998 to February 28, 2002 was performed. Anaphylaxis was defined as a severe life-threatening systemic IgE-mediated hypersensitivity reaction. Non-steroidal anti-inflammatory drug-induced idiosyncratic reactions and other non-IgE mediated reactions were excluded. Hypotension and bronchospasm were not required to make a diagnosis. The aetiology was determined from clinical history followed by measurement of allergen-specific IgE levels, skin prick test with commercially-available allergen extracts or prick-prick test with the fresh/cooked/canned food products. RESULTS: The mean age of patients was 32.9 +/- 10.9 (range 19-57) years. There were 44 (65.7 percent) males and 23 (34.3 percent) females. The main causes were food (44.8 percent), insect stings (32.8 percent) and idiopathic (22.4 percent). There were no cases due to drugs or natural rubber latex. Seafood (crustaceans and molluscs) comprised 66.7 percent of food-induced anaphylaxis. Honeybee and wasp stings together comprised 45 percent of insect venom anaphylaxis. The most common manifestations were dyspnoea (59.7 percent), urticaria (58.2 percent), angioedema (44.8 percent), and syncope (43.3 percent). Hypotension was documented in only 28.4 percent of cases. CONCLUSION: Food (crustaceans and molluscs) was the most common cause followed by insect stings or bites. The inability to identify the causative insect in 50 percent of cases with insect venom anaphylaxis limited the role of specific immunotherapy. Compared to other reported series, there were no cases of drug or latex anaphylaxis.

Disseminated Mycobacterium flavescens in a probable case of chronic granulomatous disease.

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.

Laboratory tests in rheumatic diseases: a guide for clinicians.

In the practice of rheumatology, just as in other disciplines of medicine, laboratory tests are meant to supplement a thorough history and physical examination. The clinician should have a purpose for ordering each test; to screen for a disorder, confirm a diagnosis, exclude a possible diagnosis, monitor therapy or determine prognosis. Many of the rheumatic diseases have in common processes and features that are inflammatory and many of the tests merely establish the presence of an inflammatory process. The measurement of ESR and C-reactive protein are two such tests most widely used. The systemic rheumatic diseases also manifest serologically with the continual production of non-organ specific autoantibodies. Few of these antibodies are specific for a particular disease. The majority of the autoantibodies are positive in various disease states and are only useful as adjuncts to the diagnosis of rheumatic diseases. This discussion deals with commonly ordered tests in rheumatic diseases; how to use the tests appropriately while keeping in mind their limitations.

Hereditary angioedema: diagnosis and management.

Hereditary angioedema is a rare autosomal dominant disorder due to the deficiency of functionally active C1-inhibitor. It is characterised by recurrent episodes of subcutaneous and mucosal edema. We report a case of hereditary angioedema presenting with the classic features of recurrent swelling of the extremities, abdominal pain and laryngeal edema. Serum complement C3 level was normal but C4 was low. She responded well to danazol and had no further attacks of angioedema.

Mortality patterns in a medical intensive care unit.

We studied the mortality rate and patterns in a 6-bedded Medical Intensive Care Unit in a busy general hospital. We found a high mortality rate (26% in-ICU and 42% in-hospitalization) and that mortality was strongly associated with the following factors: cardiac arrest, respirator support, duration of stay in ICU, infection and the immunocompromised state. Lack of formal patient selection and entry criteria and Critical-Care Specialists may be contributing factors.

Left ventricular myxoma, adrenal tumour and cutaneous vasculitis--a case report.

Cardiac myxoma has myriad presentations including cutaneous vasculitis. It has also been associated with endocrine neoplasm in Carney's Complex. We report a Chinese patient with cutaneous vasculitis and Raynaud's phenomenon suggesting a collagen vascular disease. In the course of investigation, echocardiogram showed a possible left ventricular myxoma and computed tomography of the abdomen demonstrated a left adrenal tumour. Cardiac myxoma should be considered in the differential diagnosis of vasculitis.

Relapsing polychondritis--an Oriental case series.

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.

Infections in systemic lupus erythematosus.

A prospective study was carried out on the occurrence of infections in 28 hospitalised systemic lupus erythematosus (SLE) patients. In 38 episodes of infections, 23 were bacterial (60.5%), 4 were viral (10.6%) and culture negative infections were present in 10 (26.3%). The most common isolated organisms were Staphylococcus aureus (30.4%), Salmonella species (21.7%), Pseudomonas species (13.0%), and Klebsiella species (13.0%). The care rate was 94.7%. Death occurred in 2 patients. Lupus activity, impaired renal function, and cytotoxic therapy did not predispose to infection.

Primary immunodeficiency diseases in Singapore--the last 11 years.

OBJECTIVES: To describe the clinical features, disease complications, treatment modalities and overall outcome of 39 local patients with Primary Immunodeficiency Diseases (PID) in Singapore over the last 11 years. METHODS: Paediatric and adult patients who presented to the The Children's Medical Institute, National University Hospital, Tan Tock Seng Hospital and KK Women's and Children's Hospital between January 1990 and December 2000 were identified. Their diagnoses were categorised into six groups according to the IUIS (International Union of Immunological Societies, affiliated to World Health Organisation) classification: antibody deficiencies, combined immunodeficiencies, immunodeficiencies associated with other major defects, congenital phagocytic defects, complement deficiencies and other well-defined immunodeficiency syndromes. Patients were selected from screening of inpatients with discharge diagnoses associated with primary immunodeficiency and of patients undergoing tests for immunodeficiency. Patient data were collated from case files and compiled using a standard questionnaire. RESULTS: There were 39 Singaporean patients diagnosed and treated for PID during the study period. The age at diagnosis ranged from three weeks to 69 years. Antibody deficiency (41%) was the most common form of PID. Seven patients had a family history of PID. Recurrent bacterial respiratory tract infections were the most common clinical manifestation. Associated conditions included autoimmune diseases, allergies and malignancies. Infection was the commonest cause of mortality. Eighteen patients (46.2%) with antibody or combined deficiencies received regular intravenous immunoglobulin (IVIG) as the primary treatment modality. Two children successfully received sibling-matched haematopoietic stem cell transplantation (HSCT). CONCLUSIONS: Antibody deficiencies are the most common form of PID in Singapore. Treatment with antibiotics, IVIG and HSCT are the main therapeutic modalities currently available. Early referral to an immunologist is needed to achieve good outcomes.

Hepatitis B virus infection in patients with systemic lupus erythematosus.

Sera from 76 patients with systemic lupus erythematosus (SLE) were examined for HBsAg, anti-HBsAb and total anti-HBcAB by radioimmunoassay. Fifteen patients (19.7%) had one or more of these serological markers of HBV infection. This is comparable to the sero-prevalence in 100 sex- and age-matched healthy individuals (19%). There was no significant difference in the prevalence of HBV infection in patients who had received immunosuppressants compared with those who had not. Patients who had received transfusion of blood or blood products had a higher prevalence of serological markers but this was not statistically significant.

Coincident cold urticaria in a married couple: case report and a literature review.

We describe an interesting coincidence in which a woman developed acquired idiopathic cold urticaria and her husband systemic cold urticaria eight months later. The occurrence of cold urticaria in a tropical country like Singapore is rare. Each case illustrates the typical features of that particular type of cold urticaria, including the appropriate response to the challenge test and its self-limited nature.

Adult-onset Still's disease in an oriental population: manifestations, course and outcome in 16 patients.

This retrospective descriptive study aims to characterise and compare the clinical manifestations, course and outcome of 16 Oriental patients with adult-onset Still's disease diagnosed in the last 4 years with published data based on Western populations and another Oriental (Japanese) series. Like the Japanese, we found a female preponderance, an older age at onset, and fewer patients with abdominal pain, myalgia, sore throat and serositis compared to the Western series. A longer delay in diagnosis occurred in patients lacking either arthritis or rash at presentation. Most patients had mild hyponatraemia and 2 patients had overt syndrome of inappropriate anti-diuretic hormone secretion. All patients showed a dissociation of elevated aldolase with normal to low creatine kinase levels. Over 50% relapsed within a year from diagnosis and needed slow-acting anti-rheumatic drugs as steroid-sparing agents. Two were given intravenous pulse cyclophosphamide therapy for progressive pneumonitis. Outcome was generally good with minimal functional impairment and no mortality.

A retrospective study of 13 Oriental children with juvenile dermatomyositis.

This is a retrospective study of 13 Oriental children with juvenile dermatomyositis (JDM). We reviewed data found in the hospital records of children diagnosed to have definite (n = 4), probable (n = 7) and possible (n = 2) JDM who presented over a 10-year period at 4 centres in Singapore and compared our results with the experience of others. We found an overall female preponderance (female to male ratio of 3.3:1) but an equal sex ratio in children below 5 years of age. The majority (92%) had insidious onset and good outcome. Diagnosis was often delayed because of the insidious onset, and because weakness occurred late, was mild or absent. Only one child had an acute presentation and refractory course. She died despite aggressive therapy. Clinical features, complications and mainstay medication used were similar to Western studies.

The Bone and Joint Decade 2000-2010: for prevention and treatment of musculoskeletal disease.

The Bone and Joint Decade 2000-2010 has been established to increase awareness of the scale and impact of musculoskeletal disorders on the individual, health care systems and the society. It is a multi-disciplinary initiative involving professional bodies, patient care groups, research organisations and the community.

Intermittent epoprostenol infusions in systemic lupus erythematosus associated pulmonary hypertension--a series of three cases.

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.