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.

Anaplastic thyroid carcinoma with destructive thyrotoxicosis in a patient with preexisting multinodular goiter.

Presentation of anaplastic thyroid carcinoma with thyrotoxicosis is extremely rare and its occurrence in a patient with Wegener's granulomatosis has not been reported previously. We describe an elderly lady with Wegener's granulomatosis who developed a rapidly growing anaplastic thyroid carcinoma in a preexisting multinodular goiter and discuss the mechanism of thyrotoxicosis in this patient.

Cerebral infarct mimicking glioma in Sjogren's syndrome.

A 50-year-old Chinese woman with a chronic 20-year history of ataxic gait associated with dry eyes and mouth, was admitted to hospital after a single episode of syncope. Magnetic resonance imaging scans showed a large left frontal hypodense lesion suggestive of a glioma. Craniotomy was performed and the lesion excised, with histology showing only infarcted tissue and no malignant cells. Further diagnostic evaluation revealed that the patient had primary Sjogren's syndrome, with demyelinating polyneuropathy. In the absence of risk factors for stroke, it was considered likely that the cerebral infarct was secondary to autoimmune-related vasculitis. Functional neuroimaging, such as magnetic resonance spectroscopy, should be considered in evaluating doubtful or unusual brain lesions in patients with autoimmune disease.

Ankylosing spondylitis in Singaporean Chinese--a clinical profile.

The clinical characteristics of 38 local Chinese ankylosing spondylitis patients were studied by interview, clinical examination and review of casenotes. The sex ratio was 3.2:1 in favour of males. The average duration from onset of symptoms till diagnosis of disease was 7.25 years. Peripheral joint involvement occurred in 71% of the patients. Extra-articular complications were uncommon; only three patients had a history of uveitis and one patient had biopsy proven IgA nephropathy. 26.3% of patients had significant disability due to the disease. Early diagnosis of the disease should be made as it may improve the prognosis of the patients.

Methylprednisolone in systemic lupus erythematosus.

39 patients who received pulse methylprednisolone for disease manifestations of systemic lupus erythematosus were studied for zero to twenty-four weeks following therapy. Pulse methylprednisolone was given as intravenous infusions of methylprednisolone (10 mg/kg body weight) over one hour each day for three consecutive days. 27 (69.2%) patients were treated for lupus nephritis, 12 (30.8%) patients for non-renal manifestations of lupus. 17 (63.0%) of the renal lupus patients and 7 (58.3%) of the non-renal lupus patients showed clinical response. 11 (28.2%) patients had infections from which 7 (63.6%) died. Overall, 15 (38.5%) patients died. Early deaths (occurring within the first two weeks) were mainly due to disease activity while later deaths were mainly due to infection. In conclusion, the majority of lupus patients appeared to have had a beneficial response to pulse methylprednisolone therapy.

Clinical efficacy of sulbactam/ampicillin in the treatment of moderately severe bacterial infections.

20 patients with moderately severe bacterial infections were studied to determine the clinical efficacy and safety of parenteral sulbactam/ampicillin. There were 9 female and 11 male patients. Their mean age was 51 years. 8 patients had pneumonia, 5 urinary tract infection, 4 cellulitis of the leg and 3 had pustular tonsillitis. 85% of patients had resolution of fever and symptoms within 48 hours of commencing treatment. 95% had successful treatment outcome. The organisms isolated included E. Coli, Klebsiella sp, Branhamella catarrhalis and Bacillus species. In 2 patients, the organisms isolated demonstrated in-vitro ampicillin resistance. However, they recovered fully with sulbactam/ampicillin therapy. No adverse side-effects were reported and dosage adjustment was not required in the elderly.

Ophthalmic manifestations in Asian patients with systemic lupus erythematosus.

AIM OF STUDY: To determine the spectrum and prevalence of ophthalmic manifestations of systemic lupus erythematosus (SLE) in Asian patients. METHODS: We performed a standardised ophthalmic examination on consecutive Asian patients with SLE referred from a tertiary rheumatology unit to an ophthalmology department. RESULTS: Seventy patients were included in the study. There were 66 females (94%) and 4 males (6%). The mean (range) age of the patients was 32.9 (9-67) years. Five patients (7%) had ophthalmic symptoms while 65 (93%) were asymptomatic. Eighty-three eyes of 45 patients had abnormal Schirmer's #1 test and 27 of these eyes of 17 patients also had concomitant rose bengal staining of the cornea and/or conjunctiva. Seventeen eyes of 9 patients had retinal vascular lesions. Fourteen of these eyes had mild microangiopathic retinopathy with best-corrected visual acuity (BCVA) 6/12 or better and 3 had retinal vaso-occlusive disease with BCVA worse than 6/12. Twenty-eight eyes of 14 patients had cataract and 3 eyes of 2 patients had raised intraocular pressure. Twelve eyes of 7 patients had BCVA worse than 6/12 because of optic neuropathy (4 eyes), posterior subscapsular cataract (4 eyes), retinal vaso-occlusive disease (3 eyes) and phthisis bulbi (1 eye). None had any eyelid lesion, extraocular motility disorder or retrochiasmal disorder of vision. CONCLUSIONS: Asymptomatic dry eye is the most common ocular finding in patients with SLE. Sight-threatening complications of SLE include retinal vaso-occlusive disease and optic neuropathy.

Rheumatoid arthritis--a review.

Rheumatoid arthritis, a common chronic inflammatory arthritis, tends to run a more benign course in patients from the community than those seen at hospitals. The aetiology is unknown but the disease is postulated to result from the interaction between genetic and environmental factors. The strongest genetic association is with the major histocompatibility complex (MHC) Class II antigen HLA DR 4, although not more than 50% of the genetic susceptibility is due to MHC genes. In early disease the pathogenesis is thought to be T cell mediated whereas in late disease the mechanisms are T cell independent, with destruction contributed to by autonomous fibroblast like synoviocytes. The diagnosis is made on clinical groups. Management is directed at controlling active synovitis so that joint damage is limited. The early use of a slow acting anti-rheumatic drug is now advocated, as studies have shown that they can potentially prevent or limit the progression of disease. Biological therapies are still experimental but may hold promise for the future.

Malignant histiocytosis--a clinicopathologic study of 5 cases.

The clinico-pathological features of 5 patients with malignant histiocytosis aged 18 years to 73 years seen over a three year period from 1980 to 1983 at the Department of Haematology Singapore General Hospital were studied. Haematological, cytological and histopathological findings of the disease are described. Diagnosis of malignant histiocytosis was established from biopsies of bone marrow, liver, spleen or lymph nodes. Three out of the 5 patients died rapidly after diagnosis despite cytotoxic chemotherapy. One patient was lost to follow up while another is alive surviving so far for 3 months since diagnosis. The differential diagnosis of malignant histiocytosis is also discussed.

Polymorphism of the regulatory region of tumour necrosis factor alpha gene in patients with systemic lupus erythematosus.

A single-base change in the regulatory region of the tumour necrosis factor alpha (TNF-alpha) gene and the TNF2 allele said to be associated with Caucasian lupus patients has been reported. We studied this genetic polymorphism in 89 normal individuals and 67 Chinese lupus patients, 45% of whom has renal involvement. The allelic frequencies of TNF1 and TNF2 alleles in our male controls (n = 49) were 0.86 and 0.14 respectively, in the female controls (n = 40) they were 0.91 and 0.09 respectively, and as a combined group they were 0.88 and 0.12 respectively. The corresponding frequencies in our lupus patients were 0.81 and 0.19 respectively. Comparing the allelic frequencies of the combined control and patient group as well as only between the female control and female lupus patients, we did not find any association between the TNF2 allele and systemic lupus erythematosus in our cohort of Chinese patients. The TNF2 gene may be in linkage disequilibrium with the DR3 allele.

Vibrio vulnificus infections: case reports and literature review.

Vibrio vulnificus is an emerging opportunistic pathogen that is responsible for one of the most fulminant food-borne diseases in immunocompromised hosts. The infection should be suspected in patients with underlying liver disorders who present with a prominent skin rash, hypotension and septic parameters especially if they give a history of seafood or shellfish ingestion. Awareness and early recognition of this infection will result in a better outcome for the patient.

Clinical predictors of nephritis in systemic lupus erythematosus.

We identified clinical predictors of lupus nephritis presenting more than 6 months after the diagnosis of lupus in a cohort of 335 lupus patients. Almost 24% (80/335) of patients developed nephritis more than 6 months after the diagnosis of lupus. Using a Cox proportional hazards model, we found hypertension, thrombocytopaenia and leukopaenia to be associated with lupus nephritis presenting more than 6 months after diagnosis, with adjusted relative risks of 2.5 (95% CI 1.3 to 4.7), 4.3 (95% CI 1.7 to 10.8) and 3.2 (95% CI 1.7 to 6.2) respectively. In this cohort, hypertension, thrombocytopaenia and leukopaenia were associated with lupus nephritis presenting more than 6 months after the diagnosis of lupus.

Systemic lupus erythematosus: initial manifestations and clinical features after 10 years of disease.

We studied the initial manifestations and late features in our lupus patients. The clinical data of patients fulfilling the American College of Rheumatology criteria for systemic lupus erythematosus (SLE) were entered prospectively for newly diagnosed patients and cumulatively for those with at least 10 years of disease duration. Ninety-seven Group A (newly diagnosed; 86 females and 11 males; mean age 31 years; 83 Chinese, 11 Malays, and 3 Indians) and 58 Group B (more than 10 years disease duration; 56 females and 2 males; mean age 41 years; 50 Chinese, 5 Malays, and 3 Indians) lupus patients were studied. The commonest clinical features in Group A were: haematological (73%), arthritis (57%), malar rash (43%), renal disorder (31%) and photosensitivity (30%). Group B patients had haematological (78%), malar rash (73%), arthritis (69%), renal disorder (59%) and photosensitivity (33%). Renal disorder was significantly increased over the years (P < 0.001). Hypertension was present in 18% (Group A) and 59% (Group B) (P < 0.00001), diabetes mellitus in 5% (Group A) and 10% (Group B) (P = ns), atherosclerosis in 2% (Group A) and 7% (Group B) (P = ns). Cataract formation was not present in Group A patients but was present in 10% of Group B patients. Renal disorders and morbidity factors like hypertension and cataracts increased significantly over the years. Optimum treatment of lupus patients should therefore include close attention to these factors.

Antinuclear antibodies in systemic lupus erythematosus.

Autoantibodies to the three extractable nuclear antigens (ENA), Anti-SSA (Ro), Anti-Sm, Anti-RNP and antinuclear antibodies were determined in 150 patients with SLE. Seventy patients (46.7%) had Anti-SSA (Ro), 40 (26.7%) Anti-Sm and 25 (16.7%) Anti-RNP antibodies. Ninety four percent patients had a positive Fluorescent anti-nuclear antibody (FANA) test. The commonest FANA pattern is the speckled pattern. Subclinical keratoconjunctivitis sicca (KCS) was present in 60% patients. No correlation could be demonstrated between the presence of ENA autoantibodies and the clinical features of patients.