Atherogenic serum lipid profile is an independent predictor for gouty flares in patients with gouty arthropathy.

OBJECTIVE: Atherogenic serum lipid profile possesses pro-inflammatory properties and is associated with more active RA. While prevalent in patients with gout, whether atherogenic lipid profile is associated with gouty flares is unknown. This study aims to investigate whether atherogenic serum lipid predicts gouty flares in patients with gout. METHODS: Adult patients (age > or =21 yrs) who suffered from gout were prospectively followed between September 2006 and November 2007 and their demographic, clinical and laboratory data were collected. Episodes of gouty flares over this observation period were recorded and factors predictive of gouty flares were studied by regression models. RESULTS: Of the 100 patients, 80 were men, 65 were ethnic Chinese, 31 were Malay and the rest were Indian and Caucasian. The mean age and duration of gout (+/-S.D.) were 61.9 +/- 14.0 and 6.6 +/- 7.8 yrs, respectively. The mean serum uric acid and creatinine levels were 537.6 +/- 142.8 and 173.6 +/- 119.9 micromol/l, respectively. In univariate analysis, longer duration of gout, higher adjusted mean serum creatinine, lower adjusted mean fasting serum, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels were associated with gouty flares. After adjustment for potential confounders in multivariate regression models, longer duration of gout and lower adjusted mean fasting serum HDL-C level remained independently predictive of gouty flares. CONCLUSIONS: Low serum high-density lipoprotein cholesterol level was an independent predictor for gouty flares. Whether optimizing serum HDL-C level can benefit patients with gout in terms of reducing gouty flares needs to be addressed by controlled trials.

Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma.

Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS.

The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus.

To gain insight into the mechanisms of autoantibody induction, sera from 40 patients with systemic lupus erythematosus (SLE) were tested by ELISAs for antibody binding to denatured individual histones, native histone-histone complexes, histone-DNA subnucleosome complexes, three forms of chromatin, and DNA. Whole chromatin was the most reactive substrate, with 88% of the patients positive. By chi-square analysis, only the presence of anti-(H2A-H2B), anti-[(H2A-H2B)-DNA], and antichromatin were correlated with kidney disease measured by proteinuria > 0.5 g/d. SLE patients could be divided into two groups based on their antibody-binding pattern to the above substrates. Antibodies from about half of the patients reacted with chromatin and the (H2A-H2B)-DNA subnucleosome complex but displayed very low or no reactivity with native DNA or the (H3-H4)2-DNA subnucleosome complex. An additional third of the patients had antibody reactivity to chromatin, as well as to both subnucleosome structures and DNA. Strikingly, all sera that bound to any of the components of chromatin also bound to whole chromatin, and adsorption with chromatin removed 85-100% of reactivity to (H2A-H2B)-DNA, (H3-H4)2-DNA, and native DNA. Individual sera often bound to several different epitopes on chromatin, with some epitopes requiring quaternary protein-DNA interactions. These results are consistent with chromatin being a potent immunogenic stimulus in SLE. Taken together with previous studies, we suggest that antibody activity to the (H2A-H2B)-DNA component signals the initial breakdown of immune tolerance whereas responses to (H3-H4)2-DNA and native DNA reflect subsequent global loss of tolerance to chromatin.

Cytokine concentrations in the synovial fluid and plasma of rheumatoid arthritis patients: correlation with bony erosions.

Cytokines are important protein mediators in inflammatory joint diseases. The synovial fluid and plasma concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IF-alpha) and interferon-gamma (IF-gamma) were measured by RIA and ELISA in 28 rheumatoid arthritis (RA) patients (5 males and 23 females). Ten patients with knee effusions due to other causes (osteoarthritis, psoriasis, gout, rheumatic fever, systemic lupus erythematosus) were also studied. Eight of the RA patients had erosive disease. The synovial fluid IL-1 alpha and IL-2 concentrations were higher in Group 1 (erosive) [IL-1 alpha: 524 pg/ml (SEM: 127), IL-2: 3.28 ng/ml (SEM: 1.0)] than in either Group 2 (non-erosive) [IL-1 alpha: 241 pg/ml (SEM: 24), IL-2: 1.93 ng/ml (SEM: 0.6)] or Group 3 (non-RA) [IL-1 alpha: 267 pg/ml (SEM: 58), IL-2: 0.35 ng/ml (SEM: 0.6)] (p < 0.003 and p < 0.06 respectively). Plasma IL-1 and IL-2 levels were higher in Group 1 [IL-1 alpha: 408 pg/ml (SEM: 107), IL-2: 4.20 ng/ml (SEM: 1.5)] than in Group 2 [IL-1 alpha 150 pg/ml (SEM: 15), IL-2: 2.58 ng/ml (SEM: 0.7)] or Group 3 [IL-1 alpha: 140 pg/ml (SEM: 11), IL-2: 1.93 ng/ml (SEM: 0.3)] (p < 0.01, p < 0.009 respectively). There were no differences in the IFN-alpha, IFN-gamma or TNF-alpha levels between groups. These findings suggest that plasma cytokines levels may reflect synovial levels and that IL-1 alpha may play a significant role in erosive joint disease.

Cerebral infarction in systemic lupus: association with anticardiolipin antibodies.

We report fifteen patients, thirteen with systemic lupus and two patients with a "lupus-like" illness who developed cerebral infarction. All fifteen patients were shown to have elevated anticardiolipin antibody levels using a newly devised solid phase radioimmunoassay. The lupus anticoagulant was detected in all eleven patients tested. It is proposed that anticardiolipin antibodies and the lupus anticoagulant make up a population of antiphospholipid antibodies capable of causing cerebral vascular injury and thrombosis resulting in cerebral infarction. These antibodies may also play a pathogenic role in autoimmune disorders other than lupus where cerebral thrombotic disease is a prominent feature.

Antithrombin III in systemic lupus erythematosus.

Plasma antithrombin III (AT III) was studied in 39 patients with systemic lupus erythematosus (SLE) and in 12 patients with other connective tissue disorders. AT III was measured immunologically by the Mancini method as well as by functional assay using thrombin and the chromogenic substrate, chromozyn TH (Boehringer). Reduced AT III activity was found in 17 patients; 8 had thrombosis. In 6 patients low AT III correlated with disease exacerbations and 2 had systemic vasculitis. No significant correlation could be demonstrated between low AT III levels and thromboembolic disease. A marked variation of functional AT III activity was observed in 30 patients in whom the presence of the lupus anticoagulant was demonstrated. The significance of this association is discussed.

Renal vein thrombosis in systemic lupus erythematosus: association with the "lupus anticoagulant".

Two patients with lupus erythematosus and renal vein thrombosis are described. Both patients had the "lupus anti-coagulant" in their serum. It is postulated that in these patients the clotting tendency could be favoured by a cross reaction of the "lupus anti-coagulant" with phospholipids in the endothelial cell membrane, resulting in inhibition of prostacyclin release.

Treatment strategies in rheumatoid arthritis.

Intervention therapies in rheumatoid arthritis (RA) are directed at the immune dysregulation and chronic inflammatory events in the joint. An ideal therapeutic program would rapidly control inflammation, prevent joint damage and preserve function. The various strategies of treatment involve the use of disease-modifying anti-rheumatic agents (DMARDs) either singly or in combination. Gold salts, penicillamine, sulphasalazine, methotrexate and hydroxychloroquine are used when NSAIDs fail to control inflammation. RA not only decreases the functional disability but the life-span of patients. The traditional pyramid strategy which uses single DMARDs consecutively has been found to be inadequate and slow in suppressing joint inflammation. Hence the race to find treatment regimes and strategies that will favourably alter the outcome of RA patients. Both the "step-down bridge" approach and saw-tooth strategy have been advocated in the attempt to break the progression of joint disease. None of the known regimes can be said to be most beneficial and least toxic.

Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a syndrome commonly affecting young women. The clinical manifestations are extremely varied and any major organ of the body may be involved. Misdiagnosis is not uncommon in early SLE where symptoms and signs may be few. Auto-antibodies to DNA, RNA and other cell nucleus antigens are frequently present. Circulating immune complexes may deposit in major organs, causing inflammation and tissue damage by a number of mechanisms. The lupus disease is marked by exacerbations and remissions. Management is dependent on accurate assessment of clinical activity and severity. Patient education and co-operation in management affect outcome of the disease. With good management, the ten year survival may exceed 90%.

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.

The antiphospholipid syndrome.

The antiphospholipid syndrome (APS) describes an entity characterised by recurrent thrombosis, recurrent spontaneous abortions, thrombocytopenia, and elevated levels of antiphospholipid antibodies (IgG or IgM). The clinical features of APS include manifestations of thrombosis and/or cell damage. There is usually an associated underlying connective tissue disorder. The primary antiphospholipid syndrome refers to the presence of these clinical features without evidence of an associated autoimmune disorder. Detection of these antibodies include the lupus anticoagulant test, VDRL test and assays for anticardiolipin antibodies. Overlapping populations of these antibodies are detected by various immunologic tests. Management is based on the use of immunosuppressives, platelet inhibitors and anticoagulants.

Inflammatory myopathies.

Inflammatory myopathies encompass a wide range of disorders. This article deals with the idiopathic inflammatory myopathies. Classification and diagnostic criteria proposed by Bohan and Peter are still widely used. Diagnosis is based on clinical features, muscle enzyme abnormalities, electromyographic findings and muscle biopsy results. There are known associations with malignancy and lung disease which may affect the prognosis. Management consists of the prudent use of corticosteroids. In refractory cases, cytotoxic agents, cyclosporin and plasmapheresis have been used.

Pregnancy in patients with systemic lupus erythematosus.

The view that SLE in pregnancy is associated with poor maternal and perinatal outcome is generally accepted. Consequently, there is a mistaken but commonly held belief that termination of such pregnancies will safeguard maternal health. However, because of advances in diagnostic technology, improved antenatal and neonatal surveillance, wider treatment options and a clearer understanding of the pathological processes involved, such a view is no longer tenable. This article outlines the changes in obstetric practice that have made pregnancy in women with SLE a relatively safe process. In particular, it emphasizes the need for a multidisciplinary approach to caring for such pregnancies. It also draws out some of the experiences we have had with the management of such pregnancies in Singapore that will reinforce the view that women with SLE can reproduce safely and successfully given appropriate care.

Systemic lupus erythematosus (SLE) presenting as acute pancreatitis--a case report.

Acute pancreatitis is an uncommon manifestation of systemic lupus erythematosus (SLE). In most reported cases, it occurs in the setting of SLE with multi-organ involvement. We report an unusual case of SLE in a Sri Lankan woman presenting with acute pancreatitis with the pancreas as the sole major organ affected. The diagnosis of acute pancreatitis was based on clinical features, serum and urinary amylase levels and computerised tomography. She responded well to high-dose corticosteroid. We also review the literature and discuss the prevalence, theories of pathogenesis and treatment of this condition.

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.

Renal arteriovenous fistula following kidney biopsy in systemic lupus erythematosus.

Patients with lupus nephritis frequently undergo renal biopsies. A rare complication of this procedure is the development of renal arteriovenous fistulas. We report two patients with systemic lupus erythematosus (SLE) who developed this vascular complication several years after renal biopsy.

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.

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.

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.