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Central nervous system (CNS) tuberculosis (TB) is a rare but catastrophic event in patients with systemic lupus erythematosus (SLE). Here we report a case of cerebral TB in a patient with lupus myocarditis and nephritis, following cyclophosphamide immunosuppression. To our knowledge this is the first reported case of cerebral TB in SLE in a non-endemic country. A 31-year-old female with SLE and a history of regular travel to Kenya presented to our centre with clinical features of acute heart failure. She was diagnosed with severe lupus myocarditis, and a renal biopsy also confirmed lupus nephritis. Prior to admission, she had also had a cough, fever and weight loss and was under investigation for suspected TB infection. She was treated with ivabradine, beta-blockers and diuretics together with methylprednisolone and cyclophosphamide immunosuppression. Subsequent sputum cultures confirmed TB and she was commenced on triple therapy. Despite this, she developed confusion, dizziness, blurred vision and fluctuating consciousness. Magnetic resonance imaging (MRI) and lumbar puncture revealed CNS TB infection resulting in meningitis. This was later complicated by obstructive hydrocephalus due to TB abscesses. A ventriculoperitoneal (VP) shunt was inserted and TB medications were given intravenously (IV) with dexamethasone. Following a prolonged hospital admission, the patient eventually recovered and rituximab treatment was used to control her SLE. TB infection has been associated with SLE flares. It is likely in this case that TB exacerbated a lupus flare and subsequent immunosuppression resulted in mycobacterial dissemination to the CNS. Systemic and CNS features of TB and SLE are difficult to distinguish and their contemporaneous management represents a diagnostic and therapeutic challenge. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess the impact of systemic lupus erythematosus (SLE) on patients and carers. Methods Adults with SLE and carers of SLE patients completed a UK-specific online survey covering many aspects of the disease. Surveys were developed in collaboration with an NHS lupus unit and a lupus patient organization. Results A total of 121 patients and 31 carers completed the surveys. Of the 70% of patients initially misdiagnosed with another condition, 59% received treatment for the misdiagnosis. Fatigue was the most debilitating symptom, experienced daily by 79% of patients. The proportion of patients not reporting flares to healthcare providers varied with flare severity: mild flares (43%), moderate flares (15%) and severe flares (5%). Most patients (89%) reported reduced ability to socialize, and 76% had changed employment; of these, 52% stopped working completely. Over one-half (52%) of carers in paid employment missed time from work, and 55% of carers reported a worsened financial status. Most carers (87%) experienced interference with social activities. Conclusion SLE is commonly misdiagnosed and has a considerable impact on the physical, social and financial status of patients and carers. Increased awareness of the disease among healthcare providers and employers of patients and their carers is needed. [ABSTRACT FROM AUTHOR]

Aim: The creation of a physician-administered questionnaire to screen patients with Systemic Lupus Erythematosus (SLE) for the presence of symptoms suggestive of neuropsychiatric involvement (NPSLE).Methods: The development of the questionnaire followed three phases. First, a list of manifestations was prepared based on the ACR case definitions for NPSLE. A first questionnaire was constructed including 119 items. To reduce their number, a Delphi analysis was carried out and a second questionnaire with 62 questions was developed. This questionnaire was administered to 139 patients with SLE (58 with NPSLE: 29 active, 29 inactive; and 81 without NPSLE: 39 active, 42 inactive). Questions relevant to the screening of patients were selected on the basis of the receiver operating characteristic (ROC) curve analysis.Results: Twenty-seven questions concerning central nervous system and psychiatric manifestations were found to be relevant; the remaining could be eliminated without significantly affecting AUC. The area under the ROC curve (AUC) was 0.69 (95% CI 0.61–0.78). A score above 17 was considered as suggestive of the presence of NPSLE with a sensitivity of 92.9% (95% CI 85.1–97.3 %) and specificity of 25.4% (95% CI 14.7–39.00 %).Conclusions: This questionnaire could represent a ‘core set’ of questions that could help in clinical practice to identify patients with neuropsychiatric symptoms requiring further evaluation. [ABSTRACT FROM AUTHOR]

Affinity maturation is a process by which low-affinity antibodies are transformed into highly specific antibodies in germinal centres. This process occurs by hypermutation of immunoglobulin heavy chain variable (IgH V) region genes followed by selection for high-affinity variants. It has been proposed that statistical tests can identify affinity maturation and antigen selection by analysing the frequency of replacement and silent mutations in the complementarity determining regions (CDRs) that contact antigen and the framework regions (FRs) that encode structural integrity. In this study three different methods that have been proposed for detecting selection: the binomial test, the multinomial test and the focused binomial test, have been assessed for their reliability and ability to detect selection in human IgH V genes. We observe first that no statistical test is able to identify selection in the CDR antigen-binding sites, second that tests can reliably detect selection in the FR and third that antibodies from nasal biopsies from patients with Wegener's granulomatosis and pathogenic antibodies from systemic lupus erythematosus do not appear to be as stringently selected for structural integrity as other groups of functional sequences. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) has been described as a cause of microangiopathic haemolytic anaemia (MAHA), however there is little literature to support this assertion. We report on three patients presenting with SLE and MAHA with a clinical picture indistinguishable from thrombotic thrombocytopenic purpura (TTP), who had underlying lupus nephritis. They all had significant proteinuria and normal Von Willebrand Factor cleaving protease (vWF-CP) levels. Their MAHA fitted better for haemolytic syndrome (HUS) and their cerebral signs were explained either by malignant hypertension or cerebral lupus. Their MAHA only improved when the appropriate treatment for lupus nephritis was given. We propose that the previously described association between SLE and MAHA, in actuality relates to the underlying presence of lupus nephritis causing haemolytic uraemic syndrome, not TTP. Significant proteinuria was present in all cases of MAHA due to lupus nephritis, so may be a useful discriminatory sign. Furthermore the demonstration of a normal vWF-CP assay aided in the distinction between TTP and MAHA due to lupus nephritis. All our patients responded to mycophenolate mofetil suggesting this may be useful in other cases of lupus nephritis causing HUS. [ABSTRACT FROM AUTHOR]

The antiphospholipid syndrome (APS) is a prothrombotic disorder characterised by recurrent thrombotic events and pregnancy morbidity in the context of autoantibodies against phospholipid binding proteins. There is increasing evidence that these autoantibodies are associated with accelerated atherosclerosis. The presence of stenotic lesions radiologically and abnormalities of the ankle-brachial index, flow-mediated dilatation and carotid abnormalities supports this view and this clinical evidence is reviewed. [ABSTRACT FROM PUBLISHER]

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders. [ABSTRACT FROM AUTHOR]

The primary systemic necrotizing vasculitides are a severe group of diseases, which untreated have a high mortality. The majority respond to treatment with high dose steroids and cyclophosphamide, however a significant proportion of those treated suffer morbidity due to the side effects of these agents, and a number of patients are refractory to treatment. We review and discuss alternative and emerging treatment options for patients who fail or cannot tolerate conventional therapy. An interesting subgroup of patients with systemic vasculitis and antiphospholipid antibodies provides an additional diagnostic and therapeutic challenge. We review what is known about this subgroup, and suggest screening for antiphospholipid antibodies in all patients with systemic vasculitis. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome in association with vasculitis is highlighted in this report. The combination of thrombotic and inflammatory processes resulted in endocarditis, aneurysm formation and thrombosis. To our knowledge this is the first presentation of a large vessel aneurysm in these conditions. Anticoagulation and immunosuppression are the treatment modalities of choice. [ABSTRACT FROM AUTHOR]

The antiphospholipid (Hughes) syndrome (APS), is characterized by arterial and/or venous thrombosis and pregnancy morbidity in association with antiphospholipid antibodies (aPL). Since its classical description 21 years ago, the clinical spectrum of Hughes syndrome has embraced the realms of obstetrics, nephrology, cardiology, neurology, gastroenterology and now, possibly orthopaedics. This is not surprising, given that this disease can affect virtually any organ system and blood vessel of any size and nature. Just as venous thrombosis may affect limbs and internal organs, arterial thrombosis has been shown to affect organs such as the brain, eye, heart, kidney, liver and may also involve the skeleton. In this review, the skeletal aspects of Hughes syndrome, postulated pathogenesis and possible implications of anticoagulation will be discussed. Finally, the approach to APS patients undergoing orthopaedic surgery shall also be outlined. [ABSTRACT FROM AUTHOR]

Mycophenolate mofetil (MMF) has been reproducibly shown to inhibit lymphocyte adhesion and penetration of endothelial cell surfaces. The mechanism is not yet elucidated. In vitro studies on the effects of MMF on cell adhesion molecules (CAM) using human umbilical vein endothelial cells (HUVEC) have shown conflicting results. Different studies have independently shown that MMF increased, decreased or had no effect on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1). Several studies suggest MMF may reduce the endothelial expression of E-selectin. Recent studies have been unable to replicate initial work, which suggested that MMF impaired glycosylation of lymphocyte CAM. The same studies concluded that MMF had no effect on the surface expression of lymphocyte CAM, but altered the binding ability of these molecules. ICAM-1/LFA-1 (lymphocyte function-associated antigen-1), VCAM-1/VLA-4 (very late antigen-4) and P-selectin/ PSGL-1 (P-selectin glycoprotein ligand-1) ligand pairs are most likely to be involved. Few in vivo and no conclusive human studies have been carried out. The literature relevant to cell adhesion molecules in systemic lupus erythematosus (SLE) is reviewed in detail. [ABSTRACT FROM AUTHOR]

Renal thrombotic manifestations have been reported since the earliest descriptions of the antiphospholipid (Hughes) syndrome (APS). The spectrum of clinical features associated with antiphospholipid nephropathy continues to widen. This review will highlight recent developments such as the prevalence of hypertension, livedo reticularis and renal artery stenosis as well as the ultrastructural changes seen in antiphospholipid nephropathy. The increasing risks of renal transplantation in antiphospholipid antibody positive patients is also discussed leading some authors to question whether these patients should undergo transplantation at all. [ABSTRACT FROM AUTHOR]

Discusses the link between renal artery stenosis and hypertension using the experiments of H. Goldblatt on induced hypertension from kidney disorders. Range of clinical signs of patients with antiphospholipid syndrome (APS) complications; Indications of different APS complications from various clinical diagnosis; Need for further studies of the renal anatomy of APS patients with uncontrolled hypertension.

Antimalarial therapy has a long and successful track record in the management of patirents with mild SLE. Medium to long term use of hydroxychloroquine, alone or in combination with mepacrine, ameliorates lupus and may reduce the relapse rate. Recent guidelines for monitoring hydroxychloroquine have reduced the need for frequent visual checks. Antimalarials have other beneficial effects on lipid and glucose metabolism as well as having weak anticoagulant activity. They should be considered for most patients with mild lupus. [ABSTRACT FROM AUTHOR]

Objective: To establish the relationship between T cell responses to integrin coreceptor stimulation and B cell hyperreactivity as measured by pathologic autoantibody production. Methods: Peripheral blood mononuclear cells from 42 patients with SLE according to the American Rheumatism Association criteria were examined for their ability to adhere to plate-immobilised fibronectin. Co-stimulation assays were performed on the same cells using anti-CD3 antibody alone or co-immobilised with an anti-β[sub 1]-integrin antibody. Proliferative responses were measured by [sup 3][H]thymidine pulsing on day 3 and activation was determined using a commercial protein kinase C assay, the protocol being established by our group in association with Promega. β[sub 1]-Integrin expression was established by FACS analysis. Results: An impaired PKC response to integrin-mediated activation was found in T-lymphocytes from 6/21 (29%) SLE patients, which correlated significantly with an absence of anti-dsDNA antibody in patient sera, irrespective of prednisolone treatment. Integrin co-stimulation of TcR/CD3-induced proliferation and T cell adhesion to fibronectin were also impaired among 5/21 (24%) and 6/15 (40%) patients studied, respectively. Conclusion: We hypothesise that the integrity of β[sub 1]-integrin signalling pathways may influence pathological antibody production in SLE by affecting T-lymphocyte activation and interactions between T- and B-lymphocytes. [ABSTRACT FROM AUTHOR]

Vasculitis frequently complicates SLE, is associated with significant morbidity and mortality, and its pathophysiology is poorly understood. In seriously ill lupus patients with vasculitis, immunosuppression should almost always be considered. [ABSTRACT FROM AUTHOR]

We describe a patient with systemic lupus erythematosus (SLE), whose pregnancy was com plicated by fulminant lupus pneumonitis and pericarditis. Maternal disease responded to therapy and twin girls were delivered, both with thrombocytopenia, one of whom died of an intraventricular haemorrhage. Pneumonitis is a rare complication of lupus in pregnancy which may be fatal. We suggest patients with previous severe pneumonitis should have lung function tests at the onset of pregnancy, and treatment be modified to suppress flare if there is any indication of severe pneumonitis in early pregnancy. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented which discusses a case study of a 45-year-old Jamaican male with systemic lupus erythematosus (SLE) who was treated using one gram (g) of rituximab for two weeks.

The treatment of lupus nephritis has evolved over many decades and cyclophosphamide has become the standard of care for proliferative lupus nephritis. This article describes the development of a protocol that utilises fixed low doses of cyclophosphamide followed sequentially by azathioprine as a maintenance agent, which has stood the test of time. As novel therapies and biologic agents are more widely used, it is likely that cyclophosphamide use will decline. In particular the prolonged high-dose regimen pioneered by the National Institutes of Health studies will no longer be used on account of its toxicity. [ABSTRACT FROM AUTHOR]

The author reflects on the causes of Syndrome X. He explores the excrement that suggests the possible association of thrombotic events and myocardial infarction in patients with anti-phospholipid syndrome (APS). He stresses that the findings of the excrement support the hypothesis that the thrombosis and subsequent endothelial dysfunction observed in APS patients may be responsible for Syndrome X.

We present two patients with low-grade non-Hodgkin MALT lymphoma (mucosa-associated lymphoid tissue) occurring years before clinical evidence of autoimmune disorders. While the strong association between autoimmune disorders, in particular Sjögren's syndrome and MALToma, is well described, the developement of MALToma years before the onset of an autoimmune disease is very unusual. [ABSTRACT FROM AUTHOR]

This article presents author's views on pulse cyclophosphamide regime, instituted by the U.S. National Institutes of Health. While there has been broad agreement that this treatment has contributed significantly to the outcome of lupus nephritis, the costs in terms of adverse effects have been high. Ninety systemic lupus erythematosus patients with class IV lupus nephritis were randomly assigned to a high-dose IV cyclophosphamide regimen or a low-dose IV cyclophosphamide regimen as above, each of which was followed by azathioprin. There has been emerging experience of mycophenolate mofetil (MMF) as an immunosuppressive drug in lupus, particularly lupus nephritis. MMF is an ester pro-drug of the bioactive mycophenolic acid, which inhibits inosine monophosphate dehydrogenase.

Reviews several studies on the application of high-dose intravenous cyclophosphamide therapy in severe systemic lupus erythematosus (SLE). Discussion on the effectiveness of the therapy; Prospect of the therapy.