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Query: UMLS:C0409974 (lupus)
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In patients with rheumatic and, especially, connective tissue diseases many organ systems apart from the joints may be involved, such as the skin, muscles, salivary glands, nerves, kidneys and blood vessels. Biopsies of these tissues may help in establishing a diagnosis, in assessing the extent and severity of the disease and in monitoring the success of therapy. In this chapter, indications for biopsy, technical procedures, potential results and possible complications are described. The emphasis is on when a biopsy is indicated, how the patient is prepared, how the biopsy is performed, what results can be expected from the biopsy and what are the possible sequelae. For full details of the histology of e.g. a renal biopsy in a lupus patient, the reader is referred to the relevant textbooks.
Best Pract Res Clin Rheumatol 2005 Jun
PMID:Procedures related to connective tissue disease. 1593 67

The assessment of disease activity in systemic lupus erythematosus (SLE) is a task faced by clinicians in every day care, but it is also required for clinical research and in randomised controlled trials. It is crucial to distinguish disease activity from infection, chronic damage and co-morbid disease. Over the past 20 years, many indices have been developed to objectively measure lupus disease activity and several of these have been validated. The most widely used indices are the British Isles Lupus Assessment Group (BILAG) index, the European Consensus Lupus Activity Measurement (ECLAM), the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Lupus Activity Index (LAI). All these indices have been validated and have excellent reliability, validity and responsiveness to change. In addition to the assessment of disease activity, the evaluation of damage using the validated SLICC/ACR damage index and health-related quality of life is advised for clinical research.
Best Pract Res Clin Rheumatol 2005 Oct
PMID:Assessment of patients with systemic lupus erythematosus and the use of lupus disease activity indices. 1615 Mar 98

The diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is complex not only on account of the heterogeneous nature of neurological presentation but also because of the difficulty of differentiating lupus-related pathology from other neuropsychiatric diseases. Magnetic resonance imaging (MRI) remains the gold standard for the non-invasive assessment of NPSLE but there are problems, both with sensitivity and specificity. Both T(2) quantitation and the use of gadolinium have shown promise in differentiating acute from chronic lesions. Nonetheless, the lack of sensitivity of conventional MRI has led to the exploration of other MR-based techniques. Magnetic resonance spectroscopy (MRS) allows the measurement of brain metabolites, whereas diffusion weighted imaging and diffusion tensor imaging allow assessment of white matter structure and integrity. MRS studies in NPSLE have consistently shown a reduction in N-acetyl aspartate (a neuronal marker). Diffusion weighted imaging has had only limited application in lupus and the results to date have shown abnormal diffusivity in lupus patients consistent with inflammation and loss of white matter structure. These techniques remain research tools at this early stage. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) have also been explored as functional imaging tools in lupus and both appear to be more sensitive in detecting subtle brain changes in NPSLE but there are issues with specificity which deter their use in the clinical setting.
Best Pract Res Clin Rheumatol 2005 Oct
PMID:Imaging in CNS lupus. 1615 Apr

Gastrointestinal (GI) manifestations of systemic lupus erythematosus (SLE) are protean. Any part of the GI tract and the hepatobiliary system can be involved. Up to two-third of SLE patients develop GI symptoms at some stage of their illnesses. Clinical presentations of GI lupus are non-specific and can be difficult to differentiate from infective, thrombotic, therapy-related and non-SLE etiologies. Clinical acumen and appropriate endoscopic, biopsy and imaging procedures are essential for establishing the correct diagnosis. Acute abdominal pain in SLE patients can herald an intra-abdominal catastrophe and should be evaluated promptly. Surgical intervention should be instituted without delay if conservative management fails or when there is clinical or radiological suspicion of visceral perforation or intra-abdominal collections.
Best Pract Res Clin Rheumatol 2005 Oct
PMID:Investigations and management of gastrointestinal and hepatic manifestations of systemic lupus erythematosus. 1615 Apr 1

Skin disease in patients with lupus erythematosus can be subdivided into two broad categories-those lesions that, when biopsied, demonstrate an interface dermatitis and those that do not demonstrate an interface dermatitis. The skin lesions that are represented by the interface dermatitis include discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus. Many patients with these cutaneous lesions can be managed with "standard" therapies, including sunscreens, protective clothing and behavioral alteration, and topical corticosteroids with or without an oral antimalarial agent. These standard therapies are often not used appropriately, resulting in a situation in which the patient is felt to have refractory disease. This chapter discusses these therapies and defines what is meant by refractory disease and how the author approaches these patients.
Best Pract Res Clin Rheumatol 2005 Oct
PMID:Management of "refractory" skin disease in patients with lupus erythematosus. 1615 Apr 2

Nervous system disease in systemic lupus erythematosus (SLE) is manifested by a wide variety of clinical manifestations. Despite the development of a universal classification for neuropsychiatric (NP) lupus in 1999, there continues to be considerable variability in the reported prevalence of NP syndromes between different lupus cohorts. Due to the lack of specificity of individual NP manifestations, non-SLE causes such as complications of therapy and co-morbidities must be considered in advance of attributing the event to one or more primary immunopathogenic mechanisms. These include intracranial microangiopathy, autoantibodies to neuronal and non-neuronal antigens, and the generation of proinflammatory cytokines and mediators. The diagnosis of NP-SLE remains largely one of exclusion and is approached in individual patients by thorough clinical evaluation, supported when necessary by autoantibody profiles, diagnostic imaging, electrophysiologic studies and objective assessment of cognitive performance. Given the diversity in clinical manifestations, the management is tailored to the specific needs of individual patients. In the absence of controlled studies, the use of symptomatic therapies, immunosuppressives, anticoagulants and non-pharmacologic interventions is supported by case series and clinical experience.
Best Pract Res Clin Rheumatol 2005 Oct
PMID:Management of neuropsychiatric lupus. 1615 Apr 4

High-dose immunosuppression followed by autologous hematopoietic stem cell therapy (HSCT) has the promise of long-term response after a short, intense period of immunosuppressive therapy but it is associated with an increased risk of serious short-term complications. HSCT induces major clinical responses in about 65% of patients with SLE who failed standard therapies. In some of these patients such responses are durable for at least several years, but the curative potential of this procedure in severe SLE is still unknown. Procedure-related mortality varies among studies between 5 and 12% and seems to be lower in relatively larger single center studies. Until more reliable estimates of the actual risks and long-term outcomes become available, patients with potentially life-threatening or disabling major organ involvement who are in acceptable general medical condition should be considered for autologous HSCT if they have failed a reasonable course of standard immunosuppressive therapy. To accomplish the best therapeutic and scientific results, it is necessary to treat all patients in carefully planned protocols by specialized teams of lupus specialists and transplanters. All immunoablative protocols should incorporate carefully planned studies of immune reconstitution to understand the mechanisms of cure or failure.
Best Pract Res Clin Rheumatol 2005 Oct
PMID:The role of immune ablation and stem cell transplantation in severe SLE. 1615 Apr 6

Although systemic lupus erythematosus (SLE) is indeed a complex autoimmune disease, recent advances in our understanding of lupus pathogenesis have suggested new, targeted approaches to therapy. The purpose of this review is to discuss the underlying scientific rationale and results of first clinical studies of new treatment approaches to SLE, with a focus on cell-depleting therapies and cytokine blockade. It has become clear that the B lymphocyte plays a key role in disease pathogenesis by both autoantibody-dependent and autoantibody-independent mechanisms. Additionally, aberrant interactions between B and T cells are critical to disease emergence and progression. New agents that directly target immune cells abnormal in SLE include the B-cell depleting or modulating antibodies, rituximab (anti-CD20) and epratuzumab (anti-CD22) and the anti-dsDNA tolerogen LJP394. Another promising approach has been to block co-stimulatory interactions between T and B cells, for example by inhibiting the CD40-CD40 ligand pathway with anti-CD40 ligand monoclonal antibody or the B7 pathway with CTLA-4Ig. Immune cells can also be manipulated indirectly through cytokine effects. For B cells, anti-BAFF (B-cell activation factor of the tumor necrosis family) provides an example of this approach. Other, more pleiotropic cytokines can likewise be blocked in SLE. In addition to the blockade of interleukin-10 (IL-10), the first anti-cytokine approach examined, it is mainly anti-tumor necrosis factor therapy that has come into focus, holding promise for some patients with lupus nephritis. The majority of the available data on these new treatment approaches stems from open-label trials, but controlled trials are under way. Moreover, many additional cytokines, such as interleukin (IL)-6, IL-18, and the type I interferons, represent interesting future targets.
Best Pract Res Clin Rheumatol 2005 Oct
PMID:New treatments for SLE: cell-depleting and anti-cytokine therapies. 1615 Apr 7

Management of pregnant women with renal disease involves awareness of, and allowance for, physiological changes including decreased serum creatinine and increased proteinuria. For women with systemic lupus erythematosus (SLE), pregnancy increases likelihood of flare. These can occur at any stage, and are more difficult to diagnose, as symptoms overlap those of normal pregnancy. Renal involvement is no more common in pregnancy. Worsening proteinuria may be lupus flare but differential includes pre-eclampsia. In women with chronic renal disease, pregnancy may accelerate decline in renal function and worsen hypertension and proteinuria, with increased risk of maternal (eg, pre-eclampsia) and fetal (eg, IUGR, IUD) complications, strongly correlating with degree of renal impairment peri-conception. Pregnancy success rate varies from 20% to 95% depending on base-line creatinine. Best outcome is obtained if disease was quiescent for >6 months pre-conception. Women on dialysis or with renal transplants can achieve successful pregnancy but have higher maternal and fetal complication rates. Acute on chronic renal failure can develop secondary to complications such as HELLP and AFLP. Management needs to be by a multidisciplinary team involving physicians and obstetricians, ideally beginning with pre-pregnancy counselling. Treatment of flares includes corticosteroids, hydroxychloroquine, azothioprine, NSAIDs and MME Blood pressure is controlled with methyldopa, nifedipine or hydralazine.
Lupus 2006
PMID:Lupus nephritis and renal disease in pregnancy. 1663 68

Women with systemic lupus erythematosus (SLE) face significant risks when embarking on a pregnancy, but attending a multidisciplinary clinic staffed by an experienced team can improve pregnancy outcome for women and their babies. Pregnancy in SLE should be planned and a management strategy should be agreed in full consultation with the patient, prior to conception. Pregnancy increases the likelihood of a lupus flare. It is not possible to predict when, or if, an individual patient will flare, although flare is more likely if disease has been active within 6 months of conception. Worsening of proteinuria in pregnancy could herald a lupus flare, but the differential diagnosis also includes the physiological response to pregnancy and pre-eclampsia. Corticosteroids, hydroxychloroquine and azathioprine are safe to use in pregnancy, with no adverse fetal effects reported despite many years of experience with their use. Correct identification of patients with antiphospholipid syndrome is important because treatment of affected women during pregnancy can improve fetal and maternal outcome. Neonatal SLE, although rare, carries a significant mortality and morbidity when the fetal heart is the targeted organ. Prophylaxis therapies, including treatment with intravenous immunoglobulin, await larger trials.
Best Pract Res Clin Rheumatol 2006 Aug
PMID:Systemic lupus erythematosus and pregnancy. 1697 32


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