Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired von Willebrand syndrome (AVWS) associated with hypothyroidism is of type I, results from a decreased synthesis of factor VIII and von Willebrand factor (VWF), responds to desmopressin with normal half-life times for factor VIII and VWF parameters, and disappears after treatment with I-thyroxine. AVWS type I or III, which occurs in a minority of patients with Wilms' tumour in the complete absence of an inhibitor against VWF and no absorption of factor VIII or VWF onto nephroblastoma cells, responds to chemotherapy and/or tumour resection. Hyaluronic acid produced by nephroblastoma cells may be the causative factor in atypical AVWS in Wilms' tumour. AVWS associated with thrombocythaemia of various myeloproliferative disorders is characterized by normal factor VIII and von Willebrand factor antigen (VWF: Ag) levels and a selective deficiency of functional ristocetin co-factor activity (VWF: RCo) and collagen-binding activity (VWF: CBA). AVWS type II in thrombocythaemia is caused by a platelet-dependent proteolysis of large VWF multimers, given the inverse relationship between platelet count and large VWF multimers in plasma and specific increases in the number of proteolytic VWF fragments in plasma. The laboratory findings of AVWS associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy are characterized by a prolonged bleeding time and activated partial thromboplastin time, decreased or absent ristocetin-induced platelet activity, low to very low levels of factor VIII coagulant activity (mean 15%), VWF: Ag (mean 10.7%) and VWF: RCo (mean 6.2%), and a type II multimeric pattern of VWF. Neutralizing and non-neutralizing anti-VWF autoantibodies, usually IgG, have been detected in patient plasma either free or tightly bound to the intermediate and high molecular weight VWF factor VIII particles. The bound auto antibody-antigen complex is rapidly cleared from the circulation, resulting in low levels of factor VIII, VWF parameters as documented by a poor response to desmopressin and VWF factor VIII concentrate. High-dose intravenous immunoglobulin transiently corrects the factor VIII coagulant and VWF levels, lasting for a few weeks in AVWS type II associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy. Prednisolone is effective in AVWS associated with autoimmune disorder. Prednisolone and chemotherapy will not affect AVWS associated with IgG benign monoclonal gammopathy because the monoclonal IgG protein remains to act as an anti-VWF autoantibody. An absorption of VWF to malignant cells has been documented in a few patients with various lymphoproliferative disorders or adrenal carcinoma and suggested to result in a depletion of VWF. The clinical picture of AVWS associated with early-stage IgG multiple myeloma, chronic lymphocytic leukaemia or non-Hodgkin's lymphoma without a paraprotein or no detectable underlying disorder is similar to that of AVWS type II in IgG benign monoclonal gammopathy but poorly documented with regard to the underlying immune mechanism of AVWS. The mechanical destruction of large VWF multimers may be of relevance in conditions in which the shear rate of flowing blood is increased, as may occur in cases of aortic stenosis, other heart valve defects or stenosed vessels. Drug-induced AVWS has been described in association with the use of pesticides valproic acid, ciprofloxacin, griseofulvin, tetracycline, thrombolytic agents and hydroxyethyl starch.
Best Pract Res Clin Haematol 2001 Jun
PMID:Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. 1168 7

Animal models of autoimmune disease and case reports of patients with these diseases who have been involved in bone marrow transplants have provided important data implicating the haemopoietic stem cell in rheumatic disease pathogenesis. Animal and human examples exist for both cure and transfer of rheumatoid arthritis, systemic lupus erythematosus (SLE) and other organ-specific diseases using allogeneic haemopoietic stem cell transplantation. This would suggest that the stem cell in these diseases is abnormal and could be cured by replacement of a normal stem cell although more in vitro data are required in this area. Given the morbidity and increased mortality in some patients with severe autoimmune diseases and the increasing safety of autologous haemopoietic stem cell transplantation (HSCT), pilot studies have been conducted using HSCT in rheumatic diseases. It is still unclear whether an autologous graft will cure these diseases but significant remissions have been obtained which have provided important data for the design of randomized trials of HSCT versus more conventional therapy. Several trials are now open to accrual under the auspices of the European Bone Marrow Transplant Group/European League Against Rheumatism (EBMT/EULAR) registry. Future clinical and laboratory research will need to document the abnormalities of the stem cell of a rheumatic patient because new therapies based on gene therapy or stem cell differentiation could be apllied to these diseases. With increasing safety of allogeneic HSCT it is not unreasonable to predict cure of some rheumatic diseases in the near future.
Best Pract Res Clin Rheumatol 2001 Dec
PMID:Stem cells in the aetiopathogenesis and therapy of rheumatic disease. 1181 17

Nitric oxide (NO) is synthesized via the oxidation of arginine by a family of nitric oxide synthases (NOS), which are either constitutive (ie. endothelial (ec)NOS and neuronal (nc)NOS) or inducible (iNOS). The production of nitric oxide plays a vital role in the regulation of physiological processes, host defence, inflammation and immunity. Pro-inflammatory effects include vasodilation, oedema, cytotoxicity and the mediation of cytokine-dependent processes that can lead to tissue destruction. Nitric oxide-dependent tissue injury has been implicated in a variety of rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis and osteoarthritis. Conversely, the production of NO by endothelial cell NOS may serve a protective, or anti-inflammatory, function by preventing the adhesion and release of oxidants by activated neutrophils in the microvasculature. In this chapter we describe the multifaceted role of nitric oxide in inflammation and address the potential therapeutic implications of NOS inhibition.
Best Pract Res Clin Rheumatol 2001 Dec
PMID:The role of nitric oxide in tissue destruction. 1181 24

Much progress has been made in the field of haemopoietic stem cell transplants (HSCTs) for severe autoimmune disorders. Theoretical considerations, animal data and anecdotal evidence suggested some time ago that intensive immunoablation followed by autologous HSCT could restore normal immune reactivity in patients with severe autoimmune disorders. Based on a concept statement issued in 1995, two European societies, the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) began collecting phase I/II trial data in an international collaborative network. Sufficient information from more than 350 patients allows a preliminary assessment with level three evidence. Autologous HSCTs can induce remissions in all disease categories tested so far. Remissions can be transient or durable. HSCTs are associated with significant morbidity and mortality. Treatment-related mortality (TRM) is near 10% at 1 year and is associated with the intensity of the conditioning and the stage of the disease at the time of transplant. Marked interdisease differences exist. There are few data available in haematological autoimmune diseases, more in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA) and multiple sclerosis (MS). Patient selection has been recognized as a crucial element from the phase I-II trials. Patients with advanced disease, severely compromised organ function or irreversible organ damage should not be considered as candidates for HSCT. Prospective randomized studies should now determine the value of HSCT compared to standard therapy. Such trials are ongoing for patients with systemic sclerosis (ASTIS trial--Autologous Stem Cell Transplantation International Scleroderma Trial) or are planned for patients with multiple sclerosis (ASTIMS trial--Autologous Stem Cell Transplantation International Multiple Sclerosis Trial) and rheumatoid arthritis (ASTIRA trial--Autologous Stem Cell Transplantation International Rheumatoid Arthritis Trial). More phase II data are needed for other indications such as SLE and JIA.
Best Pract Res Clin Haematol 2001 Dec
PMID:Stem cell transplantation for autoimmune diseases. 1192 20

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease, as yet of unknown aetiology, with diverse clinical manifestations and a variable course and prognosis. The diagnosis is based on recognizing the overall pattern of clinical and laboratory abnormalities. However, even today, there is often a significant delay between onset of symptoms and diagnosis. Over the last two decades there has been great progress in identifying the profile of antinuclear antibodies that characterizes SLE, and in this chapter we describe how serological techniques can be important tools for the clinician in the early diagnosis of this disorder. Also described is the lupus band test, which has rather fallen out of favour as a diagnostic tool but which can still provide valuable evidence for the diagnosis in patients in whom the clinical and serological features are inconclusive. Nevertheless, because the presentation of lupus is protean, and the early manifestations are often non-specific, SLE can still be easily confused with a wide range of other conditions. Here, we describe some of the common clinical conundrums encountered in patients referred to the Lupus Clinic to 'rule out lupus', providing a framework for diagnosis. Finally, the chapter considers the major problem that clinicians who treat patients with SLE frequently face in distinguishing between a flare of lupus and infection. Diagnosis of SLE is still a great clinical challenge, and while it is important to recognize patients with potentially aggressive disease and treat them appropriately at an early stage it is also important to be able to recognize patients with potentially benign disease and avoid over-treatment.
Best Pract Res Clin Rheumatol 2002 Apr
PMID:Is it SLE? 1204 47

Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease (ARD) characterized by flares and remissions. SLE has protean and often complex manifestations, necessitating careful clinical assessment. However, it is important to remember that not all clinical problems reported by a lupus patient are due to the disease. Some may be a consequence of therapy and others may be unrelated to lupus. Therefore it is important to understand the totality of the effect of the disease on the patient. In order to do this measures are needed which distinguish current, potentially reversible disease activity, permanent organ damage and the effect of the disease on the patients' health status. Several measures are in current use in clinical trials, but not all are suitable for use in the routine clinical setting. This chapter discusses the current measures available to assess disease activity and damage in SLE.
Best Pract Res Clin Rheumatol 2002 Apr
PMID:How does one assess and monitor patients with systemic lupus erythematosus in daily clinical practice? 1204 48

The clinical and renal biopsy predictors of assistance in determining therapy are reviewed. While pulse cyclophosphamide remains the most effective treatment for proliferative nephritis, there is increasing interest in other agents, such as azathioprine, particularly to maintain remission. While lupus membranous nephropathy has attracted limited study, preliminary work suggests a role for cyclophosphamide. Newer therapies, including cyclosporine A, mycophenolate mofetil, immunoadsorption, intravenous immune globulin, LJP-394, high-dose immunoablation and nucleoside analogues require further study but offer hope for those failing conventional treatments.
Best Pract Res Clin Rheumatol 2002 Apr
PMID:How to manage patients with lupus nephritis. 1204 49

Systemic lupus erythematosus (SLE) is a connective tissue disease characterized by the formation of autoantibodies and immune complexes. The heart and lungs are among the organ systems commonly affected in SLE. Pericarditis, premature coronary atherosclerosis, pleuritis and pulmonary infections are the most prevalent cardiopulmonary manifestations. Other rare associations include myocarditis, coronary arteritis, acute lupus pneumonitis/pulmonary haemorrhage, acute reversible hypoxaemia and 'shrinking lung' syndrome. Current imaging modalities may provide earlier detection of subclinical disease, which may aid in preventing these potentially fatal complications. The response to treatment varies, depending on the presentation of disease. In this chapter we address the frequency, diagnosis and monitoring, and treatment regimens of cardiac and pulmonary involvement in patients with SLE.
Best Pract Res Clin Rheumatol 2002 Apr
PMID:How to manage patients with cardiopulmonary disease? 1204 50

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves a wide range of focal and diffuse central and peripheral nervous system disorders and affects up to 75% of SLE patients. NPSLE can occur any time in the course of SLE, even during periods in which no SLE disease activity is detected, and is likely to be caused by multiple factors, including autoantibody production, microvasculopathy and pro-inflammatory cytokines. Central to the diagnosis of NPSLE is the question of whether the presenting neuropsychiatric symptoms are due to SLE-mediated organ dysfunction, infection, medication side-effects or metabolic abnormalities (e.g. uraemia), or are due to an unrelated condition. The diagnostic inference of NPSLE can be made only after these secondary causes have been excluded. There is no one single diagnostic tool specific to NPSLE, and clinical diagnostic impressions must be based on the combined use of immunoserological testing, functional and/or structural neuroimaging and standardized neurological, rheumatological, psychiatric and neuropsychological assessments. The management of NPSLE includes symptomatic and/or immunosuppressive treatment strategies depending on the specific presenting neuropsychiatric symptoms and whether these occur in the setting of an SLE disease activity flare.
Best Pract Res Clin Rheumatol 2002 Apr
PMID:Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). 1204 51

Oral contraceptives containing oestrogens and hormone replacement therapy are generally not prescribed for women with systemic lupus erythematosus (SLE). The concern regarding oestrogens is based on the greater incidence of SLE in women, abnormalities of oestrogen metabolism, murine models of lupus, several anecdotes of patients having disease flares while receiving hormones, and one retrospective study in patients with pre-existing renal disease. For healthy women and those with SLE, there are clinical settings in which exogenous oestrogens provide benefit. For pre-menopausal women, these include provision of safe and effective birth control, protection against bone loss, and the consideration of oral contraceptives to preserve fertility in patients taking cyclophosphamide. For post-menopausal women, these include treatment of hot flushes and vaginal dryness, prevention of osteoporosis and, more controversial, prevention of atherosclerosis. Other exogenous hormones (clomiphene citrate, gonadotropins, gonadotropin-releasing hormones) may be used to elevate levels of endogenous oestrogen and stimulate ovulation in patients with diminished fertility. This chapter focuses on three broad categories: birth control, assisted reproduction and hormone replacement.
Best Pract Res Clin Rheumatol 2002 Apr
PMID:Reproductive health in SLE. 1204 53


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