SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Systemic lupus erythematosus is a multisystem inflammatory disease characterized by antinuclear antibody production. The diagnosis of this disease is established on the basis of a constellation of clinical and serologic features. Therapy is directed to specific disease manifestations and involves an array of anti-inflammatory and immunosuppressive agents that are administered judiciously to limit toxicity.
The nature of the antibodies responsible for lupus erythematosus (LE) cells in systemic lupus erythematosus (SLE) remains obscure. We examined whether polyanion-restricted anti-histone antibodies were present in serum of patients with SLE using Western blotting analysis. Dextran sulfate or alginate was used as a polyanion compound in place of DNA. Antibodies which recognized dextran sulfate-histone complexes were present in serum of patients with SLE (17/34, 50%). These antibodies were detected in most SLE patients positive for LE cells (17/18, 94%) but not in those negative for LE cells or in patients with other collagen diseases. Similar results were obtained using alginate-histone complexes as antigens for Western blotting analysis. The antibodies to dextran sulfate-histone or alginate-histone complexes in serum of SLE patients were completely absorbed by treatment of serum with DNA-histone complexes, while they were unaffected by treatment with DNA only. The presence of antibodies to free histones and dextran sulfate-histone complexes did not seem to be related to the titer of anti-single stranded DNA antibody and anti-double stranded DNA antibody. We demonstrated the presence of polyanion-restricted antibodies in SLE, which may be responsible for the LE factor.
A case of procainamide-induced lupus erythematosus with prominent cutaneous features is presented. The patient subsequently showed typical lesions of lichen planus, which has been associated with spontaneously occurring lupus erythematosus, but not previously reported with drug-induced lupus or as a result of procainamide therapy. A review of the immunologic alterations induced by procainamide raises questions about possible mechanisms causing the lupus and lichen planus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the synthesis of antinuclear antibodies. Nucleosomes- the disc-like structural units of chromatin, composed of histones and DNA-are the primary antigenic structure that induces the formation of complement-activating antigen-antibody complexes in basement membranes. The autoreactivity in SLE has been elucidated in drug-induced SLE: hypomethylation of DNA leads to overexpression of integrin CD11a/ CD18, increased binding of T-cells to macrophages and B-cells, a higher rate of apoptosis of macrophages, and elevated B-cell activity with consecutive production of autoantibodies. Disturbances of apoptosis (e.g. mutation of Fas gene) are relevant also in non-drug-induced SLE. The morphologic diagnosis-by light microscopy, immunohistology and electron microscopy-of skin and renal biopsies can confirm the diagnosis and help in prognostic assessment as well as therapeutic decisions in SLE. The value of the morphologic diagnosis in SLE is enhanced by reporting semiquantitative scores of disease activity and chronicity. The antiphospholipid syndrome (APS) is characterized by thrombosis, thrombocytopenia, recurrent fetal loss and antiphospholipid antibodies. APS associated with SLE or other systemic autoimmune diseases has been termed secondary APS. Antibodies in APS are directed against phospholipids and phospholipid-protein complexes. One of these proteins is beta 2-glycoprotein 1. An important mechanism of the increased rate of thrombosis in APS is probably the inhibition of the protein C-catalyzed inactivation of clotting factors V and VIII. Venous thrombosis with recurrent pulmonary emboli and arterial thrombi in brain, heart and kidney (thrombotic microangiopathy) can lead to divergent clinical manifestations in APS.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the synthesis of antinuclear antibodies. Nucleosomes-the disc-like-structural unit of chromatin being composed of histones and DNA-are the primary antigenic structure that induces the formation of complement-activating antigen-antibody complexes in basement membranes. The autoreactivity in SLE has been elucidated in drug-induced SLE: Hypomethylation of DNA leads to overexpression of integrin CD 11a/CD 18, increased binding of T-cells to macrophages and B-cells, a higher rate of apoptosis of macrophages and elevated B-cell activity with consecutive production of autoantibodies. Disturbances of apoptosis (e.g. mutation of Fas gene) are relevant also in non drug-induced SLE. The morphologic diagnosis-by light microscopy, immunohistology and electron microscopy-of skin and renal biopsies can confirm the diagnosis and help in prognostic assessment as well as therapeutic decisions in SLE. The value of the morphologic diagnosis in SLE is enhanced by reporting semiquantitative scores of disease activity and chronicity. The antiphospholipid syndrome (APS) is characterized by thrombosis, thrombocytopenia, recurrent fetal loss and antiphospholipid antibodies. APS associated with SLE or other systemic autoimmune diseases has been termed secondary APS. Antibodies in APS are directed against phospholipids and phospholipid-protein complexes. One of these proteins is beta 2-glycoprotein 1. An important mechanism of the increased rate of thrombosis in APS is probably the inhibition of the protein C catalyzed inactivation of clotting factors V and VIII. Venous thrombosis with recurrent pulmonary emboli and arterial thrombi in brain, heart and kidney (thrombotic microangiopathy) can lead to divergent clinical manifestations in APS.
Ten Ro(SS-A) antibody-positive patients with Sjögren's syndrome and lupus erythematosus are described. These patients have a disease process characterized by the frequent appearance of annular polycyclic lupus lesions of subacute cutaneous lupus erythematosus (SCLE), as well as neurologic and pulmonary disease. The Ro(SS-A) antibody-positive patients may have Sjögren's syndrome for many years and then suddenly develop lupus erythematosus, and vice versa. These studies demonstrate that the patient with Ro(SS-A) antibody may exhibit a dynamic clinical disease expression over time and that there is a closer pathologic relationship between Sjögren's syndrome and SCLE in these patients with Ro(SS-A)-antibody than has previously been appreciated. Furthermore, Ro(SS-A)-positive patients with Sjögren's syndrome and lupus erythematosus appear to have a much more guarded prognosis than those Ro(SS-A)-positive lupus patients described under the classifications of antinuclear antibody-negative lupus erythematosus and SCLE.
BACKGROUND: Recently, the induction of subacute cutaneous lupus erythematosus (SCLE) and exacerbation of systemic lupus erythematosus by terbinafine have been reported. OBJECTIVE: We describe 4 cases of SCLE, one associated with chilblain lupus, which occurred during therapy with oral terbinafine for onychomycosis. METHODS: Of 21 consecutive patients with SCLE attending the outpatient dermatology department at Muenster University clinic during a 1-year period, 4 patients with terbinafine-induced SCLE were seen. Patients were examined fully and photographed; histologic findings as well as serologic and follow-up data were evaluated. RESULTS: In addition to high titers of antinuclear antibodies (ANA) with a homogeneous pattern, anti-Ro(SS-A) antibodies were present; in 3 of 4 women, anti-La(SS-B) antibodies were also found. All patients had anti-histone antibodies as in drug-induced lupus and showed the characteristic genetic association of SCLE with the HLA-B8,DR3 haplotype; moreover, in 2 cases, HLA-DR2 was also present. After discontinuation of terbinafine, ANA titers decreased; anti-histone antibodies also became undetectable within 4(1/2) months in 3 patients concomitant with subsidence of the SCLE eruption in all patients. CONCLUSION: Terbinafine is a drug that appears to infrequently induce SCLE with high titers of ANAs and anti-histone antibodies in genetically susceptible persons.
PURPOSE OF REVIEW: Over the past 2 decades, there has been a marked improvement in survival among patients with juvenile-onset systemic lupus erythematosus. As a result of the increased life expectancy, children and adolescents with systemic lupus erythematosus are now faced with considerable morbidity resulting from sequelae of disease activity, side effects of medications, and comorbid conditions. This morbidity affects physical and psychosocial well-being. Therefore, the need is increasing for monitoring the development of irreversible organ damage and the effect of the disease and its treatment on daily life. This review summarizes the recent advances in the investigation on survival, accumulated damage, and health-related quality of life in patients with juvenile-onset systemic lupus erythematosus. RECENT FINDINGS: The 5-year survival rate of patients with juvenile-onset systemic lupus erythematosus approaches 100%, and the 10-year survival rate is close to 90%. The development of cumulative organ damage has been observed in 50-60% of patients. Children and adolescents with systemic lupus erythematosus have been found to have poorer health-related quality of life, particularly in the physical domain, and lower socioeconomic achievements than their healthy peers. SUMMARY: The prolongation of the life span of patients with juvenile-onset systemic lupus erythematosus has been accompanied by a substantial risk of damage accumulation and has not been paralleled by an improvement in health-related quality of life. This problem highlights the need of measuring cumulative organ damage and health-related quality of life in the long-term follow-up of patients with juvenile-onset systemic lupus erythematosus and of designing new treatments and treatment strategies that are aimed not only at improving control of disease activity but also at minimizing the development of nonreversible damage.
A case of systemic lupus erythematosus (SLE) complicated by multiple myeloma is presented; the lupus diagnosis was put together with the diagnosis of myeloma but the symptoms had commenced a few years before. The putative mechanisms underlying this unusual combination are discussed.
A case of systemic lupus erythematosus (SLE) complicated by multiple myeloma is presented. The lupus diagnosis was established together with the diagnosis of myeloma but the symptoms had commenced a few years before. The putative mechanisms underlying this unusual combination are discussed.
Two cases of systemic lupus erythematosus with hemodynamically significant mitral valve dysfunction and associated lupus anticoagulant are reported. Both patients underwent valve replacement and both had thrombus formation on the mitral valve, one pre- and the other postoperatively. Both patients suffered a number of extracardiac thromboses at different times in the course of their illness. The contribution of the lupus anticoagulant to the thrombotic problems, and its possible relationship to the pathogenesis of Libman-Sacks endocarditis are discussed.
To determine whether serum C3 or C4 is more likely to be normal during systemic lupus erythematosus (SLE) remission and abnormal during SLE relapse we studied twelve SLE patients who presented with severe nephritis. The patients were followed long term (12 to 77 months) through multiple relapses (N = 41) and remissions (N = 13) defined by protocol. A total of 471 serum samples were obtained at defined intervals during these relapses and remissions and were analyzed for C3 and C4 levels by two different methods: nephelometry (N) and radial immunodiffusion (R). During SLE remission (defined by protocol and without reference to serum complement levels), C3 measured by N-assay (C3N) and by R-assay (C3R) tended to be normal (specificity of 93% and 71%, respectively). By contrast, C4 measured by N-assay (C4N) and by R-assay (C4R) showed no such tendency (specificity of 50% for both C4N and C4R). During SLE relapse (defined by protocol and without reference to serum complement levels), C3N and C3R were more likely to be abnormal (sensitivity 95% and 85%, respectively) compared with C4N and C4R (sensitivity 56% and 54%, respectively, P less than 0.001 compared with corresponding values for the C3 assay). Analysis by receiver-operator characteristic (ROC) curves demonstrated that the reduced diagnostic sensitivity of C4 versus C3 is not explained by use of an inappropriate lower limits of normal (LLN) for C4.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: To find the common clinical features, pattern of visceral involvement, treatment received and outcome in patients diagnosed as having systemic lupus erythematosus (SLE) on American Rheumatological Association (ARA) criteria. SETTING: Clinic for patients referred or admitted to the University Medical Unit, National Hospital of Sri Lanka, Colombo, with diagnosed or suspected SLE. DESIGN AND METHODS: A prospective descriptive study. Clinical features of patients collected at time of registration in the clinic were maintained in a database. Patients were followed up prospectively and changes recorded. Data were analysed after 3 years of follow up. RESULTS: Of the 111 patients registered during this period, 96 (86%) were clinically diagnosed as having SLE. Of these, 77 patients (80%) satisfied ARA criteria for diagnosis of SLE. 72 were females (93%). The mean age of patients who satisfied the ARA criteria was 32 years (range 11 to 58), and the mean duration of disease 7 years (range 1 to 15). The commonest presentation was with mucocutaneous features (98%) and alopecia in 87%. Systemic features were found in 92% of patients. 67 (87%) of patients had visceral involvement with 60 (78%) having it at time of diagnosis. 53 (69%) had renal, 42 (54%) haematological, 33 (42%) neurological, 12 (16%) cardiac and 8 patients pulmonary involvement. Five patients died during the 3-year follow up and 2 developed chronic renal failure. Three patients underwent successful pregnancy after diagnosis of SLE. CONCLUSIONS: Our study confirmed the wide variability of clinical features seen in SLE. Alopecia and visceral involvement were common in Sri Lankan patients.
Mucocutaneous manifestations occur frequently in systemic lupus erythematosus (SLE). Common non-lupus dermatoses may be confused with lupus rashes, with important clinical consequences. A study of 84 consecutive patients with SLE was performed to determine the comparative frequency of lupus and non-lupus mucocutaneous abnormalities, the comparative sensitivity of routine histology and immunofluorescence in the diagnosis of lupus rashes, and the association of skin manifestations with other clinical and serological features. Thirty-five patients had dermatoses attributable to SLE (mean 3.7 per patient) and 58 had dermatoses which were not directly attributable to SLE (mean 2.1 per patient), highlighting the need for accurate diagnosis of skin rashes in SLE patients. Routine histology confirmed the clinical diagnosis of typical cutaneous lupus in 100% of malar lupus rashes and in approximately 90% of subacute cutaneous and discoid lupus rashes. Direct immunofluorescence of the affected skin provided supportive evidence of cutaneous lupus in 60% of malar lupus rashes and approximately 50% of subacute cutaneous and discoid lupus rashes. This reaffirmed the poor sensitivity of immunofluorescence, compared with routine histology, in the diagnosis of lupus rashes. The association of subacute cutaneous lupus with anti-Ro antibodies was confirmed.
Of twelve patients with discoid lupus erythematosus and dysgammaglobulinaemia, eight had a monoclonal gammopathy with a benign course to date, two had 'smouldering' myeloma, and two developed overt multiple myeloma. Six patients had generalized discoid lupus erythematosus, and six had skin lesions localized to the head and neck. Further screening of patients with discoid lupus erythematosus by serum protein electrophoresis is indicated to determine the significance of these findings.
Controversy exists concerning the prevalence of headache in systemic lupus erythematosus (SLE) and its importance as a neuropsychiatric manifestation, especially when it occurs independently of disease activity and with the typical characteristics of primary chronic headache. Most reports to date have either studied both types of headache, whether or not related to systemic lupus erythematosus, or have not used adequate controls. This study determines the prevalence and types of chronic primary headache in patients with systemic lupus erythematosus in a case-control study which we performed in a tertiary care hospital. We studied 71 consecutive patients with systemic lupus erythematosus and 71 healthy unrelated subjects matched for age and sex from the same geographical area. Clinical evaluation using a specific standard protocol for the presence and characteristics of headache according to the operative classification criteria of the International Headache Society. The overall prevalence of headache, tension-type headache, and migraine was similar among patients and controls [33 (46.5%), 17 (23.9%) and 16 (22.5%) vs 31 (43.7%), 17 (23.9%) and 13 (18.3%), respectively]. The mean age of onset of headache was higher in the patients (28.7 +/- 14.3 vs 18.5 +/- 5.6 y; P = 0.001) and the subjective response to analgesics was lower than in the controls [19 (63%) vs 28 (93.3%); P = 0.004]. There were no differences in the presence of precipitating factors or family history of headache. There were no relevant clinical or immunological differences among the patients regarding the presence or absence of tension-type headache or migraine. Patients with systemic lupus erythematosus do not differ from healthy controls for the presence and type of chronic or recurrent headache.
Epidermolysis bullosa acquisita may be associated with various systemic diseases, including systemic lupus erythematosus. We describe the clinical and immunological findings in a 38-year-old women with epidermolysis bullosa acquisita and systemic lupus erythematosus. The epidermolysis bullosa acquisita preceded a dramatic flare of systemic lupus erythematosus and fatal cerebral vasculitis. If serologic evidence of lupus erythematosus develops during the course of epidermolysis bullosa acquisita, a thorough investigation is warranted to rule out potentially life-threatening systemic lupus erythematosus.
The digestion of bacterial DNA by peripheral blood monocytes was impaired both in patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE). The monocytes of these patients had both a small quantitative defect in the solubilization of DNA and a marked qualitative defect in the extent to which this DNA was degraded. In addition, neutrophils from patients with SLE released significantly less high molecular-weight DNA than control cells. Digestion of bacterial RNA and protein by phagocytes was not defective in either disease. The reduced digestion of DNA by phagocytes resulted in concomitantly larger amounts of high molecular-weight DNA remaining in these cells. Such sequestration of DNA may contribute to the persistence of fairly large DNA fragments in the tissue of patients with lupus erythematosus.