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Limiting dilution analysis of Epstein-Barr virus infectable B cells secreting anti-Ro/SSA and anti-La/SSB antibodies in neonatal lupus erythematosus and systemic lupus erythematosus.

Neonatal lupus erythematosus (NLE) is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies. In order to better determine the risk of delivery of a child with NLE, we examined the frequency of anti-Ro and anti-La antibody secreting cells in mothers of children with NLE and in mothers at risk to deliver a child with NLE. We established limiting dilution experiments, using EBV-infected peripheral blood mononuclear cells, from 10 mothers following delivery of a child with NLE and from six mothers with anti-Ro and anti-La antibodies who delivered an unaffected child. Supernatants were assessed, by Poisson analysis, to determine the frequency of IgG and IgM anti-Ro and anti-La antibody-secreting B cells. We found that the frequency of anti-Ro and anti-La IgM antibody secreting B cells was greater than the frequency of IgG antibody secreting B cells of the same autoantibody specificity. We found no correlation between serum IgM and IgG anti-Ro or anti-La antibody titres and their respective precursor cell frequencies. We found that the mothers of children with NLE who later developed SLE tended to have higher anti-Ro and anti-La antibody-committed B cells than did the mothers who remained well. Although anti-Ro and anti-La antibody precursor frequencies were similar within a patient, they varied significantly from patient to patient. We found that most of the experiments with a precursor frequency of < 1 per million were from mothers of children with NLE rather than the mother with SLE who delivered normal children. Overall, we found that, in anti-Ro and anti-La antibody-positive women, a low anti-Ro or anti-La antibody B cell precursor frequency tended to be associated with the birth of a child with NLE.

Antibodies, Antinuclear↗

The expression of C3b receptors in the differentiation of discoid lupus erythematosus and systemic lupus erythematosus.

We studied the expression of the C3b receptor, CR1, on erythrocytes (E-CR1) of patients who, in spite of having mild systemic symptoms, were diagnosed as having discoid lupus erythematosus and followed accordingly. We found that E-CR1 was markedly reduced in these patients, similar to that seen in patients with systemic disease. In contrast, those patients with completely asymptomatic discoid lupus erythematosus had the same expression of E-CR1 as the normal population.

Complement C3b↗

Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: a population-based neuropsychological study.

We present a cross-sectional, population-based neuropsychological study of systemic lupus erythematosus (SLE) patients identified within Tampere University Hospital district, Finland with 440,000 inhabitants. Patients with definite SLE in the age range of 16-65 years (n = 46) and matched controls (n = 46) underwent neurological examination and comprehensive neuropsychological testing. On the basis of medical examination, the SLE patients were divided into neuropsychiatric (NP+; n = 15) and nonneuropsychiatric (NP-; n = 31) cases. The neuropsychological test results revealed more prevalent cognitive impairment in the NP+ patients, indicating that this subgroup mostly accounts for neuropsychological changes in SLE. Most characteristic changes in NP+ were observed in domains of memory, psychomotor speed, and complex attention. This suggests nonspecific CNS involvement, which is in line with neurological manifestations of the disease.

Adolescent↗

Stroke subtypes among young patients with systemic lupus erythematosus.

PURPOSE: Systemic lupus erythematosus (lupus) is a systemic inflammatory disease associated with premature atherosclerosis, vasculitis, coagulopathy, and excessive incidence of stroke, especially among young patients. Little is known about subtypes of stroke in lupus. METHODS: A 20% sample of all the hospitalizations in the United States in the years 2001 and 2002 (N approximately 15 million) were analyzed to identify hospitalizations of young patients (age < or =50 years) with systemic lupus erythematosus (n=25704). Proportions of hospitalization for stroke subtypes were compared between the lupus group and the general population group. Age- and sex-adjusted odds ratios for stroke were calculated with logistic regression models. RESULTS: In the lupus group, there were 313 hospitalizations for stroke of which 206 hospitalizations had stroke as the primary diagnosis. Age- and sex-adjusted stroke risk was higher among the lupus group (odds ratio 1.5, 95% confidence interval 1.3-1.8). Patients with lupus had higher risk for all stroke subtypes except in subarachnoid hemorrhage in which a trend toward a lower risk was observed (odds ratio 0.57, 95% confidence interval 0.34-0.96). Although 12.3% (n=38) of stroke admissions in the lupus group resulted in in-hospital death, this case fatality rate was not statistically different from that for stroke in the general population group. CONCLUSIONS: Stroke is an important poor outcome in young patients with lupus. Compared with the general population, patients with lupus are more likely to be hospitalized for the risk of ischemic stroke and intracerebral hemorrhage. The risk of subarachnoid hemorrhage, however, seems to be lower in patients with lupus.

Adolescent↗

Lupus erythematosus tumidus in systemic lupus erythematosus: novel association and possible role of early treatment in prevention of discoid lupus erythematosus.

Skin involvement in systemic lupus erythematosus (SLE) occurs in varied forms. Lupus erythematosus tumidus (LET) is not known to occur with SLE. In our patient presented below, LET occurred in a patient with SLE. Some of the lesions progressed to scarring discoid lesions, while others responded very well to hydoxychloroquine treatment. We, as rheumatologists, are not very aware of this entity, which is so amenable to prevention and treatment if recognized correctly.

Adult↗

Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus.

BACKGROUND: Neuropsychiatric involvement in systemic lupus erythematosus is complex and several clinical presentations are related to this disease such as: convulsions, chronic headache, transverse myelitis, vascular brain disease, psychosis and neural cognitive dysfunction. This systematic review is an update of a review performed in 2000. OBJECTIVES: To assess the efficacy and safety of cyclophosphamide and methylprednisolone in the treatment of neuropsychiatric manifestations of systemic lupus erythematosus. SEARCH STRATEGY: We searched EMBASE, LILACS, Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE up to and including May 2005. Additional articles were sought through handsearching in relevant journals. There were no language restrictions. SELECTION CRITERIA: All randomised controlled trials that compared cyclophosphamide to methylprednisolone were included. Patients of any age and gender were included as long as they fulfilled the criterion of the American College of Rheumatology for the diagnosis of systemic lupus erythematosus and presented with any one of the following neuropsychiatric events: convulsions, organic brain syndrome and cranial neuropathy. Outcome measures included the following: a) overall mortality (primary event); b) motor and psychiatric deficit (primary event); c) clinical improvement (secondary event). DATA COLLECTION AND ANALYSIS: Data was independently extracted by two reviewers and cross-checked. The methodological quality of each trial was assessed by the same two reviewers. Details of the randomisation (generation and concealment), blinding, and the number of patients lost to follow-up were recorded. Dichotomous data was presented as relative risks with corresponding 95% confidence intervals and a clinical relevance table was produced. MAIN RESULTS: We found one randomised controlled trial of 32 patients comparing cyclophosphamide versus methylprednisolone for the treatment of neuropsychiatric involvement in the systemic lupus erythematosus. A significantly greater number of people responded to treatment in the cyclophosphamide group. Treatment response was found in 94.7% (18/19) of patients using cyclophosphamide compared with 46.2% (6/13) in the methylprednisolone group at 24 months (RR 2.05, 95% CI 1.13, 3.73) The NNT for response to treatment is 2. Cyclophosphamide use was associated with a reduction in prednisone requirements. A significant decrease in the number seizures per month was observed in the cyclophosphamide group. All the patients in the cyclophosphamide group had electroencephalographic improvement. No significant differences in adverse effects between the groups were found. It was not possible to extract more data from the study because there was a small number of patients in the others clinical subgroups of neurological manifestations and the authors did not provide sufficient information for data extraction. AUTHORS' CONCLUSIONS: This systematic review found one randomised controlled trial with a small number of patients in the different clinical subgroups of neurological manifestation. It seems that cyclophosphamide is more effective in the treatment of neuropsychiatric involvement in systemic erythematosus lupus compared with methylprednisolone. However, properly designed randomised controlled trials that involve large, representative numbers of individuals, with explicit clinical and laboratory diagnosis criteria, sufficient duration of follow-up and description of all relevant outcome measures are necessary to guide practice.

Cyclophosphamide↗

Age-related changes in serum growth hormone, insulin-like growth factor-1 and somatostatin in system lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. METHODS: Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. RESULTS: Serum growth hormone levels failed to correlate with age (r2 = 3.03) in the entire group of normal subjects (i.e. 20 - 80 years). In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092). Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269) in the 20 - 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 - 80 yrs) or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p < 0.001) in systemic lupus erythematosus patients, but only when compared to the entire group of normal subjects. Serum somatostatin levels differed from normal subjects only in older (i.e. >55 yrs) systemic lupus erythematosus patients. CONCLUSIONS: These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal hyperostosis and hypermobility syndrome where significantly higher serum growth hormone levels were found. Somatostatin levels in elderly systemic lupus erythematosus patients may provide a clinical marker of disease activity in these patients.

Adult↗

Nonmyeloablative stem cell transplant in a patient with advanced systemic sclerosis and systemic lupus erythematosus.

Systemic sclerosis (SSc) is an uncommon connective tissue disease characterized by excessive collagen deposition within the skin and internal organs. Most patients with diffuse severe SSc are treated with immunosuppressive agents, but patients with advanced disease have very high 5-year mortality rates despite adequate therapy. We describe a patient with both diffuse cutaneous SSc and systemic lupus erythematosus who showed mixed chimerism 29 months after undergoing nonmyeloablative stem cell transplant. She experienced remission of both diseases.

Adult↗