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Renal infarction in a child with systemic lupus erythematosus.

Although patients with systemic lupus erythematosus (SLE), especially those with antiphospholipid antibodies, have a high incidence of arterial and venous thrombotic manifestations, renal infarction has been rarely reported in these patients and is probably underestimated. A 9-year-old boy with renal infarction, diagnosed by computed tomography and scintigraphy, is described. Initially he complained of severe flank pain; he had no urinary abnormalities and his blood pressure was normal. No evidence of systemic disease was found. He responded well to antibiotic treatment without the need for immunosuppressive therapy. In subsequent years he presented a spectrum of clinical symptoms, including fever, malaise, arterial hypertension headache, and mononeuritis multiplex, accompanied by an increased erythrocyte sedimentation rate and transitory proteinuria. This suggested vasculitis involving peripheral vessels as well as the central nervous system. Treatment with oral prednisone and azathioprine led to remission. Four years after the renal infarction, the child presented with recurrence of systemic disease. The diagnosis of SLE was established, with positive antiphospholipid antibodies. The sudden appearance of severe unexplained flank pain should alert the clinician to a possible underlying renal vessel thrombosis. Renal venous thrombosis is probably much more common; however, renal arterial thrombosis and infarction in association with SLE with positive antiphospholipid antibodies should be added to the differential diagnosis.

Antibodies, Antiphospholipid↗

Heart rate variability in patients with systemic lupus erythematosus.

As patients with systemic lupus erythematosus (SLE) survive their episodes of disease activity, increasing morbidity is shown to be related to chronic cardiovascular complications. The objective of this study was to assess the cardiac parasympathetic autonomic functional status, as reflected by heart rate variability, in SLE patients with and without corticosteroid treatment. A cross-sectional study of SLE patients attending the Arthritis Clinic was done, using age and gender-matched controls. Thirty-four female patients, age 39 +/- 11, were entered, 20 of whom were receiving steroids at the time of study. Time and frequency domain heart rate variability indices were significantly reduced in the SLE groups with and without corticosteroid therapy, as compared to controls. The indices were not, however, significantly different in the two SLE groups.

Adrenal Cortex Hormones↗

Atypical cutaneous findings in a patient with systemic lupus erythematosus.

A previously diagnosed systemic lupus erythematosus patient presented with arthralgia, skin rash and muscular weakness. When treated with high-dose corticosteroids and methotrexate she improved, except for a persistent lesion in the hand which evolved into a profound ulcer, along with tender subcutaneous nodules in the calf. A skin biopsy disclosed necrotizing vasculitis with giant cell granuloma revealing acid fast positive bacteria on ziels nilsen staining. A chest X-ray disclosed miliary tuberculosis (TB). The patient was diagnosed as miliary TB with prominent cutaneous involvement and treated with four anti-tuberculous drugs with slow resolution of her systemic, pulmonary and skin signs.

Adult↗

Acute cerebrovascular episodes in systemic lupus erythematosus.

Twelve patients with systemic lupus erythematosus (SLE) who developed major acute cerebrovascular episodes are described. All patients were female, with a mean age of 43.3 years and they had suffered from SLE for between 1 month and 22 years (mean 9.3 years) at the time of stroke. All patients had multiple clinical and laboratory features of systemically active SLE. Stroke was the initial neurological feature in nine patients. Cerebral infarction was confirmed in eight patients and cerebral haemorrhage in two; the two remaining patients had convincing clinical evidence of thromboembolic neurological complications. Characteristic clinical and serological features of antiphospholipid antibodies were observed in six patients (50 per cent). Five patients died as a direct result of stroke and two other patients died within one year.

Acute Disease↗

Influence of Corynebacterium parvum-PER on disease progression in the NZB/W model of systemic lupus erythematosus.

Murine models of systemic lupus erythematosus (SLE) exhibit some, but not all, of the characteristics of human disease. Disease progression in the animal models is regulated by autoantibodies, genetics and inflammatory processes. In the present study, the influence of the pyridine extract residue of Corynebacterium parvum Type I (CP-PER) on disease progression in the NZB/W model of SLE was investigated. CP-PER is known to activate the reticuloendothelial (RE) system of mice and can alter a number of host responses. Injection of NZB/W females with CP-PER at 10 weeks of age, prior to the onset of overt disease, led to a transient activation of the RE system which then appeared to return to levels observed in untreated animals. Sera from treated and untreated animals were analyzed for anti-nuclear antibodies, and anti-ssDNA antibodies. The most prominant change in the treated animals was an increase in the titer of anti-ssDNA. On average, animals in the early treatment group also lived somewhat longer than those in the untreated control group. Treatment of animals with CP-PER at 6 months of age, when the disease was evident, again led to transient RES activation and an altered autoantibody profile. Animals treated with CP-PER at 6 months of age exhibited a slightly accelerated death rate when compared with the untreated controls. These results indicate that bacterial response modifiers such as C. parvum-PER, which contains primarily the RES activating activity of C. parvum, can alter disease progression in the NZB/W model.

Animals↗

Diagnostic evaluation of the lupus band test in discoid and systemic lupus erythematosus.

BACKGROUND: The usefulness of the lupus band test (LBT) in the diagnosis of cutaneous lupus erythematosus remains controversial. The study was done to determine the sensitivity, specificity, and predictive value of the LBT in discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE). METHODS: During the study period, 32 patients with SLE and 28 patients with DLE were included. The final classification of cases was based on the American Rheumatism Association Criteria (ARA) for SLE, histopathology, and consensus of the clinical staff. Thirty controls, 15 each for DLE and SLE, were chosen from a group of patients, who had lesions clinically simulating DLE and SLE, but could be excluded by histopathology, laboratory tests, and follow-up. Histopathologic examinations and direct immunofluorescence (DIF) tests were done on lesional skin. RESULTS: In DLE, the sensitivity of the LE band test was 58% and the specificity 87%. The positive predictive value was 95% and negative predictive value was 32%. In SLE the sensitivity was 93% and specificity 87%. The positive predictive value was 64% and negative predictive value 98%. CONCLUSIONS: The high negative predictive value of LBT in SLE suggests that it is valuable in excluding diseases clinically similar to SLE.

Adolescent↗

Hyperlipoproteinemia and multifocal neurologic dysfunction in systemic lupus erythematosus.

Two patients with systemic lupus erythematosus, including one with neuropathologic findings, had recurrent multifocal neurologic dysfunction and hyperlipoproteinemia. The lipoprotein disturbances were complex and variable over time. Deficient lipoprotein lipase was found in both patients and appeared to be related temporally to neurologic deterioration. One of these patients had neurologic disease and lipoprotein abnormalities 2 1/2 years before SLE could be documented serologically. These studies suggest that lipoprotein lipase deficiency may be a marker for the endothelial disorder causing cerebral vasculopathy in SLE.

Adolescent↗

Brain protein kinase in synaptic vesicles is inhibited by a factor in sera from systemic lupus erythematosus patients with central nervous system manifestations.

Sera from systemic lupus erythematosus patients with clinical central nervous system manifestations had a high mean percent of brain synaptic vesicle protein kinase inhibition (62 +/- 9.3, P less than 0.001). This conclusion was derived from screening sera of a total of 287 patients with heterogeneous diseases and from 12 healthy controls. Low levels of synaptic vesicle protein kinase inhibition also were detected in the sera of patients with certain autoimmune, inflammatory, neurological and/or psychiatric symptoms. Because 87.5% of the patients whose sera showed strong synaptic vesicle protein kinase inhibition (over 50%) had neuropsychiatric manifestations, we postulate this relationship may be due to the presence of an inhibitor factor, of which the etiology and molecular characteristics were investigated.

Adult↗

[Immunogenetic bases of systemic lupus erythematosus in humans].

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown pathogenesis. Familial studies and concordance rates among affected twins suggest that human SLE has a strong genetic basis. CURRENT KNOWLEDGE AND KEY POINTS: Recent studies have emphasized that SLE, like other autoimmune diseases, is a complex genetic trait with contributions of both major histocompatibility complex (MHC) associated genes and multiple non-MHC genes. Recent significant advances have been made in the genetic analysis of complex traits, which allow the identification of new candidate genes in SLE. Among the genes reviewed in this article, some polymorphisms of Fc gamma receptor genes and other genes or loci localized on the long arm of the human chromosome 1 appear to be very promising. FUTURE PROSPECTS AND PROJECTS: The identification of new susceptibility genes in SLE will certainly provide important insights into the breakdown of self-tolerance mechanisms leading to autoimmune diseases. To achieve this objective, the recruitment of a large number of genetic traits of multiplex families presenting with SLE is therefore essential. More than 125 multiplex families have been collected to date in France.

Animals↗

Thyroid-gonad relationship in systemic lupus erythematosus.

Thirty women with systemic lupus erythematosus (SLE) were examined to assess the thyroid-gonad relationship. Significant decreases in mean serum tri-iodo-thyronine and testosterone levels and increases in mean serum estradiol and luteinizing hormone levels were observed in SLE patients as compared to control subjects. The serum levels of thyroxine, thyrotropin, tri-iodo-thyronine uptake, free thyroxine index and prolactin were, however, not significantly different in both groups. The interpretation of these findings is unclear but SLE could be regarded as one of the nonthyroidal systemic illness since low serum tri-iodo-thyronine with normal thyrotropin levels were observed in our patients. Furthermore, high levels of estradiol and low levels of testosterone in our female patients may indicate involvement of sex steroids in the pathogenesis of SLE.

Adolescent↗

High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus.

All patients with systemic lupus erythematosus (SLE) (American Rheumatism Association criteria with positive antinuclear antibody titre) and who attended any of the three general hospitals in Leicester over a 10 year period were ascertained using several complementary sources. Eighty seven subjects (26 Asian, 61 white) were identified. The estimated prevalence of SLE in Leicester is 0.4/1000 for Asian and 0.2/1000 for white subjects. Mean age of onset of the disease was 24 years in Asian and 31 years in white subjects, with both groups showing a female preponderance. Proteinuria (greater than 1 g/24 h) was noted in 15 (58%) Asian and 21 (35%) white subjects; neuropsychiatric disease in 10 (38%) Asian and 8 (13%) white subjects; myalgic symptoms with raised muscle enzymes in 9 (35%) Asian and 3 (5%) white subjects. Nineteen (73%) Asian subjects were positive for extractable nuclear antigens as well, at some stage of their disease, compared with 6 (10%) white subjects. Immunosuppressive treatment was required in 12 (46%) Asian and 12 (20%) white subjects, and deaths of seven Asian and five white subjects were attributed to SLE. These findings show that Asian subjects have a higher prevalence of SLE with greater systemic disease and mortality.

Adult↗

Pulmonary hemorrhage and immune-complex deposition in the lung. Complications in a patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus (LE) was admitted with an acute illness characterized by dyspnea, hemoptysis, fever, and diffuse infiltrates revealed by chest roentgenograms. An open-lung biopsy specimen showed massive intrapulmonary hemorrhage, and immunofluorescence and electron microscopic examinations showed granular deposits of IgG within the alveolar walls and pulmonary vessels. Rare, widely scattered foci of infiltration of vessel and alveolar walls by polymorphonuclear leukocytes were also observed. The patient was treated with large doses of prednisone and her condition improved, but she had a second episode of massive hemorrhage eight days after discharge despite maintenance of the prednisone therapy. Her condition again improved over several days, and she has had no pulmonary symptoms for nine months. In some instances, pulmonary hemorrhage in patients with systemic LE may be mediated by polymorphonuclear leukocytes attracted by immune-complex deposits.

Adult↗

Influence of biological response modifiers of bacterial origin on disease progression in the MRL-lpr model of systemic lupus erythematosus.

Murine models of systemic lupus erythematosus exhibit some, but not all of the characteristics of human disease. Disease progression in the animal models is related to autoantibodies, genetics, and inflammatory processes. In this report the effects of two bacterial biological response modifiers (BRM) on disease progression in the MRL-lpr model were investigated. The two BRM tested were C. parvum and Bacillus-Calmette-Guerin (BCG), both of which are stimulators of the reticuloendothelial system and both of which have been shown by others to influence disease progression in NZB/W mice. Treatment of 10-week-old mice with C. parvum led to transient alterations in hepatosplenomegaly and plasma proteinase regulation, which then returned to control values. Treatment with BCG led to even more transient effects on the mice. Neither BRM appeared to impact on disease-associated alterations in autoantibody titres, hepatosplenomegaly, or elevations in plasma proteinase activity. Likewise, treatment of 17-week-old MRL-lpr mice with C. parvum did not influence disease progression as evidenced by survival, autoantibody production, or hepatosplenomegaly. Therefore, in contrast to the NZB/W strain, treatment of the MRL-lpr strain with these BRM does not appear to impact on disease progression. This difference may be due to the influence of the lpr accelerator gene in this model.

Aging↗

Etiology, environmental relationships, epidemiology, and genetics of systemic lupus erythematosus.

The etiology of systemic lupus erythematosus (SLE) and the many lupuslike syndromes continues to challenge investigators. Focus is now on the role of heat-shock proteins, apoptosis, the possible role of diet factors, and in particular, the role of lipids. The role of various infections as either triggering mechanisms or in contributing to morbidity is receiving close attention. In particular, retroviruses are being carefully studied with all the molecular tools available. This area has real promise and carries with it the possibility of anti-infection treatments. Considerably more attention is being paid to the hormonal aspects of SLE and their modulation of the immune system. Environmental associations continue to intrigue investigators and clinicians, and both drugs and other environmental factors provide excellent investigational models. We continue to need good prevalence and incidence studies. Genetically, there is an increasing sophistication in the type of studies, and the ensuing data may well provide real insights into various subsets of SLE.

Environment↗

Colonic perforations in systemic lupus erythematosus.

Five patients with systemic lupus erythematosus (SLE), four of whom died with colonic perforations, are reported. Perforation of the colon constituted the most frequent cause of death among 107 patients with SLE admitted to the Rheumatic Disease Unit during a three year period. All five patients with colonic perforation had clinical and laboratory manifestations of active SLE in addition to the abdominal syndrome. Most striking was evidence of active arteritis in all patients with either central nervous system involvement and/or peripheral arteritis, in addition to that found in the gastrointestinal tract. Hyperglobulinemia and rheumatoid factor as well as antinuclear antibodies were present at some time in all patients. The abdominal syndrome was characterized by the insidious onset of lower quadrant pain which was intermittent and colicky. Although direct abdominal tenderness was eventually present in all patients, rebound tenderness and hypoactive bowel sounds were variable and abdominal rigidity occurred only in one patient and late in the course. The differential diagnosis of abdominal pain in SLE is reviewed and possible mechanisms for the production of colonic perforations are discussed. It is suggested that the presence of rheumatoid factors in conjunction with circulating immune complexes may be the pathogenetic mechanism via the production of a mesenteric arteritis.

Adrenal Cortex Hormones↗

Interleukin-2 and systemic lupus erythematosus--fifteen years later.

Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder in which multiple immunologic abnormalities have been described. In this review, we thoroughly analyse the impaired T cell production of, and response to, interleukin-2 (IL-2) characteristic of patients with SLE. Since it was first reported, several articles have provided us with enlightening, but somewhat confusing, data that reveal the complexity of the subject. The IL-2 production by T cells is part of a complex network in which a discrete alteration is capable of disrupting the whole system. On the other hand, regulatory mechanisms exist that, in an attempt to compensate the primary alteration, provoke secondary defects. Evidence indicates that this defect is not intrinsic, but rather, results from multiple microenvironmental influences that act on the T cell and modify its activation state and its cytokine production. Abnormalities in co-stimulatory mechanisms and in cytokines that may be related to the IL-2 production deficiency, have been described in patients with SLE. We also consider the information derived from murine SLE models, IL-2 knockout models and reports concerning the immune dysregulation present in patients with SLE.

Autoimmunity↗

Fractionation of cells on a discontinuous Ficoll gradient. Study of subpopulations of human T cells using anti-T-cell antibodies from patients with systemic lupus erythematosus.

Patients with active systemic lupus erythematosus (SLE) had a decrease in a subpopulation of cells (fraction D) when peripheral blood lymphocytes were separated on a discontinuous Ficoll gradient. Preincubation of SLE cells at 37 degrees C for 30 min led to a marked decrease in this fraction, composed primarily of thymus-derived (T) cells. Supernates of such preincubations were found to cause a reduction in fraction D cells from normal humans. The active factor in the supernate was found to be an IgG antibody. Similarly, serum from patients with active SLE produced a reduction in fraction D cells from normal donors. This activity was also found in the IgG fraction, and could be absorbed with a pure T-cell population. Depletion of macrophages and complement did not reduce the SLE anti-T-cell antibody-mediated loss of cells from fraction D; however, heat-aggregated human gamma globulin led to impairment of the reaction. These findings suggest that antibody-dependent direct lymphocyte-mediated cytotoxicity may play a role in T-cell lymphopenia of SLE. It was further noted that the SLE anti-T-cell antibodies, in contrast to rabbit antihuman thymocyte serum, recognized fraction D cells but not fraction E cells from normals. Since both fractions are largely T cells, it appeared that the SLE serum was directed against cell-membrane antigenic determinants present on fraction D T cells, which were absent or reduced in quantity on fraction E T cells. Thus, evidence was presented indicating the presence of at least two subpopulations of cells in man. This was supported by differential absorption of the anti-T-cell sera with fractions D and E.

Antibodies↗

[Antibodies to poly (adenosine diphosphate-ribose) in systemic lupus erythematosus and drug induced lupus].

The difference between anti poly (ADP-ribose) antibodies was studied in patients with systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) and drug-induced lupus (DIL). Radioimmunoassay showed that high concentrations of anti poly (ADP-ribose) antibodies (10.3-22.2%) were induced by phenobarbital, phenytoin, valproic acid (anti-epileptic agent) and procainamide (anti-arrhythmic agent). Poly (ADP-ribose) antibodies were separated by hydroxylapatite column chromatography. The average chain length of the polymer consisted of 2.4, 10.8 and 28.2 ADP-ribose units. Anti poly (ADP-ribose) antibodies from patients with SLE and PSS reacted with 2.4, 10.8, and 28.2 ADP-ribose units in RIA, but those from patients with DIL reacted only with 28.2 ADP-ribose units in RIA. The binding specificity of anti poly (ADP-ribose) antibodies from pregnant women was found to be very similar to that of the antibodies from case of DIL. The present results clearly demonstrated that anti poly (ADP-ribose) antibodies found in systemic autoimmune diseases bound not only to poly (ADP-ribose) with an average chain length of more than 20 ADP-ribose units, but also to oligo (ADP-ribose) with an average chain length of about 2 ADP-ribose units. Anti poly (ADP-ribose) antibodies found in DIL cases and pregnant women, however, bound only to poly (ADP-ribose) with an average chain length of more than 20 ADP-ribose units.

Antibodies↗