Changes In Systemic Lupus Erythematosus Research Articles

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.

Osteoporosis in murine systemic lupus erythematosus--a laboratory model.

The aim of this study was to assess the skeletal metabolism in a murine model of systemic lupus erythematosus (SLE). MRL/n and MRL/l mice (respectively representing a benign and a malignant form of the disease) were observed from 1.5 to 6.5 months of life. The monthly follow-up included: biochemical and histomorphometrical studies of the femoral bone, serum biochemistry, immunoglobulins and osteocalcin, and histological evaluation of the kidney tissue. The results showed a higher femoral weight (+11.5%), calcium (+4.4%) and protein bone content (+11.4%) and a significantly higher (+77%) phosphorus bone content in the MRL/n group; significantly lower (-48.9%) bone alkaline phosphatase enzymatic activity, lower bone alkaline/acid phosphatase enzymatic activities ratio (-40.8%) and lower (-38.4%) serum osteocalcin values in the MRL/l group (which might suggest reduced bone formation in these animals); markedly smaller trabecular bone volume (BV/TV) in the femoral head (-36.2%) and femoral neck (-39.8%), and smaller cortical and femoral areas in the mid-femoral shaft (-38.8% and -38.1% respectively) in the MRL/l group; higher serum immunoglobulins, increased serum blood urea nitrogen (BUN) and creatinine and a higher index of activity in the kidney histology in the MRL/l group, indicating increased activity of the disease in this substrain. The MRL mice, through their two substrains, may serve as a valuable laboratory animal model for study of the skeletal changes in SLE and of the influence of the disease activity on the skeletal metabolism.

Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus.

To determine the degree to which changes in anti-double-stranded DNA (anti-dsDNA), as determined by Crithidia and enzyme-linked immunosorbent assays (ELISAs), precede or coincide with changes in systemic lupus erythematosus (SLE) activity, as measured by 5 clinical indices, the physician's global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLAM), and the modified British Isles Lupus Assessment Group (M-BILAG). Disease activity and anti-dsDNA were measured monthly in 53 SLE patients who were followed up for 1 year. Lupus flare was defined as an increase in PGA of > or = 1.0, M-SLEDAI > or = 3, M-LAI > or = 0.1, SLAM > or = 3, and M-BILAG > or = 4 within a 1-month period. Flare rates were calculated for groups, which were defined by "previous" (1 month prior to the flare) or "concurrent" (at the time of the flare) changes in anti-dsDNA. Logistic regression models were used to determine the significance of the association between recent changes in anti-dsDNA and flare, controlling for the prednisone dosage. Flares occurred at 12% of visits, based on the PGA measure of disease activity. Using the other indices, flare rates were 19% (M-SLEDAI), 25% (M-LAI), 13% (SLAM), and 12% (M-BILAG). A concurrent decrease in anti-dsDNA (ELISA) was associated with significantly higher flare rates based on PGA (18 of 84, 21%; P = 0.0014), M-SLEDAI (27 of 89, 30%; P = 0.0019), M-LAI (37 of 89, 42%; P = 0.0001), and M-BILAG (19 of 89, 21%; P = 0.0264) scores. Flare rates were also significantly higher after a previous increase in anti-dsDNA (ELISA) based on M-SLEDAI (26 of 93, 30%; P = 0.0022) and M-LAI (34 of 93, 37%; P = 0.0117) scores. Flare rates tended to be lowest when there was a concurrent increase in anti-dsDNA (ELISA). Analysis of specific organ systems showed that a concurrent decrease in anti-dsDNA (ELISA) was significantly associated with increases in renal disease activity. Similar results were obtained using the Crithidia assay. A previous increase in anti-dsDNA levels occurred before SLE flares, as measured by the M-SLEDAI and M-LAI only. However, during lupus flares, including the subset of renal flares, anti-dsDNA levels frequently decreased. We hypothesize that this decrease in anti-dsDNA represents deposition in tissue at the time of flare.

A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus.

To determine the degree to which changes in C3 and C4 precede or coincide with changes in systemic lupus erythematosus (SLE) activity, as measured by 5 global activity indices, the physician's global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLAM), and the modified British Isles Lupus Assessment Group (M-BILAG), and to evaluate the association between changes in C3 and C4 levels and SLE activity in individual organ systems. Fifty-three lupus patients were observed monthly for 1 year in a longitudinal study. Lupus disease activity and complement levels were measured at each visit. Lupus flare was defined as a 1.0 (or greater) increase in the PGA, a 3-point increase in the M-SLEDAI, a 0.1 increase in the M-LAI, a 3-point increase in the SLAM, or a 4-point increase in the M-BILAG within a 1-month period. Flare rates were calculated for subgroups defined by previous (1 month before) or concurrent changes in complement levels. Logistic regression models were used to determine the significance of the association between recent changes in complement levels and flare, controlling for prednisone dosage. Similar models were used to assess the association between changes in C3 or C4 levels and increased SLE activity in specific organ systems. Lupus flares occurred at 12% of visits based on the PGA, 19% based on the M-SLEDAI, 25% based on the M-LAI, 13% based on the SLAM, and 12% based on the M-BILAG. Recent changes in C3 and C4 levels were not associated with flares based on 3 of the 5 activity indices. Flares defined by the M-LAI were more frequent when there was a concurrent decrease in C3 (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.1-3.1) or C4 (OR 2.1, 95% CI 1.3-3.6). Higher flare rates, as defined by the SLAM, were associated with previous increases in C3 (OR 1.6, 95% CI 1.0-2.6) and C4 (OR 2.2, 95% CI 1.2-3.9). When individual organ systems were analyzed, decreases in C3 and C4 were associated with a concurrent increase in renal disease activity (OR 2.2, 95% CI 1.4-3.5 and OR 1.9, 95% CI 1.1-3.4, respectively). Decreases in C3 were also associated with concurrent decreases in the hematocrit (OR 4.6, 95% CI 1.7-12.3), platelet (OR 2.5, 95% CI 1.5-4.1), and white blood cell (OR 2.2, 95% CI 1.3-3.6) counts. Previous increases in C3 levels were associated with a decrease in platelets (OR 1.7, 95% CI 1.1-2.7). A decrease in C4 was associated with a concurrent decrease in the hematocrit level (OR 3.2, 95% CI 1.3-7.5) and platelet count (OR 1.6, 95% CI 1.0-2.5). Decreases in complement levels were not consistently associated with SLE flares, as defined by global measures of disease activity. However, decreasing complement was associated with a concurrent increase in renal and hematologic SLE activity.

Neuroendocrine changes in systemic lupus erythematosus and Sjögren's syndrome

Neuroendocrine changes in systemic lupus erythematosus and Sjögren's syndrome

Neuroendocrine changes in systemic lupus erythematosus and Sjögren's syndrome

It has become clear that the neuroendocrine and immune systems are closely linked and interdependent. The exact mechanisms of this interaction are only beginning to be unravelled. The complexity of these connections may partly explain why the aetiopathogenesis of autoimmune diseases remains obscure and why genetic, hormonal, microbial, environmental, as well as a host of other factors, have all been put forward as explanations. What has become clear is that a number of neuroendocrine and hormonal factors have important immunomodulatory roles in health and disease.

Severe hepatic involvement without inflammatory changes in systemic lupus erythematosus: report of two cases and review of the literature

Hepatic diseases in systemic lupus erythematosus (SLE) are not rare, but liver biopsies of those cases are usually reported as chronic hepatitis or steroid-induced steatosis. We describe two unusual patients with active SLE who displayed liver dysfunction without inflammatory changes or associated with drug administration. A liver biopsy in case 1 showed massive hepatic cell damage resulting in acute hepatic failure. In case 2, the liver specimen revealed diffuse fatty degeneration without symptoms specific to liver dysfunction. No inflammatory cell infiltrate was observed in the liver tissue of either patient. After steroid pulse therapy (case 1) and the administration of 60 mg/day of prednisolone (case 2), liver function improved in parallel with the stabilization of the other manifestations of SLE. No other causes for liver damage except for SLE were observed in either case. Therefore it is supposed that the liver impairments in these cases were one manifestation of SLE.

Cerebral and Retinal Vascular Changes in Systemic Lupus Erythematosus

A 16-year-old white boy with acute systemic lupus erythematosus (SLE) who presented with chorea and florid retinopathy died in renal failure three months after diagnosis. Pathological studies revealed two types of lesion in both the cerebral and ocular vessels. Some meningeal and choroidal vessels showed a typical vasculitis with fibrinoid necrosis, whereas other meningeal and retinal vessels were occluded by amorphous hyaline material in the absence of vasculitis.

Needle biopsy of skeletal muscle: a review of 10 years experience.

Over 1,000 needle biopsies have been carried out at University College Hospital in London. Needle biopsy has been used by us for histochemical and electron microscopic examination of muscle during the diagnosis and treatment of neuropathic and myopathic disorders, for the diagnosis of mitochondrial myopathies, to study the course of recovery in polymyositis, and for investigations into muscle changes in systemic lupus erythematosus (SLE) and other autoimmune conditions. We have developed a microprocessor system for the measurement of muscle fiber areas, and needle biopsy specimens provide suitable material for such measurements. We have also used needle biopsy specimens for studies of protein turnover using stable isotopes and for trace metal and electrolyte analyses. Needle biopsy is safe and rapid. As the patient usually experiences only minimal discomfort and there is no permanent scar, repeat biopsies are well tolerated allowing follow-up studies after treatment.

Pulmonary vascular disease in systemic lupus erythematosus.

The pulmonary vascular changes in systemic lupus erythematosus (SLE) have been investigated from 20 autopsies performed at the Mount Sinai Hospiral from 1964 to 1973. Acute lesions included fibrinoid necrosis and vasculitis. Chronic lesions consisted of intimal fibrosis, medial hypertrophy, alteration of elastic laminae, periadventitial fibrosis, and, in one case, aneruysmal dilatation. These changes were found variously in arterioles, arteries and veins. The fibrotic and occlusive vascular lesions may account for the syndrome of "unexplained breathlessness" that occurs in SLE. These lesions may progress in certain individuals to overt pulmonary hypertension; the concept of coexisting primary pulmonary hypertension and SLE should be re-examined.

Pulmonary and pleural changes in systemic lupus erythematosus

Uber die Atiologie und die Pathogenese des SLE wissen wir sehr wenig und unsere Vorstellungen daruber beruhen in erster Linie auf Hypothesen.

Small bone changes secondary to systemic lupus erythematosus.

Since 1960 there have been several reports in the literature which stress the osseous changes in systemic lupus erythematosus. In 1960 Dubois and Cozen reported avascular necrosis of the femoral heads in 11 out of 400 cases (1). Most of the patients had been on steroids, and their average age was thirty-six years, with an equal sex ratio. There was an average five-year span between the lupus diagnosis and the onset of the avascular necrosis. Other authors have since reported similar findings in the head of the humerus (2–5). In addition to these findings, there are known arthritic changes of joint erosion, narrowing, and effusion with juxta-articular demineralization and subluxation, some of which are more consistent with rheumatoid arthritis than with systemic lupus erythematosus. In a disease in which the underlying pathologic process is vasculitis it would be logical to expect more generalized osseous involvement. Case Report J. C., a 28-year-old Negro male, presented himself on Sept. 18, 1959, with a chief complaint of shortness of breath and skin rash. Skin eruptions dated back to childhood when he received a diagnosis of atopic eczema. The arms and neck were involved recurrently. At the age of thirteen, the patient had contracted tuberculosis, for which he was hospitalized for two and a half years. One month prior to admission there developed shortness of breath and extension of the rash to the face. No definitive therapy had been administered for the dermatitis. At admission the blood pressure was 110∕80 and the pulse rate 116 per minute. He was well developed but emaciated. Atopic skin was seen with erythematous areas over the malar region of the face, the bridge of the nose, and the neck. There were confluent papillary lesions over the entire body. The heart showed enlargement to the anterior axillary line, and there was significant hepatomegaly. The chest film demonstrated bilateral apical fibrocalcific densities. Skin biopsy disclosed changes consistent with disseminated lupus erythematosus, and lupus erythematosus preparations were positive. The urinalysis showed 3+ albumin with 10 to 20 white blood cells and gross hematuria. The creatinine level was 0.52 mg per 100 cc. The venereal disease test was nonreactive, and the sickle-cell preparation was negative. The patient was placed on a program of isoniazid (INH) 300 mg a day, pyridoxine 50 mg t.i.d., prednisone 20 mg t.i.d., and hydrochlorothiazide (Esidrix) 50 mg a day. The prednisone was tapered to 15 mg a day and has been maintained until the present time. Since March 196O the patient has experienced intermittent bilateral ankle, heel, and knee pain and, in January 1967, bilateral hand and elbow pain. He has had intermittent ankle edema and effusion of the right knee. Radiographs of the elbows and knees in January 1967 were interpreted as osteoarthritis with multiple joint mice.

The Thymus: Experimental and Clinical Studies

This three-day symposium on the thymus was a veritable summit meeting, as reflected in participants, contents, and scope of treatment. Investigations utilizing the modern biotechnology of electron microscopy, histochemistry, immunochemistry, cytogenetics, and tissue culture have provided significant information on the physiologic role of the thymus in lymphopoiesis and the development of cellular and humoral immunologic capacities. Elaborate experimental designs that have been brought to bear on suitable animal models have furnished support for the participation of the thymus in the pathogenesis of autoimmune diseases and in some forms of carcinogenesis and leukemogenesis, especially those initiated by viruses or ionizing radiation. Another group of presentations deals expertly with human diseases now acknowledged as caused by thymic lesions or associated therewith, including genetic dysplasias of the organ, genetic or acquired immunologic deficiencies, thymoma associated with myasthenia gravis or with pure red cell anemia, thymic changes in systemic lupus erythematosus, and in some

THE CHEST RADIOGRAPH IN "JUVENILE" CIRRHOSIS (ACTIVE CHRONIC HEPATITIS).

The chest radiographs of 60 patients suffering from “juvenile” cirrhosis (active chronic hepatitis) were examined. Twenty-three patients with alcoholic cirrhosis were also studied. In 24 of the cases of juvenile cirrhosis the radiographs were abnormal. The abnormalities included pulmonary collapse, pleural effusion, cardiac enlargement, and mottled shadowing in the lung fields. There was a high incidence of disease of other organs, notably ulcerative colitis, Hashimoto's thyroiditis, and renal or joint changes of systemic lupus erythematosus. The relation of the radiographic changes to fluid retention, systematic lupus erythematosus, hyperkinetic circulation and intrapulmonary shunting is discussed.

CONTRASTING ABNORMALITIES IN THE THYMUS IN SYSTEMIC LUPUS ERYTHEMATOSUS AND MYASTHENIA GRAVIS: A QUANTITATIVE HISTOLOGICAL STUDY.

SummaryThe thymus was examined microscopically in two autoimmune diseases, systemic lupus erythematosus (9 cases) and myasthenia gravis (9 cases), and in control patients matched for age (14 cases). A quantitative method was developed for recording and comparing histological abnormalities.When compared with our controls the significant changes in systemic lupus erythematosus included total cortical atrophy, spindle epithelial cell aggregates in the medulla, increased cystic and scanty epithelial Hassall's corpuscles, and increased plasma cells: two of the nine thymuses contained germinal centres. The features in myasthenia gravis included preservation of the cortex and numerous germinal centres in the medulla. Thus the thymic pathology differs markedly in these two presumed autoimmune diseases.Thymic changes in these two diseases could reflect the result of an immuunological attack — humoral or cellular — against a vulnerable target organ—the thymus — or alternatively may indicate that a derangement of the thymus is a primary cause of autoimmune disease.

Carcinoma in Collagen Disease: With an Illustrative Case Report

The association of carcinomatous changes with lupus erythematosus of the skin has been recognised since 1886, when the first cases were described by Riessmeyer and also by Curie. In 1934 Uhlmann and Schambye’ were able to collect 107 cases from the literature. Kappesser2 analysed 140 cases in 1952 and calculated a maximal incidence of carcinomatous change of one in every 52 cases of lupus erythematosus of the skin. He found 81 of 87 of the tumours to be squamous cell carcinomas, four were basal-cell carcinomas and two were mixed-cell types. Schwarz3 (1953) found the incidence in the patients attending his clinic to be one in 213. Kopft demonstrated the first spindle-celled fibrosarcoma in such skin lesions in 1946 and Grasreiner and Sterba5 published a further spindle-celled fibrosarcoma in 1954. Tar carcinoma of a lupus erythematosus scar has been described by Rosmanith.#{176} Whether a specific etiologic relationship exists between these skin lesions and the malignant changes is controversial. Schwarz3 has outlined three possibilities: (a) the conjunction of the two conditions may be accidental; (b) the treatment of the lupus lesions by irritants such as caustics or irradiation, promotes the development of malignant change; (c) there is a specific predisposition to malignant change in the skin lesions of lupus erythematosus. In his series 10 per cent were previously untreated, and he concluded that the predisposition was not specific, but similar to that found with lupus vulgaris, burn scars, radiation damage, chronic light sensitivity, and other conditions in which skin atrophy occurs. In Montgomery’s7 experience there was a lower incidence of epitheliomatous change in lupus erythematosus than in lupus vulgaris. Whatever the ultimate conclusion about this relationship, there is no doubt that carcinomatous change is frequent in lupus erythematosus of the skin. We have not, however, been able to find a reference in any of the major publications on the subject to carcinomatous change occurring in other organs affected by the visceral changes of systemic lupus erythematosus. The association of malignant disease with other collagen diseases has been repeatedly noted in dermatomyositis. The first description of visceral changes in this disease by Urbach8 in 1930 was soon followed by Bezecny’s9 report of three cases with associated carcinoma of the ovary or breast.