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MRI and the brain in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) can affect any part of the central nervous system (CNS) from the cerebrum to the cauda eqina, giving rise to diverse neurological mainfestations. Despite clinically apparent symptoms and signs, imaging will commonly be normal while at times the magnitude of changes demonstrated on MRI may be out of proportion to the clinical presentation. We describe the MRI techniques used in CNS imaging and the pattern of presentation in SLE.

Brain↗

Some controversies of neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is accompanied by several features that can be attributed to involvement of the central or peripheral nervous system. The etiology and pathogenesis of these manifestations are mostly unknown. To which degree these neuropsychiatric conditions can be explained on the basis of chronic illness, or as part of the disease spectrum of SLE, is also a matter of debate. Some of the controversial issues on these matters are discussed in the article.

Fatigue↗

The potential pathogenetic link between peripheral immune activation and the central innate immune response in neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology. Neuropsychiatric disturbances unexplained by drugs or by other untoward manifestations of disease are present in up to one-half of SLE patients and have profound economic and social impact. In patients with neuropsychiatric SLE, structural lesions have been identified in the hippocampus and proinflammatory cytokines have been detected in the cerebrospinal fluid. Similarly, murine models of lupus, such as MRL-lpr/lpr mice display behavioral disturbances which map to the hippocampus and exhibit overexpression of proinflammatory cytokine genes in hippocampal homogenates. Neuropsychiatric SLE typically occurs in the presence of serologically and clinically active lupus. In animal models of SLE, such as MRL-lpr/lpr, NZB, BXSB, and [NZB x NZW]F(1), uncontrolled autoreactivity in the periphery is accompanied by behavioral disturbances that are chronic and progressive. These observations suggest the hypothesis that central nervous system disease in SLE is driven by cross-talk between the peripheral immune system and the brain's innate immune system, which results in the inexorable activation of astrocytes, microglia, and/or neurons within the hippocampus. This leads to overproduction of brain cytokines, which induce the synthesis of pro-oxidant molecules, such as eicosanoids and reactive oxygen species, with resultant tissue injury. The cascade becomes self-perpetuating and eventuates in neuronal death, which is followed by impaired cognition. A better understanding of the molecular events that operate in the pathogenesis of neuropsychiatric SLE may provide the basis for a more rational therapeutic approach to this incompletely understood disease.

Animals↗

A Potential Role for PGE and IL-14 (HMW-BCGF) in B-Cell Hyperactivity of Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a disease characterized by the prolonged production of high-affinity autoantibodies resulting in direct and immune complex-mediated tissue damage. Because autoantibody responses occur over several years, memory B cells are likely to be involved. Interleukin-14 (IL-14) is a cytokine implicated in the generation and maintenance of normal memory B cells. Many of the actions of IL-14, including inhibition of antibody synthesis and upregulation of IL-14 receptors (IL-14R), are dependent on the formation of prostaglandin E (PGE) and subsequently cAMP. We observed that IL-14 induces phospholipase A(2) (PLA(2))-dependent release of arachidonic acid from phosphatidylcholine and phosphatidylinositol. Production of PGE is blocked by the PLA(2) inhibitor bromophenacyl bromide. Exogenous PGE (misoprostol) induces similar inhibition of antibody synthesis and increases in IL-14R as IL-14. Lymphocytes from patients with inactive SLE were noted to spontaneously produce PGE. Lymphocytes from normal donors produced PGE only after Sac-activation and IL-14 stimulation. Peripheral B and T lymphocytes from SLE patients, but not normal donors, spontaneously produced IL-14. Increased numbers of peripheral B lymphocytes from patients with inactive SLE expressed IL-14R, when compared to normal donors. Thus, increased production of IL-14 and PGE in SLE may result in expansion of a memory B-cell population capable of long-term autoantibody production. Further study will be necessary to confirm these preliminary findings and to examine in greater depth the regulation of PGE and IL-14 in SLE patients and normal donors.

Journal Article↗

Health-related quality of life and support group attendance for patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with variable symptoms. Severity of disease has been associated with mental and physical health-related quality of life (HRQoL). The potential effects of support groups have not been examined. We examined the possible improvement in mental and physical HRQoL of women with SLE who attended support groups. Thirty-four women who attended support groups and 71 comparison women with SLE were recruited. Self-administered surveys included the Medical Outcomes Study Short-Form 36 (SF-36) and a 3-level rating of disease activity.Mean SF-36 Mental Health Summary Scale scores (MCS) were significantly lower for women attending groups (31.5) compared with nonattending SLE women (39.8). MCS scores were lower for blacks compared with whites (33.7 vs. 39.2, P <0.05). Women with high and moderate disease activity had lower MCS scores compared with those with low activity (28.6 or 35.6 vs. 42.7, P <0.05). In linear regression, 27% of the variation in MCS was explained by support group attendance, disease activity, race, and age.Overall, women with SLE reported lower MCS and physical health summary scales (PCS) scores than published population values, indicating markedly reduced quality of life. Any potential positive effects of support groups will need to be tested in a prospective random design to assess improvements in HRQoL.

Journal Article↗

Interstitial lung disease in systemic lupus erythematosus.

Systemic lupus erythematosis (SLE) is a heterogenous disease of unknown etiology. It is not uncommon to see pleuropulmonary involvement in isolation or along with the involvement of other organ systems in SLE. Pulmonary manifestations of SLE can involve the pleura, lung parenchyma, airways, pulmonary vasculature, and the respiratory muscles. In this review we discuss two important pulmonary manifestations of SLE: acute lupus pneumonitis and diffuse interstitial lung disease. These two conditions have a major impact on the mortality and morbidity of patients with SLE and it is essential to recognize and treat them appropriately. High-resolution computed tomographic scans of the chest and pulmonary function tests help to establish a diagnosis and aid long-term follow-up of these patients. High-dose corticosteroids are the mainstay of treatment for the two conditions, although other agents such as cyclophosphamide, azathioprine, intravenous gamma globulin, and plasmapheresis have been used with varying degrees of success.

Acute Disease↗

The circulating lymphocyte profiles in patients with discoid lupus erythematosus and systemic lupus erythematosus suggest a pathogenetic relationship.

BACKGROUND: Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are chronic inflammatory diseases of unknown aetiology; the relationship of DLE with SLE has been a subject of debate for many years. OBJECTIVES; To find evidence for systemic immune activation in DLE by analysis of the immunophenotypic profiles of circulating lymphocytes, and to compare these changes with those in patients with SLE. METHODS: The immunophenotypic profile of peripheral blood lymphocyte subsets from 23 DLE patients without clinical or laboratory evidence of systemic disease, 25 SLE patients and 38 healthy donors was characterized by two-colour immunofluorescence flow cytometry analysis. None of the patients was receiving corticosteroid or immunosuppressive treatment. RESULTS: Patients with DLE had increased numbers of circulating HLA-DR+ CD3+ T cells and HLA-DR+ CD4+ T cells, indicating systemic T-cell activation, and an expansion of CD5+ CD19+ B cells. Decreased numbers of T-cell subsets expressing the differentiation markers CD11b and CD16/56, and of CD16/56+ natural killer cells were also found. In SLE, the changes were similar but more pronounced. In addition, a profound CD4+ T-cell lymphopenia and an increase of HLA-DR+ CD8+ T cells were found only in SLE. CONCLUSIONS: Our data provide evidence for systemic activation of the cellular immune system in patients with purely cutaneous DLE. Similarities in the lymphocyte immunophenotypic profiles in patients with DLE compared with SLE suggest that there are common immunopathological processes in these two conditions.

Adolescent↗

OxLDL/beta2GPI complexes and autoantibodies in patients with systemic lupus erythematosus, systemic sclerosis, and antiphospholipid syndrome: pathogenic implications for vascular involvement.

Oxidized low-density lipoprotein (oxLDL) interacts with beta2GPI, forming oxLDL/beta2GPI complexes. Autoimmune vascular inflammation (and oxidative stress) may promote the formation of these complexes. The coexistence of oxLDL/beta2GPI complexes with autoantibodies to these complexes suggests an active pro-atherogenic role in vascular thrombosis and atherosclerosis. Immunoglobulin G (IgG) anti-oxLDL/beta2GPI antibodies have been regarded as pro-atherogenic, whereas IgM antibodies are thought to be anti-atherogenic. For this study, oxLDL/beta2GPI complexes, IgG, and IgM anti-oxLDL/beta2GPI antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Measurements were taken in two patient groups: (1) those with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA); and (2) those with primary and secondary antiphospholipid syndrome (APS). For oxLDL/beta2GPI complexes, SLE and SSc patients had the highest mean optical densities (ODs) (P <.001), followed by RA (P = .139) and healthy controls. IgG anti-oxLDL/beta2GPI antibody distribution followed the same pattern observed with oxLDL/beta2GPI complexes, SLE and SSc (P <.001), RA (P = .08), and controls. IgM antibodies showed a reverse pattern, with the highest mean OD in RA (P <.001), followed by SSc (P = .007) and SLE (P = 143). Both IgG and IgM anti-oxLDL/beta2GPI antibodies were significantly higher in secondary APS patients compared with SLE controls without APS. In addition, the highest mean OD and prevalence of IgG anti-oxLDL/beta2GPI antibodies were observed in APS patients with a history of arterial thrombosis. These results may reflect the widespread vascular involvement seen in SLE and SSc, in contrast to the relatively low vascular involvement in RA. In SLE and SSc, high serum levels and prevalence of circulating oxLDL/beta2GPI complexes and IgG anti-oxLDL/beta2GPI antibodies indicate significant vascular oxidative stress as well as a possible pathogenic role in autoimmune-mediated atherosclerosis.

Antiphospholipid Syndrome↗

Antibodies to ribonucleic acids detected by ELISA in systemic lupus erythematosus, systemic sclerosis and rheumatoid arthritis.

The natural and synthetic antiribonucleic acid antibodies (anti-RNA) are more frequently found in systemic lupus erythematosus (SLE) (80%) than in systemic sclerosis (66%) or in rheumatoid arthritis (RA) (54.5%). SLE sera contain antibodies directed against a broader variety of RNA than systemic sclerosis sera and most RA sera. Fifty-two percent of SLE and 29.2% of systemic sclerosis sera recognized at least 5 of the 7 RNA types studied, whereas RA sera recognized only one or 2. Synthetic antipolynucleotide antibody activities are mainly antipolyriboguanylic-ribocytidylic acid (prG-rC), antipolyriboadenylic-ribouridylic acid (prA-rU) and polyriboadenylic acid (prA) antibody in SLE, antipolyriboguanylic acid (prG) and antipolyribocytidylic acid (prC) antibody in systemic sclerosis and anti-prG-rC, anti-prC antibody in RA.

Arthritis, Rheumatoid↗

A case of overlap syndrome with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and secondary Sjögren's syndrome.

We report an unusual case of overlap syndrome that had the coexistence of five autoimmune diseases. A 45-year-old woman initially developed seropositive erosive rheumatoid arthritis (RA) 11 years ago. She then developed progressive systemic sclerosis (PSS) (including pulmonary hypertension, esophageal dysfunction, cardiac involvement and sclerodactilitis), systemic lupus erythematosus (SLE) (including photosensitivity, nephritis, leukopenia, lymphopenia, thrombocytopenia and Coombs positive hemolytic anemia and positive anti-dsDNA), and secondary Sjögren's syndrome (SSS) in the last 7 years before she was admitted to our clinic. The patient fulfilled classification criteria for RA, SLE, PSS and SSS, as determined by American College of Rheumatology. Hypothyroidism with positive autoantibodies due to Hashimoto's thyroiditis, the beginning of which could not be defined, was coexistent with this overlap syndrome. In the literature, although overlap syndromes in different combinations were reported, we very rarely observed a complex case like this patient. In our opinion, this is the first well-documented case of RA, PSS, SLE, SSS and Hashimoto's thyroiditis existing together in the same patient. Although immunosuppressive therapy was administered, the disease rapidly deteriorated and the patient died.

Arthritis, Rheumatoid↗

Malignant lymphoma in patients with systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis): a clinicopathologic study of 24 Japanese cases.

We conducted clinicopathologic and immunohistochemical analyses of the prevalence of Epstein-Barr virus (EBV) among 24 patients with malignant lymphoma complicating systemic rheumatic diseases. (SRD) These 24 patients included 17 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 2 with systemic sclerosis (SS), and 2 with dermatomyositis (DM). There were 2 men and 22 women ranging in age from 30 to 86 years (mean: 64 years). The interval between the onset of rheumatic disease and that of malignant lymphomas ranged from 3 months to 35 years (mean: 142 months). The use of immunosuppressive drugs before the onset of malignant lymphoma was recorded in 15 patients. Among them, 5 patients received methotrexate (MTX) therapy. Malignant lymphomas were found at extranodal sites in 9 patients, and the disease was in the advanced stage in 17 patients. Histologic and immunohistochemical studies demonstrated that 18 cases (75%) were B-cell lymphoma (RA=12, SLE=2, SS=2, DM=2), 3 (12.5%) were peripheral T-cell lymphoma (RA=3), and 3 (12.5%) were classical Hodgkin lymphoma (RA=2, SLE=1). As in previous reports, there was an increased frequency of diffuse large B-cell lymphoma (50%) in the present series. Moreover, a majority of the diffuse large B-cell lymphomas exhibited activated B-cell phenotype. EBV-encoded small RNAs (Epstein-Barr early region [EBER]-) and/or LMP-1+tumor cells were identified in only 3 cases of classical Hodgkin lymphomas. Our findings suggested EBV-associated lymphoma comprised only a small fraction of all non-Hodgkin's lymphomas in the general SRD patient population.

Adult↗

Choroiditis in systemic lupus erythematosus: systemic steroid therapy and focal laser treatment.

PURPOSE: To report a rare case of choroiditis in association with systemic lupus erythematosus (SLE). CASE: A 49-year-old woman with a 17-year history of SLE experienced acute vision impairment of her left eye during the remission stage of systemic SLE. Fundus examination revealed a gray-white subretinal exudate with serous retinal detachment. Angiographic examination disclosed choroidal inflammation at the macula and a breakdown of the blood retinal barrier. Retinal burns were applied to the subretinal exudate with an argon laser as in the treatment of central serous retinopathy. Afterward, her visual acuity showed prompt recovery due to the regression of the serous retinal detachment. However, the choroidal inflammation remained until the systemic condition was controlled with steroid therapy. RESULTS: Laser treatment of a subretinal exudate was helpful for the resolution of serous detachment and the prompt improvement of visual acuity, whereas systemic steroid therapy was effective for choroidal inflammation. CONCLUSIONS: Systemic steroid therapy is thought to be effective for SLE choroiditis; however, this therapy is also known to cause serous retinal detachment. Thus, in SLE choroiditis, laser photocoagulation at a leakage point, in addition to systemic steroid therapy, may be helpful for the prompt restoration of vision in patients with serous retinal detachment.

Blood-Retinal Barrier↗

Subacute cutaneous lupus erythematosus versus systemic lupus erythematosus: diagnostic criteria and therapeutic implications.

BACKGROUND: The nosologic position of subacute cutaneous lupus erythematosus (SCLE) is controversial. More than four American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE) are found in a proportion of patients diagnosed as having SCLE; thus such cases could be classified as SLE. OBJECTIVE: Our purpose was to determine whether ARA criteria for SLE are helpful in differentiating SCLE from SLE and whether cutaneous and visceral changes, immunologic findings, and photosensitivity provide a basis for diagnosis of SCLE. METHODS: A cohort of 143 patients (79 with SCLE, 58 with SLE, and six with overlapping features of SCLE and SLE) was studied clinically, histologically, and immunologically as well as by phototesting. The patients were observed for up to 10 years, and the course of the disease and response to therapy were evaluated in each group. RESULTS: SCLE differed from SLE by cutaneous changes, significantly less frequent kidney involvement, serositis and arthritis, and the rare presence of double-stranded DNA, U1RNP, and Sm antibodies characteristic of SLE. Ro(SS-A) and La(SS-B) antibodies were detected with similar frequency, and photosensitivity was not related to the presence of Ro antibody. In contrast, photoreproduction (appearance of LE lesion in irradiated area) was significantly more frequent in patients with SCLE. The course of SCLE in older patients was less severe than in younger patients, and aggressive therapy was usually not required. CONCLUSION: Patients with SCLE (although the majority fulfill more than four ARA criteria for SLE) show significant differences from those with SLE in terms of cutaneous and visceral involvement, immunologic findings, photosensitivity, course of the disease, and the requirement for therapy. Therefore SCLE should be recognized as a separate subset. However, cases of overlapping SLE and SCLE suggest a close relation.

Adult↗

Cutaneous lupus erythematosus without systemic lupus erythematosus: clinical and laboratory features.

Sixty-seven patients with cutaneous lupus erythematosus (CLE) were followed up as part of a series of 570 lupus erythematosus patients seen in a private practice between 1980 and 1989. Clinical and laboratory features, treatment, and natural course were observed. Findings of interest included (1) a ratio of at least one CLE case for every seven cases of systemic lupus erythematosus (SLE); (2) occurrence of CLE in fewer women and apparently associated with an older age at diagnosis than SLE; (3) similar frequency of cutaneous lupus subsets in CLE and SLE; (4) strong family history for SLE but not CLE in CLE patients; (5) other cutaneous and musculoskeletal features in a majority of CLE patients and constitutional symptoms in 10%; (6) positive ANA titers, high sedimentation rates, and leukopenia common in CLE; (7) anticardiolipin antibody in 31% of CLE patients but not associated with systemic complications; (8) antimalarials required by 75% of patients and systemic steroids by 33%; and (9) an excellent prognosis associated with CLE, organ-threatening disease being rare.

Adult↗