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PubMed2001

The great pretender. Systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem disorder with a multitude of clinical symptoms and a wide variety of presentations. OBJECTIVE: To outline the variety of possible clinical presentations of SLE. DISCUSSION: Although joint symptoms and a rash are common at onset it may present as a neurological, cardiovascular or obstetric problem without more obvious clues to the diagnosis and lupus should be considered in the differential diagnosis of a wide variety of clinical problems. The prevalence of lupus, however, is low and over-reliance on a positive antinuclear antibody, especially at low titre, can lead to error, especially in the context of musculoskeletal symptoms.

Adolescent↗
PubMed2003

Analysis of polymorphisms affecting immune complex handling in systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a polygenic disorder of dysregulated inflammation. Numerous specific candidate genes have been identified and most relate to the handling of immune complexes or antigen presentation. This is consistent with the classic finding of immune complex deposition in affected end organs. We wished to examine combinatorial effects of polymorphic variants of genes involved in immune complex clearance in susceptibility to lupus. METHODS: This study examined the occurrence of polymorphisms in genes which encode proteins known to be involved in immune complex handling and clearance. Each polymorphic variant of a complement protein (C2, mannose binding protein and C4), complement receptor (CR1) or Fc receptor (FcgammaRIIA and FcgammaRIIIA) gene is known to affect function adversely. One hundred and sixty SLE patients and 212 control subjects were genotyped using polymerase chain reaction methods. RESULTS: We found an increasing association of SLE with increasing numbers of gene defects. Combinations of severe defects in FcgammaRIIA and FcgammaRIIIA were particularly deleterious for both African American and Caucasian patients, even though only one defective variant was individually statistically significantly associated with SLE. CONCLUSIONS: The results of the study suggest that genes may interact in ways that either synergize or modify the effect of a single genetic effect and imply that association studies must be interpreted within the genetic background of the populations.

Antigen-Antibody Complex↗
PubMed2004

Targeting interferon-alpha: a promising approach for systemic lupus erythematosus therapy.

System lupus erythematosus (SLE) is an autoimmune disease with multicellular pathogeneic components. Recent studies suggest an important role for interferon-alpha (IFN) in the immunopathogenesis of SLE. Data demonstrating a correlation between IFN-alpha and SLE disease severity range from elevated IFN-alpha levels in patients' serum and induction of IFN-regulated genes in peripheral blood mononuclear cells, to drug induced lupus disease in hepatitis C or cancer patients treated with recombinant IFN-alpha. In addition, mouse models of lupus in which the IFNR is deleted fail to develop disease manifestations. Thus, targeting IFN-alpha promises to be therapeutically efficacious for SLE.

Animals↗
PubMed2003

Poikilodermatous subacute cutaneous lupus erythematosus.

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) is a distinct subset of lupus erythematosus with unique clinical, immunological and genetic features. Among the unusual variants of SCLE, there is a poikilodermic presentation. However, to date, only 1 case of poikilodermatous SCLE has been reported. OBJECTIVE: Our goal was to summarize the clinical characteristics and course as well as the pathological, laboratory and immunofluorescence findings of 4 patients with poikilodermatous SCLE. METHODS: A retrospective study was conducted including 54 patients diagnosed as having SCLE between 1980 and 2002. RESULTS: Four patients (7.4%) had SCLE. All patients were alive, and none developed severe systemic involvement in up to 36 years (median, 24 years) after the onset of disease. The most noteworthy laboratory finding was the cutaneous deposition of amyloid. CONCLUSION: Poikilodermatous SCLE represents an uncommon variant within the clinicopathological spectrum of SCLE following a favorable course, in spite of extensive cutaneous involvement. Photosensitivity is the pathomechanism explaining, theoretically, the development of both poikiloderma and cutaneous amyloidosis in such cases.

Adult↗
PubMed1988

Cerebral systemic lupus erythematosus.

Cerebral systemic lupus erythematosus is uncommon in childhood. Three further cases are presented to draw attention to the unusual and varied clinical manifestations of this condition.

Brain Diseases↗
PubMedDate not supplied

Outpatient management of systemic lupus erythematosus.

SUMMARY: Systemic lupus erythematosus (SLE) is often managed by primary care practitioners, who must coordinate the care with the support of subspecialists. The management of patients with such a serious and chronic disease can be both rewarding and challenging. This article reviews common problems and suggests management strategies. KEY POINTS: Measurement of serum antinuclear antibodies can lead to an erroneous diagnosis if used as the sole basis for diagnosis. Infections are the leading cause of death in lupus patients, and immunizations and antibiotic prophylaxis need to be considered. Acute cutaneous SLE is exacerbated by exposure to ultraviolet light. Patients should avoid sun exposure. Specific treatment of cutaneous SLE includes topical corticosteroids and antimalarial agents. Some of the most perplexing problems seen in SLE relate to neuropsychiatric features. NSAIDs, corticosteroids, and antimalarials are the most commonly used medications for SLE.

Adrenal Cortex Hormones↗
PubMed2000

Neurologic, ophthalmic, and neuropsychiatric manifestations of pediatric systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune, multisystem disorder with diverse manifestations. There are limited reports on the neuro-ophthalmic and neuropsychiatric findings in childhood SLE. CASE REPORT: An 8-year-old patient with suspected SLE with a history of skin rash, joint pain, transient hematologic abnormality, headaches, seizures, and psychosis, presented with papilledema secondary to acquired, obstructive hydrocephalus. DISCUSSION: SLE-related ocular and neuropsychiatric findings are reviewed. Proposed mechanisms for ocular and cerebral lupus include immune complex deposition, vascular thrombosis, and postinflammatory lesions. CONCLUSION: The prevalent neurologic and neuropsychiatric complications of pediatric SLE require close follow-up and interdisciplinary management.

Child↗
PubMed2006

Rapamycin reduces disease activity and normalizes T cell activation-induced calcium fluxing in patients with systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin. Current treatment options are often ineffective or poorly tolerated. Recent observations have revealed mitochondrial hyperpolarization and enhanced Ca2+ fluxing in T cells from SLE patients. Rapamycin, a lipophilic macrolide antibiotic that regulates mitochondrial transmembrane potential and Ca2+ fluxing, has been used safely and effectively to treat renal transplant rejection since 1999. In addition, rapamycin has been shown to ameliorate T cell function and to prolong survival in lupus-prone MRL/lpr mice. We therefore undertook the present study to investigate whether rapamycin is beneficial in patients with SLE. METHODS: Nine patients with clinically active SLE that had been treated unsuccessfully with other immunosuppressive medications began therapy with rapamycin, 2 mg/day orally. Disease activity was assessed with the British Isles Lupus Assessment Group (BILAG) score, SLE Disease Activity Index (SLEDAI), and requirement for prednisone therapy. Mitochondrial transmembrane potential and Ca2+ fluxing were assessed by flow cytometry. RESULTS: In patients treated with rapamycin, the BILAG score was reduced by a mean +/- SEM of 1.93 +/- 0.9 (P = 0.0218), the SLEDAI by 5.3 +/- 0.8 (P = 0.00002), and concurrent prednisone use by 26.4 +/- 6.7 mg/day (P = 0.0062) compared with pre-rapamycin treatment. While mitochondrial hyperpolarization persisted, pretreatment cytosolic and mitochondrial Ca2+ levels and T cell activation-induced rapid Ca2+ fluxing were normalized in rapamycin-treated patients. CONCLUSION: Rapamycin appears to be a safe and effective therapy for SLE that has been refractory to traditional medications. Mitochondrial dysfunction and Ca2+ fluxing could serve as biomarkers to guide decisions regarding future therapeutic interventions in SLE.

Adolescent↗
PubMed1999

Neuropsychiatric systemic lupus erythematosus.

The systemic lupus erythematosus (SLE) patients with neuropsychiatric complaints requires a comprehensive and timely diagnostic approach. Despite the obvious difficulties in diagnosing neuropsychiatric SLE, the neurologic complications of SLE can be approached in a careful, logical manner with gratifying results.

Algorithms↗
PubMed2005

QT-interval parameters are increased in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) patients have increased cardiovascular morbidity and mortality. QT-interval parameters are presumed markers of cardiovascular risk and have not been previously evaluated in SLE. Standard 12-lead ECGs were obtained from 140 female SLE outpatients and 37 age and body mass index-matched controls. QT interval was measured in each lead and heart rate-corrected maximum QT-interval duration (QTcmax) and QT-interval dispersion (QTd) were calculated. Risk factors for cardiovascular disease and lupus clinical features, disease treatment, disease activity and damage index were recorded. SLE patients have increased QT-interval parameters when compared to controls (QTcmax: 427.91 +/- 31.53 ms(1/2) versus 410.05 +/- 15.45 ms(1/2), P < 0.001; QTd: 52.38 +/- 22.21 ms versus 37.12 +/- 12.88 ms, P < 0.001). These differences persisted after excluding those patients with arterial hypertension, diabetes and with ECG abnormalities (QTcmax: 419.90 +/- 28.78 ms(1/2) versus 409.15 +/- 15.85 ms(1/2), P = 0.041; QTd: 54.74 +/- 26.00 ms versus 37.96 +/- 13.05 ms, P = 0.001). Multivariate linear regression for factors associated with QTcmax selected the presence of electrocardiographic left ventricular hypertrophy (ECG-LVH) (P = 0.003), nonspecific ST-T-wave abnormalities (P = 0.022) and left atrial enlargement (P = 0.044). Multivariate associates with QTd were age (P = 0.018), ECG-LVH (P = 0.022) and ST-T abnormalities (P = 0.031). In conclusion, SLE patients have increased QT interval parameters when compared to controls. This prolongation may lead to an increased cardiovascular risk. This finding might be due to subclinical atherosclerotic cardiovascular disease.

Adult↗
PubMed2005

Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients.

OBJECTIVE: To determine to what extent the diagnosis of systemic lupus erythematosus (SLE) in deceased lupus patients is under-reported in death certificates, and the patient characteristics associated with such an occurrence. METHODS: The death certificates of 76 of the 81 deceased SLE patients from two US lupus cohorts (LUMINA for Lupus in Minorities: Nature vs Nurture and CLU for Carolina Lupus Study), including 570 and 265 patients, respectively, were obtained from the Offices of Vital Statistics of the states where the patients died (Alabama, Georgia, North Carolina, South Carolina, Tennessee and Texas). Both cohorts included patients with SLE as per the American College of Rheumatology criteria, aged > or =16 yr, and disease duration at enrolment of < or =5 yr. The median duration of follow-up in each cohort at the time of these analyses ranged from 38.1 to 53.0 months. Standard univariable analyses were performed comparing patients with SLE recorded anywhere in the death certificate and those without it. A multivariable logistic regression model was performed to identify the variables independently associated with not recording SLE in death certificates. RESULTS: In 30 (40%) death certificates, SLE was not recorded anywhere in the death certificate. In univariable analyses, older age was associated with lack of recording of SLE in death certificates [mean age (standard deviation) 50.9 (15.6) years and 39.1 (18.6) yr among those for whom SLE was omitted and included on the death certificates, respectively, P = 0.005]. Patients without health insurance, those dying of a cardiovascular event and those of Caucasian ethnicity were also more likely to be in the non-recorded group. In the multivariable analysis, variables independently associated with not recording SLE as cause of death were older age [odds ratio = (95% confidence interval) 1.043 (1.005-1.083 per yr increase); P = 0.023] and lack of health insurance [4.649 (1.152-18.768); P = 0.031]. CONCLUSIONS: A high proportion of SLE diagnoses are not recorded in death certificates. Older patients and those without health insurance are more prone to have SLE not recorded. These findings do have implications for the assessment of the impact of this disease in epidemiological studies conducted using vital statistics records.

Adolescent↗
PubMed2004

Gender differences in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is known to be much more prevalent in females than in males, but the cause of this sexual predilection is not established. In addition, much controversy surrounds the differences in manifestations of SLE in both sexes. OBJECTIVE: This article reviews the possible etiologies of the greater prevalence of SLE in females, as well as the differences in the clinical presentation of the disease in both sexes. METHODS: Relevant studies were identified through a PubMed search for articles published between 1960 and 2001; no language restrictions were applied. Search terms included lupus, SLE, and gender differences. Books and online resources were also consulted. RESULTS: Potential causes of the female predilection for SLE included the effects of estrogen and its hydroxylation, decreased androgen levels, hyperprolactinemia, and differences in gonadotropin-releasing hormone (GnRH) signaling. Clinical manifestations of SLE included females having more frequent relapses, but the incidence of severe relapses was the same in both sexes. Raynaud phenomenon, arthritis, and leukopenia were more common in women, whereas skin manifestations, serositis, and renal involvement were more common in men. For neurologic manifestations, females with SLE experienced more psychiatric symptoms and headaches, whereas males with SLE experienced more seizures and peripheral neuropathy. Males with SLE also tended to have more severe renal disease and cardiorespiratory involvement. CONCLUSIONS: The increased frequency of SLE among women may be attributed to differences in the metabolism of sex hormones and/or GnRH. Though less common in men, when it does occur SLE tends to run a more severe course-an important consideration in the diagnosis and follow-up of male patients with SLE.

Female↗
PubMed1984

Exophthalmos in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE) exophthalmos is distinctly rare. This article describes the first patients with SLE in whom exophthalmos was preceded by pseudotumor cerebri. The apparent lack of resolution of the exophthalmos with corticosteroids in our case emphasizes the potential need for therapeutic alternatives such as immunosuppressive agents, orbital irradiation, and/or plasmapheresis.

Adult↗
PubMedDate not supplied

Lack of type C virus antibodies in systemic lupus erythematosus.

Twelve systemic lupus erythematosus (SLE) and 10 normal sera were similarly reactive in an assay for cytotoxic antibody to type C virus-infected and uninfected cells, but both were less cytotoxic for infected cells. Thus antibodies to type C viruses were not detected in SLE or normal sera, but type C infection may interfere with antibody recognition of other cell membrane antigens.

Animals↗
PubMed2002

Pregnancy in women with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder which may be affected by hormonal changes, such as those of pregnancy. Women with SLE have increased adverse pregnancy outcomes. STUDY DESIGN: A retrospective analysis of the gynecologic and immunologic case history of 140 women with SLE and the outcome of 263 pregnancies in 99 women with SLE. RESULTS: In patients diagnosed with SLE, the proportion of pregnancies ending with live birth at term decreased to one-third compared with three quarters in those without a diagnosis of SLE and the incidence of pre-term deliveries and spontaneous abortions increased by 6.8 and 4.7 times, respectively. When SLE was associated with secondary antiphospholipid (APL) syndrome, and lupus anticoagulant (LA) or beta2-glycoprotein antibodies were present, a further increase in the incidence of pregnancy loss was observed. Pregnancy did not cause a flare-up of SLE in all cases, the disease remained stable in about 30% of the patients. Lupus was mild in the majority of the women who carried out their pregnancy to term. We also observed mothers with active SLE who successfully carried out pregnancies to term. CONCLUSION: These findings accord with previous literature and should inform rheumatologists, obstetricians and neonatologists who guide patients in their reproductive decisions.

Adolescent↗
PubMed2006

Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Published data have revealed that serum levels of proinflammatory cytokines are increased in SLE patients. The aim of our study was to evaluate whether monotherapy with chloroquine phosphate affects IL-1beta, IL-6, IL-18 and TNF-alpha serum levels in SLE patients. The study group consisted of 25 SLE patients with mild or moderate disease activity and 25 age- and sex-matched healthy control subjects. In SLE patients the cytokine levels were measured just before and three months after starting chloroquine treatment at a dose of 125 mg twice daily. Although the majority of SLE patients had a low systemic lupus activity measure (SLAM) index, the levels of IL-6, IL-18 and TNF-alpha were significantly higher than in the control group. After three-months of chloroquine therapy the mean level of IL-6, IL-18 and TNF-alpha decreased significantly. Minimal erythema doses (MEDs) were significantly increased in SLE patients after three months of chloroquine therapy. The results indicate that chloroquine treatment lowers some proinflammatory cytokines and may provide a photoprotective effect.

Adult↗
PubMed1997

Role of autoantibody tests in the diagnostic evaluation of neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) can be defined as a significant and unequivocal change in the baseline neurologic and psychiatric function identified by history and physical examination. NPSLE can involve the central nervous system and/or the peripheral autonomic nervous system. This article reviews the clinical manifestations, pathology, and immunopathogenesis of NPSLE. The use and importance of diagnostic procedures including autoantibody assays in the evaluation of NPSLE are discussed.

Autoantibodies↗