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PubMed1999

CYP2C19 genotype does not represent a genetic predisposition in idiopathic systemic lupus erythematosus.

BACKGROUND: The aetiology of systemic lupus erythematosus (SLE) is still unknown. In several cases, however, chemicals or drugs were identified as aetiological agents and associations with certain phenotypes of drug metabolising enzymes have been reported. The purpose of this study was to discover if there is an association between CYP2C19 polymorphism and susceptibility to SLE. METHODS: Racemic mephenytoin (100 mg orally) was given to healthy volunteers (n = 161) and SLE patients (n = 37) and then S-mephenytoin and R-mephenytoin were determined in eight hour urine samples. A 10 ml blood sample was obtained from healthy volunteers (n = 80) and SLE patients (n = 69) for genotypic assay. Each blood sample was tested for the detection of CYP2C19*1 and CYP2C19*2 (formerly wt and m1 respectively) by oligonucleotide ligation assay. RESULTS: The ratio of S/R-mephenytoin ranged from < 0.1 to 1.293 in healthy subjects and from < 0.1 to 1.067 in SLE patients. PM phenotype was observed in 2 of 37 patients with idiopathic SLE (5.4%) and 6 of 161 healthy subjects (3.7%). There were no significant differences in the frequency of PM phenotypes between the groups (Fisher's exact test, p = 0.64) or in the frequency distribution profiles of ratios of S-mephenytoin to R-mephenytoin. No significant differences in distribution of overall genotypes and in allele frequencies were observed between the two groups. No significant relation was found between clinical features and the overall genotype. CONCLUSION: The results of this study indicate that CYP2C19 genotype does not represent a genetic predisposition in idiopathic SLE patients.

Adult↗

PubMed2004

Infective thyroiditis in two cases of systemic lupus erythematosus.

We report on two patients with systemic lupus erythematosus, both of whom developed suppurative thyroiditis. One suffered from Staphylococcus aureus-induced thyroiditis and the other had tuberculous thyroiditis. The occurrence of tuberculous thyroiditis in systemic lupus erythematosus has not previously been reported. The diagnoses were made by fine-needle aspiration biopsy and subsequent bacteriological confirmation. Transient alteration of thyroid function was observed in both patients. In patients with systemic lupus erythematosus who present with fever and anterior neck pain, infection of the thyroid gland should be considered, and appropriate investigations undertaken.

Adult↗

PubMed1987

Nifedipine in the treatment of hypertension in systemic lupus erythematosus.

Treatment of hypertension in systemic lupus erythematosus (SLE) may be complicated by unwanted immunologic vascular and renal side effects of drugs. The safety of long-acting nifedipine tablets was studied in 8 SLE hypertensive subjects for six months. Nifedipine reduced blood pressure from a mean 151.9 +/- 10/103.7 +/- 8.6 mmHg to a mean of 130 +/- 14.1/87.5 +/- 5 mmHg. There was no deterioration of renal function or of hematologic or immunologic indices during that period. We believe nifedipine is a safe and effective hypotensive drug in SLE, either alone or combined with beta blockers and diuretics.

Antibodies↗

PubMed2005

Sources of autoantigens in systemic lupus erythematosus.

PURPOSE OF REVIEW: A hallmark of systemic lupus erythematosus is the production of autoantibodies that recognize nuclear antigens. However, the underlying events and mechanisms that lead to the selection of these molecules for the autoimmune response remain poorly understood. In this review, we will examine some of the proposed explanations for sources of systemic lupus erythematosus-specific autoantigens. We will focus on events related to apoptosis, viral infection, cytokine production, innate immune system components, and alternative splicing of pre-mRNA transcripts. RECENT FINDINGS: Definitive proof of a viral etiology for lupus remains elusive. However, recent observations have added to increasing evidence that viruses contribute to the bypass of tolerance in systemic lupus erythematosus. Also, events associated with apoptosis - most notably proteolytic autoantigen cleavage by caspases and granzyme B - have been implicated in the initiation of autoimmune responses for over a decade. Results obtained from animal models and human systems suggest complex functions for pro-apoptotic pathways in the regulation of immune responses. Inducible antigen expression and alternatively spliced transcripts may represent additional ways of generating autoantigenic material. Finally, toll-like receptor family members may play critical roles in the induction of antibody responses to nucleic acids in systemic lupus erythematosus. SUMMARY: Several factors may contribute to the generation of systemic lupus erythematosus-specific autoantigens. Determining the underlying causes of autoantibody production may provide important insight into the etiology and pathogenesis of this disease.

Animals↗

PubMed1999

Orbital infarction and melting in a patient with systemic lupus erythematosus.

OBJECTIVE: To present a patient with systemic lupus erythematosus who developed infarction and melting of the orbit secondary to her systemic disease. DESIGN: A case report. PARTICIPANT: A 61-year-old white woman with a 5-year history of systemic lupus erythematosus. METHODS: The patient presented with left orbital pain, limitation of extraocular movements, and a fistula from the ethmoid sinus to the upper eyelid. A detailed examination with computerized tomography, ultrasound, and a comprehensive medical evaluation with laboratory testing was performed. Histopathologic analysis with special stains of the orbital tissues was also performed. RESULTS: Histopathologic examination of the biopsy specimens revealed the features of an inflammatory process involving the orbit, similar to a panniculitis. These include a lymphocytic reaction with a predominance of plasma cells, vasculitis with occlusion, and thickening of the vessel walls, necrosis, and hyalinization of fat. CONCLUSION: This is a unique case in which infarction and melting of the entire orbital structures occurred in the presence of systemic lupus erythematosus. The underlying disease process is a lupus-related panniculitis. The authors stress that this is a very rare entity and that other diseases should be ruled out before entertaining this diagnosis.

Eye Diseases↗

PubMed1995

[Systemic lupus erythematosus in children in Israel].

Systemic lupus erythematosus (SLE) is a rare disease in children that might possibly be modulated by genetic and environmental factors. In order to delineate the characteristic features of SLE among Israeli children, we reviewed the medical records of 38 cases from 8 pediatric rheumatology clinics. All fulfilled the 1982 American Rheumatism Association revised criteria for SLE. The illness became apparent at the age of 16 years or younger and the mean age of onset was 11.9 +/- 2.4 y (range 7-16) and the mean duration of follow-up 4.0 +/- 4.8 y (range 0.5-15). The female to male ratio was 2.8:1; 28 were Jewish and 10 Arabs. Systemic complaints, such as fever, malaise and weight loss, were noted in 90%, malar rash in 65%, and other skin manifestations in 40%. Arthritis was noted in 57% and additional musculoskeletal complaints in 70%; 90% had hematological abnormalities. Major organ system involvement included: renal disease in 50% pulmonary involvement 28% and CNS involvement 28%. 2 patients are currently on renal dialysis and 1 died from hypertensive crisis. We conclude that the features of SLE in children in Israel are not influenced by ethnic or geographic factors, and are similar to those reported worldwide.

Adolescent↗

PubMedDate not supplied

[Seronegative systemic lupus erythematosus (author's transl)].

Seronegative systemic lupus erythematosus is defined as a SLE devoided of antinuclear factors as well as of LE cells when at least 4 out of the 14 ARA criteria are present. We describe herein two case reports and review previous literature concerning this topic. This kind of SLE is characterized by a high incidence of Raynaud's disease, photosensitivity, oral ulcerations, alopecia and perhaps less frequent kidney and central nervous system involvement. The hypotheses about the absence of ANF are discussed. The awareness of such a SLE ("devoided of ANF rather than" seronegative") is to be kept in mind from a chemical, therapeutic and pathophysiologic point of view.

Adult↗

PubMed1988

Choroidopathy in systemic lupus erythematosus.

Choroidopathy in association with systemic lupus erythematosus (SLE) is a clinically unusual manifestation, previously described in only six patients, to our knowledge. We have followed up six patients with SLE and choroidopathy manifested by multifocal, serous elevations of the retinal pigment epithelium and sensory retina. In four patients, macular involvement was present, and they suffered visual loss. Two eyes of two patients progressed to large, bullous, exudative retinal detachments. In the three patients in whom control of the systemic disease was achieved, the serous detachments resolved. The pathogenesis is most likely related to choroidal vascular disease with resultant pigment epithelial damage and serous fluid leakage beneath the retina.

Adult↗

PubMed1984

Systemic lupus erythematosus with membranous lupus nephropathy in Malaysian patients.

Thirty-one patients with systemic lupus erythematosus had membranous lupus nephropathy (MLN). They were divided into two groups. Group I consisted of 13 patients who had pure MLN but the patients in Group 2 had segmental proliferation in up to 35 per cent of their glomeruli. The rest of the glomeruli had purely membranous change. The patients of Group 2 were no different from the other MLN patients in terms of age, sex and race. The extrarenal disease in both groups was extensive and severe. The renal disease was usually associated with the nephrotic syndrome or oedema but was asymptomatic throughout in one patient. Both renal and extrarenal features responded to treatment initially but relapses were frequent and often severe. Relapses often occurred as treatment was discontinued or medication reduced. Survival at six years in Group I was 62 per cent and in Group 2 was 50 per cent. Only one patient died with renal failure although five patients had impaired renal function at death. The chief causes of death were disease of the central nervous system and infection.

Adolescent↗

PubMed2005

Defective B cell tolerance checkpoints in systemic lupus erythematosus.

A cardinal feature of systemic lupus erythematosus (SLE) is the development of autoantibodies. The first autoantibodies described in patients with SLE were those specific for nuclei and DNA, but subsequent work has shown that individuals with this disease produce a panoply of different autoantibodies. Thus, one of the constant features of SLE is a profound breakdown in tolerance in the antibody system. The appearance of self-reactive antibodies in SLE precedes clinical disease, but where in the B cell pathway tolerance is first broken has not been defined. In healthy humans, autoantibodies are removed from the B cell repertoire in two discrete early checkpoints in B cell development. We found these checkpoints to be defective in three adolescent patients with SLE. 25-50% of the mature naive B cells in SLE patients produce self-reactive antibodies even before they participate in immune responses as compared with 5-20% in controls. We conclude that SLE is associated with abnormal early B cell tolerance.

Adolescent↗

PubMed2005

Bullous Systemic Lupus Erythematosus as an Initial Manifestation of SLE.

Bullous systemic lupus erythematosus (BSLE) is a rare subset of systemic lupus erythematosus that is often associated with autoimmunity to type VII collagen. We describe a 45-year-old woman with BSLE who presented with vesiculobullous lesions as an initial manifestation of SLE. The patient first noticed a widespread urticarial, erythematous eruption associated with tense blisters, erosions, and crusting. She was diagnosed with bullous pemphigoid and underwent a one-month course of treatment with betamethazone. Because of the appearance of marked proteinuria, a subsequent renal biopsy, and serological tests, the patient was diagnosed with rapidly progressive glomerulonephritis and systemic lupus erythematosus. The patient's IgG circulating antibodies labeled the dermal floor of salt-split skin and recognized type VII collagen in immunoblot studies. Although methylprednisolone pulse therapy for glomerulonephritis did not alleviate the vesicullobullous eruption, treatment with dapsone resulted in dramatic disappearance of the lesions. Cessation of dapsone therapy due to hemolysis with Heinz-body formation did not aggravate the bullous disease. Our case illustrates that a generalized vesiculobullous eruption can be the sole presenting manifestation of SLE. It also emphasizes the close temporal relationship between BSLE and lupus nephritis.

Betamethasone↗

PubMed2006

Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus.

Survival of patients with systemic lupus erythematosus (SLE) has improved over the past decade, thanks to improved treatment of the disease, which now results in fewer fatal complications. This improvement has allowed physicians to focus their attention on the prevention of organ damage caused by this chronic, inflammatory disease, and by the medications used to control the disease. Osteoporosis is common in SLE patients; risk factors for osteoporosis include prolonged use of glucocorticoids, cyclophosphamide and possibly gonadotropin-releasing-hormone agonists. In premenopausal women with SLE, inflammation or SLE-related medications can increase bone turnover, which eventually weakens bone architecture, then reduces bone strength and increases the risk of fracture. Prevention and treatment of osteoporosis in SLE patients should entail a multifaceted approach. Levels of calcium, vitamin D and homocysteine should be evaluated, and age-appropriate supplementation instituted. The bone loss that results from systemic inflammation should be treated by reduction of the inflammation with glucocorticoids, potent anti-inflammatory agents or antiresorptive agents. The efficacy of this therapy can be monitored using bone mineral density scans. This Review briefly discusses the pathophysiology of the localized and generalized osteoporosis and osteonecrosis in SLE patients and recommends therapies to both prevent and treat these unfortunate complications of this disease.

Female↗

PubMed1985

Heart disease in systemic lupus erythematosus: diagnosis and management.

Most patients suffering from systemic lupus erythematosus develop secondary heart disease at some time during the course of the primary illness. The most common forms of this type of heart disease are acute fibrinous pericarditis and hypertension. By means of echocardiography, an increased incidence of pericardial effusion has been demonstrated. Although commonly noted at autopsy, myocarditis is often clinically silent. However, endomyocardial biopsy may confirm its presence during life. Libman-Sacks endocarditis, although encountered in 40 to 50% of hearts at autopsy, is rarely diagnosed during life. When significant valve dysfunction such as aortic insufficiency or mitral regurgitation develops during the course of systemic lupus erythematosus, then Libman-Sacks endocarditis should be strongly suspected. Cardiac arrhythmias, first degree AV block, and acquired complete heart block may develop either de novo or in association with lupus pericarditis, myocarditis, vasculitis, etc. Complete congenital heart block has been reported in newborns of mothers with systemic lupus erythematosus, particularly those who have an antibody to a soluble tissue ribonucleoprotein antigen called RO(SS-A). Coronary arteritis and premature coronary atherosclerosis manifesting in either angina pectoris or myocardial infarction in young adults, particularly women suffering from systemic lupus erythematosus, have received attention recently. The development of hypertension and hyperlipidemia while such patients are receiving prolonged corticosteroid therapy has been incriminated as the significant risk factor in premature coronary atherosclerosis. Longstanding hypertension and congestive heart failure have unfavorable prognoses. This report is based on a cumulative review of 50 patients with acute and chronic systemic lupus erythematosus seen at our institution and in private practice during the last 10 years.

Journal Article↗

PubMedDate not supplied

Systemic lupus erythematosus and lupus syndromes in Senegal. A retrospective study of 30 patients seen over 10 years.

OBJECTIVE: To define the presenting manifestations, course and prognosis of systemic lupus erythematosus in Senegal. PATIENTS AND METHODS: Thirty cases of systemic lupus erythematosus and lupus syndromes seen over a ten-year period were reviewed retrospectively. Nineteen patients met American College of Rheumatology criteria for systemic lupus erythematosus. All 30 patients were Senegalese-born black women. Mean age at diagnosis was 30 years (range, 16-73 years). RESULTS: Polyarthritis was the most common presenting picture (n = 8), followed by discoid lupus (n = 6). Eight per cent of patients had at least a combination of skin and joint symptoms at diagnosis. Prevalences of organ involvement were as follows: skin, 97%; joints, 97%; kidneys, 57%; serous membranes, 43%; nervous system, 23% and blood, 83%. Mean symptom duration at diagnosis was 24 months in systemic lupus erythematosus patients and 43 months in lupus syndrome patients. This significant diagnostic delay explains why as many as five of the 30 patients (17%) died either before or within five months of treatment initiation. Eight patients (32% of treated patients) who had a favorable course under therapy were lost to follow-up after discharge. The overall mortality rate was 26%. Renal failure was the main cause of death, followed by infectious and neurologic complications. CONCLUSION: We anticipate that the reported prevalence of lupus in Senegal will rise in the near future as a result of improvements in diagnostic tools and of increased interest for lupus among physicians. We also hope that improved detection of mild and early forms, together with close long-term follow-up of patients, will translate into a better overall prognosis.

Adolescent↗

PubMed1987

Cerebral blood flow in systemic lupus erythematosus with and without central nervous system involvement.

Regional cerebral blood flow (rCBF) was studied by the intravenous 133Xe method in 38 patients with systemic lupus erythematosus (SLE); 21 patients had neuropsychiatric manifestations (N+) and 17 did not (N-). Twelve of the N+ patients had had neuropsychiatric episodes less than one year before measurement of CBF ("recent" N+), while seven patients in this group had had episodes over a year before measurement ("old" N+). The results were compared with those obtained from a group of 27 age-matched normal healthy subjects. It was found that, in most of the N+ and N- patients, rCBF was evenly distributed bilaterally, but there was a "patchwork" of high/normal and low flow areas. This disturbance of rCBF distribution was significantly greater in "recent" N+ patients than in "old" N- patients, but was not a function of the potential evolution of systemic lupus erythematosus. It was also found that there was a reduction in the physiological high frontal rCBF in the "old" N+ patients. No correlation could be found between rCBF, the topography of the neuropsychological lesions, other neurological investigations or the glucocorticoid dosage and treatment schedules.

Adolescent↗

PubMed2007

Effect of glutathione S-transferase polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: results from the Roxbury lupus project.

OBJECTIVE: The high prevalence of systemic lupus erythematosus (SLE) among African American women may be due to environmental exposures, genetic factors, or a combination of factors. Our goal was to assess association of residential proximity to hazardous waste sites and genetic variation in 3 glutathione Stransferase (GST) genes (GSTM1, GSTT1, and GSTP1) with age at diagnosis of SLE. METHODS: Residential histories were obtained by interviewing 93 SLE patients from 3 predominantly African American neighborhoods in Boston. Residential addresses and locations of 416 hazardous waste sites in the study area were geocoded using ArcView software. Time-varying Cox models were used to study the effect of residential proximity to hazardous sites, GST genotype, and interaction between genotype and exposure in determining age at diagnosis. RESULTS: The prevalence of SLE among African American women in these neighborhoods was 3.56 SLE cases per 1,000. Homozygosity for GSTM1-null and GSTP1 Ile105Val in combination was associated with earlier SLE diagnosis (P = 0.03), but there was no association with proximity to 416 hazardous sites. Available data on specific site contaminants suggested that, at a subset of 67 sites, there was higher potential risk for exposure to volatile organic compounds (P < 0.05 with Bonferroni correction). GST genotypes had a significant interaction with proximity (P = 0.03) in analyses limited to these sites. CONCLUSION: There was no independent association between residential proximity to hazardous waste sites and the risk of earlier SLE diagnosis in this urban population. However, analysis of a limited number of sites indicated that the risk of earlier SLE associated with proximity to hazardous sites might be modulated by GST polymorphisms.

Adolescent↗

PubMed2002

Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by several immunological abnormalities. The pathogenic importance of T cells in this disease is well established. Interleukin-16 (IL-16) is a cytokine which is mainly produced by CD8+ T cells and induces chemotaxis of CD4+ T cells and monocytes. IL-16 levels have been shown to be elevated in SLE patients in a cross-sectional study, but the mechanism is unknown. To explore whether the increased IL-16 levels are associated with genetic background or the disease itself, we investigated the IL-16 level in healthy first-degree family members of SLE patients and SLE patients who were followed over time with regard to disease activity. We observed high IL-16 levels in SLE patients with severe disease compared to SLE patients with non-severe disease and healthy controls. Furthermore, IL-16 levels in first-degree relatives were not different from those in healthy controls. These results suggest that high IL-16 levels are associated with severity of SLE, but not with genetic susceptibility to SLE. Finally, we followed the disease activity of SLE patients over time, which showed significant correlation between the SLE disease activity index and IL-16, ESR and the complement components C3, C4 and CH50. In conclusion, these results implicate an association of IL-16 with SLE.

Adult↗

PubMed2002

Severe pulmonary hypertension in a patient with systemic lupus erythematosus and minimal lupus activity.

Pulmonary hypertension (PH) sometimes occurs in patients with systemic lupus erythematosus (SLE). We report a case of 51-year-old-woman with PH associated with SLE. She had been diagnosed as SLE on the basis of pericardial effusion, hematological disorder, positive antinuclear antibody, and hypocomplementemia. Despite minimal lupus activity, she had marked elevation of pulmonary arterial pressure (101/53 mmHg) and decreased cardiac index (1.5 l/min/m2). Symptoms related to PH were progressive under treatment with oral corticosteroids, oxygen, calcium antagonists, and warfarin. After 17 months of epoprostenol treatment, she died of pulmonary infarction. SLE-associated PH is often severe and progressive even in association with minimal activity.

Anticoagulants↗