Comparison of renal disease severity and outcome in patients with primary antiphospholipid syndrome, antiphospholipid syndrome secondary to systemic lupus erythematosus (SLE) and SLE alone

OBJECTIVE: To ascertain the clinical presentation, histopathology and outcome of renal involvement in patients with primary antiphospholipid syndrome (PAPS), antiphospholipid syndrome secondary to systemic lupus erythematosus (SAPS) and systemic lupus erythematosus alone. METHOD: A retrospective analysis was undertaken of 20 patients with PAPS, 25 patients with SAPS and 275 patients with systemic lupus erythematosus to ascertain the frequency and pattern of renal involvement. RESULTS: Renal involvement was found most frequently in patients with SAPS, in whom it occurred in 68% of patients. Renal disease was equally common in patients with PAPS and systemic lupus erythematosus alone where it was seen in 30% of patients. Patients with systemic lupus erythematosus most frequently presented with nephrotic syndrome due to glomerulonephritis, whereas those with PAPS and SAPS were more likely to present with hypertension and reduced glomerular filtration rate. No patients with PAPS developed end-stage renal failure compared with 5.9% of patients with SAPS and 16.9% of patients with systemic lupus erythematosus alone; 23.5% of patients with SAPS died compared with 15.7% of patients with systemic lupus erythematosus alone and no patients with PAPS. CONCLUSION: Renal involvement is a major feature of both PAPS and SAPS, where renal thrombosis frequently leads to reduced glomerular filtration rate and hypertension. One-third of patients with systemic lupus erythematosus alone develop glomerulonephritis leading to renal disease which most commonly presents with nephrotic syndrome. Patients with PAPS were less likely to develop end-stage renal failure or die during the follow-up period.     

New insights from murine lupus: disassociation of autoimmunity and end organ damage and the role of T cells

PURPOSE OF REVIEW: This review summarizes current literature on genetic regulation of different phenotypes in systemic lupus erythematosus in context of end-organ disease. Recent findings conflicting with the current paradigm that loss of tolerance to chromatin is the critical step for end-organ injury are discussed. RECENT FINDINGS: Systemic lupus erythematosus is a prototype immune complex disease with circulating autoantibodies to chromatin, histone proteins, Sm/La, and other nuclear and cytoplasmic proteins. Extensive studies have been carried out on the regulation of B-cell and autoantibody production in lupus mice. However, the hypothesis that autoantibodies are primary mediators of organ damage fails to explain the heterogenous presentation in patients. Studies in murine models of systemic lupus erythematosus clearly dissociate genetic control of autoantibody responses to classic lupus antigens and kidney disease. There is increasing evidence to support the role of autoreactive T cells and genetic control of end organ susceptibility. These studies suggest complex interactions between innate and adaptive immunity resulting in end-organ damage. This review focuses on autoimmune responses and renal involvement in spontaneous systemic lupus erythematosus using murine models of lupus nephritis. SUMMARY: Studies in murine models demonstrate complex genetic interactions regulating spontaneous systemic lupus erythematosus. Although detection of serum autoantibodies is considered a hallmark for clinical diagnosis of systemic lupus erythematosus, recent evidence shows that autoantibodies to classic lupus antigens are neither required nor sufficient for end-organ damage. Thus, murine models provide new insights into the pathogenesis of systemic lupus erythematosus.     

Biomarkers for systemic lupus erythematosus: a review and perspective

PURPOSE OF REVIEW: Despite decades of extensive work in the understanding of the etiopathogenesis of systemic lupus erythematosus, few biomarkers have been validated and widely accepted for this disease. The lack of reliable, specific biomarkers not only hampers clinical management of systemic lupus erythematosus but also impedes development of new therapeutic agents. This paper reviews briefly the historical aspects of systemic lupus erythematosus biomarkers and summarizes recent studies on candidate biomarkers. RECENT FINDINGS: Recognizing the urgent need for lupus biomarkers, a Lupus Biomarker Working Group has recently been initiated to facilitate collaborative efforts aimed at identifying and validating biomarkers for systemic lupus erythematosus. Based on available data, several laboratory markers have shown promise as biomarkers for susceptibility, diagnosis, and disease activity. These include Fc receptor genes (disease susceptibility), complement C4d-bound erythrocytes (diagnosis or disease activity), CD27 plasma cells (disease activity), 'interferon signature' (disease activity), and anti-C1q antibodies (disease activity and organ involvement). SUMMARY: There is a longstanding and recently rejuvenated enthusiasm for biomarkers that precisely and specifically reflect the pathophysiologic and clinical changes in systemic lupus erythematosus. Promising candidate biomarkers have been identified but must still be validated through rigorous, large-scale multicenter studies.     

Clinical manifestations of disease activity, its measurement, and associated morbidity in systemic lupus erythematosus.

Although nephritis remains a very important clinical disease manifestation of systemic lupus erythematosus (SLE), the focus has shifted from issues of mortality to morbidity. An improved method for measuring renal function is presented, and the value of renal biopsy, specifically the chronicity index, is confirmed as a predictor of end-stage renal disease. Several studies detailing the generally favorable course in SLE patients with renal failure who have eventually required chronic dialysis or renal transplantation are discussed. A high frequency of cardiovascular manifestations, often subclinical, is documented, including abnormalities of ventricular and valvular function. The clinical course and response to treatment of SLE patients with diffuse interstitial lung disease and pulmonary hypertension are outlined. Cases of the unusual gastrointestinal presentation of protein-losing enteropathy in SLE have been described by several authors. The clinical correlates and significance of persistent rheumatoid-like arthritis and radiologic erosive and cystic bony lesions in SLE are discussed. Serologic markers of specific SLE disease manifestations and general predictors of disease activity are evaluated. Complications related to infection, malignancy, and pregnancy are described.     

Lupus nephritis in children

In systemic lupus erythematosus renal involvement is more frequent in children than in adults. Overall, 60-80% of children with systemic lupus erythematosus have urinary or renal function abnormalities early in the disease course. In 90% of patients, renal disease occurs within two years from disease onset. Clinically significant renal involvement ranges from asymptomatic urinary findings to nephrotic syndrome and renal failure. Long-term prognosis is similar to that observed in adults. Treatment aspects that are peculiar to children include drug side-effects, such as growth inhibition induced by steroids, the need to consider morbidity-related issues with respect to the very long life expectancy of patients and the problems related to the impact of disease in adolescents. The recent availability of a childhood SLE definition of improvement and the presence of large international paediatric rheumatology networks should, in the future, facilitate the implementation of controlled clinical trials devoted to paediatric SLE.     

Lupus: improving long-term prognosis

Over recent decades short- and medium-term survival has greatly improved in patients affected with systemic lupus erythematosus, but long-term prognosis still remains poor mainly due to complications of the disease and/or its treatment. To improve long-term prognosis in systemic lupus erythematosus, we should try to adopt, early in the disease course, strategies that can contribute to reducing long-term complications, including screening for and prophylaxis against infections, control of risk factors for atherosclerosis, and cancer surveillance. However, in patients with systemic lupus erythematosus all these preventive strategies are often not sufficient. Indeed, two important systemic lupus erythematosus-related factors play a relevant role in all these complications: severe disease manifestations, such as glomerulonephritis and central nervous system involvement, and corticosteroid and cyclophosphamide use. Therefore, to prevent long-term complications, we should try to control disease activity and severity using the lowest effective dosage of these drugs. Moreover, strategies directed at preventing clinical manifestations in asymptomatic antinuclear antibody-positive individuals or in antiphospholipid antibody-positive systemic lupus erythematosus patients, as well as at preventing severe manifestations in patients with mild systemic lupus erythematosus at the time of the diagnosis should be considered.     

Malignancy-associated remission of systemic lupus erythematosus maintained by autologous peripheral blood stem cell transplantation

Many investigators worldwide are currently exploring the role of peripheral blood stem cell transplantation (PBSCT) in managing autoimmune diseases. We report the case of a woman with systemic lupus erythematosus (SLE) with mucocutaneous and renal involvement, who underwent PBSCT for stage IVB Hodgkin's disease. Following the development of the lymphoma, she has had a prolonged clinical and serologic remission of the SLE. The potential effects of lymphoproliferative disorders and PBSCT on the course of SLE are considered.     

Mitral valve prolapse in systemic lupus erythematosus

Despite a low incidence of clinical manifestations, autopsy data suggest endocardial and myocardial disease in about 50% of patients with systemic lupus erythematosus. To investigate whether mitral valve prolapse can be considered a clinical manifestation of cardiac involvement in systemic lupus erythematosus, we carried out an echocardiographic study in 51 affected subjects and 102 normals matched for age and sex. Prevalence of mitral valve prolapse was 25% in patients with systemic lupus erythematosus and 9% in healthy controls with a statistically significant difference (p less than 0.01). Neither pericardial effusion nor prolonged (more than 12 months) treatment with corticosteroids were associated with higher prevalence of mitral valve prolapse. Libman-Sacks verrucae on the mitral valve apparatus as well as focal myocardial scars affecting the papillary muscles and adjacent myocardium could be responsible for the development of the valvular dysfunction. We suggest that mitral valve prolapse can be considered a manifestation of cardiac involvement in patients with systemic lupus erythematosus.     

Crohn's disease and systemic lupus erythematosus

A 28-year-old man with inflammatory bowel disease with complex extraintestinal involvement was found to have diagnostic features of both systemic lupus erythematosus and Crohn's disease. Although some of the systemic complications of these diseases may overlap, both diseases may occur as primary disorders. Coexistence of systemic lupus erythematosus should be considered in patients with inflammatory bowel disease and complex extraintestinal manifestations.     

UNUSUAL TRANSFORMATIONS OF RENAL INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract: :The clinical course of a woman with systemic lupus erythematosus demonstrated that renal involvement in this disease can change, both in the predominant site of renal injury and in the pattern of glomerular lesions. Over 50 months she had first tubulo-interstitial lupus nephritis with no glomerular change, then a membranous nephropathy with disappearance of tubulo-interstitial inflammation, and finally crescentic glomerulonephritis. This case emphasizes the need for close follow-up of all lupus patients regardless of their initial renal manifestations and pathology.     

Disease activity in systemic lupus erythematosus patients with end-stage renal disease: systematic review of the literature

It is not unusual that patients with systemic lupus erythematosus (SLE) progress to terminal renal failure and subsequently require renal replacement therapy. Previous studies have shown that clinical and/or serological remission in patients with SLE is common in those who develop end-stage renal disease (ESRD). On the other hand, the persistence of lupus activity among patients undergoing long-term dialysis is not rare, either. The aim of this study is to define, by means of a systematic review, the course of SLE activity in patients who developed ESRD. Data were obtained through searches for articles in the MEDLINE (1966 to 2011), SCielo, and LILACS databases, using the following keywords: "chronic renal failure", "systemic lupus erythematosus", "end-stage renal disease", "lupus activity", "disease activity", "lupus flare", "hemodialysis", and "renal replacement therapy" and their corresponding translations in Portuguese. Twenty-four articles were found which evaluated the degree of lupus activity in patients with ESRD. Fifteen of these studies spoke of a substantial reduction of clinical and/or serological activity after the development of ESRD, while nine articles found that the amount of clinical and/or serological activity was similar to that of the phase prior to terminal renal failure, or it occurred in at least 50% of the patients studied. Although the majority of studies showed that lupus flares tend to decrease in frequency in patients who develop ESRD, in this scenario, one should be prepared to correctly diagnose a recurrence of the disease, as well as to perform appropriate therapy.     

Prognosis of systemic lupus erythematosus and the factors that affect it.

The prognosis of systemic lupus erythematosus has improved over the past four decades. Articles published in the past year continue to demonstrate this improved survival, both overall and in patients with renal disease. Several factors may be associated with improved survival, including earlier diagnosis, better treatment for systemic lupus erythematosus, and improved medical therapy in general. Hydroxychloroquine has now clearly been shown to prevent flares, and ancrod has been shown to improve renal disease in patients with glomerular thrombosis. Treatment with dialysis and transplantation resulted not only in improved survival but also in improved renal status, and reduction in overall disease activity. Specific organ damage continues to be an issue, primarily with regard to kidney disease and neurocognitive impairment. The inclusion of health status assessment in the evaluation of patients with lupus, and as an outcome measure, is discussed.     

Clinical significance of antibodies to PCNA

Antibodies to proliferating cell nuclear antigen (PCNA) were first reported by Miyachiet al. as autoantibodies which were specifically detected in sera from patients with systemic lupus erythematosus (SLE). PCNA has been identified as a nuclear protein with a molecular weight of 33 kDa and an isoelectric point of 4.8, and sequential studies have revealed that PCNA plays an important role in DNA replication as an auxiliary protein of DNA polymerase °. The clinical characteristics of patients with anti-PCNA were not well known because of the low frequency in lupus patients (2–3.4%), but several studies in different ethnic groups showed that the occurrence of anti-PCNA antibodies is predominantly in lupus patients or patients with clinical features associated with SLE. In addition, a higher prevalence of renal involvement and CNS lupus was observed in two different reports. The strong relation of the antibody titer to the activity of renal involvement was also revealed as a common observation. In addition to anti-PCNA antibodies, detection of PCNA-expressing peripheral blood mononuclear cells is useful for the evaluation of the disease activity in lupus. The mechanism of anti-PCNA production is not known; however, recent studies suggest that serum autoantigen plays an important role.     

Serotonin content of platelets in inflammatory rheumatic diseases

Significantly decreased platelet serotonin contents were measured in rheumatoid arthritis, systemic lupus erythematosus (SLE), progressive systemic sclerosis, and mixed connective tissue disease. An inverse relationship between platelet serotonin levels and clinical disease activity was observed in both rheumatoid arthritis and systemic lupus erythematosus. SLE patients with multiple organ involvement showed the lowest platelet serotonin values. No correlation was observed between platelet serotonin contents and nonsteroidal antiinflammatory drug treatment, presence of circulating platelet reactive IgG, or the amount of circulating immune complexes. The results are interpreted as indicating platelet release occurring in vivo during inflammatory episodes of the rheumatic disorders investigated.     

Ticlopidine-induced lupus: a report of 4 cases

Drug-induced lupus has been associated with various medications. Ticlopidine hydrochloride is a platelet aggregation inhibitor that has been associated with thrombotic thrombocytopenic purpura, which is believed to be immune mediated. We describe 4 patients with drug-induced lupus following the institution of ticlopidine therapy. The 4 patients, who had systemic lupus erythematosus following ticlopidine use, were examined between 1997 and 1999. The clinical features of these patients, namely, older age of onset, presence of pleurisy and arthritis, and paucity of central nervous system, renal, or skin involvement, are consistent with drug-induced lupus. All had detectable antihistone antibodies. All 4 patients had clinical and serological improvement following ticlopidine withdrawal, allowing cessation or reduction of corticosteroid therapy. We suspect that ticlopidine can cause drug-induced lupus, and that this exposure should be considered particularly in the examination of elderly patients with systemic lupus erythematosus.     

Childhood systemic lupus erythematosus: a review of 30 cases

We review 30 cases of pediatric systemic lupus erythematosus followed over an 8-year period at our institution. The female to male ratio was 3.3:1; the age at diagnosis ranged between 3.5 and 16 years. On first admission, renal involvement was detected in the majority of the patients, as assessed by laboratory findings and/or clinical manifestations. Other frequently observed symptoms were fever, skin rashes, arthralgias and/or arthritis and serositis. All of the patients were treated with corticosteroids and most of them also received immunosuppressive drugs in order to control disease activity. Two patients were lost to the follow-up, five died and only one of the 23 evaluable patients is off therapy after a median follow-up of 5 years. This study confirms that pediatric systemic lupus erythematosus is a very aggressive disease.     

Manifestaciones pulmonares en lupus eritematoso sistémico: afección pleural,neumonitis aguda,enfermedad intersticial crónica y hemorragia alveolar difusa

Systemic lupus erythematosus is the diffuse autoimmune connective tissue disease that most frequently involves pulmonary involvement, affecting 20% of 90% of the patients. The percentage varies depending on the defining criteria (symptoms, pulmonary tests or histopathological studies). At least once during the disease course, 50% of those affected have pleural and/or pulmonary manifestations, which are associated with higher morbidity and mortality. Pulmonary involvement has no correlation with lupus activity biomarkers, and it is necessary to rule out infectious processes in the initial approach. Bacterial infection is most frequently the cause of lung involvement in lupus and is one of the most important causes of death. Pulmonary involvement is considered to be primary when it is associated with disease activity, and secondary when other causes participate. Drugs have been reported to be associated with pulmonary damage, including interstitial disease. The incidence of malignant lung diseases is increased in systemic lupus erythematosus. Treatment depends on the type and severity of pulmonary involvement.     

Diagnosis and management of lupus pleuritis

Systemic lupus erythematosus is a chronic inflammatory autoimmune disorder that can affect any organ system. Predominant manifestations include arthralgia, rash, photosensitivity, pleuritis, renal and central nervous system involvement. Fortunately, pleuritis in systemic lupus erythematosus is not usually as life threatening as may be the renal or central nervous system complications. Nevertheless, pleuritis does occur in systemic lupus erythematosus and may be a significant cause of morbidity. In addition to primary pleuritis attributed to systemic lupus erythematosus, secondary pleural complications, especially infections, may occur as a consequence of systemic lupus erythematosus. Pleuritis in patients with systemic lupus erythematosus may therefore frequently challenge the diagnostic and therapeutic acumen of physicians.     

Predictive value of IgG autoantibodies against C1q for nephritis in systemic lupus erythematosus.

OBJECTIVES--Antibodies against C1q (C1qAb) have been demonstrated in the serum of patients with several immune complex diseases. Patients, particularly those with lupus nephritis, were found to have increased serum titres of IgG C1qAb in a cross-sectional analysis. In the present prospective study correlations were sought between serum titres of IgG C1qAb and clinical as well as laboratory parameters of disease activity in patients with systemic lupus erythematosus (SLE). METHODS--Titres of IgG C1qAb in the serum of 68 SLE patients were measured serially during a three year period. At the same time clinical and laboratory parameters of disease activity were assessed. RESULTS--Increased titres of IgG C1qAb were found in the serum of 56% of SLE patients during the study. Significant correlations were found between increased titres of IgG C1qAb and renal involvement. Clinical signs of renal involvement were found to be associated with significant increases of serum titres of IgG C1qAb in the six months preceding this appearance. Fifty per cent of the increases in serum titres of IgG C1qAb were followed by the development of renal involvement. Elevated serum titres of IgG C1qAb were especially related to proliferative forms of glomerulonephritis. Furthermore, significant correlations were found between serum titres of IgG C1qAb and serum levels of immune complexes, levels of complement components, and titres of antibodies to DNA. CONCLUSIONS--The results suggest that IgG C1qAb play a pathogenic role in the development of lupus nephritis and that serial measurement of serum titres of IgG C1qAb is useful in the management of SLE patients.     

Cardiac tamponade as the first manifestation of systemic lupus erythematosus in the elderly

Although pericardial involvement is very frequent in systemic lupus erythematosus, cardiac tamponade is extremely rare as the first manifestation of the disease. On the other hand, systemic lupus erythematosus is a disease that predominantly affects young women, and it is a very uncommon condition in the elderly. We report a 91-year-old woman diagnosed with cardiac tamponade, which was the presenting clinical feature of a previously undiagnosed case of systemic lupus erythematosus.