Childhood-onset Systemic Lupus Erythematosus (childhood-onset + systemic_lupus_erythematosus)

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Selected Abstracts

Neutrophil gelatinase,associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity

Claas H. Hinze
Objective To determine whether neutrophil gelatinase,associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE). Methods One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models. Results Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score. Conclusion Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity. [source]

Urinary neutrophil gelatinase,associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus

Hermine I. Brunner
Objective Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase,associated lipocalin (NGAL) is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis. Methods A cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood-onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double-blind, cross-sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme-linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls. Results NGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood-onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r , 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of >0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood-onset SLE patients with biopsy-proven nephritis. Conclusion Urinary NGAL is a promising potential biomarker of childhood-onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes. [source]

Risk factors for damage in childhood-onset systemic lupus erythematosus: Cumulative disease activity and medication use predict disease damage

Hermine I. Brunner
Objective The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index measures damage in adult patients with systemic lupus erythematosus (SLE), but its usefulness in patients with childhood-onset SLE has not been examined. This study was conducted to evaluate the sensibility of the SLICC/ACR Damage Index, to investigate how cumulative disease activity is related to damage in childhood-onset SLE, and to identify other risk factors for damage in childhood-onset SLE. Methods Disease activity and damage in 66 patients with newly diagnosed childhood-onset SLE were assessed retrospectively, and information on potential risk factors for damage (age, race, sex, medications, duration of disease, hypertension, body mass index, antiphospholipid antibodies, kidney disease, acute thrombocytopenia) was obtained. In addition, a group of physicians was surveyed to establish the sensibility of the SLICC/ACR Damage Index in childhood-onset SLE. Results The SLICC/ACR Damage Index was found to have face, content, and construct validity when used in children. The mean SLICC/ACR Damage Index score of the patients was 1.76 (mean followup 3.3 years). Cumulative disease activity over time was the single best predictor of damage (R2 = 0.30). Other, possibly important risk factors for damage were corticosteroid treatment, the presence of antiphospholipid antibodies, and acute thrombocytopenia. It was determined that immunosuppressive agents may be protective. Conclusion The SLICC/ACR Damage Index, though useful in childhood-onset SLE, may benefit from the introduction of weightings and redefinition of some of the items. Ongoing disease activity leads to disease damage, and treatment should be prompt. Prolonged use of high-dose corticosteroids may further increase damage, but use of immunosuppressive agents may protect against disease damage; this latter finding may have potential implications for the treatment of childhood-onset SLE and deserves further study. The relationship between disease activity and concomitant use of medication also requires further investigation. [source]

Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis

Stephen D Marks
Abstract There is still a significant morbidity and mortality associated with childhood-onset systemic lupus erythematosus (SLE), despite an increasing armamentarium of immunosuppressive agents. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of treatment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accrued over the years. Each patient should have individualized treatments tailored to their organ involvement, disease severity and history of flares together with recent clinical, haematological and immunological parameters to avoid further flares of disease activity and side-effects of treatment, especially severe infections and future malignancies. The most commonly cited side-effects of medications include Cushingoid features of corticosteroids, infective complications of cyclophosphamide and gastrointestinal side-effects of mycophenolate mofetil. There is increasing evidence to support the use of oral mycophenolate mofetil as opposed to cyclophosphamide for both induction and maintenance therapies in many children with SLE with or without lupus nephritis (LN). Recently, case series utilizing B-lymphocyte depletion therapies with rituximab look promising for patients with severe or refractory disease activity. In this article, we explore current evidence to effectively treat children and adolescents with SLE with or without LN. Conclusion:, Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and rituximab. [source]