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Longitudinal disease- and steroid-related damage among adults with childhood-onset systemic lupus erythematosus.

ABSTRACT: OBJECTIVES:Determine whether adults with childhood-onset systemic lupus erythematosus (cSLE) are at increased risk for disease- and steroid-related damage as compared to individuals with adult-onset SLE (aSLE), and whether they continue to accumulate disease damage in adulthood. METHODS:Data derive from the 2007-2015 cycles of the Lupus Outcomes Study, a longitudinal cohort of adults with confirmed SLE. The Brief Index of Lupus Damage (BILD), a validated, patient-reported measure, was used to assess SLE-associated damage. Participants with baseline BILD were included (N?=?1035). Diagnosis at age < 18 years was defined as cSLE (N?=?113). Outcome variables included BILD score at baseline and follow-up, clinically significant change in BILD score over follow-up period, and presence of steroid-related damage (cataracts, osteoporosis-related fracture, avascular necrosis or diabetes mellitus). RESULTS:Mean time between baseline and follow up BILD assessment was 6.3?±?1.7 years. In adjusted analyses, participants with cSLE and aSLE had similar levels of disease-related damage, and accumulated damage at similar rates. Participants with cSLE were more likely to report steroid-related damage (OR 1.7, 95% CI 1.1-2.8) in the adjusted analysis as compared to those with aSLE. Likelihood of steroid-related damage increased with disease duration for both groups, but was consistently higher among cSLE participants. CONCLUSION:In this longitudinal cohort of adults with SLE, participants continued to accumulate damage at similar rates over time, regardless of age at onset or disease duration. Childhood-onset predicted increased risk of steroid-related damage. Aggressive use of steroid-sparing treatment strategies during childhood may be important to prevent steroid-related damage in adulthood.

SUBMITTER: Heshin-Bekenstein M

PROVIDER: S-EPMC7480934 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Longitudinal disease- and steroid-related damage among adults with childhood-onset systemic lupus erythematosus.

Heshin-Bekenstein Merav M Trupin Laura L Yelin Ed E von Scheven Emily E Yazdany Jinoos J Lawson Erica F EF

Seminars in arthritis and rheumatism 20190603 2

<h4>Objectives</h4>Determine whether adults with childhood-onset systemic lupus erythematosus (cSLE) are at increased risk for disease- and steroid-related damage as compared to individuals with adult-onset SLE (aSLE), and whether they continue to accumulate disease damage in adulthood.<h4>Methods</h4>Data derive from the 2007-2015 cycles of the Lupus Outcomes Study, a longitudinal cohort of adults with confirmed SLE. The Brief Index of Lupus Damage (BILD), a validated, patient-reported measure, ...[more]

PMID: 31235075

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Project description:ObjectivesTo delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN).MethodsIn this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy.ResultsAdiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient (r) = - 0.49; p < 0.0001] but not proteinuria (r = 0.20; p > 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p < 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP.ConclusionIn combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline.Key messages• Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.

Project description:ObjectiveChildhood-onset systemic lupus erythematosus (SLE) is a severe, lifelong, multisystem autoimmune disease. Long-term outcome data are limited. This study was undertaken to identify clinical characteristics and health-related quality of life (HRQoL) of adults with childhood-onset SLE.MethodsPatients participated in a single study visit comprising a structured history and physical examination. Disease activity (scored using the SLE Disease Activity Index 2000 [SLEDAI-2K]), damage (scored using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and HRQoL (scored using the Short Form 36 Health Survey) were assessed. Medical records were reviewed.ResultsIn total, 111 childhood-onset SLE patients were included; the median disease duration was 20 years, 91% of patients were female, and 72% were white. Disease activity was low (median SLEDAI-2K score 4), and 71% of patients received prednisone, hydroxychloroquine (HCQ), and/or other disease-modifying antirheumatic drugs. The vast majority of new childhood-onset SLE-related manifestations developed within 2 years of diagnosis. Damage such as myocardial infarctions began occurring after 5 years. Most patients (62%) experienced damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems. Cerebrovascular accidents, renal transplants, replacement arthroplasties, and myocardial infarctions typically occurred at a young age (median age 20 years, 24 years, 34 years, and 39 years, respectively). Multivariate logistic regression analysis showed that damage accrual was associated with disease duration (odds ratio [OR] 1.15, P < 0.001), antiphospholipid antibody positivity (OR 3.56, P = 0.026), and hypertension (OR 3.21, P = 0.043). Current HCQ monotherapy was associated with an SDI score of 0 (OR 0.16, P = 0.009). In this cohort, HRQoL was impaired compared to the overall Dutch population. The presence of damage reduced HRQoL scores in 1 domain. High disease activity (SLEDAI-2K score ≥8) and changes in physical appearance strongly reduced HRQoL scores (in 4 of 8 domains and 7 of 8 domains, respectively).ConclusionThe majority of adults with childhood-onset SLE in this large cohort developed significant damage at a young age and had impaired HRQoL without achieving drug-free remission, illustrating the substantial impact of childhood-onset SLE on future life.

Project description:Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery (?HRR) (that is, the difference between HR at peak exercise and at both the first (?HRR1) and second (?HRR2) minutes of recovery after exercise).The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ?HRR1 and ?HRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.NCT01515163.

Project description:OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33 ± 4.50), 64 first-degree relatives (mean age 39.95 ± 5.66), and 57 healthy (mean age 19.30 ± 4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

Dataset Information

Longitudinal disease- and steroid-related damage among adults with childhood-onset systemic lupus erythematosus.

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Longitudinal disease- and steroid-related damage among adults with childhood-onset systemic lupus erythematosus.

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