Pediatric Lupus Patients Research Articles

Improving lupus care index documentation in patients with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (c-SLE) presents unique challenges due to increased risk for severe morbidity and mortality compared to adult-onset SLE. Effective disease management relies on accurate disease assessment and documentation. Our project aimed to improve the documentation of the Lupus Care Index (LCI), a disease assessment bundle, by implementing a quality improvement (QI) initiative. A QI project was conducted at Nationwide Children's Hospital (NCH), targeting patients with c-SLE. The LCI, comprising the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) Physician Global Assessment (PGA) and patient-reported pain score, was introduced to capture comprehensive disease assessment. Interventions included provider education, standardization of documentation procedures, and electronic health record (EHR) modifications. Automated reports tracked documentation rates, and Pareto charts identified areas for targeted interventions. Baseline analysis revealed incomplete documentation of LCI components in only one-third of c-SLE patients. Following interventions, documentation rates improved from 38% to 90%, with sustained improvement over at least a year. Enhancing documentation of LCI in patients with c-SLE is crucial for optimizing disease management. Our quality improvement initiative demonstrated the feasibility of improving documentation practices through targeted interventions and system modifications. Future research should explore the impact of comprehensive documentation on clinical outcomes in pediatric lupus patients. Improving documentation of LCI in patients with c-SLE is essential for optimizing care delivery and clinical outcomes; our QI initiative highlights the effectiveness of systemic interventions in enhancing documentation practices and underscores the importance of continued efforts to improve pediatric lupus care.

Population-level single-cell genomics reveals conserved gene programs in systemic juvenile idiopathic arthritis.

Systemic autoimmune and autoinflammatory diseases are characterized by genetic and cellular heterogeneity. While current single-cell genomics methods provide insights into known disease subtypes, these analysis methods do not readily reveal novel cell-type perturbation programs shared among distinct patient subsets. Here, we performed single-cell RNA-Seq of PBMCs of patients with systemic juvenile idiopathic arthritis (SJIA) with diverse clinical manifestations, including macrophage activation syndrome (MAS) and lung disease (LD). We introduced two new computational frameworks called UDON and SATAY-UDON, which define patient subtypes based on their underlying disrupted cellular programs as well as associated biomarkers or clinical features. Among twelve independently identified subtypes, this analysis uncovered what we believe to be a novel complement and interferon activation program identified in SJIA-LD monocytes. Extending these analyses to adult and pediatric lupus patients found new but also shared disease programs with SJIA, including interferon and complement activation. Finally, supervised comparison of these programs in a compiled single-cell pan-immune atlas of over 1,000 healthy donors found a handful of normal healthy donors with evidence of early inflammatory activation in subsets of monocytes and platelets, nominating possible biomarkers for early disease detection. Thus, integrative pan-immune single-cell analysis resolved what we believe to be new conserved gene programs underlying inflammatory disease pathogenesis and associated complications.

IRF5 risk variants contribute to pre-symptomatic SLE by enhancing the levels of circulating NET antigens

Abstract SLE is a complex multifactorial autoimmune disease characterized by high levels of autoantibodies that impact many organs. Neutrophil extracellular traps (NETs) are a potential source of antigen leading to the production of autoantibodies, as antibodies against NET components are detected in SLE patients. Higher level of NETs and decreased clearance of NETs are associated with SLE and other autoimmune diseases. Neutrophils play an key role in pediatric lupus and NETs from pediatric lupus patients activate plasmacytoid dendritic cells (pDCs) to produce high levels of IFN-α. Polymorphisms within and around the IRF5 gene associate with risk of developing SLE. We previously reported that healthy donor neutrophils from IRF5 homozygous risk carriers underwent increased spontaneous NETosis, as compared to non-risk donors, that resulted in increased IFN-α production, plasma cell differentiation and autoantibody production. Whether the observed increase in neutrophil-mediated ETosis is a systemic signature of IRF5-driven pre-symptomatic SLE is not known, nor is it known whether these IRF5 risk carriers have defects in NET clearance. We thus developed and optimized new assays to detect small quantities of NET remnants in plasma samples using a combined MPO-CitH3 antibody cocktail followed by detection of DNA by ELISA. Further, we designed a novel immunofluorescence technique to visualize and quantify plasma NETs in healthy donor risk and non-risk carriers, as compared to pediatric and adult SLE patients. In addition, plasma DNase 1 and DNase 1L3 levels were measured. This study will report on the mechanisms by which circulating NETs are increased in pediatric and adult SLE, as well as the contribution of IRF5 genetic risk to NET clearance. Supported by Lupus Research Alliance Department of Defense CDMRP LRP W81XWH-18-1-0674

Rituximab use in pediatric systemic lupus erythematosus: Indications, efficacy and safety in an Indian cohort.

Introduction: Children with systemic lupus erythematosus have a more challenging and difficult course as compared to their adult counterparts. Today, the aim of therapy for any child with lupus is to keep the child in a state of sustained remission with minimal or no use of steroids. This laudable goal is often difficult to achieve for the child with lupus. In addition to the use of disease modifying agents, sometimes in combination, Rituximab (RTX) is also used as an off-label indication to manage such patients.Objectives: To study the use, efficacy and safety of RTX in a cohort of patients with pediatric lupus followed at a single tertiary level center in Northern India.Methods: This paper is a retrospective review looking at the use of RTX in children with systemic lupus at a tertiary level pediatric rheumatology center in North India over a period of seventeen years. This paper describes the indications, use, efficacy and safety of RTX in childhood systemic lupus erythematosus.Results: RTX was used in 17 of 225 pediatric lupus patients (7.5%), with the most common indication being resistant renal disease (53%). Significant improvement was seen in all domains studied: The mean SLEDAI was 16.25 prior to RTX and reduced to 1.43 six months after the RTX (p value 0.001), steroid use dropped from 100% pre- RTX to 33% at 2 years, there was a sustained reduction in proteinuria in the patients with nephritis from a mean urine spot protein creatinine ratio of 3.1 pre RTX to 0.4 at one year post RTX (p= .006). Finally, 82% of the children had no flare during the follow up (median 24 months). No patient had any adverse event.Conclusions: This study confirms that RTX is very effective in childhood lupus and can be safely used even in a country with a very high burden of infectious diseases. This data adds to the scarce literature in this area from the developing world.

Understanding patient-provider discordance in adolescents with lupus: The role of pain and antidepressant medication use.

The current study examines depression and pain as potential contributors to patient-provider discordance in the assessment of lupus disease activity. The study conducted a secondary analysis of data obtained from the Childhood Arthritis and Rheumatology Research Alliance registry, with N = 859 adolescent participants. Assessments of pain, disease activity, and antidepressant medication use were collected from the patient and provider. Results indicated that depression might be underdiagnosed in pediatric lupus patients. While psychotropic medication and pain scores were independently related to greater patient-provider discordance regarding health status, pain mediated this relationship. Implications for treatment outcomes are discussed.

Influence of air pollution on renal activity in patients with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000. Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20UI/mL and on 24-h urine protein and serum complement (C3) levels. An interquartile range (IQR) increase of 18.12μg/m3 in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM2.57-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1μg/m3) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels. This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.

Development and Validation of a Fast Ultra-High Performance Liquid Chromatography-Fluorescent Method for the Quantification of Hydroxychloroquine and Its Metabolites in Patients With Lupus.

Hydroxychloroquine (HCQ) is approved for the treatment of systemic lupus erythematosus (SLE). Therapeutic drug monitoring of HCQ is necessary to detect nonadherence and to improve treatment efficacy in patients with SLE. Liquid chromatographic-tandem mass spectroscopy and high performance liquid chromatography (HPLC)-fluorescent methods are currently used to measure whole blood concentrations of HCQ and its 2 main metabolites desethylhydroxychloroquine and desethylchloroquine in patients with SLE. This study reports the development and validation of an ultra-HPLC (U-HPLC) method with fluorescence detection for the simultaneous quantification of HCQ and its metabolites in whole blood. After adding chloroquine (internal standard) to the samples, a single-step protein precipitation and a subsequent filtration were used for blood sample preparation. Analytes were separated under isocratic elution on a U-HPLC RP18 column with a total run time of 7 minutes. The mobile phase consisted of piperazine buffer (46.4 mM, pH = 9.8) and acetonitrile (68:32, vol/vol), which was delivered at a flow rate of 0.4 mL/min. Fluorescence excitation and emission wavelengths were 335 and 390 nm, respectively. Assay performance parameters were evaluated per FDA bioanalytical guidelines. The calibration curve was linear from 125 to 4000 ng/mL for HCQ. The lower limit of quantification was 10 ng/mL for all analytes. For HCQ, desethylchloroquine, and desethylhydroxychloroquine, accuracies and imprecisions ranged from -7.90% to 7.85% and 1.14% to 8.78%, respectively. A sensitive, accurate, and fast U-HPLC-fluorescent method was validated and successfully applied to quantify whole blood concentrations to perform therapeutic drug monitoring of HCQ in pediatric and adult lupus patients.

X-chromosome inactivation maintenance is perturbed in T cells from lupus mouse models and human lupus patients

Abstract Sex differences exist with immune responses, yet females are more susceptible to autoimmune and inflammatory disorders. One important biological factor underlying this sex bias is the X-chromosome, which is enriched for immunity-related genes. Female mammals use X-Chromosome Inactivation (XCI) to equalize gene expression between the sexes, which generates a transcriptionally silent inactive X-chromosome enriched with heterochromatic modifications and the long noncoding RNA Xist. We have discovered that mature naïve T cells are missing Xist RNA and heterochromatin marks on the inactive X (Xi), and these marks return to most cells with in vitro stimulation. During T cell development in the thymus, Xist RNA is not localized to the Xi and heterochromatin marks are progressively lost. Xist RNA returns to the Xi in mature T cell subsets between days 2 and 3 of in vitro activation. During lupus disease progression in the female-biased mouse model NZB/W F1, Xist RNA signals aberrantly appear in naïve T cells and Xist RNA becomes mis-localized from the Xi in activated T cells. These abnormal XIST RNA localization patterns are also observed in activated T cells from pediatric lupus patients in disease remission. Using next-generation sequencing, we found significant overexpression of X-linked genes across the X in female SLE T cells compared to healthy females. We propose that the dynamic mechanism of XCI maintenance female lymphocytes predisposes the Xi to become partially reactivated and to overexpress immunity-related genes. Our work provides the first mechanistic evidence for the female-specific enhanced immune responses and increased susceptibility for autoimmunity.

Immunogenicity of sequential 13-valent conjugated and 23-valent unconjugated pneumococcal vaccines in a population of children with lupus.

Pneumococcal vaccination is recommended as a quality indicator for management of children with systemic lupus erythematosus. Literature on the immunogenicity of pneumococcal vaccines (PCVs) in children is scant. We sought to prospectively evaluate via an observational study, the immunogenicity to sequential children with lupus. Out of a cohort of 26 patients, approximately 65% achieved > 70% vaccinated serotype antibody levels of > 1.3 mcg/dL following PCV13, and of 22 patients followed through PPSV23 vaccination, 59% achieved the same. Patients with rituximab exposure in the 6 months prior to a vaccination were more likely to not achieve protective serotype levels ( p < 0.01 for PCV13, trend p = 0.07 for PPSV23). Three of 22 patients with no apparent risk factors did not achieve protective serotype levels. Non-responders to PCV13 generally did not respond to PPSV23. Retrospective healthy controls achieved 100% protective levels in response to PPSV23 vaccination, with 95% of serotypes being > 1.3 mcg/dL. Thus, sequential 13- and 23-valent pneumococcal vaccines achieve protective status for approximately two thirds of pediatric lupus patients in our population. Lack of response to vaccine may be secondary to induced or inherent functional impairments in the patient.

Delays to Care in Pediatric Lupus Patients: Data From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.

Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist. We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (within <1 month of symptom onset), between 1-3 months (typical presentation), with moderate delays (3-12 months), and with severe delays (≥1 year). Factors associated with early presentation, moderate delay, and severe delay were determined by multinomial logistic regression. Forty-four percent of patients presented early, while 23% had moderate delays and 9% had severe delays. Family history of lupus, absence of discoid rash, and location in a state with a higher density of pediatric rheumatologists were associated with earlier presentation. Younger age, low household income (<$25,000 per year), and a family history of lupus were associated with severe delay. Delays to care ≥1 year exist in a notable minority of pediatric lupus patients from the CARRA Legacy Registry. In this large and diverse sample of patients, access to care and family resources played an important role in predicting time to presentation to a pediatric rheumatologist.

Evaluation of quality indicators and disease damage in childhood-onset systemic lupus erythematosus patients.

The aim of this study was to describe compliance with select quality indicators and assess organ-specific dysfunction in a childhood-onset systemic lupus erythematosus population by using a validated damage index and to evaluate associations between compliance with quality indicators and disease damage. A retrospective chart review was performed on patients diagnosed with systemic lupus erythematosus prior to age 18 followed at a single center in the USA from 1999 to 2012 (n=75). Data regarding quality indicators and outcome variables, including the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, were collected. The median disease duration was 3.8years. The proportion of patients or patient-years in which care complied with the proposed quality measures was 94.4% for hydroxychloroquine use, 84.3% for vitamin D recommendation,75.8% for influenza vaccination (patient-years), 67.2% for meningococcal vaccination, 49.0% for ophthalmologic examination (patient-years), 31.7% for pneumococcal vaccination, and 28.6% for bone mineral density evaluation. Disease damage was present in 41.3% of patients at last follow-up, with an average damage index score of 0.81. Disease damage at last follow-up was associated with minority race/ethnicity (p=0.008), bone mineral density evaluation (p=0.035), and vitamin D recommendation (p=0.018). Adherence to quality indicators in a childhood-onset systemic lupus erythematosus population is varied, and disease damage is prevalent. This study highlights the importance of quality improvement initiatives aimed at optimizing care delivery to reduce disease damage in pediatric lupus patients.

Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best oligonucleotide binders in surface plasmon resonance studies to analyze binding and kinetic aspects of interactions between antigens and target DNA. These DNA and LNA/DNA sequences showed improved binding in enzyme-linked immunosorbent assay using human samples of pediatric lupus patients. Our results suggest that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies.

A Cross-Cultural Validation of a Quality of Life Measure Using the Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY©) among Filipino Pediatric Lupus Patients

Background: Systemic lupus erythematosus (SLE) is one of the most common autoimmune disorders in women of childbearing age. Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) is the only health related quality of life (HRQOL) tool for pediatric SLE, which has been translated into many languages but is not yet available in Filipino. Objective: The primary objective of this study was to develop a Filipino translation of the SMILEY and to test the validity and reliability of this translation. Methodology: The SMILEY was translated into Filipino by a bilingual individual and back-translated by another bilingual individual blinded from the original English version. The translation was evaluated for content validity by a panel of experts and subjected to pilot testing. In the pilot, the SMILEY, together with the previously validated Pediatric Quality of Life Inventory (PEDSQL) 4.0 Generic Core Scale were administered to pediatric lupus patients and their parents on two separate occasions: a baseline and a re-test seven to fourteen days apart. Tests for convergent validity, internal consistency, and test-retest reliability were performed. Results: A total of fifty children and their parents were recruited. The mean age was 15.38±2.62 years (range 8-18 years), mean education level was high school. The mean duration of SLE was 28 months (range 1-81 months). Subjects found the questionnaires to be relevant, easy to understand and to answer. The validity of the SMILEY was demonstrated in terms of content validity, convergent validity, internal consistency, and test-retest reliability. Age, socioeconomic status and educational attainment did not significantly impact the scores. The difference between scores reported by children and parents was significant with SMILEY Total (p=0.0214), effect on Social Life (p=0.0000), and PEDSQL Physical Function (p=0.0460), with children reporting higher scores for these domains compared to their parents. Conclusion: SMILEY is a brief, easy to understand, valid and reliable tool for assessing specific HRQOL in pediatric SLE. It will be useful in providing better care, understanding and may offer critical information regarding the effect of SLE in the quality of life of our pediatric lupus patients. It will help physician understands the needs of their patient not only on treatment of the specific disease but as well as the impact of the treatment on their daily lives.

Pediatric systemic lupus erythematosus presenting with coronary arteritis: A case series and review of the literature

ObjectivePediatric-onset systemic lupus erythematosus (pSLE) is typically more aggressive in presentation than adult-onset lupus. Presenting manifestations of lupus in children and adults involve similar organ systems, with renal and neuropsychiatric involvement more common in pSLE. Cardiac manifestations are similar in the 2 groups, with pericarditis accounting for the majority of cardiac lupus at presentation. There are no reports to our knowledge of coronary arteritis as a presenting feature of pSLE. MethodsThis is a retrospective case series describing 4 pediatric lupus patients who presented with prominent coronary artery dilatation and a review of the literature regarding coronary artery involvement in lupus. ResultsCoronary arteritis appears to be a more common feature of pSLE than previously thought. Based on our experience, coronary artery changes tend to resolve once the SLE is treated. ConclusionsEarly recognition of this disease manifestation may guide therapy and result in improved long-term cardiovascular outcomes.

Depression and anxiety and their association with healthcare utilization in pediatric lupus and mixed connective tissue disease patients: a cross-sectional study.

BackgroundDepression and anxiety adversely affects outcomes in systemic lupus erythematosus (SLE) and healthcare utilization is high for pediatric SLE. We aimed to characterize the prevalence of depression and anxiety in pediatric SLE, and their association with healthcare utilization.MethodsWe conducted a cross-sectional analysis of pediatric SLE and mixed connective tissue disease (MCTD) subjects and healthy controls aged 8 years and above. We used the Patient Health Questionnaire 9 (PHQ-9) and the Screen for Childhood Anxiety Related Disorders (SCARED) to identify depression, suicidal ideation and anxiety symptoms, respectively. We compared symptom prevalence in SLE/MCTD and healthy subjects using logistic regression. For SLE/MCTD subjects, we calculated the rate of annual outpatient visits [rheumatology/nephrology, primary care provider (PCP) and emergency department], hospitalizations and rheumatology/nephrology telephone consultations in the preceding year. We compared these outcomes in those with and without depression and anxiety using negative binomial regression.ResultsWe identified depression symptoms in 10 (20%) SLE/MCTD and 4 (8%) healthy subjects, representing a trend towards increased prevalence in unadjusted analysis (OR = 2.9, 95% CI 0.8-9.9, p = 0.09). Adjusted analysis did not show a significant difference; however, non-white race was a statistically significant independent risk factor for depression symptoms compared to white race (OR = 5.4, 95% CI 1.1-27.2, p = 0.04). We identified anxiety symptoms in 11 (22%) SLE/MCTD and 13 (26%) healthy subjects, which was not statistically different. Suicidal ideation was present in 7 (14%) SLE/MCTD and 2 (4%) healthy subjects, which was a statistically significant difference (OR = 5.4, 95% CI 1.02-28.3, p = 0.047). Of the 34% of SLE/MCTD subjects with any symptoms, only 24% had previous mental health care. Those with depression symptoms had a statistically significant lower rate of visits to the PCP (IRR = 0.38, 95% CI 0.19-0.76, p < 0.001). Anxiety symptoms were not associated with the healthcare utilization outcomes.ConclusionsDepression and anxiety symptoms were prevalent, and suicidal ideation significantly more common in SLE/MCTD than in healthy subjects. Non-white race was an independent risk factor for depression. Despite prevalent symptoms, there were poor rates of prior mental health treatment, and less frequent PCP visits among those with depression symptoms. Further investigation of barriers to mental health care and interventional strategies for symptomatic youth with SLE/MCTD is needed.

PReS-FINAL-2351: Children with probable SLE by ACR criteria may need more aggressive lupus treatment early in the disease course

The pediatric lupus patients are required to meet the American College of Rheumatology (ACR) minimum criteria to be included in the research cohort and considered for aggressive therapy. This approach may delay early aggressive therapy.

Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis

To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Cell surface CD154 expression (pre- and postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-kappaB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.

Laboratory medicine in pediatric lupus

AbstractPediatric lupus encompasses a broad variety of clinical manifestations of a systemic disease. Routine laboratory testing, autoantibodies, and complement levels can confirm the diagnosis and help monitoring and therapy of the disease, to ultimately improve outcomes. Additionally, tests can help to identify subsets of patients with specific risk factors and/or the involvement of selected organs/systems. The availability, refinement and accuracy of laboratory tests are instrumental to improve the diagnosis, treatment and prognosis of pediatric lupus patients.

MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus

Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients. We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis. We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002-2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES. Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management. MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults.

Childhood- and adult-onset lupus: an update of similarities and differences

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune rheumatic disease. Although its highest prevalence is among women of childbearing age, the disease is not confined within this population. A total of 15–20% of cases of SLE are diagnosed in children younger than 16 years (childhood-onset lupus). Although there have been few studies directly comparing childhood- to adult-onset lupus, there is substantial evidence to suggest that pediatric lupus patients display some differences in their disease profile compared with adult-onset populations. Overall, an increased male-to-female ratio, a higher prevalence of nephritis and CNS involvement necessitating a more sustained need for steroids and immnosuppressive drugs, and a higher prevalence of progression to end-stage renal disease are distinguishing features of childhood-onset lupus. In contrast, a higher prevalence of pulmonary involvement, arthritis and discoid lupus are reported in adult-onset SLE patients. Furthermore, childhood-onset lupus patients may experience a serious negative impact on their psychosocial and physical development, issues that pose extra challenges to healthcare providers. Growth delay, osteoporosis, the psychological effect of steroid-induced alterations of the physical image, and often poor treatment compliance are the issues that need to be addressed in pediatric lupus populations. In this review, we compare the epidemiological, clinical and laboratory features, and treatment options of childhood- and adult-onset lupus, and comment on the applicability of the instruments that measure activity, severity and cumulative disease damage in childhood-onset disease. In addition, we highlight special issues of concern for pediatric lupus patients, discussing the significance in the transition from pediatric to adult rheumatology care.