Juvenile-onset Systemic Lupus Erythematosus Research Articles

The influence of carrying MEFV gene variants on juvenile systemic lupus erythematosus.

Juvenile-onset systemic lupus erythematosus (jSLE) patients typically have a more severe disease course than adults with SLE. We aimed to assess the prevalence and disease course of jSLE patients carrying MEFV variants. MEFV variant analyses were performed in 44 jSLE patients and effect of these variants on disease severity and course was analyzed by SLEDAI score and SLICC/ACR index. Ten of the patients (22.7%) had a MEFV variant. The median (min-max) SLEDAI score and SLICC/ACR index were 2(0-13) and 0(0-3), respectively. Median age at disease onset, disease duration, SLICC/ACR indexes, SLEDAI scores, clinical and laboratory findings of the patients were comparable in carriers of variants and non-carriers. Nineteen patients (43.2%) had biopsy-proven lupus nephritis and four of these patients had MEFV variants. There was no significant difference between patients with and without MEFV carriers in terms of lupus nephritis. Even though not significant statistically, renal involvement was milder in MEFV carriers than non-carriers. The presence of MEFV variants does not increase the overall susceptibility to jSLE in our cohort, while larger number of patients is required to display the protective role of MEFV variants in jSLE.

Risk factors for bone loss in juvenile-onset systemic lupus erythematosus: a prospective study.

Juvenile-onset systemic lupus erythematosus (JoSLE) is associated with low bone mass for age and fractures; nevertheless, risk factors for bone impairment are poorly understood. The aim of this study was to evaluate risk factors for bone mass loss in JoSLE patients. Forty-nine female JoSLE patients were evaluated at baseline and after a 3.5-year follow-up regarding clinical, laboratory (including bone turnover markers), areal bone mineral density (aBMD) and bone microarchitecture parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Based on the difference between final and baseline aBMD value, the patients were divided into three groups: aBMD gain (BG), aBMD loss (BL) and aBMD no change (NC). The mean patient age was 18.7 ± 3.3 years. Sixty-one percent of patients presented with aBMD gain, 18.4% aBMD loss, and 20.4% remained stable during this follow-up period. Comparing the BL with the BG group, there was a higher frequency of alcohol consumption (p = 0.009), a higher frequency of inadequate calcium intake (p = 0.047) and lower levels of baseline procollagen type 1 amino-terminal propeptide (P1NP) (p = 0.036) in the BL group. Moreover, worsening of HR-pQCT parameters trabecular volumetric density (p = 0.003) and cortical thickness (p = 0.009) was observed in the BL group. In addition, a higher frequency of renal activity was observed comparing the BL + NC with the BG group (p = 0.036). This is the first longitudinal study that has analyzed the risk factors of bone loss in JoSLE patients. The authors emphasize the importance of evaluating lifestyle habits and renal disease activity in these young women. Furthermore, this study suggests that trabecular and cortical compartments deteriorated, and low levels of P1NP may be a predictor of bone impairment in JoSLE.

The human glomerular endothelial cells are potent pro-inflammatory contributors in an in vitro model of lupus nephritis

Juvenile-onset lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus patients (JSLE). As the exact role of human renal glomerular endothelial cells (GEnCs) in LN has not been fully elucidated, the aim of this study was to investigate their involvement in LN. Conditionally immortalised human GEnCs (ciGEnCs) were treated with pro-inflammatory cytokines known to be involved in LN pathogenesis and also with LPS. Secretion and surface expression of pro-inflammatory proteins was quantified via ELISA and flow cytometry. NF-κΒ and STAT-1 activation was investigated via immunofluorescence. Serum samples from JSLE patients and from healthy controls were used to treat ciGEnCs to determine via qRT-PCR potential changes in the mRNA levels of pro-inflammatory genes. Our results identified TNF-α, IL-1β, IL-13, IFN-γ and LPS as robust in vitro stimuli of ciGEnCs. Each of them led to significantly increased production of different pro-inflammatory proteins, including; IL-6, IL-10, MCP-1, sVCAM-1, MIP-1α, IP-10, GM-CSF, M-CSF, TNF-α, IFN-γ, VCAM-1, ICAM-1, PD-L1 and ICOS-L. TNF-α and IL-1β were shown to activate NF-κB, whilst IFN-γ activated STAT-1. JSLE patient serum promoted IL-6 and IL-1β mRNA expression. In conclusion, our in vitro model provides evidence that human GEnCs play a pivotal role in LN-associated inflammatory process.

Vasculitis in Juvenile-Onset Systemic Lupus Erythematosus.

Juvenile-onset systemic lupus erythematosus (JSLE) is a rare, heterogeneous multisystem autoimmune disease that can affect any organ, and present with diverse clinical and serological manifestations. Vasculitis can be a feature of JSLE. It more commonly presents as cutaneous vasculitis than visceral vasculitis, which can affect the central nervous system, peripheral nervous system, lungs, gut, kidneys, heart, and large vessels. The incidence and prevalence of vasculitis in JSLE has not been well described to date. Symptoms of vasculitis can be non-specific and overlap with other features of JSLE, requiring careful consideration for the diagnosis to be achieved and promptly treated. Biopsies are often required to make a definitive diagnosis and differentiate JSLE related vasculitis from other manifestations of JSLE, vasculopathies, and JSLE related antiphospholipid syndrome. Visceral vasculitis can be life threatening, and its presence at the time of JSLE diagnosis is associated with permanent organ damage, which further highlights the importance of prompt recognition and treatment. This review will focus on the presentation, diagnosis, management and outcomes of vasculitis in JSLE, highlighting gaps in the current evidence base.

Challenges of achieving clinical remission in a national cohort of juvenile-onset systemic lupus erythematosus patients.

The multisystem involvement and variable course of juvenile-onset systemic lupus erythematosus (JSLE) make it difficult to assess disease activity over time. International consensus definitions of inactive disease and clinical remission have been proposed. The aim of this study was to determine the proportion of patients meeting these criteria in a large national cohort of JSLE patients and the association between achieving inactive disease and clinical remission with disease activity at presentation and time to diagnosis. Patients diagnosed with JSLE aged ≤17 years with a minimum of 12 months follow-up participating in the UK JSLE Cohort Study were assessed against these criteria at baseline, 1 year and final clinic visit. A total of 218 patients with mean follow-up duration of 4.7 years were included and analyzed at baseline visit, of which 93 and 209 were available for analysis at the 1-year and the last follow-up visits, respectively. Eighty-five percent at 1 year and 62% at final follow-up still had active disease while only 6% and 9%, respectively, achieved inactive disease according to the proposed criteria. The majority of patients continued to require immunosuppressive treatment despite their prolonged follow-up with only two patients achieving clinical remission on medication and none off medication. A large number of patients did not meet the criteria for inactive disease due to isolated laboratory abnormalities such as reduced lymphocyte count. Isolated low lymphocyte count was the reason for not fulfilling the inactive disease criteria in 20/79 (25%) patients at 1 year and 14/130 (11%) patients at final follow-up visit. No statistically significant differences in relation to time to diagnosis and disease activity at presentation were found between patients achieving inactive disease compared to those who did not, at 1 year and final follow-up. The majority of patients failed to achieve the proposed criteria for inactive disease and continued to require immunosuppressive treatment. This reflects the high burden of disease in JSLE despite immunosuppressive therapy. A significant proportion of patients had isolated laboratory abnormalities of potentially limited clinical significance, suggesting that some modifications of the proposed criteria may be required.

Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration.

Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty.

Assessment of Health Related Quality of Life (HRQL) in Egyptian Children with Rheumatic Diseases; Its Relation to Disease Activity and Functional Disability

Background Many pediatric rheumatic diseases persist into adulthood, with negative squeal from the disease or its treatment. We aimed to assess health related quality of life in a group of children with rheumatic diseases and its relation to disease activity and functional disability. Materials and Methods Fifty one patients were divided into three groups: Group 1 includes 27 patients diagnosed as juvenile idiopathic arthritis (JIA), Group 2 includes 15 patients diagnosed as juvenile onset systemic lupus erythematosus (SLE) and Group 3 includes nine patients; three diagnosed as Juvenile Dermatomyositis, three diagnosed as Familial Mediterranean Fever and three female’s patients diagnosed as Juvenile Scleroderma. Childhood Health Assessment Questionnaire (CHAQ), Pediatric Quality of Life generic core scale version 4.0, Visual analogue scale for pain and Visual analogue scale (VAS) for global assessment were recorded. The activity index was assessed in each patient according to the nature of the disease. Results In JIA patients, the mean PedsQL score was 73.6+ 15.4, the mean CHAQ score was 0.7+ 0.7, the mean DAS28 was 3.5+ 0.9, with a significant negative correlation between PedsQL and CHAQ (p=0.48), VAS pain (p=0.001), and DAS 28 activity index (p=0.017). In SLE patients, the mean PedsQL was 66.4 + 20.3, mean CHAQ score was 0.7 + 0.67 and mean SLEDAI-2K was 24.2 + 14.6 with no significant correlation between functional disability and SLEDAI-2K (p=0.539). PedsQL showed a significant negative correlation with SLEDAI-2k (p=0.001), and positive correlation between CHAQ (p=0.022). Conclusion Health related quality of life in patients with juvenile rheumatic diseases is correlated with disease activity and functional disability and should be assessed in regular basis.

Heart rate variability in juvenile systemic lupus erythematosus patients.

Başaran Ö, Çetin İİ, Aydın F, Uncu N, Çakar N, Ekici F, Çelikel Acar B. Heart rate variability in juvenile systemic lupus erythematosus patients. Turk J Pediatr 2019; 61: 733-740. Although neurological involvement has been well recognized in patients with systemic lupus erythematosus (SLE), autonomic nervous system (ANS) involvement has rarely been studied, and has shown conflicting results. The aim of this study was to evaluate the ANS functions by using heart rate variability (HRV) in juvenile patients with SLE. Sixteen juvenile-onset SLE patients and 16 healthy controls were enrolled in the study. All participants underwent 24-hour Holter electrocardiogram monitoring and HRV indices were assessed. The SLE disease activity index (SLEDAI) score was used to assess the disease activity. We analyzed the correlation between disease duration, the SLEDAI score, and the HRV domains. Overall HRV was diminished in patients with SLE compared to controls. There were negative correlations between day and night RMSSD (root-mean-square of the successive normal sinus NN interval differences) and PNN50 (percentage of successive normal sinus NN intervals > 50 ms) values, and SLEDAI (r= -0.588 p=0.017; r= - 0.607 p= 0.013; r= -0.498 p=0.049; r= -0.597 p=0.015, respectively). There were positive correlations between both day and night LF/HF values and SLEDAI (r=0.766 p=0.001; r=0.635 p=0.008, respectively). The results suggest that autonomic dysfunction exists in juvenile patients with SLE. As these children are at increased risk for cardiovascular disease, they need to be assessed for the development of autonomic dysfunction.

Growing international evidence for urinary biomarker panels identifying lupus nephritis in children – verification within the South African Paediatric Lupus Cohort

A urinary biomarker panel including alpha-1-acid-glycoprotein (AGP), lipocalin-like-prostaglandin-D-synthase (LPGDS), transferrin and ceruloplasmin demonstrates an 'excellent' ability for identifying active lupus nephritis in UK/US children. This study aimed to assess whether this panel identifies active lupus nephritis within the South African Paediatric Lupus Cohort. Juvenile-onset-systemic lupus erythematosus (JSLE) patients aged < 19 years at diagnosis and healthy controls were recruited. Patients were categorized as having active lupus nephritis (renal BILAG score; A/B and previous histological confirmation) or inactive lupus nephritis (renal BILAG score: D/E). Urinary biomarkers were quantified by ELISA. Mann-Whitney U-test compared biomarker levels between groups. Binary logistic regression and receiver operating curve analysis assessed biomarker combinations. Twenty-three juvenile-onset-systemic lupus erythematosus patients were recruited with a median age of 13.5 years (interquartile range (IQR) 12.7-14.9) and disease duration of 2.6 years (IQR 1.8-4.0). Eighteen healthy controls had a median age of 11.0 years (IQR 10.0-12.0). AGP, LPGDS, transferrin, ceruloplasmin and VCAM-1 were significantly higher in active than in inactive lupus nephritis patients (corrected p-values, all pc < 0.05), with no difference between inactive lupus nephritis patients and healthy controls (all pc = 1.0). The optimal biomarker combination included AGP, ceruloplasmin, LPGDS and transferrin (area under the curve = 1.0). A urinary biomarker panel comprising AGP, ceruloplasmin, LPGDS and transferrin previously validated within UK/US cohorts also performed excellently within a racially distinct South African cohort which displayed more severe lupus nephritis.

The effectiveness and safety of biological therapeutics in juvenile-onset systemic lupus erythematosus (JSLE): a systematic review

To systematically review and summarize the available literature regarding the effectiveness and safety of biologics in the treatment of juvenile-onset systemic lupus erythematosus. PubMed was systematically searched for relevant literature (2012-2017 inclusive) using the following criteria: (1) patients diagnosed with juvenile-onset systemic lupus erythematosus (≤18 years at diagnosis); (2) treatment with any biological agent; and (3) outcome measures assessing effectiveness and safety. Systematic literature reviews, meta-analyses, randomized controlled trials, cohort studies, case control studies, cross sectional surveys and case-series with ≥3 patients were included. Independent extraction of articles by two authors using predefined criteria was performed. The quality of each study was assessed using CASP tools and Oxford CEBM Levels of Evidence. Nine articles met inclusion criteria: six cohort studies, two case series and one pilot study, totalling 230 patients. All but one article reported the effects of rituximab, the other those of belimumab. Overall, patients had active disease refractory to standard of care regimens using corticosteroids and immunosuppressants. Available evidence for rituximab demonstrated improvements in disease activity, complement levels and anti-dsDNA titres accompanying a steroid-sparing effect. Rituximab can be considered an effective treatment in juvenile-onset systemic lupus erythematosus patients with severe disease manifestations and/or refractory disease. Based on current evidence, use of belimumab in juvenile-onset systemic lupus erythematosus patients cannot be recommended. The long-term safety of these biological agents remains uncertain. Further prospective studies, ideally robust randomized controlled trials, are urgently needed to obtain more accurate data on the effectiveness and long-term safety of rituximab, belimumab and other biologics in juvenile-onset systemic lupus erythematosus.

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER)

ObjectivesTo identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. MethodsThis is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. ResultsMean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). ConclusionsIn a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

Clinical predictors of active LN development in children - evidence from the UK JSLE Cohort Study.

Juvenile-onset systemic lupus erythematosus (JSLE) patients may develop lupus nephritis (LN) during their initial presentation, or later in their disease. This study aimed to assess whether clinical/demographic factors characterize patients with LN within the United Kingdom JSLE Cohort Study, and whether such factors predict subsequent LN development. Univariate logistic regression modelling compared clinical/demographic factors in patients with and without LN at baseline. For those who subsequently developed LN, Cox proportional-hazard modelling was used to test the association between such factors and time to LN development. Covariates with p < 0.2 univariately were included within a multiple-regression model. A total of 121/331 (37%) patients presented with active LN at baseline, with first American College of Rheumatology (ACR) score ( p < 2.0 × 10-16), severe hypertension ( p = 0.0006), proteinuria ( p < 2.0 × 10-16), creatinine ( p = 1.0 × 10-16), erythrocyte sedimentation rate ( p = 1.0 × 10-16), neutrophils ( p < 2.0 × 10-16), complement 3 (C3) ( p = 4.0 × 10-16) and ethnicity ( p = 3.0 × 10-13) differing between those with and without LN. Of the 210 individuals without active LN at baseline, 13 patients had a single visit and were excluded from further analysis. Thirty-four of 197 (17%) developed LN after a median of 2.04 years (interquartile range, 0.8-3.7), with higher ACR scores ( p = 0.014 , hazard ratio (HR) = 1.45, 95% confidence interval (CI) = 1.08-1.95) and lower C3 levels ( p = 0.0082 , HR = 0.27, 95% CI = 0.10-0.68) demonstrated as predictors of subsequent LN. Clinical and demographic factors can help to characterize patients at increased risk of LN.

Podocytes contribute, and respond, to the inflammatory environment in lupus nephritis.

Lupus nephritis (LN) affects up to 80% of juvenile onset systemic lupus erythematosus patients, leading to end stage renal failure requiring dialysis or transplantation in 10–15%. Podocytes are specialized epithelial cells of the glomerulus known to be a key site of damage in glomerular diseases. However, their roles in LN have yet to be fully identified. This project aims to identify structural and functional roles of podocytes in an in vitro model of LN. Conditionally immortalized podocytes were treated with proinflammatory cytokines (IL-1β, TNF-α, IFN-α, and IFN-γ) alone and in combination in an in vitro model of LN and were assessed for their structural and functional characteristics. Podocytes produce TNF-α, IL-6, IL-8, VEGF, granulocyte-monocyte colony stimulating factor (GM-CSF), and macrophage colony stimulating factor (M-CSF) at relatively low levels under basal conditions; stimulation with IL-1β led to increased secretion of IL-6 (P = 0.011), IL-8 (P = 0.05), VEGF (P = 0.02), and M-CSF (P = 0.03). Stimulation with TNF-α led to increased secretion of M-CSF (P = 0.049) and stimulation with IFN-γ led to novel production of IL-10 (P = 0.036) and interferon-γ-inducible protein-10 (P = 0.036). Podocytes demonstrate a reduction in the area covered by filamentous-actin in response to IL-1β treatment within 1 h (P = 0.011), which is restored by 24 h, associated with an increase in the level of intracellular calcium but not with increased cell death. Podocytes contribute to the inflammatory milieu in LN through cytokine/chemokine secretion and respond to the inflammatory milieu via rearrangement of the actin cytoskeleton leading to effacement, a well-known method of protection against apoptosis in these cells. This demonstrates that podocytes are involved in the pathogenesis of LN.

CURRENT INTERNATIONAL GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF JUVENILE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) with its onset in childhood or adolescence is a significant problem in the practice of pediatricians and rheumatologists due to diagnostic difficulties, clinical features, and the greater likelihood of unfavorable prognosis. About 20% of SLE patients fall ill at the age of 18 years. Only 13% of patients with juvenile-onset SLE have a drug-free remission in adulthood and have a lower quality of life than population controls. The paper discusses the latest international guidelines for the diagnosis, monitoring, and treatment of SLE in children and adolescents, which were published in 2017, with comments based on the data available in the literature and on practical experiences in managing these patients.

Neuropsychiatric Involvement in Juvenile-Onset Systemic Lupus Erythematosus.

Objective Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by multisystem involvement, including the nervous system. In the present study, we aimed to assess neuropsychiatric manifestations in juvenile-onset systemic lupus erythematosus (JSLE) in Iran. Methods One hundred and forty-six pediatric onset patients with SLE who had registered in our pediatric rheumatology database were evaluated prospectively and cross sectionally within 2013-2015. Data including sex, age, age at the time of diagnosis, age at the time of study, physical examination, laboratory review, and neuropsychiatric inventory were extracted from this database. Classification of neuropsychiatric JSLE was according to the 1999 American College of Rheumatology (ACR) neuropsychiatric manifestations of SLE case definitions. Result A total number of 41 patients with neuropsychiatric symptoms were selected. The patients' average age was 12.2 years. The most common neuropsychiatric symptoms were seizures, migraine, and depression. The mean age at the onset of symptoms was 10.2 ± 3 years. Mean follow-up period was 57±34 (range: 12-120) months. From 41 SLE patients, 18 (43.9) presented symptoms at the time of diagnosis. In thirteen (31.7%) patients, neurological symptoms were developed more than 1 year after SLE diagnosis. Headache was the most common feature (13%), followed by seizure (9.5%) and chorea (3.4%). Other neurological manifestations included cranial nerve involvement (0.7%), loss of consciousness (2.7%), and impaired deep tendon reflex neuropathy (2.5%). The least common neuropsychiatric JSLE manifestation was aseptic meningitis seen in only one patient (0.7%). Conclusion The presence of headache, mood disorders, psychosis, depression, and other neuropsychological manifestations in a patient with JSLE should prompt investigations into diagnosis of the primary nervous system involvement in order to reduce mortality and morbidity.

STAT4 gene polymorphism in two major autoimmune diseases (multiple sclerosis and juvenile onset systemic lupus erythematosus) and its relation to disease severity

BackgroundMultiple sclerosis (MS) and systemic lupus erythematosus (SLE) are chronic autoimmune mediated diseases with strong genetic and environmental components. The aim of this study is to evaluate the association of STAT4 gene polymorphism with multiple sclerosis (MS) and juvenile onset systemic lupus erythematosus (JO-SLE) and its relation to disease severity.MethodsGroup 1 consisted of 40 MS patients while group 2 included 40 JO-SLE patients. Forty healthy volunteers (controls) were included in this study. STAT4 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe STAT4 CC genotype and GC genotype frequencies were significantly more detected in MS and JO-SLE patients than in controls. The frequency of the STAT4 C allele was significantly higher in patients with MS and those with JSLE compared to controls. Malar rash, photosensitivity, and hair falling were significantly more detected in CC subtype. Malar rash, photosensitivity, and hair falling were significantly more detected in CC subtype. Increased 24-h protein in urine (mg/24 h) and ANA positivity, anti-ds-DNA, anti Sm antibodies’ detection and decreased C3 and C4 levels showed a significantly difference in CC patients. Meanwhile, only increased 24-h protein in urine (mg/24 h) and ANA positivity were significantly more detected in GC patients. STAT4 CC genotype showed a significant increase in the SLE activity index (SLEAI) score and damage index as compared to the STAT4 GG genotype patients. No significant difference was detected in MS Kurtzke’s Expanded Disability Status Scale (EDSS) comparing different STATE 4 genotypes.ConclusionsSTAT4 polymorphism was significantly associated with MS and JO-SLE. Though homozygous JO-SLE patients are more risky for severe disease manifestations, homozygous MS patients are not risky for severe disease disability.

O30 The immunopathogenesis of juvenile-onset SLE could be associated with altered immune cell plasma membrane lipids and lipoprotein metabolism

O30 The immunopathogenesis of juvenile-onset SLE could be associated with altered immune cell plasma membrane lipids and lipoprotein metabolism

Depression Risk in Young Adults With Juvenile- and Adult-Onset Lupus: Twelve Years of Followup.

To compare major depression risk among young adults with juvenile-onset and adult-onset systemic lupus erythematosus (SLE), and to determine demographic and health-related predictors of depression. Young adults with SLE ages 18-45 years (n = 546) in the Lupus Outcomes Study completed annual telephone surveys from 2002-2015, including assessment of depression using the Center for Epidemiologic Studies Depression Scale (CES-D), and self-report measures of sociodemographics and health characteristics. Juvenile-onset SLE was defined as age <18 years at diagnosis (n = 115). Repeated-measures analysis was performed to assess the risk for major depression (CES-D ≥24) at any point in study, and logistic regression was used to assess for recurrent (present on ≥2 assessments) major depression. Major depression was experienced by 47% of the cohort at least once during the 12-year study period. In adjusted analyses, juvenile-onset SLE patients had an increased risk of having a major depressive episode (odds ratio [OR] 1.7 [95% confidence interval (95% CI) 1.0-2.7]) and recurrent episodes (OR 2.2 [95% CI 1.2-4.3]), compared to participants with adult-onset SLE. Older age, lower educational attainment, and physical function, higher disease activity, and a history of smoking were associated with an increased depression risk. Juvenile-onset SLE patients had a higher risk of major depression across all educational groups. Young adults with SLE, particularly those with juvenile-onset disease, are at high risk for major depression, which is associated with increased disease activity, poorer physical functioning, and lower educational attainment. Early depression intervention in young adults with SLE has the potential to improve both medical and psychosocial outcomes.

The management of lupus in young people.

Juvenile onset systemic lupus erythematosus (JSLE) accounts for 20% of all SLE presentations. It most commonly develops around adolescence. It is a serious and complex autoimmune disease that, although requiring specialist care, will benefit from the active involvement of general practice. JSLE is a chronic autoimmune disease that can affect any part of the body including skin, joints, and the major organs. It most commonly presents around adolescence (median age at diagnosis 12–14 years). The female preponderance is less marked in adolescents than in adults.1 JSLE patients have a more aggressive disease than adults. They have higher rates of organ involvement including renal and liver disease, are more likely to die in the acute phase of the illness, and sustain more organ damage. In contrast with some juvenile arthritis patients, JSLE patients do not ‘grow out’ of the disease. They will therefore have a lengthy disease duration and incur a great burden of medication and its unwanted effects. JSLE patients are still about 18 times more likely to die than their peers (standardised mortality rate [SMR] JSLE 18.3, confidence interval [CI] = 11.8 to 28.3), in contrast with adults (SMR 3.1, CI = 2.6 to 3.9).1 Deaths usually relate to active JSLE with organ involvement, often in the context of suboptimal treatment adherence. Counselling patients with organ involvement about the controllable but serious nature of the illness is difficult but essential. JSLE symptoms are highly variable from a relatively mild disease such as a rash with joint pains and fatigue, to a …

Cutaneous manifestations of juvenile onset lupus erythematosus: A clinical study

Introduction: Juvenile-onset systemic lupus erythematosus (SLE) is one of the most common systemic autoimmune connective tissue disorders in children. Studies focusing on the mucocutaneous manifestations of childhood lupus are scanty in literature. Objectives: This study was an attempt to describe the cutaneous changes seen in Pediatric Lupus and to correlate with the histopathological and immunofluoresecence findings. Methods: This was a retrospective study. All children under the age of 18 years who were diagnosed to have SLE according to the ACR criteria and presented to the dermatology outpatient department during a period of 1 year were included in the study. Details including clinical features, investigation findings including immunological tests and skin biopsy findings were noted. The analysis was performed using descriptive statistical tools such as percentage and frequency. Results: A total of 14 cases, average age at presentation was 10.14 years. Among the cutaneous manifestations, the most common presenting feature was urticarial vasculitis. Malar rash was seen in 57% of cases. Other cutaneous features seen were diffuse alopecia, oral ulcers. Antinuclear antibody was positive in all cases. Conclusion: Pediatric lupus tends to have a more aggressive course than adult lupus. Early diagnosis and treatment is necessary to prevent progression and development of complications.