Pediatric Systemic Lupus Erythematosus Patients Research Articles

IKZF1 rs4132601 and rs11978267 gene polymorphisms and paediatric systemic lupus erythematosus; relation to lupus nephritis.

The demographic factors, the socioeconomic status and the ethnicity of populations are important players that determine the incidence, the prevalence and the spectrum of systemic lupus erythematosus (SLE) clinical presentations in different populations. Therefore, the purpose of the present research was to investigate the possible association between the Ikaros family zinc finger 1 gene (IKZF1) rs4132601 and rs11978267 single nucleotide polymorphisms (SNPs) and SLE susceptibility and clinical presentations including lupus nephritis (LN) among Egyptian paediatric patients. After DNA extraction from Ethylenediaminetetraacetic acid (EDTA) blood samples for 104 paediatric SLE (pSLE) patients and 286 healthy controls, the investigated SNPs (IKZF1 rs4132601 and rs11978267) were genotyped using TaqMan-Real-time Polymerase chain reaction (PCR). The G allele, GG and GT genotypes of IKZF1 rs4132601 were associated with pSLE (pc<.001, OR 2.97, 3.2 and 2.25, respectively). The GG and GA haplotype were more frequent in pSLE patients than other haplotypes (pc<.001, OR 3.47 and pc=.004, OR=2.8, respectively). The studied SNPs have no impact on the distinctive features of pSLE. The rs4132601 TG genotype was significantly associated with proliferative LN (pc=.03) The IKZF1 rs4132601 can be considered a risk factor for SLE in the cohort of Egyptian children. The TG genotype of the IKZF1 rs4132601 may predispose to proliferative LN.

Risk Factors for Pneumocystis jirovecii Pneumonia in Children With Systemic Lupus Erythematosus Exposed to Prolonged High-Dose Glucocorticoids.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection in immunocompromised children with systemic lupus erythematosus (SLE). Prophylaxis against PJP in high-risk children is crucial, but the risk factors for PJP in children with SLE are not adequately characterized. This study sought to identify the risk factors for PJP in long-term glucocorticoid-treated pediatric SLE patients. This study encompassed 71 treatment episodes involving 64 children with prolonged (≥4 weeks) high-dose (≥20 mg/d prednisone) steroid regimens. Fourteen treatment episodes involved the PJP, whereas others did not. Risk factors for PJP were assessed through Cox regression. The predictive value of these factors was evaluated using receiver operating characteristic curves. The incidence of PJP in different risk groups was compared using the Kaplan-Meier method. The creatinine (hazard ratio, 1.009; 95% confidence interval [CI], 1.001-1.017; p = 0.021) and the lowest lymphocyte count (hazard ratio, 0.007; 95% CI, 0.000-0.373; p = 0.014) were independent risk factors for PJP in children with SLE. The receiver operating characteristic curve showed that using creatinine greater than 72.5 μmol/L and the lowest lymphocyte count less than 0.6 × 109/L as risk predictors for PJP resulted in an area under the curve value of 0.934 (95% CI, 0.870-0.997; p < 0.001). The study revealed a significant increase in PJP prevalence (p < 0.001) in children with elevated creatinine levels and low lymphocyte count. Elevated levels of creatinine and decreased lymphocyte count are identified as distinct risk factors for PJP in children with SLE who receive prolonged high-dose steroid therapy.

Clinical profiles in pediatric systemic lupus erythematosus: a retrospective study

Aims: This study aimed to analyse clinical and laboratory findings, prognosis, and survival of systemic lupus erythematosus (SLE) patients, differentiating according to gender, pubertal status, and renal involvement. Methods: Ninety-six pediatric SLE patients, diagnosed using ACR criteria, were retrospectively analyzed. Inclusion criteria comprised age under 18, meeting at least four ACR criteria, and six months of monitoring. Data encompassed demographics, symptoms, diagnosis, organ involvement, autoantibodies, treatment, prognosis, and survival. Categorization was based on gender and pubertal status. Renal biopsies followed WHO-ISN classification, with asymptomatic findings termed “silent lupus nephritis.” Biopsied patients were divided into proliferative and non-proliferative lupus nephritis categories, excluding irreversible damage cases. Outcomes studied included remission, relapse, end-stage renal failure, and mortality. Results: Among 96 participants, females constituted 82.3%, males 17.7%, resulting in a female-to-male ratio of 4.6:1. Mean age at diagnosis was 11.9 years, with 37 prepubertal (38.5%) and 59 pubertal (61.5%) cases. Oral-nasal ulcers (p=0.01) were more prevalent in males related to system involvement. Nephrotic syndrome prevalence increased from 21.6% in prepubertal to 44.1% in pubertal cases (p=0.025). Positive Anticardiolipin IgM antibodies decreased from 56.2% in prepubertal to 25.9% in pubertal cases (p=0.047). Type IV lupus nephritis was predominant, followed by Type II, in prepubertal and pubertal groups and both genders. Proliferative lupus nephritis showed higher rates of renal involvement (95.7% vs. 65.6%), nephrotic syndrome (46.8% vs. 21.9%), proteinuria (89.4% vs. 62.5%), hematuria (57.4% vs. 28.1%), elevated creatinine (43.5% vs. 9.7%), and low albumin (67.4% vs. 23.3%). Cases with proliferative lupus nephritis had higher neuropsychiatric involvement (36.2% vs. 12.5%), seizures (25.5% vs. 3.1%, p=0.008), and increased hemolytic anemia rates (78.7% vs. 56.2%, p=0.033). Thirteen had silent lupus nephritis, revealing various types through biopsy. All reported deaths occurred within the first five years, resulting in stable 91% survival rates at 5, 10, and 15 years. Conclusion: This study provides insights into the clinical, prognostic, and survival characteristics of pediatric systemic lupus erythematosus (SLE), revealing notable patterns related to gender, pubertal development, and renal involvement. There is an association between proliferative lupus nephritis and renal involvement, nephrotic syndrome, and neuropsychiatric symptoms. Significantly, silent lupus nephritis highlights the complex renal implications, necessitating diligent surveillance for prompt intervention.

Coexistence of Allergic Diseases in Pediatric Systemic Lupus Erythematosus Patients: Prevalence, Clinical manifestation and Severity.

Objective. This study aimed to evaluate allergic diseases in pediatric patients with SLE and their association with SLE disease activity. Method. Patients with SLE aged ≤18 years were enrolled. Allergic diseases were screened using the International Study of Asthma and Allergies in Childhood questionnaire. Patients with a positive allergic disease screen were evaluated by a pediatric allergist for diagnostic confirmation and severity assessment. Results. Out of 118 patients, 16 patients (13.56%) were confirmed to have 1 or more allergic diseases; fourteen with allergic rhinitis, 4 with asthma, and 2 with atopic dermatitis. Two patients had severe-persistent allergic rhinitis and one patient had undiagnosed, uncontrolled severe asthma. No statistically significant correlations between the severity of allergic diseases and SLE disease activity were identified. Conclusions. The overall prevalence of allergic disease among pediatric patients with SLE is within the range of the general population. Severe and undiagnosed allergic diseases and SLE can coexist.

Interleukin-6 and disease activity in childhood systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a complex disease with various manifestations. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities which plays an important role in immune regulation and inflammation. Serum level of IL-6 may be used as a parameter of disease activity, especially in pediatric SLE patients with mild disease activity or total remission with conflicting clinical manifestations and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores.&#x0D; Objective To identify the characteristics of serum IL-6 concentration in pediatric SLE with mild disease activities and total remission.&#x0D; Methods This case-control study was performed at the allergy-immunology outpatient clinic, Department of Child Health Dr. Cipto Mangunkusumo Hospital, Jakarta and Dr. Sardjito Hospital, Yogyakarta. Serum IL-6 concentration and disease activity were assessed in all pediatric SLE patients aged 1-18 years old. Disease activity was assessed with SLEDAI scores and serum level of IL-6 was measured by enzyme-linked immunosorbent assay.&#x0D; Results Among 60 subjects included in this study, 30 subjects with mild activities were in the case group and 30 subjects with total remissions were in the control group. There was no difference in serum IL-6 concentration between the case and control group (OR 0.483; 95%CI 0.041to 5.628; P=0.500). In this study, 2 subjects with urinary tract infection had high serum IL-6 concentrations.&#x0D; Conclusion There is no difference in serum IL-6 concentration between pediatric SLE patients with mild disease activities compared to total remissions.

Limited sampling strategy and population pharmacokinetic model of mycophenolic acid in pediatric patients with systemic lupus erythematosus: application of a double gamma absorption model with SAEM algorithm.

Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is widely used in the treatment of systemic lupus erythematosus (SLE). It has been shown that its therapeutic drug monitoring based on the area under the curve (AUC) improves treatment efficacy. MPA exhibits a complex bimodal absorption, and a double gamma distribution model has been already proposed in the past to accurately describe this phenomenon. These previous population pharmacokinetics models (POPPK) have been developed using iterative two stage Bayesian (IT2B) or non-parametric adaptive grid (NPAG) methods. However, non-linear mixed effect (NLME) approaches based on stochastic approximation expectation-maximization (SAEM) algorithms have never been published so far for this particular model. The objectives of this study were (i) to implement the double absorption gamma model in Monolix, (ii) to compare different absorption models to describe the pharmacokinetics of MMF, and (iii) to develop a limited sampling strategy (LSS) to estimate AUC in pediatric SLE patients. A data splitting of full pharmacokinetic profiles sampled in 67 children extracted either from the expert system ISBA (n = 34) or the hospital Saint Louis (n = 33) was performed into train (75%) and test (25%) sets. A POPPK was developed for MPA in the train set using a NLME and the SAEM algorithm and different absorption models were implemented and compared (first order, transit, or simple and double gamma). The best limited sampling strategy was then determined in the test set using a maximum-a-posteriori Bayesian method to estimate individual PK parameters and AUC based on three blood samples compared to the reference AUC calculated using the trapezoidal rule applied on all samples and performances were assessed in the test set. Mean patient age and dose was 13years old (5-18) and 18.1mg/kg (7.9-47.6), respectively. MPA concentrations (764) from 107 occasions were included in the analysis. A double gamma absorption with a first-order elimination from the central compartment best fitted the data. The optimal LSS with samples at 30min, 2h, and 3h post-dose exhibited good performances in the test set (mean bias - 0.32% and RMSE 21.0%). The POPPK developed in this study adequately estimated the MPA AUC in pediatric patients with SLE based on three samples. The double absorption gamma model developed with the SAEM algorithm showed very accurate fit and reduced computation time.

Accuracy and adequacy of photoprotection in pediatric systemic lupus erythematosus patients, and the effect of education on photoprotection: a prospective study

BackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease that is associated with multiple organ involvement and leads to significant morbidity and mortality. One of the important environmental factors that influences the exacerbation of preexisting SLE is ultraviolet (UV) radiation, so photoprotection is essential. The aims of this study were to evaluate the accuracy and adequacy of photoprotection in pediatric SLE patients, and to investigate the effect of education on photoprotection.MethodsSLE patients aged ≤ 18 years who attended pediatric outpatient clinics were prospectively enrolled. The accuracy and adequacy of photoprotection were assessed by the questionnaire, and compared between baseline and the ≥ 3-month follow-up timepoint. Comprehensive written and verbal photoprotection education was provided to all patients and parents/caregivers after the first assessment.ResultsOne hundred patients were included (mean age 13.6 ± 2.5, 92% female). At the first assessment, 79% of patients used sunscreen with a sunburn protection factor ≥ 30 (77%) and protection grade of ultraviolet A + + + (63%). Fifty-two percent of patients applied sunscreen every day. A minority of patients applied an adequate amount of sunscreen (32%), used water-resistant sunscreen (34%), used lip balm with sunscreen (23%) and reapplied sunscreen when sweating (13%). The most commonly missed areas when applying sunscreen were the ears and dorsum of the feet. The least often practiced sun protection behavior was wearing sunglasses. The most often reported activities during the peak UV index, were playing with friends and walking to the cafeterias. At the second assessment, the majority of photoprotection practices were improved in all aspects except using water-resistant sunscreen, reapplying sunscreen when sweating, applying sunscreen on the ears and dorsum of feet, and wearing sunglasses. The main reason for not using sunscreen switched from thinking it was unnecessary at the first assessment to disliking its texture at the second assessment.ConclusionsEducation on photoprotection was effective in improving photoprotection practices. The photoprotection practices that need to be specifically emphasized are applying an adequate amount of sunscreen and using lip balm with sunscreen. The photoprotection which were least practiced at both the first and seconds assessments were reapplying sunscreen when sweating, applying sunscreen on the ears and dorsum of the feet, and wearing sunglasses.

THU420 Analysis Of Factors Affecting Bone Mineral Density In Children And Adolescents With Systemic Lupus Erythematosus

Abstract Disclosure: M. Ahn: None. S. Park: None. B. Suh: None. Background: Children and adolescents with chronic disease are at risk of developing bone fragility. In particular, low bone mineral density(BMD) is increasingly recognized in pediatric patients with glucocorticoid treated rheumatic disease. The purpose of this study was to evaluate the clinical characteristics of children and adolescents with systemic lupus erythematosus(SLE), and to analyze the factors associated with a lower BMD in these patients. Methods: Children and adolescents diagnosed with SLE who had received GC treatment were included. Clinical and laboratory data including anthropometry, GC exposure, other anti-rheumatic drug treatment, biochemical markers related to bone metabolism, serologic markers of disease activity in SLE, lateral thoracolumbar(D-L) spine radiography, and BMD were collected. Lumbar spine bone mineral density (LSBMD) was measured by Dual-energy x-ray absorptiometry(DXA). The correlation between BMD and anthropometry, steroid and anti-rheumatic treatment, biochemical variables was investigated. Results: A total of 30 patients with median age of 17.5 years (range 12 -25years) were included. Of the 29 patients who had DXA done, 7 patients had LSBMD z score lower than −2.0, and diagnosed as osteoporosis. SLE patients with osteoporosis were compared with those with a z score higher than −2.0. These patients had longer GC exposure, higher cumulative GC dose, longer hydroxychloroquine exposure. The main factor correlated with a low BMD was duration of GC exposure. BMD was positively correlated with height at diagnosis. Bone metabolic markers and serologic markers of disease activity in SLE had no significant correlation with BMD. Conclusion: Children and adolescent SLE patients with OP had longer GC exposure, higher cumulative GC dose compared with those with LSBMD z score higher than −2.0. The main factor correlated with a low BMD was duration of GC exposure. Therefore, efforts should be made to reduce the duration of GC exposure and reduce medication to the lower possible maintenance dose. Since longer treatment duration affects BMD, close monitoring during the treatment period is recommended to prevent further loss of bone mass in pediatric SLE patients. Presentation: Thursday, June 15, 2023

Increase in Serum Ferritin Level as a Marker of Disease Activity in Pediatric Sys-temic Lupus Erythematosus (pSLE) Patients

Ferritin is an acute-phase reactant that is elevated in autoimmune disorders, including systemic lupus erythematosus (SLE). However, their correlation with disease activity scores has not been confirmed. Pandemic Covid-19 makes children visitation to hospital to get the treatment of SLE were delayed. This study aimed to evaluate correlation between serum ferritin and disease activity and its role in screening for flare in pediatric SLE (pSLE) patients during pandemic Covid-19. This is a cross-sectional study conducted in Saiful Anwar General Hospital Malang. Sampling was carried out sequentially on pediatric patients who met the criteria for Systemic Lupus International Collaborating Clinics (SLICC) and were recorded between July 2021-May 2022. All patients were interviewed and assessed for disease activity using SLE Disease Activity Index 2000 (SLEDAI-2k). A score &lt;4 was categorized as inactive disease. Biochemical, serological tests including markers of disease activity and ferritin level were measured by standard laboratory procedure. Comparison, correlation and ROC curve analyses were performed with SPSS software. There were 38 females pSLE participated in this study. The mean age of the patients were 12.6 ± 3.02 years. Serum ferritin significantly higher in active disease compared to inactive disease 84.50 ng/mL (68.00-151.75 ng/mL) ng/mL and 815.00 ng/mL (451.25-1570.00 ng/mL), a value of p&lt;0.05 was determined to be statistically significant. A significant correlation was found between serum ferritin with SLEDAI 2K (r = 0.890, p = 0.000). Correlation was also found between serum ferritin and IgM anti-double stranded-DNA (r = 0.325, p = 0.046), but not with other laboratory and serological parameters. In ROC curve analysis, we found that Area Under The Curve (AUC) 0.989, 95%CI 0.964-1.014, p value 0,000, with cut off value 297.50 with sensitivity 85% and specificity 94.4%. Ferritin was increased in active disease as compared to inactive disease and correlated with SLEDAI score and IgM-dsDNA. Thus, ferritin may be potential as an affordable and available marker of disease activity in pSLE during pandemic Covid-19.

Association of Serum Vitamin D with Active Human Cytomegalovirus Infections in Chinese Children with Systemic Lupus Erythematosus

Vitamin D (VD) plays an important role in infectious and autoimmune diseases. We investigated the association between the serum VD levels and active human cytomegalovirus (HCMV) infections in pediatric systemic lupus erythematosus (SLE) patients. From January 2015 to June 2021, 120 children were diagnosed with SLE, and 100 healthy children were enrolled. The serum 25-hydroxyvitamin D [25(OH)D] levels were detected using ELISA. The serum anti-HCMV IgM antibodies were measured by a chemiluminescence immunoassay. Comparisons of the 25(OH)D levels between SLE patients and healthy children were performed, as well as subgroups of SLE patients with or without active HCMV infections. The serum 25(OH)D levels of SLE patients were significantly lower than those of healthy children (35.3 ± 12.9 vs. 49.3 ± 15.3, P < 0.001). The VD deficiency ratio was higher in SLE patients (89.2%) than that in healthy children (52.0%). The serum 25(OH)D levels in the positive anti-HCMV IgM group were significantly lower than those of the negative anti-HCMV IgM group (30.6 ± 12.3 vs. 38.2 ± 12.5, P < 0.001). A severe VD deficiency ratio was significantly higher in HCMV-IgM(+)-SLE patients (42.2%) than that in HCMV-IgM(-)-SLE patients (13.3%). This study suggested that the serum VD level is associated with active HCMV infections in pediatric SLE patients.

Risk factors for mortality in systemic lupus erythematosus patients: Analysis of adult and pediatric cohorts in Taiwan.

Overall survival of systemic lupus erythematosus (SLE) patients significantly increased in recent decades, however, the relative risk of mortality is still high. Long-term survival outcome of pediatric SLE remains unclear. This study aims to explore the long-term survival rate and its predictors in patients with systemic lupus erythematosus (SLE). A retrospective, hospital-based cohort study was performed between 2004 and 2018 in a tertiary referral medical center in Taiwan. Data on comorbidities, medications, and causes of admission were collected for risk factor analysis using time-dependent multivariate Cox proportional hazards models. A total of 2392 adults and 115 pediatric SLE patients were enrolled (female, n = 2157 and 95, respectively). The 10-year survival rates were 93.2%, 90.2%, 98.9%, and 100% in adult women, adult men, girls, and boys with SLE, respectively. The overall mortality rate was 2.09 case/100 patient-years (PY) for male SLE and 1.39 case/100 PY for female SLE patients. Male SLE patients did not have a statistically significantly higher mortality rate than female SLE patients in each age stratification. Infectious disease (n = 119), heart failure (n = 21), and cerebrovascular accident (n = 14) were the leading causes of death in adult SLE patients. Advanced age (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.03-1.05), treatment with mean dosage of systemic glucocorticoid equivalent to >10 mg/d of prednisolone (HR: 1.71, 95% CI: 1.14-2.57), comorbidities with malignancy (HR: 1.94, 95% CI: 1.22-3.09), chronic kidney disease (HR: 1.86, 95% CI: 1.25-2.77), hypertension (HR: 1.42, 95% CI: 1.01-1.98), and admission due to bacterial pneumonia (HR: 1.92, 95% CI: 1.12-3.31) and sepsis (HR: 2.78, 95% CI: 1.51-5.13) were independent risk factors for mortality in SLE patients. SLE patients with advanced age, malignancy, chronic kidney disease, hypertension, treated with a higher average dosage of glucocorticoids, and admission due to bacterial pneumonia and sepsis have an increased risk of mortality.

Immunogenicity of Hepatitis B Vaccine in Pediatric Systemic Lupus Erythematosus Patients.

Pediatric patients with systemic lupus erythematosus (SLE) are at increased infectious risk caused by underlying immunologic dysregulation and immunosuppressive therapy. Hepatitis B virus (HBV) could be reactivated during the immunosuppressive treatment in patients with past HBV infections. Information on immunogenicity after hepatitis B (HB) immunization and reimmunization are still scarce. SLE patients 5-18 years of age who had completed a primary HB immunization were enrolled. Anti-HBs levels at enrollment and after each vaccine dose were determined. Patients with anti-HBs levels < 10 mIU/mL were administered 1 booster dose. After 1 booster dose, patients with negative anti-HBs levels were administered 2 more booster doses. Ninety-three SLE patients were enrolled. The prevalence of seroprotection assessed by anti-HBs > 10 mIU/mL after completion of a primary HB immunization was 25.8% (95% CI: 17.2-34.4). Lupus nephritis was associated with unprotective anti-HBs levels [odds ratio (OR): 4.341; 95% CI: 1.044-18.040]. The anti-HBs seroconversion was 72.3% (95% CI: 61.5-83.0) after 1 booster dose and increased up to 93.4% (95% CI: 86.9-98.4) after 3 booster doses. SLE Disease Activity Index-2000 score ≥ 4 (OR: 4.625; 95% CI: 1.45-14.80) was significantly associated with nonseroconversion after the first booster dose. Hypocomplementemia before the first and second booster doses (OR: 27; 95% CI: 1.26-578.35) was significantly associated with nonseroconversion after 3 booster doses. All pediatric SLE patients should be evaluated for HBV serological status before immunosuppressive treatment. SLE patients with SLE Disease Activity Index-2000 score > 4 should need 3 booster doses if their anti-HBs level was < 10 mIU/mL.

44 Pediatric onset systemic lupus erythematosus (p-SLE)

BackgroundPediatric onset Systemic lupus erythematosus (p-SLE) is multisystem autoimmune disease with disease onset before the 18th birthday. It is a highly complex disease with marked heterogeneity between patients, causing anything from mild to life-threatening disease.ObjectiveTo assess thrombomodulin (TM) and D-dimer levels in pediatric systemic lupus erythematosus patients and their correlation to disease activity.MethodsThis study included 40 children diagnosed with systemic lupus erythematosus. They were grouped according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score into group (A) [Mild activity] included 20 children with SLEDAI score less than or equal to 4, group (B) [Moderate-high activity] included 20 children with SLEDAI score >4. Also, 40 apparently healthy children were included as a control group. They were age and sex matched, with the children having SLE.ResultsThe two studied groups had significantly higher TM level than controls, furthermore group B had significantly higher TM level than group A (p< 0.008 in all). The two studied groups had significantly higher frequency of abnormally high TM level than controls, furthermore group B significantly had higher frequency of abnormally high TM level than group A (p< 0.02 in all). SLE children had significantly higher D dimer level than controls, furthermore group B had significantly higher D dimer level than group A (p≤ 0.006 in all). The two studied groups had significantly higher frequency of abnormally high D dimer level than controls, furthermore group B had significantly higher frequency of abnormally high D dimer level than group A (p≤ 0.03 in all). TM had a significant positive correlation with SLEDAI score as r = 0.342 and p = 0.031. D dimer had a significant positive correlation with SLEDAI score as r = 0.42 and p = 0.007.ConclusionThrombomodulin and D dimer are potentially valuable markers of the disease activity and thrombotic tendency in p SLE patients. Thus, regular evaluation may be useful for early detection of thrombotic complications.

The impact of excessive weight gain on hypertension, steroid induced diabetes, and disease parameters in pediatric systemic lupus erythematosus patients

Systemic inflammation, corticosteroids therapy, and reduced physical activity may predispose the accumulation of body fat in patients with systemic lupus erythematosus (SLE). However, less is known about its impact in children.(1,2) This study aims to explore the impact of excessive weight gain on pediatric SLE patients.

Systemic Lupus Erythematosus in Filipino Children: A 10-year Retrospective Analysis of Mortality, Morbidity and Survival

Background. Systemic Lupus Erythematosus (SLE) in children has been estimated to account for 15 to 20% of all SLE cases worldwide. It was described to have more severe disease at presentation including renal, neuropsychiatric, and hematologic involvements; more disease activity over time, and a significantly higher risk of organ damage. Thus, considered a significant risk factor for mortality among adult SLE patients.&#x0D; Objective. This is a retrospective cohort study aimed to determine the clinical profile, outcome, and survival of SLE among Filipino children.&#x0D; Methods. All SLE patients, less than 19 years old, diagnosed in the pediatric department of a tertiary hospital from January 2008 to December 2017 were included in the study. Their medical charts were retrieved for data gathering. Demographics, and clinical disease characteristics were collected from admission and on subsequent follow ups. Lost to follow up patients were contacted for updates of their current clinical status.&#x0D; Results. A total of 261 pediatric SLE patients were gathered. Average age at diagnosis is 14.5 years old (±2.7), with female to male ratio of 16:1. Symptoms starts at 3 months prior to consult (±2.1). Upon diagnosis, most of the patients have fever, malar rash, alopecia, oral ulcers, and proteinuria. Most common systemic organ involvement through time were mucocutaneous, hematologic, and renal. Steroids were the mainstay management for all patients, in which 95% started on oral Prednisone, while 71% needed IV Methylprednisolone in at least once during the disease course. Two patients received biologic treatment. Overall mortality rate was 14.9%, identified to be secondary to sepsis and/or SLE activity. Myocarditis, pleural effusion, and seizures were identified as significant risk factors for mortality. Survival rate at 1 year and 10 years were 92% and 79%, respectively.&#x0D; Conclusion. SLE in Filipino children mostly presents with mucocutaneous symptoms. Presence of seizures, myocarditis, and pleural effusion at any time of the disease entails risk for mortality. SLE nephritis is a substantial cause of morbidity due to its chronicity. The survival rate of Filipino children with SLE is comparable with the data from other developing countries.

Association of Human Leucocyte Antigen Class II, with viral load and immune response to Epstein-Barr virus in adult and pediatric Systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known to be associated with HLA-DRB1 and Epstein-Barr virus (EBV) infection. In the Indian subcontinent where there is high seroendemicity of EBV, we postulated that the association of this virus in adult SLE (aSLE) and pediatric SLE (pSLE) patients would be different and differentially associate with the HLA-DRB1 susceptibility and protective genes. A total of 109 aSLE, 52 pSLE, 215 adult healthy and 63 pediatric healthy controls were recruited. HLA-DRB1 genotyping by PCR-SSP, EBV load estimation by real-time PCR and antibody profiling (IgG & IgM) to EBV antigens by line blot assay were performed. DRB1*15 was found predominant in pSLE patients and DRB1*03 in aSLE patients. DRB1*15/X heterozygous was predominant in overall SLE patients, although disease severity, like hypocomplementemia, higher autoantibody levels and more organ involvement was observed in *15/*15 homozygous state. EBV strongly associated with pSLE patients showing higher percent of EA-D IgG (p < 0.0001) and p22 IgG (p = 0.035) along with higher viral load (p = 0.001) as compared to healthy controls. In addition, the higher EBV DNA load significantly associated with anti-EA-D IgG (p = 0.013) and DRB1*15/*15 (p = 0.007) in pSLE patients as compared to aSLE patients. This study therefore indicates that different HLA-DRB1 allotypes confer susceptibility to SLE in children and adults and disease may be triggered by increased EBV reactivation.

Linear growth and systemic glucocorticoid therapy in children with systemic lupus erythematosus

Background The use of long-term oral glucocorticoid therapy, specifically in the treatment of systemic lupus erythematosus (SLE), has increased in the past two decades. Chronic glucocorticoid use may lead to a linear growth disturbances.&#x0D; Objective To determine the association between linear growth and systemic glucocorticoid therapy in pediatric SLE patients.&#x0D; Methods This retrospective cohort study used medical record data of pediatric SLE patients. All subjects received systemic glucocorticoids. The linear growth parameters recorded in this study were height-for-age z-score (HAZ) and height velocity at 0, 6, and 12 months of treatment. We recorded potential risk factors of linear growth disturbance, such as pubertal status, sex, SLE severity, pulse methylprednisolone use, daily glucocorticoid dose, and nutritional status.&#x0D; Results Of 42 patients with SLE, 83.3% were female, with a mean age of 13 years at diagnosis. Eighteen subjects (42.9%) experienced abnormal height velocity. There was a significant reduction in HAZ between 0, 6, and 12 months of treatment (P=0.016). Between 0 and 6 months of treatment, there was a mean HAZ decrease of 0.11 (P=0.015). There was a trend towards a risk for decreased HAZ at 6 and 12 months of treatment with pulse methylprednisolone (RR 1.25 and 1.27, respectively), as well as for abnormal height velocity (RR 1.73), but they did not reach statistical significance.&#x0D; Conclusion There is a reduction in linear growth in the first 12 months of systemic glucocorticoid therapy in children with SLE. Administration of systemic glucocorticoid significantly reduced HAZ in the first six months of therapy.

Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement (p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings (p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041-7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065-1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Follow-up and management of serologically active clinically quiescent cases in pediatric systemic lupus erythematosus.

ObjectivesOur aim is to identify the presence of serologically active clinically quiescent (SACQ) episodes in pediatric systemic lupus erythematosus (SLE) patients. We aim to identify serologic biomarkers associated with SACQ episodes and discuss risks and benefits of escalating treatments.Material and methodsWe evaluated 25 pediatric SLE patients, 13 of whom experienced SACQ episodes. Serologically active clinically quiescent was defined as two consecutive clinic visits without any clinical symptoms or clinical examination findings of a lupus flare with a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of zero, but either elevated anti-ds-DNA antibodies or low complement (C3 and/or C4) levels.ResultsAmong the 13 patients who experienced a SACQ episode, there were a total of 24 episodes, with each patient experiencing 1–4 SACQ episodes. Erythrocyte sedimentation rate (ESR) was the most commonly elevated laboratory marker in a SACQ episode, followed by low hemoglobin levels, and then elevated anti-dsDNA antibodies. Of the 17 episodes treated during a SACQ episode, 15 (88%) did not progress to a clinical flare within six months, while two did. Furthermore, of the 7 patients who were not treated during their SACQ episode, 2 (29%) continued to be SACQ without flare, whereas 5 led to a clinical flare within six months.ConclusionsSerologically active clinically quiescent episodes were identified in pediatric SLE patients, suggesting that the presence of SACQ is not limited to adults with SLE. Serologic markers such as increased ESR, hemoglobin, and elevated anti-dsDNA antibodies are preliminarily associated with pediatric SACQ episodes. Treating these SACQ episodes in pediatric SLE patients was less likely to lead to a clinical flare within six months when compared to not treating (p < 0.05). More research with a larger sample size is needed to define SACQ episodes, determine the prevalence in pediatric SLE patients, and establish SACQ treatment guidelines.

Blood Genomics Identifies Three Subtypes of Systemic Lupus Erythematosus: "IFN-High," "NE-High," and "Mixed".

Purpose Systemic lupus erythematosus (SLE) is a systemic and multifactorial autoimmune disease, and its diverse clinical manifestations affect molecular diagnosis and drug benefits. Our study was aimed at defining the SLE subtypes based on blood transcriptome data, analyzing functional patterns, and elucidating drug benefits. Methods Three data sets were used in this paper that were collected from the Gene Expression Omnibus (GEO) database, which contained two published data sets of pediatric and adult SLE patients (GSE65391, GSE49454) and public longitudinal data (GSE72754) from a cohort of SLE patients treated with IFN-α Kinoid (IFN-K). Based on disease activity scores and gene expression data, we defined a global SLE signature and merged three clustering algorithms to develop a single-sample subtype classifier (SSC). Systematic analysis of coexpression networks based on modules revealed the molecular mechanism for each subtype. Results We identified 92 genes as a signature of the SLE subtypes and three intrinsic subsets (“IFN-high,” “NE-high,” and “mixed”), which varied in disease severity. We speculated that IFN-high might be due to the overproduction of interferons (IFNs) caused by viral infection, leading to the formation of autoantibodies. NE-high might primarily result from bacterial and fungal infections that stimulated neutrophils (NE) to produce neutrophil extracellular traps (NETs) and induced individual autoimmune responses. The mixed type contained both of these molecular mechanisms and showed an intrinsic connection. Conclusions Our research results indicated that identifying the molecular mechanism associated with different SLE subtypes would benefit the molecular diagnosis and stratified therapy. Moreover, repositioning of IFN-K based on subtypes also revealed an improved therapeutic effect, providing a new direction for disease treatment and drug development.