O004. Assessment of the impact of lupus nephritis on clinical, biological parameters, disease activity and mortality in pediatric Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Kidney involvement is one of the most frequent and severe manifestations of pediatric systemic lupus erythematosus (pSLE), seriously affecting the prognosis. It usually manifests as glomerulonephritis of varying severity. Objective: Knowledge of the correlation of lupus nephritis (LN) with clinical, biological, immunological parameters, disease activity and mortality in pediatric systemic lupus erythematosus is limited. This study aims to describe the impact of renal involvement with these different determinants. Methods This was a prospective, multicenter, descriptive 36-month study (January 2015 - December 2018) including patients less than 16 years of age with LN. The presence of LN was defined according to the American College of Rheumatology classification SLE criteria. The LN class was determined by renal biopsy and was classified according to the Morphology in Kidney International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2004 classification of lupus nephritis. The disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children. Means, percentages and Chi-square tests were specified. P values less than 0.05 were considered statistically significant. Results We included 83 patients in this study. 37/83 patients (44.6%) developed LN with the following urinary signs: 92% of proteinuria (mean 3366.147 mg ± 2785.93 / 24h) including 2/3 of cases of nephrotic syndrome, 81% of hematuria, 14% of acute renal failure with significant reduction in glomerular filtration rate (average creatinine clearance of 32.42 ml / min) and 12% high blood pressure. Out of a total of 30 renal biopsies interpreted at disease diagnosis, 73.4% diffuse proliferative glomerulonephritis forms were observed: (III (30%), IV (36.7%) and VI (6, 7%)). Lupus nephritis were significantly correlated with hypocomplementemia in its C3 (P = 0.00002) and C4 (P = 0.00005) fraction, lymphopenia (P = 0.02), anti-DNA antibodies (P = 0.026), SLEDAI (P = 0.00001) and mortality (P = 0.03). The most frequently used induction drugs for LN classes III, IV and VI were pulsed intravenous methylprednisolone (500 mg daily for 3 doses) in combination with low dose intravenous cyclophosphamide (23%) in the short term (500 mg/m2/15 days X 6) followed by mycophenolate mofetil (28%) (600mg/ m2 in two daily doses) as maintenance treatment associated with a daily dose of oral glucocorticoids with a gradual decrease until reaching the minimum amount necessary to control the disease. All of our SLE patients with nephritis were treated with HCQ with a significant correlation with the decrease in SLEDAI. During the first two years of disease progression, the frequency of LN increased to 43/83 (51.8%) mainly in these severe forms: (IV (41.7%), V (2.8 %). The progression to chronic renal failure had a prevalence of 6, 9% (3/43) of cases; these were mainly patients with severe lupus nephritis (III, and IV) Conclusion Nephritis is a major risk factor for morbidity and mortality in pSLE; LN in children is most often proliferating and more active. The early diagnosis and management of kidney damage are the only guarantee of a good course and prevention of the progression of chronic renal failure. Keywords lupus nephritis; child; systemic lupus erythematosus; disease activity, mortality.

P043 Predictors of mortality in childhood-onset Systemic Lupus Erythematosus

Background Pediatric Systemic Lupus Erythematosus (pSLE) is a severe autoimmune disease due to its serious multi-visceral disorders, its morbidity causing deleterious and sometimes permanent effects. The objective is to determine the prognostic predictive factors of death in pSLE. Methods This was a prospective, descriptive, multicentre study, including patients less than16 years of age with SLE according to the criteria SLE of the American College of Rheumatology over a period of 36 months (2015–2018) carried out in the CHU Nefissa Hamoud in Algiers. The number of deaths during this follow-up period was determined and compared with surviving patients in several parameters (demographic, clinical, laboratory, therapeutic and disease activity). Disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children and damage and sequelae were appreciated by the Systemic Lupus International Collaborating Clinics (SLICC). Means, percentages and χ2 tests were specified. The multivariate analysis of logistic regression was used to determine prognostic factors associated with the outcome variable. P values <0.05 were considered statistically significant. Results 83 patients were collected and divided into two groups: deceased and survivors in which different parameters were compared and analyzed. Results: Female: male ratio 1: 4.9, mean age at diagnosis 11.3 ± 3.62. Clinical involvements at diagnosis were: cutaneous (100%), hematological (79.5%), articular (65, 1%), renal (44, 6%), neurological (41%), hepato-digestive (41%), cardiac (27, 7%), pleuropulmonary (19, 3%) and ocular involvement (7, 2%). The mean of SLEDAI was 22.11 ± 11.87 [interquartile range 2–53]. The prevalence of death was 11% of cases with an average age of death of 11 years [interquartile range 5–15 years]. The comparison of the two groups demonstrated a significant association between death and the following parameters: renal and neurological damage respectively: ((P = 0.03), (P = 0.02)), macrophage activation syndrome (MAS) (P = 0.0002), infections (P = 0.027), disease activity (P = 0.006) and damage score (P = 0.001). The mean SLEDAI activity in deceased patients was 32 ± 11.9 [interquartile range 17–53], compared with surviving patients which was 20.9 ± 11.4 [interquartile range 2–51]. Multivariate analysis with logistic regression revealed two major predictors of death, namely neurological involvement (odds ratio = 6,093 95% confidence interval ((1,1 8 0 ∼ 31 446)) and macrophage activation syndrome. Adherence to treatment was a protective factor: ([0.016 (0.001–0.353)]. Conclusion These results showed that pediatric systemic lupus erythematosus exhibits an aggressive and severe phenotype with an unpredictable course. Studies are needed in children in order to specify and develop prognostic predictive factors and to identify patients at high risk of early mortality in order to design early and effective care of this vulnerable entity of lupus disease. Keywords Child, Systemic Lupus Erythematosus, mortality

Pediatric onset lupus nephritis in western India—is it different from the rest of the country?

Aim To determine the clinicopathological characteristics and outcomes of children diagnosed with lupus nephritis in a tertiary hospital in western Rajasthan and compare it with the data available from other parts of India. Material and methods: A retrospective review of children presenting to a tertiary care center in western Rajasthan, India, with a diagnosis of pediatric Systemic Lupus Erythematosus (p SLE), between July 2017 and July 2020 was done. Comparisons of pediatric lupus in western India to other parts of country were done. Results 19 children with SLE with Renal involvement were enrolled and followed up. The median age at presentation was 15 years (IQR-16–9.5) (73% females). 8/19 (42%) children presented with AKI, of which 62% children presented as rapidly progressive renal failure. Six (37.5%) patients required dialysis at presentation. 84.21% of children were evaluated with renal biopsy, 16 biopsies were done in 19 children, among which class II, III, and IV lupus nephritis were reported in 21%,42%, and 35% respectively(4 crescentic). Antiphospholipid antibodies were positive in 8/15(53%), children which is much higher than a reported incidence of 30% in other Indian studies. Ten patients (52%) had neurological involvement, with seizures being the most common form of presentation (60%). Seven patients (36%) developed hepatitis. We noted many uncommon presentations in the small group like Autoimmune Pancreatitis, Mononeuritis multiplex, and peripheral digital gangrene. Cyclophosphamide was used in 10 out of 19 patients for inducing remission with class 3 and 4 nephritis and MMF in 8 children. 55% patients attained remission (after completing induction), of which 4 relapsed during the follow up. Four patients were lost to follow-up. A total of 27% patients died and 10% patients developed end stage renal failure. It was seen that those who died had more cardiac and neurological involvement at presentation, higher grade of proteinuria, lower GFR, and need for dialysis at admission. Conclusion: We found a more severe form of clinical manifestation in pediatric SLE patients at the time of the first presentation in the form of severe renal and extrarenal manifestation compared to other parts of the country.

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.

COVID-19 triggered systemic lupus erythematosus in a child: a case report

The COVID-19 pandemic has continued to wreak havoc globally during the second wave. Even though it tends to be asymptomatic or cause only a trivial illness in children, it is reported to be associated with a delayed hyper-inflammatory response syndrome resulting in multi-organ dysfunction in children. It is possible that through unknown mechanisms, it could also result in triggering of other auto-immune disorders. We report a case of pediatric systemic lupus erythematosus (SLE) with lupus nephritis suspected to be triggered by SARS-CoV-2 virus which is not reported in the literature so far.

Hyperferritinemia Wins Again: Defining Macrophage Activation Syndrome in Pediatric Systemic Lupus Erythematosus

Macrophage activation syndrome (MAS) is a potentially life-threatening condition of hyperinflammation that can be secondary to an underlying chronic rheumatic condition, commonly systemic juvenile idiopathic arthritis (sJIA) but also childhood-onset systemic lupus erythematosus (cSLE). MAS is characterized by excessive activation of T lymphocytes and macrophages that lead to overproduction of cytokines and results in cytopenia, liver dysfunction, and coagulopathy1.