Classification Criteria For SLE Research Articles

Barriers and facilitators to medical care retention for pediatric systemic lupus erythematosus in South Africa: a qualitative study

BackgroundSystemic lupus erythematosus (SLE) is a life-threatening, chronic, autoimmune disease requiring long term subspecialty care due to its complex and chronic nature. Childhood-onset SLE (cSLE) is more severe than adult-onset, and the cSLE population in South Africa has been reported to have an even higher risk than patients elsewhere. Therefore, it is critical to promptly diagnose, treat, and manage cSLE. In this paper, we aim to describe and evaluate barriers and enablers of appropriate long-term care of cSLE South Africa from the perspective of caregivers (parents or family members).MethodsCaregivers (n = 22) were recruited through pediatric and adult rheumatology clinics. Individuals were eligible if they cared for youth (≤ 19 years) who were diagnosed with cSLE and satisfied at least four of the eleven ACR SLE classification criteria. Individual in-depth, semi-structured interviews were conducted between January 2014 and December 2014, and explored barriers to and facilitators of ongoing chronic care for cSLE. Data were analyzed using applied thematic analysis.ResultsFour barriers to chronic care engagement and retention were identified: knowledge gap, financial burdens, social stigma of SLE, and complexity of the South African medical system. Additionally, we found three facilitators: patient and caregiver education, robust support system for the caregiver, and financial support for the caregiver and patient.ConclusionThese findings highlight multiple, intersecting barriers to routine longitudinal care for cSLE in South Africa and suggest there might be a group of diagnosed children who don’t receive follow-up care and are subject to loss to follow-up. cSLE requires ongoing treatment and care; thus, the different barriers may interact and compound over time with each follow-up visit. South African cSLE patients are at high risk for poor outcomes. South African care teams should work to overcome these barriers and place attention on the facilitators to improve care retention for these patients and create a model for other less resourced settings.

Heterogeneity of right ventricular echocardiographic parameters in systemic lupus erythematosus among four clinical subgroups, as stratified by clinical organ involvement in observational cohort

BackgroundSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Cardiac involvement in SLE is rare but plays an important prognostic role. The degree of cardiac involvement according to SLE subsets...

Evaluation of a novel particle-based assay for detecting SLE-related autoantibodies

Anti-dsDNA, anti-Sm, and anti-ribosomal-P autoantibodies are hallmarks of systemic lupus erythematosus (SLE), being anti-dsDNA and anti-Sm included in 2019-ACR/EULAR SLE-Classification Criteria. Enzyme-linked (ELISA) and chemiluminescence assays (CIA) are widely established in immunology laboratories, but new technologies, such as particle-based multi-analyte technology (PMAT), are nowadays available. The present study aimed to compare the presence of anti-dsDNA and anti-Sm autoantibodies measured by CIA and PMAT and analyze diagnostic and clinical SLE activity performance. Anti-ribosomal-P autoantibodies by PMAT were also included. Consequently, anti-dsDNA and anti-Sm detected by CIA showed substantial agreement with PMAT (Cohen's kappa = 0.662 and 0.671, respectively). Anti-dsDNA autoantibodies measured by PMAT showed a positive correlation with clinical SLEDAI-2K (p < 0.001) and a negative correlation with complement consumption (p < 0.001). Anti-Sm and anti-ribosomal-P autoantibodies showed a positive correlation with SLEDAI-2K (p < 0.001 and p = 0.001, respectively) and a negative correlation with complement consumption (p < 0.001 and p = 0.001, respectively). Finally, anti-Sm autoantibodies were associated with renal involvement (p < 0.05).

P159 Development of digital neuropsychological battery: a use case in Indian SLE patients

Abstract Background/Aims While cognitive dysfunction and mood disorders are frequently reported as adverse effects of SLE, there is a scarcity of neuropsychological (NP) data for Asian SLE patients. Existing English-centric NP tests are inadequate for the linguistic and culturally diverse population. This study examines SLE's effects on mood and cognitive functions using an indigenously developed language-neutral digital NP test battery and validated anxiety, stress, depression and quality of life instruments. Methods We recruited SLE patients fulfilling 2012 SLE classification criteria as cases and caregivers (CG) and college students (CS) as controls aged above 18 years and at least 10th standard education. All participants provided written informed consent. Institutional ethics committees approved the study. The NP battery comprised five cognitive tasks: Montreal Cognitive Assessment (MoCA) and modified versions of attention network test (ANT), sustained attention to response task (SART), picture naming and N-back, and five psychological tests (PHQ-9, GAD-7, STAI-T, PSS-4 and WHOQOL-BREF). Mann-Whitney test with conditional Bonferroni's corrections was used to compare cases with CG and CS. Results Total of 142 volunteers (age: median = 25.0, IQR = 9.0, cases [n = 82], CG [n = 40] and CS [n = 20]) participated in the study. Cases exhibited delayed response latencies in N-back, SART, and picture naming tasks compared to controls. They demonstrated reduced accuracy in all N-back conditions, with significant differences observed in hit rate, miss rate, false alarms, and d-prime scores compared to CS with effect size ranging from 0.298 to 0.736 (Table 1). However, the difference was only significant in the 2-back condition compared to CG. Cases displayed lower accuracy in SART Go trials (higher omission errors) than controls but better inhibition in SART No-Go trials (lower commission errors). No differences were observed in alerting, orienting and executive control functions. Cases showed significantly lower scores in MOCA than controls. Cases reported poorer psychological health through increased anxiety and stress levels and reduced WHO-quality of life scores compared to CG. Conclusion Contrary to earlier research that often relied on isolated cognitive assessments, our pioneering approach introduces a tailored test battery to establish cognitive baselines for Indian SLE patients. Disclosure P. Singhal: None. P. Srivastava: None. L. Rajasekhar: None. N. Samhitha: None.

Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus

BackgroundCranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and...

Declining Incidence of Systemic Lupus Erythematosus in Norway 1999-2017: Data From a Population Cohort Identified by International Classification of Diseases, 10th Revision Code and Verified by Classification.

The goal of this study was to provide complete, robust data on annual systemic lupus erythematosus (SLE) incidence rates over nearly two decades from the Southeast Norway area (2.9 million inhabitants) and assess accuracy of SLE-specific International Classification of Diseases (ICD) codes for SLE diagnosis. From administrative databases, we identified all cases International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coded as SLE during 1999 through 2017 in Southeast Norway. We manually reviewed the chart of every case ICD-10 coded as SLE to either confirm or reject SLE diagnosis. Using SLE classification criteria, we classified all cases with confirmed SLE. We estimated annual incidence rates of classified SLE, and subsets, defined by age at diagnosis, sex, and parental country of birth. The chi-square test was applied for linear time-trend analyses of incidence. Among the 3,488 cases ICD-10 coded as SLE, chart reviews confirmed SLE diagnosis in 1,558 (45%), of which 797 had new-onset disease during 1999 through 2017. Annual SLE incidence rates fell during 1999 to 2017. The fall was most pronounced in female persons 50 to 59 years old at diagnosis, in whom incidence fell from 3.4 to 1.1 per 100,000 persons (P trend < 0.001). Concurrent ecological data from the study area showed a 74% reduction in prescriptions of menopausal hormone treatment. Accuracy of ICD-10 codes for incident SLE diagnosis was acceptable in juveniles and young adults (up to 20 years) but otherwise low. In a presumably complete population-based cohort, we identified decreasing incidence of SLE, especially among female persons 50 to 59 years old. Although reasons for declining incidence are not clear, ecological data indicate a possible role of environmental factors, for example, menopausal hormone treatments.

Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment.

Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI. Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated. Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI. In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.

Incomplete systemic lupus erythematosus. Own observation and literature review

The term of “incomplete” systemic lupus erythematosus (iSLE) is used when patients have typical clinical and immunological signs of lupus without fulfilling the classification criteria for SLE. Autoantibodies appear in patients years before diagnosis, and the most common clinical manifestations are nonspecific and may be the only symptom of the disease for some time. Progression to definite SLE occurs in 5–57% of patients with iSLE within 1–10 years. There are currently no recommendations for monitoring and treatment of iSLE patients. This article presents the results of our own research and literature analysis on clinical and pathogenetic problems of iSLE.

Clinical implications of discordance between anti-dsDNA antibodies by multiplex flow immunoassay and Crithidia luciliae assay in a multiethnic racial cohort of patients with SLE

ObjectiveAnti-dsDNA antibodies (anti-dsDNA) are a component of all classification schemes in SLE and comprise one of the domains in validated activity indices. Anti-dsDNA is frequently measured commercially by an enzyme...

Identification and assessment of classification criteria attributes for systemic lupus erythematosus in a regional medical record data network

ObjectiveTo assess the application and utility of algorithms designed to detect features of SLE in electronic health record (EHR) data in a multisite, urban data network.MethodsUsing the Chicago Area Patient-Centered...

Systemic Lupus Erythematosus Risk Probability Index: ready for routine use? Results from a Chinese cohort

ObjectivesTo evaluate the performance of Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in patients with SLE using a Chinese cohort.MethodsThe Chinese cohort included 352 patients with and 385 without SLE...

Quality indicators and satisfaction with care in patients with systemic lupus erythematosus.

Grading the quality of care in patients with systemic lupus erythematosus and determining its relationship with care satisfaction may recognize gaps that could lead to better clinical practice. Eighteen quality indicators (QIs) were recently developed and validated for patients with SLE based on the 2019 EULAR management recommendations. Few studies have analyzed the relationship between quality of care and care satisfaction in patients with lupus. This was a cross-sectional study. We included patients at least 18years old who met the EULAR/ACR 2019 classification criteria for SLE. We interviewed patients and retrieved data from medical records to assess their compliance with a set of 18 EULAR-based QIs. We calculated each QI fulfillment as the proportion of fulfilled QI divided by the number of eligible patients for each indicator. Care satisfaction was evaluated with the satisfaction domain of LupusPRO version 1.7. Spearman correlation coefficient was used to determine the relationship between quality of care and care satisfaction. Seventy patients with a median age of 33 (IQR 23-48) were included, 90% were women. Overall adherence was 62.29%. The median care satisfaction was 100. Global adherence to the 18-QIs and the care satisfaction score revealed no correlation (r = 0.064, p = 0.599). Higher QI fulfillment was found in the group with remission versus the moderate-high activity group (p = 0.008). In our study, SLE patients in remission had higher fulfillment of quality indicators. We found no correlation between the quality of care and satisfaction with care.

#5479 EXPLORING CANADIAN PATIENT EXPERIENCES OF LIVING WITH LUPUS NEPHRITIS

Abstract Background and Aims Lupus nephritis (LN) is one of the most severe manifestations of SLE; however, the Canadian patient experience remains understudied. This research investigated patient experiences and perspectives of 1) LN diagnosis; 2) living with LN; and 3) LN healthcare and treatment. Method Patients aged ≥18 years with biopsy-proven pure or mixed ISN/RPS Class III, IV, or V LN and fulfilling the ACR 1997 or SLICC 2012 Classification Criteria for SLE were purposefully recruited from a Canadian lupus cohort to participate in semi-structured in-depth interviews. These were conducted virtually and transcribed verbatim for subsequent thematic analysis using NVivo Qualitative Data Analysis Software. Results Thirty patients with LN were interviewed; 86.7% were female, mean (SD) age was 42.1 (16.4) years, mean (SD) age at SLE diagnosis was 29.8 (15.3) years (Table 1). Patients reported challenges seeking, receiving and adjusting to the LN diagnosis, and all described emotional impacts associated with diagnosis. Most patients had limited knowledge of LN prior to diagnosis, and this lack of understanding made it difficult to contextualise their illness (Figure 1). Patients reported both emotional wellbeing and physical health impacts associated with living with LN. While most have continued in paid employment, patients identified altered career aspirations, role changes, and the need for accommodations in the workplace. Patients also described modified leisure and social activities (Figure 1). While many identified supportive friends and family, a lack of nuanced understanding of their experiences by others was reported. LN was described as a factor in family planning considerations amongst those of childbearing age. Specifically, fear of changing LN medications and their reproductive side effects, fear of experiencing a flare while pregnant/when parenting, and concerns about passing on LN/other autoimmune conditions to their children emerged (Figure 1). Numerous aspects of LN management present challenges for patients, including visiting a range of healthcare providers, taking medication, monitoring diet, stress management and ensuring adequate rest. While many reported successful LN management with medication, others expressed concern with cost and side effects. The challenges associated with a lack of LN-specific information and resources were identified (Figure 1). Conclusion A lack of individual and public understanding of LN coupled with the uncertainties of diagnosis/living with LN create a substantial psychosocial burden as patients negotiate acceptable risk in the face of uncertainty (e.g., in family planning, treatment, paid employment, leisure). Results emphasize the need for wider LN awareness and will inform the development of LN-specific patient resources to increase understanding of LN and better support decision-making.

Prevalence and clinical associations of ultrasound-confirmed enthesitis in systemic lupus erythematosus.

To assess the prevalence of ultrasound (US)-confirmed enthesitis in a cohort of patients with systemic lupus erythematosus (SLE) and to analyze the clinical associations to enthesitis during the course of SLE. In a retrospective analysis of the SLE cohort of the Lupus Unit of the Careggi University Hospital, US examinations of SLE patients presenting with tender and/or swollen joints were retrieved to assess the presence of enthesitis. Patients with US-proven enthesitis were compared with SLE controls with tender and/or swollen joints who showed no US-evidence of enthesitis. Clinical and laboratory features were compared at disease onset and during follow-up. A total of 400 patients fulfilling EULAR/ACR classification criteria for SLE were assessed. Of them, 106 underwent articular US examination. Evidence of enthesitis was found in 31/106 (29.2%) patients. Seventy-one patients without US-enthesitis were included as controls, 4 were excluded due to lack of follow-up data. Laboratory and clinical features were comparable between cases and controls at disease onset. Throughout a median follow-up of 10.0 (IQR 8.3-23.3) years for cases and 12.4 (IQR 7.2-13.3) years for controls, patients with enthesitis were less likely to develop renal involvement (22.6% vs 46.5%, p= 0.028) and failed B cell depletion more frequently (75.0% vs 0%). In SLE patients with clinically active joints, US-proven enthesitis is a fairly common finding. Enthesitis in SLE could be the hallmark of a distinct disease phenotype with less renal involvement, more arthritis, and low response to anti-CD 20 therapy, potentially requiring a tailored treatment.

HLA‐DQ and ‐DR alleles in patients with SLE: A tertiary hospital‐based case–control study in Bangladesh

AbstractBackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the involvement of multiple organs and autoantibody production. This study aimed to determine the association of human leukocyte antigen (HLA)‐DQ and ‐DR alleles with SLE at a tertiary hospital in Bangladesh.MethodsThis case–control study was conducted in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. The patients who fulfilled the 1997 revised American College of Rheumatology classification criteria for SLE were considered cases (n = 41). The controls (n = 32) were selected from the hospital staff of BSMMU, including doctors and nurses who did not suffer from any known rheumatic diseases, and there was no such disease in their first‐degree relatives. Polymerase chain reaction using a sequence‐specific primer (PCR‐SSP) in a low‐resolution typing method was carried out on blood samples collected for HLA‐DQ and ‐DR allele typing.ResultsThe cases and controls had comparable mean ages (31 vs. 32 years), and most cases were female (95.1% vs. 34.4%). The most frequent clinical manifestations were mucocutaneous (85.4%), followed by musculoskeletal (70.7%) and constitutional symptoms (58.5%). The cases had a significantly higher frequency of HLA‐DR2 allele compared with healthy controls (70.7% vs. 43.8%; odds ratio: 3.1; 95% confidence interval: 1.2–8.2). In addition, HLA‐DQ6 allele was found to have a significant association with mucocutaneous manifestations of the cases (88.9%, P = 0.03).ConclusionsBangladeshi adults having HLA‐DR2 may be more susceptible to SLE. HLA‐DQ6 allele might be associated with mucocutaneous manifestations of SLE.

Genetics of osteonecrosis in children and adults with systemic lupus erythematosus.

Genetics plays an important role in SLE risk, as well as osteonecrosis (ON), a significant and often debilitating complication of SLE. We aimed to identify genetic risk loci for ON in people with childhood-onset (cSLE) and adult-onset (aSLE) SLE. We enrolled participants from two tertiary care centres who met classification criteria for SLE. Participants had prospectively collected clinical data and were genotyped on a multiethnic array. Un-genotyped single nucleotide polymorphisms (SNPs) were imputed, and ancestry was inferred using principal components (PCs). Our outcome was symptomatic ON confirmed by imaging. We completed time-to-ON and logistic regression of ON genome-wide association studies (GWASs) with covariates for sex, age of SLE diagnosis, five PCs for ancestry, corticosteroid use and selected SLE manifestations. We conducted separate analyses for cSLE and aSLE and meta-analysed results using inverse-variance weighting. Genome-wide significance was P < 5 × 10-8. The study included 940 participants with SLE, 87% female and 56% with cSLE. ON was present in 7.6% (n = 71). Median age of SLE diagnosis was 16.9 years (interquartile range [IQR]: 13.5, 29.3), with median follow-up of 8.0 years (IQR: 4.2, 15.7). Meta-GWAS of cSLE and aSLE time-to-ON of 4 431 911 SNPs identified a significant Chr.2 SNP, rs34118383 (minor allele frequency = 0.18), intronic to WIPF1 (hazard ratio = 3.2 [95% CI: 2.2, 4.8]; P = 1.0 × 10-8). We identified an intronic WIPF1 variant associated with a 3.2 times increased hazard for ON (95% CI: 2.2, 4.8; P = 1.0 × 10-8) during SLE follow-up, independent of corticosteroid exposure. The effect of the SNP on time-to-ON was similar in cSLE and aSLE. This novel discovery represents a potential ON risk locus. Our results warrant replication.

Challenges in administering immunosuppressive therapy in severe bacterial infection interfering crisis and refractory childhood systemic lupus erythematosus

Background: Childhood Systemic Lupus Erythematosus (cSLE) mostly come with severe manifestation compared to the adult. Infection aggravated the multisystem inflammation and interfering immunosuppressive agent protocol. Case: A 12-year-old girl was hospitalized for a month with massive edema and fever after being diagnosed with nephrotic syndrome and taken prednison for four weeks. The patient was completely bedridden, presented with hypertension, large erythematous striae across the trunk and limbs, and darkened skin. Further evaluation showed the EULAR/ACR classification criteria for SLE with score of 26. Cellulitis was suspected when a red, pinprick-sized papule appeared on the patient's right leg be increased significantly in size within two hours. Following the collection of a wound culture and blood culture specimen, triple antibiotics were given. Seven days after the wound has healed, administered of cyclophosphamide was started. Cyclophosphamide is used as an emergency treatment for lupus crises, as she experienced seizure and delirium. Seven days after cyclophosphamide administration, the wound was revived. Initial blood and wound cultures indicated an infection caused by Serratia marcescens; however, the second wound culture revealed infections caused by Klebsiella oxytoca and Enterobacter cloacae. We commenced Meropenem based on a sensitivity test to establish protection for the following administration of high-dose methylprednisolone with rituximab and cyclophosphamide. The lupus crisis was precipitated by an infection-induced inflammatory response. On day 17, after the calf and back wounds were completely healed, the antibiotic was withdrawn. In order to protect organ functionality, physiotherapy and nutritional support were employed. Conclusion: Clinicians need to be mindful and closely observe patient with severe SLE accompanied with infection to balancing intervention for immunosuppressant therapy and antibiotic.

SLE classification criteria: Science-based icons or algorithmic distractions - an intellectually demanding dilemma.

It is, so to say, not a prerogative authority assigned to SLE classification criteria that allow them to declare something definitively important about SLE. This is particularly true as criteria-based classification processes overrule the highly needed evolution of concise diagnostic criteria. It is classification criteria that allocate SLE patients into cohorts intended to describe the nature of their disease. Therefore, all major SLE classification criteria since the 1971 preliminary criteria usurp the role of diagnostic criteria. Today´s practice silently accept that the SLE classification process “diagnose” SLE patients despite the fact that classification criteria are not accepted as diagnostic criteria! This is a central paradox in contemporary SLE research strategies. Contemporary SLE cohorts are designed to investigate SLE´s etiological features. However, each cohort that is categorized by classification criteria has one central inherent problem. From theoretical and practical arguments, they embody multiple distinct clinical phenotypes. This raises the critical and principal question if phenotypically heterogenic SLE cohorts are useful to identify basic SLE-specific etiology(ies) and disease process(es). In times to come, we must prioritize development of firm diagnostic criteria for SLE, as the classification criteria have not contributed to reduce the enigmatic character of the syndrome. No radical improvements are visible in the horizon that may lead to concise investigations of SLE in well-defined homogenous SLE cohorts. We must develop new strategies where studies of phenotypically standardized cohorts of SLE must be central elements. Problems related to contemporary SLE classification criteria are contemplated, analyzed, and critically discussed in this study.

Performances of different classification criteria for systemic lupus erythematosus in a single-center cohort from Turkey.

Sensitivity and specificity of SLE classification criteria may vary in different populations and clinical settings. In this study, we aimed to compare the performances of three criteria sets/rules (1997, 2012, and 2019) in a large cohort of patients and relevant diseased controls. The medical records of consecutive SLE patients and diseased controls were reviewed for clinical and laboratory features relevant to all sets of criteria. Criteria sets/rules were analyzed based on sensitivity, positive predictive value, specificity, and negative predictive value, using clinical diagnosis with at least 6 months of follow-up as the gold standard. A subgroup analysis was performed in ANA positive patients. A total of 393 SLE patients and 308 non-SLE diseased controls were included. Sensitivity was 78.4% for 1997 criteria and was more than 90% for both 2012 (91.9%) and 2019 (94.4%) criteria. Specificity was the highest (95.1%) for 1997 ACR criteria, 91.5% for 2012 SLICC criteria and 91.2% for 2019 EULAR/ACR criteria. When only ANA positive patients were analyzed, sensitivity of each criteria increased by 1%, 0.8%, and 2.2%, respectively. Specificity of 1997 criteria decreased by 2% and specificity of 2012 and 2019 criteria both decreased to less than 90%. EULAR/ACR criteria were more sensitive than 1997 criteria and had a comparable performance with SLICC criteria. When only ANA positive patients were analyzed, the presence of false positive results (originated from patients with Sjögren's disease and antiphospholipid syndrome mainly) decreased the specificity of both SLICC and EULAR/ACR criteria.

Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5.Case presentationAmong the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy.ConclusionsGenetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment.