Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study.

BACKGROUND: The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1-7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers. METHODS: Serum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher's exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated. RESULTS: 808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1-1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1-2.9). CONCLUSIONS: Using the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.

A single-center model for implementation of SLEDAI documentation adherence in childhood-onset systemic lupus erythematosus (cSLE).

BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease with variable disease expression but noted association with significant disease-related damage, morbidity, and mortality. The European Alliance of Associations for Rheumatology (EULAR) recommends routine monitoring of SLE through validated disease activity and chronicity indices, including the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Despite this, physician adherence with SLEDAI documentation remains elusive at various academic institutions. The aim of our study was to determine baseline SLEDAI documentation rates at our center and assess the change in adherence in SLEDAI documentation rate with electronic clinical decision support (CDS) reminders facilitated through the electronic medical record (EMR) over a 2-year period. METHODS: All SLE encounters over a 24-month period at a pediatric academic center were reviewed in order to obtain baseline SLEDAI documentation percentages. Physicians subsequently received monthly email reminders, initiated at month 4 of project initiation, with subsequent CDS reminder 13 months after project initiation prompted by anti-dsDNA lab result. Chart review was repeated continuously for each provider, and SLEDAI documentation rates were emailed to each provider monthly. Physicians completed a post-intervention survey regarding barriers to SLEDAI documentation at the end of the study. RESULTS: A total of 1980 SLE encounters were reviewed for this study. Baseline SLEDAI documentation rates were 10%. Following the introduction of monthly emails reminding physicians to document SLEDAI, rates increased to 55%. After the initiation of electronic in-basket reminders prompted by lab results, rates increased to 60%. Noted barriers to documentation were cited to be forgetfulness (67%) and lack of time (33%). CONCLUSION: Our study demonstrates that monthly email reminders as well as EMR-mediated electronic in-basket reminders increased SLEDAI documentation rates at an academic center. Noted barriers to documentation were reported to be forgetfulness (67%) and lack of time (33%).

Lung involvement in juvenile idiopathic inflammatory myopathy: A systematic review.

OBJECTIVE: Juvenile idiopathic inflammatory myopathies (JIIM) are a group of connective tissue disorders characterized by muscle inflammation and variable systemic involvement, including interstitial lung disease (ILD). Available data on JIIM-associated ILD are very limited. We performed a systematic review of the available clinical, laboratory, and radiological features of JIIM-associated ILD. METHODS: A systematic literature review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of 90 patients were identified, of whom 77.8% had JDM, 10% amyopathic JDM, 7.8% anti-synthetase syndrome, 3.3% overlap syndrome, and 1.1% juvenile polymyositis. Anti-melanoma differentiation-associated gene 5 (MDA-5/CADM-140) was the most frequently reported myositis-specific antibody (32.2%). At diagnosis of ILD, 55.5% of patients had respiratory symptoms. Ground glass opacity was the most reported radiological feature (52.9%). Thirty-three % of patients developed rapidly progressive (RP) lung disease; 26.7% were admitted to the intensive care unit (ICU); 28.9% died; all deaths were due to ILD, with a median interval of 2 months (IQR 1.5-4.7) between the onset of respiratory symptoms and death. Patients admitted to the ICU and who died of ILD were more likely to be male, to have a rapidly progressive pattern, progression of radiological features, and a higher level of KL-6. CONCLUSIONS: MDA-5/CADM-14 is associated with RP-ILD. ILD is a rare but severe manifestation among the spectrum of systemic involvement associated with JIIM, with a high rate of ICU admission and mortality. Early recognition and aggressive treatment are needed to prevent a severe outcome.

Improving Hepatitis B Screening Prior to Rituximab: A Quality Improvement Project.

Rituximab, used in the treatment of some rheumatic and kidney diseases, can lead to hepatitis B virus (HBV) reactivation; HBV screening is recommended for those starting this medication. We aimed to improve by 50% the proportion of patients undergoing HBV screening by implementing multimodal interventions to support clinicians in this evidence-based practice. We conducted a quality improvement project from November 2020 to June 2022 at a tertiary care pediatric hospital system, including patients with rheumatic and/or kidney diseases starting rituximab. Multimodal interventions targeting clinicians included electronic health tools (dot phrase, display of screening recommendations and screening results in rituximab order sets/therapy plans), educational meetings, and e-mail/paper reminders. The primary outcome was the proportion of patients with complete HBV screening, while the secondary outcome was utilization of each laboratory component, tracked using statistical process control charts. Pre- and post-intervention data were compared using Fisher's test. One hundred eighty-two patients who had been prescribed rituximab were included, of which 98 (54%) were post-intervention. The proportions of patients undergoing complete HBV screening (6% vs. 44%; p < 0.001), HBsAg collection (60% vs. 79%; p = 0.006), anti-HBsAb collection (14% vs. 54%; p < 0.001), and total anti-HBcAb collection (8% vs. 52%; p < 0.001) were significantly higher in the post-intervention period. Improvement was sustained over 18 months, with shifts and/or data points above the control limits in all measures. Forty-five patients were HBV-non-immune. In this study, multimodal interventions including electronic health tools and education of the provider significantly increased the proportion of patients screened for HBV prior to rituximab and identified immunization opportunities.

Impact of follow-up adherence on disease activity in childhood-onset systemic lupus erythematosus (cSLE).

BACKGROUND/PURPOSE: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, with a potential for significant disease damage, morbidity, and mortality. In comparison to the adult population, childhood-onset SLE (cSLE) tends to be more aggressive given the higher preponderance of renal and neuropsychiatric disease and increased disease activity. There is a paucity of literature examining relationship between disease activity, rheumatology follow-up visits, and health care utilization. The objective of this study is to determine whether adherence with outpatient clinic visits would affect disease activity in patients with childhood-onset systemic lupus erythematosus (cSLE). METHODS: 41 children <18 years of age at time of diagnosis with SLE who met Systemic Lupus International Collaborative Clinics (SLICC) criteria and not evaluated in clinic within the previous 120-day period were identified as eligible for inclusion. Patients were continuously searched between December 2021 and July 2022 for eligibility evaluation. Through retrospective chart review, we assessed disease activity (SLE Disease Activity Index) at the last clinic visit. The patients were stratified into two cohorts of lower and higher disease activity, with SLE disease activity index (SLEDAI) ≤ 3 and SLEDAI ≥ 4, respectively. Descriptive statistics and Willcox Rank Sum (numerical variables) and Fisher's test (categorical variables) were used to compare these two groups. RESULTS: Clinical, epidemiological, and serological data were compared between the two groups, with observed statistically significant differences to include current use of high dose prednisone associated with higher SLEDAI scores (p = 0.019). In nonparametric analysis, time to follow-up (p < 0.001), hospitalizations (p = 0.017), and Emergency Department visits (ED) (p < 0.001) were found to be associated with higher SLEDAI scores. CONCLUSION: Our findings suggest that cSLE patients with higher disease activity are at risk for increased health care utilization with respect to ED visits as well as hospitalizations in the setting of follow-up nonadherence. While further studies are required to enhance our understanding of this association, this links the importance of disease-related outcome and routine outpatient visits in this particularly vulnerable patient population.

Longitudinal program evaluation of an inter-institutional mentorship network for pediatric rheumatology using a quality improvement framework.

Background: The American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance (CARRA) Mentoring Interest Group (AMIGO) is an inter-institutional mentorship program launched to target mentorship gaps within pediatric rheumatology. Initial program evaluation indicated increased mentorship access. Given the small size of the pediatric rheumatology workforce, maintaining a consistent supply of mentors was a potential threat to the longevity of the network. Our aims were to: (i) describe the sustainability of AMIGO over the period 2011-2018, (ii) highlight ongoing benefits to participants, and (iii) describe challenges in the maintenance of a mentorship network. Methods: A mixed-methods approach centered on a quality improvement framework was used to report on process and outcomes measures associated with AMIGO annual cycles. Results: US and Canada Pediatric rheumatology workforce surveys identified 504 possible participants during the time period. As of fall 2018, 331 unique individuals had participated in AMIGO as a mentee, mentor or both for a program response rate of 66% (331/504). Survey of mentees indicated high satisfaction with impact on general career development, research/scholarship and work-life balance. Mentors indicated increased sense of connection to the community and satisfaction with helping mentees despite minimal perceived benefit to their academic portfolios. Based on AMIGO's success, a counterpart program, Creating Adult Rheumatology Mentorship in Academia (CARMA), was launched in 2018. Conclusions: Despite the challenges of a limited workforce, AMIGO continues to provide consistent access to mentorship opportunities for the pediatric rheumatology community. This experience can inform approaches to mentorship gaps in other academic subspecialties.

Clinical Determinants of Childhood Onset Systemic Lupus Erythematosus among Early and Peri-Adolescent Age Groups.

Introduction: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is associated with significant morbidity and mortality. SLE disproportionately affects women and minorities. Childhood-onset SLE (cSLE) in particular tends to be more aggressive than adult-onset SLE. Despite substantial improvements in the treatment of cSLE, there is significant variability in treatment responses and long-term outcomes. Furthermore, there is a paucity of studies involving cSLE, and in particular, cSLE among different age groups. The aim of this study was to test the hypothesis that an early-onset cSLE cohort would demonstrate unique characteristics with distinctive clinical and laboratory features at disease onset. We specifically investigated whether clinical, epidemiological, or serological factors are differentially associated with early- and late-onset cSLE. This could have direct impact on clinical management with the goal of improving outcomes and quality of life for children with SLE. Methods: Our study was conducted at a large tertiary center. We included 213 subjects seen at our pediatric rheumatology clinic aged 4−17 years. Epidemiologic, clinical phenotype, disease severity, serology, treatment, and outcome data were compared between subjects with cSLE onset prior to 10 years of age (early-onset disease, n = 43) and those with cSLE onset greater than 10 years of age (peri-adolescent disease, n = 170). We compared clinical features between early- and peri-adolescent onset cSLE in order to investigate the association between age at disease onset of cSLE and clinical disease expression and outcomes. Results: Of the 213 subjects with cSLE in our study, 43 subjects had early-onset disease (age 2 to ≤9 years) and 170 patients had peri-adolescent onset disease. We found that early-onset cSLE was associated with a higher prevalence of positive anti-dsDNA antibody at cSLE diagnosis, higher anti-dsDNA antibody titer at cSLE diagnosis, rash, and azathioprine use (p < 0.001, p = 0.004, p = 0.011, and p = 0.008, respectively). In contrast, we found that peri-adolescent onset cSLE (≥10 years of age) was associated with worse disease activity (SLEDAI range 0−24) (p < 0.001), higher SLICC at diagnosis (p < 0.001), as well as a higher rate of mycophenolate mofetil and hydroxychloroquine use (p = 0.003 and p < 0.001, respectively). There were no significant differences in the prevalence of neuropsychiatric symptoms or the development of Class IV/Class V lupus nephritis between the early-onset and peri-adolescent groups.

Severe Immediate and Delayed Hypersensitivity Reactions to Biologics in a Toddler With Systemic Juvenile Idiopathic Arthritis.

Many pediatric rheumatic diseases can be safely managed with biologic therapy. Severe allergic reactions to these medications are uncommon. We report the case of a 2-year-old male with systemic-onset juvenile idiopathic arthritis and secondary macrophage activation syndrome (MAS), whose treatment was complicated by severe allergic reactions to biologics, including drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity reaction (DIHR) likely due to anakinra, and anaphylactoid reaction to intravenous tocilizumab. These required transition to canakinumab, cyclosporine, and corticosteroids, with later development of interstitial lung disease and MAS flare needing transition from canakinumab to tofacitinib, which led to disease control. Whether lung disease is a manifestation of DRESS/DIHR to canakinumab remains unclear. High index of suspicion of hypersensitivity reactions for timely diagnosis and drug discontinuation is critical, especially in patients with active disease who might be at increased risk of these adverse events.

Association with HLA-DRß1 position 37 distinguishes juvenile dermatomyositis from adult-onset myositis.

Juvenile dermatomyositis (JDM) is a rare, severe autoimmune disease and the most common idiopathic inflammatory myopathy of children. JDM and adult-onset dermatomyositis (DM) have similar clinical, biological and serological features, although these features differ in prevalence between childhood-onset and adult-onset disease, suggesting that age of disease onset may influence pathogenesis. Therefore, a JDM-focused genetic analysis was performed using the largest collection of JDM samples to date. Caucasian JDM samples (n = 952) obtained via international collaboration were genotyped using the Illumina HumanCoreExome chip. Additional non-assayed human leukocyte antigen (HLA) loci and genome-wide single-nucleotide polymorphisms (SNPs) were imputed. HLA-DRB1*03:01 was confirmed as the classical HLA allele most strongly associated with JDM [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.46, 1.89; P = 1.4 × 10-14], with an independent association at HLA-C*02:02 (OR = 1.74; 95% CI 1.42, 2.13, P = 7.13 × 10-8). Analyses of amino acid positions within HLA-DRB1 indicated that the strongest association was at position 37 (omnibus P = 3.3 × 10-19), with suggestive evidence this association was independent of position 74 (omnibus P = 5.1 × 10-5), the position most strongly associated with adult-onset DM. Conditional analyses also suggested that the association at position 37 of HLA-DRB1 was independent of some alleles of the Caucasian HLA 8.1 ancestral haplotype (AH8.1) such as HLA-DQB1*02:01 (OR = 1.62; 95% CI 1.36, 1.93; P = 8.70 × 10-8), but not HLA-DRB1*03:01 (OR = 1.49; 95% CR 1.24, 1.80; P = 2.24 × 10-5). No associations outside the HLA region were identified. Our findings confirm previous associations with AH8.1 and HLA-DRB1*03:01, HLA-C*02:02 and identify a novel association with amino acid position 37 within HLA-DRB1, which may distinguish JDM from adult DM.

International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis.

OBJECTIVE: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. METHODS: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. RESULTS: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). CONCLUSION: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.

Chronic recurrent multifocal osteomyelitis causing optic neuropathy.

We present the case of an 8-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) involving the orbit and facial bone and causing left optic neuropathy. She presented with intermittent left periorbital swelling and a history of CRMO diagnosed 5 years earlier. Her disease responded well to adalimumab; however, delayed presentation resulted in permanent unilateral optic nerve atrophy and reduced vision. Orbital inflammatory disease is a rare manifestation of CRMO, and early recognition of the disease and treatment may prevent irreversible vision loss.

Giant Coronary Aneurysms in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection.

Multisystem inflammatory syndrome in children (MIS-C) can cause a myriad of cardiac manifestations, including coronary dilation and aneurysms; giant aneurysms are infrequent. We describe 3patients with giant coronary aneurysms associated with MIS-C, including the youngest case reported to date, treated with intravenous immunoglobulin, corticosteroids, and biologic agents. (Level of Difficulty: Intermediate.).

Predictors for early readmission in patients hospitalized with new onset pediatric lupus nephritis.

OBJECTIVE: The objective is to determine the 30-day hospital readmission rate following a hospitalization due to pediatric lupus nephritis of recent onset and characterize the risk factors associated with these early readmissions. METHODS: The study included 76 children hospitalized from 01/01/2008 to 4/30/2017 due to a new diagnosis of lupus nephritis. We calculated the 30-day hospital readmission rate and compared the characteristics of the patients that were readmitted to patients that were not readmitted using univariable and multivariable analysis. RESULTS: The 30-day readmission rate was 17.1%. Factors that predicted hospital readmission in unavailable analysis were male gender (38.5 vs 14.3%, p = 0.04), not receiving pulse steroids (30.8 vs 3.2%, p = < .001), receiving diuretic treatment (69.2 vs 34.9%, p = .02), receiving albumin infusions (46.2 vs 12.7%, p = .004), stage 2 hypertension on day one of admission (76.9 vs 41.3%, p = .02), a higher white blood cell count on discharge (13.7 × 103/mm3 vs 8.8 × 103/mm3, p = .023), need for non-angiotensin converting enzyme (ACE) antihypertensive drugs (76.9 vs 46%, p = .042), and being discharged on nonsteroidal anti-inflammatory drugs (NSAIDs) (23.1 vs 4.8%, p = .025). Multivariable analysis demonstrated an increased risk of readmission for patients not treated with intravenous pulse methylprednisolone (IVMP) (OR = 17.5 (1.81-168.32) p = .013), and for those who required intravenous albumin assisted diuresis for hypervolemia (OR=6.25 (1.29-30.30) p = .022). CONCLUSION: In all, 17% of children hospitalized due to new onset lupus nephritis were readmitted within 30 days of discharge. Absence of IVMP and receiving intravenous albumin assisted diuresis during initial hospitalization increase the risk of early readmission in new onset pediatric lupus nephritis.

Outcomes of COVID-19 in a cohort of pediatric patients with rheumatic diseases.

BACKGROUND: There are few reports of COVID-19 in pediatric patients with rheumatic diseases. This study describes the clinical presentation and outcomes of COVID-19 in this population. METHODS: We analyzed a single-center case series of pediatric patients with rheumatic diseases and laboratory-confirmed COVID-19. Demographic, baseline and COVID-19 associated clinical features were compared between ambulatory and hospitalized patients using univariate analysis. RESULTS: Fifty-five cases were identified: 45 (81.8%) in the ambulatory group and 10 (18.2%) hospitalized. African American race (OR 7.78; 95% CI [1.46-55.38]; p = 0.006) and cardiovascular disease (OR 19.40; 95% CI 2.45-254.14; p = 0.001) predominated in hospitalized patients. Active rheumatic disease (OR 11.83; 95% CI 1.43-558.37; p = 0.01), medium/high-dose corticosteroid use (OR 14.12; 95% CI [2.31-106.04]; p = 0.001), mycophenolate use (OR 8.84; 95% CI [1.64-63.88]; p = 0.004), rituximab use (OR 19.40; 95% CI [2.45-254.14]; p = 0.001) and severe immunosuppression (OR 34.80; 95% CI [3.94-1704.26]; p = < 0.001) were associated with increased odds of hospitalization. Fever (OR 7.78; 95% CI [1.46-55.38]; p = 0.006), dyspnea (OR 26.28; 95% CI [2.17-1459.25]; p = 0.003), chest pain (OR 13.20; 95% CI [1.53-175.79]; p = 0.007), and rash (OR 26.28; 95% CI [2.17-1459.25]; p = 0.003) were more commonly observed in hospitalized patients. Rheumatic disease flares were almost exclusive to hospitalized patients (OR 55.95; 95% CI [5.16-3023.74]; p < 0.001).. One patient did not survive. CONCLUSIONS: Medium/high-dose corticosteroid, mycophenolate and rituximab use, and severe immunosuppression were risk factors for hospitalization. Fever, dyspnea, chest pain, and rash were high-risk symptoms for hospitalization. Rheumatic disease activity and flare could contribute to the need for hospitalization.

Intravenous administration of anakinra in children with macrophage activation syndrome.

BACKGROUND: Subcutaneous anakinra is an interleukin-1 inhibitor used to treat juvenile idiopathic arthritis. Recent reports suggest anakinra can be a valuable addition to the treatment of COVID-19 associated cytokine storm syndrome and the related multisystem inflammatory syndrome (MIS-C) in children. Herein, we describe our experience with intravenously administered anakinra. FINDINGS: 19 Patients (9 male) received intravenous (IV) anakinra for treatment of macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE), systemic JIA (SJIA) or secondary hemophagocytic lymphohistiocytosis (sHLH). In most cases the general trend of the fibrinogen, ferritin, AST, and platelet count (Ravelli criteria) improved after initiation of IV anakinra. There were no reports of anaphylaxis or reactions associated with administration of IV anakinra. CONCLUSION: Intravenous administration of anakinra is an important therapeutic option for critically ill patients with MAS/HLH. It is also beneficial for those with thrombocytopenia, subcutaneous edema, neurological dysfunction, or very young, hospitalized patients who need multiple painful subcutaneous injections.

Risk factors associated with Pneumocystis jirovecii pneumonia in juvenile myositis in North America.

OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is associated with significant morbidity and mortality in adult myositis patients; however, there are few studies examining PJP in juvenile myositis [juvenile idiopathic inflammatory myopathy (JIIM)]. The purpose of this study was to determine the risk factors and clinical phenotypes associated with PJP in JIIM. METHODS: An research electronic data capture (REDCap) questionnaire regarding myositis features, disease course, medications and PJP infection characteristics was completed by treating physicians for 13 JIIM patients who developed PJP (PJP+) from the USA and Canada. Myositis features and medications were compared with 147 JIIM patients without PJP (PJP-) from similar geographic regions who enrolled in National Institutes of Health natural history studies. RESULTS: PJP+ patients were more often of Asian ancestry than PJP- patients [odds ratio (OR) 8.7; 95% CI 1.3, 57.9]. Anti- melanoma differentiation associated protein 5 (MDA5) autoantibodies (OR 12.5; 95% CI 3.0, 52.4), digital infarcts (OR 43.8; 95% CI 4.2, 460.2), skin ulcerations (OR 12.0; 95% CI 3.5, 41.2) and interstitial lung disease (OR 10.6; 95% CI 2.1, 53.9) were more frequent in PJP+ patients. Before PJP diagnosis, patients more frequently received pulse steroids, rituximab and more immunosuppressive therapy compared with PJP- patients. Seven PJP+ patients were admitted to the intensive care unit and four patients died due to PJP or its complications. CONCLUSIONS: PJP is a severe infection in JIIM that can be associated with mortality. Having PJP was associated with more immunosuppressive therapy, anti-MDA5 autoantibodies, Asian race and certain clinical features, including digital infarcts, cutaneous ulcerations and interstitial lung disease. Prophylaxis for PJP should be considered in juvenile myositis patients with these features.

Impact of autoimmune cytopenias on severity of childhood-onset systemic lupus erythematosus: A single-center retrospective cohort study.

OBJECTIVE: To assess whether children with autoimmune cytopenias prior to or at diagnosis of systemic lupus erythematosus (cSLE), differ phenotypically from other cSLE patients; and have a lower risk and severity of lupus nephritis (LN) as observed in prior adult studies. To assess the effect of prior immune therapy for autoimmune cytopenias on 2-year risk of LN. METHODS: This was a retrospective cohort study of incident cSLE cases. We included patients aged less than 17 years at diagnosis. We excluded patients with LN at cSLE diagnosis. Our follow-up period was 2 years. We defined autoimmune cytopenias as either autoimmune hemolytic anemia, immune thrombocytopenia or Evan's syndrome. RESULTS: Forty-three (33%) of the 130 patients had autoimmune cytopenias before or at cSLE diagnosis. Those with autoimmune cytopenias had significantly more neuropsychiatric symptoms and higher mean ESR but less arthritis, malar rash and myositis versus those without autoimmune cytopenias. They had lower 2-year incidence proportion of LN compared to other cSLE patients (7% vs 15%). Of the 16 patients who developed LN, those with autoimmune cytopenias had mostly class V (2 of 3 patients) versus mostly class III and IV in those without autoimmune cytopenias (6 of 12 patients). None of the 13 patients pre-treated for autoimmune cytopenias developed LN. CONCLUSION: Patients with autoimmune cytopenias before or at cSLE diagnosis have intriguing differences from other cSLE patients. They may represent a unique sub-type of cSLE patients and should be further explored.