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ObjectivesTo delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN).MethodsIn this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy.ResultsAdiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient (r) = − 0.49; p < 0.0001] but not proteinuria (r = 0.20; p > 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p < 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP.ConclusionIn combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline.Key messages• Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis.• Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance.• Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.

AimsMethotrexate (MTX) is standard treatment in pediatric chronic anterior uveitis (CAU). Addition of tumor necrosis factor-α inhibitors (TNFi) is often needed. We describe the timing and risk factors for TNFi use in children with CAU on MTX.MethodsIn this retrospective study, we reviewed 51 records, and 46 met inclusion criteria. Primary outcome was the addition of TNFi due to active CAU per Standardization of Uveitis Nomenclature criteria. Time to TNFi and factors associated with their addition were assessed using survival analysis models.ResultsOf 46 children treated with MTX for uveitis (36 juvenile idiopathic arthritis-associated uveitis, 10 idiopathic CAU), 72% had ocular complications. MTX was started a median of 5.0 months, and TNFi 43 months from uveitis diagnosis. Kaplan–Meier estimates suggest that cumulatively, 12% (95% CI: 4–23%) start TNFi within 6 months of MTX, 21% (12–37%) within 1 year, and 39% (24–54%) within 2 years. On Cox Proportional Hazard regression analysis, children with idiopathic CAU required TNFi earlier in their uveitis course (at 3 months (Hazard Ratio 6.06; 95% confidence interval (1.25–29.41))). Females appeared less likely to require TNFi early. Children treated in 2012 and later were more likely to receive TNFi earlier than those treated before 2012.ConclusionLittle is known about optimal time to initiate treatment or factors associated with the need to add TNFi in children on MTX. Children with idiopathic CAU and males required TNFi earlier in their course. Factors associated with these potential risk factors for TNFi warrant further investigation.

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 limited perceived benefit to their academic portfolios. Based on AMIGO’s success, a counterpart program for adult rheumatology, 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.

BackgroundBiomarkers in easily obtained specimens that accurately predict uveitis in children with juvenile idiopathic arthritis (JIA) are needed. Aqueous humor has been studied for biomarkers, but is not routinely available. We evaluated tears from children with chronic anterior uveitis (CAU) for biomarkers reported in aqueous humor.In this pilot study, we used Schirmer strips to collect tears from seven children (nine eyes); three children had JIA- associated uveitis (JIA-U) and four had idiopathic disease (I-CAU). Liquid chromatography-tandem mass spectrometry was used to identify and quantify tear proteins. The Mann-Whitney U test identified differential tear protein expression between children with JIA-U and those with I-CAU.ResultsS100A9, LAP3, TTR, MIF, sCD14, S100A8, and SAA1 were detected in tears of all children; the same cytokines have been reported in aqueous humor of children with JIA-U. Tears from children with JIA-U had higher expression of proteins associated with inflammatory arthritis (SEMA3G, TIMP1, HEXB, ERN1, and SAA1) than tears from those with I-CAU. In addition, we found higher expression of sCD14, S100A8, and SAA1, but lower expression of S100A9, LAP3, TTR, and MIF, in tears from children with JIA-U compared to tears from those with I-CAU.ConclusionsTears contain similar cytokine profiles to aqueous humor in children with CAU and may be a clinically useful source of disease biomarkers. Tears from children with JIA-U also contain cytokines associated with inflammatory arthritis; furthermore, differential expression of other tear proteins as well may provide clues to intrinsic differences between JIA-U and I-CAU, despite their similar clinical phenotypes.

Objective To determine the demographic and clinical characteristics associated with use of the EuroLupus or modified National Institutes of Health (NIH) cyclophosphamide (CYC) regimen for treatment of lupus nephritis (LN) at North American pediatric centers. Methods A retrospective cohort study was conducted at 11 North American centers. Patients <22 years of age with active LN treated with CYC using the EuroLupus or NIH regimen between July 2014 and June 2021 were included. Data were extracted via electronic medical record review. Demographic and clinical characteristics were compared at CYC initiation. A multivariable generalized estimating equation with logit link was fit to model EuroLupus use. An exchangeable correlation structure was used to account for correlation within centers. Independent variables were chosen using elastic net regression. Results The cohort consisted of 191 patients (85 EuroLupus, 106 NIH) with a median age of 15.3 years at CYC initiation. In multivariable analysis, characteristics significantly associated with EuroLupus regimen use (vs NIH regimen use) included more recent year of CYC initiation, longer disease duration, Hispanic ethnicity and Asian race (as compared to Black), previous CYC treatment, renal impairment (dialysis or mild kidney impairment), and absence of neuropsychiatric involvement. Conclusion For children and young adults with LN requiring CYC, use of the EuroLupus regimen increased over time and is associated with demographic and clinical factors such as race or Hispanic ethnicity, renal impairment, and absence of neuropsychiatric involvement. The differences in regimen use with severe renal impairment and neuropsychiatric lupus highlight areas for future study in CYC dosing.

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.

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.

Dermatomyositis (DM) and juvenile dermatomyositis (JDM) are inflammatory myopathies affecting multiple organs, including muscle and skin. Calcinosis is a complication of DM/JDM that causes significant morbidity; however, few tools exist to assess calcinosis in DM/JDM patients This study aimed to evaluate the reliability of durometry measurements to assess the firmness of calcinosis lesions in DM and JDM patients. Calcinosis firmness was measured using a handheld digital durometer. Six investigators across 3 institutions examined DM/JDM calcinosis lesions by durometry, as well as control readings in healthy unaffected skin/subcutaneous tissue in similar anatomic areas, recording three readings per site. Intra-rater and inter-rater intraclass correlations were evaluated. We enrolled 57 patients and gathered 709 measurements (443 calcinosis lesions; 266 control lesions) over eleven anatomic regions. Intra-rater reliability was high across sites, while inter-rater reliability varied, being moderate to good in most areas, but poor in the thigh and anterior calf. Durometry readings were higher in calcinosis lesions than control sites overall. Measurements moderately correlated with qualitative physician assessments. Due to our study's cross-sectional nature, we could not assess calcinosis over time. Durometry is a novel, reliable, quantitative measure in assessing and characterizing targeted calcinosis lesions of DM/JDM patients.

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.

Calcinosis is a severe manifestation of juvenile and adult idiopathic inflammatory myopathies, which can lead to pain, limited range of motion, disfigurement, and infection. It is more common in juvenile idiopathic inflammatory myopathies, especially in juvenile dermatomyositis (JDM). Calcinosis can be visible on cutaneous surfaces, although can also present in muscles and internal organs, making a thorough assessment difficult without imaging modalities. In this narrative review, we discuss different imaging modalities used in evaluating JDM-associated calcinosis including X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US).