- Pediatric Rheumatology
- systemic lupus erythematosus
- lupus nephritis
Clinical Associate Professor, Pediatrics - Rheumatology
Honors & Awards
site primary investigator for CARRA Registry, Childhood Arthritis and Rheumatology Research Alliance
ACR/ REF/ LRI Lupus Investigator Fellowship Award, American College of Rheumatology (2004-2007)
Boards, Advisory Committees, Professional Organizations
Member, American College of Rheumatology (2003 - Present)
Member, Childhood Arthritis and Rheumtology Research Alliance (CARRA) (2004 - Present)
Member, Pediatric Rheumatology Care and Outcomes Improvement Network (PR COIN) (2011 - Present)
Internship, UCLA Medical Center Pediatric Residency (2000)
Residency, UCLA Medical Center Pediatric Residency (2002)
Medical Education: Washington University School Of Medicine Registrar (1999) MO
Fellowship: Stanford University Pediatric Rheumatology Fellowship (2006) CA
Board Certification: American Board of Pediatrics, Pediatrics (2002)
Board Certification: American Board of Pediatrics, Pediatric Rheumatology (2006)
BA, UC Berkeley, Molecular & Cell Biology (1995)
MD, Washington University, Medicine (1999)
MS, Stanford University, Health Research and Policy (2007)
Community and International Work
Opportunities for Student Involvement
Current Research and Scholarly Interests
Pediatric Systemic Lupus Erythematosus;
Racial/Ethnic Differences in Pediatric Lupus Patients
Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry
Continuation of the CARRA Registry as described in the protocol will support data collection on patients with pediatric-onset rheumatic diseases. The CARRA Registry will form the basis for future CARRA studies. In particular, this observational registry will be used to answer pressing questions about therapeutics used to treat pediatric rheumatic diseases, including safety questions.
Profiling Behavioral and Psychological Symptoms in Children undergoing treatment for Spondyloarthritis and Polyarthritis.
The Journal of rheumatology
OBJECTIVE: Few studies examine psychopathology in different juvenile idiopathic arthritis (JIA) subtypes and disease activity states. We aimed to 1) Evaluate emotional and behavioral symptoms in children with spondyloarthritis (SpA) and polyarticular arthritis (PolyA) as compared to a national normative population using the Child Behavior Checklist (CBCL), and 2) Evaluate the relationship between CBCL scores and disease activity.METHODS: JIA patients aged 6-17 years with SpA or PolyA were recruited from our Pediatric Rheumatology clinic from April 2018 to April 2019 and the CBCL and Juvenile Arthritis Disease Activity Score (cJADAS10) were completed. Primary outcome measures were CBCL total competence, internalizing, externalizing and total problems raw scores. We compared outcomes from each group to national CBCL normative data. To investigate the relationship between CBCL scores and disease activity, we ran a generalized linear regression model for all arthritis patients with cJADAS10 as the main predictor.RESULTS: There were 111 patients and 1753 healthy controls. Compared to healthy controls, SpA or PolyA patients had worse total competence and internalizing scores. Higher cJADAS10 scores were associated with worse total competence, worse internalizing, and higher total problems scores. Most of these differences reached statistical significance (p<0.01). Self-harm/ suicidality was almost four-fold higher in patients with PolyA than healthy controls (OR 3.6, 95% CI 1.3-9.6, p=0.011).CONCLUSION: Our study shows that SpA and PolyA patients with more active disease have worse psychological functioning in activities, school and social arenas and more internalized emotional disturbances suggesting the need for regular mental health screening by rheumatologists.
View details for DOI 10.3899/jrheum.210489
View details for PubMedID 35105715
Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE.
Pediatric rheumatology online journal
2021; 19 (1): 137
BACKGROUND: Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare.METHODS: Members of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination.RESULTS: Seventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15% of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50% agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59% of nephrologists, but only 38% of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58% of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43%) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p<0.05).CONCLUSIONS: Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.
View details for DOI 10.1186/s12969-021-00627-w
View details for PubMedID 34461932
Inflammatory Bowel Disease in Children with Systemic Juvenile Idiopathic Arthritis.
The Journal of rheumatology
The incidence of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) is higher than in the general pediatric population. However, reports of IBD in the systemic JIA (sJIA) subtype are limited. We sought to characterize sJIA patients diagnosed with IBD and to identify potential contributing risk factors.Using an internationally distributed survey, we identified 16 sJIA patients who were subsequently diagnosed with IBD (sJIA-IBD cohort). 522 sJIA patients without IBD were identified from the CARRA Legacy Registry and served as the sJIA-only cohort for comparison. Differences in demographic, clinical characteristics and therapy were assessed using chi-square test, Fisher's exact test, t-test, and univariate and multivariate logistic regression as appropriate.75% of sJIA-IBD patients had a persistent sJIA course; 25% had a history of MAS. sJIAIBD subjects were older at sJIA diagnosis, more often non-White, had a higher rate of IBD family history, and were more frequently treated with etanercept or canakinumab compared to sJIA-only subjects. 69% of sJIA-IBD patients successfully discontinued sJIA medications following IBD diagnosis, and sJIA symptoms resolved in 9/12 patients treated with TNF-α inhibitors.IBD in the setting of sJIA is a rare occurrence. The favorable response of sJIA symptoms to therapeutic TNF-α inhibition suggests that the sJIA-IBD cohort may represent a mechanistically distinct sJIA subgroup. Our study highlights the importance of maintaining a high level of suspicion for IBD when gastrointestinal involvement occurs in sJIA patients and the likely broad benefit of TNF-α inhibition in those cases.
View details for DOI 10.3899/jrheum.200230
View details for PubMedID 32541073
- Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis PEDIATRIC RHEUMATOLOGY 2018; 16
Adiposity in Juvenile Psoriatic Arthritis
JOURNAL OF RHEUMATOLOGY
2018; 45 (3): 411–18
Adult patients with psoriatic arthritis are at increased risk for obesity and metabolic syndrome, but data regarding adiposity in children with juvenile psoriatic arthritis (JPsA) are limited. Our study assessed adiposity in children with JPsA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.Patients with JPsA in the CARRA registry were divided into nonoverweight and overweight groups using recommendations from the US Centers for Disease Control, and differences in demographic and clinical characteristics between groups at baseline and after 1-year followup were assessed using chi-square test, Fisher's exact test, T test, or Mann-Whitney U test, as appropriate. The prevalence of overweight status in the JPsA registry patients was compared to rheumatoid factor-positive and -negative polyarticular juvenile idiopathic arthritis (RF+polyJIA; RF-polyJIA) registry cohorts and the US pediatric population, using a chi-square goodness-of-fit test.Overweight children represented 36.3% of this JPsA cohort (n = 320). Compared to nonoverweight children, they were significantly older at symptom onset and rheumatologist's first assessment, and scored significantly worse on patient/physician outcome measures. At 1-year followup, changes in body mass index were not associated with changes in clinical features or outcome measures. The prevalence of overweight and obesity in patients with JPsA was significantly higher than in RF+polyJIA patients, RF-polyJIA patients, and the US pediatric population.In this registry, almost 1 in 5 patients with JPsA were obese and more than one-third were overweight. This is significantly more than expected compared to the US pediatric population, and appropriate longterm followup of this JPsA subgroup is warranted.
View details for PubMedID 29247150
Analysis of relationships between 25-hydroxyvitamin D, parathyroid hormone and cathelicidin with inflammation and cardiovascular risk in subjects with paediatric systemic lupus erythematosus: an Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study
LUPUS SCIENCE & MEDICINE
2018; 5 (1): e000255
Previous studies demonstrated associations between reduced serum 25-hydroxyvitamin D (25OHD), inflammation and disease activity in paediatric systemic lupus erythematosus (pSLE). The goal of this study was to assess parathyroid hormone (PTH) in its relationship to vitamin D and inflammation, as well as to better understand the role of human cathelicidin (LL-37) in pSLE.Frozen serum samples collected at baseline of the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study were assayed to determine 25OHD, PTH and LL-37 levels. Pearson's correlations and Χ2 tests were used to evaluate the relationships between 25OHD, PTH, LL-37, inflammation, disease activity and infection using baseline values collected as part of the APPLE study.201/221 APPLE participants had serum available for analysis. Serum 25OHD was inversely associated with serum PTH, but not LL-37. Serum PTH was not associated with high sensitivity C-reactive protein, carotid intima media thickness or high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol, but was negatively associated with lipoprotein(a) levels. Despite no association with serum 25OHD, LL-37 was negatively associated with total cholesterol, HDL and LDL cholesterol and positively associated with age. There was no significant difference in mean LL-37 levels in participants with reported infection as an adverse event during the 3-year APPLE study.Despite links to vitamin D levels in other studies, LL-37 levels were not associated with baseline serum 25OHD concentrations in paediatric patients with pSLE. Despite the lack of correlation with 25OHD, LL-37 levels in this study were associated with cholesterol levels. Some subjects with pSLE have significantly elevated levels of LL-37 of unknown significance. These exploratory results addressing the role of LL-37 levels in pSLE appear worthy of future study.
View details for DOI 10.1136/lupus-2017-000255
View details for Web of Science ID 000495994400008
View details for PubMedID 29955369
View details for PubMedCentralID PMC6018862
Resilience and Transition Readiness in Pediatric SLE Patients
View details for Web of Science ID 000411824106499
Corticosteroid Regimen Use in the Pilot Study of Consensus Treatment Plans for Induction Therapy in Childhood Proliferative Lupus Nephritis
WILEY. 2017: 141–42
View details for Web of Science ID 000399787200094
The Juvenile Psoriatic Arthritis Cohort in the CARRA Registry: Clinical Characteristics, Classification, and Outcomes
JOURNAL OF RHEUMATOLOGY
2017; 44 (3): 342-351
Children with clinically diagnosed juvenile psoriatic arthritis (JPsA) who were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry (CARRA-JPsA) were classified according to pediatric International League of Associations for Rheumatology (ILAR) and adult criteria [Classification criteria for Psoriatic Arthritis (CASPAR)]. Data on demographic and clinical features at baseline and 1-year followup were analyzed and compared.Cross-sectional analysis was performed of CARRA-JPsA patients enrolled between May 2010 and December 2013 and stratified according to age at disease onset (≤ or > 4 yrs). Features of patients fulfilling ILAR and CASPAR criteria were compared at baseline and followup using chi square, Fisher's exact, Mann-Whitney-McNemar, Wilcoxon signed rank, and t tests, as appropriate.Among 361 children enrolled as CARRA-JPsA, 72.02% had symptom onset at > 4 years of age, with a male predominance and high prevalence of enthesitis. At followup, statistically significant improvements were reported in arthritis, dactylitis, enthesitis, psoriasis, sacroiliitis, and nail pitting, but not in health questionnaire (HQ) scores. Of the patients, 80.5% fulfilled ILAR criteria for JPsA. Fifty-two patients, whose disease fulfilled CASPAR criteria but had not been included in the JPsA cohort, manifested more enthesitis, sacroiliitis, inflammatory bowel disease and uveitis and less psoriasis.The data support division of patients with JPsA into 2 clinical subgroups, according to age at disease onset. Improvement in objective findings did not correlate with changes in HQ scores. Pediatric rheumatologists currently do not diagnose JPsA in all children whose disease manifestations meet CASPAR criteria. Unification of adult and pediatric PsA classification criteria warrants consideration.
View details for DOI 10.3899/jrheum.160717
View details for Web of Science ID 000396031600013
View details for PubMedID 28148698
Enhancing Pediatric Rheumatology Education through Computer-Assisted Fellow-Taught Case Modules
View details for Web of Science ID 000417143401540
Discordance Between Physician, Patient, and Parent Disease Assessment Scores in Juvenile Idiopathic Arthritis
View details for Web of Science ID 000417143400404
A Pilot Study of Consensus Treatment Plans for Induction Therapy in Childhood Proliferative Lupus Nephritis
View details for Web of Science ID 000417143402211
Inflammatory Bowel Disease in Children with Systemic Juvenile Idiopathic Arthritis
View details for Web of Science ID 000370860202722
Adiposity in Children with Juvenile Psoriatic Arthritis (JPsA)
View details for Web of Science ID 000370860202741
Juvenile Psoriatic Arthritis Manifestations in a Cohort of 361 Patients from US and Canada
View details for Web of Science ID 000370860202734
Novel Method to Collect Medication Adverse Events in Juvenile Arthritis: Results From the Childhood Arthritis and Rheumatology Research Alliance Enhanced Drug Safety Surveillance Project
ARTHRITIS CARE & RESEARCH
2015; 67 (4): 529-537
Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP.Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution.Thirty-seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person-years (95% CI 0.95-1.19). The rates for SAEs and IMEs were 0.54 per 100 person-years (95% CI 0.45-0.63) and 0.53 per 100 person-years (95% CI 0.49-0.62), respectively.The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry.
View details for DOI 10.1002/acr.22487
View details for Web of Science ID 000352111800010
View details for PubMedID 25331530
Extension study of participants from the trial of early aggressive therapy in juvenile idiopathic arthritis.
journal of rheumatology
2014; 41 (12): 2459-2465
To follow children with juvenile idiopathic arthritis (JIA) who had completed at least 6 months of the TRial of Early Aggressive Therapy (TREAT) clinical study for an additional 2 years, describing safety of early aggressive treatment, disease activity, function, and duration of clinical inactive disease (CID) during followup.Children were treated as per provider's discretion. Physician, patient/parent, and laboratory measures of disease status as well as safety information were collected at clinic visits every 3 months for up to 2 years.Forty-eight children were followed for a mean of 28 months (range 12-42) beyond the end of the TREAT study. Half of patients were in CID for > 50% of their followup time. Overall, 88% of patients achieved CID at > 1 study visit and 54% achieved clinical remission while taking medication. Six patients were in CID for the duration of the study, and, of those, 2 achieved a full year of clinical remission while not taking medication. Active disease was mild: mean physician's global assessment 2.4, active joint count 3.5, parent global evaluation 2.4, Childhood Health Assessment Questionnaire 0.32, erythrocyte sedimentation rate 19 mm/h, and morning stiffness 23 min. There were no serious adverse events or adverse events reported at grade 3 or higher of Common Terminology Criteria for Adverse Events.Early aggressive therapy in this cohort of patients with polyarticular JIA who had high initial disease activity was associated with prolonged periods of CID in the majority of patients during followup. Those not in CID had low levels of disease activity.
View details for DOI 10.3899/jrheum.140347
View details for PubMedID 25179849
- Consensus Treatment Plans for Induction Therapy in Childhood Proliferative Lupus Nephritis-Status of Use in Daily Clinical Care WILEY-BLACKWELL. 2014: S35–S36
Results Of a 24 Month Extension Study In PatientsWhoParticipated In The Trial Of Early Aggressive Therapy In Polyarticular Juvenile Idiopathic Arthritis
WILEY-BLACKWELL. 2013: S116
View details for Web of Science ID 000325359201277
European ancestry decreases the risk of early onset, severe lupus nephritis in a single center, multiethnic pediatric lupus inception cohort
2012; 21 (4): 421-429
To determine whether pediatric SLE patients without European ancestry are at higher risk for development of severe lupus nephritis (ISN/RPS class III, IV or V).Ninety-eight of 101 patients with pediatric SLE (age <18 years at diagnosis) were enrolled. Race/ethnicity of four grandparents, socioeconomic status (SES) and language proficiency were collected. The primary outcome was time to development of severe lupus nephritis.Based on patient report of four grandparent ancestry, 29% had at least one grandparent of European ancestry (14% had all four grandparents of European ancestry). Patients without European ancestry were 46% Hispanic, 47% Asian, and 3% African American. In the entire 98 patient cohort, 12% had ≥3 different ancestries. Patients without European ancestry had significantly lower SES levels and English proficiency. There was no significant difference between patients with or without European ancestry in duration of SLE, age of onset, and lag time between symptoms and diagnosis. Patients with at least one grandparent of European ancestry had a decreased risk of developing severe lupus nephritis, which remained significant after controlling for age, gender, SES and English proficiency (hazard ratio 0.4, 95% confidence interval 0.2-0.9).This study demonstrates that presence of at least one grandparent of European ancestry decreases the risk of severe lupus nephritis, a finding that is not explained by measurable socioeconomic differences and language barriers.
View details for DOI 10.1177/0961203312437805
View details for PubMedID 22427363
Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus
ARTHRITIS CARE & RESEARCH
2012; 64 (3): 375-383
To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE).A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches.After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs.CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.
View details for DOI 10.1002/acr.21558
View details for Web of Science ID 000300831500009
View details for PubMedID 22162255
View details for PubMedCentralID PMC3457803
Developing Consensus Treatment Plans for Proliferative Nephritis in Juvenile Systemic Lupus Erythematosus: Maintenance Therapy.
WILEY-BLACKWELL. 2011: S1031
View details for Web of Science ID 000297621503204