- Pediatric Rheumatology
Clinical Assistant Professor, Pediatrics - Rheumatology
Medical Education: Tufts University School of Medicine (2004) MA
Board Certification: American Board of Pediatrics, Pediatrics (2007)
Board Certification: American Board of Pediatrics, Pediatric Rheumatology (2011)
Fellowship: Lucile Packard Children's Hospital (2010) CA
Residency: Lucile Packard Children's Hospital (2007) CA
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.
Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
2022; 40 (4): 841-848
View details for Web of Science ID 000799758700023
Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study.
Clinical and experimental rheumatology
OBJECTIVES: High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes.METHODS: Youth <18 years with pAAV, biopsy-confirmed pauci-immune glomerulonephritis and 12-month follow-up data were included from an international paediatric vasculitis registry. Presenting features and 12-month outcomes (eGFR, glucocorticoid-related adverse effects), were compared between patients receiving no, low-moderate (≤90mg/kg) and high (>90mg/kg) cumulative intravenous methylprednisolone (IVMP), and low (<0.5mg/kg/day prednisone equivalent), moderate (0.5-1.5mg/kg/day) and high (>1.5mg/kg/day) starting doses of oral glucocorticoids.RESULTS: Among 131 patients (101 granulomatosis with polyangiitis, 30 microscopic polyangiitis), 27 (21%) received no IVMP, 64 (49%) low-moderate and 29 (22%) high-dose IVMP, while 9 (7%) received low, 75 (57%) moderate and 47 (36%) high initial doses of oral glucocorticoids. Renal failure at diagnosis (p=0.022) and plasmapheresis use (p=0.0001) were associated with high-dose IVMP. Rates of glucocorticoid-related adverse effects ranged from 15-31% across dose levels, and glucocorticoid dosing did not associate with 12-month outcomes.CONCLUSIONS: Glucocorticoid dosing for pAAV-related renal disease was highly variable, and rates of adverse effects were high across all dosing groups. A significant proportion of patients received oral glucocorticoid or IVMP doses that were discordant with current adult guidelines. Higher glucocorticoid doses did not associate with improved outcomes.
View details for DOI 10.55563/clinexprheumatol/iol4k2
View details for PubMedID 35383555
Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.
Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n=110) and MIS-C (n=76), along with pediatric healthy controls (pHCs; n=76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-kappaB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.
View details for DOI 10.1038/s41591-022-01724-3
View details for PubMedID 35177862
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
Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C.
Frontiers in immunology
2022; 13: 841126
The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjogren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.
View details for DOI 10.3389/fimmu.2022.841126
View details for PubMedID 35360001
Determinants of Tumor Necrosis Factor Inhibitor Use in Juvenile Spondyloarthropathy and Impact on Clinical Disease Outcomes.
ACR open rheumatology
OBJECTIVE: The objectives of this study were to characterize the reasons for tumor necrosis factor inhibitor (TNFi) initiation in patients with juvenile spondyloarthropathy (JSpA) and identify clinical correlates and to assess the effect of TNFi therapy on JSpA disease activity.METHODS: We conducted a retrospective cohort study of 86 patients with JSpA with first-time use of a TNFi over a 7-year period at Stanford Children's Health. We assessed the physician's reason for TNFi initiation, disease activity at 6 months, and clinical disease status at 12 months following TNFi start. Changes in active joint count, enthesitis count, and pain were measured. Demographics, physician reasons for TNFi initiation, and clinical characteristics were summarized.RESULTS: The mean age at JSpA diagnosis was 12.4years (SD 4.0years), and the mean time from diagnosis to TNFi initiation was 1.6years (SD 2.3years). The most common reason for initiating a TNFi was active disease on physical examination (61%). At 6 months post TNFi initiation, patients on average had three fewer active joints and one fewer active enthesitis point. Patient-reported pain improved from moderate/severe to mild. After 12 months, 54% of patients had active disease.CONCLUSION: The physician's decision to initiate a TNFi relied mostly on physical examination findings. Despite improvement in arthritis, enthesitis, and patient-reported pain at 6 months post TNFi initiation, the majority of the patients still had active disease after 1 year of therapy.
View details for DOI 10.1002/acr2.11353
View details for PubMedID 34647693
Consensus Treatment Plans for Severe Pediatric Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Arthritis care & research
OBJECTIVE: There is no standardized approach to the treatment of pediatric antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (ped-AAV). Because of the rarity of ped-AAV, randomized trials have not been feasible. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for severe ped-AAV to enable the future study of comparative effectiveness and safety.METHODS: A workgroup of CARRA members (rheumatologists and nephrologists) formed the AAV working group. This group performed a literature review on existing evidence-based treatments and guidelines for the management of AAV. They determined that the target population for CTP development was patients <18 years with new-onset granulomatosis with polyangiitis (GPA), microscopic polyangiitis, or renal-limited AAV (eosinophilic-GPA was excluded) with presentation confined to those with severe disease i.e. organ- or life-threatening. Face-to-face consensus conferences employed nominal group techniques to identify treatment strategies for remission-induction and remission-maintenance, data elements to be systematically collected, and outcomes to be measured over time.RESULTS: The ped-AAV workgroup developed two CTPs for each of the remission-induction and remission-maintenance of severe AAV. A corticosteroid-weaning regimen for induction and maintenance, a core dataset, and outcome measures were also defined. A random sample of CARRA membership voted acceptance of the CTPs for remission-induction and remission-maintenance with a 94% (75/80) and 98% (78/80) approval rate respectively.CONCLUSION: Consensus methodology established standardized CTPs for treating severe ped-AAV. These CTPs were in principle accepted by CARRA-wide membership for pragmatic comparative effectiveness evaluation in a long-term registry.
View details for DOI 10.1002/acr.24590
View details for PubMedID 33675161
Development of CARRA Consensus Treatment Plans for Severe ANCA-associated Vasculitis - Final CARRA-wide Consensus
WILEY. 2020: 117–19
View details for Web of Science ID 000542687800067
Gaps in Mental Health Care for Youth With Rheumatologic Conditions: A Mixed Methods Study of Perspectives From Behavioral Health Providers
ARTHRITIS CARE & RESEARCH
2019; 71 (5): 591–601
View details for DOI 10.1002/acr.23683
View details for Web of Science ID 000465600400002
Pediatric Integrative Medicine in Academia: Stanford Children's Experience
2018; 5 (12)
View details for DOI 10.3390/children5120168
View details for Web of Science ID 000454708100013
Gaps in Mental Health Care for Youth with Rheumatologic Conditions: A Mixed Methods Study of Perspectives from Behavioral Health Providers.
Arthritis care & research
OBJECTIVE: To identify behavioral health provider perspectives on gaps in mental health care for youth with rheumatologic conditions.METHODS: Social workers (n=34) and psychologists (n=8) at pediatric rheumatology centers in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an online survey assessing current practices and mental health care needs of youth with rheumatologic conditions. Responses were compared to a published survey of CARRA rheumatologists (n=119). Thematic analysis of 20 semi-structured interviews with behavioral health providers was performed.RESULTS: One third of CARRA centers (n=100) had no affiliated social worker or psychologist. Only one behavioral health provider reported current universal mental health screening at their rheumatology clinic, yet routine depression screening was supported by >85% of behavioral health providers and rheumatologists. Support for anxiety screening was higher among behavioral health providers (90% vs 65%, p<0.01). Interviews illustrated a need for interventions addressing illness-related anxiety, adjustment/coping/distress, transition, parent/caregiver mental health, and peer support. Limited resources, lack of protocols, and patient cost/time burden were the most frequent barriers to intervention. Inadequate follow-up of mental health referrals was indicated by 52%. More behavioral health providers than rheumatologists favored mental health services in rheumatology settings (55% vs 19%, p<0.01). Only 7 social workers (21%) provided counseling/therapy, and interviews indicated their perceived under-utilization for these services.CONCLUSION: Behavioral health providers indicate an unmet need for mental health interventions addressing illness-related issues affecting youth with rheumatologic conditions. Implementation of mental health protocols and optimizing utilization of social workers may improve mental health care for these youth. This article is protected by copyright. All rights reserved.
View details for PubMedID 29953741
Pediatric Integrative Medicine in Residency Program: Relationship between Lifestyle Behaviors and Burnout and Wellbeing Measures in First-Year Residents
2018; 5 (4)
It is widely recognized that burnout is prevalent in medical culture and begins early in training. Studies show pediatricians and pediatric trainees experience burnout rates comparable to other specialties. Newly developed Accreditation Council for Graduate Medical Education (ACGME) core competencies in professionalism and personal development recognize the unacceptably high resident burnout rates and present an important opportunity for programs to improve residents experience throughout training. These competencies encourage healthy lifestyle practices and cultivation of self-awareness, self-regulation, empathy, mindfulness, and compassion—a paradigm shift from traditional medical training underpinned by a culture of unrealistic endurance and self-sacrifice. To date, few successful and sustainable programs in resident burnout prevention and wellness promotion have been described. The University of Arizona Center for Integrative Medicine Pediatric Integrative Medicine in Residency (PIMR) curriculum, developed in 2011, was designed in part to help pediatric programs meet new resident wellbeing requirements. The purpose of this paper is to detail levels of lifestyle behaviors, burnout, and wellbeing for the PIMR program’s first-year residents (N = 203), and to examine the impact of lifestyle behaviors on burnout and wellbeing. The potential of the PIMR to provide interventions addressing gaps in lifestyle behaviors with recognized association to burnout is discussed.
View details for PubMedID 29690631
Pediatric Integrative Medicine in Academia: Stanford Children's Experience.
Children (Basel, Switzerland)
2018; 5 (12)
Pediatric integrative medicine is an emerging field which, to date, has not been described in detail in academic medical centers in the United States. Early research of pediatric integrative medicine modalities shows promise for the treatment of common pediatric conditions such as irritable bowel syndrome, acute and chronic pain, headache, and allergy, among others. In light of the growing prevalence of pediatric illnesses and patient complexity, it is crucial to emphasize the patient's overall well-being. As academic centers around the world start to develop pediatric integrative medicine programs, the aim of this manuscript is to briefly highlight evidence of effective integrative treatments in pediatric subspecialties, to describe the establishment of our integrative medicine program, to summarize its early efforts, and to discuss potential barriers and keys to success.
View details for PubMedID 30545081
Determinants of Anti-Tumor Necrosis Factor Drug Use in Juvenile Spondyloarthropathy and Impact on Clinical Disease Outcomes
View details for Web of Science ID 000411824105128
Pediatric Integrative Medicine
2017; 140 (3)
View details for DOI 10.1542/peds.2017-1961
View details for Web of Science ID 000408820300051
Underutilization of Social Workers for Mental Health Care of Adolescents in Pediatric Rheumatology: A Mixed Methods Study
WILEY. 2017: 185–87
View details for Web of Science ID 000399787200125