Robert P Sundel

Robert P Sundel
Harvard Medical School | HMS · Department of Pediatrics

M.D.

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167
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Introduction
Skills and Expertise

Publications

Publications (167)
Article
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (ie, cognitive dysfunction and mood disorders) appear to occur with greater severity and poorer prognosis in childhood‐onset SLE (cSLE) versus adult‐onset SLE, negatively impacting school...
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Background: Macrophage activation syndrome (MAS) is a life-threatening complication of Still's disease (SD) characterized by overt immune cell activation and cytokine storm. We aimed to further understand the immunologic landscape of SD and MAS. Method: We profiled peripheral blood mononuclear cells (PBMC) from healthy controls and patients with...
Article
Objective: Kawasaki disease (KD) is a systemic vasculitis of young children that can lead to development of coronary artery aneurysms. We aimed to identify diagnostic markers to distinguish KD from other pediatric inflammatory diseases. Methods: We used the proximity extension assay (PEA) to profile proinflammatory mediators in plasma samples fr...
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Objective Although interleukin‐1 (IL‐1)/IL‐6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL‐1/IL‐6 inhi...
Article
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T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clona...
Article
Objective To compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG). Methods A management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and...
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Objective To provide evidence‐based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists. Methods Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comp...
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Objective To provide evidence‐based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists. Methods Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comp...
Article
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Introduction Juvenile idiopathic arthritis (JIA) is a cluster of autoimmune rheumatic diseases occurring in children 16 years of age or less. While it is well-known that pain may be experienced during inflammatory and non-inflammatory states, much remains ambiguous regarding the molecular mechanisms that may drive JIA pain. Thus, in this pilot stud...
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Oligoarticular juvenile idiopathic arthritis (oligo JIA) is the most common form of chronic inflammatory arthritis in children; yet, the cause of this disease remains unknown. To understand immune responses in oligo JIA, we immunophenotyped synovial fluid T cells with flow cytometry, bulk and single-cell RNA sequencing, DNA methylation studies, and...
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Objective To provide evidence‐based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody–associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods Clinical questions regarding the treatment...
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Objective To provide evidence‐based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody–associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods Clinical questions regarding the treatment...
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Objective To provide evidence‐based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PI...
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Objective To provide evidence‐based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Methods Twenty‐one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non–hepatitis B–related...
Article
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Objective To provide evidence‐based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Methods Twenty‐one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non–hepatitis B–related...
Article
Full-text available
Objective To provide evidence‐based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PI...
Article
Background Juvenile Localized Scleroderma (jLS) is a rare pediatric inflammatory disease of skin and underlying tissues that may cause significant functional impairment and disfigurement. Management approaches vary and an optimum treatment regimen is lacking. In 2012, a group of jLS researchers of Childhood Arthritis and Rheumatology Research Allia...
Article
Introduction Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging to define pain-related neurobiological features altered in JIA. Methods 16 male and female JIA patients (12.7 ± 2.8 years of age) on active treatment were enrolled, toge...
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Background Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA). Case presentation We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospec...
Article
Objectives To determine predictors of more than one emergency department (ED) visit for a Kawasaki disease diagnosis in a quaternary care pediatric hospital and compare outcomes between patients with 1 versus > 1 visit for KD diagnosis. Study design Medical records of patients evaluated for KD between January 2006 and August 2018 at Boston Childre...
Article
Objective A North American registry of JDM patients was examined for frequency of and factors associated with corticosteroid discontinuation, complete clinical response and remission. Methods We evaluated probability of achieving final corticosteroid discontinuation, complete clinical response and remission in 307 JDM patients by Weibull time-to-e...
Article
Objective: Patients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outco...
Preprint
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Background. Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA). Case presentation. We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospe...
Article
Background: Pediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail. Methods: We retrospectively studi...
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Systemic juvenile idiopathic arthritis (sJIA) begins with fever, rash, and high-grade systemic inflammation but commonly progresses to a persistent afebrile arthritis. The basis for this transition is unknown. To evaluate a role for lymphocyte polarization, we characterized T cells from patients with acute and chronic sJIA using flow cytometry, mas...
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Rasmussen encephalitis (RE) is a disorder characterized by drug-resistant seizures and progressive unihemispheric atrophy, hemiparesis, and varying degrees of cognitive decline. The pathophysiology of RE remains elusive, with hypotheses suggesting underlying autoimmune- and T cell-mediated processes. In this case report, we describe a single patien...
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Objective Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in overwhelming inflammation and multiorgan failure. The clinical features of MAS overlap with those of active sJIA, complicating early diagnos...
Article
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Background Accurate prediction of coronary artery aneurysms ( CAAs ) in patients with Kawasaki disease remains challenging in North American cohorts. We sought to develop and validate a risk model for CAA prediction. Methods and Results A binary outcome of CAA was defined as left anterior descending or right coronary artery Z score ≥2.5 at 2 to 8...
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Objective To highlight a novel, treatable syndrome, we report 4 patients with CNS-isolated inflammation associated with familial hemophagocytic lymphohistiocytosis (FHL) gene mutations (CNS-FHL).Methods Retrospective chart review.ResultsPatients with CNS-FHL are characterized by chronic inflammation restricted to the CNS that is not attributable to...
Article
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Background Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) were historically thought to be distinct entities, often managed in isolation. In fact, these conditions are closely related. A collaborative approach, which incorporates expertise from subspecialties that previously treated HLH/MAS independently, is needed...
Article
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Deficiency of adenosine deaminase 2 is characterized by vasculitis, early-onset strokes, immunodeficiency, and bone marrow failure. We describe a novel pathogenic mutation affecting a consensus N-linked glycosylation sequence and illustrate the essential role of glycosylation in the biology of ADA2.
Article
Objective: Several studies revealed the efficacy of glucocorticoids on prevention of CAL in KD patients. However, impacts of different doses of glucocorticoids on clinical outcomes of KD remain unknown. Methods: Using the Japanese Diagnosis Procedure Combination inpatient database, we evaluated KD patients who were treated with normal-dose (pred...
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Background The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960’s with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from h...
Article
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Background Accurate risk prediction of coronary artery aneurysms (CAAs) in North American children with Kawasaki disease remains a clinical challenge. We sought to determine the predictive utility of baseline coronary dimensions adjusted for body surface area (z scores) for future CAAs in Kawasaki disease and explored the extent to which addition o...
Data
Table S1. Comparison of Patients Included Versus Excluded for Lack of Echocardiography at 4 to 8 Weeks After Illness Onset Table S2. Demographic and Laboratory Variables Associated With Coronary Artery Aneurysm
Article
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Several studies revealed the epidemiology of Kawasaki disease-related hospitalizations among children in the USA and other countries. However, disparities of developing coronary artery aneurysms by race/ethnicity, patient socioeconomic status, and geographic locations remain unknown in the USA. Hospital discharge record data of patients with Kawasa...
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Background The number of trained specialists world-wide is insufficient to serve all children with pediatric rheumatologic disorders, even in the countries with robust medical resources. We evaluated the potential of diagnostic decision support software (DDSS) to alleviate this shortage by assessing the ability of such software to improve the diagn...
Article
Corticosteroids and Kawasaki disease (KD) have had a complicated relationship. Sentiment has fluctuated between the extremes, from indispensable to proscribed, even as the roles of intravenous immunoglobulin (IVIG) and aspirin have been defined. As the meta-analysis by Chen et al¹ in this issue of JAMA Pediatrics demonstrates, the findings of recen...
Article
Importance: Kawasaki disease (KD) is the most recognized vasculitis of childhood. The condition's characteristic high fever, rash, mucositis, conjunctivitis, lymphadenopathy, and extremity changes are superficially unexceptional, and resolve spontaneously within a mean of 12 days. It is the acuity and the potential for life-changing damage to the...
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At the national level, IgA vasculitis-related hospitalizations among children in the USA are scarce. Furthermore, nationwide epidemiology and hospital course of children with IgA vasculitis have not been fully described in the USA, and disparities by race/ethnicity remain unknown. Hospital discharge records of patients aged 19 years or younger were...
Article
Objective: Regulatory T (Treg) cell mediated suppression of effector T (Teff) cells is impaired in juvenile idiopathic arthritis (JIA); however, the basis for this dysfunction is incompletely understood. Animal models of autoimmunity and immunodeficiency demonstrate that a diverse Treg repertoire is essential to maintain Treg cell function. We the...
Article
Aim: To assess the performance of established Japanese risk scores (RS) to identify patients (pts) with Kawasaki disease (KD) at high-risk for developing coronary artery aneurysms (CAA). Methods: We reviewed clinical, laboratory and echocardiographic (echo) data for pts with KD treated with IVIG from 1/2006 to 5/2014. We defined CAA as z score ≥2.5...
Article
Aim: At a single pediatric tertiary care center, we assessed the performance of established Japanese risk scores (RS) to identify patients (pts) with Kawasaki Disease (KD) at higher risk for re-treatment (re-tx). We also sought to determine if the addition of baseline coronary Z-scores to RS could improve the prediction re-tx. Methods: We reviewed...
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Background Multicenter studies on idiopathic or viral pericarditis and pericardial effusion (PPE) have not been reported in children. Colchicine use for PPE in adults is supported. We explored epidemiology and management for inpatient hospitalizations for PPE in US children and risk factors for readmission. Methods and Results We analyzed patients...
Article
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Juvenile Idiopathic Arthritis (JIA) is the most common cause of non-infectious joint inflammation in children. Synovial inflammation results in pain, swelling and stiffness. Animal and adult human studies indicate that localized joint-associated inflammation may produce generalized changes in pain sensitivity. The aim was to characterize pain sensi...
Article
To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA). Eighty-five children were randomized blindly to methotrex...
Article
Background/Purpose T regulatory (Treg) function has been shown to be impaired in juvenile idiopathic arthritis (JIA) as synovial fluid (SF) Tregs are unable to suppress T effector cells (Teffs) found in the joint. The cause of this breach in immunologic tolerance is not fully understood, meriting the further study of Tregs and Teffs in JIA. The T c...
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Autoinflammatory syndromes are a group of rare conditions that cause intermittent episodes of fever and organ system inflammation. The majority of these conditions have been linked to single gene mutations that are involved in the acute inflammatory response. Many of these monogenic disorders, such as Familial Mediterranean Fever (FMF) and Hyper Ig...
Article
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The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels...
Article
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Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We...
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Background and objectives: Little information is available concerning the natural history and optimal treatment of chronic nonbacterial osteomyelitis (CNO). We conducted a retrospective review to assess the clinical characteristics and treatment responses of a large cohort of pediatric CNO patients. Methods: Children diagnosed with CNO at 3 tert...
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Objective. To determine whether adult disease severity subclassification systems for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are concordant with the decision to treat pediatric patients with cyclophosphamide (CYC). Methods. We applied the European Vasculitis Study (EUVAS) and Wegener’s Granulomatosis Etanercept Trial (WGET)...
Article
In the absence of definitive diagnostic tests, several schemes for the classification of paediatric vasculitis have been devised and periodically updated, but are these revisions necessary and useful?
Article
Rheumatoid arthritis is associated with an excess of agalactosylated (G0) IgG that is considered relatively proinflammatory. Assessment of this association in juvenile idiopathic arthritis (JIA) is complicated by age-dependent IgG glycan variation. The aim of this study was to conduct the first large-scale survey of IgG glycans in healthy children...
Article
The safety and efficacy of mycophenolate mofetil (MMF) were evaluated in adolescent patients with systemic lupus erythematosus and active or active/chronic class III-V lupus nephritis. During the 24-week induction phase, patients were randomized to oral MMF (target dose 3.0 g/day) or intravenous cyclophosphamide (IVC) (0.5-1.0 g/m(2)/month), plus p...
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Objective. Granulomatosis with polyangiitis (Wegener’s; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childho...
Article
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From 2011 Pediatric Rheumatology Symposium sponsored by the American College of Rheumatology Miami, FL, USA. 2-5 June 2011 Purpose The approximately 250 board certified Pediatric Rheu-matologists in the United States are unable to see all of the children in need of specialized rheumatologic care. Consequently, many pediatric patients receive this c...
Article
To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggre...
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Objective. There are no validated tools for measuring disease activity in pediatric vasculitis. The Birmingham Vasculitis Activity Score (BVAS) is a valid disease activity tool in adult vasculitis. Version 3 (BVAS v.3) correlates well with physician’s global assessment (PGA), treatment decision, and C-reactive protein in adults. The utility of BVAS...
Article
Lyme arthritis most commonly affects the knee. It is not commonly considered in the differential diagnosis of monoarticular hip pain. There are only a few case reports describing Lyme disease presenting with isolated hip involvement. The purpose of this study is to review our experience with primary Lyme arthritis of the hip. Clinical records at a...
Article
Musculoskeletal chest pain is the most common identifiable cause of chest pain in children and adolescents. A lesion or irritation of any layer of the anterior chest wall may lead to pain. Causes range from the common, such as costochondritis, to the rare, such as chronic recurrent multifocal osteomyelitis. Regardless of the cause, chest pain raise...
Article
To test the hypothesis that first re-treatment with infliximab, compared with intravenous immunoglobulin (IVIG), might improve outcomes in IVIG-resistant Kawasaki disease. In a two-center retrospective review from January 2000 to March 2008, we compared duration of fever and coronary artery dimensions in patients with IVIG-resistance whose first re...
Article
Children often develop arthritis secondary to Lyme disease; however, optimal treatment of Lyme arthritis in pediatric patients remains ill-defined. We sought to characterize the outcomes of a large cohort of children with Lyme arthritis treated using the approach recommended by the American Academy of Pediatrics and the Infectious Diseases Society...
Article
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The 2004 American Heart Association (AHA) statement included a clinical case definition and an algorithm for diagnosing and treating suspected incomplete Kawasaki disease (KD). We explored the performance of these recommendations in a multicenter series of US patients with KD with coronary artery aneurysms (CAAs). We reviewed retrospectively record...