Renee F. Modica

B-Cell Depletion and Immunomodulation before Initiation of Enzyme Replacement Therapy Blocks the Immune Response to Acid Alpha-Glucosidase in Infantile-Onset Pompe Disease

OBJECTIVE To evaluate whether B-cell depletion before enzyme replacement therapy (ERT) initiation can block acid alpha-glucosidase (GAA) antibody responses and improve clinical outcomes. STUDY DESIGN Six subjects with Pompe disease (including 4 cross-reacting immunologic material-negative infants) aged 2-8 months received rituximab and sirolimus or mycophenolate before ERT. Four subjects continued to receive sirolimus, rituximab every 12 weeks, and intravenous immunoglobulin monthly for the duration of ERT. Sirolimus trough levels, IgG, CD3, CD4, CD8, CD19, CD20, N-terminal pro-brain natriuretic peptide, creatine kinase, creatine kinase-MB, C-reactive protein, platelets, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase were measured regularly. RESULTS Immunomodulation achieved B-cell depletion without adverse effects. After 17-36 months of rituximab, sirolimus and ERT, all subjects lacked antibodies against GAA, 4 continued to gain motor milestones, yet 2 progressed to require invasive ventilation. The absence of infusion-associated reactions allowed the use of accelerated infusion rates. CONCLUSION B-cell depletion and T-cell immunomodulation in infants naïve to ERT was accomplished safely and eliminated immune responses against GAA, thereby optimizing clinical outcome; however, this approach did not necessarily influence sustained independent ventilation. Importantly, study outcomes support the initiation of immunomodulation before starting ERT, because the study regimen allowed for prompt initiation of treatment.

Teaching Musculoskeletal Physical Diagnosis Using A Web-based Tutorial and Pathophysiology-Focused Cases

Objective: To assess the effectiveness of an experimental curriculum on teaching first-year medical students the musculoskeletal exam as compared to a traditional curriculum. Background: Musculoskeletal complaints are common in the primary care setting. Practitioners are often deficient in examination skills and knowledge regarding musculoskeletal diseases. There is a lack of uniformity regarding how to teach the musculoskeletal examination among sub-specialists. We propose a novel web-based approach to teaching the musculoskeletal exam that is enhanced by peer practice with pathophysiology-focused cases. We sought to assess the effectiveness of an innovative musculoskeletal curriculum on the knowledge and skills of first-year medical students related to musculoskeletal physical diagnosis as compared to a traditional curriculum. The secondary purpose of this study was to assess satisfaction of students and preceptors exposed to this teaching method. Methods: This quasi-experimental study was conducted at a single LCME-accredited medical school and included a convenience sample from 2 consecutive classes of medical students during the musculoskeletal portion of their physical diagnosis class. We conducted a needs assessment of the traditional curriculum used to teach musculoskeletal examination. The needs assessment informed the development of an experimental curriculum. One class (control group) received the traditional curriculum while the second class (experimental group) received the experimental curriculum, consisting of a web-based musculoskeletal tutorial, pathophysiology-focused cases, and facilitator preparation. We used multiple-choice questions and musculoskeletal OSCE scores to assess differences between knowledge and skills in the 2 groups. Results: The sample consisted of 140 students in each medical school class. There were no statistically significant differences between the 2 groups. One hundred seven students from the control group and 120 students from the experimental group took the multiple-choice examination. The average score was 66% (95% CI= 59.7–72.3) for the control group and 66% (95% CI = 60.5–71.5) for the experimental group. There was no difference between the median musculoskeletal OSCE scores between the 2 groups. The experimental group was satisfied with the new teaching method and gained the additional benefit of a persistent resource. Conclusions: This web-based experimental curriculum was as effective as the traditional curriculum for teaching the musculoskeletal exam. Additionally, users were satisfied with the web-based training and benefited from a persistent resource.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America

BackgroundThe 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 human genes) for inflammatory myositis has been reported. In 2011–2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA).MethodsThe JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011–2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013–2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting.ResultsOne hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups.ConclusionsOur CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future.Significance and InnovationsThis is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years.This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Trimming the fat: identification of risk factors associated with obesity in a pediatric emergency department.

Objective: The purpose of this study was to assess which knowledge deficits and dietary habits in an urban pediatric emergency department (ED) population are risk factors for obesity. Methods: This cross-sectional study in an urban pediatric ED used a modified version of the Diet and Health Knowledge Survey, an in-person interview questionnaire, to collect data on demographics, dietary knowledge, and practices. All patients aged 2 to 17 years were enrolled in the study over a 4-month period. Subjects were excluded if they were in extremis, pregnant, incarcerated, institutionalized, considered an emancipated minor, or consumed only a modified consistency diet. Results: One hundred seventy-nine subjects were enrolled in this study. Based on body mass index, the prevalence of obesity in our study population was 24%. Parents with obese children answered a mean of 62.9% (95% confidence interval, 60.4%-65.5%) of knowledge questions correctly, whereas all others scored 60.3% (95% confidence interval, 58.3%-62.3%) correctly. Based on the univariate analysis, 10 predictors met inclusion criteria into logistic regression analysis: screen time (P = 0.03), race (P = 0.08), sex (P = 0.04), parental education (P = 0.08), parental estimation that child is overweight (P < 0.0001), parental estimation that child is underweight (P = 0.003), trimming fat from meat (P = 0.06), soft-drink consumption (P = 0.03), exercise (P = 0.07), and chip consumption (P = 0.04). In a multivariate analysis, only male sex, regularly trimming fat from meat, and parental assessment of obesity were independently associated with obesity. Conclusions: Knowledge deficiencies regarding healthy nutrition among parents in an urban pediatric ED population were not significantly associated with having obese children; however, specific habits were. Emergency physicians may provide a valuable role in identification and brief behavioral intervention in high-risk populations during the current epidemic of childhood obesity.

Goldenhar Syndrome Associated with Extensive Arterial Malformations

Goldenhar Syndrome is characterized by craniofacial, ocular and vertebral defects secondary to abnormal development of the 1st and 2nd branchial arches and vertebrae. Other findings include cardiac and vascular abnormalities. Though these associations are known, the specific anomalies are not well defined. We present a 7-month-old infant with intermittent respiratory distress that did not improve with respiratory interventions. Echocardiogram suggested a double aortic arch. Cardiac CT angiogram confirmed a right arch and aberrant, stenotic left subclavian artery, dilation of the main pulmonary artery, and agenesis of the left thyroid lobe. Repeat echocardiograms were concerning for severely dilated coronary arteries. Given dilation, a rheumatologic workup ensued, only identifying few weakly positive autoantibodies. Further imaging demonstrated narrowing of the aorta below the renal arteries and extending into the common iliac arteries and proximal femoral arteries. Given a physical exam devoid of rheumatologic findings, only weakly positive autoantibodies, normal inflammatory markers, and presence of the coronary artery dilation, the peripheral artery narrowings were not thought to be vasculitic. This case illustrates the need to identify definitive anomalies related to Goldenhar Syndrome. Although this infants presentation is rare, recognition of specific vascular findings will help differentiate Goldenhar Syndrome from other disease processes.

The family journey-to-diagnosis with systemic juvenile idiopathic arthritis: a cross-sectional study of the changing social media presence

Background Children with systemic juvenile idiopathic arthritis (SJIA) often encounter a delay between symptom onset and disease diagnosis, partly due to the broad differential of fever and lack of symptom recognition by providers. Families often seek multiple medical opinions and post on social media about their frustrations. This linguistic analysis observed the changing language patterns and social media posting behaviors of parents in the time leading to, during, and after SJIA diagnosis. Methods Public social media sites were manually reviewed by a linguistic team to evaluate posts about SJIA from US-based parents. Results A total of 3,979 posts between July 2001 and January 2015 were reviewed from 108 sites. Pre-SJIA diagnosis parents sought answers and shared status updates on social media, focusing primarily on the following three site types: alternative/natural lifestyle forums (39%), Facebook (27%), and disease-specific forums (17%). Posts during early prediagnosis phases were characterized by expressive language showing confidence in health care providers and trust in parental instincts. At later prediagnosis stages, parents continued to use social media, but the posts demonstrated increased frustration with delays in diagnosis and gaps in communication with providers. More objective symptom descriptions and a greatly reduced child-centered emotional focus were observed as parents shifted into caregiving roles. Once the diagnosis of SJIA was confirmed, parents used straightforward, less expressive language, and Facebook (47%) to make “announcement” posts and increased their use of SJIA websites (30%). With treatment initiation, the posts demonstrated a slow return of expressive language and an increased parental understanding of the “new normal”. Conclusion Parents use different language styles, frames of reference, and websites before and after SJIA diagnosis. Gaps in parent–provider communication, especially before diagnosis, and their new roles as caregivers lead to parental use of social media to express frustration with the health care process. Providers should tailor their discussions with parents to address these issues.

A136: Assessing the Efficacy of Pediatric Rheumatology Video‐based Curriculum

Musculoskeletal complaints are common in pediatrics. Practitioners are often under‐skilled in performing the musculoskeletal exam and deficient in basic knowledge regarding rheumatologic diseases. We sought to determine if learning the pediatric musculoskeletal exam and rheumatic conditions in a video‐enriched case‐based lecture series will improve their knowledge of rheumatic diseases.

Impact of systemic juvenile idiopathic arthritis/Still’s disease on adolescents as evidenced through social media posts

Purpose To understand the experience of adolescent systemic juvenile idiopathic arthritis (SJIA) patients and those of their parents based on their social media posts. Methods English language posts related to SJIA, Still’s disease, or juvenile arthritis were collected and analyzed. Results In total, 71 posts created between 2009 and 2015 on 15 websites were identified in November 2015. Of the 32 unique authors, 17 were SJIA patients aged 13–20 years (40 posts), 7 were mothers of SJIA patients (12 posts), and 8 patients had unspecified forms of juvenile arthritis (19 posts). Many patients posted about similar diagnostic experiences marked by 5 phases: 1) early prediagnosis: pain and fatigue overlooked until crisis occurred, 2) first misdiagnosis: doctors talked about “growing pains” and psychosocial problems (“fake pains” to avoid school), 3) second misdiagnosis: severity acknowledged, but diagnosed as leukemia or another cancer, 4) tests: tests leading to diagnosis and treatment conducted, and 5) cognitive identity: patient accepted the diagnosis and its implications. Many adolescent patients, looking back at disease onset in their childhood, described themselves as a “sleeping child” rather than the typical active child. Several patients tried to hide their illness from friends, but expressed concerns openly online. Many patients described SJIA as a powerful external enemy, using terms like “bulldozer,” “dragon,” and “monster.” Many posts from patients and their mothers used superhero language/imagery to help “fight” SJIA. Some patients also posted about the risk of death. Conclusion Although most adolescent SJIA patients openly posted about the difficulties of their disease online, they made efforts to hide their disease in the real world. They frequently used superhero words and images in describing their fight for better health. Physicians can use these insights when counseling SJIA patients to provide a narrative that meshes with the patients’ worldview and perhaps to improve physician–patient communication to increase treatment adherence.