Preventing Teen Pregnancies on Teratogenic Drugs by Quality Improvement and Behavioral Economics.

BACKGROUND: Adolescents with chronic disease engage in sexual activity similar to their healthy peers, with generally low utilization of contraception. Adolescents with rheumatic diseases prescribed teratogenic medications may be at risk for unplanned pregnancy. METHODS: Using structured quality improvement (QI) methods with behavior economic (BE) principles, a multidisciplinary team aimed to implement pregnancy prevention processes for females on high-risk medications. We leveraged BE-inspired interventions including improved accessibility of consents, utilizing distinctly colored consent forms, real-time reminders, peer comparison, and audit and feedback. Our primary aim was to increase the number of days between pregnancies for postmenarcheal females followed in rheumatology clinics who were taking teratogenic medications. Phase 1 focused on annual consenting of female adolescents prescribed teratogenic drugs. Phase 2 emphasized sexual history screening and pregnancy prevention planning at every clinic visit for females ≥12 years on teratogenic medications. RESULTS: We increased the days between pregnancies for female adolescents prescribed teratogenic medications from 52 days to >900 days by using QI methodology with BE strategies. In phase 1, annual consents for postmenarcheal patients on teratogenic medications improved from 0% in 2017 to 95% in 2021. In phase 2, sexual history screening and pregnancy prevention planning at every clinic visit improved from 2% in 2019 to over 78% in 2021. CONCLUSIONS: A multiphase, multidisciplinary QI project with integration of behavior economic strategies can improve patient and caregiver counseling to prevent unplanned pregnancies for adolescents on teratogenic medications.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging.

OBJECTIVE: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging.

OBJECTIVE: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

Translating research into practice-implementation recommendations for pediatric rheumatology; Proceedings of the childhood arthritis and rheumatology research alliance 2020 implementation science retreat.

The translation of research findings into clinical practice is challenging, especially fields like in pediatric rheumatology, where the evidence base is limited, there are few clinical trials, and the conditions are rare and heterogeneous. Implementation science methodologies have been shown to reduce the research- to- practice gap in other clinical settings may have similar utility in pediatric rheumatology. This paper describes the key discussion points from the inaugural Childhood Arthritis and Rheumatology Research Alliance Implementation Science retreat held in February 2020. The aim of this report is to synthesize those findings into an Implementation Science Roadmap for pediatric rheumatology research. This roadmap is based on three foundational principles: fostering curiosity and ensuring discovery, integration of research and quality improvement, and patient-centeredness. We include six key steps anchored in the principles of implementation science. Applying this roadmap will enable researchers to evaluate the full range of research activities, from the initial clinical design and evidence acquisition to the application of those findings in pediatric rheumatology clinics and direct patient care.

Improving Vitamin D Screening in a Pediatric Rheumatology Clinic Using Structured Quality Improvement Process.

Introduction: Monitoring levels of 25-hydroxyvitamin D (25-OHD) is an integral part of bone health assessment in the general pediatric population, especially in at-risk populations such as children with juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (c-SLE), and juvenile dermatomyositis (JDM). However, only 38% of the patients with JIA, c-SLE, and JDM receiving care at Nationwide Children's Hospital Rheumatology clinic in 2016 had a 25-OHD level ordered in the preceding year. The objective of this project was to increase the percentage of 25-OHD levels ordered in patients with JIA, c-SLE, and JDM from 38% to 80% in 11 months and sustain it for 6 months. Methods: A multidisciplinary team initiated a continuous improvement project utilizing the Lean Six Sigma methodology. The team diagrammed the clinical process and identified steps that needed improvement. In addition, the team completed a root cause analysis of the process and brainstormed subsequent countermeasures. Results: The team did not meet the 80% target but did order a 25-OHD level on 61% of patients by the end of the study period compared to 38% at the start of the study (P value 0.001). The level was sustained after the study period, with 68% of these children having a 25-OHD level ordered. Conclusion: The team successfully improved the screening processes for vitamin D deficiency in a busy subspecialty clinic setting using Lean Six Sigma methodology.

Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases.

Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or C4B isotypes. We demonstrated the diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease, such as type 1 diabetes, systemic lupus erythematosus (SLE) and encephalitis. We identified subjects with (a) the fastest migrating C4B allotype, B7, or (b) a deficiency of C4B protein caused by genetic mutation in addition to gene copy-number variation. Those variants and mutants were characterized, sequenced and specific techniques for detection developed. Novel findings were made in four case series. First, the amino acid sequence determinant for C4B7 was likely the R729Q variation at the anaphylatoxin-like region. Second, in healthy White subject MS630, a C-nucleotide deletion at codon-755 led to frameshift mutations in his single C4B gene, which was a private mutation. Third, in European family E94 with multiplex lupus-related mortality and low serum C4 levels, the culprit was a recurrent haplotype with HLA-A30, B18 and DR7 that segregated with two defective C4B genes and identical mutations at the donor splice site of intron-28. Fourth, in East-Asian subject E133P with anti-NMDA receptor encephalitis, the C4B gene had a mutation that changed tryptophan-660 to a stop-codon (W660x), which was present in a haplotype with HLA-DRB1*04:06 and B*15:27. The W660x mutation is recurrent among East-Asians with a frequency of 1.5% but not detectable among patients with SLE. A meticulous annotation of C4 sequences revealed clusters of variations proximal to sites for protein processing, activation and inactivation, and binding of interacting molecules.

Reintroduction of immunosuppressive medications in pediatric rheumatology patients with histoplasmosis: a case series.

BACKGROUND: Children with rheumatic diseases (cRD) receiving immunosuppressive medications (IM) are at a higher risk for acquiring potentially lethal pathogens, including Histoplasma capsulatum (histoplasmosis), a fungal infection that can lead to prolonged hospitalization, organ damage, and death. Withholding IM during serious infections is recommended yet poses risk of rheumatic disease flares. Conversely, reinitiating IM increases risk for infection recurrence. Tumor necrosis factor alpha inhibitor (TNFai) biologic therapy carries the highest risk for histoplasmosis infection after epidemiological exposure, so other IM are preferred during active histoplasmosis infection. There is limited guidance as to when and how IM can be reinitiated in cRD with histoplasmosis. This case series chronicles resumption of IM, including non-TNFai biologics, disease-modifying anti-rheumatic drugs (DMARDs), and corticosteroids, following histoplasmosis among cRD. CASE PRESENTATION: We examine clinical characteristics and outcomes of 9 patients with disseminated or pulmonary histoplasmosis and underlying rheumatic disease [juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), and mixed connective tissue disease (MCTD)] after reintroduction of IM. All DMARDs and biologics were halted at histoplasmosis diagnosis, except hydroxychloroquine (HCQ), and patients began antifungals. Following IM discontinuation, all patients required systemic or intra-articular steroids during histoplasmosis treatment, with 4/9 showing Cushingoid features. Four patients began new IM regimens [2 abatacept (ABA), 1 HCQ, and 1 methotrexate (MTX)] while still positive for histoplasmosis, with 3/4 (ABA, MTX, HCQ) later clearing their histoplasmosis and 1 (ABA) showing decreasing antigenemia. Collectively, 8/9 patients initiated or continued DMARDs and/or non-TNFai biologic use (5 ABA, 1 tocilizumab, 1 ustekinumab, 3 MTX, 4 HCQ, 1 leflunomide). No fatalities, exacerbations, or recurrences of histoplasmosis occurred during follow-up (median 33 months). CONCLUSIONS: In our cohort of cRD, histoplasmosis course following reintroduction of non-TNFai IM was favorable, but additional studies are needed to evaluate optimal IM management during acute histoplasmosis and recovery. In this case series, non-TNFai biologic, DMARD, and steroid treatments did not appear to cause histoplasmosis recurrence. Adverse events from corticosteroid use were common. Further research is needed to implement guidelines for optimal use of non-TNFai (like ABA), DMARDs, and corticosteroids in cRD following histoplasmosis presentation.

Exploring Pediatric Tele-Rheumatology Practices During COVID-19: A Survey of the PRCOIN Network.

Healthcare providers were rapidly forced to modify the way they practiced medicine during the coronavirus disease 2019 (COVID-19) pandemic. Many providers transitioned from seeing their patients in person to virtually using telemedicine platforms with limited training and experience using this medium. In pediatric rheumatology, this was further complicated as musculoskeletal exams typically require hands-on assessment of patients. The objective of this study was to examine the adoption of telemedicine into pediatric rheumatology practices, to assess its benefits and challenges, and to gather opinions on its continued use. A survey was sent to the lead representatives of each Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) site to collect data about their center's experience with telemedicine during the COVID-19 pandemic. Quantitative data were analyzed using descriptive statistics, and qualitative data were thematically analyzed. Responses were received from the majority [19/21 (90%)] of PR-COIN sites. All respondents reported transitioning from in-person to primarily virtual patient visits during the COVID-19 pandemic. All centers reported seeing both new consultations and follow-up patients over telemedicine. Most centers reported using both audio and video conferencing systems to conduct their telemedicine visits. The majority of respondents [13/19 (68%)] indicated that at least 50% of their site's providers consistently used pediatric Gait Arms Legs and Spine (pGALS) to perform active joint count assessments over telemedicine. Over half of the centers [11/19 (58%)] reported collecting patient-reported outcomes (PROs), but the rate of reliably documenting clinical components varied. A few sites [7/19 (37%)] reported performing research-related activity during telemedicine visits. All centers thought that telemedicine visits were able to meet providers' needs and support their continued use when the pandemic ends. Benefits reported with telemedicine visits included convenience and continuity of care for families. Conversely, challenges included limited ability to perform physical exams and varying access to technology. Pediatric rheumatology providers were able to transition to conducting virtual visits during the COVID-19 pandemic. Healthcare providers recognize how telemedicine can enhance their practice, but challenges need to be overcome in order to ensure equitable, sustainable delivery of quality and patient-centered care.

Improving eye screening practice among pediatric rheumatology patients receiving hydroxychloroquine.

OBJECTIVE: Hydroxychloroquine (HCQ) is commonly used in the treatment of various autoimmune diseases related to its many benefits and favorable safety profile. Although HCQ retinopathy was considered to be uncommon, a prevalence of 7.5% was described in a recent study making early detection critical. The most updated screening guidelines by the American Academy of Ophthalmology were published in 2016; however, it lacked pediatric-specific recommendations and the overall compliance with screening guidelines was poor in previous studies. We developed a quality improvement (QI) initiative aiming to create institutional screening recommendations. Additionally, to increase eye screening in pediatric rheumatology clinic for patients receiving HCQ from 65% to 85% in 12 months and to sustain that rate for at least 6 months. METHODS: We formed a multidisciplinary team of pediatric rheumatologists and ophthalmologists, clinical pharmacist, clinic nurses, QI specialist, quality data technician and administrative staff. We included patients receiving HCQ and who were evaluated at Nationwide Children's Hospital rheumatology clinic. A key driver diagram was formulated to identify barriers to compliance and determine possible interventions. Main interventions included summarizing screening guidelines in a step by step algorithm, increasing awareness of these guidelines among patients and providers, improving collaboration and communication with ophthalmologists, and initiating pre-visit planning. RESULTS: Baseline performance data included 164 patients. Fifty-four (33%) of those patients were at high risk for HCQ retinopathy. Of them, 50% were on HCQ dose of >5 mg/kg/day and 31.5% had been taking HCQ for ≥5 years. Two center line shifts were noticed over the course of the project. The target of 85% compliance was reached in February 2019 and was sustained until December 2019. CONCLUSIONS: Our study highlights the importance of interdisciplinary communication to increase awareness of screening guidelines among medical providers and patients. Pre-visit planning played a major role in identifying patients and opportunities for optimizing eye screening in patients at risk for HCQ retinopathy. Collaboration between rheumatologists and ophthalmologists is crucial in managing patients on HCQ. The implementation of same-day eye screening allowed this collaboration to be more efficient. Future efforts are being directed at monitoring and improving utilization of the effective interventions.

Previsit Planning Improves Pneumococcal Vaccination Rates in Childhood-Onset SLE.

BACKGROUND: Childhood-onset systemic lupus erythematosus (c-SLE) is a complex autoimmune disease that requires systemic immunosuppressive therapy. Infections are the second leading cause of death in these patients, with invasive pneumococcal infections being a major preventable cause of morbidity and mortality. Pneumococcal vaccination is recommended in this population; however, vaccination rates remain low. METHODS: The plan-do-study-act method of quality improvement was applied. We calculated baseline vaccination rates for pneumococcal conjugate and pneumococcal polysaccharide vaccines in patients with c-SLE in the rheumatology clinic from January 2015 to August 2016. We developed an age-based algorithm to simplify the vaccination guidelines. The clinical pharmacist and nurses performed weekly previsit planning to update vaccine records, make targeted recommendations, and ensure vaccine availability. The primary outcome measure was the percentage patients with of c-SLE seen per month who had received age-appropriate pneumococcal vaccination. RESULTS: The percentage of children receiving at least 1 pneumococcal vaccine increased from 24.9% to 92.7% by 12 months. By 18 months, the compliance rate with both pneumococcal vaccines increased from 2.5% to 87.3%, with sustained results. No serious adverse events or disease flares were reported. CONCLUSIONS: By identifying the major barriers to pneumococcal vaccination in our population with c-SLE, we significantly improved vaccination rates while decreasing time burden on providers. We attribute our success to a team-based quality improvement approach and plan to implement alerts in the electronic health record to streamline the process.

Opposite Profiles of Complement in Antiphospholipid Syndrome (APS) and Systemic Lupus Erythematosus (SLE) Among Patients With Antiphospholipid Antibodies (aPL).

APS is the association of antiphospholipid antibodies (aPL) with thromboses and/or recurrent pregnancy loss (RPL). Among patients with SLE, one-third have aPL and 10-15% have a manifestation of secondary APS. Animal studies suggested that complement activation plays an important role in the pathogenesis of thrombosis and pregnancy loss in APS. We performed a cross-sectional study on complement proteins and genes in 525 patients with aPL. Among them, 237 experienced thromboses and 293 had SLE; 111 had both SLE and thromboses, and 106 had neither SLE nor thrombosis. Complement protein levels were determined by radial immunodiffusion for C4, C3 and factor H; and by functional ELISA for mannan binding lectin (MBL). Total C4, C4A and C4B gene copy numbers (GCN) were measured by TaqMan-based realtime PCR. Two to six copies of C4 genes are frequently present in a diploid genome, and each copy may code for an acidic C4A or a basic C4B protein. We observed significantly (a) higher protein levels of total C4, C4A, C4B, C3, and anticardiolipin (ACLA) IgG, (b) increased frequencies of lupus anticoagulant and males, and (c) decreased levels of complement factor H, MBL and ACLA-IgM among patients with thrombosis than those without thrombosis (N = 288). We also observed significantly lower GCNs of total C4 and C4A among aPL-positive patients with both SLE and thrombosis than others. By contrast, aPL-positive subjects with SLE had significantly reduced protein levels of C3, total C4, C4A, C4B and ACLA-IgG, and higher frequency of females than those without SLE. Patients with thrombosis but without SLE (N = 126), and patients with SLE but without thrombosis (N = 182) had the greatest differences in mean protein levels of C3 (p = 2.6 × 10-6), C4 (p = 2.2 × 10-9) and ACLA-IgG (p = 1.2 × 10-5). RPL occurred in 23.7% of female patients and thrombotic SLE patients had the highest frequency of RPL (41.0%; p = 3.8 × 10-10). Compared with non-RPL females, RPL had significantly higher frequency of thrombosis and elevated C4 protein levels. Female patients with homozygous C4A deficiency all experienced RPL (p = 0.0001) but the opposite was true for patients with homozygous C4B deficiency (p = 0.017). These results provide new insights and biomarkers for diagnosis and management of APS and SLE.

Utility of Neurodiagnostic Studies in the Diagnosis of Autoimmune Encephalitis in Children.

BACKGROUND: Autoimmune encephalitis is currently a clinical diagnosis without widely accepted diagnostic criteria, often leading to a delay in diagnosis. The utility of magnetic resonance imaging (MRI) and electroencephalography (EEG) in this disease is unknown. The objective of this study was to identify disease-specific patterns of neurodiagnostic studies (MRI and EEG) for autoimmune encephalitis in children. METHODS: We completed a retrospective chart review of encephalopathic patients seen at a large pediatric hospital over a four year interval. Clinical presentation, autoantibody status, and MRI and EEG findings were identified and compared. Individuals with autoantibodies were considered "definite" cases, whereas those without antibodies or those with only thyroperoxidase antibodies were characterized as "suspected." RESULTS: Eighteen patients met the inclusion criteria and autoantibodies were identified in nine of these. The patients with definite autoimmune encephalitis had MRI abnormalities within limbic structures, most notably the anteromedial temporal lobes (56%). Only individuals with suspected disease had nontemporal lobe cortical lesions. Sixteen patients had an EEG and 13 (81%) of these were abnormal. The most common findings were abnormal background rhythm (63%), generalized slowing (50%), focal slowing (43%), and focal epileptiform discharges (31%). Sleep spindle abnormalities occurred in 38% of patients. There were no specific differences in the EEG findings between the definite and suspected cases. Focal EEG findings only correlated with a focal lesion on MRI in a single definite case. CONCLUSIONS: Pediatric patients with definite autoimmune encephalitis have a narrow spectrum of MRI abnormalities. Conversely, EEG abnormalities are mostly nonspecific. All patients in our cohort had abnormalities on one or both of these neurodiagnostic studies.

Two cases of thrombosis in patients with antiphospholipid antibodies during treatment of immune thrombocytopenia with romiplostim, a thrombopoietin receptor agonist.

INTRODUCTION: Romiplostim is a thrombopeitin-receptor agonist approved for raising platelet counts in patients with immune thrombocytopenia (ITP). Several hematologic adverse effects have been reported including acute myeloid leukemia, myelofibrosis, and thrombosis. METHODS: We report two cases, one pediatric and one adult patient, who had antiphospholipid antibodies and received romiplostim for ITP. Additionally, we conducted medline, Food and Drug Administration (FDA) Adverse Events reports website, and manufacturer's adverse events database. RESULTS: Both patients developed thrombosis with evidence for catastrophic antiphospholipid syndrome (CAPS) after treatment with romiplostim. No reports or events were found from literature and database searches in regards to thrombosis associated with romiplostim in patients with antiphospholipid syndrome. CONCLUSION: These cases illustrate the potential for thrombosis with the administration of romiplostim. The administration of this drug to patients with a history of an autoimmune disease, especially those with positive antiphospholipid antibodies, should be done with caution.