Concomitant sickle cell disease and systemic lupus erythematosus: A single-center case series.

Sickle cell disease (SCD) and systemic lupus erythematosus (SLE) are two uncommon disorders each characterized by multisystemic manifestations. Individuals with SCD exhibit abnormalities in the complement pathway, which may predispose patients to develop autoimmune disorders such as SLE. As many manifestations of SLE mimic those of SCD, diagnosis and therapeutic management of SLE in a patient with known SCD may be delayed. In this study, we describe our institutional experience of diagnosing and managing concomitant SCD and SLE. We offer insights into the complex interplay between these conditions to enhance early recognition and effective management of concurrent SCD and SLE.

Infectious profiles in pediatric anti-N-methyl-d-aspartate receptor encephalitis.

Anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE) is an antibody-mediated neurological disorder that may be caused by post-herpes simplex virus-1 meningoencephalitis (HSV ME) and ovarian teratomas, although most pediatric cases are idiopathic. We sought to evaluate if other infections precede NMDAR AE by conducting a single-center, retrospective, case-control study of 86 pediatric cases presenting to Texas Children's Hospital between 2006 and 2022. HSV ME (HSV-1 and HSV-2) was a significantly more common preceding infection in the experimental group compared to control patients with idiopathic intracranial hypertension, while there was no difference in remote HSV infection between the two groups. Recent Epstein-Barr virus infection was evident in 8/42 (19%) tested experimental patients in comparison to 1/25 (4%) tested control patients which provided evidence for a genuine measure of effect but was not statistically significant due to small sample size (p = 0.07). The other 25 infectious etiologies were not different among the two groups and not all variables were clinically indicated or obtained in every subject, highlighting the need for future standardized, multi-institutional studies on underlying infectious precursors of autoimmune encephalitis.

Arterial Spin Labeling Changes Parallel Asymmetric Perisylvian and Perirolandic Symptoms in 3 Pediatric Cases of Anti-NMDAR Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-NMDA receptor autoimmune encephalitis (NMDAR AE) is an autoantibody-mediated disorder characterized by seizures, neuropsychiatric symptoms, movement disorder, and focal neurologic deficits. Conventionally defined broadly as an inflammatory brain disease, the heterotopic localization is rarely discussed in children. Imaging findings are often nonspecific, and there are no early biomarkers of disease other than the presence of anti-NMDAR antibodies. METHODS: We conducted a retrospective analysis of our pediatric NMDAR AE cases (as determined by either positive serum or CSF antibodies or both) at Texas Children's Hospital between 2020-2021 and extracted medical record data of those patients who had arterial spin labeling (ASL) as part of their imaging workup for encephalitis. The ASL findings were described in the context of their symptoms and disease courses. RESULTS: We identified 3 children on our inpatient floor, intensive care unit (ICU), and emergency department (ED) settings who were diagnosed with NMDAR AE and had ASL performed as part of their focal neurologic symptom workup. All 3 patients presented with focal neurologic deficits, expressive aphasia, and focal seizures before the onset of other well-characterized NMDAR AE symptoms. Their initial MRI revealed no diffusion abnormalities but uncovered asymmetric and predominantly unilateral multifocal hyperperfusion of perisylvian/perirolandic regions on ASL that correlated with focal EEG abnormalities and their focal examination findings. All 3 patients were treated with first-line and second-line therapies, and their symptoms improved. DISCUSSION: We found that ASL may be a suitable early imaging biomarker to highlight perfusion changes corresponding to the functional localization of NMDAR AE in pediatric patients. We briefly highlight the neuroanatomic parallels between working models of schizophrenia, chronic NMDAR antagonist administration (ketamine abuse), and NMDAR AE affecting primarily language centers. The regional specificity seen in NMDAR hypofunction may make ASL a reasonable early and specific biomarker of NMDAR AE disease activity. Future studies are necessary to evaluate regional changes in those patients who present with primarily psychiatric phenotypes rather than classical focal neurologic deficits.

Lupus Nephritis, Autoantibody Production and Kidney Outcomes in Males with Childhood-Onset Systemic Lupus Erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) only represents 20% of all SLE patients, and males with SLE only represent 10%. To study this rare SLE subset, males diagnosed with cSLE over a 30-year period were identified. Organ involvement, autoantibody production, hypocomplementemia, and kidney biopsy findings were compared to cSLE females. Outcomes were assessed using SLE Disease Activity Index scores, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and Childhood Arthritis and Rheumatology Research Alliance definitions for nephritis responsiveness. Of 95 males and 545 females with cSLE, 62% and 57% developed nephritis, respectively. Median age of cSLE onset was 14 years in both genders. Among males, 80% of non-Hispanic whites, 64% of blacks, 59% of Hispanics, and 50% of Asians developed nephritis. The prevalence of pure and mixed class V membranous nephritis was 33%. Median follow-up was 3.2 years (range 0.1-18). Complete kidney responses were seen in 70% after a median 24 months; however, relapse rates were 46%. Kidney disease flares were 56% nephritic and 44% proteinuric. Males and females with cSLE present with comparable rates and nephritis class. While overall and kidney response rates are favorable, kidney disease relapses are common among males.

COVID-19 vaccine (mRNA BNT162b2) and COVID-19 infection-induced thrombotic thrombocytopenic purpura in adolescents.

The mRNA COVID-19 vaccine and COVID-19 infection caused by the SARS-CoV-2 virus may be immunologic triggers for the development of thrombotic thrombocytopenic purpura (TTP). There is not yet literature that discusses TTP induced by COVID-19 vaccination or infection in pediatric or adolescent patients. We describe three adolescents presenting with TTP (both de novo and relapsed disease) following administration of the Pfizer COVID-19 vaccine or after COVID-19 infection. Our observations demonstrate that the Pfizer-BioNTech mRNA vaccine and COVID-19 infection can act as triggers for the development/relapse of both congenital and acquired TTP.

Severe Pediatric COVID-19 Pneumonia Treated With Adjuvant Anakinra.

BACKGROUND AND OBJECTIVES: To compare previous hemophagocytic lymphohistiocytosis criteria with adult coronavirus disease 2019 (COVID-19)-associated hyperinflammatory syndrome (cHIS) criteria for the diagnosis of hyperinflammation in pediatric patients with COVID-19. The secondary objective was to assess treatment response to intravenous (IV) anakinra in these patients. METHODS: This case series included children admitted to the PICU for COVID-19 pneumonia with hyperinflammation and treated with IV anakinra between July 2020 to April 2021. Hyperinflammatory criteria were determined for each patient. Clinical course, chest imaging, and inflammatory marker trends were assessed pre- and post-anakinra treatment. RESULTS: All patients had a cHIS criteria score of ≥5. Two patients met 2004-hemophagocytic lymphohistiocytosis criteria. Only the patient that required extracorporeal membrane oxygenation met the H-Score cut-off value. All but one patient had a decrease in their inflammatory markers and improvement in clinical status with early initiation of adjunctive IV anakinra. CONCLUSIONS: In this case series, adult cHIS criteria were successfully used to identify pediatric COVID-19 patients with hyperinflammation. Ferritin levels decreased after the early initiation of IV anakinra.

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis.

Importance: Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear. Objective: To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. Data Sources: Systematic search in PubMed from inception to January 1, 2019. Study Selection: Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data. Data Extraction and Synthesis: Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models. Main Outcomes and Measures: The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset). Results: Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05). Conclusions and Relevance: Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine whether plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a core inflammatory signature of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Fifteen of 135 analytes were significantly different in HLH plasma compared with SIRS/sepsis, including increased interferon-γ (IFN-γ)-regulated chemokines CXCL9, CXCL10, and CXCL11. Furthermore, a 2-analyte plasma protein classifier including CXCL9 and interleukin-6 was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and activated monocytes from blood were also enriched for IFN-γ pathway signatures in peripheral blood cells from patients with HLH compared with SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH, and comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFN-γ signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH and sepsis or SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.

Inflammatory Diseases of the Central Nervous System.

Pediatric neuroinflammatory conditions are a complex group of disorders with a wide range of clinical presentations. Patients can present with a combination of focal neurologic deficits, encephalopathy, seizures, movement disorders, or psychiatric manifestations. There are several ways that pediatric neuroinflammatory conditions can be classified, including clinical presentation, pathophysiologic mechanism, and imaging and laboratory findings. In this article, we group these conditions into acquired demyelinating diseases, immune-mediated epilepsies/encephalopathies, primary rheumatologic conditions with central nervous system (CNS) manifestations, CNS vasculitis, and neurodegenerative/genetic conditions with immune-mediated pathophysiology and discuss epidemiology, pathophysiology, clinical presentation, treatment, and prognosis of each disorder.

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients.

Immune thrombocytopenia following multisystem inflammatory syndrome in children (MIS-C) - a case series.

Patients with coronavirus disease 2019 (COVID-19) from novel coronavirus (SARS-CoV-2) infection may present with immune thrombocytopenia (ITP). Multisystem inflammatory syndrome in children (MIS-C) is a serious complication of SARS-CoV-2 causing systemic organ dysfunction. This case series presents the first reported cases of patients who developed ITP following MIS-C, while completing corticosteroid tapers. These patients responded to standard of care therapies for ITP and had appropriate platelet count recovery. We emphasize the importance of careful monitoring of those recovering from COVID-19 or MIS-C, to proactively identify clinical and laboratory abnormalities, in addition to long-term cardiovascular sequelae.

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults.

Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.

Infectious and Autoimmune Causes of Encephalitis in Children.

BACKGROUND AND OBJECTIVES: Encephalitis can result in neurologic morbidity and mortality in children. Newly recognized infectious and noninfectious causes of encephalitis have become increasingly important over the past decade. METHODS: We retrospectively reviewed medical records from pediatric patients in Houston diagnosed with encephalitis in both an urban and rural catchment area between 2010 and 2017. We conducted an investigation to understand the etiology, clinical characteristics, and diagnostic testing practices in this population. RESULTS: We evaluated 231 patients who met the case definition of encephalitis, among which 42% had no recognized etiology. Among those with an identified etiology, the most common were infectious (73; 31%), including viral (n = 51; 22%), with the most frequent being West Nile virus (WNV; n = 12), and bacterial (n = 19; 8%), with the most frequent being Bartonella henselae (n = 7). Among cases of autoimmune encephalitis (n = 60; 26%), the most frequent cause was anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 31). Autoimmune causes were seen more commonly in female (P < .01) patients. Testing for herpes simplex virus and enterovirus was nearly universal; testing for anti-NMDAR encephalitis, WNV, and Bartonella was less common. CONCLUSIONS: WNV was the most common infectious cause of encephalitis in our pediatric population despite lower testing frequency for WNV than herpes simplex virus or enterovirus. Increasing testing for anti-NMDAR encephalitis resulted in frequent identification of cases. Increased awareness and testing for WNV and Bartonella would likely result in more identified causes of pediatric encephalitis. Earlier etiologic diagnosis of encephalitides may lead to improve clinical outcomes.

PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia.

Neutropenia in pediatric patients can be due to a variety of disorders. We describe two patients who underwent extensive evaluation over many years for arthralgias and moderate neutropenia of unclear etiology. Genetic testing identified a pathogenic variant in PSTPIP1 (proline-serine-threonine phosphatase-interacting protein 1) in both patients. Markedly elevated inflammatory markers and zinc levels confirmed the rare diagnosis of PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, tailoring treatment. Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in PAMI syndrome may account for the specific phenotypic features of this disorder.

Clinical presentation and outcomes of childhood-onset membranous lupus nephritis.

BACKGROUND: Best practices for managing childhood-onset membranous lupus nephritis (MLN) are not yet established. Most studies involve primarily or exclusively adult cohorts or pediatric cohorts with combinations of pure or mixed membranous and proliferative nephritis. METHODS: We performed a single-center cohort study of consecutively diagnosed children with pure MLN from 1990 and 2016. Patients received care in Houston, Texas, one of the most diverse metropolitan areas in North America. Renal outcomes were obtained using consensus definitions from the Childhood Arthritis and Rheumatology Research Alliance (CARRA). Logistic regression was used to detect predictors of complete renal response. RESULTS: A total of 56 children with MLN were identified (82% females, 44% black, 35% Hispanic) with a median follow-up time of 4.1 years. The mean age of MLN onset was 13.7 ± 3.4 years. On initial presentation 69% had nephrotic syndrome and 11% had acute kidney injury. Glucocorticoids were prescribed in 96% of patients and anti-malarials in 88%. Mycophenolate mofetil was the most common non-steroid immunosuppressive agent (69%), followed by rituximab (25%), cyclophosphamide (18%), and azathioprine (9%). Renin-angiotensin aldosterone system blocking agents were prescribed in 78% of patients. Of 37 patients with ≥2 years of follow-up, 74% achieved complete renal response at 24 months. No predictor variable of complete renal response was identified in this small cohort. Renal flares occurred in 48% of patients (86% proteinuric, 14% nephritic). On subsequent renal biopsy, 13% patients had developed proliferative nephritis. CONCLUSIONS: This single-center cohort of childhood-onset MLN showed favorable outcomes. Utilizing pediatric renal outcomes definitions, we found that response rates were high, as were rates of renal flare.

Differences in treatment of anti-NMDA receptor encephalitis: results of a worldwide survey.

The objective of the study was to identify differences in treatment strategies for anti-NMDA receptor encephalitis based on specialty of treating physicians, geographic location, and years in practice. We conducted an anonymous worldwide electronic survey through the Practice Current section of Neurology® Clinical Practice to appraise differences in decisions about first- and second-line treatment and timing for initiation of second-line treatment for anti-NMDA receptor encephalitis. 399 participants answered all questions of the survey and were included in the analysis. 261 (65%) were adult neurologists, 86 (22%) were neurologists treating children, and 52 (13%) were pediatric rheumatologists. 179 (45%) responders practiced in the US. The majority agreed on the use of steroids and/or IVIg for first-line therapy and rituximab alone as second line. Differences in initial treatment regimen based on specialty included increased use of plasma exchange by adult neurologists (27%) and rituximab by pediatric rheumatologists (29%) (χ 2(4) = 27.43, p < 0.001). Trainees opted for plasma exchange (35%) and junior faculty picked rituximab (15%) more as part of first line (χ 2(4) = 13.37, p = 0.010). There was greater usage of anti-metabolites for second-line therapy outside of the US (15%) (χ 2(4) = 11.67, p = 0.020). US physicians also utilized second-line treatment earlier than their mostly European counterparts (14 vs. 23% used later than 2 weeks; χ 2(1) = 4.96, p = 0.026). Although treatment patterns were similar, differences observed across specialties and geographic locations may guide the development of consensus-driven guidelines by multi-disciplinary task forces. These guidelines may promote treatment trials of immunomodulators in autoimmune encephalitides.

Identifying Targets for Improving Mental Healthcare of Adolescents with Systemic Lupus Erythematosus: Perspectives from Pediatric Rheumatology Clinicians in the United States and Canada.

OBJECTIVE: To identify targets for improving mental healthcare of adolescents with systemic lupus erythematosus (SLE) by assessing current practices and perceived barriers for mental health intervention by pediatric rheumatology clinicians. METHODS: Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed a Web-based survey assessing current mental health practices, beliefs, and barriers. We examined associations between provider characteristics and the frequency of barriers to mental health screening and treatment using multivariable linear regression. RESULTS: Of the 375 eligible CARRA members, 130 responded (35%) and 119 completed the survey. Fifty-two percent described identification of depression/anxiety in adolescents with SLE at their practice as inadequate, and 45% described treatment as inadequate. Seventy-seven percent stated that routine screening for depression/anxiety in pediatric rheumatology should be conducted, but only 2% routinely used a standardized instrument. Limited staff resources and time were the most frequent barriers to screening. Respondents with formal postgraduate mental health training, experience treating young adults, and practicing at sites with very accessible mental health staff, in urban locations, and in Canada reported fewer barriers to screening. Long waitlists and limited availability of mental health providers were the most frequent barriers to treatment. Male clinicians and those practicing in the Midwest and Canada reported fewer barriers to treatment. CONCLUSION: Pediatric rheumatology clinicians perceive a need for improved mental healthcare of adolescents with SLE. Potential strategies to overcome barriers include enhanced mental health training for pediatric rheumatologists, standardized rheumatology-based mental health practices, and better integration of medical and mental health services.

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding.

Autoimmune Encephalitis Following Bone Marrow Transplantation.

BACKGROUND: Neurological complications, especially encephalopathy and seizures, are commonly seen in bone marrow transplant patients. Infections, chemotoxicity, graft versus host disease, or secondary central nervous system malignancies are the most common underlying etiologies. There is increased awareness that autoimmune encephalitis may cause neurological dysfunction in immunocompetent children. The potential role of such a mechanism in children undergoing bone marrow transplantation is unknown. METHODS: We report a boy who developed autoimmune encephalitis with voltage-gated potassium channel-associated and thyroid autoantibodies subsequent to transplantation. RESULTS: A 7-year-old boy presented with a change in behavior, poor attention, cognitive deficits, and abnormal movements 15 months after undergoing transplantation for idiopathic aplastic anemia. He had clinical and subclinical seizures and brain magnetic resonance imaging hyperintensities bilaterally in the uncal regions. His evaluation revealed high titers of voltage-gated potassium channel, leucine-rich glioma-inactivated 1 protein, and thyroglobulin antibodies suggestive of autoimmune limbic encephalitis. He showed significant improvement in behavior and neuropsychological testing and has remained seizure-free on levetiracetam after immunotherapy with corticosteroids and intravenous immunoglobulin. CONCLUSION: Systemic autoimmune manifestations in bone marrow transplant patients have been well-documented, but autoimmune encephalitis after transplantation has yet to be described in children.

The spectrum of movement disorders in children with anti-NMDA receptor encephalitis.

BACKGROUND: Movement disorders are frequent but difficult to characterize in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: The phenomenology of movement disorders was characterized after a detailed examination of children with anti-NMDAR-encephalitis. RESULTS: We studied 9 children (5 females), ages 3-14 years, with confirmed anti-NMDAR-encephalitis. All patients presented with at least 1 movement disorder, including chorea (n=4), stereotypic movements (n=4), ataxia (n=3), limb dystonia (n=2), limb myorhythmia (n=2), oromandibular dystonia (n=2), facial myorhythmia, blepharospasm, opisthotonus, athetosis, and tremor (n=1, each). More than a single movement disorder was observed in 6 of these patients. Resolution of the abnormal movements was observed in all patients with immunotherapy; 1 patient improved with tetrabenazine. CONCLUSIONS: A wide variety of movement disorders, often in combination, can be observed in children with anti-NMDAR encephalitis. Patients commonly present with more than a single movement disorder.