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Background: The American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance (CARRA) Mentoring Interest Group (AMIGO) is an inter-institutional mentorship program launched to target mentorship gaps within pediatric rheumatology. Initial program evaluation indicated increased mentorship access. Given the small size of the pediatric rheumatology workforce, maintaining a consistent supply of mentors was a potential threat to the longevity of the network. Our aims were to: (i) describe the sustainability of AMIGO over the period 2011–2018, (ii) highlight ongoing benefits to participants, and (iii) describe challenges in the maintenance of a mentorship network. Methods: A mixed-methods approach centered on a quality improvement framework was used to report on process and outcomes measures associated with AMIGO annual cycles. Results: US and Canada Pediatric rheumatology workforce surveys identified 504 possible participants during the time period. As of fall 2018, 331 unique individuals had participated in AMIGO as a mentee, mentor or both for a program response rate of 66% (331/504). Survey of mentees indicated high satisfaction with impact on general career development, research/scholarship and work-life balance. Mentors indicated increased sense of connection to the community and satisfaction with helping mentees despite limited perceived benefit to their academic portfolios. Based on AMIGO's success, a counterpart program for adult rheumatology, Creating Adult Rheumatology Mentorship in Academia (CARMA), was launched in 2018. Conclusions: Despite the challenges of a limited workforce, AMIGO continues to provide consistent access to mentorship opportunities for the pediatric rheumatology community. This experience can inform approaches to mentorship gaps in other academic subspecialties. [ABSTRACT FROM AUTHOR]

Several pieces of evidence suggest immune dysregulation could trigger the onset and modulate sequelae of new onset refractory status epilepticus (NORSE), including its subtype with prior fever known as febrile infection‐related epilepsy syndrome (FIRES). Consensus‐driven recommendations have been established to guide the initiation of first‐ and second‐line immunotherapies in these patients. Here, we review the literature to date on second‐line immunotherapy for NORSE/FIRES, presenting results from 28 case reports and series describing the use of anakinra, tocilizumab, or intrathecal dexamethasone in 75 patients with NORSE. Among them, 52 patients were managed with anakinra, 21 with tocilizumab, and eight with intrathecal dexamethasone. Most had elevated serum or cerebrospinal fluid cytokine levels at treatment initiation. Treatments were predominantly initiated during the acute phase of the disease (92%) and resulted, within the first 2 weeks, in seizure control for up to 73% of patients with anakinra, 70% with tocilizumab, and 50% with intrathecal dexamethasone. Cytokine levels decreased after treatment for most patients. Anakinra and intrathecal dexamethasone were mainly initiated in children with FIRES, whereas tocilizumab was more frequently prescribed for adults, with or without a prior febrile infection. There was no clear correlation between the response to treatment and the time to initiate the treatment. Most patients experienced long‐term disability and drug‐resistant post‐NORSE epilepsy. Initiation of second‐line immunotherapies during status epilepticus (SE) had no clear effect on the emergence of post‐NORSE epilepsy or long‐term functional outcomes. In a small number of cases, the initiation of anakinra or tocilizumab several years after SE onset resulted in a reduction of seizure frequency for 67% of patients. These data highlight the potential utility of anakinra, tocilizumab, and intrathecal dexamethasone in patients with NORSE. There continues to be interest in the utilization of early cytokine measurements to guide treatment selection and response. Prospective studies are necessary to understand the role of early immunomodulation and its associations with epilepsy and functional outcomes. [ABSTRACT FROM AUTHOR]

Objective: Evidence regarding effectiveness of interleukin‐1 receptor antagonism in multisystem inflammatory syndrome in children (MIS‐C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. Methods: We conducted a retrospective cohort study of MIS‐C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0–1) were identified. We compared cases in patients ages 2–20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0–1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3–4. The secondary outcome was 50% reduction in C‐reactive protein on day 3. Results: Among 1,516 MIS‐C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0–74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88–1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98–1.75]), or C‐reactive protein reduction. Conclusion: We identified substantial variation in initial anakinra use in a real‐world population of children with MIS‐C, but no average short‐term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone. [ABSTRACT FROM AUTHOR]

Background: Febrile-infection related epilepsy syndrome (FIRES) is a rare epilepsy syndrome in which a previously healthy individual develops refractory status epilepticus in the setting of a preceding febrile illness. There are limited data regarding detailed long-term outcomes. This study aims to describe the long-term neuropsychological outcomes in a series of pediatric patients with FIRES. Methods: This is a retrospective multi-center case series of pediatric patients with a diagnosis of FIRES treated acutely with anakinra who had neuropsychological testing at least 12 months after status epilepticus onset. Each patient underwent comprehensive neuropsychological evaluation as part of routine clinical care. Additional data collection included the acute seizure presentation, medication exposures, and outcomes. Results: There were six patients identified with a median age of 11.08 years (IQR: 8.19-11.23) at status epilepticus onset. Anakinra initiation was amedian of 11 days (IQR: 9.25-13.50) after hospital admission. All patients had ongoing seizures and none of the patients returned to baseline cognitive function with a median follow-up of 40 months (IQR 35-51). Of the five patients with serial full-scale IQ testing, three demonstrated a decline in scores over time. Testing results revealed a diffuse pattern of deficits across domains and all patients required special education and/or accommodations for academic learning. Conclusions: Despite treatment with anakinra, neuropsychological outcomes in this series of pediatric patients with FIRES demonstrated ongoing diffuse neurocognitive impairment. Future research will need to explore the predictors of long-term neurocognitive outcomes in patients with FIRES and to evaluate if acute treatment interventions improve these outcomes. [ABSTRACT FROM AUTHOR]

In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL‐6, and IL‐10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL‐1 receptor antagonist that blocks biologic activity of IL‐1β) are recommended. [ABSTRACT FROM AUTHOR]

Febrile‐infection related epilepsy syndrome (FIRES) is a devastating neurological condition characterized by a febrile illness preceding new onset refractory status epilepticus (NORSE). Increasing evidence suggests innate immune dysfunction as a potential pathological mechanism. We report an international retrospective cohort of 25 children treated with anakinra, a recombinant interleukin‐1 receptor antagonist, as an immunomodulator for FIRES. Anakinra was potentially safe with only one child discontinuing therapy due to infection. Earlier anakinra initiation was associated with shorter duration of mechanical ventilation, ICU and hospital length of stay. Our retrospective data lay the groundwork for prospective consensus‐driven cohort studies of anakinra in FIRES. [ABSTRACT FROM AUTHOR]

Objective: To identify behavioral health provider perspectives on gaps in mental health care for youth with rheumatologic conditions.Methods: Social workers (n = 34) and psychologists (n = 8) at pediatric rheumatology centers in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an online survey assessing current practices and mental health care needs of youth with rheumatologic conditions. Responses were compared to a published survey of CARRA rheumatologists (n = 119). Thematic analysis of 20 semi-structured interviews with behavioral health providers was performed.Results: One-third of CARRA centers (n = 100) had no affiliated social worker or psychologist. Only 1 behavioral health provider reported current universal mental health screening at their rheumatology clinic, yet routine depression screening was supported by >85% of behavioral health providers and rheumatologists. Support for anxiety screening was higher among behavioral health providers (90% versus 65%; P < 0.01). Interviews illustrated a need for interventions addressing illness-related anxiety, adjustment/coping/distress, transition, parent/caregiver mental health, and peer support. Limited resources, lack of protocols, and patient cost/time burden were the most frequent barriers to intervention. Inadequate follow-up of mental health referrals was indicated by 52% of providers. More behavioral health providers than rheumatologists favored mental health services in rheumatology settings (55% versus 19%; P < 0.01). Only 7 social workers (21%) provided counseling/therapy, and interviews indicated their perceived underutilization of these services.Conclusion: Behavioral health providers indicated an unmet need for mental health interventions that address illness-related issues affecting youth with rheumatologic conditions. Implementation of mental health protocols and optimizing utilization of social workers may improve mental health care for these youth. [ABSTRACT FROM AUTHOR]

Pediatric neurologic conditions requiring therapeutic plasma exchange are rare in children and literature is sparse. The study aims to determine the outcomes, safety, and feasibility of therapeutic plasma exchange treatment in pediatric neurologic disorders. This retrospective analysis looked at the outcomes and safety of therapeutic plasma exchange in children (n = 50) with neurologic conditions. Patient age ranged <1 to 19 years old with a mean of 10.35 years. Of the 50 children treated with plasmapheresis, 26 patients received inpatient rehabilitation. At discharge, functional status can be summarized as follows: 24 (48%) with mental status impairment, 10 (20%) with vision impairment, 19 (38%) with bladder incontinence, and 37 (74%) with motor impairment. Three-month follow-up: 30% with mental status impairment, 10% with vision impairment, 18% with bladder incontinence, and 52% with motor impairment. Therapeutic plasma exchange is an effective and safe therapy for neurological conditions in the pediatric population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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(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(4) = 13.37, p = 0.010). There was greater usage of anti-metabolites for second-line therapy outside of the US (15%) ( χ(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(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The small size of many pediatric rheumatology programs translates into limited mentoring options for early career physicians. To address this problem, the American College of Rheumatology (ACR) and the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed a subspecialty-wide interinstitutional mentoring program, the ACR/CARRA Mentoring Interest Group (AMIGO). We sought to assess the impact of this program on mentoring within pediatric rheumatology.Methods: In a longitudinal 3-year study, participant ratings from the AMIGO pilot program were compared with those after the program was opened to general enrollment. Access to mentoring as a function of career stage was assessed by surveys of the US and Canadian pediatric rheumatologists in 2011 and 2014, before and after implementation of AMIGO.Results: Participants in the pilot phase (19 dyads) and the general implementation phase (112 dyads) reported comparable success in establishing mentor contact, suitability of mentor-mentee pairing, and benefit with respect to career development, scholarship, and work-life balance. Community surveys showed that AMIGO participation as mentee was high among fellows (86%) and modest among junior faculty (31%). Implementation correlated with significant gains in breadth of mentorship and in overall satisfaction with mentoring for fellows but not junior faculty.Conclusion: AMIGO is a career mentoring program that serves most fellows and many junior faculty in pediatric rheumatology across the US and Canada. Program evaluation data confirm that a subspecialty-wide interinstitutional mentoring program is feasible and can translate into concrete improvement in mentoring, measurable at the level of the whole professional community. [ABSTRACT FROM AUTHOR]

Objective: To determine perceived barriers to and facilitators of a career in rheumatology research, examine factors leading rheumatologists to leave an academic research career, and solicit ways to best support young physician-scientists.Methods: A web-based survey was conducted among the domestic American College of Rheumatology (ACR) membership from January through March 2014. Inclusion criteria were ACR membership and an available e-mail address. Non-rheumatologists were excluded. The survey assessed demographics, research participation, barriers to and facilitators of a career in research, reasons for leaving a research career (when applicable), and ways in which the ACR could support junior investigators. Content analysis was used to extract relevant themes.Results: Among 5,448 domestic ACR members, 502 responses were obtained (9.2% response rate). After exclusions (38 incomplete, 2 duplicates, 32 non-rheumatologists), 430 responses were analyzed. Participants included fellows, young investigators, established investigators, mentors, clinicians, and those who previously pursued a research career but have chosen a different career path. Funding and mentoring were the most highly ranked barriers and facilitators. Protection from clinical and administrative duties, institutional support, and personal characteristics such as resilience and persistence were also ranked highly. The most commonly cited reasons for leaving an academic research career were difficulty obtaining funding and lack of department or division support.Conclusion: This is the first study to examine barriers to and facilitators of a career in rheumatology research from the perspectives of diverse groups of rheumatologists. Knowledge of such barriers and facilitators may assist in designing interventions to support investigators during vulnerable points in their career development. [ABSTRACT FROM AUTHOR]

Background/Aims: There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis. Methods: Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE. Results: MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients. Conclusion: The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/aims: There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis.Methods: Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE.Results: MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients.Conclusion: The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations. [ABSTRACT FROM AUTHOR]

Polyarteritis nodosa is a systemic necrotizing vasculitis involving medium-sized muscular arteries. Polyneuropathy is the only neurologic manifestation included in the pediatric classification schema. Central nervous system manifestations include infarction, hemorrhage, and encephalitis. We report on a 13-year-old female whose initial presentation of polyarteritis nodosa included hypertension, seizures, and neuroimaging findings of vasogenic edema and posterior reversible encephalopathy syndrome. Posterior reversible encephalopathy syndrome has been reported in association with renal disease, transplantation, autoimmunity, and cytotoxic medications. Posterior reversible encephalopathy syndrome outcomes are usually favorable with supportive care and treatment of the underlying etiology. The patient’s neurologic condition improved after treatment of hypertension. Hypertension, posterior reversible encephalopathy syndrome, and abdominal pain led to a diagnostic workup. A systemic vasculitis was confirmed after detection of a perinephric hematoma and intrarenal aneurysms. This is a novel case of posterior reversible encephalopathy syndrome as an initial manifestation of pediatric polyarteritis nodosa. [ABSTRACT FROM AUTHOR]

ABSTRACT 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. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Intraventricular hemorrhage is a rare finding in patients with the posterior reversible encephalopathy syndrome and generally carries a poor prognosis. We report a unique case of an 18-year-old girl with glomerulonephritis who developed posterior reversible encephalopathy syndrome without hypertension but with a primary intraventricular hemorrhage and subarachnoid blood without demonstrable parenchymal blood. The normotensive presentation of posterior reversible encephalopathy syndrome and intraventricular hemorrhage in association with systemic vasculitis is rare. Our patient had a good initial outcome and was discharged with resolution of her symptoms and signs of raised intracranial pressure. [ABSTRACT FROM AUTHOR]

Objective To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE). Methods A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches. Results After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs. Conclusion CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE. [ABSTRACT FROM AUTHOR]

Severe manifestations of systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and thrombotic thrombocytopenic purpura (TTP) are characterized by multiorgan thrombotic microangiopathy. We describe reduction of ADAMTS13 activity and the development of systemic autoimmunity in all 8 children initially diagnosed with acquired noncongenital TTP during an 8.5-year period. Median age at diagnosis was 12.0 years (range, 2.6-17.3 years). ADAMTS13 activity was absent (<5%) in 6 patients; 3 patients had a detected inhibitor. SLE was diagnosed concurrently in 3 patients, and 4 patients were diagnosed within 5 years. Six of the children diagnosed with SLE had absent ADAMTS13 activity at diagnosis. In 6 patients with SLE, immune-mediated nephritis developed by 46 months. All surviving patients with SLE developed antiphospholipid antibodies, including some with a lupus anticoagulant. Patients with SLE did not have TTP recurrences once daily immunosuppressive regimens were started. An evaluation for SLE/APS is warranted in children and adolescents with reduced ADAMTS13 activity and thrombotic microangiopathy. [ABSTRACT FROM AUTHOR]

Introduction: Atlantoaxial instability has been described as a manifestation of ankylosing spondylitis (juvenile and adult onset), reactive arthritis, juvenile idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been reported as an early manifestation of these disorders. We present this case report to increase awareness of the condition in the hope that earlier recognition of this disease may prevent further serious injury.Case Presentation: We report the case of a 17-year-old Hispanic adolescent woman who was initially diagnosed with undifferentiated spondyloarthritis due to peripheral arthritis, enthesitis, a positive human leukocyte antigen B27 result, and inflammatory spinal pain lasting two months. Our patient experienced persistent and worsening occipitocervical pain and signs of myelopathy three months after diagnosis; consequently, we found atlantoaxial instability along with cervical spine bone erosion and pannus formation. She was treated surgically with a C1-2 posterior instrumented fusion and at six weeks post-operatively was started on tumor necrosis factor α blockade. Her occipitocervical symptoms subsided following surgery and initiation of immunomodulation.Conclusions: Our report serves to emphasize to pediatric and adult general practitioners, pediatricians, internists, family physicians, pediatric and adult rheumatologists and spine surgeons that atlantoaxial subluxation may be an early manifestation of spondyloarthritis, and that the condition is treatable by surgical intervention and immunomodulation. [ABSTRACT FROM AUTHOR]

Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients. We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis. We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002–2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES. Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management. MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults. [ABSTRACT FROM AUTHOR]

The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by autoantibody production and thrombosis or pregnancy morbidity. The most prevalent neurologic manifestation of APS is cerebrovascular ischemic events due to arterial thromboses. Antiphospholipid antibodies can also cause neurologic impairments unrelated to thrombosis, through antibody-cellular interactions, possibly because of a disrupted blood-brain barrier. Antiplatelet or anticoagulant therapies are currently indicated for APS-related ischemic strokes, but they remain controversial for non-thrombotic neurologic manifestations. Scant literature exists on neurologic manifestations and treatment regimens in childhood APS. Modifiable cardiac risk factors and valvular heart disease may worsen APS cerebrovascular outcomes. Adjunctive therapies (eg, statins, antimalarials, and angiotensin-converting enzyme inhibitors) warrant clinical trials. [ABSTRACT FROM AUTHOR]