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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]

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]

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]

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]

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]

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]

Background/Purpose: Comparisons of pediatric ANCA-associated vasculitis subtypes (AAV) are limited by the paucity of reported cases, standardized definitions, and overlapping classification criteria. Published work from ARChiVe (A Registry for Childhood Vasculitis) demonstrated modifications of validated classification algorithms applied to pediatric patients with AAV can classify each patient to mutually exclusive diagnostic categories. We compared presenting features of children with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) classified according to this methodology. Methods: A pediatric modification of the European Medicines Agency (EMA) algorithm for classifying AAV and polyarteritis nodosa (incorporating the EULAR/PRINTO/PRES pediatric classification criteria for GPA) was applied to patients in ARChiVe censored to April 2012. We compared characteristics of patients classified as having MPA and GPA. STATA (Statcorp, 2013) was used to calculate frequencies, percentages, and chi-squared with fisher's exact for categorical variables and means, standard deviations, and t-tests for continuous variables. Results: One hundred fifty-two of 227 children in ARChiVe met criteria for diagnosis of MPA (n = 22) or GPA (n = 130). Characteristics and presenting features are shown in Table . Children with MPA were younger at diagnosis (mean diff. 2.7y, p = <0.01). Renal involvement was predominant in both groups. Renal biopsies in 40% of both groups were consistent with pauci-immune, necrotizing glomerulonephritis. Children with MPA had higher rates of nephrosis, renal failure requiring dialysis, and abnormal creatinine clearance (Table ). Upper and lower airway involvement was more prevalent among those with GPA largely in accordance with surrogate GPA features used to differentiate GPA and MPA in the EMA algorithm. The majority of patients presented with constitutional symptoms, however, other organ systems were less frequently involved. Most patients received combination therapy corticosteroids and cytoxan (64% MPA, 81% GPA) with additional plasmapheresis (29% MPA, 21% GPA), rituximab (14% MPA, 3% GPA) or methotrexate (7% MPA, 1% GPA). The remainder of children received combination corticosteroids and methotrexate or rituximab, without cytoxan (12% MPA, 11% GPA). A larger proportion of patients with MPA received antihypertensive agents and/or ACE inhibitors (64% vs 35%, p = 0.01). [ABSTRACT FROM AUTHOR]

Background/Purpose: Children with SLE (cSLE) can experience neuropsychiatric SLE (NPSLE), commonly manifesting as neurocognitive dysfunction which can interfere with normal development. Formal neurocognitive testing (FNCT) is the most accepted test for diagnosing neurocognitive deficits (NCD). Access to it is limited and costly, and it is time-consuming. The Pediatric Automated Neurophysiological Assessments Metrics (PedANAM) is a computerized battery of 10 subtests measuring various aspects of cognitive ability. Concurrent validity of PedANAM test scores with FNCT has been demonstrated. However, the PedANAM generates several measures of accuracy (% of correct responses), processing speed and efficiency, and it is unclear how they can be used in a clinical setting. The usefulness of the PedANAM as a screen for NCD would be enhanced by the development of a PedANAM Cognitive Performance Score (PedANAM-CPS) to represent aspects of PedANAM task performance that are sensitive to NCD in cSLE. The purpose of this study was to develop a PedANAM-CPS for use in cSLE, using statistical methods. Methods: cSLE patients (pts) and age plus sex-matched healthy controls enrolled in a study of cognitive functioning and neuroimaging were studied. At the time of enrollment (visit 1-V1) and 18 months later (visit 2-V2), subjects completed the PedANAM and FNCT. Three candidate PedANAM-CPS measurement approaches were explored via 3 statistical methods: 1) Simple mean-of all subtest accuracy scores; 2) Logit score-via a logistic regression model; 3) PCA score-using a Principal Component Analysis (PCA) method. The latter 2 methods assigned in a different way a statistical weight to each subtest accuracy score. Fixed effect models were used to compare performance scores between groups. Receiver operating characteristic (ROC) curves were used to assess the accuracy of the CPS as predictors of NCD as determined by FNCT. Results: 77 children (female = 68%) were evaluated at V1; Nine cSLE pts with NCD, 31 with cSLE and no NCD, and 37 control with no NCD as per FNCT. At V1, age (values are mean ± standard deviation) of children was 13.6 ± 2.4 years. For cSLE pts, disease activity (SLEDAI) was 4.9 ± 4.4, and 77.5% were on oral prednisone (19.8 ± 17.4 mg). Table summarizes the PedANAM-CPS for all methods at V1. The Logit score best discriminated the groups, especially contrasting the NCD group against the other groups. The Logit and PCA scores showed g 82% area under the ROC curve during the validation stage using V2 data. [ABSTRACT FROM AUTHOR]

Background/Purpose: In pediatric rheumatology, the small size of many academic programs translates into limited mentoring options for early career physicians. To address this 'mentorship gap,' in 2011 the American College of Rheumatology (ACR) and the Childhood Arthritis and Rheumatology Research Alliance (CARRA) joined together to develop AMIGO, the ACR/CARRA Mentoring Interest Group, that now includes greater than half of pediatric rheumatology fellows and junior faculty in the US and Canada. We report ongoing program evaluation encompassing pilot (2011) and full roll-out (2012, 2013) phases of the AMIGO project. Methods: Mentees and mentors participating in the AMIGO project were surveyed via online questionnaire to determine dynamics of contact and perceived benefit. The entire pediatric rheumatology community was surveyed in 2011 to determine the state of mentoring and career development, with a repeat survey planned for early 2014. We tabulated the active dyads as of January 2014. Results: As recently reported, detailed evaluation of the pilot phase 17 months after initial roll-out found that 19 of 20 pilot AMIGO dyads were still functioning, with substantial benefit noted by mentees in career guidance, scholarship, and job satisfaction. Benefits reported by mentors included improvement of their mentoring skills and development of their academic portfolios. Both mentees and mentors reported improved connectedness to the wider pediatric rheumatology community. 83 additional dyads were matched prior to 2012 and 2013 ACR meetings. Comparison of these 17-month pilot results to a December 2013/January 2014 survey of all active AMIGO participants is ongoing. A questionnaire administered to the whole pediatric rheumatology community in 2011 (n = 135 respondents, including an estimated 64-70% response rate among fellows and junior faculty) found that approximately 60% of fellows and junior faculty had a career development mentor. We will assess whether the AMIGO program has had a global impact upon the mentoring culture in pediatric rheumatology by collecting community-wide survey data in 2014 and then comparing to 2011 data. Conclusion: The 2011 AMIGO pilot program has confirmed the feasibility of a North American inter-institutional mentoring program in pediatric rheumatology. Participants identified benefits to both mentees and mentors in multiple domains, most prominently in career guidance, a core goal of the program. Ongoing program evaluation will determine how much of this benefit has been sustained after participation was opened to the whole community, and whether the program has had a measureable impact on the overall state of mentoring in pediatric rheumatology. [ABSTRACT FROM AUTHOR]

Background/Purpose: Pulmonary hemorrhage (PH) is a rare and devastating manifestation of SLE, occurring in 1-5% of adult cohorts with mortality rates ranging from 70%-90%. The majority of PH reported in SLE refers to the adult population, and there is a paucity of data in pediatrics. Therefore, we describe our experience with PH in pediatric SLE, outlining disease presentation, treatment, and outcomes. Methods: We reviewed records of pediatric SLE patients who presented with pulmonary involvement diagnosed between January 2000 and August 2010. Inclusion criteria included > 4 SLE classification criteria and PH based on pulmonary evaluation by BAL, lung biopsy and/or characteristic imaging with worsening anemia. We describe our pediatric cohort, presenting symptoms, diagnostic modalities, various interventions and overall outcomes. Results: Seven of 401 (1.7%) SLE patients met inclusion criteria for PH. Patients were predominantly male (71.4%) and Hispanic (57.1%). Median age of PH presentation was 13.5 years (range 2.0-15.2). Episodes were primarily within the first 3 months of SLE diagnosis (71.4%) and were a presenting manifestation for SLE in 28.6% of our patients. All patients presented with a new cough, dyspnea, hypoxemia, anemia and abnormal CXR. Hemoptysis was present in 28.6%. Four out of 6 children had chest CT findings with diffuse ground glass opacities (66.6%) and 3 with nodules (50%). Additional non-pulmonary features included fever (71.4%), renal disease (57.1%), cytopenias (71.4%), cardiac disease (50.0%), and positive antiphospholipid antibodies (85.7%). Eighty-five percent required supplemental oxygen and 57.1% required mechanical ventilation. Hemosiderin-laden macrophages without infection were observed in 3 BAL's. Out of the two lung biopsies performed, both revealed diffuse hemorrhage and one demonstrated immunoglobulin and complement deposition. All were treated with pulse doses of methylprednisolone infusions. Other therapeutic interventions included cyclophosphamide (42.8%), plasma exchange (42.8%), rituximab (85.7%) and IVIG (14.2%). Survival rate was 87.5%. All patients were maintained on corticosteroids and 66.6% received monthly cyclophosphamide infusions. Subsequent outpatient therapies included IVIG (33.3%), azathioprine (16.6%) or rituximab (16.6%). No patients had recurrences of PH. No survivors required supplemental oxygen nor developed interstitial lung disease (median follow-up 2.6 years, range 1.5-5.0). Conclusion: In our review of pSLE patients with PH, the prevalence of this complication approximated that of adult SLE cohorts. However, in contrast to the adult population, PH presented earlier in the course of SLE in children. Additionally, outcomes were favorable with initiation of aggressive, multi-modal immunosuppressive therapy with no recurrences. The mortality rate was much lower than described in adult cohorts. [ABSTRACT FROM AUTHOR]

Background/Purpose: Males represent 4-22% of all SLE patients, but it is unclear if gender should influence management. A number of studies of mostly adult patients suggest genetic, hormonal and environmental aspects of gender differences contribute to differences in presentation, clinical course and outcome, including a positive association between male gender and nephritis and a negative association with disease activity and outcome. While differences may exist, these findings are supported by limited evidence, particularly for children and adolescents with SLE. Methods: We retrospectively reviewed records of the nearly 200 pediatric SLE patients actively followed in the TCH rheumatology and renal clinics between 2011 and 2013 to identify males with SLE. Characteristic autoantibody features and renal disease were defined. Results: We identified 25 males (48% Hispanic, 16% Black, 16% Asian). The mean age of onset of disease was 11.5 ± 0.6 yo. Comorbid autoimmune diseases were identified in 46% of patients and 31% had a positive family history of autoimmune disease. Hypocomplementemia was seen at least once in 54% of patients. The cumulative incidence of positive autoantibodies included 50% anti-dsDNA, 54% with antiphospholipid abs, 42% with anti-RNP, 38% with anti-Ro (SS-A), 19% with anti-Smith, 15% with anti-La (SS-B), and 8% with RF. Only 35% (9) of male SLE patients developed lupus nephritis (LN), the majority of whom had class IV lesions (77%). Class V lesions were seen in 3 patients, including one with mixed histopathology (IV/V). LN was a presenting symptom in all 9 patients. Of these, 33% had acute kidney injury and 22% had crescentic disease on biopsy. The proportion of boys with LN and anti-dsDNA antibodies was not significantly different from boys without LN (66% vs. 50%, p = 0.67); however, a significantly higher proportion of boys with LN had anti-RNP abs (77% vs. 29%, p = 0.04). Conclusion: Although SLE predominately affects females, males with SLE represent an important subset of patients about which little is known. In our male cohort, rates of autoantibody positivity were similar to those published for females, but rates of kidney invovlement seem lower than expected. In addition, autoantibody profiling may not be as useful in predicting kidney involvement in boys. Additional research is of upmost importance to improve the diagnosis, quality of care, and outcomes of male SLE patients. [ABSTRACT FROM AUTHOR]

Background/Purpose: In 1998, Sorof et al. reported 28% of 60 pediatric SLE patients had class V lesions on their first biopsy and 37% had class V lesions on their most recent biopsy. Although 19% of patients with LN transformed from other classes to class V, there were no patients with repeat biopsies who showed complete resolution of their class V lesions. The prognosis of the patients with class V LN was better than those with non-class V LN (only 5% vs. 21% developed renal dysfunction or died). Methods: We retrospectively reviewed pathology records of pediatric lupus nephritis patients who underwent renal biopsies at Texas Children's Hospital between 1990 and 2013. Results: A total of 321 biopsies were performed on 174 patients with SLE. The cumulative incidence of class V histopathology was 50% (160/321). Upon initial biopsy, 93/174 (53%) patients had Class II, III or IV LN without class V lesions, and 81/174 (47%) patients had class V lesions, either alone (n = 38), or associated with class II, III or IV LN (n = 43). Repeat biopsies were obtained in 97 cases. The median interval between first and second biopsies was 11 months (IQR 9-19m, range 3-110 m). Of the 97 patients with at least 2 renal biopsies, 36 (37%) had class V lesions on the initial biopsy, and 61 (63%) did not have class V lesions on the initial biopsy. Although transformation between classes was common, the initially non-class V LN patients frequently remained free of class V lesions at follow up (n = 42, 70%). Of the 18/61 initially non-class V LN patients who did later develop class V lesions, 6% initially had pure class II LN, 61% pure class III, and 33% pure class IV. Repeat biopsies revealed mixed class V LN in 16/18 patients, with subsequent resolution of class V lesions or transformation to pure class V in 4. Six (17%) of the 36 patients with class V lesions on the initial biopsy had pure class V lesions, and 30 (83%) had mixed class II, III or IV LNThree (50%) of the 6 patients with initially pure class V lesions showed evolution to mixed class III/V LN, and evolution to class IV with sustained absence of class V lesions in 1 (17%). Of the 30 patients with initially mixed class V LN, repeat biopsies revealed persistent mixed class V LN in 22 (73%), transformation to pure class V in 4 (13%) and sustained resolution of class V lesions in 4 (13%). Conclusion: A comparison of the WHO classification of initial and repeat biopsies showed evolution to pure class V LN, or more commonly, development of a mixed class including class V LN. Although the vast majority of patients with class V LN showed persistence of this histopathology, sustained resolution of class V lesions may be possible. [ABSTRACT FROM AUTHOR]

Objective: To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG., Methods: Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients., Results: MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4-17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0-49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6)., Conclusion: The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.