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.

Utility of the 2018 revised ISN/RPS thresholds for glomerular crescents in childhood-onset lupus nephritis: a Pediatric Nephrology Research Consortium study.

BACKGROUND: The revised 2018 ISN/RPS Classification System for lupus nephritis (LN) includes calculations for both activity index (A.I.) and chronicity index (C.I.). Unchanged were the thresholds of < 25%, 25-50%, and > 50% crescents to distinguish between mild, moderate, and severe activity/chronicity. We aimed to evaluate these thresholds for percent crescents in childhood-onset LN. METHODS: Eighty-six subjects < 21 years of age were enrolled from the Pediatric Glomerulonephritis with Crescents Registry, a retrospective multi-center cohort sponsored by the Pediatric Nephrology Research Consortium. Thresholds of 10%, 25%, and 50% for both cellular/fibrocellular and fibrous crescents were interrogated for primary outcomes of kidney failure, eGFR, and eGFR slope. RESULTS: Median age at time of initial biopsy was 14 years (range 1-21). Median follow-up time was 3 years (range 1-11). Cumulative incidence of kidney failure was 6% at 1 year and 10% at latest follow-up. Median eGFR slope was - 18 mL/1.73 m2/min (IQR - 51 to + 8) at 1 year and - 3 mL/min/1.73 m2/year (IQR - 19 to + 6) at latest follow-up. We found no difference in kidney failure at the proposed < 25% and 25-50% cellular crescents thresholds, and thus added a new provisional threshold of 10% that better predicted outcomes in children. Moreover, use of 10% and 25% thresholds for fibrous crescents showed a fourfold and sevenfold increase in risk of kidney failure. CONCLUSIONS: In children with crescentic LN, use of 10% and 25% thresholds for cellular crescents better reflects disease activity, while these thresholds for fibrous crescents better discriminates kidney disease outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

From Telemedicine to the ICU-Fever and Rash in a 9-Year-Old Girl.

A 9-year-old girl presented to her primary care pediatrician via telemedicine during the initial months of the coronavirus disease 2019 pandemic because of 4 days of warmth perceived by her mother, decreased energy, and a new rash on her upper extremities. After 10 additional days of documented fever >38°C, worsening fatigue, and 1 day of nausea, vomiting, and diarrhea, she was allowed to schedule an in-person visit with her pediatrician after testing negative for severe acute respiratory syndrome coronavirus 2. She appeared ill on arrival to clinic, and her pediatrician recommended evaluation in an emergency department. Her initial laboratory testing revealed nonspecific elevation in several inflammatory markers and leukopenia, and she responded well to intravenous hydration. Over the next 2 weeks, her fever persisted, constitutional symptoms worsened, and she developed progressively painful cervical lymphadenopathy and pancytopenia. She was evaluated in clinic by several specialists and eventually was urged to present to the emergency department again, at which time she was admitted to the PICU. After consulting additional specialists and waiting for laboratory results, the team reached a definitive diagnosis and initiated therapy; however, she experienced rapid clinical decline shortly thereafter. The specialists who assisted with identification of the underlying etiology of her symptoms were able to work together to manage the subsequent complications.

Pulmonary manifestations and outcomes in paediatric ANCA-associated vasculitis: a single-centre experience.

OBJECTIVES: ANCA-associated vasculitis (AAV) usually involves the renal and respiratory systems, but the paediatric literature on pulmonary manifestations and outcomes is limited. We aimed to describe pulmonary manifestations and outcomes after therapy in a cohort of paediatric AAV (pAAV) patients. METHODS: A retrospective chart review of all patients <19 years presenting to our institution with AAV between 1/2008 and 2/2018 was conducted. Patient demographics, clinical presentation, diagnostic testing, therapy and pulmonary outcomes over the first 3 years after presentation were evaluated. RESULTS: A total of 38 patients were included; all had ANCA positivity by immunofluorescence. A total of 23 had microscopic polyangiitis (MPA), 13 had granulomatosis with polyangiitis and 2 had eosinophilic granulomatosis with polyangiitis. A total of 30 (79%) had pulmonary manifestations, with cough (73%) and pulmonary haemorrhage (67%) being the most common. Abnormalities were noted in 82% of chest CT scans reviewed, with nodules and ground-glass opacities being the most common. At 6, 12 and 36 months follow-up, respectively, 61.8%, 39.4% and 29% of patients continued to show pulmonary manifestations. Five MPA patients with re-haemorrhage are described in detail. CONCLUSION: MPA was more common than granulomatosis with polyangiitis, with pulmonary involvement being common in both. MPA patients had more severe pulmonary manifestations. Chest CT revealed abnormal findings in a majority of cases. A subgroup of young MPA patients experienced repeat pulmonary haemorrhage. Treatment modality and response were comparable in different subtypes of AAV, except for this young MPA group. Additional prospective studies are needed to better understand the different phenotypes of pAAV.

Rapid infusion of rituximab is well tolerated in children with hematologic, oncologic, and rheumatologic disorders.

Traditional administration of rituximab requires careful titration and may involve many hours to minimize the risk of reactions. The objective of this study was to evaluate the safety of rapid infusions of rituximab in a pilot group of children with hematologic, oncologic, and rheumatologic disorders, and to determine the incidence of rate-related infusion reactions. Twenty patients enrolled in the study. All patients tolerated the rapid infusion of rituximab and no patient had an infusion-related reaction. We conclude that rapid infusions of rituximab are well tolerated and safe in our pilot group of patients.

Outcomes of children with proliferative lupus nephritis: the role of protocol renal biopsy.

Outcomes in children with proliferate lupus nephritis (PLN) show 9-15% progress to end-stage renal disease (ESRD) at 5 years. Immunosuppression improves outcome, but significant side effects are possible. Clinical and laboratory analyses are poor predictors of class and progression in PLN. We describe 28 patients with systemic lupus erythematosus (SLE), between 1990 and 2005, whose initial biopsy (Bx1) showed PLN and who received nine monthly doses of intravenously administered cyclophosphamide (CYP) (500-750 mg/m(2) up to 1 g to maintain their absolute neutrophil count (ANC) > 3,000). Continued therapy with additional quarterly intravenous (i.v). administration of CYP was dictated by repeat renal biopsy (Bx2). Bx1 was done 1 +/- 1.6 years after diagnosis of SLE. Bx2 showed histological improvement by WHO classification in 20/25 children; 3/25 were unchanged, 1/25 was categorized as new class V, and 1/25 was worse. Four patients (14%) had infectious complications requiring hospitalization (one of these died). Mean follow-up (f/u) after Bx2 was 3.5 +/- 2.3 years. At last follow-up, 26 patients had normal glomerular filtration rate (GFR), with a mean of 126 +/- 42.8 ml/min per 1.73 m(2) body surface area, one non-compliant patient had ESRD, and one had chronic renal failure. At last follow-up, most patients had minimal to no proteinuria. Clinical and biopsy results greatly improved after 9 monthly intravenously administered CYP pulses in most children with class IV PLN. Those who did not improve are at risk for flares and progression of disease. The tailoring of therapies based on findings from a biopsy after induction may improve outcomes.