Lupus Nephritis Patterns and Response to Type I Interferon in Patients With DNASE1L3 Mutations: Report of Three Cases.

DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 mutations impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 mutations is poorly characterised. Herein, we describe the clinical course of three children with monogenic SLE due to DNASE1L3 mutations who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (i.e., membranous, endo- and extra-capillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and ANCA-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. 2/3 patients had increased expression of interferon-stimulated genes in the peripheral blood and all three patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN I-mediated kidney disorders, and provide the rationale for IFN I-directed therapies in order to improve the poor outcome of this rare condition.

Early anakinra treatment improves cardiac outcome of multisystem inflammatory syndrome in children, regardless of disease severity.

OBJECTIVE: The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra. METHODS: This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up. RESULTS: Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4-1.0). CONCLUSION: We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome.

Adolescents' Utilization of a Tertiary-Level Pediatric Emergency Department in Italy.

Aim: Describe the use of the emergency department of a tertiary-level children's hospital in Italy by adolescents. Methods: This retrospective study was based on the medical records of patients aged 13 to 17 years, who accessed the emergency department of the Institute for Maternal and Child Health of Trieste, from 1 January to 31 December 2018. The primary outcome was to describe the leading causes of access, diagnoses, rate of hospitalization, and ward of destination among adolescent patients. Results: During the study period, 24,599 patients accessed the department. Among them, 3,062 were adolescents, for a total of 3,895 unscheduled visits. The principal causes of access were trauma (45.3%) and organic diseases (38.8%). Two hundred and forty nine adolescents (6.4%) had mental health problems. One hundred and forty two adolescents (3.6%) Were Admitted to the Hospital, 54 of Whom (38%) to the Neuropsychiatric Ward, for Mental Health Problems. Conclusions: Among adolescents seen in this Italian tertiary-level children's hospital, mental health problems represented a small proportion of emergency department visits but were the leading cause of urgent hospitalization.

Epidemiological trends of pediatric IBD in Italy: A 10-year analysis of the Italian society of pediatric gastroenterology, hepatology and nutrition registry.

INTRODUCTION: The present study aimed at evaluating Italian epidemiological trends of pediatric inflammatory bowel diseases (IBD) over the period 2009-2018. MATERIALS AND METHODS: Data from 1969 patients enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition Registry, by 49 pediatric IBD centers throughout the country, were analyzed, comparing three different time intervals (2009-2012, 2013-2015, 2016-2018). RESULTS: The number of new IBD diagnoses ranged from 175 to 219 per year, evenly distributed over the examined period of time. From 2009 to 2018, the minimal incidence ranged from 1.59 to 2.04 /105 inhabitants aged < 18 years, with an overall slight predominance of ulcerative colitis (UC) over Crohn's disease (CD) (ratio: 1.1). Mean diagnostic delay was 6.8 months for CD and 4.1 months for UC, with a significant reduction for CD when comparing the three-time intervals (p =0.008). The most frequent disease locations according to the Paris classification were ileocolonic for CD (41.3%) and pancolitis for UC (54.6%). CONCLUSIONS: The minimal incidence rate in Italy seems to have stabilized over the last two decades, even if it has increased when compared to previous reports. UC is still slightly more prevalent than CD in our country. Diagnostic delay significantly decreased for CD, reflecting an improved diagnostic capacity.

Phenotype and Natural History of Children With Coexistent Inflammatory Bowel Disease and Celiac Disease.

BACKGROUND: Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. METHODS: This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. RESULTS: Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97-8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn's disease and CeD than in patients with Crohn's disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13-33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). CONCLUSIONS: Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.

Parental Psychological Factors and Quality of Life of Children With Inflammatory Bowel Disease.

OBJECTIVES: Parents have a central role in the management of children with inflammatory bowel disease (IBD). Alterations in parental psychological well-being may affect the patient's health-related quality of life (HRQoL). This study aimed to evaluate the correlation between maternal and paternal distress, anxiety, depression and pain catastrophizing and the HRQoL of patients with IBD. METHODS: Children with IBD ages 8 to 18 years and their parents were prospectively recruited. Children answered questionnaires on HRQoL while parents completed an assessment of distress, anxiety, depression, and pain catastrophizing. Univariate and multivariate regression models analysis were used to evaluate correlations between parental measures and patient's HRQoL and between the factors related to children health and parental psychological suffering. RESULTS: One hundred patients (45 Crohn disease, 55 ulcerative colitis), 90 mothers and 62 fathers were enrolled. Parents had high levels of distress while anxiety, depression, and pain catastrophizing levels were relatively low. Parental distress had the most substantial correlation with children's HRQoL and was associated with patients' disease activity and recent flares. On multivariate regression analysis, parental factors explained less than 20% of the variance in the children's HRQoL scores. Mothers suffered from psychological alterations more frequently than fathers, but the parental inter-rater agreement was strong in regards to distress and anxiety. CONCLUSIONS: Parental distress is high and correlates with the HRQoL of children with IBD. Interventions aimed at evaluating and managing parental distress should be considered during the management of children with IBD.

Efficacy and safety of infliximab in very early onset inflammatory bowel disease: a national comparative retrospective study.

Background: Very few data regarding the use of infliximab in children with very early-onset inflammatory bowel disease (VEO-IBD) have been reported. Objective: We aimed to assess the efficacy and the safety of infliximab in children with VEO-IBD compared with older children. Methods: Children treated with infliximab were identified within the Italian IBD registry. The primary outcome was the rate of clinical remission at weeks 14 and 54. Secondary outcomes included the proportion of partial clinical response, treatment duration, and incidence of adverse events. Results: Forty-two children with VEO-IBD were compared with 130 children with IBD. Despite significantly higher infliximab withdrawals in VEO-IBD patients during induction (42.9% vs 7.7% p < 0.01), remission rates at week 14 were similar (28.6% vs 43.8%, p = 0.10). At week 54 fewer VEO-IBD children were in remission (15.8% vs 54.3%, p < 0.01). The treatment duration was shorter in VEO-IBD (median 12.0 vs 18.4 months, p < 0.01). During the induction phase, adverse events were more common in the VEO-IBD group (p < 0.01). Conclusion: Compared with older children, VEO-IBD patients have higher rates of infliximab failures, lower remission rates at one year, and more often experience adverse events during induction.