Canakinumab in systemic juvenile idiopathic arthritis: real-world data from a retrospective Italian cohort.

OBJECTIVE: The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA). METHODS: A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months. RESULTS: A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years. CONCLUSION: We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.

Cow's milk and egg protein threshold dose distributions in children tolerant to beef, baked milk, and baked egg.

BACKGROUND: The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing oral food challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) is 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children. METHODS: We retrospectively assessed consecutive OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children. RESULTS: Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 was 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 was 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are, respectively, 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds. CONCLUSIONS: The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared with milk in the determinism of fatal anaphylactic reactions in children.

IgE-immunoadsorption for severe allergy to multiple foods: A case series of five children.

Background: Children with severe food allergy may present high risk of fatal anaphylaxis and a highly impaired quality of life. Anti IgE-treatment has been shown to be a promising approach as monotherapy for severe allergy to multiple foods. However, very high serum total IgE levels may limit its use.This study aims to assess the efficacy of IgE-selective immunoadsorption (IgE-IA) on total IgE levels and threshold of reactivity to the culprit foods in children with history of severe anaphylaxis due to multiple foods and allergic comorbidities. Methods: In this single-center, prospective, open-label efficacy study we evaluated children with severe asthma, allergy to 2+foods and total IgE levels >2300 kUI/L. To establish the food reactivity threshold, each patient underwent oral food challenges (OFCs) before and after IgE-IA. Results: Five patients (4 males; age, 12.2 ± 5 years, mean ± SD) underwent an average of 3 (range 2-4) sessions of IgE-IA. Each session reduced IgE levels by a mean of 1958.87 kUI/L. After the IgE-IA cycle, serum total IgE dropped from 3948 ± 1652.7 (mean ± SD) to 360.8 ± 71.9 kUI/L (-10.9 folds; p = 0.01). The threshold of reactivity (No Observed Adverse Effect Level, NOAEL) tested at OFCs for the culprit foods (4 baked-milk + 2 baked-egg + 1 lentil + 2 hazelnut + 1 wheat) increased overall from 21.5 (median, IQR 1.5-82.6) protein milligrams to 1115 (837.2-4222.8) milligrams (p < 0.001), ie, up to 51.8 times higher than baseline. 8/10 OFCs were negative after IgE-IA. Conclusions: IgE-IA increased food threshold quickly. It can be considered in well-selected patients with severe food allergies and high IgE-levels especially if otherwise eligible to anti IgE treatment.

Doxofylline for Pediatric Asthma Steps 1-4. Pediatric Asthma: New Role for an Old Drug.

The panoply of anti-asthma drugs for children between 6 and 18 years is not limited to those reported in the guidelines. In this review, we will re-assess the role of doxofylline, a xanthine characterized by a much higher handling than that of theophylline, as add-on treatment in pediatric asthma grade 1-4. Ten studies evaluated doxofylline in the treatment of asthma of patients non-responsive to the first-line inhaled corticosteroids. Of these, two included children and one was exclusively pediatric. According to their results, doxofylline exerts a powerful bronchodilator and anti-inflammatory activity, which can be exploited when the inhaled oral corticosteroids are not sufficient to get the desired effect of reducing symptoms. Unlike theophylline, doxofylline does not require blood testing. It can be administered together with or as an alternative to a series of other drugs considered in additional therapy.

Post-discharge telephonic follow-up of pediatric patients affected by SARS-CoV2 infection in a single Italianpediatric COVID center: a safe and feasible way to monitor children after hospitalization.

BACKGROUND: SARS-CoV-2 infection in children is often non severe and in the majority of cases does not require long term hospitalization, nevertheless it is burdened with social issues and managing difficulties. To our knowledge there is no literature on telephonic follow up in pediatric patients with positive PCR for SARS-CoV-2 on rhino-pharyngeal swab after discharge. The aim of the study is to describe our experience in a telephonic follow up which can allow early and safe discharge from hospital while keeping the patients under close clinical monitoring. MATERIALS AND METHODS: Sixty-five children were admitted for SARS-CoV-2 infection at Bambino Gesù Pediatric Hospital COVID Center from 16th March to 3rd July. We monitored through a telephonic follow-up, using a specific survey, the patients discharged still presenting a positive PCR for SARS-CoV-2. We checked if any symptoms occurred at home until recovery, defined as two consecutive negative PCR for SARS-CoV-2 on rhino-pharyngeal swabs. RESULTS: During the follow up 7 patients had mild and self-limited symptoms related to SARS-CoV-2 infection, while 2 patients were re-hospitalized. One patient had Multisystem Inflammatory Syndrome in Children (MIS-C), the other patient had an increase in troponin and D-dimers. We also monitored the average time of viral shedding, resulting in a median duration of 28 days. CONCLUSION: Our experience describes the daily telephonic follow up as safe in pediatric patients discharged with positive PCR. As a matter of fact it could avoid long term hospitalization and allow to promptly re-hospitalize children with major complications such as MIS-C.

Respiratory Syncytial Virus Bronchiolitis in Infancy: The Acute Hospitalization Cost.

Introduction: Respiratory syncytial virus (RSV) bronchiolitis is among the leading causes of hospitalization in infants. Prophylaxis with palivizumab may reduce RSV infection, but its prescription is restricted to high-risk groups. The aim of the study is to retrospectively determine acute hospitalization costs of bronchiolitis. Materials and methods: Infants aged 1 month-1 year, admitted to Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of bronchiolitis from January 1 till December 31, 2017, were included in the study. Results: A total of 531 patients were enrolled in the study, and the mean age was 78.75 days. The main etiologic agent causing bronchiolitis was RSV, accounting for 58.38% of infections. The total cost of bronchiolitis hospitalization was 2,958,786 euros. The mean cost per patient was significantly higher in the case of RSV (5,753.43 ± 2,041.62 euros) compared to other etiology (5,395.15 ± 2,040.87 euros) (p = 0.04). Discussion: The study confirms the high hospitalization cost associated with bronchiolitis. In detail, in the case of RSV etiology, the cost was higher compared to other etiology, which is likely due to the longer hospitalization and the more frequent admission to the intensive cure department. Conclusion: This study highlights that bronchiolitis is an important cost item even in a tertiary hospital and that cost-effective interventions targeting RSV are increasingly urgent.