Inborn Errors of Immunity Associated With Type 2 Inflammation in the USIDNET Registry.

Background: Monogenic conditions that disrupt proper development and/or function of the immune system are termed inborn errors of immunity (IEIs), also known as primary immunodeficiencies. Patients with IEIs often suffer from other manifestations in addition to infection, and allergic inflammation is an increasingly recognized feature of these conditions. Methods: We performed a retrospective analysis of IEIs presenting with allergic inflammation as reported in the USIDNET registry. Our inclusion criteria comprised of patients with a reported monogenic cause for IEI where reported lab eosinophil and/or IgE values were available for the patient prior to them receiving potentially curative therapy. Patients were excluded if we were unable to determine the defective gene underlying their IEI. Patients were classified as having eosinophilia or elevated IgE when their record included at least 1 eosinophil count or IgE value that was greater than the age stratified upper limit of normal. We compared the proportion of patients with eosinophilia or elevated IgE with the proportion of samples in a reference population that fall above the upper limit of normal (2.5%). Results: The query submitted to the USIDNET registry identified 1409 patients meeting inclusion criteria with a monogenic cause for their IEI diagnosis, of which 975 had eosinophil counts and 645 had IgE levels obtained prior to transplantation or gene therapy that were available for analysis. Overall, 18.8% (183/975) of the patients evaluated from the USIDNET registry had eosinophilia and 20.9% (135/645) had an elevated IgE. IEIs caused by defects in 32 genes were found to be significantly associated with eosinophilia and/or an elevated IgE level, spanning 7 of the 10 IEI categories according to the International Union of Immunological Societies classification. Conclusion: Type 2 inflammation manifesting as eosinophilia or elevated IgE is found in a broad range of IEIs in the USIDNET registry. Our findings suggest that allergic immune dysregulation may be more widespread in IEIs than previously reported.

Inborn errors of immunity manifesting as atopic disorders.

Inborn errors of immunity are traditionally best known for enhancing susceptibility to infections. However, allergic inflammation, among other types of immune dysregulation, occurs frequently in patients with inborn errors of immunity. As such, the term primary atopic disorders (PADs) was recently coined to describe the group of heritable monogenic allergic disorders. It is becoming increasingly important for clinicians to recognize that allergic diseases such as food allergy, atopic dermatitis, and allergic asthma are expressions of misdirected immunity, and in patients who present with severe, early-onset, or coexisting allergic conditions, these can be indications of an underlying PAD. Identifying monogenic allergic disease through next-generation sequencing can dramatically improve outcomes by allowing the use of precision-based therapy targeting the patient's underlying molecular defect. It is therefore imperative that clinicians recognize PADs to be able to provide informed therapeutic options and improve patient outcomes. Here, we summarize the clinical features commonly seen with each of the currently known PADs, identify clinical warning signs that warrant assessment for PADs, and lastly, discuss the benefits of timely diagnosis and management of these conditions.

Outcomes of Neonates With Complex Medical Needs.

BACKGROUND: Children with complex medical needs (CMN) are high healthcare resource utilizers, have varying underlying diagnoses, and experience repeated hospitalizations. Outcomes on neonatal intensive care (NICU) patients with CMN are unknown. PURPOSE: The primary aim is to describe the clinical profile, resource use, prevalence, and both in-hospital and postdischarge outcomes of neonates with CMN. The secondary aim is to assess the feasibility of sustaining the use of the neonatal complex care team (NCCT). METHODS: A retrospective cohort study was conducted after implementing a new model of care for neonates with CMN in the NICU. All neonates born between January 2013 and December 2016 and who met the criteria for CMN and were cared for by the NCCT were included. RESULTS: One hundred forty-seven neonates with a mean (standard deviation) gestational age of 34 (5) weeks were included. The major underlying diagnoses were genetic/chromosomal abnormalities (48%), extreme prematurity (26%), neurological abnormality (12%), and congenital anomalies (11%). Interventions received included mechanical ventilation (69%), parenteral nutrition (68%), and technology dependency at discharge (91%). Mortality was 3% before discharge and 17% after discharge. Postdischarge hospital attendances included emergency department visits (44%) and inpatient admissions (58%), which involved pediatric intensive care unit admissions (26%). IMPLICATIONS FOR PRACTICE: Neonates with CMN have multiple comorbidities, high resource needs, significant postdischarge mortality, and rehospitalization rates. These cohorts of NICU patients can be identified early during their NICU course and serve as targets for implementing innovative care models to meet their unique needs. IMPLICATIONS FOR RESEARCH: Future studies should explore the feasibility of implementing innovative care models and their potential impact on patient outcomes and cost-effectiveness.