Researchers evaluated the ability of preexisting criteria for food protein–induced enterocolitis syndrome (FPIES) to identify pediatric patients with mild acute FPIES. These were compared with new criteria proposed by the authors.This study enrolled 15 patients who attended an academic pediatric allergy clinic in Rome, Italy. Inclusion criteria consisted of patients younger than 18 years and those who received a diagnosis of mild acute FPIES between 2004 and 2023.This retrospective study evaluated the accuracy of 3 preexisting criteria sets, along with the study’s newly developed criteria, in identifying mild acute FPIES in the study population. Preexisting criteria included (1) FPIES International Consensus Guidelines (ICG), (2) Miceli Sopa’s criteria, and (3) Vazquez-Ortiz and Infante’s criteria. The new proposed diagnostic and suspicion criteria, in which oral food challenge is unnecessary and necessary, respectively, consist of (a) symptom resolution in 6 to 8 hours, except diarrhea, (b) absence of food ingestion without adverse reactions after first episode, and (c) absence of immunoglobulin E–mediated skin or respiratory symptoms. Diagnostic criteria must include one of the following: (a) 2+ episodes of emesis 1 to 4 hours after ingestion with pallor or lethargy, (b) 3+ episodes of emesis 1 to 4 hours after ingestion without pallor or lethargy OR with pallor or lethargy in 1 episode, or (c) 3+ episodes of emesis more than 4 hours after ingestion with pallor or lethargy. Suspicion criteria must include one of the following: (a) 1 episode of emesis 1 to 4 hours after ingestion with pallor or lethargy, (b) 2 episodes of emesis 1 to 4 hours after ingestion without pallor or lethargy OR with pallor or lethargy in 1 episode, or (c) 2 episodes of emesis more than 4 hours after ingestion with pallor or lethargy.No preexisting criteria set identified all 15 cases of mild acute FPIES (FPIES ICG: 0/15, Miceli Sopa: 3/15, Vazquez-Ortiz and Infante: 11/15). The authors’ new diagnostic and suspicion criteria correctly identified all 15 cases.Preexisting criteria for FPIES can underdiagnose milder presentations of the disease. New criteria developed by the authors identified all cases of mild acute FPIES within the study population.This study highlights the challenges preexisting criteria have in accurately identifying cases of mild acute FPIES. Strengths of this study include the creation of a novel criteria set, which can benefit general pediatricians who may overlook milder cases of FPIES and lead to potential mismanagement. Although promising, this new criterion has not been prospectively validated and is limited by the study’s small sample size. However, the authors raise a valid point that no published criteria have been previously validated in prospective studies and, rather, are a product of expert opinion.

Food allergy (FA) affects pediatric growth and psychosocial well-being. The relationship between FA and feeding difficulties is poorly understood. The current study sought to investigate feeding problems in children with parent-reported immunoglobulin # (IgE)–mediated FA and/or pediatric feeding disorder (PFD) compared with healthy children and to explore factors associated with feeding problems in children with FA.This is a matched, cross-sectional cohort study using deidentified data from a series of online surveys. Survey data from 352 parents of children aged 6 months to 7 years with parent-reported IgE-mediated FA and/or PFD were categorized into 1 of 3 cohorts: 50 children with only FA, 67 children with both FA and PFD, and 235 children with only PFD. Each cohort was individually matched to data from typically developing children also collected in the original studies based on age, sex, race, and socioeconomic characteristics.Secondary analysis was performed on deidentified data from surveys conducted between 2015 and 2017. The Pediatric Eating Assessment Tool (PediEAT) was used to obtain parent ratings of the child’s feeding problems.Children with FA exhibited more feeding problems compared with matched healthy children. Children with PFD had more severe feeding problems irrespective of comorbid FA. Older age, non-white race, increased medical comorbidity, and limited dietary variety were factors associated with feeding problems in children with FA.This study adds to evidence indicating increased prevalence of feeding problems in children with FA. Clinicians treating patients with FA should screen for feeding and growth concerns and consider referral to multidisciplinary feeding programs. Children with FA who consume a limited variety of foods may experience more feeding problems.Early identification and intervention for patients with feeding problems may help prevent behavioral problems from becoming more ingrained. Early identification of multiple risk factors may be helpful in engaging at-risk patients for early intervention strategies. A potential challenge noted by the authors is the limitation of the PediEAT tool for capturing subtle concerns about food-associated behaviors.

This study evaluated the need for additional emergency treatment following food-induced anaphylaxis in children who received appropriate prehospital epinephrine.Children younger than 18 years with known immunoglobulin E–mediated food allergies who presented to one of 7 Canadian pediatric emergency departments (EDs) (2011-2023) and received at least 1 prehospital epinephrine dose. Patients not meeting National Institute of Allergy and Infectious Diseases criteria for anaphylaxis were excluded.Outcomes of interest included use of at least 2 prehospital epinephrine doses, ED epinephrine administration, and hospital admission. Data collected included demographics, suspected food triggers, symptoms, severity, and comorbidities. Reactions were categorized by the most severe symptom as mild, moderate, or severe.A total of 1127 children were studied (median age: 7 years; 60.6% male). Mucocutaneous reactions were the most common (pruritus: 47.3%, urticaria: 55.4%, angioedema: 51.9%), followed by respiratory symptoms (throat tightness: 39.5%, breathing difficulties: 40.3%), gastrointestinal symptoms (36.8%), and cardiovascular symptoms (cyanosis: 1.9%, circulatory collapse: 0.4%, hypotension: 2.4%); 7.9% of patients had severe reactions. Every patient received at least 1 prehospital dose of epinephrine; 84.3% received 1 dose, 12.4% received 2, and 3.3% received 3 or more prehospital doses. In the ED, 18.5% received additional intramuscular epinephrine and 0.9% received it intravenously. Other treatments included antihistamines, beta-agonists, corticosteroids, and intravenous fluids. Overall, 6.2% required 3 or more epinephrine doses, and 2.7% were hospitalized. Factors associated with needing additional epinephrine in the ED included reaction due to tree nuts and more severe reactions.Only a minority of patients who received prehospital epinephrine required further treatment in the ED. This supports the use of shared decision-making when talking to families about ED evaluation after epinephrine use.These results highlight how caregiver education can lead to safer care out of the hospital—ideally encouraging earlier epinephrine use and reducing associated health care costs.

To determine whether any laboratory studies may predict a predisposition for recurrent respiratory tract infections (rRTis).The cohort included 100 children younger than 10 years with RTls who were referred for immunological screening. The comparison group was family.rRTis were determined based on the age of the patient. rRTis were defined as at least 11 upper rRTis/y for age up to 2 years, 28 upper rRTis 2 to 5 years, 26 for 5 to 8 years, or at least 2 pneumonia diagnoses in a year or 3 in a lifetime. In the study cohort, a saliva and serum sample were obtained at baseline. In the control group, serum and saliva samples were collected before and 4 weeks after receiving the influenza vaccine to detect any changes in antibody levels. In the study cohort, saliva was collected at baseline and nasopharyngeal swabs were collected in the first month. The swabs were analyzed for microbiota 165 RNA sequencing and detection of 12 respiratory viruses by quantitative PCR (qPCR) and Haemophilus subtyping by qPCR. For children with rRTis, immunologic screening was done.A high proportion of salivary immunoglobulin A (IgA) polyreactive antibodies were found in saliva compared with serum in patients with rRTis. Serum antibody deficiencies were not associated with increased rRTi severity or viral burden. Decreased levels of polyreactive IgA and IgG in saliva were associated with rRTi severity. Also, Haemophilus influenzae abundance is associated with RTI symptom burden. The symptoms were monitored daily via a cell phone app.The findings support that serum antibody levels are not associated with disease burden. The study underscores that the role of H influenzae in the respiratory microbiota is associated with reduced levels of polyreactive IgA and increased RTis. This supports the need to analyze the mucosal immune system to enhance the understanding of rRTis in children.Although these data help us better understand the immune response of mixed viral and bacterial infections, we are still left with currently not having any readily available diagnostics tests that will allow identification of these abnormalities and a method of treatment that will allow intervention to halt recurrent lower respiratory tract infections.

The National Institute of Allergy and Infectious Disease (NIAID) released Prevention of Peanut Allergy guidelines in 2017. These were drafted following studies that highlighted the importance of early introduction of peanuts in infants, especially those with egg allergy and eczema. This early introduction is safe and efficacious in preventing food allergy. This study assesses the awareness of and adherence to these guidelines by clinicians who provide care for children.A third-party market research company (Dynata, Plano) identified a diverse and representative sample of online panel members including pediatricians, pediatric family physicians, advanced practice providers (APPs), and dermatologists. The study population included a total of 46 201 people who received the survey and 3849 who answered the first question, with a response rate of 8.3%. The final survey analysis included 250 pediatricians, 250 family physicians, 253 nurse practitioners, 251 physician assistants, and 253 dermatologists.The company administered the survey to panel members from June 6 through July 3, 2022. The survey included 45 items to assess for eligibility, demographic/practice information, and food allergy prevention.The primary outcome assessed participant awareness of the guidelines for peanut introduction and implementation of them. The study noted self-reported guideline awareness in 76% of the pediatricians, whereas self-reported guideline awareness was lower in nonpediatric clinicians including 58% of dermatologists, 52% of family physicians, and 45% for APPs. Of those who noted awareness, only 26% of pediatricians and 30% of dermatologists reported they followed the guidelines closely. Furthermore, within those that followed any guidelines, between 53% and 57% of the pediatricians recommended early introduction in mild to moderate atopic dermatitis, whereas 18% to 38% of nonpediatricians would recommend it. If they did not recommend the early introduction, they would refer to an allergist, order peanut-specific allergen testing, or recommend avoidance of peanuts. Barriers to implementation included lack of clinic time, parental concerns, or clinician concerns.The study noted that despite awareness of these guidelines in pediatricians and other clinicians, the reported implementation and adherence was low. Furthermore, the implementation and adherence was lower in nonpediatric clinicians including dermatologists and APPs. This suggests the need for improvement in continuing education for these clinicians.The NIAID Prevention of Peanut Allergy guidelines have been available since 2017. Despite the widespread knowledge in pediatricians, there is a significant gap in clear implementation of these guidelines in this population, especially in patients with mild to moderate eczema. This leads to missed opportunities for peanut introduction in patients who are at risk. We need to work further on minimizing barriers to this implementation, which can start with education from allergy specialists. Furthermore, as the pediatrician workforce shifts to more well-child visits completed by family medicine providers and APPS, it is essential we help educate these clinicians on these new guidelines and improve implementation. This education can help address food allergies on a population scale and is essential to the treatment/prevention of food allergies.

Medical record audits of primary care practices in the United States, Canada, and the United Kingdom suggest widespread suboptimal implementation of asthma guideline recommendations. Reasons are numerous, but there may be a perceived lack of benefit for patients. In the United Kingdom, more than 95% of scheduled asthma care is provided by primary care. The objective of this study was to determine the implementation of specific guideline-recommended clinical practices (GCPAs) and determine which children were less likely to receive these and their effectiveness at reducing exacerbations.A total of 126 483 five- to sixteen-year-old children with at least 3 asthma codes within 3 years. The study population was drawn from a longitudinal health care database of UK primary care medical records. This database covers approximately 20% of the United Kingdom. Records were individually linked to hospital admissions and emergency department (ED) data.Self-controlled case series methodology was used; each child acts as their own control and outcome events are compared prior to and following the exposure to the GCPA. These measures included asthma review (included an assessment of asthma control), inhaler technique check, and asthma management plan. Other variables included body mass index, socioeconomic status, smoking status, other atopic disease, asthma medications, and asthma exacerbations, defined as a short course of oral corticosteroids, ED visit, or hospitalization. The control period was considered the 12 months prior to guideline-recommended care, and the risk period was considered the 12 months after.In the first year following the asthma diagnosis, 56% received an annual asthma review, falling to 45% in subsequent years. Asthma management plans were provided to 42% in the first year, dropping to 30% thereafter. Inhaler technique checks were conducted in 59% in the first year and 40% in subsequent years. Children who received the GCPA were more likely to be male and older and have more severe asthma. Atopy and previous exacerbations did not distinguish those who received the GCPA. Children less likely to receive the GCPA included those with lower socioeconomic status, those with obesity, those not receiving inhaler prescriptions, and those of a younger age. Standalone annual asthma reviews were associated with a 6% reduction in exacerbations only during the first 6 months; standalone inhaler technique checks were not associated with a decrease in exacerbations, but standalone provision of an asthma management plan was associated with a 15% decrease in exacerbations that persisted. Provision of all 3 GCPAs during the same visit was associated with a 30% decrease in exacerbations that also persisted.Provision of GCPAs is underutilized in the United Kingdom, especially for all 3 given at the same visit. The most vulnerable at-risk children were the least likely to receive the GCPAs. Annual asthma reviews alone, and inhaler technique review alone, have no lasting effect on exacerbations, but asthma management plans alone do reduce exacerbations, and all 3 GCPAs at the same visit are most effective.Annual asthma visits were not noted to be effective, but the only stipulation for those are an assessment of asthma control, which could be minimal. This study adds to the evidence that guideline-recommended care is suboptimal in primary care, and most importantly, a comprehensive asthma visit with provision of all 3 GCPAs can have a significant impact on exacerbations.

Many children with immunoglobulin E–mediated cow’s milk allergy (IgE-CMA) have spontaneous resolution. Previous prospective studies have reported spontaneous resolution rates of 53% to 57% by the age of 5 years. The current extension study sought to evaluate resolution rates of IgE-CMA through the end of adolescence.From a cohort of 13 019 Israeli infants observed from birth, 54 had IgE-CMA confirmed by an oral food challenge (OFC). Persistence of IgE-CMA at 5 years was diagnosed in 23 children via a positive OFC or a recent objective allergic reaction to milk. IgE-CMA status was reassessed at age 17 in these 23 patients.Patients were evaluated at 17 years by questionnaire. Resolution was determined by regular milk consumption without adverse reaction or a negative OFC. Persistence of allergy was defined by a recent objective reaction to milk and a positive skin test greater than or equal to 8 mm or by sensitization with milk serum–specific IgE testing greater than 15 kUA/L.Of the 23 patients with persistence of IgE-CMA at 5 years, 8 (35%) had spontaneous resolution of IgE-CMA between the ages of 5 and 17 years. Overall, 39 of the 54 patients (72.2%) initially diagnosed with IgE-CMA had spontaneous resolution by 17 years. Risk factors for persistence of IgE-CMA at 17 years included skin prick test greater than 6 mm at the time of diagnosis, no cow’s milk feeding in infancy, and wheezing on diagnostic OFC or in association with a clinical adverse reaction to milk. Seven patients experienced objective adverse reactions after 5 years. Associations in these patients included wheezing or anaphylaxis on diagnostic OFC or initial reaction and current asthma.Spontaneous resolution of IgE-CMA occurs beyond 5 years. Few patients with IgE-CMA experience objective adverse reactions by late adolescence. Respiratory symptoms with early milk ingestion and asthma in adolescence were associated with persistence of IgE-CMA and of being at risk for more severe adverse reactions to milk until adolescence.The results of this population-based natural history study are interesting and may inform education and intervention strategies. The authors note the small study size, population limited to Israeli patients, and limited follow-up between the ages of 5 and 17 years for some patients as potential limitations of the current study. The authors pose an interesting query about the timeline for achievement of resolution between the ages of 5 and 17 years. This is an area for potential future study.

This study specifically wanted to better elucidate etiologies for prolonged cough or cough lasting more than 4 weeks in a multicenter pediatric cohort to better determine etiologies by age enabling diagnostic evaluation and treatments outside of consideration for asthma.Using the Swiss Paediatric Airway Cohort (SPAC), this study analyzed 363 pediatric patients (16% of the cohort) from 2017 to 2022 for etiologies for prolonged/protracted or recurrent cough as their initial presentations. The SPAC is a prospective observational national multicenter cohort with 2206 children (0–16 years of life) enrolled in 10 locations in Switzerland. Inclusion was kept broad based on a loose definition of chronic/protracted/recurrent cough as their primary referral indication. Patients were excluded if they had confirmed asthma diagnosis to better determine initial investigations or diagnostic process. Of the 363 patients analyzed, 60% were male and 36% had parental tobacco exposure. Patients were stratified by age for preschool (<5 years), with 131 children vs 232 school-aged (>5 years) children.Patient- and parent-reported baseline questionnaires were obtained during encounters including respiratory symptoms and comorbidities. Attendings’ letters were reviewed, extracting the diagnostic investigation that were performed (pulmonary function testing, allergy tests, nitric oxide, sweat chloride, radiographic evaluation), diagnosis, and treatments. Final diagnoses were grouped as (1) asthma and asthma-like conditions (cough variant asthma, episodic viral wheeze, and recurrent obstructive bronchitis); (2) nonspecific postinfectious cough; (3) respiratory tract infections (RTI) including protracted bacterial bronchitis (PBB); (4) upper airway cough syndrome (UACS); and (5) unknown or other including gastrointestinal reflux disease and somatic or tic cough.One hundred thirty-two patients (36%) were found to have asthma or asthma-like etiologies, 51 (14%) had RTI with PBB diagnosed in 7%, and 48 (13%) had UACS. For the 232 school-aged children analyzed, 90 (39%) were diagnosed with asthma, UACS in 29 (13%), postinfectious cough in 22 (9%), and RTI in 18 (8%). In the 131 preschool children, 33 (25%) had RTI, with PBB making up half of those diagnoses, and 20 (15%) were diagnosed with asthma-like conditions. Historical clues in the description of the cough (wet vs dry) and timing (daytime vs nighttime) were keys in diagnosis. Between 72% and 77% of patients had cough with activity regardless of final diagnosis. Asthma had a higher association with aeroallergen trigger and history of wheeze in 43%. The most common diagnostic tests performed were fraction of exhaled nitric oxide (73%), spirometry (71%), and allergy tests (70%). For treatments, 216 (60%) were prescribed short-acting beta-agonists, 111 of the 132 patients (84%) diagnosed with asthma were prescribed inhaled corticosteroids, and 81% of the patients with infectious etiologies were prescribed antibiotics. For UACS, 83% of patients were prescribed intranasal corticosteroids.Etiologies for chronic cough vary by age, with preschool-aged children more often having postinfection etiologies or protracted infectious etiologies more commonly with dry nighttime cough vs wet sounding, respectfully. Asthma or asthma-like diagnoses occurred at a much higher rate in school-aged children. There were challenges in each age separating chronic (persistent cough greater than 4 weeks continuously) and recurrent symptoms, which warranted further study. The diagnostic algorithm varied too much to create specific recommendations. Treatment was based on diagnosis but involved more than just treating with inhaled pharmacotherapy.Although prolonged and recurrent cough remain common chief concerns to pediatricians, allergists, and pulmonary specialists, history taking and targeted diagnostic testing modalities, including pulmonary function testing and allergy tests, are often the most important ways to reach a diagnosis. Thoughtful diagnosis with considerations for other causes are important, and asthma should not be the only etiology considered. Treatment should be tailored to the presentation. This observation study laid the framework for the importance of the standardization of the diagnostic workup in these age ranges for better clinical management recommendations.

This study investigated the prevalence and stability over time of T1 high, T2 high, and mixed T1/T2 high asthma endotypes and assessed the influence of T1 inflammation (potentially driven by subclinical viral infection) on corticosteroid responsiveness in asthma.Adult participants in the Severe Asthma Research Program-3 (SARP-3) cohort (n = 347) and healthy controls (n = 37) contributed sputum samples at baseline, after administration of intramuscular triamcinolone, and at 1- and 3-year follow-up visits. Participants were classified by expression of T-helper type 1 drive (T1) and type 2 (T2)–associated gene networks into T1 high, T2 high, mixed T1/T2 high, or low-expression endotypes.Investigators performed whole-transcriptome RNA sequencing on sputum cells to identify coexpression gene networks associated with T1 and T2 inflammation. Viral metagenomic analysis was conducted to detect respiratory viral RNA. Steroid responsiveness was measured through changes in gene network expression and spirometric response (FEV1) after triamcinolone administration as part of the Systemic Corticosteroid Response Test. The association between viral presence, gene endotype, and corticosteroid response was evaluated.T1 high and T2 high endotypes were observed in 22% and 35% of participants, respectively, while a smaller group (8.5%) displayed elevated expression in both inflammatory pathways. Individuals with a T2 high profile had more severe disease, including significantly higher blood eosinophil counts (median 394 cells/μL vs 195 cells/μL; P < .01). Administration of intramuscular triamcinolone led to marked downregulation of T2 associated gene networks (mean fold change −0.65; P < .001), whereas T1 associated gene activity was largely unchanged (−0.04; P = .45). Functional improvements in lung function, defined by an increase in forced expiratory volume in 1 second (FEV1) of at least 200 mL, occurred in 36% of patients with a T1 low/T2 high endotype compared with just 13% of those with codominant T1 high/T2 high expression. Respiratory viral transcripts were detected in 24% of samples and were strongly correlated with T1 high gene expression (odds ratio, 14.2; 95% CI, 4.1-48.3; P < .001), implicating subclinical viral carriage in shaping this corticosteroid-refractory phenotype.A distinct subset of patients with asthma exhibit T1 dominant or mixed T1/T2 airway inflammation, likely influenced by ongoing viral activity in the airways. Although corticosteroid therapy effectively targets T2 inflammation, it fails to suppress T1-driven gene expression, which may explain the limited treatment response observed in patients with mixed endotypes. These findings reinforce the clinical relevance of inflammatory profiling and suggest that patients with high T1 activity, especially in the context of chronic viral presence, may benefit from nonsteroidal, targeted interventions aimed at antiviral pathways.This study offers compelling evidence that T1 inflammation, often associated with viral exposure, is prevalent in adult asthma and mediates corticosteroid resistance. Its strengths are the inclusion of transcriptomic and viromic data over multiple time points. Clinically, the findings emphasize that not all severe asthma is T2 driven and that mixed endotypes may require novel therapeutic strategies beyond corticosteroids. Limitations include the adult-only population, and the use of intramuscular corticosteroids, which is not typically standard clinical practice. It would be interesting to see whether comparing children with asthma and healthy children, in whom viral infections are very common, would yield similar patterns. In addition, the detection of viral RNA does not necessarily confirm active infection, raising questions about causality. The study supports the advancement of precision medicine in asthma and underscores the potential need to develop and test antiviral and anti-T1 therapies in appropriately selected patients.

The aim of this study was to screen for inborn errors of immunity (IEIs) within a pediatric critical care population and further evaluate the mortality-related factors.This study included 1203 pediatric patients aged between 1 month and 18 years admitted to the pediatric intensive care unit (PICU) at Antalya Education and Research Hospital (in Turkey) between January 2020 and December 2022. Patients with chronic diseases, ongoing chronic medication regimens, other known comorbidities, traumas, postsurgical cases, poisonings, and preexisting IEI diagnoses were excluded.In this single-center prospective study, a total of 28 warning signs for IEI diagnosis were applied, including 10 per the Jeffery Modell Foundation (JMF) and 18 per literature review. Patients with severe illness requiring intensive care and at least 1 IEI warning sign were evaluated. These patients underwent standardized immunological screening, then those with abnormal findings had an extended immunologic assessment including functional analyses. Genetic analyses were conducted on those with abnormal findings concerning for IEI. Diagnoses of IEI were established using the European Society for Immunodeficiencies criteria and further categorized based on the International Union of Immunological Societies classification.Of the 1203 patients admitted to the PICU, 75 (6.2%) patients had at least 1 IEI warning sign and no exclusionary diagnoses. This study found a 4.3% confirmed IEI prevalence rate in the PICU during the 3-year study period. More than half (51.5%) of these patients presented with sepsis, 36.4% with acute respiratory failure, and 12.1% with neuroinflammatory disorders. The median age was 16 months, and there was a male predominance (60.6%). Consanguinity was present in 66.7% of the patients. History of severe viral infections was the most common IEI warning sign (61%), followed by life-threatening infections (51.7%), sibling/cousin death (25%), and a history of more than 2 episodes of pneumonia per year (22.5%). Only 31% of patients had 2 or more of the JMF warning signs. Regarding types of IEIs identified, nearly half (48.5%) were diagnosed with an immune dysregulation disorder, with the most prominent IEI diagnosis being hemophagocytic lymphohistiocytosis. Combined immunodeficiencies were also commonly identified (24.2%), followed by defects in innate immunity (15.2%) and predominant antibody deficiencies (6.1%). Genetic testing was performed on 78.8% (26/33) of patients with an IEI diagnosis. Among the 33 patients with confirmed IEI, the mortality rate was 58%.Patients with IEI can present critically ill without classic warning signs and have a high mortality rate. This highlights the need for systematic screening to reach early diagnosis and treatment, especially in critically ill children.This study highlights a significant yet underrecognized prevalence of IEI in PICUs. The identification of IEI in nearly 1 in 20 critically ill children and reported high mortality rate of 58% emphasizes the need for earlier screening and detection with targeted immunologic/genetic evaluation. The study also found that only 31% of patients exhibited 2 or more JMF warning signs, suggesting a need for wider criteria, especially in the PICU. Limitations of the study include a single-center study in a country with high consanguinity, thus limiting generalizability. There was a small sample size of only 33 patients with new IEI diagnosis, and data were limited to their hospitalization without long-term follow-up related to mortality. Despite these limitations, this study reinforces that IEIs are more common than traditionally thought and general pediatricians, as well as PICU specialists, have a critical role in early suspicion, diagnosis, and seeking immunology consultation to reduce mortality and long-term morbidity.