Increased mortality in infants with abnormal T-cell receptor excision circles.

BACKGROUND: T-Cell Receptor Excision Circles based newborn screening (TREC-NBS) allows for early detection of T-cell lymphopenia in infants with primary immunodeficiency disorders (PIDD). The utility of abnormal TREC-NBS in infants without PIDD is not well studied. We sought to evaluate the association of abnormal TREC-NBS with mortality. METHODS: 365,207 TREC-NBS from October 2011 to December 2014 were reviewed. 467 newborns had abnormal screens and did not meet the criteria for a PIDD diagnosis. Cases were matched to controls (1:3) based on gestational age, birth weight, neonatal intensive care unit status (NICU), and race. Data were obtained through NBS, birth and death certificates records from the Michigan Department of Health and Human Services (MDHHS) databases. RESULTS: Infants with abnormal TREC-NBS had higher mortality even when PIDD was ruled-out. Transient abnormal TREC-NBS was not associated with higher mortality, but unresolved or late abnormal TREC-NBS was associated with higher mortality. Infants with late abnormal TREC-NBS had severe prematurity, lower birth weight, lower Apgar scores, and higher percentage of congenital anomalies. CONCLUSION: Infants with abnormal TREC-NBS may be at a higher risk of morbidity and mortality and should be carefully followed, especially if discharged home before a repeat screen can be completed. IMPACT: This study explores the risk factors and mortality for newborns with secondary T-cell lymphopenia captured on T-Cell Receptor Excision Circles based newborn screening (TREC-NBS). Abnormal TREC-NBS allows for prompt life-saving interventions for primary immunological conditions such as Severe Combined Immunodeficiency (SCID), but can also be associated with non-immunologic conditions. Unresolved and late abnormal TREC-NBS is associated with higher mortality even without primary immunodeficiency, likely detected in infants with more severe prematurity, lower birth weight, and congenital anomalies. TREC-NBS positive infants with secondary T-cell lymphopenia require special attention and close monitoring.

Anaphylaxis: Long-term management and resources.

Background: Anaphylaxis is an acute life-threatening event that requires emergent diagnosis and treatment. However, focus on prevention of anaphylaxis is essential in reducing anaphylaxis recurrences and associated mortality. Objective: This literature review was aimed to be a comprehensive resource for practicing allergists in managing anaphylaxis in the long term. We discussed the role of the allergist in the long-term outpatient management of anaphylaxis through identifying risk factors, allergen avoidance, prevention of recurrences, and patient education. Methods: A medical literature search that focused on several areas of long-term management of anaphylaxis was conducted. Results: Patients evaluated by an allergist are more likely to have their anaphylaxis trigger identified, to have their underlying mast cell disorder diagnosed, and to receive desensitization or allergen immunotherapy. Allergists can prevent fatal anaphylaxis by preventing and treating anaphylaxis in patients with ischemic heart disease and by optimally treating patients with comorbid asthma. Allergists can offer specific prevention strategies for allergenic trigger and cofactor avoidance. Education should be focused on patients with a higher risk for recurrence of anaphylaxis, such as those patients with a history of severe symptoms or anaphylaxis, with a peanut and/or tree nut trigger, or with a history of asthma, or female gender. Patient counseling involves providing individualized action plans at each visit and discussing proper use, storage, and safety of epinephrine autoinjectors. Multiple doses of epinephrine need to be prescribed to those who are at risk for severe food-induced, venom immunotherapy-related, or venom-induced anaphylaxis. Wording on medical identification products should be reviewed by the allergist. Anaphylaxis resources for health-care providers are summarized in the article. Conclusion: Ongoing education, providing personalized anaphylaxis action plans, reducing risk factors, and avoiding triggers are key to anaphylaxis prevention and long-term management.

Sustained decrease in pediatric asthma emergency visits during the first year of the COVID-19 pandemic.

Background: On January 20, 2020, the first documented case of novel severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) was reported in the United States. The U.S. Centers for Disease Control and Prevention continues to report more morbidity and mortality in adults than in children. Early in Pandemic, there was a concern that patients with asthma would be affected disproportionately from COVID-19, but this was not manifested. It is now recognized that angiotensin-converting enzyme 2 receptors that are used by the coronavirus for infection have low expression in children with atopy that may contribute to decreased infectivity in children who are atopic. There are several early reports of decreased emergency department (ED) visits for children with asthma. The authors previously reported a decrease in pediatric ED visits in the spring of 2020, which correlated with school closure. Objective: To determine if this trend of decreased ED visits for pediatric asthma was sustained throughout the first COVID-19 pandemic year. Methods: ED data from one inner city children's hospital were collected by using standard medical claims codes. Conclusion: We reported a sustained year of decreased ED visits for children with asthma in one pediatric ED in an inner-city hospital; this seemed to be secondary to school closure and decreased exposure to upper respiratory infections.

Are primary care physicians following National Institute of Allergy and Infectious Disease guidelines for the prevention of peanut allergy? A survey-based study.

Background: The 2017 addendum to the National Institute of Allergy and Infectious Diseases (NIAID) guidelines on peanut allergy prevention significantly altered recommendations for patients at risk of developing peanut allergies. It is unknown if primary care physicians are aware of or are following these guidelines. Objective: To assess the knowledge and practice of the NIAID guidelines among primary care physicians. Methods: A survey was developed to assess the knowledge, awareness, and practice behaviors of the NIAID guidelines. It was distributed to pediatric, family medicine, and medicine-pediatric residents and attending physicians at two large academic centers. Responses were analyzed with binary logistic regression. Results: The survey was distributed to 605 providers, with a response rate of 35% (n = 210). The average score was 4.8 of seven questions answered correctly. Of the participants, 53% incorrectly recommended at-home peanut introduction in patients with egg allergy. In addition, 40% of the participants incorrectly believed that the earliest age for peanut introduction was >1 year of age. More than half of the participants were unaware of the new guidelines. On logistic regression, factors associated with adequate knowledge assessment scores were awareness of the guidelines (odds ratio [OR] 2.98 [confidence interval {CI}, 1.34-6.60]), graduation from residency within 5 years (OR 3.60 [95% CI, 1.14-11.35]), and affiliation with the medicine-pediatrics department (OR 4.59 [95% CI, 1.07-19.65]). Conclusion: The primary care providers incorrectly answer one-third of the questions related to the prevention of peanut allergy. Increasing awareness of the 2017 NIAID guidelines may provide an opportunity to improve patient outcomes. There is an urgent need to develop innovative education strategies to publicize these guidelines.

Hyper IgE syndrome-related disease treated with dupilumab: A case report.

Phosphoglucomutase 3 (PGM3) catalyzes the glycosylation of immune system precursor proteins. Its impairment leads to severe infections and other developmental, musculoskeletal, and nervous system defects. We present a case of a 2-month-old female patient with recurrent infections and diffuse eczematous dermatitis recalcitrant to corticosteroids. A next-generation sequencing NGS gene panel for inherited immune dysfunction syndromes revealed multiple variants of unknown significance in key immune regulators, specifically heterozygous mutation c.337C⟩G (p.Pro113Ala) on exon 4 of PGM3 as a novel variant in the PGM3 associated diseases. Off-label use of dupilumab resulted in rapid improvement.

Positive Newborn Screening for Severe Combined Immunodeficiency: What Should the Pediatrician Do?

Severe combined immunodeficiency (SCID) is a group of diseases characterized by low T-cell count and impaired T-cell function, resulting in severe cellular and humoral immune defects. If not diagnosed and treated promptly, infants affected by this condition can develop severe infections which will result in death. Delayed treatment can markedly reduce the survival outcome of infants with SCID. T-cell receptor excision circle (TREC) levels are measured on newborn screening to promptly identify infants with SCID. It is important for primary care providers and pediatricians to understand the approach to managing infants with positive TREC-based newborn screening as they may be the first contact for infants with SCID. Primary care providers should be familiar with providing anticipatory guidance to the family in regard to protective isolation, measures to minimize the risk of infection, and the coordination of care with the SCID coordinating center team of specialists. In this article, we use case-based scenarios to review the principles of TREC-based newborn screening, the genetics and subtypes of SCID, and management for an infant with a positive TREC-based newborn screen.

Non-infectious Pulmonary Complications in Children with Primary Immunodeficiency.

Primary immune deficiency (PID) is a large group of diseases characterized by defective immune function, leading to recurrent infections, and immune dysregulation. Clinical presentations, severity, and complications differ for each disease, based on the components of the immune system that are impacted. When patients with PID present with respiratory symptoms, infections should be initially suspected, investigated, and promptly managed. However, non-infectious complications of PID also frequently occur and can lead to significant morbidity and mortality. They can involve both the upper and lower respiratory systems, resulting in various presentations that mimic infectious diseases. Thus, clinicians should be able to detect these conditions and make an appropriate referral to an immunologist and a pulmonologist for further management. In this article, we use case-based scenarios to review the differential diagnosis, investigation, and multidisciplinary treatment of non-infectious pulmonary complications in patients with primary immune deficiencies.

Management of Anaphylaxis.

The key to managing anaphylaxis is early epinephrine administration. This can improve outcomes and prevent progression to severe and fatal anaphylaxis. Delayed or lack of administration of epinephrine is associated with fatal reactions. Positioning in a recumbent supine position, airway management, and intravenous fluids are essential in its management. Antihistamines and glucocorticosteroids should not be prescribed in place of epinephrine. ß-adrenergic agonists by inhalation are indicated for bronchospasm associated with anaphylaxis despite optimal epinephrine treatment. Long-term management of anaphylaxis includes the identification and avoidance of triggers; identification of cofactors, such as mast cell disorders; patient, parent, and caregiver education, and interventions to reduce allergen sensitivity, such as the use of venom immunotherapy for Hymenoptera hypersensitivity. Long-term management is covered in other articles. Consultation with an allergist/immunologist is recommended when necessary.

Asthma consultations with specialists: what do the pediatricians seek?

"Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma" includes guidelines for referral to an asthma specialist. Because most cases of asthma are managed by primary care physicians, we intended to explore the referral practices of pediatricians managing childhood asthma. This study was designed to identify important considerations by pediatricians while referring a child to an asthma specialist. An electronic survey was sent to 1200 graduated pediatricians enlisted in the Michigan Chapter, American Academy of Pediatrics directory. The questions explored asthma disease characteristics, physician preferences when referring children with asthma, and reasons and barriers for asthma consultations. All responses were collected anonymously. We received 240/1200 (20%) questionnaires. The majority of pediatricians considered referral to a specialist if a child had severe persistent asthma (201/236 [85.2%]) or had a single life-threatening asthma event (188/229 [82.1%]). The top two likely reasons of referral included poor asthma control (200/224 [89.3%]) and unclear diagnosis (139/224 [62.1%]). We found 74/219 (33.8%) preferred consultation to a pediatric pulmonologist when compared with 93/219 (42.5%) allergists. We found the minority of pediatricians "always" recommended referral to a specialist for the following reasons: allergy skin testing (30/222 [13.5%]), possible allergen immunotherapy (54/223 [24.2%]), and spirometry (26/221 [11.8%]). The major barrier for childhood asthma specialist consultations was issues with medical insurance coverage (137/205 [66.8%]). Allergists have to educate primary care providers about the importance of allergen control, role of allergen immunotherapy, and updating current asthma treatment guidelines when treating a child with allergic asthma.

Anaphylaxis in Children and Adolescents.

Anaphylaxis is an acute, potentially life-threatening systemic hypersensitivity reaction. Classically, anaphylaxis is an immunoglobulin (Ig) E-mediated reaction; however, IgG or immune complex complement-related immunologic reactions that lead to degranulation of mast cells can also cause anaphylaxis. Food allergy is the most common cause of anaphylaxis, followed by drugs. Patients with anaphylaxis commonly present with symptoms involving skin or mucous membranes, followed by respiratory and gastrointestinal symptoms. Epinephrine is the drug of choice for treating anaphylaxis. Patients and caregivers should be educated on the use of epinephrine autoinjectors with periodic review of symptoms and emergency action plan for anaphylaxis.

Humoral Immune Deficiencies of Childhood.

The most common primary immune deficiencies are those of the humoral immune system, and most of these present in childhood. The severity of these disorders ranges from transient deficiencies to deficiencies that are associated with a complete loss of ability to make adequate or functional antibodies, and have infectious as well as noninfectious complications. This article reviews, in a case-based discussion, the most common of the humoral immune deficiencies; their presentations, diagnoses, treatments; and, when known, the genetic defects.

Pediatric Inner-City Asthma.

Inner-city children with asthma are known to have high disease mortality and morbidity. Frequently, asthma in this high-risk population is difficult to control and more severe in nature. Several factors, including socioeconomic hardship, ability to access to health care, adherence to medication, exposure to certain allergens, pollution, crowd environment, stress, and infections, play an important role in the pathophysiology of inner-city asthma. Comprehensive control of home allergens and exposure to tobacco smoke, the use of immune based therapies, and school-based asthma programs have shown promising results in asthma control in this population.

Contact Dermatitis in Children.

Contact dermatitis (CD) is commonly encountered in the pediatric population. Allergic and irritant are the two forms of CD and both cause significant clinical problems in children, but they are often underrecognized. The skin lesions in CD may be polymorphic and closely mimic other common pediatric skin diseases. The diagnosis usually requires patch testing after obtaining a detailed history and performing a physical examination. Metals, fragrances, and certain preservatives are the most common causative agents in children. This article discusses the pathophysiology, diagnosis, and management of this common skin condition in the pediatric population. [Pediatr Ann. 2021(5):e198-e205.].

Treatment for Severe Asthma in Children: What About Biologics?

Asthma is the most common pulmonary disease in children age 5 to 17 years. Asthma is characterized by chronic airway inflammation and heterogeneous clinical phenotypes. A small proportion of patients (approximately 5% to 10%) diagnosed with severe asthma are unable to achieve asthma control even with intensive therapy. Severe asthma in children is characterized by poor asthma control, uncontrolled symptoms, poor quality of life, disrupted school-related activities and increased risk of exacerbations, health care use, and morbidities due to asthma. Several new biologic agents targeting the mediators of asthma inflammation that are now approved are likely to improve asthma outcomes in children with severe asthma. This article outlines the various biologic agents currently approved for use in children. [Pediatr Ann. 2021;50(5):e206-e213.].

Approach to Children with Hives.

Urticaria (or hives) is a pruritic and erythematous skin rash. Angioedema commonly occurs with urticaria. The term "chronic urticaria" is used when hives are present for more than 6 weeks. Acute urticaria is common in children, whereas chronic urticaria is rare. Causes of urticaria can be identified in many cases of acute urticaria with a thorough medical history. Laboratory evaluation may be needed to confirm the etiology of acute urticaria. Chronic urticaria is often idiopathic. Clinicians should avoid universal allergy testing for food allergens or aeroallergens in chronic urticaria as it usually does not help in identifying the cause, can lead to false-positive results, and unnecessary avoidance of allergens or foods. Urticarial vasculitis should be considered for lesions that are painful, present for more than 48 hours, leave scars/hyperpigmentation, or present with systemic symptoms such as fever, weight loss, and arthritis. Skin biopsy should be considered for suspected urticarial vasculitis. [Pediatr Ann. 2021(5):e191-e197.].

Allergic Broncho-Pulmonary Aspergillosis.

Allergic broncho-pulmonary aspergillosis (ABPA) is an immunologically mediated lung disease that usually occurs in people with a diagnosis of asthma or cystic fibrosis. It is a noninvasive lung disease caused by colonization of the airways with Aspergillus fumigatus. In people who are susceptible, Aspergillus leads to an exaggerated immune response and ultimately pulmonary inflammation and lung damage. Patients with ABPA typically present with poorly controlled asthma, recurrent pulmonary infiltrates, and bronchiectasis. Diagnosis of ABPA is established based on a combination of clinical manifestations as well as laboratory and radiological evaluations. Delay in diagnosis can result in airway destruction and pulmonary fibrosis, which may result in significant morbidity and mortality. This article discusses the clinical characteristics, diagnosis, and management of patients with ABPA. It aims to serve as a tool for pediatricians to aid in early recognition of this debilitating disease and consider referral, facilitating early diagnosis and treatment. [Pediatr Ann. 2021;50(5):e214-e221.].

New Concepts and Technological Resources in Patient Education and Asthma Self-Management.

Asthma is a chronic disease that is associated with significant morbidity and mortality. In general, the use of technology resources or electronic health (e-health) has been shown to have beneficial effects on patients with asthma. E-health can impact a broad section of patients and can be cost-effective and associated with high patient satisfaction. E-health may enable remote delivery of care, as well as timely access to health care, which are some of the common challenges faced by patients with asthma. Web-based asthma self-management systems have been found to improve quality of life, self-reported asthma symptoms, lung function, reduction in asthma symptoms/exacerbations, and self-reported adherence for adults. Social media is commonly being used as a platform to disseminate information on asthma to increase public awareness. It can facilitate asthma self-management in a patient friendly manner and has shown to improve asthma control test scores as well as self-esteem. Text massages reminders can increase awareness regarding asthma treatment and control, thus potentially can improve adherence to medications and asthma outcome. Mobile health applications can support asthma self-management, improve a patient's quality of life, promote medication adherence, and potentially reduce the overall costs for asthma care. Inhaler trackers have shown to be beneficial to asthma outcome in various populations by improving adherence to asthma medications. Barriers such as physician financial reimbursement as well as licensing for rendering tele-healthcare services are important concerns. Other limitations of using technology resources in health care are related to liability, professionalism, and ethical issues such as breach of patient confidentiality and privacy. Additionally, there may be less face-to-face interaction and care of the patient when e-health is used.

Elevated Glycated Hemoglobin Is Associated with Reduced Antibody Responses to Vaccinations in Children.

Background: Childhood obesity is a major health concern, and it is associated with an increased risk of infectious morbidity. Previous studies found a decrease in protective antibody titers in obese adults after hepatitis B, influenza, and tetanus vaccination. Objective: We aimed at determining whether obesity or abnormal hemoglobin A1C (HBA1C) levels are associated with altered antibody responses in children. Methods: Children (8-18 years) who have completed routine childhood immunization were recruited. Serum samples were tested by the enzyme-linked immunosorbent assay method for antibody levels to Diphtheria, Tetanus, Haemophilus influenzae type B (HIB), and Streptococcus pneumoniae, along with serum HBA1C levels. An electronic medical record review on the frequency of emergency visits for infection was conducted. Spearman rank correlation, Fisher-exact, and Pearson's Chi-squared tests were used for statistical analysis. Results: There was an overall negative correlation between body mass index (BMI) percentile and the majority of pneumococcal subtypes, Diphtheria and Tetanus titers, although not statistically significant. There was a statistically significant negative correlation between HBA1C level and the S. pneumoniae serotype P9N (P = 0.037), P4 (P = 0.017), P12 (P = 0.023), P19F (P = 0.050), and HIB (P = 0.001). On average, individuals with elevated HBA1C levels had more frequent emergency room visits for infection (P = 0.029) and more viral infections (P = 0.023) as compared with children with normal HBA1C. Conclusion: Children with higher HBA1C levels were more likely to have lower pneumococcal and HIB titers and increased rates of emergency room visits for infection in a prospective, population-based cohort study. Although not statistically significant, there was an overall negative correlation between BMI percentile and titers for routine childhood vaccines.

Anaphylaxis in Children and Adolescents.

Anaphylaxis is an acute, potentially life-threatening systemic hypersensitivity reaction. Classically, anaphylaxis is an immunoglobulin (Ig) E-mediated reaction; however, IgG or immune complex complement-related immunologic reactions that lead to degranulation of mast cells can also cause anaphylaxis. Food allergy is the most common cause of anaphylaxis, followed by drugs. Patients with anaphylaxis commonly present with symptoms involving skin or mucous membranes, followed by respiratory and gastrointestinal symptoms. Epinephrine is the drug of choice for treating anaphylaxis. Patients and caregivers should be educated on the use of epinephrine autoinjectors with periodic review of symptoms and emergency action plan for anaphylaxis.

Humoral Immune Deficiencies of Childhood.

The most common primary immune deficiencies are those of the humoral immune system, and most of these present in childhood. The severity of these disorders ranges from transient deficiencies to deficiencies that are associated with a complete loss of ability to make adequate or functional antibodies, and have infectious as well as noninfectious complications. This article reviews, in a case-based discussion, the most common of the humoral immune deficiencies; their presentations, diagnoses, treatments; and, when known, the genetic defects.