Case Report: Insulin hypersensitivity in youth with type 1 diabetes.

Objective: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D). Methods: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic. Results: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and insulin pump therapy. Multidisciplinary care involving pediatric endocrinology and allergy/immunology utilizing trials of many adjunct therapies yielded minimal improvement. Despite the use of various treatments, including antihistamines, topical therapies, immunosuppressant medications, desensitization trials, and intravenous immune globulin, cutaneous reactions, elevated hemoglobin A1c levels, and negative effects on quality of life remain persistent challenges. One patient became one of the youngest pancreas transplant recipients in the world at age 12 years due to uncontrollable symptoms and intolerable adverse effects of attempted therapies. Conclusion: Although rare, insulin hypersensitivity reactions negatively affect glycemic control and quality of life. These cases demonstrate the varying severity and presentation of insulin hypersensitivity reactions along with the limited success of various treatment approaches. Given the life-sustaining nature of insulin therapy, further studies are needed to better understand the underlying pathophysiology of insulin hypersensitivity and to develop targeted treatment approaches.

Eosinophilic Esophagitis: The Role of Environmental Exposures.

Eosinophilic esophagitis (EoE) is a chronic, non-IgE immune-mediated reaction characterized by eosinophilic infiltration leading to esophageal dysfunction, inflammation, and potential for fibrotic remodeling. Although food allergens are generally considered the leading trigger for EoE, emerging evidence suggests that modifiable environmental factors may also play a role in the pathogenesis of EoE. This article discusses the latest data regarding the role of the exposome, microbiome, and environmental allergens on the development and ongoing inflammation of EoE, focusing on the last 10 years of relevant studies.

Seafood graded oral food challenge outcomes in a pediatric tertiary care center.

BACKGROUND: There are sparse data regarding the predictors of positive oral food challenges and reaction severity for seafood in children. OBJECTIVE: Identify clinical characteristics in children with seafood allergy who were most likely to experience a negative oral food challenge (OFC). METHODS: A retrospective chart review was performed for children who had a graded OFC to seafood at a pediatric tertiary care center from 2008 through 2019. RESULTS: Sixty-three (60% male; average age 8 years; range 1-21 years) OFCs were performed, of which 21 were fish and 42 were shellfish. There were 10 (16%) positive OFCs and positive OFC rate was similar between fish (19%) and shellfish (14%). Forty-three children who underwent OFC had a reported history of IgE-mediated symptoms. Five of six children who had a history of anaphylaxis had a negative OFC. There was no difference in positive OFCs due to age, history of atopy, or initial allergic reaction history. The clinical characteristics of the positive OFCs were similar between fish and shellfish. A positive skin prick test to fish or shellfish did not increase the risk of a positive OFC. While the positive OFC rate did not differ for the shellfish food-specific IgE (FSIgE) level, there was a significant difference for fish (median <0.34 kUA/L vs. 1.63 kUA/L for pass and fail, respectively; P = 0.023). CONCLUSION: A retrospective study of OFCs to seafood showed that the rate of a positive OFC was low. While seafood allergy is thought to be rarely outgrown, children who have a low FsIgE and/or skin testing can successfully tolerate seafood.

Potential Strategies and Targets for the Prevention of Pediatric Asthma.

Asthma is the most common chronic disease of childhood in developed countries, with a continually increasing prevalence. The paradigm of asthma control is shifting from disease management to primary prevention, and the modification of numerous host and external factors have been proposed as methods to prevent recurrent wheeze and asthma in children, some with promising preliminary results. This article reviews potential asthma prevention strategies and identifies future areas of research.

Management of acute loss of asthma control: yellow zone strategies.

PURPOSE OF REVIEW: Asthma exacerbations are associated with a significant burden to both the individual patient and to the healthcare system. Patients often step-up home therapies in response to increased asthma symptoms, and the asthma action plan was created to empower patients to self-manage their asthma care. The yellow (intermediate) zone of the asthma action plan is frequently poorly defined, and current Expert Panel Report 3 guideline recommendations are not effective for all patients. This article reviews the evidence behind various recommended yellow zone intervention strategies. RECENT FINDINGS: There are many potential methods of delivering yellow zone therapy, and recent studies have assessed preventive efficacy of a scheduled increase in controller medication(s), reliever medication(s), or a symptom-driven combination of both. The literature suggests that, in certain asthma subpopulations, some methods may be more efficacious than others. SUMMARY: Multiple yellow zone approaches may be beneficial, and the yellow zone is not a 'one size fits all' narrative.

The Role of the Environment in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease with incompletely understood pathogenesis. Though disease manifestations were initially ascribed to a delayed reaction to food allergens, emerging evidence suggests that modifiable host factors and environmental allergen exposure may also play critical roles in the pathogenesis and ongoing manifestations of EoE. As with other atopic diseases, lack of early-life exposure to microbial pathogens leads to an immune tolerance defect and reprograms the commensal gut microflora toward a type 2 T helper (Th2) phenotype; the esophageal microbiota, a rich environment consisting of diverse bacterial species, is greatly altered by inflammation. Although multiple early life microbiome-altering factors are associated with EoE development, no causative, direct relationships have been identified. Interestingly, large, cross-sectional analyses of several populations identify an inverse relationship between Helicobacter pylori presence and EoE, likely via virulence factors that downregulate Th2 inflammation, though causality has not been proven. In regard to environmental allergens, some studies support seasonal variation in EoE diagnosis and flares, and EoE can be generated after a large, identifiable aeroallergen exposure. Examples include mouse models of intranasal Aspergillus dosing and following initiation of oral immunotherapy to foods or environmental allergens. Conversely, treatment of allergic rhinoconjunctivitis may improve EoE symptoms, though data is limited to case reports and small series. Unfortunately, biologic therapies for atopic conditions have failed to improve EoE symptoms despite improvement in esophageal eosinophil count, though dupilumab shows promise in ongoing studies. Overall, this chapter shows that EoE pathogenesis is likely multifactorial, and the environment is a key component in our understanding of EoE.

Patient-Centered Outcomes in Food Allergy.

PURPOSE OF REVIEW: Food allergy prevalence is increasing very rapidly, causing a significant disease burden. The threat of severe allergic reactions occurring unexpectedly and in settings that are not equipped to recognize and treat anaphylaxis is a constant source of worry for individuals and families with food allergies. Inadequate knowledge and understanding in the community significantly impairs the overall quality of life of these individuals and families. Additionally, families face challenges in finding and affording appropriate allergen-free foods. RECENT FINDINGS: Advancements have been made in understanding the impact of food allergies on patient-centered outcomes such as quality of life and economic impact, and attempts have been made to develop tools to assess patient-centered variables. Innovative national and regional initiatives are helping to spread awareness of the disease condition and to create resources, including access to allergen-free foods. While there is a growing momentum toward recognition of food allergic disorders as a condition that profoundly impacts activities of daily living, greater effort needs to be expounded to develop validated tools and interventions that can adequately address these issues.

Biological Therapies of Immunologic Diseases: Strategies for Immunologic Interventions.

The immune system possesses a vast number of potential targets for therapeutic intervention. Although therapies for many pathways have been pursued, only few have yielded significant success. Hindrances in altering biologic pathways include the potential for unwanted downstream effects, ineffectiveness owing to biological redundancy, recognition of a therapeutic molecule as foreign by the body's innate immune system, and the risks of subsequent malignancy and/or autoimmunity. This article covers currently available biotherapeutic agent classes as well as potential direction for future therapy.

Association of tree nut and coconut sensitizations.

BACKGROUND: Coconut (Cocos nucifera), despite being a drupe, was added to the US Food and Drug Administration list of tree nuts in 2006, causing potential confusion regarding the prevalence of coconut allergy among tree nut allergic patients. OBJECTIVE: To determine whether sensitization to tree nuts is associated with increased odds of coconut sensitization. METHODS: A single-center retrospective analysis of serum specific IgE levels to coconut, tree nuts (almond, Brazil nut, cashew, chestnut, hazelnut, macadamia, pecan, pistachio, and walnut), and controls (milk and peanut) was performed using deidentified data from January 2000 to August 2012. Spearman correlation (ρ) between coconut and each tree nut was determined, followed by hierarchical clustering. Sensitization was defined as a nut specific IgE level of 0.35 kU/L or higher. Unadjusted and adjusted associations between coconut and tree nut sensitization were tested by logistic regression. RESULTS: Of 298 coconut IgE values, 90 (30%) were considered positive results, with a mean (SD) of 1.70 (8.28) kU/L. Macadamia had the strongest correlation (ρ = 0.77), whereas most other tree nuts had significant (P < .05) but low correlation (ρ < 0.5) with coconut. The adjusted odds ratio between coconut and macadamia was 7.39 (95% confidence interval, 2.60-21.02; P < .001) and 5.32 (95% confidence interval, 2.18-12.95; P < .001) between coconut and almond, with other nuts not being statistically significant. CONCLUSION: Our findings suggest that although sensitization to most tree nuts appears to correlate with coconut, this is largely explained by sensitization to almond and macadamia. This finding has not previously been reported in the literature. Further study correlating these results with clinical symptoms is planned.

Pharmacogenomics in childhood rheumatic disorders: a foundation for future individualized therapy.

Investigating the effect of genotype on drug response in children is an evolving field, with many challenges, but there is great potential to optimize safe and effective use of drugs in children. An exponential increase in available medications for use in children with rheumatic disease has opened seemingly endless genotype/phenotype relationships to explore, but challenges inherent in studying rare diseases and the often overlooked role of ontogeny contribute to limitations in pharmacogenomic studies in this population. With careful recognition of the importance of development, improved phenotyping with the incorporation of biomarkers, and expanding collaborative efforts on a national and even international scale, the field of pediatric rheumatology has the opportunity to strategically study the new therapeutic armamentarium available and provide individualized/personalized safe and effective therapies to our population of patients.