Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Development and acceptability of a decision-aid for food allergy Oral immunotherapy in children.

BACKGROUND: Limited decision-support tools are available to help shared decision-making (SDM) regarding food oral immunotherapy (OIT) initiation. No current tool covers all foods, forms, and pediatric ages for which OIT is offered. METHODS: In compliance with International Patient Decision Aid Standards criteria, this pediatric decision-aid comparing OIT versus avoidance was developed in three stages. Nested qualitative data assessing OIT decisional needs were supplemented with evidence-synthesis from the OIT literature to create the prototype decision-aid content. This underwent iterative development with food allergy experts and patient advocacy stakeholders until unanimous consensus was reached regarding content, bias, readability, and utility in making a choice. Lastly, the tool underwent validated assessment of decisional acceptability, decisional conflict, and decisional self-efficacy. RESULTS: The decision-aid underwent 5 iterations, resulting in a 4-page written aid (Flesch-Kincaid reading level 6.1) explaining therapy choices, risks and benefits, providing self-rating for attribute importance for the options and self-assessment regarding how adequate the information was in decision-making. A total of n = 135 caregivers of food-allergic children assessed the decision-aid, noting good acceptability, high decisional self-efficacy (mean score 85.9/100) and low decisional conflict (mean score 20.9/100). Information content was rated adequate and sufficient, the therapy choices wording balanced, and presented without bias for a "best choice." Lower decisional conflict was associated with caregiver-reported anaphylaxis. CONCLUSIONS: This first pediatric OIT decision-aid, agnostic to product, allergen, and age has good acceptability, limited bias, and is associated with low decisional conflict and high decisional self-efficacy. It supports SDM in navigating the decision to start OIT or continue allergen avoidance.

Topical corticosteroids for hives and itch (urticaria): Systematic review and Bayesian meta-analysis of randomized trials.

BACKGROUND: Topical corticosteroids are widely used as a treatment for itch and wheals (urticaria), but their benefits and harms are unclear. OBJECTIVE: To systematically synthesize the benefits and harms of topical corticosteroids for the treatment of urticaria. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception to March 23, 2024, for randomized trials comparing topical corticosteroids with placebo for patients with urticaria (either chronic spontaneous or inducible urticaria or acute urticaria elicited from skin/intradermal allergy testing). Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects meta-analyses addressed urticaria severity, itch severity (numeric rating scale; range 0-10; higher is worse), and adverse events. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed certainty of evidence ratings. PROSPERO registration: CRD42023455182. RESULTS: A total of 19 randomized controlled trials enrolled 379 participants with a median of mean age of 30.1 (range 21.1-44.0) years. Compared with placebo, topical corticosteroids may reduce wheal size (ratio of means 0.47, 95% CI 0.38-0.59; low certainty) and itch severity (mean difference -1.30, 95% CI -5.07 to 2.46; very low certainty). Topical corticosteroids result in little to no difference in overall adverse events (94 fewer patients per 1000, 95% credible intervals 172 fewer to 12 more; high certainty). CONCLUSION: Compared with placebo, topical corticosteroids may result in a reduction of wheal size and little to no difference in overall adverse events. Topical corticosteroids may reduce itch severity, but the evidence is very uncertain. Future large, randomized trials addressing the use of topical corticosteroids would further support optimal urticaria management.

"No room for error": a qualitative interview study of experiences with health insurance coverage loss and COVID-19 pandemic relief policies among people with asthma.

OBJECTIVES: The COVID-19 pandemic led to unemployment and associated health insurance loss, prompting an unprecedented adoption of emergency policies, including economic relief efforts and health insurance coverage expansion. We sought to understand pandemic-related challenges for people with asthma and how emergency policies served families facing both chronic disease management and health insurance loss. STUDY DESIGN: Qualitative interview study. METHODS: In 2021, we conducted semi-structured telephone interviews with 21 adults who had asthma and lost employment and employer-sponsored health insurance coverage during the COVID-19 pandemic. We used thematic analysis to assess how health and economic policies affected participants' ability to access care and manage their asthma. RESULTS: Participants reported reduced access to care, as well as worry about heightened susceptibility to COVID-19 due to their asthma. While insurance loss exacerbated these challenges, participants indicated that economic relief efforts, including direct stimulus payments, helped them afford needed asthma care. Participants were more critical of enhancements to existing coverage policies such as the Affordable Care Act (ACA) Marketplace and Consolidated Omnibus Budget Reconciliation Act (COBRA) due to difficulty understanding, accessing, and affording such coverage. CONCLUSIONS: Our findings underscore that people affected by asthma and health insurance loss benefit from policies that provide flexible and easy-to-use assistance, such as direct payments, for meeting the diverse challenges posed by living with a chronic disease. Although policies that expand health insurance coverage are critical, more attention is needed to help people with chronic conditions access these programs in a timely way.

2024 Public Health Actions to Reduce the Burden of Asthma: Influenza and COVID-19 Vaccination Uptake Among People with Asthma.

This study sought to identify COVID-19 and influenza vaccination rates and barriers among people with asthma. The Asthma and Allergy Foundation of America (AAFA) conducted an online survey from April to May in 2022 among a convenience sample of 350 individuals with asthma. Most survey respondents reported that they had received an influenza vaccine for the 2021-2022 flu season (77%) and at least 1 dose of a COVID-19 vaccine (87%). Age, gender, race and ethnicity, and household income were significantly associated with influenza vaccination. Age and urban-rural classification were associated with COVID-19 vaccination. Access issues were not commonly reported as vaccination barriers, highlighting educational opportunities.

Prenatal reduction of E14.5 embryonically fate-mapped pyramidal neurons in a mouse model of autism.

Although several observations suggest that the constitutive biological, genetic or physiological changes leading to autism spectrum disorders (ASD) start in utero, their early impact on the number and density of neurons in the brain remains unknown. Using genetic fate mapping associated with the immunollabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) clearing method we identified and counted a selective population of neocortical and hippocampal pyramidal neurons in the in utero valproate (VPA) mouse model of autism. We report that 1 day before birth, the number of pyramidal neurons born at E14.5 in the neocortex and hippocampus of VPA mice is smaller than in age-matched controls. VPA also induced a reduction of the neocortical-but not hippocampal-volume 1 day before birth. Interestingly, VPA mice present an increase in both neocortical and hippocampal volumes 2 days after birth compared with controls. These results suggest that the VPA-exposed hippocampus and neocortex differ substantially from controls during the highly complex perinatal period, and specially 1 day before birth, reflecting the early pathogenesis of ASD.

Asthma care during COVID-19: differences in attitudes and expectations between physicians and patients.

OBJECTIVE: The aim of this study was to explore differences in attitudes, behaviors and expectations related to COVID-19 between physicians and patients with asthma. METHODS: An anonymous survey was distributed through email and social media to adult patients with asthma during a three-week period in April-May 2020. A separate survey was sent to physicians. The surveys asked about demographic information, specific challenges and concerns due to COVID-19, and attitudes/behaviors during this time. RESULTS: A total of 1171 patients and 225 physicians completed the surveys. Overall, patients with asthma and physicians had large differences in expectations related to COVID-19. Patients were more likely than physicians to believe that individuals with asthma are at a higher risk to get COVID-19 (37.5% vs. 12.0%, p < 0.001), have increased anxiety due to COVID-19 (79.6% vs 70.0%, p = 0.002), and should not go to work (62.7% vs 11.9%, p < 0.001). Neither patients nor physicians felt confident they could distinguish COVID-19 symptoms from asthma (61.2% and 74.5% did not feel confident, respectively). Patients with severe asthma were significantly more impacted by the pandemic (e.g., became unemployed [OR 2.15], had difficulty getting asthma medications [OR 2.37]) compared to those with nonsevere asthma. CONCLUSION: Patients with asthma and their physicians have markedly different attitudes and opinions regarding care during the COVID-19 pandemic. Such differences have important implications when providing patient-centered care.Supplemental data for this article can be accessed at publisher's website.

Food allergy treatment value: Child caregiver and patient perspectives.

BACKGROUND: Food allergy is a major health problem that significantly impacts quality of life (QoL). There is growing focus to evaluate food allergy-related QoL and treatment options' value beyond the clinical effectiveness perspective by engaging patients and caregivers. We aimed to identify and prioritize outcomes important to food allergy parents of children and patients allergic to milk, egg, and/or peanut, to guide comparative effectiveness research (CER) that focuses on evaluating food allergy treatment decisions. METHODS: We conducted a modified 3-round Delphi study to identify and derive consensus on priority treatment outcomes for parents of children and adult patients with diagnosed allergies to at least one of three major allergenic foods (milk, egg, and peanut) from across the United States. RESULTS: Round 1 yielded 44 statements for round 2, and 39 statements reached the agreement level for round 3 ranking. Statements were organized under 4 sections: 1) food allergy problems, 2) treatment experiences, 3) important treatment outcomes, and 4) value of different treatment options. CONCLUSION: Food allergy parents and patients face several social, psychological, medical, healthcare, financial, food selection, and awareness challenges. The areas of consensus on important treatment outcomes revealed shared priority for reducing the risk of potentially fatal allergic reactions and having reliable treatments. The most valued treatment options reflect hope for permanent cure and fear of serious allergic reactions.

Perspectives on Living with Chronic Spontaneous Urticaria: From Onset through Diagnosis and Disease Management in the US.

Chronic spontaneous urticaria is challenging to manage and substantially affects quality of life. This US, non-interventional qualitative study examined patients' clinical journeys and emotional burden from symptom onset through disease management. Chronic spontaneous urticaria patients participated in interviews and completed diaries focusing on disease and treatment history/perspectives, impact on personal/family life, and relationships with physicians/other healthcare providers. Physicians were interviewed about their views on disease management and patient care. Twenty-five patients, previously or currently receiving chronic spontaneous urticaria treatment(s), and 12 physicians participated. Key stages following symptom onset were identified: Crisis (associated with feelings of torment/disorientation/shock); Searching for answers (puzzlement/frustration/anxiety); Diagnosis (relief/satisfaction/fear/isolation); and Disease management (frustration/hope/powerlessness). Findings revealed patients' perceptions and experiences of chronic spontaneous urticaria, including living with a 'skinemy', experiencing their 'own personal hell' and feeling 'like an experiment'. Awareness of unmet needs in patient care/management identified in this study may ultimately improve patient support and enhance physicians' understanding of disease burden.

Enhanced Glutamatergic Currents at Birth in Shank3 KO Mice.

Autism spectrum disorders (ASD) are neurodevelopmental disorders induced by genetic and environmental factors. In our recent studies, we showed that the GABA developmental shifts during delivery and the second postnatal week are abolished in two rodent models of ASD. Maternal treatment around birth with bumetanide restored the GABA developmental sequence and attenuated the autism pathogenesis in offspring. Clinical trials conducted in parallel confirmed the usefulness of bumetanide treatment to attenuate the symptoms in children with ASD. Collectively, these observations suggest that an alteration of the GABA developmental sequence is a hallmark of ASD. Here, we investigated whether similar alterations occur in the Shank3 mouse model of ASD. We report that in CA3 pyramidal neurons, the driving force and inhibitory action of GABA are not different in naïve and Shank3-mutant age-matched animals at birth and during the second postnatal week. In contrast, the frequency of spontaneous excitatory postsynaptic currents is already enhanced at birth and persists through postnatal day 15. Therefore, in CA3 pyramidal neurons of Shank3-mutant mice, glutamatergic but not GABAergic activity is affected at early developmental stages, hence reflecting the heterogeneity of mechanisms underlying the pathogenesis of ASD.

Factors Associated With Epinephrine Use in the Treatment of Anaphylaxis in Infants and Toddlers.

BACKGROUND: Undertreatment of anaphylaxis with epinephrine continues to be an unmet need and is a particular challenge among infants and toddlers. OBJECTIVE: To address this gap by identifying barriers and solutions to appropriate and timely administration of epinephrine. METHODS: We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when younger than 36 months. Outcomes of interest included epinephrine use in community and health care settings to treat probable anaphylaxis. RESULTS: Of 264 probable anaphylaxis cases, 39% of infants (aged <12 months) and 61% of toddlers (aged 12-35 months) received epinephrine at any time during the child's most severe allergic reaction (P = .001). A previous diagnosis of a food allergy was reported in 62% of cases where epinephrine was used compared with 26% of cases where epinephrine was not used (P < .001). In children with a previous diagnosis of a food allergy, epinephrine was used in 89% of those who were prescribed an anaphylaxis action plan compared with 50% of those without a plan (P = .001). The adjusted odds ratio for the association between having an anaphylaxis action plan and epinephrine use in cases of probable anaphylaxis was 5.39 (95% confidence interval, 2.18-13.30). CONCLUSIONS: Epinephrine use at any time (including in health care settings) during probable anaphylaxis is more likely in infants and toddlers with a previously diagnosed food allergy than those without diagnosis. The provision of an anaphylaxis action plan is also associated with increased epinephrine use during probable anaphylaxis in this population.

Efficacy and Safety of Systemic Corticosteroids for Urticaria: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear. OBJECTIVE: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids. METHODS: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach. RESULTS: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty). CONCLUSIONS: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more.

Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy.

Alterations in the balance of K-Na-2Cl cotransporter (NKCC1) and Na-Cl cotransporter (KCC2) activity may cause depolarizing effect of γ-aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. NKCC1 facilitates accumulation of chloride inside neurons and favors depolarizing responses to GABA. In the current pilot study we provide the first documented look at efficacy of bumetanide, a specific NKCC1 antagonist, on reduction of seizure frequency in adult patients with temporal lobe epilepsy. According to our results, seizure frequency was reduced considerably in these patients. Furthermore, epileptiform discharges decreased in two of our patients. If the efficacy of bumetanide is proven in large scale studies, it can be used as a supplemental therapy in temporal lobe epilepsy.

The effect of tiagabine on physical development and neurological reflexes and their relationship with the γ-aminobutyric acid switch in the rat cerebral cortex during developmental stages.

In the present study, we focused on γ-aminobutyric acid (GABA) signaling through the γ-aminobutyric acid transporter (GAT) in the developing rat cerebral cortex. Tiagabine was used as a GAT inhibitor. The offspring received injections from birth until postnatal day 21 intraperitoneally. Physical development and neurological reflexes were assessed daily. Tiagabine did not influence body weight, the onset and completion of incisor eruption, or the time to appearance of cliff avoidance. However, the onset and completion of eye opening, ear unfolding, and fur growth occurred earlier in treated pups. Further, the slanted board test and righting reflex showed accelerated development (i.e. decreased time to criterion) when compared with the control group. To determine whether the obtained effects are related to the GABA switch, we examined the protein and mRNA expression of the K(+)-Cl(-) cotransporter KCC2 using western blotting and RT-PCR, respectively. Downregulation of KCC2 mRNA and protein levels was observed when GAT was inhibited. The results may indicate a role of GAT in the neurobehavioral changes that accompany the developmental switch in GABA function.

The early excitatory action of striatal cholinergic-GABAergic microcircuits conditions the subsequent GABA inhibitory shift.

Cholinergic interneurons of the striatum play a role in action selection and associative learning by activating local GABAergic inhibitory microcircuits. We investigated whether cholinergic-GABAergic microcircuits function differently and fulfill a different role during early postnatal development, when GABAA actions are not inhibitory and mice pups do not walk. We focused our study mainly on dual cholinergic/GABAergic interneurons (CGINs). We report that morphological and intrinsic electrophysiological properties of CGINs rapidly develop during the first post-natal week. At this stage, CGINs are excited by the activation of GABAA receptors or GABAergic synaptic inputs, respond to cortical stimulation by a long excitation and are linked by polysynaptic excitations. All these excitations are replaced by inhibitions at P12-P15. Early chronic treatment with the NKCC1 antagonist bumetanide to evoke premature GABAergic inhibitions from P4 to P8, prevented the GABA polarity shift and corticostriatal pause response at control postnatal days. We propose that early excitatory cholinergic-GABAergic microcircuits are instrumental in the maturation of GABAergic inhibition.

Disparities in Lupus and the Role of Social Determinants of Health: Current State of Knowledge and Directions for Future Research.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. The complex relationships between race and ethnicity and social determinants of health (SDOH) in influencing SLE and its course are increasingly appreciated. Multiple SDOH have been strongly associated with lupus incidence and outcomes and contribute to health disparities in lupus. Measures of socioeconomic status, including economic instability, poverty, unemployment, and food insecurity, as well as features of the neighborhood and built environment, including lack of safe and affordable housing, crime, stress, racial segregation, and discrimination, are associated with race and ethnicity in the US and are risk factors for poor outcomes in lupus. In this scientific statement, we aimed to summarize current evidence on the role of SDOH in relation to racial and ethnic disparities in SLE and SLE outcomes, primarily as experienced in the U.S. Lupus Foundation of America's Health Disparities Advisory Panel, comprising 10 health disparity experts, including academic researchers and patients, who met 12 times over the course of 18 months in assembling and reviewing the data for this study. Sources included articles published from 2011 to 2023 in PubMed, Centers for Disease Control and Prevention data, and bibliographies and recommendations. Search terms included lupus, race, ethnicity, and SDOH domains. Data were extracted and synthesized into this scientific statement. Poorer neighborhoods correlate with increased damage, reduced care, and stress-induced lupus flares. Large disparities in health care affordability, accessibility, and acceptability exist in the US, varying by region, insurance status, and racial and minority groups. Preliminary interventions targeted social support, depression, and shared-decision-making, but more research and intervention implementation and evaluation are needed. Disparities in lupus across racial and ethnic groups in the US are driven by SDOH, some of which are more easily remediable than others. A multidimensional and multidisciplinary approach involving various stakeholder groups is needed to address these complex challenges, address these diminish disparities, and improve outcomes.

The Multidimensional Burden of Atopic Dermatitis Among Adults: Results From a Large National Survey.

Importance: Atopic dermatitis (AD) is long term and burdensome. Studies investigating disease burden in adults are limited in scope with gaps in understanding of the adult patient lived experience. Objective: To describe the multidimensional burden of AD among mainly US adults. Design, Setting, and Participants: This survey study for an externally led patient-focused drug development meeting with the US Food and Drug Administration on adult patients with AD was conducted between August 1, 2019, and October 11, 2019. Data were analyzed betwean March 26, 2021, and June 29, 2021. Main Outcomes and Measures: We used multivariable ordinal regression to assess associations between demographic and clinical variables and patient-reported overall AD impact scores (ordinal scale from 1 [no impact] to 5 [significant impact]). Results: Among 1065 survey respondents, 114 (11%) were aged 18 to 24 years, 235 (22%) were 25 to 34 years, 242 (23%) were 35 to 50 years, 288 (27%) were 51 to 64 years, and 186 (17%) were aged 65 years or older; 881 (83%) were women. Four hundred eighty-nine (46%) participants reported low-moderate AD impact scores (2-3), 544 (51%) reported high-significant impact scores (4-5), whereas 32 (3%) reported no association of AD with disease burden (impact score, 1). Variables strongly associated with overall impact scores were current AD severity (moderate: OR, 4.13; 95% CI, 2.94-5.79; severe: OR, 13.63; 95% CI, 8.65-21.50 vs mild), and time spent managing AD (11-20 hours: OR, 2.67; 95% CI, 1.77-4.03, ≥21 hours: OR, 5.34; 95% CI, 3.22-8.85, vs <5 hours). Conclusions and Relevance: In this survey study, AD severity and time spent managing symptoms showed the strongest associations with disease burden. This analysis highlights the multidimensional burden of AD in adults and emphasizes the need for more effective treatment strategies that reduce the time patients spend managing their AD.

Caregiver-Reported Presentation of Severe Food-Induced Allergic Reactions in Infants and Toddlers.

BACKGROUND: Recognizing anaphylaxis in infants and toddlers can be challenging for health care providers and caregivers, and current diagnostic criteria and anaphylaxis action plans do not specifically address this younger population. OBJECTIVE: To describe symptoms and signs observed by primary caregivers of infants and toddlers during severe food-induced allergic reactions. METHODS: We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when less than 36 months of age. Respondents who were present during the child's most severe reaction were asked to report symptoms and signs observed. The survey asked about infant- and toddler-specific symptoms and signs in lay language for caregivers. Data were compared with patient-reported data from past studies to identify distinct patterns among the younger population. RESULTS: The survey was completed for 374 children (193 infants, 181 toddlers). The most common symptoms and signs reported were skin reactions (90%), facial and extremity swelling (59%), gastrointestinal issues (51%), and coughing/wheezing (45%). Infants (aged <12 months) more frequently experienced skin reactions, skin mottling, and ear pulling/scratching or putting fingers in ears, as compared with toddlers (aged 12-35 months). Toddlers experienced throat itching and coughing/wheezing more frequently than infants. CONCLUSIONS: Anaphylaxis presentation demonstrates similarities and differences in infants and toddlers. Modifying the terminology used in the current criteria allowed for reporting of symptoms and signs of anaphylaxis that are more common in infants and toddlers. Diagnostic criteria, clinical guidelines, and anaphylaxis action plans may be enhanced to address this young, often nonverbal, population.