Incidence and management of the main serious adverse events reported after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause-effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, and transverse myelitis reported in the context of COVID-19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post-vaccination. Regardless of the ongoing discussion about the safety of COVID-19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.

Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Food allergy in the World Health Organization's International Classification of Diseases (ICD)-11.

There are increasing global data regarding the prevalence of food allergy and food-induced anaphylaxis. However, knowledge in morbidity and mortality epidemiological data is still not optimal, and international comparable standards remain poorly accessed. This information could in turn support better clinical practice and possibly prevent future severe reactions and avoidable fatalities. The International Classification of Diseases (ICD) is the standard diagnostic tool used for epidemiology, health management, and clinical purposes supported by the World Health Organization (WHO). It is also used to determine health care payment and reimbursement of providers and health care services in hospitals. Thanks to the academic and technical efforts under the ALLERGY in ICD-11 initiative the pioneer "Allergy and hypersensitivity conditions" section has been built under the "Disorders of the Immune System" chapter of the ICD-11. The "Food hypersensitivity" (FH) subsection is classified under the "Complex allergic or hypersensitivity conditions" section and "Food-induced anaphylaxis" is under the "Anaphylaxis" section. In order to inform the development of strategies to reduce preventable FHs/food allergies, the burden of disease in different healthcare settings and patient populations and their common etiologies need to be understood. Besides, greater specificity regarding clinical conditions and services delivered will provide payers, policy makers, and providers with better information to make major refinements to countries payment and reimbursement systems, including the design and implementation of pay-for-performance program.The new classification addressed to FHs will enable the collection of more accurate epidemiological data to support quality management of patients with FHs/food allergies, and better facilitate health care planning and decision-making and public health measures to prevent and reduce their morbidity and mortality. The improved logic and standardized definitions through the ICD-11 (and other WHO classifications) will also facilitate international comparisons of quality care and the sharing of best practice globally.

Clinical and quality of life assessment in patients with latex allergy during COVID-19 pandemic: Possible protective role of continuous latex immunotherapy.

Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 ± 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.

Experience with polyethylene glycol allergy-guided risk management for COVID-19 vaccine anaphylaxis.

BACKGROUND: Polyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed. METHODS: In retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed. RESULTS: Ten patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination. CONCLUSIONS: Taking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines.

Health Equity Demands Health Literacy: Ethics in the Pediatric Emergency Department.

The ability of the patient or the parent, in pediatrics, to read, understand, and act upon health information is termed health literacy. Health literacy has been shown to be of primary importance when determining a patient's ability to achieve optimal health. As physicians, we often fail to recognize the enormous obstacles facing our patients. In the pediatric emergency department (PED), communication is complicated. Physicians must be able to effectively relay information to the patient's caregiver while still not forgetting to provide developmentally appropriate instructions to the child. Individuals who do not have a good understanding of what is needed to properly care for themselves or their children are at a disadvantage, and it is therefore the responsibility of the pediatric provider to do all they can to identify gaps in health literacy. As providers, we need to always be questioning as to whether we properly conveyed the information to our patients. Teaching which results in good understanding is the ultimate goal when treating and releasing our patients in the pediatric emergency department. Matching the method of delivery of information and education to the family's health literacy will help the care team deliver effective information so that it is applied at home hopefully preventing a rapid revisit.

Patient Carrying Time, Confidence, and Training with Epinephrine Autoinjectors: The RACE Survey.

BACKGROUND: Limited real-world data exist regarding patient carrying compliance and confidence in using different types of epinephrine autoinjectors (EAIs). OBJECTIVE: To perform a Real-world Assessment of Patients' Carrying Time and Confidence with Epinephrine Autoinjector Devices (RACE survey). METHODS: This was a noninterventional survey of patients (≥7 years) who filled 1 or more prescription for Auvi-Q or EpiPen between January 2013 and January 2014. Outcomes included proportion of patients carrying their EAI all the time in the last 7 days (primary), EAI use confidence (secondary), and EAI training experience (secondary). Multivariate regression analyses controlled for significant differences in demographic and clinical characteristics between EAI groups. RESULTS: The survey included 2,000 participants (Auvi-Q, N = 1,000 [children, n = 597; adults, n = 403]; EpiPen, N = 1,000 [children, n = 105; adults, n = 895]). After adjusting for confounding factors, we found that Auvi-Q respondents were more likely to carry their device all the time in the last 7 days versus EpiPen respondents (adjusted odds ratio [aOR], 1.91; 95% CI, 1.49-2.45; P < .001); similar trends were observed in adults and children (P < .001 both). Adults in the Auvi-Q group were more likely to feel "very confident" about correctly using their EAI (aOR, 2.02) and someone else correctly using their EAI (aOR, 2.25) versus the EpiPen group (P < .001 both). Compared with EpiPen respondents, Auvi-Q respondents were more likely to feel that EAI instructions were "very clear" (aOR, 3.10) and more likely to find the prescription pack trainer helpful (aOR, 2.29; P < .01 both). CONCLUSIONS: This study suggests significant real-world differences in patients' carrying time, confidence in use, and training experiences between Auvi-Q and EpiPen users.

Urban/rural residence effect on emergency department visits arising from food-induced anaphylaxis.

BACKGROUND: Anaphylaxis is a severe and potentially fatal allergic response. Early-life exposure to rural environments may help protect against allergic reaction. This study assesses urban/rural differences by age and race/ethnicity in emergency department (ED) pediatric visit rates for food-induced anaphylaxis. METHODS: This observational study examined 2009-2014 inpatient and ED data from New York and Florida, using ICD-9-CM diagnostic code (995.6) to identify food-induced anaphylaxis cases <18 y/o. Primary predictor of interest was urban/rural setting, with race/ethnicity and age also evaluated. Associations between ED visit rates and urban/rural setting were evaluated by multivariable hierarchical negative binomial regression with state and year fixed effects. RESULTS: ED visit rates (per 100,000) for food-induced anaphylaxis were 12.31 and 4.60 in urban and rural settings, respectively. Rates were highest among Blacks (15.26) younger urban children (17.29) and older rural children (6.99). Compared to rural, urban children had significantly higher anaphalaxis ED visit rates (IRR 2.77). CONCLUSIONS: Food-induced anaphylaxis ED visit rates were highest among younger urban children and Black children, with a notable contrast in age distribution between urban and rural rates. Higher urban rates may be attributed to Hygiene Hypothesis, though racial, economic and emergency care access disparities may also influence these outcomes.

Prevalence of anaphylaxis among adults admitted to critical care for severe asthma exacerbation.

BACKGROUND: In asthmatics, making a diagnosis of anaphylaxis could be challenging as respiratory symptoms are a common feature of both conditions. Identifying anaphylaxis is important to providing appropriate care. A prior study showed that anaphylaxis is sometimes misdiagnosed as acute asthma in children. We sought to identify the percentage of adults admitted to the intensive care unit (ICU) with asthma exacerbations who met criteria for anaphylaxis. METHODS: Retrospective chart review of adults admitted with acute asthma to the ICU at Jacobi Medical Center, a Level 1 trauma centre in Bronx, New York. Study period was January 2012 to December 2014. Using the criteria outlined in the World Allergy Organization's Anaphylaxis Guidelines, we identified patients who met criteria for anaphylaxis. RESULTS: 105 patients were identified: 17 were excluded because their main reason(s) for admission was not asthma. 7 (8%) of the 88 cases eligible for the study met diagnostic criteria for anaphylaxis while 3 (3.4%) were highly likely to have had anaphylaxis. The baseline characteristics of the seven patients were similar to that of the overall population studied. They however had shorter onset of symptoms (median (IQR): 3.5 (2-6) vs 24 hours (12-72), p<0.001), were more likely to have been intubated (71%vs31%, p=0.04), received intramuscular epinephrine by the emergency medical services or in the emergency room (86%vs42%, p=0.04) and received antihistamines (28.6%vs1.2%, p=0.02). None of these seven patients died. Only one of the seven patients was prescribed an epinephrine pen injector and referred to an allergist at discharge. CONCLUSION: In this single-centre retrospective review, 3.4% of adults admitted to the ICU for acute severe asthma also met criteria for anaphylaxis.

Allergy and Asthma: Anaphylaxis.

Anaphylaxis is an allergic reaction that occurs rapidly after exposure and is life-threatening. After symptoms of anaphylaxis occur, there is no way to reliably predict whether the patient's condition could progress quickly and become life-threatening. Immediate injection of intramuscular epinephrine is the first-line emergency treatment for anaphylaxis. Other drugs such as corticosteroids or antihistamines are secondary options and should not delay epinephrine administration. The most commonly prescribed form of epinephrine is the costly brand name autoinjector, but less expensive alternatives exist, including generic autoinjectors and prefilled epinephrine syringes. Epinephrine prescriptions should be combined with action plans that guide parents and caregivers on appropriate use. Access to epinephrine at schools, even for students who do not have a prescription, is an important component of preparedness for anaphylaxis.

Individual risk assessment in the diagnosis of immediate type drug hypersensitivity reactions to betalactam and non-betalactam antibiotics using basophil activation test: a single center experience.

BACKGROUND: Drug hypersensitivity reactions of immediate type pose a challenging problem, especially, if standard diagnostic procedures do not lead to conclusive results. The aim of this investigation is to identify, whether basophil activation test (BAT) is able to provide additional benefit in the diagnostic evaluation of immediate type drug hypersensitivity reactions to antibiotics in comparison with the routine allergological diagnostic methods. MATERIALS AND METHODS: We investigated patients, who presented to the Department of Dermatology and Allergology of the University Hospital of RWTH Aachen in Germany for diagnostic workup of type I allergic reactions to antibiotics during the period from 2009 to 2012. The analysis was performed retrospectively based on patient records. The inclusion criteria were performed standard allergological in vivo diagnostic and a BAT as a part of diagnostic workup. RESULTS: Eighty-two diagnostic investigations were performed in 52 patients. BAT was positive in 9 of 12 cases with a positive clinical history but negative skin test results. Furthermore, all patients who reported severe drug hypersensitivity reactions (anaphylactic reaction grade 2 and above) showed positive BAT (5/5), while only three of these five cases demonstrated a positive skin testing that led to the conclusion of possible immediate type drug hypersensitivity. CONCLUSIONS: Although skin tests remain the most important part of the primary diagnostic investigation, BAT is an additional valuable and sensitive in vitro test in the diagnostic procedure of immediate type allergic reactions to antibiotics. However, further standardized investigations are needed in order to calculate exact sensitivity and specificity of this diagnostic tool in both, adult and pediatric populations.

Immunogenicity assessment during the development of protein therapeutics.

OBJECTIVE: Here we provide a critical review of the state of the art with respect to non-clinical assessments of immunogenicity for therapeutic proteins. KEY FINDINGS: The number of studies on immunogenicity published annually has more than doubled in the last 5 years. The science and technology, which have reached a critical mass, provide multiple of non-clinical approaches (computational, in vitro, ex vivo and animal models) to first predict and then to modify or eliminate T-cell or B-cell epitopes via de-immunization strategies. We discuss how these may be used in the context of drug development in assigning the immunogenicity risk of new and marketed therapeutic proteins. SUMMARY: Protein therapeutics represents a large share of the pharma market and provide medical interventions for some of the most complex and intractable diseases. Immunogenicity (the development of antibodies to therapeutic proteins) is an important concern for both the safety and efficacy of protein therapeutics as immune responses may neutralize the activity of life-saving and highly effective protein therapeutics and induce hypersensitivity responses including anaphylaxis. The non-clinical computational tools and experimental technologies that offer a comprehensive and increasingly accurate estimation of immunogenic potential are surveyed here. This critical review also discusses technologies which are promising but are not as yet ready for routine use.

Laboratory Animal Bite Anaphylaxis: A National Survey: Part 2: Treatment Protocols.

OBJECTIVE: This study documents current treatment protocols for laboratory animal bite anaphylaxis in the United States. METHODS: An online survey was e-mailed to designated institutional officials at laboratory animal facilities identified by the National Institutes of Health Office of Laboratory Animal Welfare. RESULTS: One hundred eighty-nine organizations responded to the question of whether they had a treatment protocol with 32% indicating that they had a protocol. Having a case of anaphylaxis increased the likelihood of having a protocol (61%). Of those with a protocol, 58% included treatment with injectable epinephrine, if clinically indicated. Among all respondents, only 14% reported keeping injectable epinephrine at the location where animal work is performed. CONCLUSIONS: A minority of responding organizations had protocols in place to address laboratory animal bite anaphylaxis. Organizations with workers at risk should consider implementing a protocol for assessment and treatment.

The High Cost of Epinephrine Autoinjectors and Possible Alternatives.

Epinephrine autoinjectors provide potentially life-saving therapy for pediatric and adult subjects with systemic allergic reactions, including anaphylaxis. However, the cost of these devices, specifically the EpiPen (Mylan, Canonsburg, Pa), is increasing exponentially. Epinephrine autoinjectors are commonly prescribed in the United States but are not readily available worldwide. Alternatives for the self-administration of epinephrine exist and should be considered for patients who cannot afford or do not have access to these devices. The epinephrine prefilled syringe, stored in an eyeglass or pencil case, is a safe and viable option for the self-administration of epinephrine. Epinephrine prefilled syringes may not be as ideal as using autoinjectors but are superior to patients living without access to this medication.

Food-Allergic Adolescents at Risk for Anaphylaxis: A Randomized Controlled Study of Supervised Injection to Improve Comfort with Epinephrine Self-Injection.

BACKGROUND: Epinephrine self-injection is a key element in the management of food allergy, yet many adolescents report that they may not be able to use the autoinjector when needed. We hypothesized that supervised self-injection with an empty syringe would increase adolescents' comfort with self-injection. OBJECTIVE: The objective of this study was to examine the effect of supervised self-injection on self- and parent-reported comfort and anxiety during and after clinic visits in a food allergy center. METHODS: Sixty adolescent/parent pairs were randomized to self-injection versus control (education only). The predefined primary outcome was a self-reported comfort level with the injection before versus after the intervention on a Likert scale with scores of 1 (Not at all comfortable) to 10 (Extremely comfortable). The primary outcome was evaluated via within-group and between-group analyses. Secondary outcomes included adolescent and parent reports before versus after the injection, and changes in quality of life (QoL) and anxiety a month later. RESULTS: Self-injection was associated with a significant immediate increase in comfort levels (primary outcome; within-group comparison: mean scores: 6.93 preintervention vs 8.37 postintervention, P < .01; between-group ANOVA: 8.37 vs 6.69, P < .01) and with significant improvements in all other predefined (secondary) measures. On follow-up, QoL improved in 52% of intervention patients as compared with 25% of controls; similar differences were observed for anxiety. Those differences were not statistically significant. CONCLUSIONS: A self-injection (with an empty syringe) procedure in a clinic setting improves adolescents' and parents' comfort level with self-injecting. It may translate into substantial clinical benefits should self-injection be needed.

The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment.

BACKGROUND: Safety data on 'real-life' allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults. METHODS: Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs. RESULTS: A total of 1563 patients (mean ± SD age: 11.7 ± 3.9 years; rhinitis: 93.7%; asthma: 61.5%; polysensitization: 62.5%) and 1578 courses of AIT were assessed. Single-allergen AIT was administered in 89.5% of cases (n = 1412; mites: 49%; grass pollen: 25.8%; tree pollen: 8.7%; Alternaria: 4.6%; dander: 0.8%; weed pollen: 0.6%). Subcutaneous AIT (SCIT) was used in 71.4% (n = 1127) of the treatments, including 574 (50.9%) with natural extracts. Sublingual AIT (SLIT) was used for the remaining 451 treatments (drops: 73.8%; tablets: 26.2%). The mean ± SD follow-up period was 12.9 ± 3.3 months. The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT. Twenty-four patients (1.53%) experienced 29 SRs. Respiratory (55.7%) and skin symptoms (37.9%) were most frequent. Anaphylaxis was diagnosed in 3 SRs (10.3%), and adrenaline was administered in 2 of these cases. In a univariate analysis, the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization (>3), grass pollen extracts and the use of natural extracts (vs. allergoids). CONCLUSIONS: In a real-life paediatric setting, AIT is safe. SRs are infrequent and generally not severe. Pollen polysensitization, grass pollen extracts and natural extracts (vs. allergoids) were risk factors for AIT-associated SRs.

Increasing Emergency Department Visits for Anaphylaxis, 2005-2014.

BACKGROUND: Anaphylaxis is a potentially life-threatening systemic allergic reaction. Studies suggest that the incidence of anaphylaxis is increasing; however, recent trends in emergency department (ED) visits for anaphylaxis in the United States have not been studied. OBJECTIVE: To examine trends in the incidence and rates of anaphylaxis-related ED visits from 2005 through 2014. METHODS: We retrospectively analyzed data from a national administrative claims database including commercially insured and Medicare Advantage patients. We identified all ED visits for anaphylaxis and calculated rates as number of anaphylaxis-related ED visits per 100,000 enrollees. Rates were compared over time and by age and trigger. RESULTS: During the 10-year time period, 56,212 ED visits for anaphylaxis were identified. The median (interquartile range) age was 36 (17-52 years) years, and 58% were female. Most cases (57%) were due to unspecified triggers, 27% were associated with food, 12% were medication related, and 4% were due to insect venom. The overall rate of anaphylaxis per 100,000 enrollees increased by 101%, from 14.2 in 2005 to 28.6 in 2014 (P < .001). Rates of ED visits for anaphylaxis increased in all age groups, but the greatest increase was in children aged 5 to 17 years (196% increase; P < .001). The rate of food-related anaphylaxis increased by 124% (P < .001), and the rate of medication-related anaphylaxis increased by 212% (P < .001). CONCLUSIONS: ED visits for anaphylaxis increased between 2005 and 2014. Increases in ED visits were greatest among children.

Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products.

IMPORTANCE: All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established. OBJECTIVE: To compare the risk of anaphylaxis among marketed IV iron products. DESIGN, SETTING, AND PARTICIPANTS: Retrospective new user cohort study of IV iron recipients (n = 688,183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013. EXPOSURES: Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data. MAIN OUTCOMES AND MEASURES: Anaphylaxis was identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups. RESULTS: A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100,000 persons for iron dextran (95% CI, 57.8-78.7 per 100,000) and 24 per 100,000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100,000) , with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3; P < .001). At first exposure, when compared with iron sucrose, the adjusted OR of anaphylaxis for iron dextran was 3.6 (95% CI, 2.4-5.4); for iron gluconate, 2.0 (95% CI 1.2, 3.5); and for ferumoxytol, 2.2 (95% CI, 1.1-4.3). The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons, 95% CI, 70.5- 93.1) and lowest with iron sucrose (21 per 100,000 persons, 95% CI, 15.3- 26.4). CONCLUSIONS AND RELEVANCE: Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.