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Background Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. Objective We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. Methods We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale. Results The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. Conclusions We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline, nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence) (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence) (3) In people with aspirin (nonsteroidal anti-inflammatory drug) exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.

Hymenoptera stinging insects are common culprits for allergic reactions. Anaphylaxis to insect stings can be life threatening and is associated with a significant risk of recurrence. Insect allergy requires referral to an allergist/immunologist for education and for diagnostic evaluation that will direct further management and treatment. Venom immunotherapy is safe and effective; it prevents sting anaphylaxis in up to 98% of patients. Potential risk factors for side effects during testing and treatment should be assessed for every patient to mitigate risk and to guide treatment recommendations and the duration of immunotherapy.

Questions and controversies regarding venom immunotherapy (VIT) remain. It is important to recognize risk factors for severe sting anaphylaxis that guide the recommendation for testing, epinephrine injectors, and VIT. Premedication, rush VIT, and omalizumab are successful in overcoming recurrent systemic reactions to VIT. A maintenance dose is adequate in children, but higher doses are needed in high-risk patients. The consensus on risk of β-blockers and angiotensin-converting enzyme inhibitors in patients on VIT has shifted to the belief that risk is small. The decision to stop VIT after 5 years rests on known risk factors rather than any diagnostic tests.

Stinging insect allergy is uncommon but can be life threatening. Diagnosis requires clinical history and confirmative skin or blood testing by an allergist. Baseline serum tryptase level can be used to stratify risk. Treatment is supportive for all reactions except for anaphylaxis, which is treated with intramuscular epinephrine, recumbent posture, and adjunct measures such as IV fluids, and oxygen. Venom immunotherapy is most effective for long-term management in patients with a history of anaphylaxis. Venom immunotherapy rapidly reduces the risk of sting anaphylaxis by up to 98% and maintenance treatment can be stopped after 5 years in most cases.

Guidelines on insect sting allergy and venom immunotherapy (VIT) have been updated. This review describes the evolution of these guidelines and their similarities and differences.The US and European guidelines show the evolution of guideline development in the grading of recommendations and the transparency of the evaluation of evidence. The US and European guidelines on VIT are similar in most areas and complimentary in others. The European guidelines are limited to VIT and are based on a published systematic review; the US practice parameters cover all areas of the diagnosis and management of insect sting allergy and do not use the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach.There is general agreement that both children and adults with cutaneous systemic reactions do not require VIT, and that there is minimal risk associated with β-blockers and angiotensin-converting enzyme inhibitors during VIT. There are minor differences in the details of VIT dose, regimen, and choice of venom, but agreement on the duration and risk factors for relapse after VIT. The US and European guidelines are complementary in their discussion of the relation of mastocystosis and insect sting anaphylaxis and the value of measuring basal serum tryptase.The updated guidelines on insect sting allergy from the US and European groups differ in scope, with a somewhat different focus in specific areas but are complementary overall. Where they overlap, there are relatively few differences in recommendations, and these are subtle. The US practice parameter offers an annotated algorithm for the evaluation and treatment of patients with reactions to insect stings.

Background Although 5-grass pollen sublingual immunotherapy has a good safety profile in controlled clinical trials, additional safety information among pediatric patients in a real-world setting would be useful. Objective To further document the safety of 5-grass tablet among children aged 5 to 9 years with allergic rhinoconjunctivitis (ARC). Methods This multicenter, observational study included allergy immunotherapy-naive 5- to 9-year-old children with grass pollen–induced ARC prescribed with 5-grass tablet daily (3-day dose escalation to 300 index of reactivity [IR]). Patients were followed up daily for safety and tolerability over the first 30 treatment days. Adverse events (AEs) and adverse drug reactions (ADRs) were analyzed descriptively. Results Three hundred seven children (mean age, 7.1 years) were enrolled. Fifty-eight percent were confirmed as polysensitized, and 36% had mild-to-moderate asthma. Of 307 patients, 233 (76%) reported AEs, and 173/307 (56%) reported ADRs, most frequently mild application-site reactions (throat irritation, oral pruritus, oral paresthesia). Sixteen of 307 (5.2%) patients withdrew because of ADRs. In 143 of 173 (83%) patients, ADRs first occurred within 1 week of starting treatment. More than half of the ADRs lasted less than 2 days, and ADRs resolved spontaneously in 161 of 173 (93%) patients. Recurrences of ADRs were reported in 45 of 173 (26%) patients and were also mainly application-site reactions. No notable differences were found in ADRs related to whether patients had asthma at inclusion. Neither epinephrine use nor admission to intensive care unit was reported. Conclusion The safety profile of 5-grass tablet in pediatric ARC patients aged 5 to 9 years was consistent with safety findings in older patients, most ADRs being at the application site and mild to moderate. ClinicalTrials.gov identifier: NCT02295969 ; EUPAS registration number: 8104.

Insect sting anaphylaxis and mast cell disorders are intertwined in a specific and unusual way. There may be specific subsets of clonal mast cell disorders that are predisposed to sting anaphylaxis. The clinical characteristics of the sting reactions should raise suspicion of underlying mastocytosis (eg, hypotension without hives especially in a male). A baseline serum tryptase level is helpful in the evaluation of patients with insect sting anaphylaxis because it correlates with important risks for these patients, and they have a high frequency of abnormally elevated baseline levels. Elevated baseline serum tryptase level has been reported to correlate with clonal mast cell disease in patients with insect sting anaphylaxis but may also indicate one of several possible underlying syndromes, including mast cell activation syndrome (MCAS), familial hypertryptasemia, and idiopathic anaphylaxis. There is some overlap in these conditions, so it is important to evaluate the clinical pattern at presentation as well as laboratory markers, and to consider bone marrow biopsy to make a final and specific diagnosis of clonal mast cell disease. The presence of venom-IgE does not prove that the patient's previous sting reactions were IgE-mediated, but even low levels of venom-IgE in patients with mastocytosis predispose to severe sting anaphylaxis. Evaluation of all these possible factors will affect the recommendation for venom immunotherapy.

Optimal evidence-based clinical practice requires systematic summaries of the best available evidence, including ratings of the quality of that evidence, and is facilitated by the availability of trustworthy guidelines. In this review, we describe the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rating quality of evidence and moving from evidence to recommendations using examples from allergy-immunology. GRADE focuses on systematic summaries of the best evidence, systematic reviews and trustworthy guidelines, and emphasizes a structured approach to determining quality (certainty) of bodies of evidence, absolute magnitude of effects of desirable and undesirable consequences (benefits and harms), and use of evidence to develop clinical recommendations. Adopted by over 110 organizations worldwide, including the American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters, GRADE is foundational to the optimal interpretation of research evidence and its application in clinical practice. This review supports the clinician's ability to find and use the information in GRADE guidelines to help care for patients in the clinic.

This review describes improvement in diagnostic accuracy, prediction of outcomes, identifying high-risk factors, and refinements of treatment that continue to evolve over the past 5–10 years. The risk of anaphylaxis is relatively low ( 90%). Use of recombinant venom allergens and basophil activation tests may improve diagnostic accuracy. Elevated serum tryptase (and possible mastocytosis) occurs in 10% of patients with insect sting allergy, and in 25% of those with hypotensive reactions. Rush VIT is proven safe and rapidly effective. There are known high-risk factors that justify treatment beyond 5 years. Diagnostic accuracy and prediction of risk have improved in recent years. There are still knowledge gaps related to prediction and management of risk with current diagnostic and therapeutic modalities.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Background The short stability window of several hours from blood collection to measuring basophil activation has limited the use of flow cytometry-based basophil activation assays in clinical settings. We examine if it is possible to extend this window to 1 day allowing for shipment of samples between laboratories. Several options exist for reporting the results including reporting all the measured values directly, calculating ratios and reporting a single value covering all measured results. Each of these options have different stability and value to the physician. Methods Whole blood samples from peanut allergic patients were stimulated with four different peanut concentrations at Day 0, Day 1, and Day 2. Samples were stored under temperature-controlled conditions. Flow cytometry was used to analyze the samples. The basophil activation and degranulation were measured as percentage of positive CD63 basophils and CD203c MFI fold change. Shipped samples were transported under ambient conditions. Results The results show that CD63 is a stable marker at Day 1. The CD203c ratio decreases significantly at Day 1. Calculating the CD63/IgE ratio proves to be more stable than CD63 alone. The most stable readouts are the semi-quantitative results and the trajectory of the dose response curve. Finally, we confirmed that the stability can be extended to samples shipped overnight to the laboratory. Conclusions It is possible to extend the stability of the basophil activation assay to 1 day for samples stored at 18-25°C as well as samples shipped under ambient conditions as long as the temperature is within the 2-37°C range.

Venom immunotherapy is the standard of care for people with severe reactions and has been proven to reduce risk of future anaphylactic events. There is a moral imperative to ensure production, supply and worldwide availability of locally relevant, registered, standardized commercial venom extracts for diagnosis and treatment. Insects causing severe immediate allergic reactions vary by region worldwide. The most common culprits include honeybees (Apis mellifera), social wasps including yellow jackets (Vespula and Dolichovespula), paper wasps (Polistes) and hornets (Vespa), stinging ants (Solenopsis, Myrmecia, Pachycondyla, and Pogonomyrmex), and bumblebees (Bombus). Insects with importance in specific areas of the world include the Australian tick (Ixodes holocyclus), the kissing bug (Triatoma spp), horseflies (Tabanus spp), and mosquitoes (Aedes, Culex, Anopheles). Reliable access to high quality venom immunotherapy to locally relevant allergens is not available throughout the world. Many current commercially available therapeutic vaccines have deficiencies, are not suitable for, or are unavailable in vast areas of the globe. New products are required to replace products that are unstandardized or inadequate, particularly whole-body extract products. New products are required for insects in which no current treatment options exist. Venom immunotherapy should be promoted throughout the world and the provision thereof be supported by health authorities, regulatory authorities and all sectors of the health care service. Keywords: Immunotherapy, Venom, Insects, Venom immunotherapy

In early 2020, the first US and Canadian cases of the novel severe acute respiratory syndrome coronavirus 2 infection were detected. In the ensuing months, there has been rapid spread of the infection. In March 2020, in response to the virus, state/provincial and local governments instituted shelter-in-place orders, and nonessential ambulatory care was significantly curtailed, including allergy/immunology services. With rates of new infections and fatalities potentially reaching a plateau and/or declining, restrictions on provision of routine ambulatory care are lifting, and there is a need to help guide the allergy/immunology clinician on how to reinitiate services. Given the fact that coronavirus disease 2019 will circulate within our communities for months or longer, we present a flexible, algorithmic best-practices planning approach on how to prioritize services, in 4 stratified phases of reopening according to community risk level, as well as highlight key considerations for how to safely do so. The decisions on what services to offer and how fast to proceed are left to the discretion of the individual clinician and practice, operating in accordance with state and local ordinances with respect to the level of nonessential ambulatory care that can be provided. Clear communication with staff and patients before and after all changes should be incorporated into this new paradigm on continual change, given the movement may be forward and even backward through the phases because this is an evolving situation.

Given the burden of disease and the consequences of a diagnosis of peanut allergy, it is important that peanut allergy be accurately diagnosed so that an appropriate treatment plan can be developed. However, a test that indicates there is peanut sensitization present (eg, a "positive" test) is not always associated with clinical reactivity. This practice parameter addresses the diagnosis of IgE-mediated peanut allergy, both in children and adults, as pertaining to 3 fundamental questions, and based on the systematic reviews and meta-analyses, makes recommendations for the clinician who is evaluating a patient for peanut allergy. These questions relate to when diagnostic tests should be completed, which diagnostic tests to utilize, and the utility (or lack thereof) of diagnostic testing to predict the severity of a future allergic reaction to peanut.

Venom immunotherapy is the only treatment for the prevention of anaphylaxis and remains the prototypical model for its diagnosis and management. Unlike other causes of anaphylaxis, such as foods and drugs, preventative treatment using venom immunotherapy is highly effective with well-established protocols, and is widely available. Hymenoptera venoms are also unique in that the primary allergens are directly measurable in terms of micrograms, rather than labeled on the basis of potency. As such, venoms were the first truly standardized extracts. However, Hymenoptera venom presents unique challenges in collection, processing, and stabilization of the venom extract product. Historically, there have been minor variations in insect composition in venom extract content. These differences were in part based on variation in insect availability and venom collection and have created minor challenges. However, it is a recognized need that venom extracts contain an optimal and complete repertoire of relevant venoms so as to be assured of appropriate diagnosis and treatment. As such, insect availability and collection, as well as storage, stability, and sterility of venom extracts, have remained critical components to appropriate diagnosis and prevention of venom-induced anaphylaxis. In recent years there has been concerns about adequate supplies of venom for appropriate diagnosis and treatment of venom allergy, but these concerns seem to have stabilized, with the movement to a single venom supplier. This movement to a single supplier may provide its own challenges.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

Purpose of review Insect stings often induce large local reactions (LLRs) that result in morbidity. These reactions do have an immunologic basis; however, patients presenting with LLRs should be managed differently than those with systemic allergic reactions, as described in this review. Recent findings Morbidity results from the inflammation itself along with the iatrogenic consequences of treatment. The prescription of antihistamine medications and the use of antibiotics are generally not indicated for patients with LLRs because of the risks/side-effects of these medications and the low probability of benefit. Some patients are also concerned over the possibility that a future sting will evolve into a life-threatening reaction. Although these reactions do involve IgE, patients are not at sufficient risk to warrant prescription of autoinjectable epinephrine. Venom-specific immunotherapy can be considered when LLRs are frequent and associated with significant impairment. Summary Clinicians can reduce morbidity from LLRs by reassuring the patients, avoiding medications that result in side-effects when they are not indicated, and referring to an allergist when there are additional concerns, such as frequent impairment.

Objective To review GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methods and discuss the clinical application of conditional recommendations in clinical guidelines, specifically in the context of anaphylaxis. Data Sources Articles that described GRADE, evidence synthesis, evidence to recommendation frameworks, and shared decision making were used to discuss conditional recommendations of the 2020 Anaphylaxis GRADE guideline. Study Selections A narrative review detailing concepts of GRADE and approaches to translate conditional recommendations to individualized and contextualized patient care. Results GRADE methods encourage a nuanced relationship between certainty of evidence and strength of recommendations. Strength of recommendation must incorporate key factors, including the balance between benefits and harms, patient values and preferences, and resource allocation (costs), with equity, feasibility, and acceptability also often included as considerations. GRADE guidelines provide recommendations that are characterized by directionality (for or against) and strength (strong or conditional). A conditional recommendation is tailored to context and primarily applied through a lens of patient preferences related to the likelihood of outcomes of importance and a shared decision-making approach. Although the 2020 Anaphylaxis GRADE guideline better informs the practice of anaphylaxis prevention through (1) identification and mitigation of risk factors for biphasic anaphylaxis and (2) evaluation of the use of glucocorticoid and/or antihistamine pretreatment, all GRADE recommendations, although directional, are conditional and as such should not be universally applied to every circumstance. Conclusion Clinical guidelines provide an important opportunity to critically appraise evidence and translate evidence to practice. Patients, practitioners, and policy makers should appreciate the strength of recommendation and certainty of evidence and understand how this affects guideline applicability and implementation.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to

In the event of a global infectious pandemic, drastic measures may be needed that limit or require adjustment of ambulatory allergy services. However, no rationale for how to prioritize service shut down and patient care exists. A consensus-based ad-hoc expert panel of allergy/immunology specialists from the United States and Canada developed a service and patient prioritization schematic to temporarily triage allergy/immunology services. Recommendations and feedback were developed iteratively, using an adapted modified Delphi methodology to achieve consensus. During the ongoing pandemic while social distancing is being encouraged, most allergy/immunology care could be postponed/delayed or handled through virtual care. With the exception of many patients with primary immunodeficiency, patients on venom immunotherapy, and patients with asthma of a certain severity, there is limited need for face-to-face visits under such conditions. These suggestions are intended to help provide a logical approach to quickly adjust service to mitigate risk to both medical staff and patients. Importantly, individual community circumstances may be unique and require contextual consideration. The decision to enact any of these measures rests with the judgment of each clinician and individual health care system. Pandemics are unanticipated, and enforced social distancing/quarantining is highly unusual. This expert panel consensus document offers a prioritization rational to help guide decision making when such situations arise and an allergist/immunologist is forced to reduce services or makes the decision on his or her own to do so.

Large local reactions (LLRs) are IgE-mediated late-phase inflammatory reactions that can cause great morbidity but are associated with a relatively low risk of future anaphylaxis. Patients with LLR may benefit from consultation with an allergist to help clarify the relative risk, to plan the best treatment for future stings, and to determine whether or not to pursue testing or venom immunotherapy (VIT). The chance of anaphylaxis to future stings is

Key Points Question What is the cost-effectiveness of 1 hour vs 6 to 24 hours of medical observation for biphasic anaphylaxis? Findings In this economic evaluation, routine use of prolonged medical observation costs $62 374 to $230 202 per case of biphasic anaphylaxis observed, depending on the hourly costs of observation and duration of stay, with costs of prolonged observation approaching or exceeding $10 million per death prevented. Meaning Routine use of 6- to 24-hour medical observation for unselected patients with resolved anaphylaxis is a low-value medical practice unless the risk of biphasic anaphylaxis is significantly pronounced., This economic evaluation uses computer-simulated patients to examine the cost-effectiveness of short (1 hour) vs prolonged (≥6 hours) medical observation for biphasic anaphylaxis after an episode of resolved anaphylaxis., Importance Biphasic anaphylaxis may occur in up to 20% of patients with anaphylaxis; however, the optimal observation time of patients with resolved anaphylaxis is unknown. Objective To characterize the cost-effectiveness of short vs prolonged medical observation times after resolved anaphylaxis. Design, Setting, and Participants An economic evaluation was performed of computer-simulated adult patients observed in outpatient allergy clinics and emergency departments, with rates of biphasic anaphylaxis derived from a 2019 meta-analysis. Exposures Computer-simulated patients (10 000 per strategy) were randomized to undergo 1 hour of medical observation (associated with 95% negative predictive value of biphasic anaphylaxis) or 6 or more hours of observation (associated with a 97.3% negative predictive value of biphasic anaphylaxis). Main Outcomes and Measures Cost-effectiveness of 6- to 24-hour medical observation of resolved anaphylaxis evaluated at willingness-to-pay thresholds of $10 000 per case of biphasic anaphylaxis observed and $10 million per death prevented, assuming that observation is associated with a 10- to 1000-fold reduction in the risk of death due to biphasic anaphylaxis. Results Biphasic anaphylaxis occurred after hospital discharge in 365 patients observed for 1 hour and in 213 patients undergoing prolonged observation. From a health care sector perspective, with medical observation costs of $286.92 per hour, the incremental cost of extended medical observation of resolved anaphylaxis (1 hour vs 6 hours) was $62 374 per case of biphasic anaphylaxis identified ($68 411 from the societal perspective). In Monte Carlo simulations, with hourly costs ranging from $100 to $500 and extended observation ranging from 6 to 24 hours (health care sector perspective), the mean (SD) costs were $295.36 ($81.22) for 1 hour of observation vs $3540.42 ($1626.67) for extended observation. The incremental cost-effectiveness ratio was $213 439 per biphasic anaphylaxis observed ($230 202 from the societal perspective). A 6-hour observation could be cost-effective if the risk of biphasic anaphylaxis after 1-hour observation of resolved anaphylaxis was 17% or if hourly observation costs were less than $46 in the base case. Cost-effectiveness could also be achieved (willingness-to-pay of $10 million per death prevented, health care sector perspective) when a baseline fatality rate of 0.33% per biphasic anaphylactic event was assumed, with a no greater than 24% relative risk of fatality associated with 6-hour observation. Conclusions and Relevance This study indicates that prolonged medical observation (6-24 hours) for resolved anaphylaxis may not be cost-effective for patients at low risk for biphasic anaphylaxis; however, in particular clinical circumstances of low observation costs, high postdischarge risk of biphasic anaphylaxis, or large incremental fatality risk reduction associated with extended observation, longer medical observation can be justified.

Although the product package insert states that venom immunotherapy (VIT) should be administered indefinitely, there is sufficient evidence that treatment can be discontinued after 3–5 years in the majority of patients. There will always be at least a slightly increased chance of systemic reaction to a sting when VIT is stopped, with greater chance after 3 years than after 5 years of VIT. Research has provided us with some insight on the “high-risk” factors that are associated with the greatest chance of relapse and therefore justify extended or indefinite treatment. The severity of the pre-VIT sting reaction is perhaps the most important factor associated with increased risk of severe reaction. Higher risk also exists in those with elevated basal serum tryptase level, in patients who had a systemic reaction during VIT (to a sting or venom injection), and in those with frequent exposure (especially beekeepers). These “high-risk” patients may include more than 30% of all those on VIT. Some patients simply prefer the security of continued VIT at 12-week intervals.

Objective To review the methods and materials used for collection, purification, commercial production, and clinical application of Hymenoptera venoms. Data Sources Most of the sources for this review are the experience and expertise of the authors. Published reports and review articles on Hymenoptera venom collection and production were identified through database searches (PubMed). Study Selections Studies describing the methods for Hymenoptera venom collection and production were selected for review. Results Meticulous methods for identification and collection of the insects are required. Collection and purification of the venoms from the insects are based on validated methods and result in a commercial extract that is standardized for the major allergenic proteins required for accurate diagnosis and safe and effective treatment of patients allergic to insect sting. The steps required for mixing, purifying, testing, and standardizing the products are described. Conclusion Hymenoptera venom extracts were developed using many new methods for the collection, purification, and commercial production of the unique materials required for this product. Clinical applications for diagnosis and treatment are affected by the integrity and stability of the allergens after processing and purification.

Clinical studies, laboratory tests, and field observations confirm that the barbed sting of a yellowjacket wasp, Vespula maculifrons (Buysson), often becomes firmly anchored in human skin. Although the wasp cannot pull away from (i.e.autotomize) its sting when this occurs, if the insect is forcibly removed by the victim, the sting apparatus tends to be more readily torn from its abdomen than are the embedded lancets torn from the victim's skin. Associated with the release of alarm pheromone and prolonged injection of venom, this mechanism of sting loss by victim-mediated avulsion appears to be functionally equivalent to true autotomy in other social Hymenoptera. A second yellowjacket species, V. germanica (F.), exhibited the same type of sting loss, but at considerably lower frequencies.

There have been a limited number of studies examining the outcome after discontinuing venom immunotherapy (VIT), all of which showed continued protection in the great majority of patients. Several different criteria have been proposed to select patients to stop treatment based on immunologic and clinical factors. Specific high-risk factors have been reported from these published reports. There have been very few reports of the outcome more than 5 years after stopping VIT and virtually none on patients who had discontinued treatment for more than 10 years. This review will summarize the published evidence for current guidelines and recommendations, with emphasis on long-term outcomes.There has been a paucity of studies of VIT in recent years, particularly regarding long-term outcomes. These studies have raised questions about whether the long-term outcome is different with less than 3 years than with more than 3 years of treatment. Recent studies have confirmed the roughly 15% chance of systemic reaction to a sting after stopping VIT and the low risk (3%) of a severe reaction. New and meaningful observations have been made in several reports regarding the increased risk of relapse, and even death, in patients with mastocytosis or elevated baseline serum tryptase, who had discontinued VIT.This review incorporates old and new observations that provide the basis for the guidelines and practice parameters on discontinuing VIT.

The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.

Allergic reactions to insect venom can occur in individuals of all ages and may be preceded by a number of uneventful stings. These allergic reactions can be fatal. In the United States, at least 40 deaths due to insect stings occur each year; this number may be higher as some unexplained deaths may be caused by insect stings. This review details the epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, and acute and preventive treatment for allergic reactions to Hymenoptera. Figures show the honeybee, the European hornet, the Eastern yellow jacket, the red imported fire ant, the paper wasp, and the appearance of a pustule resulting from the sting of a fire ant. Tables list the risk of systemic reactions and clinical recommendations based on reaction to previous stings and venom skin test or serum immunoglobulin E test results, stinging insects of the order Hymenoptera, risk factors for severe reactions to stings, and risk factors for relapse after discontinuing venom immunotherapy. This review contains 6 highly rendered figures, 4 tables, and 62 references.