Current Trend in Immunotherapy for Peanut Allergy

Peanut allergy is a hypersensitivity reaction with symptoms varying from mild to severe anaphylaxis, tends to be lifelong and very few are able to outgrow this allergy. The prevalence of peanut allergy is highest among the Western countries and over the past decade, a 3.5 fold increase in prevalence of peanut allergy was reported among children in the United States. Increasing prevalence has also been observed among the Asian countries. As with other food allergies, peanut allergy reduces quality of life for the affected individuals and the social and economy burden of healthcare for peanut allergy is substantial. To date, there is no effective treatment for peanut allergy and disease management is by avoidance or relieve of symptoms via administration of epinephrine. Peanut allergy is a type-1 hypersensitivity reaction due to specific IgE production by activated T-helper type 2 (T_H2) cells. Studies on various immunotherapy routes such as oral immunotherapy (OIT), sublingual immunotherapy and epicutaneous immunotherapy trials using peanut have shown the ability to induce desensitisation, shifting the allergen-specific cytokine production away from a T_H2 respond. In the recent years, lactic acid bacteria probiotics have been reported to down-regulate allergy due to its inherent immunomodulatory properties. Wild-type probiotic in combination with peanut proteins or recombinant probiotics harbouring peanut allergens have been explored for OIT due to its ability to down-regulate allergen-specific-IgE production and the T_H2 responses, while increasing the beneficiary population of T_H1 regulatory T cells (T_reg). This review discusses the current strategies in immunotherapy for peanut allergy.     

Towards immunotherapy for peanut allergy

PURPOSE OF REVIEW: Food allergy is a major cause of life-threatening hypersensitivity reactions. Peanut allergy is the most serious of the hypersensitivity reactions to foods due to its persistence and high risk of severe anaphylaxis. Currently, strict avoidance of the allergenic food and ready access to self-injectable epinephrine is the 'standard of care' for food allergy. Based on extensive characterization of food allergens and a better understanding of the immunological mechanisms underlying allergic disease, promising therapeutic modalities for food allergy treatment and prevention are being developed. RECENT FINDINGS: Immunotherapeutic strategies include peptide immunotherapy, mutated protein immunotherapy and DNA immunization, which all strive to decrease the deleterious Th2 response. Another approach already in clinical trials for peanut allergy is the anti-IgE therapy which prevents circulating IgE from binding to effector cells, consequently decreasing clinical symptoms after peanut ingestion. In order to be applicable, these strategies must be well tolerated, inexpensive and easily administered. Realistic treatment options would likely involve a combination of different approaches. SUMMARY: Food allergy affects approximately 4-6% of children and 3-4% of adults. Peanut allergy can be devastating as reactions range from urticaria to severe anaphylactic shock and death. The only preventive measure for peanut allergy is strict avoidance of the incriminating food. It is likely immunotherapy will be available in the near future as a well tolerated and effective therapy for treating peanut allergy. The use of the anti-IgE therapy in conjunction with other immunotherapy would possibly be the best treatment option in the future.     

The safety of peanut oral immunotherapy in peanut-allergic subjects in a single-center trial

Background: Peanut allergy is the leading cause of food-related anaphylaxis, and accidental exposures are common. Oral immunotherapy (OIT) has been posited as a potential treatment. Methods: Patients aged 3-65 years with peanut-specific IgE ≥7 kU/l and/or a positive skin prick test with a history of an allergic reaction to peanut were recruited to undergo an OIT protocol. All adverse reactions were recorded by research staff or patients in real time. Results: Twenty-four patients received 6,662 doses. Symptoms were mostly mild (84%), and only 3 severe gastrointestinal reactions required the administration of epinephrine. Abdominal pain was the most common reaction, followed by oropharyngeal and lip pruritus. Respiratory symptoms were rare. Conclusions: In this trial of OIT in adults and children, most reactions were mild.     

Food allergy—From food avoidance to active treatment

The prevalence of food allergy (FA) has increased too rapidly, possibly due to environmental factors. The guidelines recommend strict allergen avoidance, but FA is still the main cause of anaphylaxis in all age groups. Immunotherapy is the only treatment able to change the course of allergic disease, and oral immunotherapy (OIT) is the more effective route in FA. However, it carries the risk of adverse reactions, including anaphylaxis. To improve OIT safety, adjuvant therapy with the immunoglobulin E (IgE) monoclonal antibody omalizumab has been extensively used. Results suggest particular benefit in patients with high risk of fatal anaphylaxis. An alternative approach is to use omalizumab instead of OIT to prevent severe allergic reactions upon accidental exposure. This paper reviews current evidence regarding IgE-mediated FA, focusing on natural tolerance and food sensitization acquisition, and on avoidance measures and their limitations.     

Treatment of peanut allergy with rush immunotherapy.

Peanut and peanut products are a common food in the diet. Peanuts are also one of the most common foods responsible for food-induced anaphylaxis. Patients rarely lose sensitivity to peanuts. Although the ideal treatment is avoidance, this is often not possible because of hidden exposures; therefore, a more effective treatment is needed. Subjects with confirmed peanut allergy were treated in a double-blind, placebo-controlled study with peanut immunotherapy or placebo. Objective measures of efficacy included changes in symptom score during double-blind placebo-controlled peanut challenge (DBPCPC) and titrated end point prick skin tests (PST). Three subjects treated with peanut immunotherapy completed the study. These subjects displayed a 67% to 100% decrease in symptoms induced by DBPCPC. Subjects also had a 2- to 5-log reduction in end point PST reactivity to peanut extract. One placebo-treated subject completed the study. This subject had essentially no change in DBPCPC symptom scores or PST sensitivity to peanut. Two other placebo-treated subjects underwent a second PST session. These subjects had a 1- to 2-log increase in skin test sensitivity to peanut. All peanut-treated subjects were able to reach maintenance dose, and in no case did an anaphylactic reaction occur secondary to the peanut immunotherapy. The current study provides preliminary data demonstrating the efficacy of injection therapy with peanut extract and provides a future line of clinical investigation for the treatment of this potentially lethal disease. It should be noted, however, that the rate of systemic reactions with rush immunotherapy was 13.3%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful oral tolerance induction in severe peanut allergy

Background:  Peanut allergy is common, potentially severe and rarely resolves causing impaired quality of life. No disease-modifying treatment exists and there is therefore a need to develop a therapeutic intervention.
Aims of the study:  The aim of this study was to investigate whether peanut oral immunotherapy (OIT) can induce clinical tolerance to peanut protein.
Methods:  Four peanut-allergic children underwent OIT. Preintervention oral challenges were performed to confirm clinical allergy and define the amount of protein required to cause a reaction (dose thresholds). OIT was then administered as daily doses of peanut flour increasing from 5 to 800 mg of protein with 2-weekly dose increases. After 6 further weeks of treatment, the oral challenge was repeated to define change in dose threshold and subjects continued daily treatment.
Results:  Preintervention challenges confirmed peanut allergy and revealed dose thresholds of 5–50 mg (1/40–1/4 of a whole peanut); one subject had anaphylaxis during challenge and required adrenaline injection. All subjects tolerated immunotherapy updosing to 800 mg protein and i.m. adrenaline was not required. Each subject tolerated at least 10 whole peanuts (approximately 2.38 g protein) in postintervention challenges, an increase in dose threshold of at least 48-, 49-, 55- and 478-fold for the four subjects.
Conclusions:  We demonstrated a substantial increase in dose threshold after OIT in all subjects, including the subject with proven anaphylaxis. OIT was well tolerated and conferred protection against at least 10 peanuts, more than is likely to be encountered during accidental ingestion.     

The natural history of persistent peanut allergy

BackgroundPeanut allergy affects 1% of children, and for those with persistent disease, few data have been published on trends in peanut-specific immunoglobulin E (P-IgE) levels or the value of P-IgE in predicting reaction severity.ObjectiveThe primary outcome was the frequency of inadvertent peanut exposure. Secondary outcomes included clinical characteristics, trends in P-IgE, characteristics of accidental exposures, and predictors of reaction severity in patients with persistent peanut allergy.MethodsRecords of patients with persistent peanut allergy were reviewed. Other allergic conditions, P-IgE levels, and peanut exposures were documented.ResultsSeven hundred eighty-two patients were studied, 524 of them male. The median age at initial observation was 1.4 years; the median duration of follow-up was 5.3 years. Of the 782 patients, 93.1% were avoiding other foods, 70.8% had atopic dermatitis, 57.3% allergic rhinitis, and 55.8% asthma. The median initial P-IgE was 28.0 kU/L, and the median peak P-IgE was 68.1. Six hundred eighty-five exposures were seen among 455 patients: 75.9% ingestion, 13.6% contact, 4.5% airborne. 73.7% resulted in urticaria/angioedema, 22.2% lower respiratory symptoms, 21.2% gastrointestinal symptoms, and 7.7% oral erythema/pruritus. Treatment included antihistamines (33.4%), emergency department visits (16.5%), epinephrine (13.1%), corticosteroids (7.7%), albuterol (3.2%), no treatment (26.3%), and not recorded (29.6%). The rate of postdiagnosis ingestion was 4.7%/year; exposures with severe reactions, 1.6%/year; reactions treated with epinephrine, 1.1%/year. Reaction severity did not change with repeated exposure. Severe reactions were associated with higher P-IgE, but not with age, sex, or asthma.ConclusionIn this referral population, the rates of accidental peanut exposures and severe reactions were low. There was a strong association between higher P-IgE levels and reaction severity.     

Beyond allergen avoidance: update on developing therapies for peanut allergy

PURPOSE OF REVIEW: Food allergy has emerged as a significant health problem. Peanut allergy is a major cause of food-induced fatal and near fatal anaphylactic reactions, and the incidence in children is increasing. Attempts to manage peanut allergy by strict avoidance are often unsuccessful. The purpose of this review is to highlight the most promising novel approaches for treating peanut allergy beyond allergen avoidance. RECENT FINDINGS: In the past 5 years much effort has been devoted to developing a treatment for peanut allergy. A recent clinical trial showed that monthly injections of humanized recombinant anti-IgE antibodies increased the threshold for allergic responses of peanut-sensitive individuals, at least to small amounts of peanut protein. However, this treatment cannot cure peanut allergy, and continuous monthly injections are necessary to maintain protection. Developing new therapies for the treatment of peanut allergy is essential. In reviewing publications between 2003 and 2005, several novel therapeutic approaches, tested in the murine model of peanut anaphylaxis appeared promising. Immunotherapy with engineered recombinant peanut protein and bacterial adjuvant significantly protected peanut allergic mice from anaphylaxis. It was also found that a Chinese herbal medicine formula called Food Allergy Herbal Formula-2 completely blocked anaphylaxis up to 5 weeks following therapy. These potent therapeutic effects are associated with immunoregulation of Th1 and Th2 responses. SUMMARY: Although there is no effective and safe therapy for food allergy, many novel approaches are under investigation. Some of these approaches may provide allergists with effective treatments in the near future.     

Availability of the epinephrine autoinjector at school in children with peanut allergy

BACKGROUND: Peanut allergy accounts for most severe food-related allergic reactions, and accidental exposures are frequent. Delayed administration of epinephrine and the allergic individual's failure to personally carry epinephrine contribute to fatal outcomes. OBJECTIVES: To describe epinephrine autoinjector availability at school and to determine factors that might affect autoinjector availability in children allergic to peanut. METHODS: Two hundred seventy-one children with peanut allergy living in Quebec were queried about their autoinjector. Logistic regression models were used to select factors associated with device availability. RESULTS: Four of 271 children diagnosed as having peanut allergy were not prescribed autoinjectors. Forty-eight percent of the children did not carry the autoinjector with them at school. In 78.0% of those, the autoinjector was located in the nurse's or another school office, which was staffed by a full-time nurse only in 18.5%. Of all the respondents, those administered epinephrine for a previous reaction (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3-5.7), older children (OR, 1.1; 95% CI, 1.0-1.2), and those living only with their mother (OR, 3.4; 95% CI, 1.0-11.0) were more likely to carry the autoinjector with them at school. Of children 7 years or older, those who experienced a severe reaction were more likely to carry their autoinjector (OR, 3.3; 95% CI, 1.4-8.1). CONCLUSIONS: Almost 50% of children allergic to peanut might experience a delay in anaphylaxis treatment due to limited access to their device. More education is required regarding the importance of a readily available autoinjector.     

Future therapies for food allergies

Food allergy is an increasingly prevalent problem in westernized countries, and there is an unmet medical need for an effective form of therapy. A number of therapeutic strategies are under investigation targeting foods that most frequently provoke severe IgE-mediated anaphylactic reactions (peanut, tree nuts, and shellfish) or are most common in children, such as cow's milk and hen's egg. Approaches being pursued are both food allergen specific and nonspecific. Allergen-specific approaches include oral, sublingual, and epicutaneous immunotherapy (desensitization) with native food allergens and mutated recombinant proteins, which have decreased IgE-binding activity, coadministered within heat-killed Escherichia coli to generate maximum immune response. Diets containing extensively heated (baked) milk and egg represent an alternative approach to food oral immunotherapy and are already changing the paradigm of strict dietary avoidance for patients with food allergy. Nonspecific approaches include monoclonal anti-IgE antibodies, which might increase the threshold dose for food allergen in patients with food allergy, and a Chinese herbal formulation, which prevented peanut-induced anaphylaxis in a murine model and is currently being investigated in clinical trials. The variety of strategies for treating food allergy increases the likelihood of success and gives hope that accomplishing an effective therapy for food allergy is within reach.     

Clinical update on peanut allergy.

BACKGROUND: Peanut allergy is common, potentially severe, and there has been a recent surge in clinical investigation of this important food allergen. OBJECTIVE: To provide the reader with a clinically oriented update on peanut allergy. DATA SOURCES: English language articles were selected from PubMed searches (search terms: peanut allergy, food allergy, anaphylaxis) and selected abstracts with a bias toward recent (3 years) studies judged to have immediate, practical clinical implications. RESULTS: Peanut allergy is an increasing problem in western diets that include this food. Both genetic and environmental factors influences the expression of this allergy. The at-risk subject is an atopic individual, with heightened risk for those with atopic dermatitis and/or other food allergies. The allergy is long-lived for most, may increase slightly in severity over time, but approximately 20% of young children will develop tolerance. Parameters that may identify the subset likely to achieve tolerance have been identified. Several large studies have determined laboratory parameters (skin tests, peanut-specific serum immunoglobulin E concentrations) with excellent predictive value (>95%) to diagnose current clinical reactivity or tolerance, although oral food challenges are necessary for a definitive diagnosis. Numerous practical lessons concerning management (avoidance, treatment, and prevention) have been identified. CONCLUSIONS: Recent studies provide the clinician with an armament of improved diagnostic and treatment modalities for peanut allergy. Studies are underway that are likely to provide more definitive therapies in the near future.     

Novel approaches for the treatment of food allergy

At present there is no effective therapy for IgE-mediated food allergy, and patients must rely upon food-allergen avoidance. Unfortunately, the accidental ingestion of allergen-containing foods leading to potentially severe reactions is common. Definitive therapies for food allergy are desperately needed. Although rush immunotherapy has been reported to induce tolerance in some patients, the rate of maintenance of tolerance was low, and there was an undesirably high incidence of adverse reactions. New knowledge of the immunological mechanisms underlying allergic disease has expanded the potential therapeutic options for food allergy. The establishment of animal models of food hypersensitivity, which include sensitization by the oral route and anaphylaxis upon oral challenge, have facilitated the investigation of therapies for food allergy. Novel approaches under investigation include the reduction of IgE by the infusion of anti-IgE antibodies, vaccination with plasmid DNA, the use of anti-allergy immunostimulatory sequences, cytokines and bacterial agents, immunotherapy with mutated proteins and peptides, and complementary medicine such as Chinese herbs.     

Unmet needs of children with peanut allergy: Aligning the risks and the evidence

BackgroundPeanut allergy is a potentially severe and lifelong allergy, with few effective treatments or preventive measures.ObjectiveTo convene an expert panel of allergists, pediatricians, and advocates to discuss and highlight unmet needs in the prevention and management of peanut allergies.MethodsLiterature searches of PubMed were performed. The panel evaluated published data on the prevention of peanut allergy, treatment of existing peanut allergy, and management of reactions after unintentional peanut exposures.ResultsThe following key unmet needs in the prevention and management of peanut allergy were identified: (1) enhancing and optimizing implementation of early peanut introduction as a means of preventing the development of peanut allergy, (2) developing knowledge translation strategies regarding the safety and efficacy data for current and emerging immunotherapies for peanut-allergic children to support their use in clinical practice, and (3) promoting understanding of true exposure risk in allergic individuals and ensuring access to epinephrine for unintentional exposures that provoke severe reactions. Practitioners should help educate caregivers about the actual risks associated with peanut allergy and its prevention and management so that treatment decisions can be evidence based rather than fear based. Support tools are needed to help address caregiver goals, expectations, and psychological barriers, as well as identify facilitators for prevention and treatment strategies.ConclusionThere are significant unmet needs in our understanding of peanut allergy; addressing these needs will help to enhance understanding of how to most effectively prevent and treat peanut allergy, as well as educate the food-allergic and nonallergic community regarding current evidence-based practices.     

Pepsin-digested peanut contains T-cell epitopes but no IgE epitopes

Background: Peanuts are a common cause of food-induced anaphylaxis and fatalities. Previous studies have demonstrated that rush immunotherapy to crude peanut extract reduces clinical symptoms triggered by oral peanut challenges, but the immunotherapy was associated with an unacceptably high incidence of systemic allergic reactions. One approach to reduce the frequency of allergic reactions would be to use a modified peanut antigen with low allergenic properties. Objective: We sought to determine the immunologic characteristics of crude intact peanut extract before and after pepsin digestion. Methods: We used IgE immunoblotting and assessment of T-lymphocyte responses to intact and peptic digests of peanut extracts. Results: Western blot analysis of sera from 5 subjects with peanut allergy showed multiple IgE-reactive proteins in crude intact peanut extract that were eliminated after pepsin treatment of the peanut extract. In contrast, pepsin-digested peanut induced significant T-cell proliferation responses (stimulation index = 30) in vitro in PBMCs from 7 subjects with peanut allergy, albeit at lower levels than that induced by intact peanut (stimulation index = 66). Furthermore, IFN-γ production was induced by intact peanut and pepsin-digested peanut in a concentration-dependent manner. Importantly, T-cell lines generated in response to intact peanut also reacted to pepsin-digested peanut, indicating cross-reactive T-cell epitopes in intact and pepsin-digested peanut. Conclusion: These findings suggest that pepsin-digested peanut may be useful in peanut immunotherapy because pepsin digestion eliminates IgE reactivity but maintains T-cell reactivity. (J Allergy Clin Immunol 1999;104:473-7.)     

Peanut allergy: emerging concepts and approaches for an apparent epidemic

Peanut allergy is typically lifelong, often severe, and potentially fatal. Because reactions can occur from small amounts, the allergy presents patients with significant obstacles to avoid allergic reactions. In North America and the United Kingdom, prevalence rates among schoolchildren are now in excess of 1%, framing an increasing public health concern and raising research questions about environmental, immunologic, and genetic factors that may influence outcomes of peanut allergy. This review focuses on recent observations that continue to question the influences of maternal and infant diet on outcomes of peanut allergy, and explore how peanut may be uniquely suited to induce an allergic response. We highlight studies that affect current diagnosis, management, and the nature of advice that can be provided to patients, including the utility of diagnostic tests, doses that elicit reactions, characteristics of reactions from exposure, issues of cross-reactivity, concerns about peanut contamination of manufactured goods, and the natural course of the allergy. Clinical, molecular, and immunologic advances are reviewed, highlighting research discoveries that influence strategies for improved diagnosis, prevention, and treatment. Among the therapeutic strategies reviewed are sublingual and oral immunotherapy, anti-IgE, Chinese herbal medicine, and vaccine strategies.     

Role of dendritic cells in peanut allergy

Introduction: The prevalence of peanut allergy (PA) has increased, affecting approximately 1.1% of children in Western countries. PA causes life-threatening anaphylaxis and frequently persists for life. There are no standardized curative therapies for PA, and avoidance of peanuts remains the main therapeutic option. A better understanding of the pathogenesis of PA is essential to identify new treatment strategies. Intestinal dendritic cells (DCs) are essential in the induction and maintenance of food tolerance because they present dietary allergens to T cells, thereby directing subsequent immune responses.

Areas covered: In this review, we discuss the factors related to the acquisition of oral tolerance to peanut proteins. We focus on intestinal DC-related aspects, including the latest advances in the biology of intestinal DC subtypes, effect of tolerance-inducing factors on DCs, effect of dietary components on oral tolerance, and role of DCs in peanut sensitization.

Expert commentary: Given the increasing prevalence of PA, difficulty of avoiding peanut products, and the potentially serious accidental reactions, the development of novel therapies for PA is needed. The ability of DCs to trigger tolerance or immunity makes them an interesting target for new treatment strategies against PA.     

The global burden of illness of peanut allergy: A comprehensive literature review

Peanut allergy (PA) currently affects approximately 2% of the general population of Western nations and may be increasing in prevalence. Patients with PA and their families/caregivers bear a considerable burden of self-management to avoid accidental peanut exposure and to administer emergency medication (adrenaline) if needed. Compared with other food allergies, PA is associated with higher rates of accidental exposure, severe reactions and potentially fatal anaphylaxis. Approximately 7%–14% of patients with PA experience accidental peanut exposure annually, and one-third to one-half may experience anaphylaxis, although fatalities are rare. These risks impose considerably high healthcare utilization and economic costs for patients with PA and restrictions on daily activities. Measures to accommodate patients with PA are often inadequate, with inconsistent standards for food labelling and inadequate safety policies in public establishments such as restaurants and schools. Children with PA are often bullied, resulting in sadness, humiliation and anxiety. These factors cumulatively contribute to significantly reduced health-related quality of life for patients with PA and families/caregivers. Such factors also provide essential context for risk/benefit assessments of new PA therapies. This narrative review comprehensively assessed the various factors comprising the burden of PA.     

Reaction phenotypes in IgE-mediated food allergy and anaphylaxis

ObjectiveFood allergy encompasses a range of food hypersensitivities. Different clinical phenotypes for food allergy likely exist in much the same way as endotype discovery is now a major research theme in asthma. We discuss the emerging evidence for different reaction phenotypes (ie, symptoms experienced after allergen exposure in food allergic individuals) and their relevance for clinical practice.Data SourcesPublished and unpublished literature relating to reaction phenotypes in food allergy.Study SelectionsAuthors assessment of the available data.ResultsFood anaphylaxis may be pathophysiologically different than anaphylaxis caused by nonfood triggers. Currently, there are no robust, clinically useful predictors of severity in food allergy. It is likely that patient-specific reaction phenotypes exist in food allergy, which may affect the risk of severe anaphylaxis. Allergen immunotherapy may modulate these phenotypes.ConclusionData are emerging to confirm our clinical experience that many food allergic patients experience stereotypical symptoms after allergen exposure, both in the community and at supervised oral food challenge, in a manner that varies among patients. Integrating data sets from different cohorts and applying unbiased machine-based learning analyses may demonstrate specific food allergy endotypes in a similar way to asthma. Whether this results in improvements in patient management (eg, through facilitating risk stratification or affecting the decision to prescribe an epinephrine autoinjector and, perhaps, the number of devices) remains to be determined, but given our current inability to predict which patients are most at risk of severe food allergic reactions, this will clearly be an important area of research in the future.     

A novel patient-reported outcomes instrument assessing the side effects of peanut oral immunotherapy

BackgroundPatients treated with peanut oral immunotherapy (OIT) may experience adverse reactions, particularly during up-dosing.ObjectiveTo develop the Side Effects of Peanut Oral Immunotherapy Diary (SEPOD), an electronic questionnaire assessing the daily side effects of peanut OIT in clinical trials.MethodsContent and design of the SEPOD were informed by empirical literature review and meetings with 3 allergy-immunology experts. Interviews to confirm content and inform revisions were conducted in 24 pediatric patients with peanut allergy (14 treated with peanut OIT) aged 6 to 17 years; children aged 6 to 11 years were interviewed with their caregiver.ResultsThe SEPOD was drafted after literature review and expert interviews; the initial measurement approach comprised 2 SEPOD versions, a patient-reported outcome (PRO) version for children aged 12 to 17 years, and a caregiver-administered PRO version for children aged 6 to 11 years with instructions for caregiver questionnaire administration. Pediatric patients were expected to respond independently on both versions. Patient interviews indicated that some younger children (ie, aged 6-8 years) had difficulty understanding questions, even when reading aloud; therefore, a caregiver-administered outcome version, identical in content to the caregiver-administered PRO version, was developed for this age group. The final electronic SEPOD covered 23 peanut OIT side effects within the following 7 domains: gastrointestinal, dermatologic, itching, nasal, and respiratory, swelling (eyelid or periorbital, lip, tongue, and throat), pain (tongue, mouth, and throat), and dizziness.ConclusionThis study yielded the SEPOD, a new clinical outcome assessment instrument with various methods of administration that can be used to assess the side effects of peanut OIT experienced by pediatric patients in a clinical trial setting.