The Economic Burden of Food Allergy: What We Know and What We Need to Learn.

Purpose of Review: Food allergy management and treatment require dietary modification, are associated with significant burdens, and affect food choices and behaviours. Emerging therapies, such as oral immunotherapy (OIT), provide a glimmer of hope for those living with the condition. Some burdens have received substantial focus, whereas many knowledge gaps on the significance of other impacts, including economic burden, remain. Recent Findings: Evidence from many countries, but disproportionately from the United States, supports that food allergy carries significant healthcare and societal costs. Early introduction for the prevention of food allergies is theoretically cost-effective, but remains largely undescribed. Unique considerations, such as those to cow's milk protein allergy, which affects a substantial proportion of infants, and adrenaline autoinjectors, which have a high cost-per-use, require a balance between cost-effectiveness to the healthcare system and adverse outcomes. Household costs have largely been explored in two countries, but owing to different healthcare structures and costs of living, comparisons are difficult, as are generalisations to other countries. Stock epinephrine in schools may present a cost-effective strategy, particularly in economically disadvantaged areas. Costs relating to OIT must be examined within both immediate benefits, such as protection from anaphylaxis, and long-term benefits, such as sustained unresponsiveness. Summary: Although the absolute costs differ by region/country and type of food allergy, a consistent pattern persists: food allergy is a costly condition, to those who live with it, and the multiple stakeholders with which they interact. Supplementary Information: The online version contains supplementary material available at 10.1007/s40521-022-00306-5.

The burden of food allergy on children and teens: A systematic review.

BACKGROUND: Over the last two decades, researchers have placed increasing attention on understanding how food allergy affects the health-related quality of life (HRQL) and psychosocial well-being of children and teens. In response, a number of reviews have been published that aim at synthesizing the literature. However, many of these papers focus narrowly on HRQL or suffer from methodological limitations. METHOD: The current review aims to fill this gap by providing a comprehensive overview of the burden of pediatric food allergy by synthesizing the quantitative and qualitative literature. RESULTS: Findings from the present review provide evidence of reduced HRQL among children and teens with food allergy, particularly older children and those with more severe manifestations of the condition. In comparison to HRQL, the link between food allergy and psychosocial functioning is less clear; however, some evidence can be cited linking food allergy to greater levels of psychological distress. Qualitative evidence suggests that the burden of pediatric food allergy largely stems from worries surrounding exposures outside of the home and the social consequences of the condition. The current review also highlights several gaps in the literature, including a paucity of longitudinal research, research focused on predictors of psychological distress among children and teens with food allergy as well as a dearth of studies comparing rates of bullying in food-allergic and non-food-allergic samples. CONCLUSION: More emphasis should be placed on not only alleviating the social and psychological consequences of food allergy, but also on identifying and assisting those most acutely burdened by the condition.

A scoping review of the caregiver burden of pediatric food allergy.

OBJECTIVE: Although a number of articles have described the psychosocial impact of raising a child with a food allergy, recent attempts at synthesizing this literature have been narrow in focus or methodologically limited. Consequently, this study aimed to synthesize both the quantitative and qualitative literature to achieve a better understanding of the psychosocial and financial burdens faced by families who raise children with food allergy. DATA SOURCES: Searches were performed on PubMed, Scopus, PsycInfo, and Cumulative Index to Nursing and Allied Health Literature databases for articles related to the psychosocial and financial burden experienced by individuals who care for a child with food allergy. STUDY SELECTIONS: English language, original research articles were included in this review. RESULTS: A total of 54 articles were deemed eligible for review. Results from the quantitative literature revealed that parents of children with food allergy (ie, food allergy and food protein-induced enterocolitis, proctocolitis, and enteropathy) consistently reported lower quality of life than their comparison groups. Within-group analyses suggest that this burden is increased for parents who manage multiple food allergies, severe food allergy, and comorbid allergic conditions. Thematic synthesis of the qualitative literature suggests that the psychosocial burden shouldered by parents of children with food allergy stems, in part, from the unpredictable threat of exposure and the practical and social burdens of managing a food allergy. In addition to psychosocial burdens, a small but growing body of literature suggests that families with food allergy also incur greater financial costs. CONCLUSION: Findings suggest that pediatric food allergy imposes considerable burdens on parents both quantitatively and qualitatively.

Pediatric food allergy-related household costs are influenced by age, but not disease severity.

OBJECTIVE: The economic burden of food allergy on households is poorly understood. We evaluated the household costs associated with specialist-diagnosed pediatric food allergy, with focus on age and disease severity. STUDY DESIGN: A cross-sectional study of 70 Swedish case-control pairs (59% boys) was conducted using Food Allergy Economic questionnaire. Household costs were analyzed between age- and gender-matched cases (children aged 0-17 years, with specialist-diagnosed food allergy) and controls (non-food allergic households). RESULTS: Parents were predominantly university-educated and employed full-time. Most cases had parent-reported previous anaphylaxis. Mean total annual household costs were comparable between cases and controls. However, compared to controls, cases had significantly higher direct medical-, and non-medical related costs; higher indirect medical-related costs, and higher intangible costs (all p < 0.05). In a sensitivity analyses of only cases aged 0-12 years, direct household costs, including lost earnings due to child's hospitalization, were significantly higher than controls. Results from only children with severe disease paralleled those of all cases vs. controls. CONCLUSIONS: Although pediatric food allergy is not associated with higher total annual household costs, these households have significantly higher direct medical-related, indirect and intangible costs vs. non-food allergic households. Higher household costs were identified amongst younger children, but not disease severity.

Food allergy-related concerns during the transition to self-management.

BACKGROUND: Compared to non-allergic individuals, food allergic individuals have impaired health-related quality of life (HRQL). However, effects of gender and age are unclear. The objective of our study was to describe associations between allergies to common foods and HRQL with consideration to gender and age. METHODS: Adolescents and adults (N = 137; 49.6% males) with specialist-diagnosed allergy to milk, egg and/or wheat completed age-appropriate versions of the Food Allergy Quality of Life Questionnaire (FAQLQ). We pooled common questions and calculated overall- and domain-specific HRQL in association with number and severity of symptoms and time elapse since worst reaction. RESULTS: In the entire study population, HRQL was not affected by gender or age, whereas gender-specific age categories affected HRQL among males only. For example, males 18-39 years had worse overall- (ß = 0.77; 95% CI 0.08-1.45) and domain-specific HRQL vs. males < 18 years. Among participants with 1-3 food allergy symptoms, no associations were found. Among participants with 4-6 symptoms, the domain allergen avoidance and dietary restrictions was worse among older participants (e.g. 40+ years: ß = 0.71; 95% CI 0.05-1.37 vs. < 18 years), and males 18-39 vs. < 18 years. Among participants with severe symptoms, females vs. males, and participants 18-39 vs. < 18 years had worse HRQL. At least 4 years since worst reaction was associated with worse HRQL for participants 40+ years vs. < 18 years, and older males vs. males < 18 years. Nearly all differences exceeded the clinical relevance threshold of ≥ 0.5. CONCLUSIONS: Associations between allergies to common foods and HRQL are affected by gender and age. Most affected are males 18-39 years. Among females, HRQL is more stable across age groups.

Health-related quality of life worsens by school age amongst children with food allergy.

BACKGROUND: Food allergy is negatively associated with health-related quality of life (HRQL). Although differences exist between parents and children, less is known about age-specific differences amongst children. As such, we aimed to identify if age, as well as other factors, are associated with food allergy-specific HRQL in an objectively defined population of children. METHODS: Overall, 63 children (boys: n = 36; 57.1%) with specialist-diagnosed food allergy to 1 + foods were included. Parents/guardians completed the Swedish version of a disease-specific questionnaire designed to assess overall- and domain-specific HRQL. Descriptive statistics and linear regression were used. RESULTS: The most common food allergy was hen's egg (n = 40/63; 63.5%). Most children had more than one food allergy (n = 48; 76.2%). Nearly all had experienced mild symptoms (e.g. skin; n = 56/63; 94.9%), and more than half had severe symptoms (e.g. respiratory; 39/63; 66.1%). Compared to young children (0-5 years), older children (6-12 years) had worse HRQL (e.g. overall HRQL: B = 0.60; 95% CI 0.05-1.16; p < 0.04.). Similarly, multiple food allergies, and severe symptoms were significantly associated with worse HRQL (all p < 0.05) even in models adjusted for concomitant allergic disease. No associations were found for gender or socioeconomic status. CONCLUSION: Older children and those with severe food allergy have worse HRQL.

Impaired health-related quality of life in adolescents with allergy to staple foods.

BACKGROUND: Cow's milk, hen's egg and wheat are staple foods in a typical western diet. Despite the ubiquity of these foods, the impact of staple food allergy on health-related quality of life (HRQL) amongst adolescents is incompletely understood. The aims of this study were to make use of the Swedish version of EuroPrevall's disease-specific food allergy quality of life questionnaire-teenager form (FAQLQ-TF) and to investigate the association between objectively-diagnosed staple food allergy and HRQL amongst adolescents. METHODS: In this cross-sectional study, 58 adolescents aged 13-17 years [n = 40 (69 %) boys] with objectively-diagnosed allergy to the staple foods cow's milk, hen's egg and/or wheat and living in Stockholm, Sweden were included. Adolescents completed the FAQLQ-TF, which has a corresponding scale of 1 = best HRQL, and 7 = worst HRQL. Overall HRQL and domain-specific HRQL were established. Adolescents also reported symptoms, adrenaline auto injector (AAI) prescription and presence of other food allergies. A history of anaphylaxis was defined among those reporting difficulty breathing, inability to stand/collapse, and/or loss of consciousness. Clinically different HRQL was set at a mean difference of ≥0.5. RESULTS: Overall mean HRQL was poorer than average [mean: 4.70/7.00 (95 % CI 4.30-5.01)]. The domain risk of accidental exposure was significantly associated with clinically better HRQL than the domain allergen avoidance and dietary restrictions (mean difference = 0.76; p < 0.001). Girls had clinically worse, but not statistically significantly different mean HRQL than boys (mean difference = 0.71; p < 0.07). HRQL tended to be worse amongst those with allergies to more than three foods or an AAI prescription. The number and types of symptoms, including a history of anaphylaxis were not associated with worse HRQL. CONCLUSIONS: As ascertained via a food allergy-specific questionnaire, adolescents with staple food allergy report poorer than average HRQL, specifically in relation to emerging independence and the need for support. Girls have clinically worse HRQL than boys. The number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL.

Investigating the association between allergen-specific immunoglobulin E, cancer risk and survival.

Prior findings linking allergy and cancer have been inconsistent, which may be driven by diverse assessment methods. We used serum specific immunoglobulin E (IgE) against common inhalant allergens that was assessed prior to cancer diagnosis in studying this association. We selected 8,727 Swedish men and women who had measurements of serum allergen-specific IgE and total IgE between 1992 and 1996. Multivariable Cox regression using age as a timescale was performed to assess the associations of IgE sensitization, defined by any levels of serum specific IgE ≥35 kU/L, with risk of overall and specific cancers. A test for trend was performed by assigning scores derived from allergen-specific IgE levels at baseline as an ordinal scale. Kaplan-Meier curves and log-rank test were used to assess cancer survival by IgE sensitization status. During a mean follow-up of 16 year, 689 persons were diagnosed with cancer. We found an inverse association between IgE sensitization and cancer risk, with a hazard ratio (HR) of 0.83 and 95% confidence intervals (CI) of 0.70-0.99. A similar trend was seen with specific IgE scores overall (Ptrend = 0.007) and in women (Ptrend = 0.01). Although IgE sensitization was not associated with risk of common site-specific cancers, serum specific IgE scores were inversely associated with melanoma risk in men and women combined, and with risk of female breast and gynecological cancers combined. No association with survival was observed. The association between circulating IgE levels and incident cancer may point toward a role of T-helper 2 (TH2)-biased response in development of some cancers.

Distinguishing benign from pathologic TH2 immunity in atopic children.

BACKGROUND: Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms. OBJECTIVE: We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children. METHODS: In 3 independent population samples we analyzed relationships between aeroallergen-specific IgE and corresponding allergen-specific IgG (sIgG) and associated immunophenotypes in atopic children and susceptibility to asthma and rhinitis, focusing on responses to house dust mite and grass. RESULTS: Among mite-sensitized children across all populations and at different ages, house dust mite-specific IgG/IgE ratios (but not IgG4/IgE ratios) were significantly lower in children with asthma compared with ratios in those without asthma and lowest among the most severely symptomatic. This finding was mirrored by relationships between rhinitis and antibody responses to grass. Depending on age/allergen specificity, 20% to 40% of children with allergen-specific IgE (sIgE) of 0.35 kU/L or greater had negative skin test responses, and these children also expressed the high sIgG/sIgE immunophenotype. sIgG1 from these children inhibited allergen-induced IgE-dependent basophil activation in a dose-dependent fashion. Profiling of aeroallergen-specific CD4(+) TH memory responses revealed positive associations between sIgG/sIgE ratios and IL-10-dependent gene signatures and significantly higher IL-10/TH2 cytokine (protein) ratios among nonsymptomatic children. CONCLUSION: In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor. We posit that its production during allergen-induced memory responses contributes significantly to attenuation of inflammation through promoting IgG1-mediated damping of the FcεRI-dependent acute-phase reaction. sIgG1/sIgE balance might represent a readily accessible therapeutic target for asthma/rhinitis control.

Innate IgG molecules and innate B cells expressed by immunoglobulin constant heavy G chain (Fcγ) genetic marker genes are involved in the 'allergic march' of IgE sensitization in children.

BACKGROUND: Interindividual variations of immunoglobulin constant heavy G chain (IGHG) genes on chromosome 14q32.3 are identified by alternative genetic markers (GM) of IgG3, IgG1 and IgG2, respectively. They express structurally and functionally innate IgG molecules and B cells, associated with allergic disease, replicated in several studies. MATERIALS AND METHODS: 1-year-old and 10-year-old, IgE-sensitized and non-sensitized children from the German Multicenter Allergy Study birth cohort were assessed by new serological methods for the mendelian IGHG (Fcγ) (GM) genes, as innate IgG molecules and innate B cells. RESULTS: Food allergy sensitization in thirty-five 1-year-old children (124 not sensitized) was associated with the IGHG*bfn haplotype and B*(bfn) cells (OR 1.9, 95% CI 1.2-3.1; p = 0.010). Aeroallergen sensitization in ninety-nine 10-year-old children (95 not sensitized) was associated with the same genes (OR 1.4, 95% CI 1.02-1.9; p = 0.034). The IgE sensitization was most prominent in the restrictive homozygous IGHG*bfn/*bfn diplotype, 34% at age 1, increasing to 60% at age 10, rating the highest numbers of positive IgE tests, expressing increased levels of IgE and innate IgG2*n. CONCLUSIONS: The IGHG*bfn haplotype (B*(bfn) cells) and increased innate IgG2*n levels are predictive factors for IgE sensitization in childhood. IGHG genes can be assessed for prognostic and preventive purposes in clinical care.

Household costs associated with objectively diagnosed allergy to staple foods in children and adolescents.

BACKGROUND: We previously reported that indirect and intangible costs burden households with a food allergic adult. We now extend our investigation to households with food allergic children and adolescents. OBJECTIVE: The objective of this study was to estimate direct, indirect, and intangible costs of food allergy in households with a child and/or adolescent with objectively diagnosed allergy to staple foods (cow's milk, hen's egg, and/or wheat), and to compare these costs with age- and sex-matched controls. METHODS: Direct and indirect cost parent-reported data collected via the Food Allergy Socio-Economic Questionnaire of 84 children (0-12 years) and 60 adolescents (13-17 years) with objectively diagnosed allergy to staple foods ("cases") and age- and sex-matched controls (n = 94 children; n = 56 adolescents) were compared. Annual household costs were calculated. Total household costs included direct plus indirect costs. Intangible costs included parent-reported health of their child and/or adolescent, standard of living, and perceptions of well-being. RESULTS: Amongst cases, total household costs were higher by €3961 for children and €4792 for adolescents versus controls (P < .05), and were driven by direct (eg, medications) and indirect (eg, time with health care professionals) costs. For children only, a history of anaphylaxis was associated with higher direct costs than no anaphylaxis (€13,016 vs €10,044, P < .05). Intangible costs (eg, parent-reported health of a child and/or adolescent) were significantly impacted amongst cases versus controls (P < .01). CONCLUSION: Households with a child and/or adolescent with objectively diagnosed allergy to staple foods have higher total household costs than controls. Direct and indirect costs were significantly higher for cases versus controls amongst children only. Amongst both age groups, such allergy adversely impacted intangible costs.

Health-related quality of life, assessed with a disease-specific questionnaire, in Swedish adults suffering from well-diagnosed food allergy to staple foods.

BACKGROUND: Our aim was to investigate the factors that affect health related quality of life (HRQL) in adult Swedish food allergic patients objectively diagnosed with allergy to at least one of the staple foods cow's milk, hen's egg or wheat. The number of foods involved, the type and severity of symptoms, as well as concomitant allergic disorders were assessed. METHODS: The disease-specific food allergy quality of life questionnaire (FAQLQ-AF), developed within EuroPrevall, was utilized. The questionnaire had four domains: Allergen Avoidance and Dietary Restrictions (AADR), Emotional Impact (EI), Risk of Accidental Exposure (RAE) and Food Allergy related Health (FAH). Comparisons were made with the outcome of the generic questionnaire EuroQol Health Questionnaire, 5 Dimensions (EQ-5D). The patients were recruited at an outpatient allergy clinic, based on a convincing history of food allergy supplemented by analysis of specific IgE to the foods in question. Seventy-nine patients participated (28 males, 51 females, mean-age 41 years). RESULTS: The domain with the most negative impact on HRQL was AADR, assessing the patients' experience of dietary restrictions. The domain with the least negative impact on HRQL was FAH, relating to health concerns due to the food allergy. One third of the patients had four concomitant allergic disorders, which had a negative impact on HRQL. Furthermore, asthma in combination with food allergy had a strong impact. Anaphylaxis, and particularly prescription of an epinephrine auto-injector, was associated with low HRQL. These effects were not seen using EQ-5D. Analyses of the symptoms revealed that oral allergy syndrome and cardiovascular symptoms had the greatest impact on HRQL. In contrast, no significant effect on HRQL was seen by the number of food allergies. CONCLUSIONS: The FAQLQ-AF is a valid instrument, and more accurate among patients with allergy to staple foods in comparison to the commonly used generic EQ-5D. It adds important information on HRQL in food allergic adults. We found that the restrictions imposed on the patients due to the diet had the largest negative impact on HRQL. Both severity of the food allergy and the presence of concomitant allergic disorders had a profound impact on HRQL.

Update of prevalence of self-reported allergic rhinitis and chronic nasal symptoms among adults in Sweden.

BACKGROUND: Allergic rhinitis (AR) is the most common immunologic disease, and it renders a considerable burden on both sufferers and society. The prevalence of AR has been increasing worldwide over the past century. The aim of this study was to assess the present prevalence, risk factor patterns and comorbidity of self-reported AR and chronic nasal symptoms in different age groups in Stockholm, Sweden. METHODS: A postal questionnaire was sent on two occasions, in 2006 to a population aged 30-80 years, randomly selected 10 years previously, and in 2007 to a randomly selected sample of subjects aged 20-69 years. The response rates were 83% and 68%, respectively, and in total, 9792 subjects participated. The questionnaire included questions on self-reported AR, asthma, respiratory and nasal symptoms and possible determinants. RESULTS: The prevalence of self-reported AR was 28.0% (men 26.6%, women 29.1%, P < 0.01) similar to 10 years previously and 33.6% in ages 30-40 years. Allergic heredity [odds ratio (OR) 4.76, confidence interval (CI) 95% 4.25-5.33], physician-diagnosed asthma (OR 5.29, CI 95% 4.49-6.24) and occupational exposure to dust, gases and fumes (OR 1.49, CI 95% 1.30-1.72) were determinants for AR. Prevalence of chronic nasal congestion was 16.1% and of chronic rhinorrhea 14.1%. CONCLUSIONS: As a basis for understanding the disease, as well as in planning and prioritizing health-care resources, the study provides information about the current prevalence and determinants of self-reported AR and chronic nasal symptoms. Further, comparing with previous studies, the present study suggests that a plateau in the prevalence of AR may have been reached in Sweden.

Evaluation of IgE antibodies to recombinant peanut allergens in patients with reported reactions to peanut.

BACKGROUND: Peanut may cause severe reactions in allergic individuals. The objective was to evaluate IgE antibodies to various recombinant (r) peanut and birch pollen allergens in relation to IgE levels to whole peanut extract and severe allergic reactions to peanut. METHODS: Seventy-four Swedish peanut-allergic patients (age: 14-61 years) reported previous peanut exposure and associated symptoms using a questionnaire. Their IgE reactivity to peanut, birch pollen and individual allergen components was analyzed using ImmunoCAP. RESULTS: Of the 48 subjects sensitized to Ara h 1, 2 or 3, 60% had peanut-specific IgE levels >15 kU(A)/l, while 100% of the subjects without detectable IgE to these allergens had low peanut-specific IgE levels (<10 kU(A)/l). The levels of IgE to rAra h 8, rBet v 1 and birch pollen were highly correlated (r(S) = 0.94, p < 0.0001). Fifty-eight patients reported adverse reactions after accidental or deliberate peanut exposure (oral, inhalation or skin) of whom 41 had IgE to rAra h 1, 2 or 3. Symptoms of respiratory distress were associated with sensitization to Ara h 1, 2 or 3 (56 vs. 18%, p < 0.01). Two cases of anaphylaxis were reported among the individuals sensitized to Ara h 1-3. IgE to rAra h 8, rAra h 9, profilin or cross-reactive carbohydrate determinants were not associated with severe symptoms. CONCLUSIONS: The results indicate that IgE reactivity to Ara h 1, 2 and 3 is associated with severe reactions after exposure to peanut in Swedish patients.

Allergen-specific IgG antibody levels modify the relationship between allergen-specific IgE and wheezing in childhood.

BACKGROUND: An increase in IgE antibody levels to inhalant allergens is associated with an increased likelihood of wheezing. The role of allergen-specific IgG and IgG4 in relation to wheezing is yet to be determined. OBJECTIVE: We sought to investigate whether Fel d 1-specific IgG and IgG4 antibodies modify the association between cat allergen-specific IgE and childhood wheezing. METHODS: We used data from 2 population-based birth cohorts (United Kingdom [UK], n = 473; Australia, n = 1336). Current wheeze was defined as wheezing in the previous 12 months at age 5 (UK) and 14 (Australia) years. We determined cat allergen-specific IgE (whole extract) and IgG and IgG4 antibody (purified rFel d 1) levels and used logistic regression to estimate the relationship between wheeze and the quantitative allergen antibody levels. RESULTS: In the univariate analysis risk of wheezing increased significantly with increasing cat-specific IgE levels (UK: odds ratio [OR], 1.56; 95% CI, 1.28-1.90; Australia: OR, 1.29; 95% CI, 1.19-1.40). rFel d 1-specific IgG or IgG4 had no significant effect on wheeze in either population. However, a different pattern of the relationship between antibody levels and wheezing emerged in the multivariate analysis. In the UK cat-specific IgE increased the risk of wheeze (OR, 2.01; 95% CI, 1.29-3.12; P = .002), whereas rFel d 1-specific IgG decreased the risk (OR, 0.46; 95% CI, 0.21-0.99; P = .05). This finding was replicated in Australia (IgE: OR, 1.46; 95% CI, 1.28-1.68; P < .001; IgG: OR, 0.66; 95% CI, 0.44-0.99; P = .049). There was no significant association between IgG4 antibody levels and wheezing in either population. CONCLUSIONS: rFel d 1-specific IgG but not IgG4 antibody levels significantly modify the association between cat-specific IgE and childhood wheezing, with the risk of symptoms decreasing with increasing IgG levels.

Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions.

BACKGROUND: Peanut allergy affects persons from various geographic regions where populations are exposed to different dietary habits and environmental pollens. OBJECTIVE: We sought to describe the clinical and immunologic characteristics of patients with peanut allergy from 3 countries (Spain, the United States, and Sweden) using a molecular component diagnostic approach. METHODS: Patients with peanut allergy from Madrid (Spain, n = 50), New York (United States, n = 30), Gothenburg, and Stockholm (both Sweden, n = 35) were enrolled. Clinical data were obtained either from a specific questionnaire or gathered from chart reviews. IgE antibodies to peanut extract and the peanut allergens rAra h 1, 2, 3, 8 and 9, as well as to cross-reactive birch (rBet v 1) and grass (rPhl p 1, 5, 7, and 12) pollen allergens, were analyzed. RESULTS: American patients frequently had IgE antibodies to rAra h 1 to 3 (56.7% to 90.0%) and often presented with severe symptoms. Spanish patients recognized these 3 recombinant peanut allergens less frequently (16.0% to 42.0%), were more often sensitized to the lipid transfer protein rAra h 9 (60.0%), and typically had peanut allergy after becoming allergic to other plant-derived foods. Swedish patients detected rAra h 1 to 3 more frequently than Spanish patients (37.1% to 74.3%) and had the highest sensitization rate to the Bet v 1 homologue rAra h 8 (65.7%), as well as to rBet v 1 (82.9%). Spanish and Swedish patients became allergic to peanut at 2 years or later, whereas the American children became allergic around 1 year of age. CONCLUSIONS: Peanut allergy has different clinical and immunologic patterns in different areas of the world. Allergen component diagnostics might help us to better understand this complex entity.