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BACKGROUND: In individuals without symptomatic food allergy, food-specific IgE is considered clinically irrelevant. However, recent studies have suggested that galactose-α-1,3-galactose (alpha-gal) IgE is associated with cardiovascular (CV) disease. OBJECTIVE: We sought to determine whether sensitization to common food allergens is associated with CV mortality. METHODS: The association between IgE sensitization to foods and CV mortality ascertained to 2019 was examined in the National Health and Examination Survey (NHANES) 2005-2006 and the Wake Forest site of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort; MESA enrolled adults without baseline clinical CV diseases between 2000 and 2002. Total and specific IgE was measured to cow's milk, egg, peanut, shrimp, and a panel of aeroallergens (NHANES), and to cow's milk, alpha-gal, peanut, dust mite, and timothy grass (MESA). Cox proportional hazard models were constructed, adjusting for sex, age, race/ethnicity, smoking, education, and asthma. RESULTS: A total of 4414 adults from NHANES (229 CV deaths) and 960 from MESA (56 CV deaths) were included. In NHANES, sensitization to at least 1 food was associated with higher CV mortality (hazard ratio [HR], 1.7 [95% confidence interval (CI), 1.2-2.4], P = .005). Milk sensitization was particularly associated (HR, 2.0 [95% CI, 1.1-3.8], P = .026), a finding replicated in MESA (HR, 3.8 [95% CI, 1.6-9.1], P = .003). Restricting analyses in NHANES to consumers of the relevant allergen strengthened food sensitization relationships, unmasking shrimp and peanut sensitization as additional risk factors for CV mortality. CONCLUSIONS: The finding that food sensitization is associated with increased risk of CV mortality challenges the current paradigm that sensitization without overt allergy is benign. Further research is needed to clarify mechanisms of this association.
Assuntos
Aterosclerose , Hipersensibilidade Alimentar , Adulto , Feminino , Animais , Bovinos , Humanos , Inquéritos Nutricionais , Galactose , Hipersensibilidade Alimentar/epidemiologia , Alérgenos/efeitos adversos , Leite , Imunoglobulina ERESUMO
The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERS) organized a day-long symposium at the 2024 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research and debates on the mechanisms and management of eosinophilic gastrointestinal diseases (EGIDs). Updates on recent clinical trials and consensus guidelines were also presented. Herein, we summarize the updates on EGIDs presented at the symposium.
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BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
Assuntos
Esofagite Eosinofílica , Adulto , Criança , Consenso , Endoscopia Gastrointestinal , Enterite , Eosinofilia , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/terapia , Gastrite , Humanos , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: High levels of serum food-specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics. METHODS: This was a case-control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE-negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels. RESULTS: The analysis included 123 individuals (EoE n = 93, control n = 30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p = .30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p = .24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p = .01) and the presence of sIgE to milk (OR 4.23; p = .008). CONCLUSION: Serum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non-EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study.
Assuntos
Esofagite Eosinofílica , Humanos , Animais , Estudos Prospectivos , Imunoglobulina G , Estudos de Casos e Controles , Imunoglobulina E , Alérgenos , LeiteRESUMO
BACKGROUND: Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co-localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits. METHODS: This study included adult subjects with EoE (n = 13) and non-EoE controls (n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co-localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4-food protein interactions were confirmed with co-immunoprecipitation and mass spectrometry. RESULTS: IgG4-CMP co-localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p = .02; Bos d 5, p = .002; Bos d 8, p = .002). Co-localization was also significantly higher in the active EoE group compared to non-EoE controls (Bos d 4, p = .0013; Bos d 5, p = .0007; Bos d 8, p = .0013). AutoSTOMP identified eosinophil-derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain-14 in IgG4-enriched areas. Co-immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens. CONCLUSION: These findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression.
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Esofagite Eosinofílica , Adulto , Feminino , Animais , Bovinos , Humanos , Esofagite Eosinofílica/patologia , Complexo Antígeno-Anticorpo , Imunoglobulina G , Alérgenos , Proteínas do LeiteRESUMO
PURPOSE OF REVIEW: Compelling evidence over the past decade supports the central role of epithelial barrier dysfunction in the pathophysiology of eosinophilic esophagitis (EoE). The purpose of this review is to summarize the genetic, environmental, and immunologic factors driving epithelial barrier dysfunction, and how this impaired barrier can further promote the inflammatory response in EoE. RECENT FINDINGS: Common environmental exposures, such as detergents, may have a direct impact on the esophageal epithelial barrier. In addition, the effects of IL-13 on barrier dysfunction may be reduced by 17ß-estradiol, Vitamin D, and the short chain fatty acids butyrate and propionate, suggesting novel therapeutic targets. There are many genetic, environmental, and immunologic factors that contribute to epithelial barrier dysfunction in EoE. This leads to further skewing of the immune response to a "Th2" phenotype, alterations in the esophageal microbiome, and penetration of relevant antigens into the esophageal mucosa, which are central to the pathophysiology of EoE.
Assuntos
Esofagite Eosinofílica , Gastrite , Humanos , Esofagite Eosinofílica/etiologia , Mucosa Esofágica , Fatores Imunológicos/uso terapêuticoRESUMO
BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
Assuntos
Esofagite Eosinofílica , Adulto , Criança , Consenso , Endoscopia Gastrointestinal , Enterite , Eosinofilia , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/terapia , Gastrite , Humanos , Índice de Gravidade de DoençaRESUMO
BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.
Assuntos
Enterite , Eosinofilia , Esofagite Eosinofílica , Gastrite , Humanos , Consenso , Enterite/diagnóstico , Enterite/complicações , Gastrite/diagnóstico , Gastrite/complicações , Eosinofilia/diagnóstico , Eosinofilia/complicações , Esofagite Eosinofílica/complicaçõesRESUMO
OBJECTIVE: To summarize the existing literature for several promising minimally invasive tests to measure disease activity in eosinophilic esophagitis (EoE). DATA SOURCES: Literature searches were performed using PubMed. Keyword combinations included eosinophilic esophagitis and minimally invasive techniques, including the esophageal string test, Cytosponge, transnasal endoscopy, technetium-labeled heparin, and noninvasive biomarkers. STUDY SELECTIONS: Retrospective and prospective observational studies, peer-reviewed reviews, and systematic reviews were selected. Data were reviewed and summarized. RESULTS: Various techniques have been developed in recent years to measure disease activity in EoE without the need for conventional endoscopy. Our review summarizes the data on these techniques, the benefits and limitations, and future directions for implementation in both research and clinical care. CONCLUSION: Tremendous progress has been made toward developing minimally invasive techniques to measure disease activity in EoE. Each of the techniques mentioned in this review has advantages and disadvantages, and some are closer to widespread use than others.
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Esofagite Eosinofílica , Biomarcadores , Esofagite Eosinofílica/diagnóstico , Humanos , Estudos Observacionais como Assunto , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: A syndrome of mammalian meat allergy relating to IgE specific for galactose-α-1,3-galactose (α-Gal) was first reported 10 years ago in the southeastern United States and has been related to bites of the lone star tick (Amblyomma americanum). OBJECTIVE: Here we investigated the epidemiology of the "α-Gal syndrome" in the United States and sought additional evidence for the connection to tick bites. METHODS: A survey of allergists was conducted by using a snowball approach. A second tier of the survey included questions about anaphylaxis to imported fire ants (IFAs). History of tick bites and tick-related febrile illness were assessed as part of a case-control study in Virginia. Antibody assays were conducted on sera from subjects reporting allergic reactions to mammalian meat or IFA. RESULTS: In North America the α-Gal syndrome is recognized across the Southeast, Midwest, and Atlantic Coast, with many providers in this area managing more than 100 patients each. The distribution of cases generally conformed to the reported range of A americanum, although within this range there was an inverse relationship between α-Gal cases and cases of IFA anaphylaxis that were closely related to the territory of IFA. The connection between tick bites and α-Gal sensitization was further supported by patients' responses to a questionnaire and the results of serologic tests. CONCLUSIONS: The α-Gal syndrome is commonly acquired in adulthood as a consequence of tick bites and has a regional distribution that largely conforms to the territory of the lone star tick. The epidemiology of the syndrome is expected to be dynamic and shifting north because of climate change and ecologic competition from IFA.
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Anafilaxia/etiologia , Formigas , Hipersensibilidade Alimentar/epidemiologia , Doenças Transmitidas por Carrapatos/epidemiologia , Amblyomma , Anafilaxia/imunologia , Animais , Hipersensibilidade Alimentar/etiologia , Geografia , Humanos , Imunoglobulina E/imunologia , Picadas de Carrapatos/complicações , Picadas de Carrapatos/imunologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Allergen-specific IgG4 (sIgG4) antibodies are often associated with tolerance, but sIgG4 antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG4 are not well established in the general pediatric population. OBJECTIVE: We sought to investigate serum food sIgG4 with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG4 levels. METHODS: Sera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgG4 and specific IgE (sIgE) to major cow's milk (CM) proteins (α-lactalbumin, ß-lactoglobulin, and caseins) and to wheat, soy, egg, and peanut proteins. RESULTS: In the EoE cohort high-titer sIgG4 (≥10 µg/mL) to CM proteins was more common than in control sera and achieved odds ratios for EoE ranging from 5.5 to 8.4. sIgE levels to CM proteins were mostly 4 IU/mL or less in patients with EoE, such that sIgG4/sIgE ratios were often 10,000 or greater. When adjusted for age and milk consumption, high-titer sIgG4 to CM proteins was strongly associated with EoE, with an odds ratio of greater than 20 to all 3 CM proteins in boys. CONCLUSIONS: sIgG4 to CM proteins are common and high titer in children with EoE. Although it is not clear that this response is pathogenic, sIgG4 levels imply that these antibodies are an important feature of the local immune response that gives rise to EoE.
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Esofagite Eosinofílica/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Leite/imunologia , Adolescente , Alérgenos/imunologia , Animais , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9-5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6-85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.
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Biomarcadores , Imunodeficiência de Variável Comum/diagnóstico , Imunoglobulina E/sangue , Adolescente , Adulto , Alérgenos/imunologia , Criança , Estudos de Coortes , Imunodeficiência de Variável Comum/sangue , Imunodeficiência de Variável Comum/imunologia , Feminino , Humanos , Imunização , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Masculino , Sensibilidade e Especificidade , Adulto JovemRESUMO
Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. In adults, the three most common treatment options are swallowed steroids, elimination diets, and periodic esophageal dilations. Many different elimination diets have been studied in adults, including elemental diets, allergy testing-directed diets, and empiric elimination diets. This article will review the existing data on these dietary therapies and will propose an approach to dietary management in adult EoE.
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Esofagite Eosinofílica/dietoterapia , Esofagite Eosinofílica/etiologia , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/dietoterapia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/imunologia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/imunologia , Testes Cutâneos/métodosRESUMO
OBJECTIVE: Previous data suggest that food allergy (FA) might be more common in inner-city children; however, these studies have not collected data on both sensitization and clinical reactivity or early-life exposures. METHODS: Children in the Urban Environment and Childhood Asthma birth cohort were followed through age 5 years. Household exposures, diet, clinical history, and physical examinations were assessed yearly; levels of specific IgE to milk, egg, and peanut were measured at 1, 2, 3, and 5 years of age. On the basis of sensitization (IgE ≥0.35 kU/L) and clinical history over the 5-year period, children were classified as having FA or being possibly allergic, sensitized but tolerant, or not allergic/not sensitized. RESULTS: Five hundred sixteen children were included. Overall, 55.4% were sensitized (milk, 46.7%; egg, 31.0%; and peanut, 20.9%), whereas 9.9% were categorized as having FA (peanut, 6.0%; egg, 4.3%; and milk, 2.7%; 2.5% to >1 food). The remaining children were categorized as possibly allergic (17.0%), sensitized but tolerant (28.5%), and not sensitized (44.6%). Eighteen (3.5%) reported reactions to foods for which IgE levels were not measured. Food-specific IgE levels were similar in children with FA versus sensitized but tolerant children, except for egg, levels of which were higher in patients with FA at ages 1 and 2 years. FA was associated with recurrent wheeze, eczema, aeroallergen sensitization, male sex, breast-feeding, and lower endotoxin exposure in year 1 but not with race/ethnicity, income, tobacco exposure, maternal stress, or early introduction of solid foods. CONCLUSIONS: Even given that this was designed to be a high-risk cohort, the cumulative incidence of FA is extremely high, especially considering the strict definition of FA that was applied and that only 3 common allergens were included.
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Alérgenos/análise , Hipersensibilidade a Ovo/epidemiologia , Exposição Ambiental/análise , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Amendoim/epidemiologia , População Urbana/estatística & dados numéricos , Pré-Escolar , Cidades/epidemiologia , Estudos de Coortes , Citocinas/imunologia , Poeira/análise , Hipersensibilidade a Ovo/sangue , Exposição Ambiental/efeitos adversos , Feminino , Disparidades nos Níveis de Saúde , Habitação , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Masculino , Hipersensibilidade a Leite/sangue , Hipersensibilidade a Amendoim/sangue , Prevalência , Estados Unidos/epidemiologiaAssuntos
Dessensibilização Imunológica/métodos , Esofagite Eosinofílica/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Inflamação/imunologia , Reaginas/metabolismo , Animais , Citocinas/metabolismo , Humanos , Tolerância Imunológica , Testes Imunológicos , Modelos Imunológicos , Células Th2/imunologia , Peçonhas/imunologiaAssuntos
Alérgenos/imunologia , Dermatophagoides farinae/imunologia , Penaeidae/imunologia , Periplaneta/imunologia , Hipersensibilidade a Frutos do Mar/epidemiologia , Tropomiosina/imunologia , Adolescente , Alérgenos/administração & dosagem , Animais , Proteínas de Artrópodes/administração & dosagem , Proteínas de Artrópodes/imunologia , Criança , Dermatophagoides farinae/química , Feminino , Humanos , Imunização/estatística & dados numéricos , Imunoglobulina E/sangue , Incidência , Masculino , Inquéritos Nutricionais/estatística & dados numéricos , Penaeidae/química , Periplaneta/química , Prevalência , Homologia de Sequência de Aminoácidos , Hipersensibilidade a Frutos do Mar/imunologia , Tropomiosina/administração & dosagem , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Food allergy is a common condition for which the only currently approved treatments are avoidance of the allergenic food and the administration of emergency medications upon accidental exposure. Over the past 10 years, significant advances have been made in the field of food immunotherapy, with efforts focusing on allergen exposure via the oral mucosa. Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are the two modalities that have been most extensively studied, and this article will review recent advances in our knowledge of the efficacy and safety of these treatments.