Citrin: a novel food allergen in citrus seeds and citrus-derived pectin that shows cross-reactivity with cashew and pistachio.

BACKGROUND: Patients exquisitely sensitive to cashew/pistachio are at risk for allergic reactions to citrus seeds and pectin. OBJECTIVE: In this study, we sought to evaluate whether pectin is contaminated with citrus seeds, to identify a culprit antigen in citrus seeds, and to assess for cross-reactivity among allergens in citrus seeds, citrus pectin, and cashew or pistachio. METHODS: Proteins from orange seed coats, orange seed endosperms, lemon seeds, grapefruit seeds, citrus pectin, apple pectin, and grapefruit pectin were extracted. Protein concentrations in all extracts were determined and visualized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis technique. Immunoglobulin E-binding capacity was determined with Western blot analyses and tandem mass spectrometry for the identification of the culprit allergen in citrus seeds and pectin. RESULTS: In subjects with citrus seed, pectin, and cashew allergies, there was strong immunoglobulin E-reactivity to bands between 17 to 28 kDa and 28 to 38 kDa. The tandem mass spectrometry analysis of these bands indicated the presence of citrin as the culprit allergen. Citrin and Ana o 2 are both 11S globulins belonging to the cupin superfamily, and significant homology was found between these proteins. CONCLUSION: Citrus pectin may be contaminated with citrus seeds. Citrin, a newly identified allergen in citrus seeds, seems to be the culprit antigen in citrus seeds and contaminated citrus pectin. Citrin is highly homologous with Ana o 2 in cashew and Pis v 2 in pistachio, suggesting potential for cross-reactivity and providing an explanation for co-allergenicity of cashew or pistachio, citrus seeds, and citrus pectin.

Recent trends in food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) was first described in detail in the late 20th century as a non-IgE-mediated food allergy characterized by delayed gastrointestinal symptoms after ingestion of a trigger food. Although the initial case series reported infants reacting to cow's milk- and soy-based formulas, we now recognize that FPIES affects patients across the age spectrum. This brief review highlights our evolving understanding of FPIES with a discussion of triggers, epidemiology, food challenges, and pathophysiology.

Untargeted serum metabolomic analysis reveals a role for purinergic signaling in FPIES.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Its symptoms are distinct from those of IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with TH17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood. OBJECTIVE: Our aim was to use an untargeted metabolomics approach to identify novel pathways associated with FPIES reactions. METHODS: Serum samples were obtained before, during, and after oral food challenge (OFC) (10 subjects with FPIES and 10 asymptomatic subjects), and they were analyzed by untargeted metabolomics. Two-way ANOVA with false discovery rate adjustment was used for analysis of metabolites. Stomach and duodenal biopsy specimens from non-FPIES donors were stimulated with adenosine in vitro and serotonin measured by immunoassay. RESULTS: The levels of a total of 34 metabolites, including inosine and urate of the purine signaling pathway, were increased during OFCs performed on the patients with symptomatic FPIES compared with the levels found for asymptomatic subjects. Expression of the purine receptors P2RX7 and P2RY10 and the ectonucleotidase CD73 in peripheral blood was significantly reduced after OFC of the patients with FPIES. The level of the serotonin metabolite 5-hydroxyindoleacetate was significantly elevated after reaction. Adenosine stimulation of gastric and duodenal biopsy specimens from FPIES-free donors induced a significant release of serotonin, suggesting a link between purinergic pathway activation and serotonin release. CONCLUSIONS: Activation of the purinergic pathway during FPIES reactions provides a possible mechanism connecting inflammation and vomiting by triggering serotonin release from gastric and duodenal mucosa.

Update on Food Protein-Induced Enterocolitis Syndrome (FPIES).

PURPOSE OF REVIEW: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by delayed, and potentially severe, gastrointestinal symptoms. Since the advent of a specific diagnostic code and establishment of diagnostic guidelines, our understanding of this condition has grown. RECENT FINDINGS: FPIES affects patients from early infancy into adulthood. Any food can be a trigger, and common culprit foods vary geographically and by age. An understanding of the complex underlying immune mechanisms remains elusive, although studies show pan-leukocyte activation, cytokine release, and increased gastrointestinal permeability. Management involves trigger avoidance, and patients may benefit from the support of a dietitian to ensure adequate nutrient intake. Tolerance develops over time for most children, but due to the risk of severe symptoms, re-introduction of a suspected FPIES trigger is recommended only under supervision at an oral food challenge. Studies continue to evaluate the optimal challenge protocol. Caregivers of children with FPIES report high levels of anxiety and stress, which is attributed to the dramatic symptomatology, dietary restrictions, nutritional concerns, lack of confirmatory diagnostic tests, and limited tools for management of reactions. Our understanding of the FPIES diagnosis has improved over the last few decades, but there remain opportunities, particularly regarding discerning the pathophysiology and best management practices.

Patient perspectives on penicillin allergy and testing.

Background: Most patients who report penicillin allergy are found to tolerate penicillin later in life. Few studies have examined patients' understanding and beliefs about penicillin allergy and testing. Evaluating patients' perspectives may help identify ways to improve patient education and increase testing to de-label those who can tolerate penicillin. Objective: To better understand patient perspectives on penicillin allergy testing and to identify whether patient characteristics and beliefs impact completion of testing. Methods: Patients who were visiting our allergy clinics and had documentation of a penicillin allergy in the electronic medical record (EMR) were approached to complete a survey with regard to their reaction history and knowledge and/or perspectives about penicillin allergy and testing. Eighty-eight patients completed the survey, and their medical records were reviewed to collect results of penicillin testing. Results: Fewer than half of the patients (45.5%) who had EMR-documented penicillin allergy reported awareness that testing for penicillin allergy is available. Awareness of penicillin allergy testing was significantly associated with completion of testing, whereas other patient characteristics, such as education, income, and distance to the hospital, were not. Patients who scheduled a return visit for testing at the time of their initial visit were significantly more likely to follow through with testing. Most patients were interested in penicillin testing. For patients who were not interested, the most frequently cited reason was fear of adverse effects of testing. Conclusion: Among the patients who carried a penicillin allergy label, those who were aware of penicillin allergy testing were more likely to complete testing, and ease of scheduling contributed to higher rates of testing completion. Fear about adverse effects from testing was the most reported barrier. Our findings emphasized the importance of increasing awareness of the availability and safety of penicillin testing through patient education and collaboration with other specialties.

Acute FPIES reactions are associated with an IL-17 inflammatory signature.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear. OBJECTIVE: Our aim was to identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood. METHODS: Children with a history of FPIES underwent supervised oral food challenge. Blood samples were taken at baseline, at symptom onset, and 4 hours after symptom onset. We analyzed samples from 23 children (11 reactors and 12 outgrown). A total of 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry. RESULTS: Symptomatic FPIES challenge results were associated with significant elevation of levels of cytokines and chemokines, including IL-17 family markers (IL-17A, IL-22, IL-17C, and CCL20) and T-cell activation (IL-2), and innate inflammatory markers (IL-8, oncostatin M, leukemia inhibitory factor, TNF-α, IL-10, and IL-6). The level of the mucosal damage marker regenerating family member 1 alpha (REG1A) was also significantly increased. These biomarkers were not increased in asymptomatic challenges or IgE-mediated allergy. The level of phospho-STAT3 was significantly elevated in myeloid and T cells after challenge in individuals with symptoms. Mass cytometry indicated preferential activation of nonconventional T-cell populations, including γδ T cells and CD3+CD4-CD8-CD161+ cells; however, the potential sources of IL-17 in PBMCs were primarily CD4+ TH17 cells. CONCLUSIONS: These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES.

The practical dietary management of food protein-induced enterocolitis syndrome.

OBJECTIVE: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E-mediated food allergy with potential risk of malnutrition related to the early onset of disease, frequent avoidance of cow's milk, and the possibility of multiple food triggers. This publication is aimed at providing an evidence-based, practical approach to the dietary management of FPIES. DATA SOURCES: This is a narrative review summarizing information from national and international guidelines, retrospective studies, population studies, review articles, case reports, and case series to evaluate for nutritional risk and develop guidance for risk reduction in children with FPIES. STUDY SELECTIONS: We have included retrospective clinical cohort studies, population-based studies, case reports, and case studies. We did not exclude any studies identified owing to the small number of studies addressing the nutritional management of individuals with FPIES. RESULTS: Children with FPIES are at risk of malnutrition owing to suboptimal oral intake, limited food choices, and knowledge deficits related to feeding. In particular, children with 3 or more FPIES triggers seem to be at increased risk for poor weight gain and developing food aversion. Caregivers of children with FPIES also report a high degree of psychosocial burden. CONCLUSION: Appropriate dietary management entails the following 3 essential components: supporting normal growth and development, avoidance of allergens, and advancement of complementary foods. Education to avoid the trigger food and assisting caregivers in creating an individualized, well-designed complementary feeding plan to meet the infant's nutritional needs for optimal growth and development are essential management strategies.

Management of acute food protein-induced enterocolitis syndrome emergencies at home and in a medical facility.

OBJECTIVE: Acute food protein-induced enterocolitis syndrome (FPIES) is characterized by delayed repetitive vomiting after ingestion of a trigger food, and severe reactions may lead to dehydration, hypotension, and shock. We provide recommendations on management of FPIES emergencies in a medical facility and at home. DATA SOURCES: This review summarizes the literature on clinical context, pathophysiology, presentation, and treatment of FPIES emergencies. STUDY SELECTIONS: We referred to the 2017 International Consensus Guidelines for the Diagnosis and Management of FPIES and performed a literature search identifying relevant recent primary articles and review articles on clinical management. RESULTS: Management of FPIES emergencies in a medical facility is based on severity of symptoms and involves rehydration, ondansetron, and corticosteroids. A proactive approach for reactions occurring at home involves prescribing oral ondansetron and providing an individualized treatment plan based on the evolution of symptoms and severity of past reactions. A better understanding of the pathophysiology of FPIES and randomized trials on ondansedron and cocorticosteroid use could lead to more targeted treatments. CONCLUSION: Children with FPIES are at risk for severe symptoms constituting a medical emergency. Management of FPIES emergencies is largely supportive, with treatment tailored to the symptoms, severity of the patient's condition, location of reaction, and reaction history.

Overcoming challenges to removing inappropriate penicillin allergy labels: A quality improvement report.

Over 3 months, we provided monthly education to internal medicine residents and distributed resources regarding penicillin-allergy history taking. Allergy information in the electronic record was updated more often during the intervention compared to the period before the intervention (16.1% vs 10.9%; P = .02). Education and interdepartmental collaboration have the potential to affect provider behavior.

Food allergy prevention: current evidence.

PURPOSE OF REVIEW: The aim of the article is to critically appraise the most relevant studies in the rapidly advancing field of food allergy prevention. RECENT FINDINGS: Epidemiologic studies identified atopic dermatitis as a strong risk factor for food allergy, with mounting evidence for impaired skin barrier and cutaneous inflammation in the pathogenesis. Additional risk factors include a family history of atopy, the timing of allergenic food introduction into the infant's diet, dietary diversity, vitamin D, and environmental factors, such as dog ownership. Early introduction of allergenic foods (such as peanut) into the infant diet was shown to significantly reduce the risk of food allergy in infants with risk factors, whereas studies targeting skin barrier function have produced conflicting results. Cumulative evidence supports dietary diversity during pregnancy, breastfeeding, infancy, and early childhood. SUMMARY: A variety of interventions have been evaluated for the prevention of atopic dermatitis and food allergy, often producing conflicting results. At present, official guidelines encourage breastfeeding and early allergenic food introduction for infants at risk for food allergy, with an emphasis on dietary diversity, fruits, vegetables, fish, and food sources of vitamin D during pregnancy, lactation, and early life for all infants.

Food protein-induced enterocolitis syndrome: epidemiology and comorbidities.

PURPOSE OF REVIEW: First described in the mid 20th century, it was just in the last decade that diagnostic and treatment guidelines for food protein-induced enterocolitis syndrome (FPIES) were established. Awareness of the diagnosis is improving, and epidemiologic data are emerging. RECENT FINDINGS: Recent studies suggest that FPIES may affect as many as 0.5% of children worldwide. FPIES in adults is usually triggered by seafood and may be more common than previously thought. Many patients with FPIES have other allergic disorders. SUMMARY: With refined diagnostic criteria and improved awareness, FPIES is now diagnosed with increasing frequency, and epidemiologic data are emerging. FPIES appears to be increasing in prevalence, and the frequent association with other allergic disorders suggests a shared predisposition or immune mechanism that remains to be elucidated.