Systemic allergic reactions induced by labile plant-food allergens: Seeking potential cofactors. A multicenter study.

BACKGROUND: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. OBJECTIVE: To detect the risk factors for systemic reactions induced by labile food allergens. METHODS: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. RESULTS: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. CONCLUSION: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.

Retrospective analysis of 222 oral food challenges with a single dose in acute food protein-induced enterocolitis syndrome.

BACKGROUND: The method of performing oral food challenge (OFC) in acute food protein-induced enterocolitis syndrome (FPIES) has not been systematically studied. Therefore, there is a certain variability in the choice of the various centers. METHODS: Since 2011, we have been performing OFC for acute FPIES with a single dose of culprit food, a full serving size for age. In case of atypical FPIES (skin prick test, SPT, positive), we applied this protocol only if the description of previous adverse reactions was compatible with that of a classic acute FPIES, if other IgE-mediated food allergies were absent, and if the mean diameter of the wheal evoked by the SPT with the challenged food was ≤5 mm. We have retrospectively analyzed 222 OFCs from 2011 to 2020. The grading of reactions was carried out according to the International Consensus Guidelines on FPIES of 2017. RESULTS: Forty-eight of 222 OFC (21.6%) failed. The mild reactions were 22 of 48 (45.8%), the moderate ones 22 of 48 (45.8%), and the severe ones 4 of 48 (8.4%) failed OFCs. The tested food processing (in the case of cow milk and chicken egg) did affect neither probability nor severity of the reaction. Patients with positive SPT for the tested food presented four times more severe reactions (2 of 9 failed OFC, 22.2%) than patients with negative SPT (2 of 39 failed OFC, 5.1%) (P = .316). CONCLUSIONS: The administration of a single dose in a full serving size for age appears to be a sufficiently safe method for OFC for acute FPIES, with the benefit of saving time. In patients with positive SPT for the tested food, it may be prudent to start with a smaller dose carrying on, in the absence of adverse reactions, with the administration of the full dose after a 4-hour observation.

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.

Food Protein-Induced Enterocolitis Syndrome: Proposals for New Definitions.

Acute food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated allergy and is characterized by repetitive profuse vomiting episodes, often in association with pallor, lethargy, and diarrhea, presenting within 1-4 h from the ingestion of a triggering food. In 2017, the international consensus guidelines for the diagnosis and management of FPIES were published. They cover all aspects of this syndrome, which in recent decades has attracted the attention of pediatric allergists. In particular, the consensus proposed innovative diagnostic criteria. However, the diagnosis of acute FPIES is still currently discussed because the interest in this disease is relatively recent and, above all, there are no validated panels of diagnostic criteria. We propose some ideas for reflection on the diagnostic and suspicion criteria of acute FPIES with exemplary stories of children certainly or probably suffering from acute FPIES. For example, we believe that new definitions should be produced for mild forms of FPIES, multiple forms, and those with IgE-mediated symptoms. Moreover, we propose two clinical criteria to suspect acute FPIES and to refer the child to the diagnostic oral food challenge.

Matrix effect on baked egg tolerance in children with IgE-mediated hen's egg allergy.

BACKGROUND: Children with IgE-mediated hen's egg allergy (IgE-HEA) often tolerate baked egg within a wheat matrix. OBJECTIVE: To evaluate the influence of wheat matrix and the effects of little standardized cooking procedures on baked egg tolerance. METHODS: Fifty-four children with IgE-HEA were enrolled. They underwent prick-by-prick (PbP) tests and open oral food challenges (OFC) performed with baked HE within a wheat matrix (a home-made cake, locally called ciambellone), baked HE without a wheat matrix (in the form of an omelet, locally named frittata) and boiled HE. Three months after passing ciambellone OFC, parents were asked to answer a survey. RESULTS: About 88% of children tolerated ciambellone, 74% frittata, and 56% boiled HE. Negative predictive value of PbP performed with ciambellone, frittata, and boiled HE was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. CONCLUSIONS: Wheat matrix seemed to be relevant only in few cases. If our results will be confirmed by larger studies, a negative PbP with ciambellone, frittata, or boiled HE will allow patients with IgE-HEA to eat these foods without undergoing OFC. Moreover, our study showed that very strict standardized cooking procedures do not seem to be essential, to guarantee tolerance toward baked HE.

Grass pollen sublingual immunotherapy and paediatric allergic rhinitis: A patient-oriented decision.

Guidelines and systematic review report that allergen immunotherapy (AIT) is, in general, effective in the treatment of allergic rhinitis. However, experts suggest not generalising the results of different clinical studies: for example, it would not be advisable to translate the results found in an adult population to a paediatric population or the results on the efficacy of AIT against a specific allergen to the AIT against a different allergen. Moreover, according to Evidence Based Medicine (EBM), clinical decisions are individualised and should derive from the "integration of best research evidence with clinical expertise and patient values". Taking into account the high specificity of the AIT and EBM principles, we tried to answer the question on how advisable it is to prescribe the AIT for the management of grass allergic rhinitis in children. To do this, we revised the scientific literature in order to solve a specific case scenario.

Food protein-induced enterocolitis syndrome caused by fish and/or shellfish in Italy.

BACKGROUND: The study describes the demographic features, culprit foods, clinical features and outcomes for children presenting with acute fish and/or shellfish food protein-induced enterocolitis syndrome (FPIES) in four Italian paediatric allergy centres. METHODS: A retrospective/prospective study was undertaken. All children diagnosed with fish or shellfish FPIES were enrolled. The diagnosis of FPIES was based on Sicherer's or Miceli Sopo clinical criteria. Skin prick tests (SPT) were performed in all patients, at the time of diagnosis and prior to OFC. RESULTS: Seventy children were enrolled. Mean age at first episode was 14 months (range 6-46 months); mean age at diagnosis was 34 months (range 6-164 months). Sole and cod were the fish most commonly implicated. Fifty-seven of 70 (81%) children had FPIES exclusively to fish, 37 of 57 (65%) children had single-fish FPIES, 20 of 57 (35%) multiple-fish FPIES, nine of 70 (13%) presented adverse reactions exclusively to shellfish, and four of 70 (6%) presented adverse reactions to both fish and shellfish. Only four (5.7%) children presented episodes of acute FPIES with different foods (2 to cow's milk, 1 to egg, 1 to beef); in all cases, onset was prior to that of fish or shellfish FPIES. Fifteen of 70 (21%) children tolerated fish other than the offending fish. Twenty-four of 70 (34%) children achieved tolerance (age range 24-102 months). CONCLUSIONS: The chief peculiarities of acute fish and shellfish FPIES, compared to more frequent cow's milk or soy FPIES, are (i) later age of onset, (ii) longer persistence and (iii) possibility of tolerating fish other than the offending fish. Adverse reactions with shellfish are possible.

Contact urticaria on eczematous skin by kiwifruit allergy. In vivo component-resolved diagnosis.

BACKGROUND: Kiwifruit allergy has been responsible for a variety of clinical manifestations, ranging from mild reactions, such as localised oral symptoms, to severe systemic symptoms, such as anaphylaxis. No cases of isolated contact urticaria (ICU) due to IgE-mediated allergy to kiwifruit have been reported in the literature so far. Here we describe the first three cases of ICU due to kiwi and we hypothesise about a kiwifruit allergen not described yet. METHODS: Using the available in vivo allergy tests, we performed a component-resolved diagnosis to detect the allergen involved. All the patients underwent prick-by-prick with raw and boiled kiwi pulp and latex glove, skin prick test with commercial extracts of kiwifruit, birch, latex, palm profilin and peach lipid transfer protein, rub test with raw and boiled kiwi and oral food challenges with the raw fruit. RESULTS: We found that, in our patients, the kiwifruit allergen responsible for ICU is thermolabile, gastrosensitive, and it does not show any of the most common kiwi-attributed cross-reactivity (latex, birch, profiling and lipid transfer protein). None of the 13 kiwifruit allergens already known shows all these features. CONCLUSIONS: Kiwifruit allergy can also occur with ICU, probably due to a native protein that is not yet identified. In this case the elimination diet is not required.

Chronic food protein-induced enterocolitis syndrome caused by cow's milk proteins passed through breast milk.

We describe 2 cases of food protein-induced enterocolitis syndrome (FPIES) caused by cow's milk (CM) passed through breast milk. The onset in both cases was characterized by chronic symptoms (regurgitation, colic, diarrhea, failure to thrive); in one patient, two acute episodes due to the direct consumption of CM formula by the infant were also reported. The diagnosis of FPIES through breast milk can be easily overlooked, especially in milder cases. We also discuss some important issues concerning the general management of the disease. In conclusion, (1) the diagnosis of chronic FPIES should be taken into account even in exclusively breast-fed infants who present suggestive symptoms such as persistent regurgitation, small amounts of vomiting, lethargy, failure to thrive, dehydration, diarrhea (sometimes bloody) and abdominal distention. A 2-week maternal elimination diet should be considered even in apparently mild cases. (2) CM seems to be the most frequently reported culprit food. (3) In those cases in which acute FPIES is elicited by the direct consumption of the culprit food in breast-fed infants, maternal diet may be unrestricted.

Ondansetron for food protein-induced enterocolitis syndrome.

Recently, a study on 5 patients [Holbrook et al.: J Allergy Clin Immunol 2013;132:1219-1220] documented the efficacy of the intravenous administration of ondansetron in children with acute symptoms due to food protein-induced enterocolitis syndrome (FPIES). We report on the experience at our institution using ondansetron during oral food challenge (OFC) in 5 children affected by FPIES. In all 5 cases, the use of intramuscular ondansetron led to a complete and rapid resolution of symptoms within 15 min. Intramuscular administration, without the need for intravenous access for an infusion or steroid administration, enables this therapy to be easily performed, even at home (i.e. out of a hospital setting). A home treatment with ondansetron cannot be considered as an alternative to a medical examination with eventual treatment in hospital, which is advised after any acute episode of FPIES. We consider ondansetron to be very useful in the management of acute FPIES. Further study is required to confirm its efficacy.

Constipation and cow's milk allergy: a review of the literature.

The causal association between cow's milk allergy (CMA) and constipation is not well established. Some guidelines describe constipation as a possible symptom of CMA, while others do not mention it. We conducted a literature review and found 10 prospective clinical trials. In all of them, an oral food challenge was performed, and 2 of them were randomized. These studies reported that a cow's milk (CM) protein-free diet has a beneficial effect on constipation, with a rate of successful outcomes ranging from 28 to 78%. The hypothetic pathogenic mechanism lies in increased anal pressure at rest, probably caused by allergic inflammation of the internal sphincter area due to mucosal eosinophil and mast cell infiltration. Eighty percent of patients reach tolerance within 1 year after the diagnosis of CMA-related constipation. We believe that a CM-free diet for 2-4 weeks should be proposed for children with chronic functional constipation, even if it is not severe or resistant to laxatives.

Personalization of Complementary Feeding in Children With Acute Food Protein-Induced Enterocolitis Syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a food allergy that results in repetitive vomiting, lethargy, and pallor within 1 to 4 hours of food ingestion. One of the issues in its management is the introduction of new foods. Over the past 25 years, suggestions have been made mainly based on the likelihood that a given food family could induce an episode of acute FPIES. Thus, foods have been categorized into low, moderate, and high risk. The suggestion was always to postpone the introduction of moderate- or high-risk foods, leaving the decision whether to introduce them at home or in hospital to the doctor. These suggestions were designed for all children with acute FPIES, regardless of their geographical area. However, it is true that these suggestions are the result of expert opinion. In recent years, studies have been published that have shown that the risk category of foods varies according to geographical area and so does the prevalence of single FPIES versus multiple FPIES. For this reason, we believe that the introduction of new foods in the child with acute FPIES can and should be tailored according to the geographical area.

Specific oral tolerance induction with raw hen's egg in children with very severe egg allergy: a randomized controlled trial.

BACKGROUND: Treatment of severe egg allergy is avoidance of hen's egg (HE) and carrying self-injectable epinephrine. Specific oral tolerance induction (SOTI) seems a promising alternative treatment. However, some aspects of SOTI are still considered experimental. METHODS: We evaluated the efficacy and safety of an original 6-month SOTI protocol in children with very severe HE allergy using raw HE emulsion. Twenty children (age range: 5-11 yr) were randomized equally into a SOTI treatment group and a control group. The treatment group started SOTI and underwent a second challenge 6 months later. Control children were kept on an egg-free diet for 6 months and then underwent a second challenge. RESULTS: After 6 months, 9/10 children of the SOTI group (90%) achieved partial tolerance (at least 10 ml, but <40 ml of raw HE emulsion, in a single dose) and 1 (10%) was able to tolerate only 5 ml (no tolerance). After 6 months, nine control children tested positive to the second challenge at a dose ≤0.9 ml of raw HE emulsion, and one reacted to 1.8 ml (SOTI vs. control group p<0.0001). All children in the SOTI group had side effects, but no child had a grade 5 reaction according to the Sampson grading. CONCLUSION: Six months of SOTI with raw HE emulsion resulted in partial tolerance, with regular intake, in a significant percentage of children with severe egg allergy.