IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

The role of the atopy patch test in the diagnostic work-up of non-IgE gastrointestinal food allergy in children: a systematic review.

The "Atopy Patch Test" (APT) has been proposed as a diagnostic tool for food allergies (FA), especially in children with FA-related gastrointestinal symptoms. However, its diagnostic accuracy is debated, and its usefulness is controversial. The aim of this systematic review was to evaluate the APT diagnostic accuracy compared with the diagnostic gold standard, i.e., the oral food challenge (OFC), in children affected by non-IgE mediated gastrointestinal food allergies, including the evaluation in milk allergic subgroup. Both classical non-IgE mediated clinical pictures and food induced motility disorders (FPIMD) were considered. The search was conducted in PubMed and Scopus from January 2000 to June 2022 by two independent researchers. The patient, intervention, comparators, outcome, and study design approach (PICOS) format was used for developing key questions, to address the APT diagnostic accuracy compared with the oral food challenge (OFC). The quality of the studies was assessed by the QUADAS-2 system. The meta-analysis was performed to calculate the pooled sensitivity, specificity, DOR (diagnostic odds ratio), PLR (positive likelihood ratio), and NLR (negative likelihood ratio) with their 95% confidence intervals (CI). Out of the 457 citations initially identified via the search (196 on PubMed and 261 on Scopus), 37 advanced to full-text screening, and 16 studies were identified to be included in the systematic review. Reference lists from relevant retrievals were searched, and one additional article was added. Finally, 17 studies were included in the systematic review. The analysis showed that APT has a high specificity of 94% (95%CI: 0.88-0.97) in the group of patients affected by FPIMD. Data showed a high pooled specificity of 96% (95% CI: 0.89-0.98) and the highest accuracy of APT in patients affected by cow's milk allergy (AUC = 0.93).      Conclusion: APT is effective in identifying causative food in children with food-induced motility disorders.  What is Known: • Atopy patch test could be a useful diagnostic test for diagnosing food allergy, especially in children with food allergy-related gastrointestinal symptoms. What is New: • Atopy patch test may be a useful tool in diagnosing non IgE food allergy, especially in children with food-induced gastrointestinal motility disorders and cow's milk allergy.

Update on idiopathic anaphylaxis.

Idiopathic anaphylaxis (AI) refers to anaphylaxis without a recognizable cause after a comprehensive allergic workup. The diagnostic approach usually includes an accurate clinical history aimed at excluding both the most and the less frequent causes of anaphylaxis and all pathologies that may resemble anaphylaxis. AI is more common in adults than in children. The epidemiology of AI has been reduced in recent years, probably to increase knowledge and discover new clinical entities, such as the α-gal anaphylaxis. Anaphylaxis results from the massive activation of the mast cells (MCs). Thus, it is also necessary to exclude MC disorders, such as mastocytosis and mast cell activation syndrome, and α-tryptasemia, which may manifest with IA symptoms.

Chronic cough in childhood: A systematic review for practical guidance by the Italian Society of Pediatric Allergy and Immunology.

The current systematic review presented and discussed the most recent studies on pediatric chronic cough. In addition, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to a pediatric patient with chronic cough.Several algorithms on chronic cough management have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, from birth until adulthood. Based on our findings, children and adolescents with chronic cough without cough pointers can be safely managed, initially using the watchful waiting approach and, successively, starting empirical treatment based on cough characteristics. Unlike other algorithms that suggest laboratory and instrumental investigations as a first step, this review highlighted the importance of a "wait and see" approach, consisting of parental reassurance and close clinical observation, also due to inter-professional collaboration and communication between general practitioners and specialists that guarantee better patient management, appropriate prescription behavior, and improved patient outcome. Moreover, the neonatal screening program provided by the Italian National Health System, which intercepts several diseases precociously, allowing to treat them in a very early stage, helps and supports a "wait and see" approach.Conversely, in the presence of cough pointers or persistence of cough, the patient should be tested and treated by the specialist. Further investigations and treatments will be based on cough etiology, aiming to intercept the underlying disease, prevent potentially irreversible tissue damage, and improve the general health of patients affected by chronic cough, as well as the quality of life of patients and their family.

Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology.

The current systematic review presented and discussed the most recent studies on acute cough in pediatric age. After that, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to pediatric patients, such as infants, children, and adolescents, with acute cough. An acute cough is usually consequent to upper respiratory tract infections and is self-resolving within a few weeks. However, an acute cough may be bothersome, and therefore remedies are requested, mainly by the parents. An acute cough may significantly affect the quality of life of patients and their family.Several algorithms for the management of acute cough have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, and, also, in accordance to the Italian National Health System, which regularly follows the child from birth to all lifelong. Based on our findings, infants from 6 months, children, and adolescents with acute cough without cough pointers can be safely managed using well-known medications, preferably non-sedative agents, such as levodropropizine and/or natural compounds, including honey, glycerol, and herb-derived components.

Oral desensitization in IgE-mediated food allergy: Effectiveness and safety.

The avoidance of allergenic foods and emergency medications on accidental exposure are the only currently approved treatments in food allergy. EAACI guideline on allergen immunotherapy recommends oral immunotherapy as a therapeutic option to increase the threshold of the reaction during treatment in children with persistent IgE-mediated cow's milk, hen's egg, and peanut allergy from around 4-5 years of age, but the same recommendation cannot currently be made to achieve post-discontinuation effectiveness. Both systemic and local reactions during OIT have been frequently reported. For this reason, EAACI guideline suggests several recommendations on safety, including carefully monitoring patients for allergic reactions, especially during the up-dosing phase of OIT, and monitoring for symptoms of new-onset eosinophilic esophagitis. New approaches are certainly necessary to give priority not only to effectiveness but also to safety.

Summation anaphylaxis: A challenging diagnosis.

Anaphylaxis is the most severe of allergic reactions. The most frequent triggers of anaphylaxis in childhood are food, insect venom, drugs, exercise, etc. In some cases, the presence of more than one trigger is necessary for the allergic reaction, while one trigger alone is tolerated. This rare condition is called summation anaphylaxis (SA). Food-dependent exercise-induced anaphylaxis is the most well-known SA. However, SA may also occur with the association between food and/or exercise plus one or more of the following other cofactors, such as drugs, especially non-steroidal anti-inflammatory (NSAID), alcohol, infections, temperature variation, and menstrual cycle. SA can explain some cases of idiopathic anaphylaxis, as well as cases of an apparent breakdown in a previously acquired tolerance for food, or finally, when faced with a suggestive clinical history of food allergy or exercise anaphylaxis and the provocation test is negative. In these situations, a more careful clinical history looking for other cofactors is necessary.

Oral Food Challenge.

Oral food challenge (OFC) is the gold standard for diagnosis of IgE-mediated and non-IgE mediated food allergy. It is usually conducted to make diagnosis, to monitor for resolution of a food allergy, or to identify the threshold of responsiveness. Clinical history and lab tests have poor diagnostic accuracy and they are not sufficient to make a strict diagnosis of food allergy. Higher concentrations of food-specific IgE or larger allergy prick skin test wheal sizes correlate with an increased likelihood of a reaction upon ingestion. Several cut-off values, to make a diagnosis of some food allergies (e.g., milk, egg, peanut, etc.) without performing an OFC, have been suggested, but their use is still debated. The oral food challenge should be carried out by experienced physicians in a proper environment equipped for emergency, in order to carefully assess symptoms and signs and correctly manage any possible allergic reaction. This review does not intend to analyse comprehensively all the issues related to the diagnosis of food allergies, but to summarize some practical information on the OFC procedure, as reported in a recent issue by The Expert Review of Food Allergy Committee of Italian Society of Pediatric Allergy and Immunology (SIAIP).

Cannabinoid Poisoning by Hemp Seed Oil in a Child.

We report a case of mild cannabinoid poisoning in a preschool child, after 3-week ingestion of hemp seed oil prescribed by his pediatrician to strengthen his immune system. The patient presented neurological symptoms that disappeared after intravenous hydration. A possible mild withdrawal syndrome was reported after discharge. The main metabolite of Δ-tetrahydrocannabinol was detected in urine, and very low concentration of Δ-tetrahydrocannabinol was detected in the ingested product. This is, as far as we know, the first report of cannabinoid poisoning after medical prescription of hemp seed oil in a preschool child.

Is it possible to make a diagnosis of raw, heated, and baked egg allergy in children using cutoffs? A systematic review.

The diagnosis of IgE-mediated egg allergy lies both on a compatible clinical history and on the results of skin prick tests (SPTs) and IgEs levels. Both tests have good sensitivity but low specificity. For this reason, oral food challenge (OFC) is the ultimate gold standard for the diagnosis. The aim of this study was to systematically review the literature in order to identify, analyze, and synthesize the predictive value of SPT and specific IgEs both to egg white and to main egg allergens and to review the cutoffs suggested in the literature. A total of 37 articles were included in this systematic review. Studies were grouped according to the degree of cooking of the egg used for OFC, age, and type of allergen used to perform the allergy workup. In children <2 years, raw egg allergy seems very likely when SPTs with egg white extract are ≥4 mm or specific IgEs are ≥1.7 kUA /l. In children ≥2 years, OFC could be avoided when SPTs with egg white extract are ≥10 mm or prick by prick with egg white is ≥14 mm or specific IgE is ≥7.3 kUA /l. Likewise, heated egg allergy can be diagnosed if SPTs with egg white extract are >5 and >11 mm in children <2 and ≥2 years, respectively. Further and better-designed studies are needed to determine the remaining diagnostic cutoff of specific IgE and SPT for heated and baked egg allergy.

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.

Pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity.

BACKGROUND: Pollen-induced allergic rhinoconjunctivitis (AR) is highly prevalent and rapidly evolving during childhood. General practitioners may not be fully aware of the nature and severity of symptoms experienced by patients and might underestimate the prevalence of moderate or severe disease. Thus, the relevance of early diagnosis and intervention may be overlooked. OBJECTIVES: To investigate the severity of pollen-induced AR and its determinants in Italian children referred to allergy specialists and who had never received specific immunotherapy (SIT). METHODS: Children (age 4-18 yr) affected by pollen-induced AR who had never undergone SIT were recruited between May 2009 and June 2011 in 16 pediatric outpatient clinics in 14 Italian cities. Recruited children's parents answered standardized questionnaires on atopic diseases (International Study of Allergy and Asthma in Childhood, Allergic Rhinitis and its Impact on Asthma, Global Initiative for Asthma). The children underwent skin-prick test (SPT) with several airborne allergens and six food allergens. Information on socio-demographic factors, parental history of allergic diseases, education, perinatal events, breastfeeding, nutrition and environmental exposure in early life was collected through an informatics platform shared by the whole network of clinical centers (AllergyCARD™). RESULTS: Among the 1360 recruited patients (68% males, age 10.5 ± 3.4 yr), 695 (51%) had moderate-to-severe AR, 533 (39%) asthma, and 325 (23.9%) oral allergy syndrome (OAS). Reported onset of pollen-induced AR was on average at 5.3 ± 2.8 yr, and its mean duration from onset was 5.2 ± 3.3 yr. Only 6.2% of the patients were pollen-monosensitized, and 84.9% were sensitized to ≥3 pollens. A longer AR duration was significantly associated with moderate-to-severe AR symptoms (p 0.004), asthma (p 0.030), and OAS comorbidities (p < 0.001). CONCLUSIONS: This nationwide study may raise awareness of the severity of pollen-induced AR among Italian children who have never received pollen SIT. The strong association between pollen-induced AR duration and several markers of disease severity needs replication in longitudinal studies, while suggesting that countrywide initiatives for earlier diagnosis and intervention should be planned.

Oral food challenge: safety, adherence to guidelines and predictive value of skin prick testing.

BACKGROUND: The diagnostic gold standard of food allergy is the oral food challenge (OFC). Data on severe reactions and drug use during OFC are scarce. Our aims were (i) to investigate the prevalence and spectrum of reactions' severity during OFC and to assess drug use and epinephrine use in anaphylaxis due to OFC; (ii) to investigate the predictive value of the skin prick test wheal size for the outcome of OFCs. METHODS: A retrospective charts review of children undergoing OFC at three Allergy Centres between January 2007 and December 2008 was performed. RESULTS: A total of 544 OFCs were analysed. Most frequently involved foods were egg, milk and wheat. 254/526 (48.3%) were positive. 167 (65.7%) were defined mild reactions, 81 (31.9%) multiorgan reactions and 6 (2.4%) anaphylaxis. No patients had cardiovascular symptoms. Data on treatments were available in 98.8% OFCs. In half of them antihistamines were used vs. 10% cases in which steroids were preferred. Six children (2.4%) were treated with Epinephrine inhalation, 5 (2%) with beta-2 inhalation, 8 (3.1%) with steroid inhalation. One child was treated with IM Epinephrine + IV fluids. Skin prick tests predictive cut-off were 9 mm for albumen, 7 for yolk, 13 for fresh albumen, 10 for α-lactalbumin, seven for casein, eight for ß-lactoglobulin, 20 for cow's milk and 10 for fresh cow's milk. CONCLUSION: OFCs performed in controlled settings by expert Allergists are safe. Consideration needs to be given as to whether the Anaphylaxis' Guideline need to be modified when applied in treating patients undergoing OFC.

A new model for conservative food challenge in children with immunoglobulin E-mediated cow's milk allergy.

BACKGROUND: The diagnostic gold standard for food allergy is an oral food challenge (OFC) with the suspected food. Usually, an OFC is stopped at the onset of mild objective symptoms for fear of severe reactions, but there is no consensus on this issue. OBJECTIVES: To investigate the effectiveness and side effects of a new model of oral milk challenge in order to increase the diagnostic accuracy of cow's milk protein allergy and reduce the number of useless elimination diets. This model is characterized by a conservative diagnostic protocol and "step-up cow's milk dosing." The secondary aim was to investigate possible factors influencing severe reactions. METHODS: Sixty-six children (median age 1 year, range 1-18) with suspected immunoglobulin E (IgE)-mediated cow's milk allergy performed a conservative OFC, i.e., the OFC was continued even in the presence of subjective, even repeated, or mild local or multiple organ objective symptoms. If the first objective reaction occurred when the quantity of milk was > 10 ml, the investigator would decide whether to continue the OFC or prescribe a gradual increase in milk feeding at home. RESULTS: Symptoms developed during the OFC in 42.4% of the children. Local, generalized and severe generalized reactions developed in 11 (16.7%), 11 (16.7%) and 6 (9.1%) children, respectively. Only 14/28 (50%) who developed objective symptoms during the OFC were considered to be affected by cow's milk allergy. In the remaining 14 both subjective and objective symptoms developed and the OFC was continued without further symptoms. Epinephrine was administered to 6 of the 28 children (21.4%) who developed objective symptoms. All but one had subjective symptoms following the early doses of milk, whereas all children who later tolerated milk had their first subjective or mild symptoms following doses > or = 10 ml. CONCLUSIONS: This new model of OFC criteria led to frequent severe allergic reactions; hence its use in daily practice seems inadvisable. However, our study provides evidence that a severe allergic reaction does not invariably occur if, the offending food continues to be administered after the onset of symptoms. If mild symptoms appear at doses > 10 ml, continued milk administration, on the same day or in subsequent days, seems to facilitate the development of tolerance and may reduce the number of useless elimination diets.

First Italian experience using the automated craniofacial gestalt analysis on a cohort of pediatric patients with multiple anomaly syndromes.

BACKGROUND: In this study, we used the novel DeepGestalt technology powered by Face2Gene (FDNA Inc., MA, USA) in suggesting a correct diagnosis based on the facial gestalt of well-known multiple anomaly syndromes. Only molecularly characterized pediatric patients were considered in the present research. SUBJECTS AND METHODS: A total of 19 two-dimensional (2D) images of patients affected by several molecularly confirmed craniofacial syndromes (14 monogenic disorders and 5 chromosome diseases) and evaluated at the main involved Institution were analyzed using the Face2Gene CLINIC application (vs.19.1.3). Patients were cataloged into two main analysis groups (A, B) according to the number of clinical evaluations. Specifically, group A contained the patients evaluated more than one time, while in group B were comprised the subjects with a single clinical assesment. The algorithm's reliability was measured based on its capacity to identify the correct diagnosis as top-1 match, within the top-10 match and top-30 matches, only based on the uploaded image and not any other clinical finding or HPO terms. Failure was represented by the top-0 match. RESULTS: The correct diagnosis was suggested respectively in 100% (8/8) and 81% (9/11) of cases of group A and B, globally failing in 16% (3/19). CONCLUSION: The tested tool resulted to be useful in identifying the facial gestalt of a heterogeneous group of syndromic disorders. This study illustrates the first Italian experience with the next generation phenotyping technology, following previous works and providing additional observations.

Diagnostic therapeutic care pathway for pediatric food allergies and intolerances in Italy: a joint position paper by the Italian Society for Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and the Italian Society for Pediatric Allergy and Immunology (SIAIP).

Epidemiologic data suggest an increased prevalence of pediatric food allergies and intolerances (FAIs) during the last decades. This changing scenario has led to an increase in the overall healthcare costs, due to a growing demand for diagnostic and treatment services. There is the need to establish Evidence-based practices for diagnostic and therapeutic intervention that could  be adopted in the context of public health policies for FAIs are needed.This joint position paper has been prepared by a group of experts in pediatric gastroenterology, allergy and nutrition from the Italian Society for Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and the Italian Society for Pediatric Allergy and Immunology (SIAIP). The paper is focused on the Diagnostic Therapeutic Care Pathway (DTCP) for pediatric FAIs in Italy.

Management of BNT162b2 mRNA COVID-19 vaccine in children aged 5-11 years with allergies, asthma, and immunodeficiency: consensus of the Italian Society of Pediatric Allergy and Immunology (SIAIP).

BNT162b2 vaccine, developed by BioNTech and Pfizer ha recently approved for use in children aged 5 to 11 years. Recent data show evidence of safety on the administration and serious adverse events have been rarely reported. However, allergic systemic reactions could occur. In some cases, a correct allergic evaluation allows identifying patients at risk of developing an anaphylactic reaction. Risk assessment of allergic reactions to COVID-19 vaccines is useful to limit contraindications to vaccination and help to safely vaccinate people supposed to be at risk of allergic reactions.

Risk factors for severe pediatric food anaphylaxis in Italy.

BACKGROUND: Little is known about the cause of food-induced anaphylaxis in children or about the factors that might affect its clinical severity. OBJECTIVE: The aim of this study was to investigate the cause of food-induced anaphylaxis in children in Italy and to identify factors that could influence the appearance of symptoms and the severity of anaphylaxis. METHODS: One hundred and sixty-three children with anaphylaxis consecutively attending 29 outpatient allergy clinics throughout Italy were enrolled in this prospective study. Information about past anaphylaxis episodes was collected with a standardized questionnaire. Food sensitization was evaluated by skin-prick test. RESULTS: A clinical history of asthma increased the risk of wheezing [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5] and respiratory arrest (OR 6.9; 95% CI 1.4-34.2). A clinical history of chronic/relapsing gastrointestinal symptoms increased the risk of vomiting (OR 2.1; 95% CI 0.9-4.3), hypotension (OR 7.9; 95% CI 1.9-32.0), and bradycardia/cardiac arrest (OR 9.2; 95% CI 0.9-91.3). The severity of present and previous episodes was similar only in patients with mild or moderate anaphylaxis. Peanut and egg were the most frequent causes of severe anaphylaxis. CONCLUSIONS: A clinical history of asthma and chronic/relapsing gastrointestinal symptoms (probably linked to food allergy) may predict the development of respiratory and gastrointestinal symptoms and the severity of anaphylaxis.