Food Protein-Induced Enterocolitis Syndrome in Adulthood: Clinical Characteristics, Prognosis, and Risk Factors.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) in adults is being increasingly recognized; however, little is known about its characteristics. OBJECTIVE: To describe the clinical characteristics, prognosis, and associated factors in adult FPIES. METHODS: A 10-year prospective study was conducted in the Allergy Section of Alicante General Hospital in adults diagnosed with FPIES. Detailed interviews with patients and oral food challenges (OFCs) were performed to confirm diagnosis or evaluate for tolerance. Comorbidities and possible risk factors were analyzed retrospectively through electronic medical records to assess their association with the disease. RESULTS: One hundred and seven adults with FPIES (93.5% female) were followed for a median of 6.2 years. Abdominal pain was the most common manifestation (96.3%), followed by diarrhea (72%) and vomiting (60.7%). Seafood (59.8%), egg (14%), and milk (10.3%) were the most common triggers, whereas 43.9% reacted to more than 1 food group. We performed 49 OFCs: 9 to confirm diagnosis and 40 to evaluate for tolerance. After a median 3.5 years, 16.8% achieved tolerance. Resolution was correlated inversely with duration of the disease (P = .04) and seafood (P = .023) but not with age of onset. The prevalence of gastrointestinal pathologies such as irritable bowel syndrome (IBS), eosinophilic esophagitis, inflammatory bowel disease, and celiac disease was higher than in the general population. A higher number of FPIES triggers were correlated with also having a diagnosis of IBS (P = .02). CONCLUSIONS: Although adult FPIES normally persists, some patients achieve tolerance. Adults with FPIES have a relatively high prevalence of gastrointestinal pathologies. The predominance of women may be related to hormonal factors. The clinical differences with pediatric FPIES warrant a revision of diagnostic criteria in adults.

Intestinal microbiota is modified in pediatric food protein-induced enterocolitis syndrome.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food hypersensitivity that affects the gastrointestinal system, especially in children, who often present with more severe clinical manifestations than adults do. Although its pathogenesis is poorly understood and biomarkers are still lacking, scientific evidence suggests that gut microbiota may play an important role in the development of FPIES. Objective: We aimed to compare the composition of gut microbiota in children with FPIES with that in age- and sex-matched healthy controls. Methods: We analyzed the gut microbiota profiles in fecal samples of 17 patients with FPIES (case patients) and 12 age-matched healthy children (controls) by tag sequencing of the 16S ribosomal RNA gene hypervariable V4-V5 regions. Subjects' sociodemographic, clinical, and food diary variables were described and compared between groups by using inferential statistical tests. Nonparametric linear discriminant analysis was performed for intestinal microbiota data. Results: Patients with confirmed cases FPIES (n = 17; average patient age, 7.5 ± 3.2 years) and controls without FPIES or any atopy (n = 12, average patient age, 6.9 ± 2.7 years) were included. Fish was the main FPIES-inducing allergen in 65% of the cases. The patients with FPIES showed higher proportions of Lachnospiraceae spp (P < .0286) and a lower proportion of Ruminococcaceae spp (P < .0066), Lactobacillaceae spp (P < .0075), and Leuconostocaceae spp (P < .0173) than the controls. Conclusions: Our data clearly show a different gut microbial signature in patients with FPIES, suggesting a new potential avenue for aiding the diagnosis and clinical management of FPIES. Larger studies are needed to confirm these results.

Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes.

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a "converter phenotype," which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies. Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed. Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected. Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

Lipid Transfer Protein Sensitization: Risk of Anaphylaxis and Molecular Sensitization Profile in Pru p 3-Sensitized Patients.

BACKGROUND: Component-resolved diagnosis reveals the IgE response to many inhaled, food, and other allergens, improving the understanding and diagnosis of allergic diseases. OBJECTIVE: The aims of the study are to study the recognition of different lipid transfer proteins (LTPs) and other allergen families in a large group of people sensitized to Pru p 3 and to analyze the relationship between the clinical entities and the allergens. METHODS: This cross-sectional study included a large cohort of patients with positive skin tests to peach fruit and Pru p 3 specific IgE antibodies. Respiratory and food allergy symptoms were collected, and we performed prick tests with pollen, plant food, and other allergens plus the ImmunoCAP ISAC assay. RESULTS: Our sample consisted of 421 people with a mean age of 33.25 years (range 16-68); 54.6% were women. Clinical entities included anaphylaxis (37.1%), urticaria (67.9%), and oral allergy syndrome (59.1%). Rhinitis, rhinoconjunctivitis, and/or asthma were diagnosed in 71.8% of the participants. The most pronounced correlation existed between sensitization to Pru p 3 and to Jug r 3, Pla a 3, Ara h 9, and Cor a 8. We found a higher incidence of anaphylaxis in people with 5 or more recognized LTPs. No association was observed between inhaled and food allergies. CONCLUSION: Most Pru p 3-sensitized participants were sensitized to additional allergens from the same family and, to a lesser extent, to other allergens, mainly in the profilin and PR-10 protein families. Anaphylaxis occurred in more than a third of the cases evaluated, and almost three-quarters of them had respiratory symptoms. Respiratory and food allergies involving LTPs do not seem to be associated.

Hypersensitivity reactions to heparins.

PURPOSE OF REVIEW: This article provides an update on hypersensitivity reactions to heparins and novel oral anticoagulants, with special emphasis on diagnostic methods and management of patients. RECENT FINDINGS: Although heparins are drugs widely used, hypersensitivity reactions are uncommon. Cutaneous delayed hypersensitivity reactions after subcutaneous administration affects up to 7.5% of patients. Heparin-induced thrombocytopenia is another unusual but severe condition in which early recognition is crucial. Immediate hypersensitivity reactions to heparins have been also reported, but with the novel oral anticoagulants are much more uncommon, although reports of exanthemas have been notified.Skin tests and subcutaneous provocation test are useful tools in the diagnosis of hypersensitivity reactions, except in heparin-induced thrombocytopenia in which biopsy of lesional skin and in-vitro tests are the modalities of choice to confirm the diagnosis.Management of hypersensitivity reactions includes finding an alternative depending on the type of reaction. Fondaparinux and novel oral anticoagulants may be safe alternatives. SUMMARY: Delayed skin lesions after subcutaneous heparin are the most common type of hypersensitivity reactions, followed by life-threatening heparin-induced thrombocytopenia. Immediate reactions are uncommon. Allergologic studies may be useful to find an alternative option in patients with skin lesions in which heparin-induced thrombocytopenia has been previously excluded, as well as in heparin immediate reactions.

Clinical and immunological characteristics of a pediatric population with food protein-induced enterocolitis syndrome (FPIES) to fish.

BACKGROUND: Food protein-induced enterocolitis (FPIES) is an uncommon, non-IgE-mediated food allergy that usually debuts in infancy with profuse vomiting, lethargy, and pallor 2-4 h following ingestion of the offending food. Its immune mechanism is not known. We aimed to describe the clinical features and outcome of children with fish-FPIES as well as to investigate on cellular immune response implicated. METHODS: Prospective and follow-up clinical study of children with FPIES by fish over a period between 2004 and 2013 was conducted. Measurement in vitro of both cytokine production in peripheral blood mononuclear cells (PBMCs) and expression of HLA-DR in monocyte-derived dendritic cells stimulated with fish extracts. RESULTS: Sixteen children (seven male and nine female) were included, with a mean age of onset at 10 months. Diagnosis was established after a median of 4 reactions. Twelve patients were treated in emergency room, and two were admitted in intensive care. Patch tests were positive in six patients. Skin prick tests (SPTs) and specific IgE to all fish tested were negative. Only three children reached tolerance at a mean age of 4.5 years. Eight children avoided fish because of positive oral food challenge (OFC) after 6 years of age. Other patients have not been challenged because of parent refusal to OFC or a recent diagnosis. TNF-α was increased in patients, and a significant elevation of the HLA-DR marker was also observed in these patients vs. control donors. CONCLUSIONS: FPIES caused by fish in many cases presents with severe clinical manifestations. Patch test has poor diagnostic value, and OFC is the gold standard to test tolerance. The cytokine TNF-α may be implicated in the clinical symptoms. Higher expression of HLA-DR in dendritic cells has also been detected in our patients.

From respiratory sensitization to food allergy: Anaphylactic reaction after ingestion of mushrooms (Agaricus bisporus).

We report a case of a 38-year-old mold-allergic patient who developed episodes of generalized urticaria and systemic anaphylactic shock immediately after ingesting button mushrooms. A manganese-dependent superoxide dismutase (MnSOD) and a NADP-dependent mannitol dehydrogenase (MtDH) from Agaricus bisporus mushroom were identified as patient-specific IgE-binding proteins. Cross-reactivity between A. bisporus MnSOD and mold aeroallergens was confirmed. We conclude that prior sensitization to mold aeroallergens might explain severe food reactions to cross-reacting homologs mushroom proteins.

Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr virus.

BACKGROUND: The incidence of rashes following the intake of aminopenicillins during an acute episode of infectious mononucleosis is high, but severe cutaneous reactions as erythema multiforme or Stevens-Johnson syndrome are rare manifestations in childhood. MATERIAL AND METHODS: We report the case of a 7 year old girl that developed a generalized purpuric rash with target shaped areas, 9 days after starting treatment with amoxicillin-clavulanic acid. Laboratory investigation revealed a significant increase of Epstein Barr virus (EBV) specific IgM antibody. After skin biopse she was diagnosed as erythema multiforme syndrome. Prick, intradermal and patch tests were performed with penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin, amoxicillin, cefazoline and cefotaxime, the 24 hours reading was positive for aminopenicillins. Patch tests were also positive only for aminopenicillins, other betalactams were negative. CONCLUSIONS: The interaction between an infectious agent (EBV) and amoxicillin could precipitate the severe skin reaction. Patch test and delayed intradermal reading with amoxicilllin were an useful tool for the diagnosis of the etiological agent in this reaction. The negative response to other beta-lactams, suggests that the aminobenzyl group of the side chain of amoxicillin plays a predominant role in this reaction.

Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr virus / Eritema multiforme por amoxicilina e infección recurrente por virus de Epstein-Barr

Background: The incidence of rashes following the intake of aminopenicillins during an acute episode of infectious mononucleosis is high, but severe cutaneous reactions as erythema multiforme or Stevens-Johnson syndrome are rare manifestations in childhood. Material and methods: We report the case of a 7 year old girl that developed a generalized purpuric rash with target shaped areas, 9 days after starting treatment with amoxicillin-clavulanic acid. Laboratory investigation revealed a significant increase of Epstein Barr virus (EBV) specific IgM antibody. After skin biopse she was diagnosed as erythema multiforme syndrome. Prick, intradermal and patch tests were performed with penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin, amoxicillin, cefazoline and cefotaxime, the 24 hours reading was positive for aminopenicillins. Patch tests were also positive only for aminopenicillins, other betalactams were negative. Conclusions: The interaction between an infectious agent (EBV) and amoxicillin could precipitate the severe skin reaction. Patch test and delayed intradermal reading with amoxicilllin were an useful tool for the diagnosis of the etiological agent in this reaction. The negative response to other beta-lactams, suggests that the aminobenzyl group of the side chain of amoxicillin plays a predominant role in this reaction

Antecedentes. La incidencia de reacciones exantemáticas tras tratamiento con aminopenicilinas durante un episodio de mononucleosis infecciosa es elevada, si bien las reacciones cutáneas graves tales como Eritema multiforme o Sd. de Stevens-Johnson son manifestaciones especialmente infrecuentes en la infancia. Material y métodos: niña de 7 años que desarrolló un rash purpúrico con lesiones en diana, 9 días después de estar recibiento tratamiento con amoxicilina-clavulánico por cuadro febril y amigdalitis. La analítica mostraba un aumento significativo de los anticuerpos IgM específicos a virus Epstein-Barr. La biopsia cutánea fue compatible con el diagnóstico de eritema multiforme. Se realizaron tests cutáneos mediante técnica de prick e intradermorreacción con PPL (peniciloilpolilisina), MDM (mezcla de determinantes antigénicos menores), penicilina G , ampicilina, amoxicilina, cefazolina y cefotaxima que fueron únicamente positivos para aminopenicilinas en lectura retardada. Los test epicutáneos con dichos preparados fueron igualmente positivos para aminopenicilinas también. Conclusiones. En este caso la interacción entre amoxicilina y el virus Epstein Barr pudo precipitar la reacción cutánea grave. Los tests cutáneos en lectura retardada así como los tests epicutáneos fueron útiles en el diagnóstico etiológico de esta reacción. La respuesta cutánea negativa a otros betalactámicos sugiere que el grupo aminobenzil de la cadena lateral de la amoxicilina juega un papel predominante en esta reacción