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Sekkidou M, Philippou E, Yiallouros PK, Nicolaou N. Is it time to reconsider the role of partially hydrolyzed infant formulas in the prevention of allergic diseases? Allergol Immunopathol (Madr) 2025; 53:181-193. [PMID: 40342126 DOI: 10.15586/aei.v53i3.1317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 03/28/2025] [Indexed: 05/11/2025]
Abstract
Allergic diseases are on the increase worldwide, incurring a high socioeconomic burden on patients, families, and healthcare systems. As a permanent cure for most allergies is still lacking, prevention is of paramount importance. So far, several strategies, including nutritional interventions, have been proposed to halt this phenomenon with inconclusive results. The use of partially hydrolyzed formulas (pHFs) for non-exclusively breastfed infants has been proposed by several scientific bodies; however, most have withdrawn this suggestion based on the concept of insufficient evidence. During the last few years, emerging evidence suggests that specific pHFs may reduce the risk of allergies in individuals at high risk for allergy development based on their heredity. In this article, we review the role of pHFs and propose that in non-exclusively breastfed infants at high-risk for allergy, the use of pHFs remains one of the most targeted interventions, as consistent data indicate a possible role in allergy prevention.
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Affiliation(s)
- Mikaela Sekkidou
- Asthma and Allergy Center, Limassol, Cyprus
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus;
| | - Elena Philippou
- Department of Life Sciences, School of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
| | | | - Nicolaos Nicolaou
- Asthma and Allergy Center, Limassol, Cyprus
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus
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Hage G, Sacre Y, Haddad J, Hajj M, Sayegh LN, Fakhoury-Sayegh N. Food Hypersensitivity: Distinguishing Allergy from Intolerance, Main Characteristics, and Symptoms-A Narrative Review. Nutrients 2025; 17:1359. [PMID: 40284223 PMCID: PMC12029945 DOI: 10.3390/nu17081359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 04/10/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Food hypersensitivity remains an understudied and overlooked subject globally. It is characterized by adverse reactions to dietary substances, potentially triggered by various mechanisms. Food allergy, a subset of food hypersensitivity, denotes an immune response to food proteins categorized into immunoglobulin IgE-mediated or non-IgE-mediated reactions. Conversely, food intolerance, another facet of food hypersensitivity, refers to non-immunological reactions, in which the human body cannot properly digest certain foods or components, leading to gastrointestinal discomfort and other non-immune-related symptoms. The main objective of this study was to determine and differentiate the differences, characteristics, and types of food hypersensitivity. Methods: This study involved a comprehensive review of key research from 1990 onward, including review articles, prospective studies, nested case-control studies, and meta-analyses. Results: Recognizing these differences is essential for healthcare professionals to ensure accurate diagnosis, effective management, and improved patient outcomes, while also aiding dietitians in providing optimal nutritional and dietary guidance. Conclusions: there are big differences between the main characteristics, such as symptoms, complications, and treatments between allergies, and food intolerances. Commonly reported trigger foods include cow milk, gluten, eggs, nuts, and seafood.
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Affiliation(s)
- Gregory Hage
- Department of Nutrition and Food Science, Faculty of Arts and Sciences, Holy Spirit University of Kaslik, Jounieh P.O. Box 446, Lebanon
- Hajj Medical Center-Medical & Dental Clinics, Green Zone A Building 71 Ground Floor, Naccache P.O. Box 1201, Lebanon
| | - Yonna Sacre
- Department of Nutrition and Food Science, Faculty of Arts and Sciences, Holy Spirit University of Kaslik, Jounieh P.O. Box 446, Lebanon
| | - Joanne Haddad
- Hajj Medical Center-Medical & Dental Clinics, Green Zone A Building 71 Ground Floor, Naccache P.O. Box 1201, Lebanon
- Faculty of Dental Medicine, Saint Joseph University of Beirut, Medical Sciences Campus, Damascus Road, Riad Solh, Beirut P.O. Box 11-5076, Lebanon
| | - Marcel Hajj
- Hajj Medical Center-Medical & Dental Clinics, Green Zone A Building 71 Ground Floor, Naccache P.O. Box 1201, Lebanon
| | - Lea Nicole Sayegh
- Yale New Haven Hospital, P.O. Box 1880, 20 York Street, New Haven, CT 06510, USA
| | - Nicole Fakhoury-Sayegh
- Department of Nutrition and Food Science, Faculty of Arts and Sciences, Holy Spirit University of Kaslik, Jounieh P.O. Box 446, Lebanon
- Faculty of Pharmacy, Department of Nutrition, Saint Joseph University of Beirut, Medical Sciences Campus, Damascus Road, Riad Solh, Beirut P.O. Box 11-5076, Lebanon
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Lo R, Groetch M, Brooks J, Anderson E, Rodríguez Del Río P, Anagnostou A. The Multiple Facets of Cow's Milk Allergy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2025; 13:754-760. [PMID: 39515520 DOI: 10.1016/j.jaip.2024.10.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 10/21/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024]
Abstract
Cow's milk allergy (CMA) is one of the most common food allergies in early childhood. CMA has varied presentations and multiple facets. A detailed clinical history is key for classification. In IgE-mediated CMA, skin prick testing and serum specific IgE testing are useful in the diagnosis, but an oral food challenge may still be necessary if there is doubt or to assess tolerance. Non-IgE-mediated CMA presentations include food protein-induced allergic proctocolitis, food protein-induced enterocolitis syndrome, and eosinophilic esophagitis. The diagnosis of food protein-induced allergic proctocolitis and food protein-induced enterocolitis syndrome is based on the clinical history. An esophageal biopsy is required for the diagnosis of eosinophilic esophagitis. Atopy patch testing, IgG testing, or IgG4 testing is not helpful in any CMA evaluation. Children with CMA (except those with food protein-induced allergic proctocolitis) are at risk for poor growth, and a nutritional evaluation should be part of routine care. Extensively hydrolyzed formulas are the recommended first-choice alternative formula for CMA. For IgE-mediated CMA, alternative approaches to traditional strict avoidance include oral immunotherapy and omalizumab (both as monotherapy and as an adjunct to oral immunotherapy). Multiple international guidelines have addressed evaluation and management of CMA, providing key information, support, and guidance for clinicians in daily practice.
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Affiliation(s)
- Rachelle Lo
- Department of Allergy, Kaiser Permanente Oakland Medical Center, Oakland, Calif
| | - Marion Groetch
- Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Joel Brooks
- Division of Allergy, Immunology, and Rheumatology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Erik Anderson
- Division of Allergy, Immunology, and Rheumatology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Pablo Rodríguez Del Río
- Allergy Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain; IIS La Princesa, Madrid, Spain
| | - Aikaterini Anagnostou
- Division of Allergy, Immunology & Retrovirology, Baylor College of Medicine, Houston, Texas.
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Akbulut O, Köksal BT, Aydın B, Oznacar T, Haberal A, Ozcay F. Does vitamin D deficiency predispose to allergic proctocolitis? Nutrition 2025; 131:112659. [PMID: 39740280 DOI: 10.1016/j.nut.2024.112659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 10/27/2024] [Accepted: 11/28/2024] [Indexed: 01/02/2025]
Abstract
OBJECTIVES Awareness of vitamin D (vit D) deficiency or insufficiency has increased alongside the rising prevalence of allergic diseases worldwide. We aimed to evaluate vit D levels in infants with allergic proctocolitis (AP) to explore a possible relationship between AP and vit D status. METHODS This prospective, observational, case-control study was conducted between January 2020 and December 2023, including infants aged 6 months and younger diagnosed with AP (AP group) and healthy infants of the same age (control group). Vit D levels in AP patients at the time of diagnosis were compared with those of healthy infants. RESULTS A total of 116 patients (72 AP, 44 control) were included in the study. Statistically significant differences were found in vit D levels, eosinophil count, and eosinophil percentage between the groups. Vit D was deficient or insufficient in 34.7% of AP patients. Vit D levels were significantly lower in infants with AP, and the risk of developing AP was 3.5 times higher in infants whose vit D levels were below 40.75 mcg/L. CONCLUSIONS Our finding that vit D levels are lower in infants with AP compared to healthy infants may support an association between AP and vit D deficiency. This could also provide insight into the increasing prevalence of AP linked to environmental factors. We recommend that vit D levels be assessed in infants with AP at the time of diagnosis.
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Affiliation(s)
- Ozlem Akbulut
- Department of Pediatrics, Medical Faculty, Baskent University, Ankara, Turkey.
| | - Burcu Tahire Köksal
- Department of Paediatric Allergy, Medical Faculty, Baskent University, Ankara, Turkey
| | - Beril Aydın
- Department of Pediatrics, Medical Faculty, Baskent University, Ankara, Turkey
| | - Tugce Oznacar
- Department of Biostatistics, Medical Faculty, Ankara Medipol University, Ankara, Turkey
| | - Aysegül Haberal
- Department of Biochemistry Medical Faculty, Baskent University, Ankara, Turkey
| | - Figen Ozcay
- Department of Paediatric Gastroenterology, Medical Faculty, Baskent University, Ankara, Turkey
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Carucci L, Nocerino R, Coppola S, Bedogni G, Capasso P, Giglio V, Berni Canani R. Factors influencing the natural history of non-IgE-mediated gastrointestinal food allergies in paediatric age: a prospective multicentre cohort study. BMJ Paediatr Open 2025; 9:e003203. [PMID: 39922601 PMCID: PMC11808895 DOI: 10.1136/bmjpo-2024-003203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 01/29/2025] [Indexed: 02/10/2025] Open
Abstract
BACKGROUND We aimed at identifying the factors influencing the natural history of non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFA), a group of common paediatric conditions including food protein-induced: enteropathy (FPE), allergic proctocolitis (FPIAP), enterocolitis syndrome (FPIES), and motility disorders (FPIMD). METHODS Prospective multicentre cohort study involving paediatric patients (both sexes, aged ≤14 y) with non-IgE-GIFA diagnosed and followed for 24 months at a Tertiary Centre for Paediatric Allergy, Gastroenterology and Nutrition. Anamnestic and clinical data were collected from all enrolled patients. RESULTS 123 non-IgE-GIFA patients were enrolled (56% male, median age (IQR) 150 (60-300) days): FPE (39%), FPIES (17%), FPIAP (16%) and FPIMD (28%). 42% of patients had multiple food allergies (FAs) at baseline, and 64% had a positive family history of allergy. Male sex (OR = 2.24, 95% CI 1.07 to 4.71) and every 1 month of diagnostic delay (OR=1.09, 95% CI 1.01 to 1.18) were positively associated with the occurrence of multiple FAs. At 24-month follow-up, 54% of patients acquired immune tolerance. This rate was higher in FPIAP (75%), when compared with FPIMD (62%), FPE (54%) and FPIES (24%). The odds of 24-month immune tolerance acquisition rate was lower in children with family history of allergy (OR=0.41, 95% CI 0.19 to 0.89) and in those with multiple FAs at baseline (OR=0.24, 95% CI 0.11 to 0.51). At 24-month follow-up, the rate of patients with allergic march was 0.46 (95% CI 0.38 to 0.55, n=57/123), without differences comparing the four phenotypes. The presence of multiple FAs at baseline was associated with an increased risk of developing allergic march (OR=2.22, 95% CI 1.07 to 4.61) at 24-month follow-up. CONCLUSIONS The results of the study suggest the potential role of modifiable and non-modifiable risk factors influencing the natural history of paediatric patients affected by non-IgE-GIFA.
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Affiliation(s)
- Laura Carucci
- Department of Translational Medical Science, University of Naples Federico II, Napoli, Campania, Italy
- ImmunoNutritionLab, CEINGE Advanced Biotechnologies, Napoli, Campania, Italy
| | - Rita Nocerino
- Department of Translational Medical Science, University of Naples Federico II, Napoli, Campania, Italy
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Roma, Lazio, Italy
| | - Serena Coppola
- Department of Translational Medical Science, University of Naples Federico II, Napoli, Campania, Italy
- ImmunoNutritionLab, CEINGE Advanced Biotechnologies, Napoli, Campania, Italy
| | - Giorgio Bedogni
- Department of Primary Health Care, Internal Medicine Unit addressed to Frailty and Aging, AUSL Romagna, Ospedale Santa Maria delle Croci, Ravenna, Emilia-Romagna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Emilia-Romagna, Italy
| | - Pasqualina Capasso
- Department of Translational Medical Science, University of Naples Federico II, Napoli, Campania, Italy
- ImmunoNutritionLab, CEINGE Advanced Biotechnologies, Napoli, Campania, Italy
| | - Veronica Giglio
- Department of Translational Medical Science, University of Naples Federico II, Napoli, Campania, Italy
- ImmunoNutritionLab, CEINGE Advanced Biotechnologies, Napoli, Campania, Italy
| | - Roberto Berni Canani
- Department of Translational Medical Science, University of Naples Federico II, Napoli, Campania, Italy
- ImmunoNutritionLab, CEINGE Advanced Biotechnologies, Napoli, Campania, Italy
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Marget M, Baker C, O'Connell I, Shreffler WG, Yuan Q, Martin VM. Prospective association between food protein-induced allergic proctocolitis in infancy and constipation after age 3. J Pediatr Gastroenterol Nutr 2025; 80:108-112. [PMID: 39584247 DOI: 10.1002/jpn3.12410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 10/11/2024] [Accepted: 10/11/2024] [Indexed: 11/26/2024]
Abstract
We sought to prospectively evaluate whether food protein-induced allergic proctocolitis (FPIAP) during infancy is associated with increased constipation later in childhood. Using the Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) cohort, we reviewed charts of children with prospective parent-reported constipation after age 3 to confirm the diagnosis of constipation. A diagnosis of FPIAP was based on pediatrician diagnosis and required guaiac-positive or grossly bloody stools, as previously published. Three hundred and seventy-five subjects had sufficient data for these analyses. Subjects with FPIAP had more than two times the odds of developing constipation after age 3 compared to subjects without (odds ratio [OR]: 2.62, 95% confidence interval [CI]: [1.42-4.74], p = 0.002). The use of stimulant laxatives was also higher in children with FPIAP (OR: 4.68, 95% CI: [1.47-16.04], p = 0.01). FPIAP was prospectively associated with the later development of constipation after age 3. This may suggest shared underlying pathogenesis, resultant heightened visceral hypersensitivity, and/or intestinal dysbiosis, all warranting further study.
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Affiliation(s)
- Michael Marget
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Corey Baker
- Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's, Hartford, Connecticut, USA
| | - Isabel O'Connell
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Wayne G Shreffler
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
| | - Qian Yuan
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Victoria M Martin
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
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Malekiantaghi A, Ghanaati F, Shabani-Mirzaee H, Shariat M, Mojtahedi SY, Eftekhari K. Lactobacillus rhamnosus Helps to Reduce the Duration of Bleeding in Breastfed Infants with Allergic Proctocolitis. Breastfeed Med 2025; 20:59-64. [PMID: 39417285 DOI: 10.1089/bfm.2024.0185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Background: Cow's milk protein allergy (CMPA) is the most common food allergy in infants. The current standard of care (SOC) involves eliminating the allergen from both the infant's and mother's diet for 2-4 weeks. The purpose of this study is to assess the effectiveness of Lactobacillus rhamnosus (Ramnoflor) in reducing the duration of bleeding in these infants. Methods: This randomized clinical trial was conducted at Bahrami Children's Hospital on breastfed infants who were diagnosed with CMPA and had a positive occult blood (OB) test. Patients were randomly assigned to either the control or case groups. All patients received SOC therapy, with the case group receiving Ramnoflor and the control group receiving a placebo. Data were recorded on the checklist, and the children were followed and visited three times during the study, with an OB assessment at each visit. Results: The study enrolled 48 infants. Among the infants in the case group, the OB test was positive in four cases (8.3%) on the fifth day. However, there were no positive cases on the 14th and 30th days. The prevalence of this test was significantly lower in patients who received probiotics compared to the control group on the fifth day (p < 0.001). There were no positive OB tests on the 14th and 30th days in any of the groups, and no significant difference was observed between the groups. Conclusion: The addition of L. rhamnosus to SOC therapy led to a decrease in the duration of rectal bleeding in infants with CMPA compared to the control group.
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Affiliation(s)
- Armen Malekiantaghi
- Department of Pediatric, Bahrami Children's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Ghanaati
- Department of Pediatric, Bahrami Children's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hosein Shabani-Mirzaee
- Department of Pediatric Endocrinology, Bahrami Children's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mamak Shariat
- Maternal, Fetal & Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sayed-Yousef Mojtahedi
- Department of Pediatric Nephrology, Bahrami Children's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kambiz Eftekhari
- Department of Pediatric, Pediatric Gastroenterology and Hepatology Research Center, Bahrami Children's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Lemoine A, Bamberger S. Histoire naturelle des allergies alimentaires non IgE-médiées. REVUE FRANÇAISE D'ALLERGOLOGIE 2025; 65:104174. [DOI: 10.1016/j.reval.2024.104174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Barni S, Pessina B, Fioretti L, Scarallo L, Di Siena A, Bramuzzo M, Liccioli G, Sarti L, Tomei L, Giovannini M, Renzo S, Mori F. Food Protein-Induced Allergic Proctocolitis: Real-World Experience from an Italian Cohort. Nutrients 2024; 17:98. [PMID: 39796533 PMCID: PMC11722936 DOI: 10.3390/nu17010098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 12/20/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated food allergy, usually presenting as bloody stools in breastfed, well-appearing, and regularly growing infants. The aim of our study was to describe the clinical features of Italian infants affected by FPIAP and their management and natural history in a real-life setting. Methods: A retrospective, observational study was performed at two tertiary pediatric hospitals (Florence and Trieste), including FPIAP-diagnosed infants between 2012 and 2022. Results: Most of the 100 enrolled patients were breastfed (68.0%), and the majority of those who underwent diagnostic tests (n = 51) showed normal hemoglobin and total IgE levels. A maternal elimination diet was performed in 69.0%, mostly for milk only, but 40.6% underwent multiple elimination diets. The remission rate was high both in breastfed infants (76.8%) and in those who received extensively hydrolyzed formula (81.8%). Nine subjects were left on a free diet, but six were lost at follow-up. The median time of complete remission was 30 days (IQR 14-60). Culprit food reintroduction was tolerated at a median age of 8 months (IQR 6-11), in ladder modality (for hen's egg and cow's milk) in 61.7%. Nine patients relapsed (14.3%) upon reintroduction with no associated variables identified at the regression analysis. The relapse rate was slightly higher when trigger food reintroduction was attempted > 12 months (16.7%) versus <12 months (13.0%). Conclusions: In our population, FPIAP had, as expected, a benign evolution. The early reintroduction of the suspect food in a gradual manner for cow's milk and hen's egg leads to good tolerance within the first year in most patients, avoiding unnecessary elimination diets.
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Affiliation(s)
- Simona Barni
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
| | - Benedetta Pessina
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
- Department of Health Sciences, University of Florence, 50139 Florence, Italy
| | - Lorenzo Fioretti
- Department of Health Sciences, University of Florence, 50139 Florence, Italy
- Gastroenterology and Nutrition Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
| | - Luca Scarallo
- Gastroenterology and Nutrition Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
- Department of NEUROFARBA, University of Florence, 50139 Florence, Italy
| | - Andrea Di Siena
- Division of Pediatrics, Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
| | - Matteo Bramuzzo
- Pediatric Gastroenterology, Digestive Endoscopy and Clinical Nutrition Unit, Department of Pediatrics, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, 34137 Trieste, Italy
| | - Giulia Liccioli
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
| | - Lucrezia Sarti
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
| | - Leonardo Tomei
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
| | - Mattia Giovannini
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
- Department of Health Sciences, University of Florence, 50139 Florence, Italy
| | - Sara Renzo
- Gastroenterology and Nutrition Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
| | - Francesca Mori
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
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Cook VE, Connors LA, Vander Leek TK, Watson W. Non-immunoglobulin E-mediated food allergy. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2024; 20:70. [PMID: 39702412 PMCID: PMC11656650 DOI: 10.1186/s13223-024-00933-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/15/2024] [Indexed: 12/21/2024]
Abstract
Non-immunoglobulin E (IgE)-mediated food allergies are characterized by delayed gastrointestinal (GI) manifestations that occur after exposure to an inciting food protein; they include food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and food protein-induced enterocolitis syndrome (FPIES). Although the exact mechanisms underlying these disorders are not well understood, non-IgE-mediated food allergies likely represent a spectrum of disease with shared pathophysiological processes. Typically, these non-IgE-mediated food allergies begin in infancy or early childhood, although FPIES can present across the lifespan, with increasing reports in adults in recent years. Diagnosing non-IgE-mediated food allergies can be challenging due to the lack of noninvasive confirmatory tests or biomarkers for most of these disorders and the non-specific nature of GI symptoms. Thus, the diagnosis is usually made clinically, and relies on a constellation of typical symptoms that improve upon removal of the culprit food. The primary approach to management of FPIAP, FPE and FPIES is avoidance of the triggering food, and a multidisciplinary management approach that includes allergy/immunology may be required to avoid unnecessary food restriction and guide food reintroduction. This review outlines the clinical manifestations, epidemiology, pathophysiology, diagnosis, management, and prognosis of these non-IgE-mediated food allergies.
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Affiliation(s)
- Victoria E Cook
- Division of Allergy, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
| | - Lori A Connors
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Timothy K Vander Leek
- Division of Allergy, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Wade Watson
- Division of Allergy, Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, NS, Canada
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Vallianatou GN, Douladiris N, Mageiros L, Manousakis E, Zisaki V, Galani M, Xepapadaki P, Taka S, Papadopoulos NG. Duration of food protein-induced allergic proctocolitis (FPIAP) and the role of intestinal microbiota. Pediatr Allergy Immunol 2024; 35:e70008. [PMID: 39629903 PMCID: PMC11616471 DOI: 10.1111/pai.70008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 10/31/2024] [Accepted: 11/14/2024] [Indexed: 12/08/2024]
Abstract
BACKGROUND Food protein-induced allergic proctocolitis (FPIAP) is the leading cause of rectal bleeding in infants. Tolerance is presumed to develop until the first year of age, although natural history studies are scarce, making the determination of the ideal duration for any intervention, challenging. Intestinal microbiota (IM) is crucial in food allergy development; however, data for FPIAP remain limited. This study aimed to assess FPIAP remission after 3 months of milk avoidance and its correlation with IM longitudinal changes. METHODS A prospective observational study of infants aged ≤6 months with a diagnosis of FPIAP. After 3 months of management according to a clinical algorithm, infants were subjected to a milk challenge using either a cow (CM) or a goat (GM) milk formula in a random order. Stool samples were collected longitudinally for microbiome analysis. RESULTS Out of 61 infants, 57 were challenged (29 with CM, 28 with GM). Of these, 55 (96.5%) achieved tolerance, with no difference in tolerance rates between CM (28/29) and GM (27/28). The average age of tolerance development was 6.3 months. Enterobacteriaceae clusters (Klebsiella- and Shigella-dominated) were most often represented in samples from symptomatic infants. In contrast, Bacteroides and Bifidobacteria clusters emerged later, in apparently healthy infants. CONCLUSION A 3-month intervention was sufficient for almost all infants to achieve tolerance. GM was tolerated equally well to CM. Symptomatic FPIAP is associated with immature enterotypes, while disease remission coincides with microbiome changes in time.
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Affiliation(s)
- G. N. Vallianatou
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
| | - N. Douladiris
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
| | - L. Mageiros
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
- Department of Information Technology and Biomedical SciencesThe American College of GreeceAthensGreece
| | - E. Manousakis
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
| | - V. Zisaki
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
| | - M. Galani
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
| | - P. Xepapadaki
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
| | - S. Taka
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
- Startbio PC Molecular Diagnostics and Biotechnology ServicesStartbioAthensGreece
| | - N. G. Papadopoulos
- Allergy Department, 2nd Pediatric ClinicNational and Kapodistrian University of AthensAthensGreece
- University of ManchesterManchesterUK
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12
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Sathya P, Fenton TR. L'allergie aux protéines du lait de vache chez les nourrissons et les enfants. Paediatr Child Health 2024; 29:382-396. [PMID: 39539787 PMCID: PMC11557140 DOI: 10.1093/pch/pxae042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 10/31/2023] [Indexed: 11/16/2024] Open
Abstract
L'allergie aux protéines du lait de vache (APLV) est une réaction à médiation immunitaire aux protéines du lait de vache, qui peut toucher de multiples systèmes organiques, y compris le tractus gastro-intestinal. Une réaction induite par les immunoglobulines E (IgE) entraîne l'apparition rapide de symptômes allergiques faciles à reconnaître. Cependant, des réactions tardives (non induites par les IgE ou les cellules) ou mixtes (induites par les IgE et les cellules) entraînent une série de symptômes qui ressemblent à d'autres affections et dont le moment d'apparition et la gravité sont très variables. Il est difficile de déterminer si les symptômes sont attribuables à une APLV à médiation immunitaire, à une réaction non immunologique au lait de vache ou à autre chose que l'exposition au lait de vache, mais il est essentiel d'y parvenir pour proposer une prise en charge efficace. Le tableau clinique de l'APLV non induite par les IgE peut varier, mais cette affection, généralement autorésolutive, disparaît entre l'âge de un et six ans. Il faut éviter les batteries de dosages des immunoglobulines G (IgG) pour déceler les intolérances alimentaires spécifiques aux antigènes qui ne reposent pas sur des données probantes, parce qu'elles peuvent entraîner un surdiagnostic de prétendues intolérances alimentaires. Le surdiagnostic d'APLV peut être responsable de la surutilisation de préparations fortement hydrolysées, ce qui a des répercussions financières importantes pour les familles. Le présent document de principes, qui traite de l'APLV non induite par les IgE ou les cellules, aide les professionnels de la santé à distinguer et reconnaître les diverses réactions au lait de vache, aborde le rôle des tests diagnostiques et fournit des recommandations de prise en charge en fonction des données probantes exemplaires.
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Affiliation(s)
- Pushpa Sathya
- Société canadienne de pédiatrie, comité de nutrition et de gastroentérologie, Ottawa (Ontario)Canada
| | - Tanis R Fenton
- Société canadienne de pédiatrie, comité de nutrition et de gastroentérologie, Ottawa (Ontario)Canada
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13
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Sathya P, Fenton TR. Cow's milk protein allergy in infants and children. Paediatr Child Health 2024; 29:382-396. [PMID: 39539784 PMCID: PMC11557147 DOI: 10.1093/pch/pxae043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 10/31/2023] [Indexed: 11/16/2024] Open
Abstract
Cow's milk protein allergy (CMPA) is an immune-mediated reaction to cow's milk proteins, which can involve multiple organ systems including the gastrointestinal tract. Immunoglobulin E (IgE)-mediated response results in rapid onset of allergic symptoms that are easily recognizable. However, delayed (i.e., non-IgE/cell-mediated) or mixed (IgE- and cell-mediated) reactions produce a host of symptoms that overlap with other conditions and vary widely in onset and severity. Determining whether symptoms represent immune-mediated CMPA, non-immunologic reaction to cow's milk, or are unrelated to cow's milk exposure is challenging yet essential for effective management. While the clinical presentation of non-IgE-mediated CMPA can vary, this condition is usually self-limited and resolves by 1 to 6 years of age. Food antigen-specific immunoglobulin G (IgG) panels that are not evidence-based should be avoided because they can lead to overdiagnosis of presumed food intolerances. Overdiagnosis of CMPA can result in overuse of extensively hydrolyzed formulas and have significant cost implications for families. This statement focuses on delayed non-IgE/cell-mediated CMPA and assists health care providers to distinguish between and identify varied reactions to cow's milk, discusses the role of diagnostic testing, and provides management recommendations based on best evidence.
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Affiliation(s)
- Pushpa Sathya
- Canadian Paediatric Society, Nutrition and Gastroenterology Committee, Ottawa, Ontario, Canada
| | - Tanis R Fenton
- Canadian Paediatric Society, Nutrition and Gastroenterology Committee, Ottawa, Ontario, Canada
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14
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Venter C, Meyer R, Groetch M, Nowak-Wegrzyn A, Mennini M, Pawankar R, Kamenwa R, Assa'ad A, Amara S, Fiocchi A, Bognanni A. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update - XVI - Nutritional management of cow's milk allergy. World Allergy Organ J 2024; 17:100931. [PMID: 39228431 PMCID: PMC11369454 DOI: 10.1016/j.waojou.2024.100931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 05/27/2024] [Accepted: 06/21/2024] [Indexed: 09/05/2024] Open
Abstract
Cow's milk allergy (CMA) is one of the most common presentations of food allergy in early childhood. Management of CMA involves individualized avoidance of cow's milk and other mammalian milk and foods containing these. Optimal elimination of cow's milk avoidance includes: label reading; information about safe and nutritious substitute foods; appropriate choice of infant formula or a plant-based food; establishing tolerance to baked milk and monitoring nutritional intake and growth. Substitute formulas are divided into soy formula (not hydrolyzed), milk-based extensively hydrolyzed formulas, rice based extensive, and partially hydrolyzed formulas and amino acid-based formulas. The use of other mammalian milks is not recommended for the management of cow's milk allergy due to a high level of cross-reactivity and nutritional concerns. For toddlers who are eating well, children, and adults, a suitable plant-based beverage may be a suitable alternative to a specialized formula, following careful nutritional considerations. Families need to be instructed on finding suitable nutritious foods and how to prepare suitable meals at home. Individuals with CMA also need to know how to identify and treat acute severe reactions.
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Affiliation(s)
- Carina Venter
- Section of Allergy and Immunology, University of Colorado Denver School of Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Rosan Meyer
- Department of Medicine, Imperial College, London. Department Medicine KU Leuven, Belgium. Department Nutrition and Dietetics, Winchester University, UK
| | - Marion Groetch
- Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai. New York, NY, USA
| | - Anna Nowak-Wegrzyn
- Department of Pediatrics, NYU Grossman School of Medicine, Hassenfeld Childrens' Hospital, New York, NY, USA
- Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Maurizio Mennini
- NESMOS Department, Sapienza University, Pediatric Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Ruby Pawankar
- Department of Pediatrics, Nippon Medical School, Tokyo, Japan
| | - Rose Kamenwa
- Department of Paediatrics and Child Health, Aga Khan University Hospital, Nairobi, Kenya
| | - Amal Assa'ad
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center – Cincinnati Ohio, USA
| | | | - Alessandro Fiocchi
- Division of Allergy, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome 00165, Italy
| | - Antonio Bognanni
- Clinical Epidemiology and Research Center (CERC), Humanitas University & Humanitas Research Hospital, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele (Milano), Italy
- Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada
- Department of Medicine, Evidence in Allergy Group, McMaster University, Hamilton, Ontario, Canada
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15
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Gelsomino M, Liotti L, Barni S, Mori F, Giovannini M, Mastrorilli C, Pecoraro L, Saretta F, Castagnoli R, Arasi S, Klain A, del Giudice MM, Novembre E. Elimination Diets in Lactating Mothers of Infants with Food Allergy. Nutrients 2024; 16:2317. [PMID: 39064760 PMCID: PMC11279873 DOI: 10.3390/nu16142317] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 07/10/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Breastfeeding is the most important nutrition source for infants. However, managing breastfed infants with signs and symptoms related to food allergy can be difficult. Many studies have shown the presence of different food allergens in breast milk, but the clinical role of these antigens in human milk is still much debated. Milk is the main suspect in exclusively breastfed infants with signs and symptoms attributable to food allergy, even if other foods may be responsible. This narrative review analyzes the recommendations provided by international guidelines to determine the diagnosis and management of IgE-mediated and non-IgE-mediated food allergies in exclusively breastfed infants. Dietary restrictions in lactating mothers of infants with suspected FA are usually not necessary. Only in the very few cases where significant allergy signs and symptoms occur in the infant during exclusive breastfeeding should the lactating mother follow an elimination diet for the suspected food for a short period.
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Affiliation(s)
- Mariannita Gelsomino
- Pediatric Allergy Unit, Department of Life Sciences and Public Health, University Foundation Policlinico Gemelli IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Lucia Liotti
- Pediatric Unit, Department of Mother and Child Health, Salesi Children’s Hospital, 60123 Ancona, Italy;
| | - Simona Barni
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.)
| | - Francesca Mori
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.)
| | - Mattia Giovannini
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.)
- Department of Health Sciences, University of Florence, 50139 Florence, Italy;
| | - Carla Mastrorilli
- Pediatric Hospital Giovanni XXIII, Pediatric and Emergency Department, AOU Policlinic of Bari, 70126 Bari, Italy;
| | - Luca Pecoraro
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37126 Verona, Italy;
| | - Francesca Saretta
- Pediatric Department, Latisana-Palmanova Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy;
| | - Riccardo Castagnoli
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy;
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefania Arasi
- Translational Research in Pediatric Specialties Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Angela Klain
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Michele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Elio Novembre
- Department of Health Sciences, University of Florence, 50139 Florence, Italy;
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16
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Suzuki H, Morisaki N, Nagashima S, Matsunaga T, Matsushita S, Iino A, Tanaka Y, Nishimori H, Munakata S, Kemmochi M, Murakami Y, Sato M, Toyokuni K, Yamamoto-Hanada K, Morita H, Fukuie T, Yamada Y, Ohtsuka Y, Arai K, Ohya Y, Saito H, Matsumoto K, Nomura I. A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants. Allergol Int 2024; 73:264-274. [PMID: 37914545 DOI: 10.1016/j.alit.2023.10.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 09/24/2023] [Accepted: 10/06/2023] [Indexed: 11/03/2023] Open
Abstract
BACKGROUND Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. METHODS We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). RESULTS The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. CONCLUSIONS In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.
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Affiliation(s)
- Hiroko Suzuki
- National Research Institute for Child Health and Development, Division of Eosinophilic Gastrointestinal Disorders, Tokyo, Japan; Todachuo General Hospital, Department of Pediatrics, Saitama, Japan
| | - Naho Morisaki
- National Center for Child Health and Development, Department of Social Medicine, Tokyo, Japan
| | - Saori Nagashima
- National Research Institute for Child Health and Development, Division of Eosinophilic Gastrointestinal Disorders, Tokyo, Japan
| | | | - Shoko Matsushita
- Tokyo Metropolitan Children's Medical Center, Department of Allergy, Tokyo, Japan
| | - Akira Iino
- Tokyo Metropolitan Children's Medical Center, Department of Allergy, Tokyo, Japan
| | - Yuichiro Tanaka
- National Center for Child Health and Development, Department of General Pediatrics and Interdisciplinary Medicine, Tokyo, Japan
| | - Hisashi Nishimori
- Mie Prefectural General Medical Center, Department of Pediatrics, Mie, Japan
| | - Shun Munakata
- Nagano Children's Hospital, Department of Neonatology, Nagano, Japan
| | - Manabu Kemmochi
- Kitasato University Hospital, Department of Pediatrics, Kanagawa, Japan
| | - Yoshitaka Murakami
- Ehime Prefectural Imabari Hospital, Department of Pediatrics, Ehime, Japan
| | - Miori Sato
- National Center for Child Health and Development, Allergy Center, Tokyo, Japan
| | - Kenji Toyokuni
- National Center for Child Health and Development, Allergy Center, Tokyo, Japan
| | | | - Hideaki Morita
- National Research Institute for Child Health and Development, Department of Allergy and Clinical Immunology, Tokyo, Japan
| | - Tatsuki Fukuie
- National Center for Child Health and Development, Allergy Center, Tokyo, Japan
| | - Yoshiyuki Yamada
- Tokai University School of Medicine, Department of Pediatrics, Kanagawa, Japan
| | - Yoshikazu Ohtsuka
- Juntendo University School of Medicine, Department of Pediatrics and Adolescent Medicine, Tokyo, Japan
| | - Katsuhiro Arai
- National Center for Child Health and Development, Allergy Center, Tokyo, Japan; National Center for Child Health and Development, Division of Gastroenterology, Tokyo, Japan
| | - Yukihiro Ohya
- National Center for Child Health and Development, Allergy Center, Tokyo, Japan
| | - Hirohisa Saito
- National Research Institute for Child Health and Development, Department of Allergy and Clinical Immunology, Tokyo, Japan
| | - Kenji Matsumoto
- National Research Institute for Child Health and Development, Department of Allergy and Clinical Immunology, Tokyo, Japan
| | - Ichiro Nomura
- National Research Institute for Child Health and Development, Division of Eosinophilic Gastrointestinal Disorders, Tokyo, Japan; National Center for Child Health and Development, Allergy Center, Tokyo, Japan.
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17
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Salvatore S, Folegatti A, Ferrigno C, Pensabene L, Agosti M, D'Auria E. To Diet or Not to Diet This Is the Question in Food-Protein-Induced Allergic Proctocolitis (FPIAP)-A Comprehensive Review of Current Recommendations. Nutrients 2024; 16:589. [PMID: 38474718 DOI: 10.3390/nu16050589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/13/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024] Open
Abstract
Food-protein-induced allergic proctocolitis (FPIAP) is an increasingly reported transient and benign form of colitis that occurs commonly in the first weeks of life in healthy breastfed or formula-fed infants. Distal colon mucosal inflammation is caused by a non-IgE immune reaction to food allergens, more commonly to cow's milk protein. Rectal bleeding possibly associated with mucus and loose stools is the clinical hallmark of FPIAP. To date, no specific biomarker is available, and investigations are reserved for severe cases. Disappearance of blood in the stool may occur within days or weeks from starting the maternal or infant elimination diet, and tolerance to the food allergen is typically acquired before one year of life in most patients. In some infants, no relapse of bleeding occurs when the presumed offending food is reassumed after a few weeks of the elimination diet. Many guidelines and expert consensus on cow's milk allergy have recently been published. However, the role of diet is still debated, and recommendations on the appropriateness and duration of allergen elimination in FPIAP are heterogeneous. This review summarizes and compares the different proposed nutritional management of infants suffering from FPIAP, highlighting the pros and cons according to the most recent literature data.
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Affiliation(s)
- Silvia Salvatore
- Pediatric Department, Hospital "F. Del Ponte", University of Insubria, 21100 Varese, Italy
| | - Alice Folegatti
- Pediatric Department, Hospital "F. Del Ponte", University of Insubria, 21100 Varese, Italy
| | - Cristina Ferrigno
- Department of Pediatrics, Buzzi Children's Hospital, 20154 Milan, Italy
| | - Licia Pensabene
- Pediatric Unit, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Massimo Agosti
- Pediatric Department, Hospital "F. Del Ponte", University of Insubria, 21100 Varese, Italy
| | - Enza D'Auria
- Department of Pediatrics, Buzzi Children's Hospital, 20154 Milan, Italy
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18
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Vandenplas Y, Broekaert I, Domellöf M, Indrio F, Lapillonne A, Pienar C, Ribes-Koninckx C, Shamir R, Szajewska H, Thapar N, Thomassen RA, Verduci E, West C. An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy. J Pediatr Gastroenterol Nutr 2024; 78:386-413. [PMID: 38374567 DOI: 10.1097/mpg.0000000000003897] [Citation(s) in RCA: 38] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 06/25/2023] [Indexed: 07/27/2023]
Abstract
A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.
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Affiliation(s)
- Yvan Vandenplas
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium
| | - Ilse Broekaert
- Department of Paediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Magnus Domellöf
- Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
| | - Flavia Indrio
- Department of Medical and Surgical Science, University of Foggia, Foggia, Italy
| | - Alexandre Lapillonne
- Neonatal Intensive Care Unit, Necker-Enfants Malades Hospital, Paris University, Paris, France
- CNRC, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| | - Corina Pienar
- Department of Pediatrics, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Carmen Ribes-Koninckx
- Gastroenterology and Hepatology & Instituto de Investigacion Sanitaria, La Fe University Hospital, Valencia, Spain
| | - Raanan Shamir
- Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Lea and Arieh Pickel Chair for Pediatric Research, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Hania Szajewska
- Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
| | - Nikhil Thapar
- Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
- School of Medicine, University of Queensland, Brisbane, Australia
- Woolworths Centre for Child Nutrition Research, Queensland University of Technology, Brisbane, Australia
- UCL Great Ormond Street Institute of Child Health, London, UK
| | - Rut Anne Thomassen
- Department of Paediatric Medicine, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
| | - Elvira Verduci
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Christina West
- Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
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19
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Wang Z, Wu Q, Guan M, Li Z, Pan W, Tang W. Investigation of gut microbiota changes and allergic inflammation of mice with milk protein-induced allergic enteritis. FEMS Microbiol Lett 2024; 371:fnad127. [PMID: 38066685 DOI: 10.1093/femsle/fnad127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/03/2023] [Accepted: 12/07/2023] [Indexed: 01/11/2024] Open
Abstract
This study aimed to investigate the changes of gut microbiota and allergic inflammation in mice with allergic enteritis caused by milk protein. In this study, female BALB\C mice in the whey protein (WP-sensitized) group were gavaged with WP and normal saline, the sham-sensitized group was given normal saline once a week for 5 weeks. One week later, the WP-sensitized mice were administered 60 mg β-lactoglobulin (BLG). The results showed that mice's body weight decreased, feces with loose and bloody, and systemic allergic reactions and ear swelling increased in the WP-sensitized group. The levels of WP-specific Ig, mMCP-1, calprotectin of feces, and inflammation-related factors in the WP-sensitized group were increased. WP-sensitized group intestine tissues were damaged severely and the expressions of ZO-1, Claudin-1, and Occludin reduced. The results of 16S rRNA sequencing showed that there were differences in operational taxonomic units (OUT) levels of gut microbes between the two groups, o_Clostridiales, c_Clostridia, and f_Lachnospiraceae were more abundant in the WP-sensitized group. In conclusion, the WP sensitization can induce the allergic inflammation, intestinal injury and intestinal barrier dysfunction in mice, and the gut microbes were also changed, which provided a reference for the treatment of WP-sensitized mice.
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Affiliation(s)
- Zhongmin Wang
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
| | - Qiao Wu
- Department of Pediatrics, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, China
| | - Minchang Guan
- Department of Pediatrics, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310021, China
| | - Ze Li
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
| | - Wei Pan
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
| | - Weihong Tang
- Department of Gastroenterology, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, China
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20
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Venter C, Vieira MC, Fleischer D. Tolerance development in non-IgE mediated food allergies: lessons from Brazil. J Pediatr (Rio J) 2024; 100:4-7. [PMID: 37858601 PMCID: PMC10751694 DOI: 10.1016/j.jped.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2023] Open
Affiliation(s)
- Carina Venter
- University of Colorado School of Medicine, Department of Pediatrics, Section of Allergy & Immunology, Colorado, USA; Children's Hospital Colorado, Colorado, USA.
| | - Mario C Vieira
- Hospital Pequeno Príncipe, Centro de Gastroenterologia Pediátrica, Curitiba, PR, Brazil
| | - David Fleischer
- University of Colorado School of Medicine, Department of Pediatrics, Section of Allergy & Immunology, Colorado, USA; Children's Hospital Colorado, Colorado, USA
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21
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Nunes de Castilho Santos L. [Differential diagnosis in food allergy]. REVISTA ALERGIA MÉXICO 2023; 70:260-264. [PMID: 38506869 DOI: 10.29262/ram.v70i4.1312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/29/2023] [Indexed: 03/21/2024] Open
Abstract
It is important to establish the differential diagnosis of food allergy with other disorders, for example: toxic reactions that occur in any person exposed to a sufficient amount of some allergen, and non-toxic reactions that depend on individual susceptibility (food allergy or intolerance). The differential diagnosis is decisive to establish the appropriate treatment. Food intolerance involves adverse reactions to foods without any immunological response involved, and commonly manifests with gastrointestinal symptoms (malaise, abdominal pain or diarrhea). Food allergy is an exaggerated reaction of the immune system, often mediated by IgE, that can trigger serious symptoms (hives, inflammation, respiratory distress, even anaphylaxis). The complex thing is because the symptoms sometimes overlap. To establish an accurate diagnosis, exhaustive clinical evaluation, laboratory tests and, in some cases, controlled provocation tests are required. It is important to understand these distinctions, because treatment and management vary significantly. Food intolerance involves the elimination or reduction of the food that triggers the allergic reaction and requires rigorous measures (complete avoidance of the allergen and availability of epinephrine in cases of severe reactions).
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Affiliation(s)
- Liziane Nunes de Castilho Santos
- Alergólogo e Inmunólogo; Responsable Técnico y Profesor del sector de Alergia e Inmunología del Instituto Nacional de Salud de la Mujer, del Niño y del Adolescente Fernandes Figueira IFF/Fiocruz,
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22
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Rojo Gutiérrez MI, Ballesteros González D, Ortiz Durán AK. [Non-IgE-mediated food allergy]. REVISTA ALERGIA MÉXICO 2023; 70:269-279. [PMID: 38506871 DOI: 10.29262/ram.v70i4.1338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/29/2023] [Indexed: 03/21/2024] Open
Abstract
Food allergy is an immune response to proteins in food. It usually affects 8% of children and 2% of adults in Western countries. Non-IgE-mediated food allergy mainly affects the gastrointestinal tract. Gastrointestinal food allergies are classified, by their underlying pathogenesis, as: IgE-mediated, non-IgE-mediated, or mixed. The symptoms of patients with food protein-induced allergic proctocolitis originate from local inflammation of the distal colon, which causes hematochezia in neonates. It can affect the entire gastrointestinal tract and cause symptoms of intractable emesis, with subsequent metabolic disorders and hypovolemic shock. Food protein-induced enterocolitis syndrome is a non-IgE-mediated allergy that usually appears in childhood, with prolonged repetitive vomiting, starting 1 to 4 hours after ingestion of food. The manifestation in adults is usually triggered by the consumption of shellfish. Atopic diseases affect 40-60% of patients with food protein- induced enterocolitis syndrome, including 40-50% of those with food protein-induced enteropathy and proctocolitis. Probiotics (Lactobacillus GG) can alleviate the symptoms of allergic proctocolitis induced by food proteins, by altering the composition of the intestinal microbiota. Fecal microbiota transplantation (FMT) can change intestinal microecology efficiently compared to food or probiotics.
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Affiliation(s)
- María Isabel Rojo Gutiérrez
- Alergóloga e Inmunóloga clínica, Máster en Ciencias y Educación; Miembro de la Mesa Directiva de SLAAI; miembro activo del Colegio Mexicano de Inmunología Clínica y Alergia; Directora de Alergología en la Unidad Médica Zúrich, Ciudad de
| | - Diego Ballesteros González
- Médico Cirujano y Partero, Escuela Superior de Medicina, Instituto Politécnico Nacional; Alergia e inmunología clínica, Hospital Juárez de México
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23
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Vandenplas Y, Meyer R, Nowak-Wegrzyn A, Salvatore S, Venter C, Vieira MC. The Remaining Challenge to Diagnose and Manage Cow's Milk Allergy: An Opinion Paper to Daily Clinical Practice. Nutrients 2023; 15:4762. [PMID: 38004156 PMCID: PMC10675216 DOI: 10.3390/nu15224762] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/07/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Guidelines and recommendations for the diagnosis and management of cow's milk allergy (CMA) in childhood are based on scientific review of the available evidence. While this approach is the most rigorous, guidelines may not fully address all scenarios encountered by clinicians. Many symptoms of CMA overlap with other common childhood illnesses and are subjectively reported by the caregivers of the infant, as is the interpretation of the dietary interventions. Additionally, many healthcare professionals and caregivers do not follow the recommendations to perform an oral food challenge or reintroduction of cow's milk after a diagnostic elimination diet because (1) the infant is doing well and (2) the carer's fear of symptoms relapsing with this procedure. As a result, CMA in infants may be either under-diagnosed leading to reduced quality of life for families or over-diagnosed, resulting in unnecessary long-term elimination diets and increasing the risk for nutritional deficiencies. This paper discusses some of these controversial topics, focusing on misdiagnosis and mismanagement in clinical practice. The lack of objective diagnostic criteria can hamper the diagnosis and management of CMA in daily practice.
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Affiliation(s)
- Yvan Vandenplas
- UZ Brussel, KidZ Health Castle, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium
| | - Rosan Meyer
- Department Paediatrics, Imperial College London, London SW7 2BX, UK
- Department Dietetics, Winchester University, Winchester SO23 4NR, UK
- Department Medicine, KU Leuven, 3001 Leuven, Belgium
| | - Anna Nowak-Wegrzyn
- Department of Pediatrics, NYU Grossman School of Medicine, Hassenfeld Children’s Hospital, New York, NY 10016, USA
- Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Silvia Salvatore
- Department of Pediatrics, Hospital “F. Del Ponte”, University of Insubria, 21100 Varese, Italy;
| | - Carina Venter
- Section of Pediatric Allergy and Immunology, Children’s Hospital Colorado, University of Colorado, Aurora, CO 80045, USA
| | - Mario C. Vieira
- Center for Pediatric Gastroenterology, Hospital Pequeno Príncipe, Curitiba 80250, Brazil;
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24
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Rosow R, Virkud YV, Martin VM, Young M, Su KW, Phadke N, Shreffler WG, Yuan Q. Longitudinal assessment of early growth in children with IgE- and non-IgE-mediated food allergy in a healthy infant cohort. Ann Allergy Asthma Immunol 2023; 131:362-368.e1. [PMID: 37236540 PMCID: PMC10524541 DOI: 10.1016/j.anai.2023.05.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 05/09/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023]
Abstract
BACKGROUND There are conflicting associations reported between food allergies (FAs) and poor growth, with some indication that children with multiple FAs are at highest risk. OBJECTIVE We analyzed longitudinal weight-for-length (WFL) trajectories from our healthy cohort to evaluate growth in children with IgE-mediated FAs and food protein-induced allergic proctocolitis (FPIAP), a non-IgE-mediated FA. METHODS Our observational cohort of 903 healthy newborn infants was prospectively enrolled to evaluate the development of FAs. Longitudinal mixed effects modeling was used to compare differences in WFL among children with IgE-FA and FPIAP, compared with unaffected children, through age 2. RESULTS Among the 804 participants who met inclusion criteria, FPIAP cases had significantly lower WFL than unaffected controls during active disease, which resolved by 1 year of age. In contrast, children with IgE-FA had significantly lower WFL than unaffected controls after 1 year. We also found that children with IgE-FA to cow's milk had significantly lower WFL over the first 2 years of age. Children with multiple IgE-FAs had markedly lower WFL over the first 2 years of age. CONCLUSION Children with FPIAP have impaired growth during active disease in the first year of age which resolves, whereas children with IgE-FA, particularly those with multiple IgE-FA, have impaired growth more prominently after the first year of age. It may be appropriate to focus nutritional assessment and interventions accordingly during these higher risk periods in these patient populations.
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Affiliation(s)
- Rachael Rosow
- Food Allergy Center at MGH, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts
| | - Yamini V Virkud
- Food Allergy Center at MGH, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Food Allergy Science Initiative at the Broad Institute, Cambridge, Massachusetts; Division of Pediatric Allergy & Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
| | - Victoria M Martin
- Food Allergy Center at MGH, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Food Allergy Science Initiative at the Broad Institute, Cambridge, Massachusetts
| | - Marielle Young
- Food Allergy Center at MGH, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts
| | - Kuan-Wen Su
- Department of Pediatrics, Keelung Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Neelam Phadke
- Harvard Medical School, Boston, Massachusetts; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Wayne G Shreffler
- Food Allergy Center at MGH, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Food Allergy Science Initiative at the Broad Institute, Cambridge, Massachusetts
| | - Qian Yuan
- Food Allergy Center at MGH, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Food Allergy Science Initiative at the Broad Institute, Cambridge, Massachusetts
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25
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Barni S, Mori F, Giovannini M, Liotti L, Mastrorilli C, Pecoraro L, Saretta F, Castagnoli R, Arasi S, Caminiti L, Gelsomino M, Klain A, del Giudice MM, Novembre E. Allergic Proctocolitis: Literature Review and Proposal of a Diagnostic-Therapeutic Algorithm. Life (Basel) 2023; 13:1824. [PMID: 37763228 PMCID: PMC10533178 DOI: 10.3390/life13091824] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 08/22/2023] [Accepted: 08/25/2023] [Indexed: 09/29/2023] Open
Abstract
Allergic proctocolitis (AP) is a benign condition, frequent in childhood, that is classified as a non-IgE-mediated food allergy. The prevalence is unknown; however, its frequency appears to be increasing, especially in exclusively breastfed infants. Clinical manifestations typically begin in the first few months of life with the appearance of bright red blood (hematochezia), with or without mucus, in the stool of apparently healthy, thriving infants. Most cases of AP are caused by cow's milk proteins; however, other allergens, such as soy, egg, corn, and wheat, may be potential triggers. Diagnosis is based on the patient's clinical history and on the resolution of signs and symptoms with the elimination of the suspected food antigen from the diet and their reappearance when the food is reintroduced into the diet. The treatment of AP is based on an elimination diet of the trigger food, with resolution of the symptoms within 72-96 h from the beginning of the diet. The prognosis of AP is good; it is a self-limiting condition, because most children can tolerate the trigger food within one year of life, with an excellent long-term prognosis. The purpose of this review is to provide an update on the current knowledge and recommendations in epidemiological, diagnostic, and therapeutic terms to the pediatricians, allergists, and gastroenterologists who may find themselves managing a patient with AP.
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Affiliation(s)
- Simona Barni
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
| | - Francesca Mori
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
| | - Mattia Giovannini
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
- Department of Health Sciences, University of Florence, 50139 Florence, Italy
| | - Lucia Liotti
- Pediatric Unit, Department of Mother and Child Health, Salesi Children’s Hospital, 60123 Ancona, Italy;
| | - Carla Mastrorilli
- Pediatric and Emergency Department, Pediatric Hospital Giovanni XXIII, AOU Policlinic of Bari, 70126 Bari, Italy;
| | - Luca Pecoraro
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37126 Verona, Italy;
| | - Francesca Saretta
- Pediatric Department, Latisana-Palmanova Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy;
| | - Riccardo Castagnoli
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy;
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefania Arasi
- Translational Research in Pediatric Specialties Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Lucia Caminiti
- Allergy Unit, Department of Pediatrics, AOU Policlinico Gaetano Martino, 98124 Messina, Italy;
| | - Mariannita Gelsomino
- Department of Life Sciences and Public Health, Pediatric Allergy Unit, University Foundation Policlinico Gemelli IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Angela Klain
- Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Michele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Elio Novembre
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
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26
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Marget M, Virkud YV, Shreffler WG, Martin VM, Yuan Q. Factors influencing age of common allergen introduction in early childhood. Front Pediatr 2023; 11:1207680. [PMID: 37497302 PMCID: PMC10366355 DOI: 10.3389/fped.2023.1207680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023] Open
Abstract
Objectives We evaluated factors influencing the timing of allergen introduction in the U.S., including updated peanut introduction guidelines. Study design The Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) study is a prospective observational cohort in suburban Massachusetts. Infants' caregivers enrolled between 2014 and 2017, and they reported when they introduced common allergens to their child. Multivariable linear and survival regression analyses were used to examine factors influencing time of introduction of allergens. Results By 9 months, children old enough to be potentially affected by NIAID's 2017 peanut introduction guidelines were more often introduced to peanut than children enrolled well before guidelines publication [54% vs. 42%, OR: 1.63, CI: (1.03, 2.57), P = 0.03]. At any given time, Black children were 73% [HR: 0.27, CI: (0.11, 0.69), P = 0.006] less likely to be introduced to peanut as early as White children. Asian children were, respectively, 36% [HR: 0.64, CI: (0.47, 0.86), P = 0.003] and 26% [HR: 0.74, CI: (0.55, 0.97), P = 0.03] less likely to be introduced to peanut and egg as early as White children. A first child was 27% [HR: 1.27, CI: (1.04, 1.56), P = 0.02] more likely to have been introduced to peanut earlier than a non-first child. There was no association between age of introduction and sex, gestational age, family history of food allergy, or other allergic comorbidities. Conclusion Updated introduction guidelines, race, and birth order all influenced earlier introduction of peanut. Further studies to evaluate current practices for allergen introduction with a focus on potential disparities are needed.
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Affiliation(s)
- Michael Marget
- Food Allergy Center, Massachusetts General Hospital, Boston, MA, United States
- Division of Pediatric Allergy and Immunology,Massachusetts General Hospital, Boston, MA, United States
| | - Yamini V. Virkud
- Food Allergy Center, Massachusetts General Hospital, Boston, MA, United States
- Division of Pediatric Allergy and Immunology,Massachusetts General Hospital, Boston, MA, United States
- Division of Pediatric Allergy & Immunology, University of North Carolina, Chapel Hill, NC, United States
| | - Wayne G. Shreffler
- Food Allergy Center, Massachusetts General Hospital, Boston, MA, United States
- Division of Pediatric Allergy and Immunology,Massachusetts General Hospital, Boston, MA, United States
- Department of Pediatrics, Harvard Medical School, Boston, MA, United States
| | - Victoria M. Martin
- Food Allergy Center, Massachusetts General Hospital, Boston, MA, United States
- Department of Pediatrics, Harvard Medical School, Boston, MA, United States
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, MA, United States
| | - Qian Yuan
- Food Allergy Center, Massachusetts General Hospital, Boston, MA, United States
- Department of Pediatrics, Harvard Medical School, Boston, MA, United States
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, MA, United States
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27
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Meyer R, Venter C, Bognanni A, Szajewska H, Shamir R, Nowak-Wegrzyn A, Fiocchi A, Vandenplas Y, WAO DRACMA Guideline Group. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update - VII - Milk elimination and reintroduction in the diagnostic process of cow's milk allergy. World Allergy Organ J 2023; 16:100785. [PMID: 37546235 PMCID: PMC10401347 DOI: 10.1016/j.waojou.2023.100785] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/28/2023] [Accepted: 05/12/2023] [Indexed: 08/08/2023] Open
Abstract
The diagnosis of cow's milk allergy (CMA) in infants and young children remains a challenge because many of the presenting symptoms are similar to those experienced in other diagnoses. Both over- and under-diagnosis occur frequently. Misdiagnosis carries allergic and nutritional risks, including acute reactions, growth faltering, micronutrient deficiencies and a diminished quality of life for infants and caregivers. An inappropriate diagnosis may also add a financial burden on families and on the healthcare system. Elimination and reintroduction of cow's milk (CM) and its derivatives is essential for diagnosing CMA as well as inducing tolerance to CM. In non-IgE mediated CMA, the diagnostic elimination diet typically requires 2-4 weeks before reintroduction, while for IgE mediated allergy the time window may be shorter (1-2 weeks). An oral food challenge (OFC) under medical supervision remains the most reliable diagnostic method for IgE mediated and more severe types of non-IgE mediated CMA such as food protein induced enterocolitis syndrome (FPIES). Conversely, for other forms of non-IgE mediated CMA, reintroduction can be performed at home. The OFC cannot be replaced by the milk ladder after a diagnostic elimination diet. The duration of the therapeutic elimination diet, once a diagnosis was confirmed, can only be established through testing changes in sensitization status, OFCs or home reintroduction, which are directed by local protocols and services' availability. Prior non-evidence-based recommendations suggest that the first therapeutic elimination diet should last for at least 6 months or up to the age of 9-12 months, whichever is reached first. After a therapeutic elimination diet, a milk-ladder approach can be used for non-IgE mediated allergies to determine tolerance. Whilst some centers use the milk ladder also for IgE mediated allergies, there are concerns about the risk of having immediate-type reactions at home. Milk ladders have been adapted to local dietary habits, and typically start with small amounts of baked milk which then step up in the ladder to less heated and fermented foods, increasing the allergenicity. This publication aims to narratively review the risks associated with under- and over-diagnosis of CMA, therefore stressing the necessity of an appropriate diagnosis and management.
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Affiliation(s)
- Rosan Meyer
- Faculty Medicine, Imperial College London, Department Nutrition and Dietetics, Winchester University, UK and Faculty Medicine, KU Leuven, Belgium
| | - Carina Venter
- Children's Hospital Colorado, University of Colorado, Denver, CO, USA
| | - Antonio Bognanni
- Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada
- Evidence in Allergy Group; Department of Medicine and Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Hania Szajewska
- Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
| | - Raanan Shamir
- Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Anna Nowak-Wegrzyn
- Hassenfeld Children's Hospital, Department of Pediatrics, NYU Grossman School of Medicine, New York, NY, USA
| | - Alessandro Fiocchi
- Allergy Unit - Area of Translational Research in Pediatric Specialities, Bambino Gesù Children's Hospital, Rome, Italy
| | - Yvan Vandenplas
- Vrije Universiteit Brussel, UZ Brussel, KidZ Health Castle, Brussels, Belgium
| | - WAO DRACMA Guideline Group
- Faculty Medicine, Imperial College London, Department Nutrition and Dietetics, Winchester University, UK and Faculty Medicine, KU Leuven, Belgium
- Children's Hospital Colorado, University of Colorado, Denver, CO, USA
- Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada
- Evidence in Allergy Group; Department of Medicine and Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
- Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Israel
- Hassenfeld Children's Hospital, Department of Pediatrics, NYU Grossman School of Medicine, New York, NY, USA
- Allergy Unit - Area of Translational Research in Pediatric Specialities, Bambino Gesù Children's Hospital, Rome, Italy
- Vrije Universiteit Brussel, UZ Brussel, KidZ Health Castle, Brussels, Belgium
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28
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Su KW, Cetinbas M, Martin VM, Virkud YV, Seay H, Ndahayo R, Rosow R, Elkort M, Gupta B, Kramer E, Pronchick T, Reuter S, Sadreyev RI, Huang JL, Shreffler WG, Yuan Q. Early infancy dysbiosis in food protein-induced enterocolitis syndrome: A prospective cohort study. Allergy 2023; 78:1595-1604. [PMID: 36635218 PMCID: PMC10534226 DOI: 10.1111/all.15644] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 11/27/2022] [Accepted: 12/14/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND The microbiome associations of food protein-induced enterocolitis syndrome (FPIES) are understudied. We sought to prospectively define the clinical features of FPIES in a birth cohort, and investigate for the evidence of gut dysbiosis. METHODS We identified children diagnosed with FPIES in the Gastrointestinal Microbiome and Allergic Proctocolitis Study, a healthy infant cohort. Children were assessed and stools were collected at each well child visit. The clinical features of the children with FPIES were summarized. Stool microbiome was analyzed using 16S rRNA sequencing comparing children with and without FPIES. RESULTS Of the 874 children followed up for 3 years, 8 FPIES cases (4 male) were identified, yielding a cumulative incidence of 0.92%. The most common triggers were oat and rice (n = 3, each) followed by milk (n = 2). The children with FPIES were more likely to have family history of food allergy (50% vs. 15.9% among unaffected, p = .03). The average age of disease presentation was 6 months old. During the first 6 months of life, stool from children with FPIES contained significantly less Bifidobacterium adolescentis, but more pathobionts, including Bacteroides spp. (especially Bacteroides fragilis), Holdemania spp., Lachnobacterium spp., and Acinetobacter lwoffii. The short-chain fatty acid (SCFA)-producing Bifidobacterium shunt was expressed significantly less in the stool from FPIES children. CONCLUSIONS In this cohort, the cumulative incidence over the 3-year study period was 0.92%. During the first 6 months of life, children with FPIES had evidence of dysbiosis and SCFA production pathway was expressed less in their stool, which may play an important role in the pathogenesis of FPIES.
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Affiliation(s)
- Kuan-Wen Su
- Department of Pediatrics, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- Department of Pediatrics, Chang Gung University, Taoyuan, Taiwan
| | - Murat Cetinbas
- Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Victoria M. Martin
- Harvard Medical School, Boston, Massachusetts, USA
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Yamini V. Virkud
- Department of Pediatrics, School of Medicine, University of North Carolina, North Carolina, USA
| | - Hannah Seay
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Renata Ndahayo
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Rachael Rosow
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Michael Elkort
- Harvard Medical School, Boston, Massachusetts, USA
- Pediatrics at Newton Wellesley, P.C., Newton, Massachusetts, USA
| | - Brinda Gupta
- Pediatrics at Newton Wellesley, P.C., Newton, Massachusetts, USA
| | - Eileen Kramer
- Pediatrics at Newton Wellesley, P.C., Newton, Massachusetts, USA
| | | | - Susan Reuter
- Pediatrics at Newton Wellesley, P.C., Newton, Massachusetts, USA
| | - Ruslan I. Sadreyev
- Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Jing-Long Huang
- Department of Pediatrics, Chang Gung University, Taoyuan, Taiwan
- Department of Pediatrics, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan
| | - Wayne G. Shreffler
- Harvard Medical School, Boston, Massachusetts, USA
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Qian Yuan
- Harvard Medical School, Boston, Massachusetts, USA
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
- Pediatrics at Newton Wellesley, P.C., Newton, Massachusetts, USA
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Vassilopoulou E, Mazzocchi A, De Cosmi V. Editorial: Dietary management in children with immune-related diseases. Front Nutr 2023; 10:1185724. [PMID: 37051125 PMCID: PMC10083356 DOI: 10.3389/fnut.2023.1185724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Affiliation(s)
- Emilia Vassilopoulou
- Department of Nutrition and Dietetics, International Hellenic University, Thessaloniki, Greece
- *Correspondence: Emilia Vassilopoulou
| | - Alessandra Mazzocchi
- Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy
| | - Valentina De Cosmi
- Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy
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AL-Iede M, Sarhan L, Alshrouf MA, Said Y. Perspectives on Non-IgE-Mediated Gastrointestinal Food Allergy in Pediatrics: A Review of Current Evidence and Guidelines. J Asthma Allergy 2023; 16:279-291. [PMID: 36942164 PMCID: PMC10024490 DOI: 10.2147/jaa.s284825] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 02/17/2023] [Indexed: 03/15/2023] Open
Abstract
Food allergy is an immune-mediated disease that can result in considerable morbidity and even mortality, with a significant negative impact on patients' quality of life. It is characterized by allergic symptoms that can occur shortly after a relevant food allergen ingestion, or can be delayed or chronic, which make it more difficult for diagnosis. The symptoms of this disease can range from mild to severe, and rarely can cause anaphylaxis, a life-threatening allergic reaction. The prevalence of non-immunoglobulin E (IgE)-mediated food allergy is poorly established outside of cow's milk allergy, with an adjusted incidence ranging between 0.13% and 0.72%. Several disorders are classified as non-immunoglobulin E (IgE)-mediated food allergies that predominantly affect the gastrointestinal tract including food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced allergic enteropathy (FPE), and food protein-induced dysmotility disorders (GORD and constipation). Eosinophilic esophagitis (EoE) is listed in this group, even though it considered by some authorities to be mixed reaction with both IgE and cell-mediated immune response to be involved in the reaction. The most common types of non-IgE-mediated food allergy are food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). These disorders typically present in infancy and are often triggered by cow's milk protein. Patients with FPIES present with profuse emesis and dehydration, while FPIAP patients present with hematochezia in otherwise healthy infants. Since there are no specific confirmatory non-invasive diagnostic laboratory tests, the diagnosis is usually made clinically when typical symptoms improve upon the removal of the culprit food. Food reintroduction should be attempted, when possible, with documentation of symptoms of relapse to confirm the diagnosis. The management includes dietary avoidance, supportive treatment in the case of accidental exposure, and nutritional counseling. This review focuses on the clinical manifestations, epidemiology, management, and recent guidelines of the most common non-IgE-mediated food hypersensitivity disorders (FPIES, FPIAP, and FPE).
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Affiliation(s)
- Montaha AL-Iede
- Division of Pediatric Pulmonology and Sleep Medicine, Department of Pediatrics, Jordan University Hospital, Amman, Jordan
| | - Lena Sarhan
- Department of Pediatrics, Jordan University Hospital, The University of Jordan, Amman, 11942, Jordan
| | - Mohammad A Alshrouf
- Department of Pediatrics, Jordan University Hospital, The University of Jordan, Amman, 11942, Jordan
| | - Yazan Said
- Division of Allergy, Immunology, and pulmonology, Department of Pediatrics, King Fahad Specialist Hospital, Dammam, Saudi Arabia
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Xiong J, Liao XS, Yin T, Liu XC, Bao L, Li LQ. Alterations of the gut microbiota and short chain fatty acids in necrotizing enterocolitis and food protein-induced allergic protocolitis infants: A prospective cohort study. Front Cell Infect Microbiol 2022; 12:1030588. [PMID: 36478672 PMCID: PMC9720398 DOI: 10.3389/fcimb.2022.1030588] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/04/2022] [Indexed: 11/22/2022] Open
Abstract
Background Even though presenting with similar clinical manifestations, necrotizing enterocolitis (NEC) and food protein-induced allergic protocolitis (FPIAP) have completely different treatments and prognosis. Our study aimed to quantify and evaluate differences in gut microbiota and short chain fatty acids (SCFAs) between infants with NEC and FPIAP to better identify these two diseases in clinical settings. Methods A total of 43 infants with NEC or FPIAP in Children's Hospital of Chongqing Medical University, China between December 2020 and December 2021 were enrolled. Stool samples were prospectively collected and froze. Infants defined as NEC were those who presented with clinical courses consistent with NEC and whose radiographs fulfilled criteria for Bell's stage 2 or 3 NEC, while those who were healthy in appearance and had blood in the stool (visible or may be microscopic), had normal bowel sounds in physical examination, were resolved after eliminating the causative food, and/or had recurrence of symptoms after oral food challenge (OFC) were defined as FPIAP. Primers specific for bacterial 16S rRNA genes were used to amplify and pyrosequence fecal DNA from stool samples. Gas chromatography-mass spectrometry (GC-MS) technology was used to determine the concentrations of SCFAs. Results Among the 43 infants, 22 were diagnosed with NEC and 21 were diagnosed with FPIAP. The microbial community structure in NEC infant stools differed significantly from those in FPIAP infant stools. NEC infants had significantly higher proportion of Actinobacteria and reduced proportion of Bacteroidetes compared with FPIAP infants, and the proportions of Halomonas, Acinetobacter, Bifidobacterium, and Stenotrophomonas in NEC infants were significantly higher than that of FPIAP infants. In addition, infants with NEC had significantly lower levels of acetic acid, propionic acid, butyric acid, isovaleric acid, and total SCFAs, and higher level of hexanoic acid as compared to the infants of the FPIAP group. Conclusions The differences of gut microbiota composition and concentrations of SCFAs might represent suitable biomarker targets for early identification of NEC and FPIAP.
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Affiliation(s)
- Jing Xiong
- Neonatal Diagnosis and Treatment Center of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, China
| | - Xing-Sheng Liao
- Department of Neonatology, The first People’s Hospital of Jiulongpo District, Chongqing, China
| | - Tong Yin
- Neonatal Diagnosis and Treatment Center of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, China
| | - Xiao-Chen Liu
- Neonatal Diagnosis and Treatment Center of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, China
| | - Lei Bao
- Neonatal Diagnosis and Treatment Center of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, China,*Correspondence: Lei Bao, ; Lu-Quan Li,
| | - Lu-Quan Li
- Neonatal Diagnosis and Treatment Center of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, China,*Correspondence: Lei Bao, ; Lu-Quan Li,
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Liu EG, Zhang B, Martin V, Anthonypillai J, Kraft M, Grishin A, Grishina G, Catanzaro JR, Chinthrajah S, Sindher T, Manohar M, Quake AZ, Nadeau K, Burks AW, Kim EH, Kulis MD, Henning AK, Jones SM, Leung DYM, Sicherer SH, Wood RA, Yuan Q, Shreffler W, Sampson H, Shabanova V, Eisenbarth SC. Food-specific immunoglobulin A does not correlate with natural tolerance to peanut or egg allergens. Sci Transl Med 2022; 14:eabq0599. [PMID: 36383680 PMCID: PMC10219469 DOI: 10.1126/scitranslmed.abq0599] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
ImmunoglobulinA (IgA) is the predominant antibody isotype in the gut, where it regulates commensal flora and neutralizes toxins and pathogens. The function of food-specific IgA in the gut is unknown but is presumed to protect from food allergy. Specifically, it has been hypothesized that food-specific IgA binds ingested allergens and promotes tolerance by immune exclusion; however, the evidence to support this hypothesis is indirect and mixed. Although it is known that healthy adults have peanut-specific IgA in the gut, it is unclear whether children also have gut peanut-specific IgA. We found in a cohort of non-food-allergic infants (n = 112) that there is detectable stool peanut-specific IgA that is similar to adult quantities of gut peanut-specific IgA. To investigate whether this peanut-specific IgA is associated with peanut tolerance, we examined a separate cohort of atopic children (n = 441) and found that gut peanut-specific IgA does not predict protection from development of future peanut allergy in infants nor does it correlate with concurrent oral tolerance of peanut in older children. We observed higher plasma peanut-specific IgA in those with peanut allergy. Similarly, egg white-specific IgA was detectable in infant stools and did not predict egg tolerance or outgrowth of egg allergy. Bead-based epitope assay analysis of gut peanut-specific IgA revealed similar epitope specificity between children with peanut allergy and those without; however, gut peanut-specific IgA and plasma peanut-specific IgE had different epitope specificities. These findings call into question the presumed protective role of food-specific IgA in food allergy.
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Affiliation(s)
- Elise G. Liu
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA
- Department of Medicine, Section of Rheumatology, Allergy, and Immunology, Yale University School of Medicine, New Haven, CT 06519, USA
| | - Biyan Zhang
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore 138648, Singapore
| | - Victoria Martin
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Food Allergy Center, Massachusetts General Hospital, MGH Professional Office Building, Suite 530, 275 Cambridge Street, Boston, MA 02114, USA
- Food Allergy Science Initiative, Broad Institute, Cambridge, MA 02142, USA
| | - John Anthonypillai
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA
- Department of Medicine, Section of Rheumatology, Allergy, and Immunology, Yale University School of Medicine, New Haven, CT 06519, USA
| | - Magdalena Kraft
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA
| | - Alexander Grishin
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Galina Grishina
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Jason R. Catanzaro
- Section of Pulmonology, Allergy, Immunology, and Sleep Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Sharon Chinthrajah
- Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94040, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
| | - Tina Sindher
- Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94040, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
| | - Monali Manohar
- Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94040, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
| | - Antonia Zoe Quake
- Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94040, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
| | - Kari Nadeau
- Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94040, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
| | - A. Wesley Burks
- University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
| | - Edwin H. Kim
- University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
| | - Michael D. Kulis
- University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
| | | | - Stacie M. Jones
- Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Little Rock, AR 72205, USA
| | - Donald Y. M. Leung
- Department of Pediatrics, Division of Pediatric Allergy-Immunology, National Jewish Health, Denver, CO 80206, USA
| | - Scott H. Sicherer
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Robert A. Wood
- Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Qian Yuan
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Food Allergy Center, Massachusetts General Hospital, MGH Professional Office Building, Suite 530, 275 Cambridge Street, Boston, MA 02114, USA
- Food Allergy Science Initiative, Broad Institute, Cambridge, MA 02142, USA
- Pediatrics at Newton Wellesley, Newton, MA 02462, USA
| | - Wayne Shreffler
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Food Allergy Center, Massachusetts General Hospital, MGH Professional Office Building, Suite 530, 275 Cambridge Street, Boston, MA 02114, USA
- Food Allergy Science Initiative, Broad Institute, Cambridge, MA 02142, USA
- Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Hugh Sampson
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Veronika Shabanova
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Stephanie C. Eisenbarth
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA
- Department of Medicine, Section of Rheumatology, Allergy, and Immunology, Yale University School of Medicine, New Haven, CT 06519, USA
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Cow's milk-induced gastrointestinal disorders: From infancy to adulthood. World J Clin Pediatr 2022; 11:437-454. [PMID: 36439902 PMCID: PMC9685681 DOI: 10.5409/wjcp.v11.i6.437] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/01/2022] [Accepted: 10/14/2022] [Indexed: 11/07/2022] Open
Abstract
Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders. Cow's milk protein allergy (CMPA) is the most common food allergy, especially in infancy and childhood, which may persist into adulthood. There are three main types of CMPA; immunoglobulin E (IgE)-mediated CMPA, non-IgE-mediated CMPA, and mixed type. CMPA appears before the first birthday in almost all cases. Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis. CMPA (often non-IgE mediated) can present with symptoms of gastroesophageal reflux, eosinophilic esophagitis, hemorrhagic gastritis, food protein-induced protein-losing enteropathy, and food protein-induced enterocolitis syndrome. Most CMPAs are benign and outgrown during childhood. CMPA is not as common in adults as in children, but when present, it is usually severe with a protracted course. Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose. Lactose intolerance has four typical types: Developmental, congenital, primary, and secondary. Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults. They are also common in inflammatory bowel diseases. Milk consumption may have preventive or promoter effects on cancer development. Milk may also become a source of microbial infection in humans, causing a wide array of diseases, and may help increase the prevalence of antimicrobial resistance. This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Department of Pathology, Microbiology Section, Salmaniya Medical Complex, Manama 26671, Bahrain
- Department of Pathology, Microbiology Section, Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Chest Diseases, University Medical Center, Arabian Gulf University, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
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Practice Variations in the Management of Infants With Non-IgE-Mediated Cow's Milk Protein Allergy. J Pediatr Gastroenterol Nutr 2022; 75:444-449. [PMID: 35797449 DOI: 10.1097/mpg.0000000000003556] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Infants with non-IgE-mediated food allergies are often referred to gastroenterologists or immunologists. We hypothesized that there are practice variations between these disciplines in the diagnosis and management of such infants. METHODS A computerized questionnaire was distributed between pediatric gastroenterologists and immunologists. The questions addressed diagnosis, management, and follow-up in 3 scenarios of infants with concern for food protein-induced allergic proctocolitis (FPIAP) due to non-IgE-mediated responses to cow's milk. RESULTS Three cases of infants with suspected FPIAP were presented: milk-based formula-fed (case 1) or breast-fed (case 2) infants that are well appearing and thriving, and a breast-fed infant who is not growing appropriately along with a personal and family history of atopy (case 3). Fifty-eight pediatric gastroenterologists and 32 immunologists completed the questionnaire. Significant differences between gastroenterologists and immunologists were noted regarding the recommended dietary changes in these scenarios. Moreover, despite available guidelines generated by both societies, most physicians confirm the diagnosis based on resolution of symptoms after the dietary change, without re-exposure to the the suspected trigger. In addition, time for recommended re-exposure in infants with FPIAP was also different; most gastroenterologists recommended waiting until 12 months of age, while immunologists suggested reintroduction earlier, up to 6 months of age. CONCLUSIONS We identified significant practice variations in diagnosis and management of FPIAP between pediatric gastroenterologists and immunologists, with lack of adherence to society guidelines. Joint task forces of primary care pediatricians, gastroenterologists, and immunologists should provide uniform guidelines to standardize care.
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Martin VM, Virkud YV, Dahan E, Seay HL, Itzkovits D, Vlamakis H, Xavier R, Shreffler WG, Yuan Q, Yassour M. Longitudinal disease-associated gut microbiome differences in infants with food protein-induced allergic proctocolitis. MICROBIOME 2022; 10:154. [PMID: 36138438 PMCID: PMC9503280 DOI: 10.1186/s40168-022-01322-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 07/02/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Complex interactions between the gut microbiome and immune cells in infancy are thought to be part of the pathogenesis for the marked rise in pediatric allergic diseases, particularly food allergies. Food protein-induced allergic proctocolitis (FPIAP) is commonly the earliest recognized non-immunoglobulin E (IgE)-mediated food allergy in infancy and is associated with atopic dermatitis and subsequent IgE-mediated food allergy later in childhood. Yet, a large prospective longitudinal study of the microbiome of infants with FPIAP, including samples prior to symptom onset, has not been done. RESULTS Here, we analyzed 954 longitudinal samples from 160 infants in a nested case-control study (81 who developed FPIAP and 79 matched controls) from 1 week to 1 year of age by 16S rRNA ribosomal gene sequencing as part of the Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) study. We found key differences in the microbiome of infants with FPIAP, most strongly a higher abundance of a genus of Enterobacteriaceae and a lower abundance of a family of Clostridiales during the symptomatic period. We saw some of these significant taxonomic differences even prior to symptom onset. There were no consistent longitudinal differences in richness or stability diversity metrics between infants with FPIAP and healthy controls. CONCLUSIONS This study is the first to identify differences in the infant gut microbiome in children who develop FPIAP, some even before they develop symptoms, and provides a foundation for more mechanistic investigation into the pathogenesis of FPIAP and subsequent food allergic diseases in childhood. Video abstract.
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Affiliation(s)
- Victoria M. Martin
- Food Allergy Center, Massachusetts General Hospital, Boston, MA USA
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, MA USA
- Department of Pediatrics, Harvard Medical School, Boston, MA USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, MA USA
| | - Yamini V. Virkud
- Food Allergy Center, Massachusetts General Hospital, Boston, MA USA
- Department of Pediatrics, Harvard Medical School, Boston, MA USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, MA USA
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, MA USA
| | - Ehud Dahan
- The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Hannah L. Seay
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, MA USA
| | - Dvir Itzkovits
- The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Hera Vlamakis
- Microbiome and Infectious Diseases, The Broad Institute of MIT and Harvard University, Cambridge, MA USA
| | - Ramnik Xavier
- Food Allergy Science Initiative of the Broad Institute, Cambridge, MA USA
- Microbiome and Infectious Diseases, The Broad Institute of MIT and Harvard University, Cambridge, MA USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA USA
- Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA USA
| | - Wayne G. Shreffler
- Food Allergy Center, Massachusetts General Hospital, Boston, MA USA
- Department of Pediatrics, Harvard Medical School, Boston, MA USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, MA USA
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, MA USA
| | - Qian Yuan
- Food Allergy Center, Massachusetts General Hospital, Boston, MA USA
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, MA USA
- Department of Pediatrics, Harvard Medical School, Boston, MA USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, MA USA
- Pediatrics at Newton Wellesley, P.C, Newton, MA USA
| | - Moran Yassour
- The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
- Microbiology & Molecular Genetics Department, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Jensen SA, Fiocchi A, Baars T, Jordakieva G, Nowak-Wegrzyn A, Pali-Schöll I, Passanisi S, Pranger CL, Roth-Walter F, Takkinen K, Assa'ad AH, Venter C, Jensen-Jarolim E. Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation. World Allergy Organ J 2022; 15:100668. [PMID: 36185551 PMCID: PMC9483786 DOI: 10.1016/j.waojou.2022.100668] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/17/2022] [Accepted: 06/19/2022] [Indexed: 11/30/2022] Open
Abstract
Background The immunopathogenesis of cow's milk protein allergy (CMPA) is based on different mechanisms related to immune recognition of protein epitopes, which are affected by industrial processing. Purpose The purpose of this WAO DRACMA paper is to: (i) give a comprehensive overview of milk protein allergens, (ii) to review their immunogenicity and allergenicity in the context of industrial processing, and (iii) to review the milk-related immune mechanisms triggering IgE-mediated immediate type hypersensitivity reactions, mixed reactions and non-IgE mediated hypersensitivities. Results The main cow’s milk allergens – α-lactalbumin, β-lactoglobulin, serum albumin, caseins, bovine serum albumins, and others – may determine allergic reactions through a range of mechanisms. All marketed milk and milk products have undergone industrial processing that involves heating, filtration, and defatting. Milk processing results in structural changes of immunomodulatory proteins, leads to a loss of lipophilic compounds in the matrix, and hence to a higher allergenicity of industrially processed milk products. Thereby, the tolerogenic capacity of raw farm milk, associated with the whey proteins α-lactalbumin and β-lactoglobulin and their lipophilic ligands, is lost. Conclusion The spectrum of immunopathogenic mechanisms underlying cow's milk allergy (CMA) is wide. Unprocessed, fresh cow's milk, like human breast milk, contains various tolerogenic factors that are impaired by industrial processing. Further studies focusing on the immunological consequences of milk processing are warranted to understand on a molecular basis to what extent processing procedures make single milk compounds into allergens.
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Affiliation(s)
- Sebastian A Jensen
- Institute of Pathophysiology and Allergy Research, Centre of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,University Clinics for Ear Nose and Throat, Medical University Vienna, Austria.,The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria
| | - Alessandro Fiocchi
- Allergy Unit - Area of Translational Research in Pediatric Specialities, Bambino Gesù Children's Hospital, Rome, Italy
| | - Ton Baars
- Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
| | - Galateja Jordakieva
- Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna, Austria
| | - Anna Nowak-Wegrzyn
- Department of Pediatrics, NYU Grossman School of Medicine, Hassenfeld Childrens' Hospital, New York, NY, USA.,Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Isabella Pali-Schöll
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,AllergyCare - Allergy Diagnosis Center Vienna, Private Clinics Döbling, Vienna, Austria
| | - Stefano Passanisi
- Department of Human Pathology of Adult and Developmental Age, University of Messina, Italy
| | - Christina L Pranger
- Institute of Pathophysiology and Allergy Research, Centre of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria
| | - Franziska Roth-Walter
- University Clinics for Ear Nose and Throat, Medical University Vienna, Austria.,The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria
| | | | - Amal H Assa'ad
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Carina Venter
- Childrenás Hospital Colorado, University of Colorado, Denver, CO, USA
| | - Erika Jensen-Jarolim
- Institute of Pathophysiology and Allergy Research, Centre of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.,AllergyCare - Allergy Diagnosis Center Vienna, Private Clinics Döbling, Vienna, Austria
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Nicolaou N, Pancheva R, Karaglani E, Sekkidou M, Marinova-Achkar M, Popova S, Tzaki M, Kapetanaki A, Iacovidou N, Boutsikou T, Iliodromiti Z, Papaevangelou V, Sardeli O, Xepapadaki P, Papathoma E, Thijs-Verhoeven I, Kudla U, Ulfman LH, Schaafsma A, Manios Y. The Risk Reduction Effect of a Nutritional Intervention With a Partially Hydrolyzed Whey-Based Formula on Cow's Milk Protein Allergy and Atopic Dermatitis in High-Risk Infants Within the First 6 Months of Life: The Allergy Reduction Trial (A.R.T.), a Multicenter Double-Blinded Randomized Controlled Study. Front Nutr 2022; 9:863599. [PMID: 35694159 PMCID: PMC9174747 DOI: 10.3389/fnut.2022.863599] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 04/19/2022] [Indexed: 11/29/2022] Open
Abstract
Background The role of partially hydrolyzed formulas (pHF) as part of nutritional interventions to prevent the development of allergic manifestations (AM) is questioned, and efficacy of each specific pHF should be substantiated. Objective To investigate the risk-reduction effect of a whey-based pHF on the development of cow's milk protein allergy (CMPA) and atopic dermatitis (AD) in infants at high-risk for allergy within the first 6 months of life. Materials and Methods In a multicenter double-blinded randomized controlled setting, healthy non-exclusively breastfed full-term infants, received either a specific whey-based pHF or a standard cow's milk-based formula (SF) and were clinically assessed for AM at 2, 4, and 6 months of age, supported by the objective scoring tools SCORAD and CoMiSS. CMPA was confirmed by open food challenge. Intention-to-Treat (ITT) and Per-Protocol (PP) analyses were performed. Results Of 331 randomized subjects (ITT analysis set), 160 received the pHF and 171 the SF. Six (3.8%) infants in the pHF and 12 (7%) in the SF group developed CMPA (p = 0.186). AD incidence was significantly lower in those receiving pHF as compared to SF (10.6% vs. 18.7%, p = 0.024) with a relative risk (RR, 95% CI) of 0.54 (0.32, 0.92), in particular when adjusting for family history of AD [6.5% vs. 27.3%, RR 0.24 (0.07, 0.78), p = 0.018] representing a risk reduction of 76%. The PP analysis showed similar results. Conclusion This specific whey-based pHF reduced the risk of AD development, particularly in those with a family history of AD, and tended to reduce the development of CMPA in non-exclusively breastfed infants at high-risk for allergy. The A.R.T. study suggests that this particular pHF may contribute to measures aimed at prevention of allergic manifestations. However, further studies are needed to confirm this risk-reduction effect.
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Affiliation(s)
- Nicolaos Nicolaou
- Asthma and Allergy Centre, Limassol, Cyprus
- University of Nicosia Medical School, Nicosia, Cyprus
| | - Rouzha Pancheva
- Department of Hygiene and Epidemiology, Faculty of Public Health, Medical University of Varna, Varna, Bulgaria
- *Correspondence: Rouzha Pancheva
| | - Eva Karaglani
- Department of Nutrition & Dietetics, School of Health Science & Education, Harokopio University, Athens, Greece
| | | | - Miglena Marinova-Achkar
- Department of Hygiene and Epidemiology, Faculty of Public Health, Medical University of Varna, Varna, Bulgaria
| | - Simoneta Popova
- Department of Hygiene and Epidemiology, Faculty of Public Health, Medical University of Varna, Varna, Bulgaria
| | | | | | - Nicoletta Iacovidou
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece
| | - Theodora Boutsikou
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece
| | - Zoi Iliodromiti
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece
| | - Vassiliki Papaevangelou
- Third Department of Pediatrics, National and Kapodistrian University of Athens, ATTIKON General University Hospital, Athens, Greece
| | - Olympia Sardeli
- Third Department of Pediatrics, National and Kapodistrian University of Athens, ATTIKON General University Hospital, Athens, Greece
| | - Paraskevi Xepapadaki
- Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelia Papathoma
- Neonatal Intensive Care Unit, Alexandra University and State Maternity Hospital, Athens, Greece
| | | | | | | | | | - Yannis Manios
- Department of Nutrition & Dietetics, School of Health Science & Education, Harokopio University, Athens, Greece
- Institute of Agri-Food and Life Sciences, Hellenic Mediterranean University Research Centre, Heraklion, Greece
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Seay HL, Martin VM, Virkud YV, Marget M, Shreffler WG, Yuan Q. Prospective associations between acid suppressive therapy and food allergy in early childhood. Clin Exp Allergy 2022; 52:711-714. [PMID: 35285103 PMCID: PMC9248370 DOI: 10.1111/cea.14123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/05/2022] [Accepted: 03/08/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Hannah L. Seay
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Victoria M. Martin
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, Massachusetts, USA
| | - Yamini V. Virkud
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, Massachusetts, USA
| | - Michael Marget
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Wayne G. Shreffler
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, Massachusetts, USA
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Qian Yuan
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, Massachusetts, USA
- Pediatrics at Newton Wellesley, P.C., Newton, Massachusetts, USA
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Martin VM, Marget M, Yuan Q, Shreffler WG. In response to Frequency of guideline-defined cow's milk allergy symptoms in infants: Secondary analysis of EAT trial data by Vincent et al. Clin Exp Allergy 2022; 52:581-582. [PMID: 34981585 PMCID: PMC9274452 DOI: 10.1111/cea.14090] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 12/30/2021] [Indexed: 11/27/2022]
Affiliation(s)
- Victoria M Martin
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Michael Marget
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Qian Yuan
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Wayne G Shreffler
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts, USA
- Food Allergy Science Initiative of the Broad Institute, Cambridge, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
- Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA
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Vassilopoulou E, Feketea G, Konstantinou GN, Zekakos Xypolias D, Valianatou M, Petrodimopoulou M, Vourga V, Tasios I, Papadopoulos NG. Food Protein-Induced Allergic Proctocolitis: The Effect of Maternal Diet During Pregnancy and Breastfeeding in a Mediterranean Population. Front Nutr 2022; 9:843437. [PMID: 35433785 PMCID: PMC9005850 DOI: 10.3389/fnut.2022.843437] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 02/11/2022] [Indexed: 12/21/2022] Open
Abstract
Background The aim of the current investigation was to explore the association of food protein-induced allergic proctocolitis (FPIAP) with the maternal diet during pregnancy and breastfeeding in Greek infants. Methods A multicenter retrospective case-control study was conducted in 6 regions in Greece, with 96 mothers of infants with and 141 mothers of infants without a history of FPIAP. Maternal dietary habits during pregnancy and breastfeeding were evaluated with the following validated questionnaires: (a) The Mediterranean Diet Score and (b) The Mediterranean Oriented Culture-Specific Semi-Quantitative Food Frequency Questionnaire. Results FPIAP was associated with cow's milk (83.6%), egg (7.3%), wheat (6.4%), and beef (6.4%) in the maternal diet. Adherence to Mediterranean Diet was similar among the mothers. Mothers of FPIAP infants consumed more vegetables. Elastic net prediction models showed that, in this Mediterranean population, increased consumption during pregnancy and lactation of common allergens, whole grain products, homemade food, fish and shellfish, and fruits was associated with a decreased risk of FPIAP. Conversely, a high intake of vegetables, sugar and total fat, and non-stick/grilled cooking, were associated with increased risk of FPIAP, as was a high intake of salt and white flour during lactation only. Conclusions Components of a maternal Mediterranean Diet may protect against FPIAP when traditional cooking methods are adopted and fish, fruit, and whole wheat products are consumed frequently during pregnancy and breastfeeding.
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Affiliation(s)
- Emilia Vassilopoulou
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
| | - Gavriela Feketea
- PhD School, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Pediatrics, Pediatric Allergy Outpatient Clinic, Hospital Unit of Amaliada, General Hospital of Ilia, Amaliada, Greece
- *Correspondence: Gavriela Feketea
| | - George N. Konstantinou
- Department of Allergy and Clinical Immunology, 424 General Military Training Hospital, Thessaloniki, Greece
| | - Dimitris Zekakos Xypolias
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
| | - Mina Valianatou
- Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Petrodimopoulou
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
| | - Vasiliki Vourga
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
| | - Ioannis Tasios
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
| | - Nikolaos G. Papadopoulos
- Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
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Zhang S, Sicherer S, Berin MC, Agyemang A. Pathophysiology of Non-IgE-Mediated Food Allergy. Immunotargets Ther 2022; 10:431-446. [PMID: 35004389 PMCID: PMC8721028 DOI: 10.2147/itt.s284821] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 12/24/2021] [Indexed: 12/12/2022] Open
Abstract
Non-IgE-mediated food allergies are a group of disorders characterized by subacute or chronic inflammatory processes in the gut. Unlike IgE mediated food allergies that may result in multi-organ system anaphylaxis, the non-IgE mediated food allergies primarily affect the gastrointestinal tract. This review outlines the clinical manifestations, epidemiology, pathophysiology, and management of non-IgE-mediated food allergies. An updated literature search of selected non-IgE-mediated food allergies was conducted for this review using PubMed database to the current year (2021). Reviewed disorders include food protein-induced enterocolitis syndrome (FPIES), food-protein enteropathy (FPE), food protein-induced allergic proctocolitis (FPIAP), and eosinophilic gastrointestinal disorders (EGIDs) such as eosinophilic esophagitis (EoE). While extensive gains have been made in understanding FPIES, FPIAP, FPE, and EoE, more information is needed on the pathophysiology of these food allergies. Similarities among them include involvement of innate immunity, T-lymphocyte processes, alteration of the intestinal lumen at the cellular level with the appearance of inflammatory cells and associated histologic changes, and specific cytokine profiles suggesting food-specific, T-cell, and immune-mediated responses. While FPIES and FPIAP typically resolve in early childhood, EGIDs typically do not. Emerging new therapies for EoE offer promise of additional treatment options. Further studies identifying the immunopathogenesis, associated biomarkers, and mechanisms of tolerance are needed to inform prevention, diagnosis and management.
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Affiliation(s)
- Shouling Zhang
- Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, Kravis Children's Hospital, The Elliot and Roslyn Jaffe Food Allergy Institute, New York, NY, USA
| | - Scott Sicherer
- Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, Kravis Children's Hospital, The Elliot and Roslyn Jaffe Food Allergy Institute, New York, NY, USA
| | - M Cecilia Berin
- Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, Kravis Children's Hospital, The Elliot and Roslyn Jaffe Food Allergy Institute, New York, NY, USA
| | - Amanda Agyemang
- Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, Kravis Children's Hospital, The Elliot and Roslyn Jaffe Food Allergy Institute, New York, NY, USA
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Sekkidou M, Muhardi L, Constantinou C, Kudla U, Vandenplas Y, Nicolaou N. Nutritional Management With a Casein-Based Extensively Hydrolysed Formula in Infants With Clinical Manifestations of Non-IgE-Mediated CMPA Enteropathies and Constipation. FRONTIERS IN ALLERGY 2021; 2:676075. [PMID: 35387002 PMCID: PMC8974831 DOI: 10.3389/falgy.2021.676075] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 05/03/2021] [Indexed: 12/02/2022] Open
Abstract
Background: The majority of mixed-fed infants with non-IgE-mediated cow's milk protein allergy (CMPA) enteropathies are managed with an extensively hydrolysed cow's milk based infant formula (eHF). Given the high variability in peptide distribution of available eHFs, it is important to understand the suitability of a specific product in the management of distinct phenotypes. Objective: To assess the symptom resolution of various phenotypes of clinical manifestations of CMPA enteropathies and constipation managed by a casein-based eHF. Methods: The data of 20 full-term infants (n = 15 with non-IgE-mediated CMPA and n = 5 with constipation) attending a paediatric allergy clinic in Cyprus and managed with a casein-based eHF were retrospectively analysed. Results: Based on the clinical symptoms and history, infants were classified into the following phenotypes: (a) 11/15 (73.3%) FPIAP, (b) 3/15 (20%) FPIES, and (c) 1/15 (6.7%) severe diarrhoea. Overall, 14 (93.3%) patients were successfully managed with the casein-based eHF and 1 (6.7%) required an AAF. This formula was effective in 91% of patients with FPIAP, in 100% with FPIES and with diarrhoea. Three (60%) patients with constipation responded to the eHF. Conclusion: This case-series report supports the efficacy of a particular casein-based eHF for the nutritional management of non-IgE mediated CMPA enteropathies.
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Affiliation(s)
| | - Leilani Muhardi
- Friesland Campina AMEA, Singapore, Singapore
- *Correspondence: Leilani Muhardi
| | | | | | - Yvan Vandenplas
- Kidz Health Castle University Hospital Brussels, Brussels, Belgium
| | - Nicolaos Nicolaou
- N Asthma and Allergy Center, Limassol, Cyprus
- University of Nicosia Medical School, Nicosia, Cyprus
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43
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Allergic Food Sensitization and Disease Manifestation in the Fetus and Infant: A Perspective. ALLERGIES 2021. [DOI: 10.3390/allergies1020009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Even though allergic disease is identified in the first year of life, it is often in a less forward fashion, with elements of a wait and see approach. If the infant does not have an anaphylactic food reaction, other less dramatic allergic phenomenon is often under-emphasized, waiting for additional concerns. We approached this with a conception to first conduct birthday surveys, attempting to link intrauterine and peri-birth circumstances to affect better allergy recognition in young infants.
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Lu Y, Zhang ZQ. Food protein-induced enterocolitis syndrome presenting after necrotizing enterocolitis in a preterm neonate: a case report. Transl Pediatr 2021; 10:1393-1398. [PMID: 34189099 PMCID: PMC8192982 DOI: 10.21037/tp-21-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
When bloody stools occur in a very-low-birth-weight infant in the neonatal intensive care unit (NICU), necrotizing enterocolitis (NEC) is a prime consideration, though food protein-induced enterocolitis syndrome (FPIES) can be causative and is difficult to distinguish from NEC. Food allergy is an adverse reaction following exposure to food due to an abnormal immunologic response to food, and cow's milk allergy (CMA) is the most likely form of food allergy in infants. The clinical features and proper management of patients with FPIES are important to differentiate FPIES from NEC. However, there are very few study reports of preterm infants presenting with food allergy-induced enterocolitis after NEC. Here, we report a case of a very-low-birth-weight infant born at 28 weeks of gestational age who developed recurrent episodes of bloody stools when he was fed cow's milk or given breast milk fortified with milk after NEC recovery on day of life (DOL) 29, 46, and 54. A male preterm infant born at 28 weeks of gestational age presented with bloody stools on DOL 7. He was diagnosed with early-onset NEC with abdominal tenderness, sluggish bowel sounds, increased C-reactive protein (CRP) level and pneumatosis intestinalis (PI). After recovery from NEC on DOL 20, the infant developed three recurrent episodes of bloody stools after being fed cow's milk or breast milk fortified with dairy milk. He was suspected of having recurrent episodes of NEC, but the infant was fairly healthy and did not present abdominal tenderness or abnormal bowel sounds on physical examination. Consecutive blood tests revealed normal CRP levels and increasing eosinophil levels. Abdominal radiograph revealed mild thickening of the small bowel, with no evidence of PI. The infant was finally diagnosed with FPIES in addition to NEC. After the infant received hydrolyzed formula, the bloody stool symptoms were finally resolved. Our case suggests that infants with recurrent episodes of bloody stools with increasing systemic eosinophils count should be considered for the diagnosis of FPIES with cow's milk formula. Rapid improvement and non-progression of systemic symptoms and signs after removing exposure to milk protein may differentiate FPIES from NEC.
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Affiliation(s)
- Yan Lu
- Department of Neonatology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhi-Qun Zhang
- Department of Neonatology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Barni S, Giovannini M, Mori F. Epidemiology of non-IgE-mediated food allergies: what can we learn from that? Curr Opin Allergy Clin Immunol 2021; 21:188-194. [PMID: 33394702 DOI: 10.1097/aci.0000000000000721] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE OF REVIEW To underline the main characteristics of the non-Immunoglobulin E (IgE)-mediated food allergies (food protein-induced allergic proctocolitis food protein-induced enteropathy and food protein-induced enterocolitis syndrome ), which are common diseases in primary care and in allergy and gastroenterology specialty practices evaluating children. RECENT FINDINGS Non-IgE-mediated food allergies comprise a spectrum of diseases with peculiar features affecting infants and young children. The most prominent features of these diseases are symptoms that affect mainly the gastrointestinal tract. SUMMARY It is of paramount importance to provide the clinicians with the tools for non-IgE-mediated food allergy recognition in clinical practice to avoid the misdiagnosis with unnecessary laboratory tests and detrimental treatments.
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Affiliation(s)
- Simona Barni
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
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Su KW, Shreffler WG, Yuan Q. Gastrointestinal immunopathology of food protein-induced enterocolitis syndrome and other non-immunoglobulin E-mediated food allergic diseases. Ann Allergy Asthma Immunol 2021; 126:516-523. [PMID: 33667639 DOI: 10.1016/j.anai.2021.02.024] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/20/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide a concise summary of the current literature regarding gastrointestinal immunopathology of food protein-induced enterocolitis syndrome (FPIES) and other non-immunoglobulin E (IgE)-mediated food allergic diseases. DATA SOURCES Data were extracted from PubMed, MEDLINE, and ScienceDirect databases. STUDY SELECTIONS Original articles, review articles, and guidelines published in the past 5 years in peer-reviewed journals were first summarized. The original articles cited were then reviewed and relevant results were extracted. RESULTS Patients with FPIES and non-IgE-mediated food allergic diseases developed vomiting, diarrhea, and food aversion expelled food allergen from their bodies. Aside from T helper type 2 (TH2) immunity, TH1, TH17, innate immunity, and epithelial mucosal barrier defect were also found to be important in the pathogenesis. Eosinophils, widely identified in the biopsy samples, were key players or were late-recruited cells for tissue repairs in those diseases. Intestinal dysbiosis and their metabolites stimulated enterochromaffin cells or enteroendocrine cells to produce serotonin, interfering with intestinal motility and subsequently affecting brain function. FPIES and non-IgE-mediated food allergic diseases were likely part of the atopic march. Allergic inflammation in intestinal mucosa might result in subsequent inflammation in the airway mucosa, suggesting the theory of "one mucosa, one disease." CONCLUSION The immune responses of FPIES and non-IgE-mediated food allergic diseases were not limited to the gastrointestinal tract, but also trigger wider inflammatory responses beyond it. Further research will be required to determine the systemic effect and intestinal microbiome of those diseases.
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Affiliation(s)
- Kuan-Wen Su
- Department of Pediatrics, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan, Republic of China
| | - Wayne G Shreffler
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts; Division of Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
| | - Qian Yuan
- Food Allergy Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Massachusetts General Hospital, Boston, Massachusetts.
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Portal vein thrombosis and food protein-induced allergic proctocolitis in a premature newborn with hypereosinophilia: a case report. BMC Pediatr 2021; 21:49. [PMID: 33485314 PMCID: PMC7825155 DOI: 10.1186/s12887-021-02510-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 01/18/2021] [Indexed: 01/10/2023] Open
Abstract
Background Peripheral blood eosinophilia is identified in numerous medical conditions associated with allergic, infectious, and inflammatory processes mostly as reactive eosinophilia with or without tissue eosinophilia. In hospitalized neonates, eosinophilia is common with an inverse relationship with gestational age and occurs solely as mild eosinophilia in the majority of cases. In the literature, eosinophilia has been proposed as a possible risk factor for venous thromboembolism. However, few reports are found on thromboembolic events including portal vein thrombosis (PVT) associated with eosinophilia in the newborn period. Neonates, particularly preterm infants, are vulnerable to thrombosis due to the immature and developing hemostatic system with little reserve capacity, which occurs as catheter-related thrombosis in most cases. Case presentation A male newborn at 34+ 5 weeks’ gestation presented with a left portal venous thrombus and hematochezia after initial cow’s milk feeding in the setting of blood hypereosinophilia for a prolonged period of time without central venous catheterization. The infant was diagnosed with PVT and food protein-induced allergic proctocolitis (FPIAP) and showed complete resolution of the conditions with expectant management with food avoidance, including the normalized eosinophil count. Conclusions Our experience suggests that in the setting of hypereosinophilia with a prolonged duration in premature neonates, FPIAP should be suspected in case of hematochezia in otherwise healthy infants, and considering the increased thrombotic risk by the hypereosinophilia and premature newborn status, evaluation for neonatal thrombosis may be needed, including PVT with the potential risk for the more serious, but uncommon, late complications encompassing portal hypertension.
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48
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Calvani M, Anania C, Cuomo B, D’Auria E, Decimo F, Indirli GC, Marseglia G, Mastrorilli V, Sartorio MUA, Santoro A, Veronelli E. Non-IgE- or Mixed IgE/Non-IgE-Mediated Gastrointestinal Food Allergies in the First Years of Life: Old and New Tools for Diagnosis. Nutrients 2021; 13:226. [PMID: 33466746 PMCID: PMC7829867 DOI: 10.3390/nu13010226] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/06/2021] [Accepted: 01/09/2021] [Indexed: 12/11/2022] Open
Abstract
non-IgE and mixed gastrointestinal food allergies present various specific, well-characterized clinical pictures such as food protein-induced allergic proctocolitis, food protein-induced enterocolitis and food protein-induced enteropathy syndrome as well as eosinophilic gastrointestinal disorders such as eosinophilic esophagitis, allergic eosinophilic gastroenteritis and eosinophilic colitis. The aim of this article is to provide an updated review of their different clinical presentations, to suggest a correct approach to their diagnosis and to discuss the usefulness of both old and new diagnostic tools, including fecal biomarkers, atopy patch tests, endoscopy, specific IgG and IgG4 testing, allergen-specific lymphocyte stimulation test (ALST) and clinical score (CoMiss).
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Affiliation(s)
- Mauro Calvani
- Operative Unit of Pediatrics, S. Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Caterina Anania
- Immunology and Allergology Unit, Department of Mother-Child, Urological Science, Sapienza University of Rome, 00161 Rome, Italy;
| | - Barbara Cuomo
- Operative Complex Unit of Pediatrics, Belcolle Hospital, 00100 Viterbo, Italy;
| | - Enza D’Auria
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (E.D.); (M.U.A.S.)
| | - Fabio Decimo
- Department of Woman, Child and of General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy;
| | - Giovanni Cosimo Indirli
- Pediatric Allergology and Immunology (SIAIP) for Regions Puglia and Basilicata, 73100 Lecce, Italy;
| | - Gianluigi Marseglia
- Pediatric Clinic, Pediatrics Department, Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy;
| | - Violetta Mastrorilli
- Operative Complex Unit of Pediatrics and Emergency, Giovanni XXIII Hospital, 70056 Bari, Italy;
| | - Marco Ugo Andrea Sartorio
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (E.D.); (M.U.A.S.)
| | - Angelica Santoro
- Pediatric Clinic, Mother-Child Department, University of Parma, 43121 Parma, Italy;
| | - Elisabetta Veronelli
- Food Allergy Committee of the Italian Society of Pediatric Allergy and Immunology (SIAIP), Pediatric Department, Garbagnate Milanese Hospital, ASST Rhodense, 70056 Garbagnate Milanese, Italy;
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49
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Eisenstein AS, Hilliard B, Silwal S, Wang A. Food Allergy: Searching for the Modern Environmental Culprit. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2020; 93:733-747. [PMID: 33380935 PMCID: PMC7757057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Food allergy is a modern disease. Its exponential increase in prevalence in the last 70 years cannot be explained by genetic factors alone. In this review we discuss the hypotheses that have been suggested previously, and the evidence that supports them, to explain this rise in prevalence as well as the medical treatments that have developed as a result of basic exploration within these paradigms. We argue that one major area of fruitful exploration that would help generate new ideas may be systematic analyses of the unknown factors of the modern environment that may contribute to the formation of food allergy. Through this lens, we review the current understanding of food allergy pathogenesis and propose novel research directions, with implications for the current strategies for managing food allergy.
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Affiliation(s)
- Anna S. Eisenstein
- Department of Dermatology, Yale University School of Medicine, New Haven, CT,To whom all correspondence should be addressed: Anna Eisenstein, The Anlyan
Center, 300 Cedar Street, New Haven, CT, 06519; Tel: 203-500-3918; Fax: 203-785-7053;
. Andrew Wang, The Anlyan Center, 300 Cedar Street, New
Haven, CT, 06519; Tel: 203-785-2454; Fax: 203-785-7053;
| | - Brandon Hilliard
- Department of Dermatology, Yale University School of Medicine, New Haven, CT,Department of Immunobiology, Yale University School of Medicine, New Haven, CT
| | | | - Andrew Wang
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT,Department of Medicine (Rheumatology), Yale
University School of Medicine, New Haven, CT,To whom all correspondence should be addressed: Anna Eisenstein, The Anlyan
Center, 300 Cedar Street, New Haven, CT, 06519; Tel: 203-500-3918; Fax: 203-785-7053;
. Andrew Wang, The Anlyan Center, 300 Cedar Street, New
Haven, CT, 06519; Tel: 203-785-2454; Fax: 203-785-7053;
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50
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Martin VM, Virkud YV, Phadke NA, Su KW, Seay H, Atkins MR, Keet C, Shreffler WG, Yuan Q. Increased IgE-Mediated Food Allergy With Food Protein-Induced Allergic Proctocolitis. Pediatrics 2020; 146:e20200202. [PMID: 32855350 PMCID: PMC8323611 DOI: 10.1542/peds.2020-0202] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/08/2020] [Indexed: 12/14/2022] Open
Affiliation(s)
- Victoria M Martin
- Food Allergy Center and
- Divisions of Pediatric Gastroenterology, Hepatology and Nutrition and
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts
- Food Allergy Science Initiative, Broad Institute, Cambridge, Massachusetts
| | - Yamini V Virkud
- Food Allergy Center and
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts
- Food Allergy Science Initiative, Broad Institute, Cambridge, Massachusetts
- Pediatric Allergy and Immunology, MassGeneral for Children, and
| | - Neelam A Phadke
- Pediatric Allergy and Immunology, MassGeneral for Children, and
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Kuan-Wen Su
- Food Allergy Center and
- Department of Pediatrics, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Hannah Seay
- Pediatric Allergy and Immunology, MassGeneral for Children, and
| | - Micaela R Atkins
- Divisions of Pediatric Gastroenterology, Hepatology and Nutrition and
| | - Corinne Keet
- Division of Pediatric Allergy and Immunology, The John's Hopkins Hospital and Department of Pediatrics, School of Medicine, The Johns Hopkins University, Baltimore, Maryland; and
| | - Wayne G Shreffler
- Food Allergy Center and
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts
- Food Allergy Science Initiative, Broad Institute, Cambridge, Massachusetts
- Pediatric Allergy and Immunology, MassGeneral for Children, and
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Qian Yuan
- Food Allergy Center and
- Divisions of Pediatric Gastroenterology, Hepatology and Nutrition and
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts
- Food Allergy Science Initiative, Broad Institute, Cambridge, Massachusetts
- Pediatrics at Newton Wellesley, Newton, Massachusetts
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