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1. 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

Author

Carina Venter, Rosan Meyer, Marion Groetch, Anna Nowak-Wegrzyn, Maurizio Mennini, Ruby Pawankar, Rose Kamenwa, Amal Assa'ad, Shriya Amara, Alessandro Fiocchi, Antonio Bognanni, Ignacio Ansotegui, Stefania Arasi, Sami L. Bahna, Roberto Berni Canani, Martin Bozzola, Jan Brozek, Derek Chu, Lamia Dahdah, Christophe Dupont, Motohiro Ebisawa, Ramon T. Firmino, Elena Galli, Gideon Lack, Haiqi Li, Alberto Martelli, Nikolas G. Papadopoulos, Maria Said, Mario Sánchez-Borges, Holger Schunemann, Raanan Shamir, Jonathan Spergel, Hania Szajewska, Luigi Terracciano, Yvan Vandenplas, Susan Waserman, Amena Warner, and Gary W.K. Wong

Subjects
Cow's milk allergy, Nutrition, Baked milk, Hypoallergenic formulas, Plant based alternatives, Immunologic diseases. Allergy, RC581-607
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.

Published
2024
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2. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XII – Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA

Author

Antonio Bognanni, MD, PhD (c), Alessandro Fiocchi, MD, Stefania Arasi, MD, MSc, PhD, Derek K. Chu, MD, PhD, Ignacio Ansotegui, MD, PhD, Amal H. Assa'ad, MD, Sami L. Bahna, MD, DrPH, Roberto Berni Canani, MD, PhD, Martin Bozzola, MD, Lamia Dahdah, MD, Christophe Dupont, MD, PhD, Piotr Dziechciarz, MD, PhD, Motohiro Ebisawa, MD, PhD, Ramon T. Firmino, MD, Alexandro Chu, BHSc(Hons), Elena Galli, MD, PhD, Andrea Horvath, MD, PhD, Rose Kamenwa, MD, Gideon Lack, MBBCh, Haiqi Li, MD, Alberto Martelli, MD, Anna Nowak-Węgrzyn, MD, PhD, Nikolaos G. Papadopoulos, MD, PhD, Ruby Pawankar, MD, PhD, Yetiani Roldan, MD, Maria Said, RN, Mario Sánchez-Borges, MD, Raanan Shamir, MD, PhD, Jonathan M. Spergel, MD, PhD, Hania Szajewska, MD, Luigi Terracciano, MD, Yvan Vandenplas, MD, PhD, Carina Venter, PhD, RD, Siw Waffenschmidt, PhD, Susan Waserman, MD, MSc, Amena Warner, RN, SN (PG Dip), Gary W.K. Wong, MD, Holger J. Schünemann, MD, MSc, PhD, and Jan L. Brozek, MD, PhD

Subjects
Milk allergy, Milk replacement formulas, Probiotics, Clinical practice guidelines, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as “conditional” following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers’ values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Published
2024
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3. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update – X – Breastfeeding a baby with cow's milk allergy

Author

Vicki McWilliam, PhD, AdvAPD, Merryn J. Netting, PhD, BSc, BND, Evelyn Volders, PhD, AdvAPD, Debra J. Palmer, PhD, BSc, BND, Ignacio Ansotegui, Stefania Arasi, Amal H. Assa'ad, Sami L. Bahna, Roberto Berni Canani, Antonio Bognanni, Martin Bozzola, Jan Brozek, Derek Chu, Lamia Dahdah, Christophe Dupont, Piotr Dziechciarz, Motohiro Ebisawa, Ramon T. Firmino, Alessandro Fiocchi, Elena Galli, Rose Kamenwa, Gideon Lack, Haiqi Li, Alberto Martelli, Anna Nowak-Węgrzyn, Nikolas G. Papadopoulos, Ruby Pawankar, Maria Said, Mario Sánchez-Borges, Holger Schunemann, Raanan Shamir, Jonathan Spergel, Hania Szajewska, Luigi Terracciano, Yvan Vandenplas, Susan Waserman, Carina Venter, Amena Warner, and Gary W.K. Wong

Subjects
Breastfeeding, Infant, IgE-mediated cow's milk allergy, Non-IgE-mediated cow's milk allergy, Maternal nutrition, Immunologic diseases. Allergy, RC581-607
Abstract

Cow's milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow's milk allergy, it is critical to examine the evidence for and against any form of cow's milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow's milk proteins detectable in human milk cause infant cow's milk allergy symptoms. Current clinical practice recommendations advise a 2–4 week trial of maternal cow's milk dietary elimination for: a) IgE-mediated cow's milk allergy only if the infant is symptomatic on breastfeeding alone; b) non-IgE-mediated associated symptoms only if the history and examination strongly suggest cow's milk allergy; and c) infants with moderate to severe eczema/atopic dermatitis, unresponsive to topical steroids and sensitized to cow's milk protein. There should be a clear plan for home reintroduction of cow's milk into the maternal diet for a period of 1 week to determine that the cow's milk elimination is responsible for resolution of symptoms, and then subsequent reoccurrence of infant symptoms upon maternal cow's milk reintroduction. The evidence base to support the use of maternal cow's milk avoidance for the treatment of a breastfed infant with cow's milk allergy is of limited strength due to a lack of high-quality, adequately powered, randomised controlled trials. It is important to consider the consequences of maternal cow's milk avoidance on reducing immune enhancing factors in breast milk, as well as the potential nutritional and quality of life impacts on the mother. Referral to a dietitian is advised for dietary education, along with calcium and vitamin D supplementation according to local recommendations, and a maternal substitute milk should be advised. However, for most breastfed infants with cow's milk allergy maternal cow's milk dietary elimination will not be required, and active support of the mother to continue breastfeeding is essential.

Published
2023
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4. WAO consensus on DEfinition of Food Allergy SEverity (DEFASE)

Author

Stefania Arasi, MD, PhD, MSc, Ulugbek Nurmatov, MD, Audrey Dunn-Galvin, PhD, Graham Roberts, DM, Paul J. Turner, FRCPCH, PhD, Sayantani B. Shinder, MD, PhD, Ruchi Gupta, MD, MPh, Philippe Eigenmann, MD, Anna Nowak-Wegrzyn, MD, PhD, Ignacio J. Ansotegui, MD, PhD, Montserrat Fernandez Rivas, MD, Stavros Petrou, PhD, Luciana K. Tanno, MD, PhD, Marta Vazquez-Ortiz, MD, PhD, Brian Vickery, MD, PhD, Gary Wong, MD, FRCPC, Montserrat Alvaro-Lozano, MD, PhD, Miqdad Asaria, PhD, Philippe Begin, MD, MSc, Martin Bozzola, MD, Robert Boyle, MD, Helen Brough, MD, PhD, Victoria Cardona, MD, PhD, R. Sharon Chinthrajah, MD, PhD, Antonella Cianferoni, MD, Antoine Deschildre, MD, David Fleischer, MD, Flavio Gazzani, PhD, Jennifer Gerdts, Marilena Giannetti, PhD, Matthew Greenhawt, MD, MBA, MSc, Maria Antonieta Guzmán, MD, Elham Hossny, MD, PhD, FAAAAI, Paula Kauppi, MD, Carla Jones, Francesco Lucidi, PhD, Olga Patricia Monge Ortega, MD, PhD, Daniel Munblit, MD, PhD, Antonella Muraro, MD, Giovanni Pajno, MD, Marcia Podestà, Pablo Rodriguez del Rio, MD, PhD, Maria Said, Alexandra Santos, MD, MSc, MRCPCH, PGCAP, FHEA, PhD, Marcus Shaker, MD, Hania Szajewska, MD, PhD, Carina Venter, PhD, Cristopher Warren, PhD, Tonya Winders, Motohiro Ebisawa, MD, PhD, and Alessandro Fiocchi, MD

Subjects
Consensus, Definition, Food allergy, Severity, e-Delphi study, Immunologic diseases. Allergy, RC581-607
Abstract

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods: Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as “strongly agree” to “agree” after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

Published
2023
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5. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XIII – Oral immunotherapy for CMA – Systematic review

Author

Antonio Bognanni, MD, Derek K. Chu, MD, Ramon T. Firmino, DDS, PhD, Stefania Arasi, PhD, MSc, Siw Waffenschmidt, Arnav Agarwal, MD, Piotr Dziechciarz, MD, PhD, Andrea Horvath, MD, PhD, Rime Jebai, MSc, MPH, Hanako Mihara, MD, MPH, Yetiani Roldan, MD, Maria Said, RN, Raanan Shamir, MD, PhD, Martin Bozzola, MD, Sami Bahna, MD, DrPH, Alessandro Fiocchi, MD, Susan Waserman, MD, MSc, Holger J. Schünemann, MD, MSc, PhD, Jan L. Brożek, MD, PhD, Ignacio J. Ansotegui, MD, PhD, Stefania Arasi, MD, PhD, Amal H. Assa'ad, MD, Sami L. Bahna, MD, DrPH, Roberto Berni Canani, MD, PhD, Jan Brozek, MD, PhD, Derek K. Chu, MD, PhD, Lamia Dahdah, MD, Christophe Dupont, MD, PhD, Motohiro Ebisawa, MD, PhD, Ramon Targino Firmino, MD, Elena Galli, MD, PhD, Rose Kamenwa, MD, Gideon Lack, MBBCh, Haiqi Li, MD, Alberto Martelli, MD, Anna H. Nowak-Wegrzyn, MD, PhD, Nikolaos G. Papadopoulos, MD, PhD, Ruby Pawankar, MD, PhD, Mario Sánchez-Borges, MD, Jonathan M. Spergel, MD, PhD, Hania Szajewska, MD, Luigi Terracciano, MD, Yvan Vandenplas, MD, PhD, Carina Venter, PhD, RD, Amena Warner, RN, SN (PG Dip), and GaryW.K. Wong, MD

Subjects
Milk allergy, Oral immunotherapy, Systematic review, Meta-analysis, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's milk allergy. We previously published the systematic review of OIT for cow's milk allergy (CMA) in 2010 as part of the World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Objective: To systematically synthesize the currently available evidence about OIT for IgE-mediated CMA and to inform the updated 2022 WAO guidelines. Methods: We searched the electronic databases including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations. We included all studies irrespective of the language of the original publication. The last search was conducted in February 2021. We registered the protocol on Open Science Framework (10.17605/OSF.IO/AH2DT). Results: We identified 2147 unique records published between 2010 and 2021, including 13 randomized trials and 109 observational studies addressing cow's milk OIT. We found low-certainty evidence that OIT with unheated cow's milk, compared to elimination diet alone, increased the likelihood of being able to consume ≥150 ml of cow's milk in controlled settings (risk ratio (RR): 12.3, 95% CI: 5.9 to 26.0; risk difference (RD): 25 more per 100, 95% CI 11 to 56) as well as accidently ingest a small amount (≥5 ml) of cow's milk (RR: 8.7, 95% CI: 4.7 to 16.1; RD: 25 more per 100, 95% CI 12 to 50). However, 2–8 weeks after discontinuation of a successful OIT, tolerance of cow's milk persisted in only 36% (range: 20%–91%) of patients. OIT increased the frequency of anaphylaxis (rate ratio: 60.0, 95% CI 15 to 244; rate difference 5 more anaphylactic reactions per 1 person per year, 95% CI: 4 to 6; moderate evidence) and the frequency of epinephrine use (rate ratio: 35.2, 95% CI: 9 to 136.5; rate difference 268 more events per 100 person-years, 95% CI: 203 to 333; high certainty). OIT also increased the risk of gastrointestinal symptoms (RR 6.9, 95% CI 1.6–30.9; RD 28 more per 100, CI 3 to 100) and respiratory symptoms (RR 49.0, 95% CI 3.12–770.6; RD 77 more per 100, CI 62 to 92), compared with avoidance diet alone. Single-arm observational studies showed that on average 6.9% of OIT patients (95% CI: 3.8%–10%) developed eosinophilic esophagitis (very low certainty evidence). We found 1 trial and 2 small case series of OIT with baked milk. Conclusions: Moderate certainty evidence shows that OIT with unheated cow's milk in patients with IgE-mediated CMA is associated with an increased probability of being able to drink milk and, at the same time, an increased risk of serious adverse effects.

Published
2022
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6. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update – XIV – Recommendations on CMA immunotherapy

Author

Jan L. Brozek, Ramon T. Firmino, Antonio Bognanni, Stefania Arasi, Ignacio Ansotegui, Amal H. Assa'ad, Sami L. Bahna, Roberto Berni Canani, Martin Bozzola, Derek K. Chu, Lamia Dahdah, Christophe Dupont, Piotr Dziechciarz, Motohiro Ebisawa, Elena Galli, Andrea Horvath, Rose Kamenwa, Gideon Lack, Haiqi Li, Alberto Martelli, Anna Nowak-Węgrzyn, Nikolaos G. Papadopoulos, Ruby Pawankar, Yetiani Roldan, Maria Said, Mario Sánchez-Borges, Raanan Shamir, Jonathan M. Spergel, Hania Szajewska, Luigi Terracciano, Yvan Vandenplas, Carina Venter, Siw Waffenschmidt, Susan Waserman, Amena Warner, Gary W.K. Wong, Alessandro Fiocchi, and Holger J. Schünemann

Subjects
Milk allergy, Immunotherapy, Practice guidelines, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Background: The prevalence of cow's milk allergy (CMA) is approximately 2–4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled “conditional” due to the low certainty about the health effects based on the available evidence. Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.

Published
2022
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7. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update – I – Plan and definitions

Author

Alessandro Fiocchi, MD, Antonio Bognanni, MD, Jan Brożek, MD, PhD, Motohiro Ebisawa, MD, PhD, Holger Schünemann, MD, Ignacio J. Ansotegui, MD, PhD, Stefania Arasi, MD, Amal H. Assa'ad, MD, Sami L. Bahna, MD, DrPH, Roberto Berni Canani, MD, PhD, Martin Bozzola, MD, Derek Chu, Lamia Dahdah, MD, Christophe Dupont, MD, PhD, Ramon Targino Firmino, Elena Galli, MD, PhD, Rose Kamenwa, MD, Gideon Lack, MD, Haiqi Li, MD, Alberto Martelli, MD, Anna Nowak-Węgrzyn, MD, Nikolas G. Papadopoulos, MD, PhD, Ruby Pawankar, MD, PhD, Maria Said, RN, Mario Sánchez-Borges, Raanan Shamir, PhD, Jonathan M. Spergel, MD, PhD, Hania Szajewska, MD, Luigi Terracciano, MD, Yvan Vandenplas, MD, PhD, Carina Venter, PhD, RD, Amena Warner, Susan Waserman, MD, MSc, and Gary W.K. Wong, MD

Subjects
Food allergy, Cow's milk allergy, Oral immunotherapy, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Since the World Allergy Organization (WAO) Diagnosis and Rationale against Cow's Milk Allergy (DRACMA) Guidelines were published 10 years ago, new evidence has accumulated about the diagnosis, therapy, and specific immunotherapy for cow's milk allergy (CMA). For this reason, WAO has felt the need to update the guidelines.We introduce here this update. The new DRACMA guidelines aim to comprehensively address the guidance on diagnosis and therapy of both IgE non-IgE-mediated forms of cow's milk allergy in children and adults. They will be divided into 18 chapters, each of which will be dedicated to an aspect. The focus will be on the meta-analyzes and recommendations that will be expressed for the 3 most relevant clinical aspects: (a) the diagnostic identification of the condition; (b) the choice of the replacement formula in case of CMA in infancy when the mother is not able to breastfeed, and (c) the use of specific immunotherapy for cow's milk protein allergy.

Published
2022
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8. Alergia e intolerancia a antiinflamatorios no esteroideos en pediatría Comité Nacional de Alergia

Author

Cesar Martin Bozzola, María Paula Sarraquigne, Andrea Irene Mariño, and Juan Manuel Suárez García

Subjects
Drug, Allergy, Innate immune system, biology, business.industry, medicine.drug_class, media_common.quotation_subject, Provocation test, Antibiotics, medicine.disease, Hypersensitivity reaction, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Immunology, biology.protein, Medicine, Cyclooxygenase, Antibody, business, media_common
Abstract

Nonsteroidal anti-inflammatory drugs are widely prescribed in children. They are the second cause of drug's reactions in pediatrics after beta-lactam antibiotics, however only a part of them are hypersensitivity reactions. The prevalence of these reactions to nonsteroidal anti-inflammatory drugs in children is 0.3 %, increasing to 5 % in asthmatics. The different physiopathological mechanisms involved (inhibition of cyclooxygenase, immunoglobulin E-mediated hypersensitivity, reactive T lymphocytes and/or disturbance of innate immunity) will cause different clinical entities with diverse symptoms. The confusion between the common symptoms of a viral infection and a hypersensitivity reaction, and the variability of the clinical presentations make diagnosis a real challenge. A detailed clinical history, laboratory, skin and controlled provocation tests will provide strategies for each patient, without labeling a child who is not an allergic one, or taking unnecessary risks with those who are sensitized.

Published
2020
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9. Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance

Author

Juan C. Martinez, Kevin P. Fennelly, Ziyue Xu, Sally Hunsberger, Les R. Folio, Kenneth N. Olivier, Chyi-Chia Richard Lee, Michael Allgäuer, Douglas B. Kuhns, Julie E. Niemela, Theo Heller, Michail S. Lionakis, Gary Kleiner, Peter D. Burbelo, Kerry Dobbs, Elise M. N. Ferré, Dirk Darnell, Jean K. Lim, Thomas A. Fleisher, Arun Rajan, Amy P. Hsu, Martin Bozzola, Kevin W. Hoffman, Megan A. Cooper, Muthulekha Swamydas, Dakai Jin, Laquita N. Snow, Robin R. Deterding, Anamaria Bondici, Karen K. Winer, Timothy J. Break, Daniel J. Mollura, Samar Ojaimi, David E. Kleiner, Wenjuan Gu, Luigi D. Notarangelo, and Steven M. Holland

Subjects
Adult, Male, animal structures, Adolescent, T-Lymphocytes, Autoimmunity, medicine.disease_cause, Article, Autoimmune Diseases, Pulmonary function testing, Immune tolerance, Young Adult, Immunopathology, Humans, Medicine, Lymphocytes, Prospective Studies, Child, Autoantibodies, Pneumonitis, B-Lymphocytes, Lung, medicine.diagnostic_test, business.industry, Infant, Newborn, Autoantibody, Infant, Pneumonia, General Medicine, Middle Aged, respiratory system, medicine.disease, Bronchoalveolar lavage, medicine.anatomical_structure, Child, Preschool, Immunology, Female, business
Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by AIRE mutations, presents with several autoimmune diseases. Among these, endocrine organ failure is widely recognized, but the prevalence, immunopathogenesis, and treatment of non-endocrine manifestations such as pneumonitis remain poorly characterized. We enrolled 50 patients with APECED in a prospective observational study and comprehensively examined their clinical and radiographic findings, performed pulmonary function tests, and analyzed immunological characteristics in blood, bronchoalveolar lavage fluid, and endobronchial and lung biopsies. Pneumonitis was found in >40% of our patients, presented early in life, was misdiagnosed despite chronic respiratory symptoms and accompanying radiographic and pulmonary function abnormalities, and caused hypoxemic respiratory failure and death. Autoantibodies against BPIFB1 and KCNRG and the homozygous c.967_979del13 AIRE mutation are associated with pneumonitis development. APECED pneumonitis features compartmentalized immunopathology, with accumulation of activated neutrophils in the airways and lymphocytic infiltration in intraepithelial, submucosal, peribronchiolar, and interstitial areas. Beyond APECED, we extend these observations to lung disease seen in other conditions with secondary AIRE deficiency (thymoma and RAG deficiency). Aire-deficient mice had similar compartmentalized cellular immune responses in the airways and lung tissue, which was ameliorated by deficiency of T and B lymphocytes. Accordingly, T and B lymphocyte-directed immunomodulation controlled symptoms and radiographic abnormalities and improved pulmonary function in patients with APECED pneumonitis. Collectively, our findings unveil lung autoimmunity as a common, early, and unrecognized manifestation of APECED and provide insights into the immunopathogenesis and treatment of pulmonary autoimmunity associated with impaired central immune tolerance.

Published
2019
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10. Reacciones alérgicas a betalactámicos en pediatría: recomendaciones para su diagnóstico y tratamiento Comité Nacional de Alergia

Author

Cesar Martin Bozzola, María Paula Sarraquigne, Andrea Irene Mariño, and Juan Manuel Suárez García

Subjects
medicine.medical_specialty, business.industry, medicine.drug_class, Drug allergy, Antibiotics, biochemical phenomena, metabolism, and nutrition, medicine.disease, Clavulanic acid, Pediatrics, Perinatology and Child Health, polycyclic compounds, Medicine, Cefoxitin, Monobactams, business, Adverse effect, Intensive care medicine, Anaphylaxis, medicine.drug, Moxalactam
Abstract

The Allergic Reactions to Betalactam Antibiotics are adverse events that cannot be explained by their pharmacological action, but mediated by an immunological mechanism. They are the most frequent cause of drug allergy in the world. Betalactam antibiotics include penicillins, cephalosporins, carbapenems, monobactams, cefems (moxalactam, cefoxitin), and clavulanic acid. They can produce immediate, accelerated or delayed allergic reactions. Its diagnostic methodology is complex and it is carried out by well-defined stages. Its timely diagnosis is very important due to the risk involved and the associated costs that demand the alternative use of other antibiotics that supplant them.

Published
2019
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11. Recomendaciones para la vacunación segura en niños con riesgo de padecer reacciones alérgicas a componentes vacunales

Author

Alejandro Lozano, María Paula Sarraquigne, Cesar Martin Bozzola, and RICARDO SARANZ

Subjects
Vaccination, medicine.medical_specialty, Allergy, Immunization, business.industry, Manufacturing process, Public health, Pediatrics, Perinatology and Child Health, Child population, medicine, Intensive care medicine, medicine.disease, business
Abstract

Vaccines are one of the most important advances in medicine as a public health tool for the control of immunopreventable diseases. Occasionally, adverse reactions may occur. If a child has a reaction to a vaccine, it is likely to disrupt his immunization schedule with risks to himself and the community. This establishes the importance of correctly diagnosing a possible allergy and defining appropriate behavior. Allergic reactions to vaccines may be due to the immunogenic component, to the residual proteins in the manufacturing process and to antimicrobial agents, stabilizers, preservatives and any other element used in the manufacturing process. Vaccination should be a priority in the entire child population, so this document describes particular situations of allergic children to minimize the risk of immunizations and achieve safe vaccination.

Published
2018
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12. The global impact of the DRACMA guidelines cow's milk allergy clinical practice

Author

Holger J. Schünemann, Arabella Martelli, Jonathan M. Spergel, Lamia Dahdah, Ignacio J. Ansotegui, Sami L. Bahna, Raanan Shamir, Martin Bozzola, Yvan Vandenplas, Jan Brozek, Alessandro Fiocchi, Rose Kamenwa, Maria Said, Amal Assa'ad, Hugh A. Sampson, Mario Sánchez-Borges, Carina Venter, Roberto Berni Canani, Luigi Terracciano, Gary Wong, Haiqi Li, Susan Waserman, Ruby Pawankar, Gideon Lack, Motohiro Ebisawa, Christophe Dupont, Elena Galli, Clinical sciences, Growth and Development, Pediatrics, Fiocchi, Alessandro, Schunemann, Holger, Ansotegui, Ignacio, Assa'Ad, Amal, Bahna, Sami, Canani, Roberto Berni, Bozzola, Martin, Dahdah, Lamia, Dupont, Christophe, Ebisawa, Motohiro, Galli, Elena, Li, Haiqi, Kamenwa, Rose, Lack, Gideon, Martelli, Alberto, Pawankar, Ruby, Said, Maria, Sánchez-Borges, Mario, Sampson, Hugh, Shamir, Raanan, Spergel, Jonathan, Terracciano, Luigi, Vandenplas, Yvan, Venter, Carina, Waserman, Susan, Wong, Gary, and Brozek, Jan

Subjects
Pulmonary and Respiratory Medicine, 030201 allergy, medicine.medical_specialty, Oral food challenge, business.industry, Immunology, Scopus, MEDLINE, Public policy, Milk allergy, Review, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Food allergy, Family medicine, medicine, Immunology and Allergy, Overdiagnosis, Grading (education), business, health care economics and organizations
Abstract

Background: The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. Objectives & methods: Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. Results: DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA's metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. Conclusions: DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician's knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.

Published
2018

13. Prevención de las enfermedades alérgicas en la infancia: entre la teoría y la realidad

Author

María Paula Sarraquigne, RICARDO SARANZ, Juan Manuel Suárez García, Cesar Martin Bozzola, and Alejandro Lozano

Subjects
Allergy, medicine.medical_specialty, Psychotherapist, business.industry, Alternative medicine, Health related, Context (language use), medicine.disease, Pediatrics, Perinatology and Child Health, medicine, Etiology, In real life, business, Intensive care medicine, Tertiary Prevention, Asthma
Abstract

Allergic diseases have an increasing worldwide prevalence and a great impact on the health related costs. The research is focused on the study of etiological and risk factors of allergic diseases that can potentially be modified with primary, secondary and tertiary prevention strategies. Many of these measures do not have a definitively proven effect taking place in a controlled context different to what happens in real life. This paper aims to review the latest evidence on prevention of allergic diseases considering certainties and unresolved issues and focuses mainly on environmental, dietary, pharmacological and immunological preventive strategies for different levels of prevention. It is imperative to have a better understanding of genetic and environmental factors that cause allergic diseases to optimize preventive measures that are effective in reversing the increasing trend in the prevalence of allergic illnesses in childhood.

Published
2016
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14. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines

Author

Haiqi Li, Andrea von Berg, Hugh A. Sampson, Massimo Landi, Sami L. Bahna, Alessandro Fiocchi, F. Rancé, María Antonieta Guzmán, Kirsten Beyer, Holger J. Schünemann, Airton Tetelbom Stein, Martin Bozzola, Luigi Terracciano, Jan L. Brozek, Enrico Compalati, Ralf G. Heine, Gideon Lack, M. Ebisawa, Stefan Vieths, Julia Bradsher, Paul K. Keith, and Alberto Maria Martelli

Subjects
Pulmonary and Respiratory Medicine, Grande bretagne, medicine.medical_specialty, Allergy, education, Immunology, Cow milk allergy, hydrolyzed soy formula, specific IgE, Milk allergy, Review Article, Primary care, oral food challenge, Cow's milk allergy, Epidemiology, medicine, Immunology and Allergy, Humans, DBPCFC, Child care, SOTI, Oral food challenge, business.industry, Medical school, medicine.disease, Dermatology, hydrolyzed rice formula, humanities, skin prick test, amino acid formula, GRADE, Action (philosophy), OIT, Family medicine, Pediatrics, Perinatology and Child Health, hydrolyzed milk formula, epidemiology, Pediatric allergy, Biostatistics, Milk Hypersensitivity, business
Abstract

Alessandro Fiocchi, MD, Pediatric Division, Department of Child and Maternal Medicine, University of Milan Medical School at the Melloni Hospital, Milan 20129, Italy. Holger Schunemann, MD, Department of Clinical Epidemiology & Biostatistics, McMaster University Health Sciences Centre, 1200 Main Street West Hamilton, ON L8N 3Z5, Canada. Sami L. Bahna, MD, Pediatrics & Medicine, Allergy & Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130. Andrea Von Berg, MD, Research Institute, Children s department , Marien-Hospital, Wesel, Germany. Kirsten Beyer, MD, Charite Klinik fur Padiatrie m.S. Pneumologie und Immunologie, Augustenburger Platz 1, D-13353 Berlin, Germany. Martin Bozzola, MD, Department of Pediatrics, British Hospital-Perdriel 74-CABA-Buenos Aires, Argentina. Julia Bradsher, PhD, Food Allergy & Anaphylaxis Network, 11781 Lee Jackson Highway, Suite 160, Fairfax, VA 22033. Jan Brozek, MD, Department of Clinical Epidemiology & Biostatistics, McMaster University Health Sciences Centre, 1200 Main Street West Hamilton, ON L8N 3Z5, Canada. Enrico Compalati, MD, Allergy & Respiratory Diseases Clinic, Department of Internal Medicine. University of Genoa, 16132, Genoa, Italy. Motohiro Ebisawa, MD, Department of Allergy, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Kanagawa 228-8522, Japan. Maria Antonieta Guzman, MD, Immunology and Allergy Division, Clinical Hospital University of Chile, Santiago, Chile. Santos Dumont 999. Haiqi Li, MD, Professor of Pediatric Division, Department of Primary Child Care, Children’s Hospital, Chongqing Medical University, China, 400014. Ralf G. Heine, MD, FRACP, Department of Allergy & Immunology, Royal Children’s Hospital, University of Melbourne, Murdoch Children’s Research Institute, Melbourne, Australia. Paul Keith, MD, Allergy and Clinical Immunology Division, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Gideon Lack, MD, King’s College London, Asthma-UK Centre in Allergic Mechanisms of Asthma, Department of Pediatric Allergy, St Thomas’ Hospital, London SE1 7EH, United Kingdom. Massimo Landi, MD, National Pediatric Healthcare System, Italian Federation of Pediatric Medicine, Territorial Pediatric Primary Care Group, Turin, Italy. Alberto Martelli, MD, Pediatric Division, Department of Child and Maternal Medicine, University of Milan Medical School at the Melloni Hospital, Milan 20129, Italy. Fabienne Rance, MD, Allergologie, Hopital des Enfants, Pole Medicochirurgical de Pediatrie, 330 av. de Grande Bretagne, TSA 70034, 31059 Toulouse CEDEX, France. Hugh Sampson, MD, Jaffe Food Allergy Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, NY 10029-6574. Airton Stein, MD, Conceicao Hospital, Porto Alegre, Brazil. Luigi Terracciano, MD, Pediatric Division, Department of Child and Maternal Medicine, University of Milan Medical School at the Melloni Hospital, Milan 20129, Italy. Stefan Vieths, MD, Division of Allergology, Paul-EhrlichInstitut, Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Str. 51-59, D-63225 Langen, Germany.

Published
2010

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