Correct nomenclature of wheat allergy dependent on augmentation factors

With interest, we read the new article on food-induced anaphylaxis of the European Anaphylaxis Registry.1Dolle-Bierke S. Hofer V. Francuzik W. Naher A.F. Bilo M.B. Cichocka-Jarosz E. et al.Food-induced anaphylaxis: data from the European Anaphylaxis Registry.J Allergy Clin Immunol Pract. 2023; 11: 2069-2079.e7Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar This study confirms that the clinical manifestations of wheat anaphylaxis (WAn) are different compared with that of other food types, just as the authors had already published in a previous issue of The Journal of Allergy and Clinical Immunology: In Practice.2Kraft M. Dolle-Bierke S. Renaudin J.M. Rueff F. Scherer Hofmeier K. Treudler R. et al.Wheat anaphylaxis in adults differs from reactions to other types of food.J Allergy Clin Immunol Pract. 2021; 9: 2844-2852.e5Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Wheat anaphylaxis in the registry was predominant in adults. This probably has led to the significant findings described: WAn was highly associated with exercise, it had the highest rate of recurrent reactions (70.1%), and high allergen doses were required to elicit a reaction, mostly with an augmentation factor. Conversely, when reactions were elicited, the risk for severe cardiovascular involvement was increased, either associated with age or with augmentation factors as demonstrated for alcohol. These findings confirm original studies on patients with wheat-dependent exercise-induced anaphylaxis (WDEIA).3Brockow K. Kneissl D. Valentini L. Zelger O. Grosber M. Kugler C. et al.Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis.J Allergy Clin Immunol. 2015; 135: 977-984.e4Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar, 4Christensen M.J. Eller E. Mortz C.G. Brockow K. Bindslev-Jensen C. Exercise lowers threshold and increases severity, but wheat-dependent, exercise-induced anaphylaxis can be elicited at rest.J Allergy Clin Immunol Pract. 2018; 6: 514-520Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 5Christensen M.J. Eller E. Mortz C.G. Brockow K. Bindslev-Jensen C. Wheat-dependent cofactor-augmented anaphylaxis: a prospective study of exercise, aspirin, and alcohol efficacy as cofactors.J Allergy Clin Immunol Pract. 2019; 7: 114-121Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar The term WDEIA has historically been used to describe augmentation factor-dependent WAn, when exercise was needed to reveal the concealed food allergy. In this study, exercise appeared to be prominent in patients with WAn and was reported in 89% of patients with WAn in a previous analysis of the registry.2Kraft M. Dolle-Bierke S. Renaudin J.M. Rueff F. Scherer Hofmeier K. Treudler R. et al.Wheat anaphylaxis in adults differs from reactions to other types of food.J Allergy Clin Immunol Pract. 2021; 9: 2844-2852.e5Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Nevertheless, the authors restricted the analysis of their results to the full patient population with WAn, which is smart, because apart from exercise (WDEIA), other factors may be relevant, which substantially complicates terminology (Figure 1). Those patients, who obligatorily need augmentation factors to reach reaction threshold levels, tolerate everyday amounts of wheat products in the daily diet. However, it has been shown that reactions can experimentally be elicited with supraphysiologically high amounts of wheat gluten.3Brockow K. Kneissl D. Valentini L. Zelger O. Grosber M. Kugler C. et al.Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis.J Allergy Clin Immunol. 2015; 135: 977-984.e4Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar,4Christensen M.J. Eller E. Mortz C.G. Brockow K. Bindslev-Jensen C. Exercise lowers threshold and increases severity, but wheat-dependent, exercise-induced anaphylaxis can be elicited at rest.J Allergy Clin Immunol Pract. 2018; 6: 514-520Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar The name WDEIA does not reflect that patients may react to other augmentation factors, such as alcohol, nonsteroidal anti-inflammatory drugs, or menstruation. In fact, different augmentation factors appear interchangeable.3Brockow K. Kneissl D. Valentini L. Zelger O. Grosber M. Kugler C. et al.Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis.J Allergy Clin Immunol. 2015; 135: 977-984.e4Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar, 4Christensen M.J. Eller E. Mortz C.G. Brockow K. Bindslev-Jensen C. Exercise lowers threshold and increases severity, but wheat-dependent, exercise-induced anaphylaxis can be elicited at rest.J Allergy Clin Immunol Pract. 2018; 6: 514-520Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 5Christensen M.J. Eller E. Mortz C.G. Brockow K. Bindslev-Jensen C. Wheat-dependent cofactor-augmented anaphylaxis: a prospective study of exercise, aspirin, and alcohol efficacy as cofactors.J Allergy Clin Immunol Pract. 2019; 7: 114-121Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar Thus, wheat anaphylaxis dependent on augmentation (factors) is a more appropriate all-embracing terminology. Furthermore, patients requiring additional factors may first experience nonanaphylactic reactions (eg, urticaria) instead of WAn, which then is best described as wheat allergy dependent on augmentation (factors). In our current patient population of 51 patients with wheat allergy in adults from the past 5 years, all were augmentation factor-dependent (wheat allergy dependent on augmentation factors). Six patients had reacted with urticaria or angioedema and 45 patients had wheat anaphylaxis dependent on augmentation. Of these, 26 had WDEIA in its strict definition (all reactions were related to exercise), whereas 19 reported reactions also with other factors (14 additionally with and 5 exclusively with augmentation factors different from physical activity). Other authors circumvented using this terminology by describing patients as ω5-gliadin allergic.6Kennard L. Thomas I. Rutkowski K. Azzu V. Yong P.F.K. Kasternow B. et al.A multicenter evaluation of diagnosis and management of omega-5 gliadin allergy (also known as wheat-dependent exercise-induced anaphylaxis) in 132 adults.J Allergy Clin Immunol Pract. 2018; 6: 1892-1897Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar However, although ω5-gliadin has been associated with WDEIA, this is also unhelpful because all of these reactions may occur in ω5-gliadin–positive and in ω5-gliadin–negative wheat allergic patients alike.7Faihs V. Kugler C. Schmalhofer V. Scherf K.A. Lexhaller B. Mortz C.G. et al.Wheat-dependent exercise-induced anaphylaxis: subtypes, diagnosis, and management.J Dtsch Dermatol Ges. 2023; 21: 1131-1135Google Scholar Thus, we recommend appropriately naming the subsets of wheat allergy as outlined in Figure 1. However, for the study of Dölle-Bierke et al, we congratulate the authors that they have not tried to dive into complicated nomenclature, but have used WAn, which is the correct terminology for their focused registry and for the aim of the study. The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available owing to privacy restrictions. Food-Induced Anaphylaxis: Data From the European Anaphylaxis RegistryThe Journal of Allergy and Clinical Immunology: In PracticeVol. 11Issue 7PreviewFood is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years. Full-Text PDF Open AccessReply to “Correct nomenclature of wheat allergy dependent on augmentation factors”The Journal of Allergy and Clinical Immunology: In PracticeVol. 11Issue 11PreviewWe have read the commentary entitled "Correct nomenclature of wheat allergy dependent on augmentation factors"1 with great interest and agree with the authors that the current term of wheat-dependent exercise-induced anaphylaxis is not ideal and probably based on historical observations.2 Full-Text PDF