Reply to Correspondence: “Anaphylaxis Induced by Goat's and Sheep's Milk—A Rare Entity in Europe”

We would like to thank Cichocka-Jarosz et al. for their comments on our recent article [1] and respond as follows. Between 2007 and 2024, 2590 pediatric food-induced anaphylaxis (FIA) cases were recorded by the European Anaphylaxis Registry (NORA), after exclusion of cases reported by the Allergy-Vigilance Network (AVN), and 11 (0.42%) were elicited by goat's-sheep's milk (GSM). Cichocka-Jarosz et al. estimated that the higher rate of GSM-induced anaphylaxis reported in France (73 cases among 1846 FIA cases in children [3.95%], [2002–2024]) may be related to geographical particularities, mainly regarding the high production and consumption of GSM in our country. They concluded that GSM-induced anaphylaxis in children is a rather rare event in Europe. We recognize the high quality of data and information related to real-life anaphylaxis provided by the NORA. Taking part in the NORA, the AVN is an international registry of French-speaking countries, mainly France, collecting anaphylaxis data since 2002. As with many registries across the world, data collection of both registries is based on voluntary declaration. Only a minority of anaphylaxis registries operate under a mandatory framework and that is one weakness point for the epidemiological representativeness of our datasets [2]. Consequently, only a limited proportion of all anaphylaxis cases are reported which induces reporting bias. Surprisingly, we noticed that no GSM-induced anaphylaxis cases have been reported to the NORA from Mediterranean countries (e.g., Spain, Italy) where GSM is frequently produced and consumed [3], as well as in other countries (Poland, Bulgaria, Romania, Brazil and Austria). One explanation might be that the pediatric FIA cases are mainly reported from France and Germany (n = 1762 of whom 855 are recorded in the NORA database, and n = 1316, respectively) whereas 6 out of 11 countries participating in the NORA (Italy and Spain among others) have declared less than 100 cases. This is in line with the small number of specialized allergy centers participating in the NORA in those countries. For example, after personal communication, we noticed that, in Italy, 19 GSM-induced anaphylaxis cases are recorded in one tertiary pediatric center (2010–2025) but not declared to the NORA. In Madrid, in one allergy center, 10 out of 24 children with an isolated GSM allergy, had experienced an anaphylaxis (2009–2019). Beyond epidemiological considerations, Cichocka-Jarosz et al. confirmed the potential severity of GSM as an anaphylaxis elicitor underscored by our data. They found that Grade III reactions were reported in 4/11 (36%) cases compared to 28/73 (38%) in our series. In addition, 4 (5%) Grade IV (including 2 deaths) reactions were reported by the AVN. In line with our data, Cichocka-Jarosz et al. also confirmed that GSM allergy may be a specific entity, given the high proportion of individuals with a GSM-induced anaphylaxis tolerating cow's milk (CM). These findings are well illustrated in a single-center retrospective study in Spain [4]. Among 61 children with a confirmed CM allergy who were all desensitized after oral immunotherapy, 9 (15%) still experienced anaphylaxis reaction after oral challenges to GSM. Considering this apparent discrepancy between data, we call for harmonization and collaboration between registries to report anaphylaxis data. Both NORA and AVN are collaborating with a fruitful partnership, collecting data on real-life anaphylaxis to highlight valuable information on various aspects. However, medical registries are faced with many challenges including data quantity, reliability, consistency and exhaustivity to provide a picture, as representative as possible, of anaphylaxis epidemiology and real-world clinical care. Given these limitations, we still call for vigilance towards GSM allergy because of rising production and consumption of GSM across the world, mainly in low-income countries [5]. We also firmly encourage allergists to participate in anaphylaxis registries, to help address issues regarding epidemiological data in this field and improve the European mandatory labeling food list. G.P. analyzed, and wrote the draft. S.I.H., T.G.-B., S.A., A.D.-C., D.S.-L. were major contributors in reviewing the draft and improving the paper with critical analysis. All authors read and approved the final manuscript. G.P. has provided consultation and speaker services for Bioprojet, Viatris, Stallergenes, Novartis, DVB technology, ALK-Abello; serves as a medical consultant/advisor for Bioprojet, Viatris, and Theravia. A.D.-C. outside of the submitted work, reports grants from Don du Souffle, Novartis, ARAIRLOR, CICBAA; consulting fees from Sanofi, Stallergenes, ALK, AImmune Therapeutics; payment for presentations for AImmune Therapeutics, Novartis, ALK, DBV; support for attending meetings from Mead Johnson, Nutricia, AImmune Therapeutics, Novartis, ALK; stocks from Essilor Luxottica. The other authors declare no conflicts of interest. This article is linked to Pouessel et al. and Cichocka-Jarosz et al. papers. To view these articles, visit https://doi.org/10.1111/all.16581 and https://doi.org/10.1111/all.70051. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.