Reply to “Diagnostic criteria sets sensitivity”

We have read with interest the comment by Dr Miceli Sopo1Miceli Sopo S. Diagnostic criteria sets sensitivity.J Allergy Clin Immunol Pract. 2020; 8: 2840Abstract Full Text Full Text PDF Scopus (1) Google Scholar on our paper recently published in JACI In Practice on diagnostic criteria sets (DCSs) for acute food protein–induced enterocolitis syndrome (FPIES).2Vazquez-Ortiz M. Argiz L. Machinena A. Echeverria L. Blasco C. Prieto A. et al.BIO-FPIES study network. Diagnostic criteria for acute FPIES: What are we missing?.J Allergy Clin Immunol Pract. 2020; 8: 1717-1720.e2Abstract Full Text Full Text PDF Scopus (10) Google Scholar We very much value his expertise and contribution in this field, and we share an interest in improving diagnostic methods and management strategies in this poorly understood condition. Dr Miceli Sopo rightly flags a difficulty when applying his DCSs,3Miceli Sopo S. Greco M. Monaco S. Tripodi S. Calvani M. Food protein-induced enterocolitis syndrome, from practice to theory.Expert Rev Clin Immunol. 2013; 9: 707-715Crossref PubMed Scopus (49) Google Scholar in which diarrhea is listed as a diagnostic criterion despite being an infrequent finding. In this context, it seems that diarrhea has rather a descriptive value than being a criterion in itself. In the more recent DCSs by Lee and Nowak-Wegrzyn used in our work,2Vazquez-Ortiz M. Argiz L. Machinena A. Echeverria L. Blasco C. Prieto A. et al.BIO-FPIES study network. Diagnostic criteria for acute FPIES: What are we missing?.J Allergy Clin Immunol Pract. 2020; 8: 1717-1720.e2Abstract Full Text Full Text PDF Scopus (10) Google Scholar clinical features compatible with acute FPIES are classified as major or minor diagnostic criteria, and a set number of the latter is needed to reach a clinical diagnosis. This seems a useful approach for features present only in a subset of patients, such as diarrhea or more severe manifestations such as hypotension. Dr Miceli Sopo suggests removing diarrhea as a criterion in his DCSs to increase sensitivity to 100%. If reinterpretations of published DCSs were to be made, for instance in the DCSs by Leonard4Leonard S.A. Nowak-Węgrzyn A. Clinical diagnosis and management of food protein-induced enterocolitis syndrome.Curr Opin Pediatr. 2012; 24: 739-745Crossref PubMed Scopus (54) Google Scholar and Powell modified by Sicherer,5Sicherer S.H. Eigenmann P.A. Sampson H.A. Clinical features of food protein induced enterocolitis syndrome.J Pediatr. 1998; 133: 214-219Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar and the criterion “younger than 9 months at diagnosis” was to be removed, 100% sensitivity would also be reached for these DCSs in our cohort, as represented in Figure E1 (available this article's Online Repository at www.jaci-inpractice.org). As discussed in our paper, clinical DCSs need to carefully balance sensitivity and specificity to avoid misdiagnosis, and particularly the false-positive rate when sensitivity increases potentially at the expense of reducing specificity. It is worth mentioning that these 3 DCSs3Miceli Sopo S. Greco M. Monaco S. Tripodi S. Calvani M. Food protein-induced enterocolitis syndrome, from practice to theory.Expert Rev Clin Immunol. 2013; 9: 707-715Crossref PubMed Scopus (49) Google Scholar, 4Leonard S.A. Nowak-Węgrzyn A. Clinical diagnosis and management of food protein-induced enterocolitis syndrome.Curr Opin Pediatr. 2012; 24: 739-745Crossref PubMed Scopus (54) Google Scholar, 5Sicherer S.H. Eigenmann P.A. Sampson H.A. Clinical features of food protein induced enterocolitis syndrome.J Pediatr. 1998; 133: 214-219Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar require patients to have experienced more than 1 reaction to the same food to reach the diagnosis of acute FPIES. Although this is very reasonable as reproducibility is a major feature of allergic reaction to foods, and adding this clearly increases specificity, we would like to think of a scenario where patients did not have to go through multiple reactions to be diagnosed. In our view, our study results, as well as this debate, highlight our limitations in relying on clinical features to diagnose a potentially severe condition like acute FPIES that significantly affects quality of life of patients and their families. Future research should focus on better understanding FPIES pathophysiology with the aim to identify differential biomarkers for prompt and accurate diagnosis, as colleagues within our BIO-FPIES network are successfully working on for other nonallergic diseases.6Herberg J.A. Kaforou M. Wright V.J. Shailes H. Eleftherohorinou H. Hoggart C.J. et al.(IRIS Consortium)Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children.JAMA. 2016; 316: 835-845Crossref PubMed Scopus (177) Google Scholar Importantly, recent data from our group indicate that developing such a diagnostic test is perceived as a key unmet need by the FPIES parent community.7Meyer J, LeFew A, Yuan Q, Martinon-Torres F, Infante S, Vazquez-Ortiz M. Parental perspectives on clinical and research needs in food protein-induced enterocolitis syndrome. EAACI 2020 Congress. Late Breaking thematic poster session 11. Available from: https://medialibrary.eaaci.org/mediatheque/media.aspx?mediaId=83005&channel=8518. Accessed July 28, 2020.Google Scholar Many thanks for giving us the opportunity to reply to the comment on our paper. Diagnostic criteria sets sensitivityThe Journal of Allergy and Clinical Immunology: In PracticeVol. 8Issue 8PreviewI was very pleased to read the paper by Vazquez-Ortiz et al “Diagnostic criteria for acute FPIES: what are we missing?”.1 The study is undoubtedly original and useful. The authors1 have compared the performance of different diagnostic criteria sets (DCSs)2-6 in a cohort of 51 pediatric patients with high clinical suspicion of acute food protein–induced enterocolitis syndrome (FPIES) from Southern Europe. Full-Text PDF