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Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review

BACKGROUND: Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along wit...

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Autores principales: Apraxine, Matveï, Van den Eynde, Marc, De Cuyper, Astrid, Pirson, Françoise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783773/
https://www.ncbi.nlm.nih.gov/pubmed/36550565
http://dx.doi.org/10.1186/s13223-022-00752-5
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author Apraxine, Matveï
Van den Eynde, Marc
De Cuyper, Astrid
Pirson, Françoise
author_facet Apraxine, Matveï
Van den Eynde, Marc
De Cuyper, Astrid
Pirson, Françoise
author_sort Apraxine, Matveï
collection PubMed
description BACKGROUND: Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA. CASE PRESENTATION: Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly. CONCLUSIONS: These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner’s attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing.
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spelling pubmed-97837732022-12-24 Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review Apraxine, Matveï Van den Eynde, Marc De Cuyper, Astrid Pirson, Françoise Allergy Asthma Clin Immunol Case Report BACKGROUND: Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA. CASE PRESENTATION: Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly. CONCLUSIONS: These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner’s attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing. BioMed Central 2022-12-22 /pmc/articles/PMC9783773/ /pubmed/36550565 http://dx.doi.org/10.1186/s13223-022-00752-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Apraxine, Matveï
Van den Eynde, Marc
De Cuyper, Astrid
Pirson, Françoise
Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
title Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
title_full Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
title_fullStr Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
title_full_unstemmed Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
title_short Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
title_sort hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783773/
https://www.ncbi.nlm.nih.gov/pubmed/36550565
http://dx.doi.org/10.1186/s13223-022-00752-5
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