How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?

Abstract Lysosomal Storage Diseases (LSDs) encompass a range of genetic disorders characterized by enzyme deficiencies that lead to substrate accumulation and progressive tissue damage. Enzyme Replacement Therapy (ERT) is the primary treatment for LSDs, yet it is often associated with hypersensitivi...

Full description

Saved in:
Bibliographic Details
Main Authors: Federico Spataro, Antonio Giovanni Solimando, Vanessa Desantis, Angelo Vacca, Attilio Di Girolamo, Roberto Ria
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Orphanet Journal of Rare Diseases
Subjects:
Online Access:https://doi.org/10.1186/s13023-025-03844-8
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850224355485679616
author Federico Spataro
Antonio Giovanni Solimando
Vanessa Desantis
Angelo Vacca
Attilio Di Girolamo
Roberto Ria
author_facet Federico Spataro
Antonio Giovanni Solimando
Vanessa Desantis
Angelo Vacca
Attilio Di Girolamo
Roberto Ria
author_sort Federico Spataro
collection DOAJ
description Abstract Lysosomal Storage Diseases (LSDs) encompass a range of genetic disorders characterized by enzyme deficiencies that lead to substrate accumulation and progressive tissue damage. Enzyme Replacement Therapy (ERT) is the primary treatment for LSDs, yet it is often associated with hypersensitivity reactions (HSRs), ranging from mild rashes to severe anaphylaxis. These reactions, frequently driven by anti-drug antibodies, pose significant challenges in treatment adherence and patient outcomes. This paper outlines a stepwise approach to managing HSRs during ERT, focusing on three escalating strategies. The first-line approach involves premedication using antihistamines, corticosteroids, antileukotrienes, and bronchodilators to prevent or reduce the severity of HSRs. For patients who continue to experience HSRs despite premedication, desensitization protocols are recommended, involving the gradual reintroduction of ERT in controlled, increasing doses. In cases of refractory HSRs, omalizumab, a monoclonal antibody targeting IgE, has been successfully used as a third-line intervention. This comprehensive, stepwise strategy aims to provide clinicians a guide to manage these challenges, offering practical steps for optimizing treatment while ensuring patient safety. Future research is needed to further validate these management techniques and explore new therapeutic options for optimizing care in this rare but critical patient population.
format Article
id doaj-art-2126b45ecb5a4d4e96a5ec041b98b97d
institution OA Journals
issn 1750-1172
language English
publishDate 2025-06-01
publisher BMC
record_format Article
series Orphanet Journal of Rare Diseases
spelling doaj-art-2126b45ecb5a4d4e96a5ec041b98b97d2025-08-20T02:05:39ZengBMCOrphanet Journal of Rare Diseases1750-11722025-06-012011610.1186/s13023-025-03844-8How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?Federico Spataro0Antonio Giovanni Solimando1Vanessa Desantis2Angelo Vacca3Attilio Di Girolamo4Roberto Ria5Post Graduate School in Allergology and Internal Medicine “Guido Baccelli”, Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), School of Medicine, University of Bari Aldo MoroGuido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), School of Medicine, Aldo Moro University of BariDepartment of Precision and Regenerative Medicine and Ionian Area - DiMePRe-J, Section of Pharmacology, School of Medicine, University of Bari Aldo MoroGuido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), School of Medicine, Aldo Moro University of BariPost Graduate School in Allergology and Internal Medicine “Guido Baccelli”, Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), School of Medicine, University of Bari Aldo MoroGuido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), School of Medicine, Aldo Moro University of BariAbstract Lysosomal Storage Diseases (LSDs) encompass a range of genetic disorders characterized by enzyme deficiencies that lead to substrate accumulation and progressive tissue damage. Enzyme Replacement Therapy (ERT) is the primary treatment for LSDs, yet it is often associated with hypersensitivity reactions (HSRs), ranging from mild rashes to severe anaphylaxis. These reactions, frequently driven by anti-drug antibodies, pose significant challenges in treatment adherence and patient outcomes. This paper outlines a stepwise approach to managing HSRs during ERT, focusing on three escalating strategies. The first-line approach involves premedication using antihistamines, corticosteroids, antileukotrienes, and bronchodilators to prevent or reduce the severity of HSRs. For patients who continue to experience HSRs despite premedication, desensitization protocols are recommended, involving the gradual reintroduction of ERT in controlled, increasing doses. In cases of refractory HSRs, omalizumab, a monoclonal antibody targeting IgE, has been successfully used as a third-line intervention. This comprehensive, stepwise strategy aims to provide clinicians a guide to manage these challenges, offering practical steps for optimizing treatment while ensuring patient safety. Future research is needed to further validate these management techniques and explore new therapeutic options for optimizing care in this rare but critical patient population.https://doi.org/10.1186/s13023-025-03844-8Drug allergyEnzyme replacement therapyLysosomal storage diseasesDesensitizationOmalizumab
spellingShingle Federico Spataro
Antonio Giovanni Solimando
Vanessa Desantis
Angelo Vacca
Attilio Di Girolamo
Roberto Ria
How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?
Orphanet Journal of Rare Diseases
Drug allergy
Enzyme replacement therapy
Lysosomal storage diseases
Desensitization
Omalizumab
title How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?
title_full How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?
title_fullStr How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?
title_full_unstemmed How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?
title_short How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?
title_sort how to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases
topic Drug allergy
Enzyme replacement therapy
Lysosomal storage diseases
Desensitization
Omalizumab
url https://doi.org/10.1186/s13023-025-03844-8
work_keys_str_mv AT federicospataro howtomanagehypersensitivityreactionstoenzymereplacementtherapyinlysosomalstoragediseases
AT antoniogiovannisolimando howtomanagehypersensitivityreactionstoenzymereplacementtherapyinlysosomalstoragediseases
AT vanessadesantis howtomanagehypersensitivityreactionstoenzymereplacementtherapyinlysosomalstoragediseases
AT angelovacca howtomanagehypersensitivityreactionstoenzymereplacementtherapyinlysosomalstoragediseases
AT attiliodigirolamo howtomanagehypersensitivityreactionstoenzymereplacementtherapyinlysosomalstoragediseases
AT robertoria howtomanagehypersensitivityreactionstoenzymereplacementtherapyinlysosomalstoragediseases