Drug desensitization procedures may be a safe and effective way to avoid the discontinuation of enzyme replacement therapy in patients with lysosomal storage disorders such as lysosomal acid lipase deficiency (LAL-D) who have previously experienced hypersensitivity reactions, according to an article published in Pediatric Allergy and Immunology.

To evaluate the effectiveness of different desensitization procedures, the researchers reviewed MEDLINE, LILACS, and the ISI Web of Science databases for original articles, clinical trials, case reports, abstracts from congresses, and editorial letters from inception to January 31, 2023. They included 33 relevant articles in their systematic review.

According to the results, desensitization procedures were performed successfully in 52 patients. Skin tests, with the culprit recombinant enzyme, were found positive in 29 patients and doubtful in 2 patients, while they were not performed in 4 patients. Moreover, 29 of the 52 desensitization protocols used at the first infusion were performed without any breakthrough reactions.

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The 3-bag (solutions), 12-step desensitization protocol was used most frequently and it yielded positive results even in high-risk patients. Two treatment-resistant patients responded well to premedication with omalizumab, while allergen immunotherapy-like desensitization was successfully applied to the other 3 patients.  

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“In case of a mild reaction and negative skin test slowing down the infusion rate may be sufficient to prevent hypersensitivity reactions. If hypersensitivity reactions occur, a 12-step 3-bag protocol is suggested. In case of moderate reaction, regardless of the skin test results, a 12-step 3-bag protocol is suggested. If a hypersensitivity reaction occurs, a change in premedication is suggested, and a switch to the 16-step 4-bag protocol. In case of a severe reaction, a 16-step 4-bag protocol should be started. If hypersensitivity reactions occur, change in premedication, or/and omalizumab, or/and allergen immunotherapy-like desensitization should be considered,” Spataro and colleagues concluded.

Lysosomal storage disorders include a heterogeneous group of approximately 70 different rare diseases marked by diverse genetic impairments causing the loss of specific enzymes and subsequent metabolite accumulation in the lysosomes. At present, the gold-standard treatment enzyme replacement therapy is associated with hypersensitivity, most likely type 1 (immunoglobulin E-mediated) reactions.  


Spataro F, Carlucci P, Loverre T, Macchia L, Di Bona D. Hypersensitivity reaction during enzyme replacement therapy in lysosomal storage disorders. A systematic review of desensitization strategiesPediatr Allergy Immunol. Published online June 26, 2023. doi:10.1111/pai.13981