IgE-Mediated Hypersensitivity and Desensitisation with Recombinant Enzymes in Pompe Disease and Type I and Type VI Mucopolysaccharidosis

Abstract

Enzyme replacement therapy (ERT) is important for the treatment of lysosomal storage disorders. Hypersensitivity reactions with ERT have been reported, and in these cases, desensitisation with the enzyme is necessary. Here we report the cases of 3 patients with lysosomal storage disorders, including Pompe disease and mucopolysaccharidosis type I and VI, who had IgE-mediated hypersensitivity reactions and positive skin tests. Successful desensitisation protocols with the culprit enzyme solution were used for these patients. All 3 patients were able to safely receive ERT with the desensitisation protocol.

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…It is usually indicated in patients who have an IgE-mediated reaction appearing within a few hours after the start of infusion [204]. Effective desensitization has been reported in patients treated with laronidase, idursulfase, galsulfase and elosulfase [202,[205][206][207][208].…”

Enzyme replacement therapy desensitization in a child with infantile onset Pompe disease

“…In case reports of IgE mediated IAR, skin prick test was negative in all patients and IgE sensitisation was proven by anti-rhGAA IgE and intradermal testing of varying concentration from 1:1000 8 to 1:100. 10,12 For our patient, an IgE mediated mechanism was highly likely given her negative anti-rhGAA IgG and a skin prick test that measured 2 mm above negative diluent. After discussion with her parents, factoring in potential discomfort with intradermal testing and health resources, we proceeded with desensitisation therapy without pursuing the cause of IAR mechanism.…”

“…Desensitisation is performed only in IgE independent or IgE dependent reaction in which mast cell degranulation occurs. 14 Whilst desensitisation to Myozyme has been reported in literature, the numbers are small and mostly published as case reports 11 or case series 12 500 mcg/kg/hr requiring a decrease in infusion rate to 250 mcg/kg/hr and gradual increase up to 2000 mcg/kg/hr (2 mg/ kg/hr) with rashes noted at each two-fold concentration increment. Despite reactions, she was able to complete the full Myozyme dose on the second cycle.…”

Desensitization to drugs in children

“…Desensitization has been successfully described in laronidase (type-I mucopolyssacharidosis [MPS-I]), arylsulfatase B (MPS-VI), galsufase (MPS-VI), aglucosidase alfa (Pompe disease), and sebelipase alfa (lysosomal acid lipase deficiency) (Table 1). [36][37][38][39][40][41]…”