Introduction
Pompe disease is an inherited lysosomal storage due to decreased or absent alpha-glucosidase activity. Current treatment with enzyme replacement therapies (ERT) can result in frequent infusion related reactions (up to 35%), which can lead to medication discontinuation. We report two patients with Pompe disease with NCI CTCAE grade 2 reactions who were able to tolerate infusions with a modified ERT protocol.
Case Description
A 16-year-old male was initiated on avalglucosidase alfa for Late Onset Pompe disease. Five minutes into his third infusion, the patient developed shortness of breath and a raised, pruritic rash. Symptoms resolved with infusion discontinuation and diphenhydramine. For subsequent infusions, cetirizine was added as premedication and he underwent a rapid single bag desensitization protocol, which he tolerated well and has facilitated continuing regular infusions.
A 12-year-old male with history of asthma was started on alglucosidase alfa at 40 days old for Infantile Onset Pompe disease. He developed recurrent urticaria to his arms and face during infusions that resolved with diphenhydramine. The patient also experienced worsening asthma following infusions. Cetirizine was added as premedication, and the patient was started on budesonide-formoterol for his asthma; his infusion rate was decreased by 50% with gradual titration as tolerated. The patient tolerated subsequent infusions.
Discussion
Alglucosidase Alfa and avalglucosidase alfa can result in acute infusion reactions. Currently, there are no established guidelines concerning ERT discontinuation or reintroduction after an infusion related reaction. We report two patients with grade 2 systemic reactions who were able to subsequently restart and tolerate ERT with a modified infusion protocol, which is consistent with a complement-activation related pseudoallergy (CARPA) reaction. CARPA reactions are not driven by an IgE mediated response to the enzyme therapy and often respond well to decreasing infusion rates and increasing premedication, allowing patients to continue critical treatments for Pompe’s disease.