D2.457 - Hypersensitivity reactions for Enzyme Replacement Therapy in a Patient with Hunter syndrome

Background. Recombinant forms of iduronate-2-sulfatase (idursulfase and idursulfase beta) are effective enzyme replacement therapies (ERT) for the treatment of mucopolysaccharidosis type II (MPS II).

Patients and Methods. A 10-year-old patient with MPS II had been receiving ERT with idursulfase alfa at a dose of 0.5 mg/kg per injection once weekly since the age of 2.5 years. No reactions to the first 3.5 years of infusions were observed.

Results. Hypersensitivity reactions to ERT first occurred at the age of 6 years. The initial adverse reaction manifested as urticaria of the upper limbs during idursulfase infusion. Upon resumption of ERT, the child again developed urticarial rashes; therefore, switching ERT was recommended. Idursulfase was replaced with idursulfase beta. However, despite premedication with antihistamines and glucocorticosteroids, the patient developed urticaria accompanied by itching during idursulfase beta infusion. The infusion was stopped, and a decision was made to temporary suspend ERT.

Subsequently, clinical deterioration was observed during the period without ERT, including joint contractures, ataxia, and developmental regression. An attempt was made to resume ERT with idursulfase beta; however, after administration of two-thirds of the dose, the patient again developed an allergic reaction characterized by urticaria, angioedema, cough, and respiratory difficulty. Given the vital need to continue ERT, combination therapy was initiated, consisting of cyclosporine at a dose of 2.5 mg/kg/day (6 month)  and omalizumab at a dose of 300 mg/month (14 month) administered subcutaneously. A personalized idursulfase beta therapy with an individual desensitization protocol was developed.

Conclusion. Allergic reactions are not uncommon in children with lysosomal storage diseases and are often controlled with antihistamine premedication. However, in severe cases, combination therapy may be required to enable continuation of ERT. The presented continued personalized combined therapy by anti-IgE biological agent and an immunosuppressive  drug successfully prevented hypersensitivity reactions during ERT in a patient with Hunter syndrome.