D2.288 - Idursulfase Hypersensitivity Reactions: Unpacking Immunological Mechanisms Beyond Clinical Manifestations

Mucopolysaccharidosis type II, stemming from iduronate-2-sulfatase deficiency, necessitates idursulfase replacement to avert the perilous accumulation of glycosaminoglycans within lysosomes. It is crucial to recognize that hypersensitivity reactions frequently erupt during infusions. Given the absence of alternative treatments, drug desensitization protocols have proven effective in enhancing enzyme tolerance.

Case 1:* A 10-year-old male (AMM) from an endogamic community (Pedro Ascencio Alquisiras, Mexico) with a family history of mucopolysaccharidosis. Diagnosis was unequivocally confirmed through detection of low iduronate sulfatase levels and identification of a homozygous variant c.189T>C (Asn63Lys).

*Case 2:* A 4-year-old male (ITSP) from Mexico City diagnosed with mucopolysaccharidosis type II, exhibiting low levels of iduronate sulfatase.

In both cases, enzyme administration triggered extensive cutaneous reactions, irrespective of premedication efforts. AMM faced two severe anaphylactic episodes. Consequently, a rigorous 13-step desensitization protocol was implemented. For AMM, weekly procedures with intermittent cutaneous manifestations commenced from August 2022 to January 2024. Following this, infusion with premedication (acetylsalicylic acid, montelukast, hydrocortisone, and cloropiramine) was resumed from February to June 2024, yielding tolerance until anaphylaxis reoccurred in July 2024. This led to the reinitiation of the 13-step desensitization protocol, incorporating adrenaline infusion and an additional dose of cloropiramine at step 11. However, hives emerged at step 13. In October 2024, a monthly administration of omalizumab was introduced as adjunct therapy, effectively halting further manifestations.

For ITSP, the initial event comprised generalized erythema, pruritus, and a dry cough, resulting in the implementation of premedication (hydrocortisone, cloripiramine, and paracetamol). Despite these efforts, hives and dry cough reappeared, necessitating the initiation of a 13-step desensitization protocol. To date, hives continue to manifest.

Both cases employed specific IgE and basophil activation tests as vital diagnostic tools. AMM demonstrated a positive specific IgE and basophil activation test; conversely, ITSP’s results were negative, suggesting non-IgE mediated hypersensitivity reactions that elucidate the observed cutaneous manifestations. Limitations persist in exploring other immunological mechanisms and accurately measuring enzyme activity.

Desensitization procedures are indispensable for the reintroduction of hypersensitivity-inducing drugs when alternatives are unavailable, as seen in mucopolysaccharidosis. It is evident that standardized protocols for idursulfase treatments are deficient. Thus, it is imperative to adopt strategies established in a variety of protocols to ensure effective treatment outcomes.