This document presents a case study of a patient with Wolman disease and secondary hemophagocytic lymphohistiocytosis (HLH) who experienced hypersensitivity to sebelipase alfa, an enzyme replacement therapy (ERT). The patient was successfully treated using a desensitization protocol, resulting in sustained clinical improvements without the need for HLH-specific treatments or immunotherapy. The document also emphasizes the challenges in distinguishing between infusion reactions and hypersensitivity reactions and the importance of skin testing in diagnosis and management. Overall, this case study suggests that desensitization protocols may be effective for sebelipase alfa hypersensitivity in patients with Wolman disease and secondary HLH. [Extracted from the article]