Abstract
Hydroxyurea is a cornerstone therapy for myeloproliferative disorders such as early-stage myelofibrosis. However, rare hypersensitivity reactions can complicate its use and require careful management. This case describes a patient with early-stage myelofibrosis, with JAK2 V617F mutation, and Grade 1 reticulin fibrosis on bone marrow biopsy. He was started on hydroxyurea 500 mg daily. The patient developed delayed hypersensitivity characterized by fever, chills, and fatigue. Symptoms initially resolved with self-discontinuation, but rechallenge twice with alternate-day dosing led to rapid recurrence following each dose. Discontinuation of hydroxyurea resolved symptoms permanently, and the patient was transitioned to ruxolitinib for management of the underlying disease. This case highlights the importance of recognizing hypersensitivity reactions during hydroxyurea therapy and implementing alternative strategies to optimize patient outcomes.