Allopurinol is a widely prescribed medication for gout, but it carries a risk of severe hypersensitivity reactions, particularly in individuals with the HLA-B*5801 allele. This case report describes a 70-year-old Caucasian female who developed Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome following an increase in her allopurinol dosage. The patient presented with a diffuse, erythematous maculopapular rash, acute kidney failure, and elevated liver enzymes. She was found to be positive for the HLA-B*5801 allele and used a thiazide diuretic as risk factors for allopurinol hypersensitivity. After discontinuing allopurinol and initiating treatment, her condition improved, but she later died from a ruptured aneurysm unrelated to the hypersensitivity reaction. This case highlights the potential for dose-dependent hypersensitivity reactions to allopurinol, particularly in the presence of the HLA-B*5801 allele. Despite the rarity of such reactions in Caucasian populations, clinicians should remain vigilant, especially during the initial treatment phase.