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Induction therapy with all- trans  retinoic acid (ATRA) is effective for acute promyelocytic leukemia (APL). ATRA induces neutrophil differentiation and its associated side effects. The differentiation syndrome is the most characterized ATRA-induced adverse effect. Sweet’s syndrome, also known as neutrophilic dermatosis, is another form of ATRA-associated disease characterized by neutrophil infiltrating erythema that develops with fever. This is a case of a 34-year-old Japanese man diagnosed with APL. At the onset, the patient did not have skin involvement of APL cells. He was treated with ATRA and induction chemotherapy with idarubicin and cytarabine. Scrotal skin rash occurred at day 14, which developed into scrotal ulceration up to day 28 even after eliminating APL cells in his peripheral blood. Sweet’s syndrome is a pathological diagnosis of scrotal skin ulceration representing neutrophil infiltration. The infiltrating neutrophils showed PML-RARα rearrangement. The patient was diagnosed with ATRA-associated Sweet’s syndrome with skin ulcer. His cutaneous lesion did not respond to intravenous prednisolone therapy; thereby, ATRA was discontinued. After the cessation of ATRA, the skin lesion improved in the next week. We confirmed he achieved a complete response after induction chemotherapy. In our observation, ATRA-associated Sweet’s syndrome is characterized by the following clinical manifestations: preferable occurrence in the scrota, tend to progress into skin ulcer, and pathogenicity associated with PML-RARα-positive matured neutrophils. The etiology, pathogenesis, and risk factors of ATRA-associated scrotal ulceration were discussed in the literature review.

Distinct Characteristics of Sweet’s Syndrome of the Scrotum Caused by All- trans Retinoic Acid in a Patient with Acute Promyelocytic Leukemia