All-trans-retinoic acid (ATRA)-induced genital ulcers are a rare, self-limited complication of ATRA therapy. ATRA is a generally well-tolerated induction chemotherapeutic agent used for acute promyelocytic leukemia, leading to complete remission rates of approximately 90% in this specific subtype of leukemia. Although the pathophysiology of ATRA-induced genital ulcers is not fully understood, some have suggested that they may result from ATRA-induced release of cytokines and interleukins resulting in leukocyte activation and tissue damage. Some suspect that ATRA-induced genital ulcerations may be a localized form of a neutrophilic dermatosis, similar to a form of drug-induced Sweet syndrome.

Patients with ATRA-induced genital ulcers typically present with ulcerations 2-4 weeks after initiating treatment, but ulcers have been documented as early as 7 days after beginning ATRA induction therapy. Areas of genital involvement include the scrotum, penis, perineum, labia, and vulva. Some cases of genital ulcers have also been reported to be accompanied by oral ulcers. These ulcerations are commonly associated with fever and leukocytosis, but the ulcers themselves are often painless in nature. There is no clear age predominance, with cases reported in patients ranging in age from 8-63 years.

Immunocompromised patient considerations: In immunocompromised patients, evaluation for infectious etiologies, such as herpes simplex virus (HSV) or cytomegalovirus (CMV), is critical before making a diagnosis of ATRA-induced genital ulcers.