Flagellate erythema and flagellate pigmentation are well-known cutaneous complications following bleomycin sulfate therapy. Studies have shown an incidence rate of 8%-66% of patients on bleomycin developing this patterned eruption. The dose of bleomycin required to produce such an effect is usually more than 100 U, and eruptions are considered to be dose dependent. However, reactions have been seen with doses as low as 15 U intravenously (IV) and 30 U intrapleurally. Intraperitoneal and intramuscular injection have also produced the eruption, as have intralesional bleomycin given for venous malformation sclerosis and intralesional therapy for wart treatment. Other chemotherapeutic agents including peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab are additional causes of flagellate erythema and pigmentation.

Flagellate erythema appears as linear, whip-like, erythematous streaks on the upper torso and, less frequently, on the extremities. The eruption may be preceded by severe, generalized pruritus and is itself usually very pruritic. Flagellate erythema may occur within 24 hours of receiving the culprit medication, or there may be a lag time of up to 6 months. It has a self-limited course and usually subsides, leaving a residual postinflammatory hyperpigmentation that may persist for months. In some cases, patients note minimal or absent pruritus or erythema, and hyperpigmentation is the initial presentation.

The pathogenesis of flagellate erythema is unclear. Scratching is thought to disrupt the dermal vasculature with subsequent drug leakage into the dermis. Bleomycin is metabolized by bleomycin hydrolase in the subcorneal layer. This enzyme is absent from the dermis and so the drug might accumulate there and cause its toxic effects. Immunologic mechanisms, including type I and type II responses, have also been postulated.

Pediatric Patient Considerations
Bleomycin-induced flagellate erythema and pigmentation have been reported in the pediatric population as well.