Incidence and Risk Factors for Hyperpigmentation Following Intralesional Bleomycin Injections for the Treatment of Vascular Anomalies

Purpose: To investigate the incidence of hyperpigmentation and identify associated risk factors in patients treated with intralesional bleomycin for vascular anomalies.

Materials and Methods: This retrospective cohort study was conducted on 320 patients with vascular anomalies treated with intralesional bleomycin between April 2009 and January 2024. Patient demographics, lesion type, location, and bleomycin dosage were recorded. Hyperpigmentation incidence was noted, and logistic regression was used to evaluate the relationship between patient characteristics, lesion type, and bleomycin dosage on the risk of hyperpigmentation. Data analyses were performed using SAS, focusing on the effects of weight-adjusted bleomycin dosage (u/kg/procedure) on the development of hyperpigmentation.

Results: Out of 320 patients (female = 57%, male = 43%, mean age = 14.0 years), 18 (5.6%) developed hyperpigmentation after 18 procedures (3.3%). Hyperpigmentation development after an average of 2 months (SD = 0.5, range = 1 week to 8 months). There was no change in hyperpigmentation in 10 (56%) patients, mild fading in 4 (22%), completion resolution in 3 (17%), and a slight increase in hyperpigmentation in 1 (6%) after a mean follow-up of 1.3 years.
The mean age of patients with hyperpigmentation was significantly lower (7.3 vs 14.4 years, p = 0.005), and they had a lower mean weight (32.0 vs 48.9 kg, p = 0.036) than those without hyperpigmentation. Male patients were more likely to develop hyperpigmentation (OR = 2.79, p = 0.045). The odds of hyperpigmentation increased with higher weight-adjusted procedural doses (u/kg/procedure) of bleomycin (OR = 9.15, p = 0.016), while procedural dose (u/procedure) was not significantly associated. The most common lesion types associated with hyperpigmentation were macrocystic and microcystic lymphatic malformations (OR = 9.84, p < 0.001). Lesions on the head, neck, and trunk were also more likely to develop hyperpigmentation than those on the extremities (OR = 3.32, p = 0.04).

Conclusion: The study shows that hyperpigmentation is an uncommon but significant complication of intralesional bleomycin, especially in younger patients with macrocystic or microcystic lymphatic malformations. Higher weight-adjusted bleomycin doses notably increase the risk. Identifying these risk factors can guide clinical decisions and help set realistic expectations for potential side effects in treating vascular anomalies.