Abstract
BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare but aggressive vascular tumor, potentially life-threatening when associated with Kasabach-Merritt phenomenon (KMP). Oral sirolimus is effective but may cause systemic adverse effects in infants. Oral propranolol offers a safer alternative in early infancy, but its efficacy may plateau over time. Sequential topical sirolimus may enhance outcomes while minimizing systemic toxicity. OBJECTIVE: To evaluate the additive therapeutic effect and safety of topical sirolimus in KHE patients with suboptimal response after oral propranolol. METHODS: This retrospective study included five pediatric patients with cutaneous KHE treated at Beijing Children's Hospital from October 2018 to October 2022. All had received oral propranolol for ≥24 months and showed therapeutic plateau (tumor shrinkage ≤70%). They were subsequently treated with 0.1% topical sirolimus ointment twice daily for at least six months and followed for one year. Efficacy was assessed by Visual Analog Scale (VAS), Doppler ultrasound, and a four-grade evaluation system; safety was monitored throughout. RESULTS: All patients showed significant improvement within 6-12 months (mean: 9.6 months), achieving Grade III or IV response. Doppler imaging revealed reduced or absent blood flow signals, and lesions nearly regressed in some cases. Symptoms such as pain and localized hyperthermia resolved, and skin appearance normalized. Two patients experienced mild local irritation; no systemic adverse effects or recurrences were observed. CONCLUSION: Sequential topical sirolimus following oral propranolol offers a safe and effective treatment strategy for KHE, especially after therapeutic plateau. It enhances efficacy, avoids systemic toxicity, and may accelerate lesion regression. Further large-scale studies are warranted to optimize individualized treatment protocols.