Differential therapy of diffuse neonatal hemangiomatosis

Introduction: Hemangiomas are the most common tumors of infancy. Hemangiomas are present at birth in up to 2,5% and more than 10% in the caucasic population show hemangiomas in their first year of life. Hemangiomas, benign vascular lesions usually show a tendency to grow rapidly during the first 8–12 months of life, followed by an involution phase that could take several years. Most hemangiomas do not require specific treatment because of the high rate of spontaneous regression. However, a small number of hemangiomas require therapy including hemangiomas endangering vision, oral intake and organ functions.

Diffuse neonatal hemangiomatosis (DNH) is a rare, frequently fatal disorder characterized by multiple cutaneous and visceral hemangiomas. In most cases of DNH hemangiomas are either present at birth or develop during the first week of life. In addition to the cutaneous hemangiomas other possibly involved organs include the liver, then less frequently pleura, lungs, intestines, central nervous system and eyes. A combined manifestation of skin and liver without other organs being involved is found in most patients. Children with DNH have a grave prognosis (mortality rate 50–95%). The main reason is high-output cardiac failure due to high-flow liver hemangiomas. Other complications could be liver failure including consumption coagulopathy, as well as cutaneous, gastrointestinal and cerebral bleeding.

Many efforts have been made in treating DNH. Published treatment regimes include systemic corticosteroids, subcutaneous interferon alpha 2a or 2b, liver radiation, partial liver resection, hepatic artery embolization and the use of antiangiogenetic chemotherapeutic agents like vincristine and cyclophosphamide. Cyclophosphamide was reported to offer promising results in so far 9 published cases of children suffering from DNH.

Case reports: We present two cases of neonates with multiple cutaneous lesions together with high-flow hemangiomas of the liver and in one patient additional pulmonary and cerebellar angiomas. We prescribed cyclophosphamide 10mg/kg/day on 4 consecutive days after failure of corticosteroids. Cyclophosphamide induced a fast regression of the lesions with no side effects in both infants. We could stop medication after 3 respectively 4 courses of cyclophosphamide in both infants because of the excellent response.

Discussion: Concerning the high mortality rate of DNH, especially when associated with high-output cardiac failure, we feel that an early and aggressive treatment is warranted. Comparing therapy duration, side effects and mortality rates of the different above mentioned therapeutic options cyclophosphamide offers some unique advantages including low acute toxicity, rapid effect and low costs.

Conclusion: In our opinion cyclophosphamide should be considered as a reasonable safe, quick-working and short therapy in children with corticosteroid-unresponsive life-threatening diffuse neonatal hemangiomatosis.