Acral erythema caused by high-dose methotrexate therapy in patients with osteogenic sarcoma

High doses of methotrexate (MTX) have been incorporated in the treatment of osteogenic sarcoma since the 1970s. Unfortunately, high-dose MTX (HD-MTX) can cause untoward side effects that may complicate the proper management of these patients. Two cases of MTX-induced acral erythema are described and the possible implications of this complication are reviewed, with a discussion of the pathophysiology of this adverse effect. Two young female patients suffering from osteogenic sarcoma received HD-MTX (12 g/m2) according to the chemotherapeutic protocol. A 17-year-old patient with osteogenic sarcoma of the head developed painful acral erythema of her palms and soles after the fifth dose of MTX, and a 22-year-old patient with osteosarcoma of the femur developed severe acral erythema after the sixth dose. The severity of the reaction was significant enough to cancel further treatment with HD-MTX in both patients. All symptoms resolved without sequellae several weeks later in both cases. Acral erythema may pose a significant albeit transient phenomenon adversely influencing chemotherapy in patients suffering from osteosarcoma and treated with HD-MTX. The pathophysiology of this side effect is not completely understood and further investigation of the pharmacokinetics of HD-MTX in this patient population is needed.