A cutaneous side effect of intravenous fluorouracil infusion

This 61-year-old man with recently diagnosed, inoperable esophageal squamous-cell carcinoma was treated with induction chemotherapy combining cisplatin and fluorouracil and concurrent radiotherapy. Because of worsening renal function, the use of cisplatin was suspended, and the chemotherapy was shifted to weekly high-dose fluorouracil and leucovorin. After the seventh infusion of fluorouracil–leucovorin, thrombosis developed in the right jugular and subclavian veins. This venous thrombosis prohibited further use of the permanent tunneled central-infusion catheter. The eighth infusion of fluorouracil–leucovorin was administered continuously over a 24-hour period by means of a peripheral catheter in the left forearm.

A day later, the patient noticed a mildly stinging rash that traced the path of the injected chemotherapeutic agents. Over the next few days, this erythema spread centripetally and became brown (arrows). This condition, known as serpentine supravenous hyperpigmentation, is a cutaneous side effect of intravenous fluorouracil infusion that is thought to result from extravasation of the cytotoxic agent after endothelial damage, causing epidermal basal hyperpigmentation and dermal melanin incontinence. Unlike tender, clot-forming thrombophlebitis, serpentine supravenous hyperpigmentation is characterized by underlying vessels that are patent.
Other chemotherapeutic agents, such as vinorelbine, fotemustine, and docetaxel, have also been found to cause serpentine supravenous hyperpigmentation. This complication is self-limiting and can be prevented by avoiding, if possible, peripheral infusion of these chemotherapeutic drugs, as well as fluorouracil. In this patient, the serpentine supravenous hyperpigmentation faded and had completely resolved 2 months after diagnosis.