We read with interest the article on ifosfamide-induced hyperpigmentation by Teresi et al.' In our experience, this is a widespread, if underreported phenomenon.
In Newcastle, United Kingdom, children with nonmetastatic soft tissue sarcomas are initially treated with five courses of ifosfamide (IF) and etoposide before reassessment and local therapy. IF (9 g/m') is administered as a continuous infusion over 72 hours. Hydration (3 I/m2/day) containing MESNA (3 g/m2/day) is given concurrently and continued for 12 hours after completion of the IF infusion. Etoposide (200 mg/m2) is given on each of these 3 days. We have treated seven children with this regimen during the last 18 months (Table 1).
Among this small group, hyperpigmentation developed in five (71%). In one case, this was only noticeable under an occlusive dressing and faded rapidly upon its removal. The most common sites were the dorsal and plantar surfaces of the hands and feet. Hyperpigmentation of the scrotum occurred in two boys. In severe cases, large areas of the trunk were affected. Only one child had nail involvement. The onset of pigmentation was variable but appeared to be more rapid among children of mixed race. A generalized increase in pigmentation was noted in one child after a single course of treatment. Persistence is variable-Patient 3 remains hyperpigmented 6 months after completing 16 courses of IF. In other cases, hyperpigmentation faded despite continued treatment with IF.
Teresi and colleagues speculate that IF-induced hyperpigmentation may be linked to concurrent renal impairment, implying that it may be secondary to reduced drug or metabolite clearance and/or altered metabolism. We recently described the pharmacokinetics and metabolism of continuousinfusion IF in 17 children, including those described here.' These data do not suggest altered pharmacokinetics or metabolism in the hyperpigmented group. Chloracetaldehyde generated by dechlorethylation of IF has been implicated in the pathogenesis of n e p h r ~p a t h y . ~
We did not detect an increase