ABSTRACT
Hand-foot syndrome (HFS) was first described in 1974 as a complication following mitotane therapy. The likelihood of developing HFS seems to increase in a dose-dependent fashion as drugs and formulations with longer half-lives and prolonged serum drug levels are associated with higher incidences. The distribution of HFS may be further explained by keratinocyte enzyme variations at different anatomical areas. Keratinocytes in the palms and soles demonstrate increased thymidine phosphorylase activity, an enzyme responsible for converting the prodrug capecitabine into the active 5-fluorouracil. HFS is a clinical diagnosis with the differential diagnosis including contact dermatitis, vasculitis, allergic drug eruptions, erythema multiforme, erythromelalgia, acral bleomycin toxicity, and graft-versus-host disease. Classifying and grading the severity of HFS is important and can help dermatologists and oncologists better assess and communicate a patient's clinical status. Retrospective and prospective studies have shown lower HFS rates in patients using icepacks or ice water immersion for their palms and soles during pegylated liposomal doxorubicin infusion.
