Painful Rashes on the Palms and Soles.

Answer: E A 72-year-old male of Caucasian descent was referred for consideration of systemic therapy after receiving a diagnosis of hepatocellular carcinoma (HCC). His past medical history was unremarkable with no comorbidities and he was not on any other medications. Computer tomography (CT) scan revealed multifocal HCC, and a biopsy of which confirmed HCC. There was no underlying cirrhosis or features of portal hypertension. His viral hepatitis profile was negative, as were his autoimmune screen. His iron studies, copper levels and thyroid function were all in the normal range. He was well with a performance status of Eastern Cooperative Oncology Group (ECOG) 0. He was started on a trial of sorafenib at a dose of 400 mg twice daily. Nine weeks later, he presented with well demarcated, tender well defined yellowish hyperkeratotic plaques on his plantar surfaces (Fig. 1) and erythematous patches on the palmar surfaces (Fig. 2). It gradually spread to the arms and legs forming pustules and blisters with raw ulcerated surfaces. What is the most likely diagnosis of his skin condition? A. Plaque psoriasis B. Pityriasis rubra pilaris C. Cutaneous infiltration of malignancy D. Keratoderma blennorrhagica E. Palmar-plantar erythrodysesthesia Discussion Hand-foot syndrome (HFS) or palmar-plantar erythrodysesthesia is an adverse cutaneous reaction seen with multikinase antineoplastic therapy. In our patient, sorafenib which has been approved for use in the treatment of HCC and renal cell carcinomas was the causative drug. Other anticancer drugs commonly implicated in HFS are capecitabine and 5-FU.1 Sorafenib is a molecule capable of multilevel kinase inhibition, simultaneously inhibiting molecular components of the Raf-MEK-ERK signalling pathway, abrogating tumour growth and vascular endothelial growth factor receptor (VEGFR-1, VEGFR-2, VEGFR-3,) and plateletderived growth factor receptor (PDGFR-β). This gives the drug a pro-apoptotic and anti-angiogenic effect.2 The safety and efficacy of sorafenib in treating HCC was established in the Phase III SHARP Trial (Sorafenib in Advanced Hepatocellular Carcinoma) in patients with advanced disease if they were not eligible for or have had disease progression after surgical or locoregional therapies.3 In the SHARP Trial, 21% of patients developed HFS and it was severe (grade 3) in 8%. This drug-related adverse event has been previously observed in its use in the treatment of renal cell carcinoma, leading to dose reductions and interruptions in a subgroup of patients.4