Figure 1.

Palmar–plantar erythrodysesthesia syndrome, grades 1–3, according to the National Cancer Institute Common Terminology Criteria for Adverse events, version 4 [84]. Grade 1: numbness, dysesthesia, paresthesia, tingling, painless swelling, erythema, or discomfort of the hands or feet that does not disrupt the patient's normal activities. Grade 2: painful erythema and swelling of the hands or feet and/or discomfort that affects the patient's instrumental activities of daily living. Grade 3: moist desquamation, ulceration, blistering, or severe pain of the hands or feet, or severe discomfort that causes the patient to be unable to work or perform self-care activities of daily living. Note that, as discussed in the text, hand–foot skin reaction due to small-molecule kinase inhibitors may have a different manifestation, so the descriptions here may not match symptoms experienced by patients receiving regorafenib. Photos provided by Siegfried Segaert and Eric Van Cutsem.