Hand-foot syndrome
HFS; palmar-plantar erythrodysesthesia; PPE; acral erythema; chemotherapy-induced acral erythema
Hand-foot syndrome is a common cutaneous toxicity of selected systemic anticancer therapies — most prominently multikinase tyrosine kinase inhibitors (sorafenib, sunitinib, regorafenib, cabozantinib, pazopanib) and certain cytotoxic chemotherapies (capecitabine / 5-FU, liposomal doxorubicin, cytarabine). Two distinct phenotypes are recognised. The multikinase-inhibitor pattern is acutely painful, localised to pressure points and surfaces of friction, with hyperkeratosis and yellow-rimmed blisters. The cytotoxic / fluoropyrimidine pattern is diffuse, symmetrical, palmar-plantar erythema with desquamation and dysaesthesia. Both are managed with proactive prophylaxis and reactive dose modification.
Two distinct phenotypes
- Multikinase-inhibitor (TKI) HFS — sorafenib, sunitinib, regorafenib, cabozantinib, pazopanib. Localised to pressure / friction points (toes, ball of foot, fingertips); painful hyperkeratotic plaques with surrounding erythema; tense yellow-rimmed blisters; sharply demarcated. Onset within 2–6 weeks.
- Cytotoxic HFS — capecitabine, 5-fluorouracil, liposomic doxorubicin (Caelyx, Doxil), cytarabine. Diffuse, symmetrical palmar-plantar erythema with dysaesthesia / paresthesia, desquamation, sometimes intense pain. Onset variable, often after several cycles.
- Both can severely impair quality of life and lead to dose reductions or treatment interruption.
CTCAE grading
- Grade 1 — minimal skin changes (erythema, swelling, hyperkeratosis) without pain.
- Grade 2 — skin changes with pain, not limiting instrumental ADLs.
- Grade 3 — severe skin changes with pain, limiting self-care ADLs.
Prophylaxis
- Patient education before treatment — examine hands and feet, treat hyperkeratoses (calluses, corns), wear cushioned footwear.
- Daily emollients with urea 10–20% on palms and soles.
- Avoid friction and pressure — supportive shoes, gel insoles, avoid prolonged hot water immersion.
- Photoprotection.
- Pyridoxine (vitamin B6) — historically used but limited evidence; not routinely recommended.
- Topical or oral celecoxib — emerging evidence for capecitabine-related HFS reduction.
Management
- Grade 1 — emollients, urea creams, supportive footwear, continue treatment.
- Grade 2 — topical clobetasol or potent steroid; analgesia; consider 50% dose reduction or treatment interruption depending on the drug.
- Grade 3 — interrupt treatment until G ≤ 1, then resume at reduced dose; topical steroid; consider oral steroid for severe inflammation.
- Pain management — paracetamol, NSAID, sometimes neuropathic agents (gabapentin) for cytotoxic dysaesthesia.
- Multidisciplinary — dermatology referral for refractory or atypical cases.
Differential
- Acral psoriasis or eczema — preceding history.
- Erythromelalgia — episodic burning, not localised to pressure points.
- Chronic GVHD — broader skin involvement, not isolated to palms / soles.
- Pyogenic / fungal infection — culture if any doubt.
- Drug-induced palmoplantar pustulosis — pustules in absence of erythema / pain typical of HFS.
References
- Lacouture ME et al. Evolving strategies for the management of hand-foot skin reaction associated with multikinase inhibitors. Oncologist; 2008.
- Miller KK et al. Chemotherapy-induced hand-foot syndrome — review. J Am Acad Dermatol; 2014.
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