Acral erythema, also known as palmoplantar erythrodysesthesia and hand-foot syndrome, has been described following treatment with several systemic chemotherapeutic agents. The exact pathogenic mechanisms of this disorder are still unknown. Typically, the eruption involves the hands and feet and often occurs within the first week of treatment. Common provoking agents include cytarabine (cytosine arabinoside), 5-fluorouracil, doxorubicin (particularly pegylated liposomal doxorubicin), hydroxyurea, capecitabine, and mercaptopurine.

Reactions may occur sooner (24 hours to 3 weeks) and more severely with bolus chemotherapy than with low-dose continuous infusion and are usually reproducible with challenge. It is characterized by a painful erythematous rash, often associated with edema located on the palms, fingers, and soles, preceded by dysesthesia.

Acral erythema may occur as part of a broader eruption, known as toxic erythema of chemotherapy (TEC). Variant presentations of acral erythema and TEC include:

• Malignant intertrigo: This variant involves the axillary folds, antecubital / popliteal fossae, neck, inguinal folds, buttocks, and genitals. Involvement of the ears can be seen following cytarabine treatment.
• Periarticular thenar erythema with onycholysis (PATEO) syndrome: Has distinct nail changes and involvement of the dorsal hands and/or base of the thumb. This variant is often associated with taxanes.
• Fixed erythrodysesthesia plaque: This lesion is usually a fixed erythematous plaque at the infusion site and does not involve the palms of the hands or the soles of the feet. It commonly occurs with intravenous injections of docetaxel.
• Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN)-like presentation: This is a bullous variant that has been reported following cytarabine or high-dose methotrexate, particularly in children, and following enfortumab.