Toxic erythema of chemotherapy (TEC) refers to a range of nonallergic cutaneous eruptions that develop in the setting of chemotherapy. Key clinical features include formation of erythematous or edematous patches and plaques on the hands, feet, and intertriginous areas (axillae, groin, scrotum), associated with dysesthesia, pain, and pruritus. Elbows, knees, and ears may also be involved, and the eruption can become generalized. Affected skin may appear violaceous, and bulla formation may occur in severe cases. The lesions are self-limited and will desquamate and resolve spontaneously.

The range of entities classified under TEC is broad and includes acral erythema (palmoplantar erythrodysesthesia, hand-foot syndrome, dorsal hand-foot syndrome – also known as periarticular thenar erythema with onycholysis syndrome [PATEO]), intertriginous eruption of chemotherapy (malignant intertrigo), and neutrophilic eccrine hidradenitis, among others. Generalized eruptions resembling Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) have also been reported.

TEC eruptions typically develop within a few days or weeks after chemotherapy administration; however, presentations can be delayed in patients who are receiving lower-dose continuous chemotherapy infusions or oral agents. The most commonly implicated agents are conventional cytotoxic chemotherapies such as anthracyclines (doxorubicin), capecitabine and 5-fluorouracil analogues, cytarabine, taxanes (docetaxel, paclitaxel), and methotrexate, among others. Recently, antibody-drug conjugate therapies (which consist of monoclonal antibodies linked with cytotoxic chemotherapy agents) have emerged as another common cause of TEC. Enfortumab-vedotin comprises an antibody against nectin-4 (a protein expressed in urothelial carcinoma cells and skin epithelium) paired to a cytotoxic chemotherapeutic agent that has been associated with particularly severe presentations of TEC.

It is important to note that TEC does not represent a hypersensitivity reaction or allergic reaction to chemotherapy. TEC is thought to result from a toxic effect of chemotherapy agents on eccrine cells and on the epidermis as the chemotherapy is extravasated from eccrine ducts. TEC may recur with drug rechallenge and can worsen with increased doses of the causative chemotherapeutic agent. However, routine TEC eruptions are typically not a contraindication to drug rechallenge. Appropriate diagnosis of TEC can therefore help maintain patients on life-saving chemotherapies.