Hyperkeratotic Skin Adverse Events Induced by Anticancer Treatments: A Comprehensive Review (Drug Safety)

Abstract Hyperkeratotic skin adverse events are a group of toxic effects, characterized by the disruption of epidermal homeostasis and interaction with keratinocyte proliferation/differentiation or keratinocyte survival, and frequently reported with systemic anticancer treatments. These types of reactions include hand-foot skin reaction or palmoplantar keratoderma, induced psoriasis, keratosis pilaris-like or pityriasis rubra pilaris-like rashes, Grover`s disease, and contact hyperkeratosis. Cutaneous squamoproliferative lesions are also described because of the presence of abnormal keratinocyte proliferation. They are usually observed with tyrosine kinase inhibitors but have also been described in association with cytotoxic chemotherapeutic agents. Their pathogenesis is related mainly to the disruption of epidermal homeostasis and interaction with keratinocyte proliferation/differentiation or keratinocyte survival caused by anticancer treatment. Early recognition and adequate management are critical to prevent exacerbation of the lesions, to limit treatment interruption, and to minimize impairment of quality of life. This review summarizes the current knowledge concerning the presentation, pathogenesis, and management of secondary hyperkeratotic reactions to anticancer therapies. It also includes hyperkeratotic reactions that have been more recently described with newly approved targeted therapies or immune checkpoint inhibitors, such as keratosis pilaris-like exanthema with second-generation BCR-ABL inhibitors, lamellar ichthyosis-like lesions with ponatinib, pityriasis rubra pilaris with the newly approved selective phosphoinositide 3 kinase inhibitor idelalisib, or psoriasis with anti-programmed death-1 and programmed death ligand-1.