Cutaneous Reactions to Tyrosine Kinase Inhibitors

Abstract

Tyrosine kinase inhibitors (TKIs) are a new and unique class of orally administered, small- molecule therapeutics that have found their way into the standard of care treatment in almost all types of malignancy. The number of TKIs being developed and the number of indications for which they are being tested and approved is growing exponentially. As promising as TKIs are in helping patients avoid some of the side effects of traditional cytotoxic chemotherapy, they do come with a variety of cutaneous side effects. These are unique and variable and include skin rashes of many different types and severities, dry skin, hand–foot syndrome, pruritus, ocular, and hair and nail changes.

As patient survival is often directly correlated with successful therapeutic drug delivery, the management of TKI-induced skin diseases is critical. Making a correct clinical diagnosis of a TKI side effect ensures proper treatment and may avoid discontinuation or reduction of the medication.

TKIs can be grouped into three main classes based on the molecular pathway inhibited. These include (1) EGFR and the HER family inhibitors; (2) VEGF/PDGF/mixed inhibitors and (3) other inhibitors, including the BCR-ABL c-KIT and RET inhibitors. Characteristic skin conditions are associated with each of these classes of TKIs, which are described along with management strategies.

The key to successful management is clinician and patient education. Several general principals need to be emphasized: TKI-induced skin rashes are inflammatory in nature and not contagious; patients treated with TKIs should be instructed to use an alcohol-free emollient cream applied twice daily, preferably to their entire body; patients should avoid sun exposure and use protective clothing and broad spectrum UVA/UVB sunscreen. Care should be taken when treating cutaneous manifestations, as the wrong treatment can exacerbate the side effects.