Review
Cutaneous side effects of epidermal growth factor receptor inhibitors: Clinical presentation, pathogenesis, and management

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The growing investigation and use of epidermal growth factor receptor (EGFR) inhibitors in anticancer therapy has been motivated by their specificity for EGFR, which improves their ability to target cancer cells and enhances their safety profile compared with many other conventional chemotherapeutic agents. However, their growing use has been accompanied by an increasing incidence of cutaneous toxicities, which can cause serious discomfort and be disabling. This review illustrates the common cutaneous side effects seen in patients receiving EGFR inhibitors and discusses various options for management. With effective management of these side effects, dermatologists can play an integral role in facilitating compliance with anti-EGFR therapy and aid with effective oncologic management.

Section snippets

EGFR inhibitors

Most of the EGFR inhibitors can be classified into two categories: monoclonal antibodies and tyrosine kinase inhibitors. Monoclonal antibodies compete with the endogenous ligands EGF and transforming growth factor alpha, thereby blocking ligand-induced activation of the receptor tyrosine kinase.10 They also induce antibody-mediated receptor dimerization, resulting in down-regulation of the receptor.10 Cetuximab, in particular, also inhibits the production of angiogenic factors, mediates

Acneiform eruption

Acneiform eruptions occur in more than 50% of cases, although cetuximab can demonstrate incidences as high as 75% to 100% of cases.5, 21, 22, 23, 24, 25, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 The incidence and degree of toxicity of the eruption appear to correlate with increasing doses of and treatment duration with EGFR inhibitors.21, 22, 34, 36, 45, 46 The eruption usually occurs after 1 week of treatment, though it can occur after only 2 days and as late as 6 weeks after

Paronychia

Paronychia occurs less frequently than acneiform eruptions, with some authors estimating its occurrence in 10% to 15% of patients treated with cetuximab and gefitinib.21, 24, 26, 27, 28, 29, 78, 79 It typically develops approximately 4 to 8 weeks, and sometimes as late as 6 months, after treatment initiation and frequently involves multiple fingers and the great toes (Fig 2).21, 26, 27, 28, 29, 78, 79 Paronychia may be painful, particularly when associated with ingrowth of the nails.79 It can

Xerosis

Xerosis occurs in up to 35% of patients receiving anti-EGFR therapy and is seen more frequently in patients undergoing gefitinib therapy.1, 21, 32, 38, 42, 44, 48, 79 Patients who are older, have a history of atopic eczema, and have had previous therapy with cytotoxic agents are more susceptible to EGFR inhibitor–induced xerosis.21 Xerosis typically presents as dry, scaly, itchy skin and is found particularly in areas that were previously or are simultaneously affected with an acneiform

Other cutaneous side effects

Anti-EGFR therapy is also associated with other less common cutaneous toxicities. Progressive skin hyperpigmentation has been seen in patients receiving gefitinib treatment. The hyperpigmentation is likely postinflammatory in nature and usually occurs after an EGFR-induced acneiform eruption or eczema.21, 27 It often develops on the face, trunk, and legs after several months of EGFR inhibitor therapy.27 Sun exposure worsens the hyperpigmentation.21, 27 Histopathologic findings include increased

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    Funding sources: None.

    Conflicts of interest: None identified.

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    Copyright © 2007 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.