Cutaneous Adverse Effects of Epidermal Growth Factor Receptor Inhibitors

by Anthony Fernadez, MD, and Christie Warren, MD

Note: This is an abridged version of an article originally published in the Cleveland Clinic Journal of Medicine.

Biologic therapies have revolutionized medicine and offer targeted therapy for an increasing number of diseases, particularly in rheumatology, gastroenterology, hematology/oncology and dermatology. But along with these advances and their ensuing expanded use have come many unique adverse effects.

Some of the most commonly reported adverse effects with these new therapies are cutaneous, and can potentially limit the use of these agents and add cost to already expensive treatment regimens.1

It is important for physicians and other healthcare providers to be aware of these effects, have a basic understanding of how to manage patients with these reactions, and to know when to refer to a dermatologist. This is the second article in a four-part series that reviews recent literature on cutaneous adverse reactions experienced with commonly prescribed biologic and targeted therapies.

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that, when activated, leads to the autophosphorylation of tyrosine kinase receptor, initiating a cascade of downstream signaling pathways involved in regulating cellular proliferation, differentiation and survival. EGFR inhibitors block this pathway in tumor cells and are predominantly used in non-small cell lung cancer, colorectal cancer, pancreatic cancer, and head and neck cancer. Examples include gefitinib, cetuximab, erlotinib and panitumumab.

Acneiform reactions

The most common cutaneous reaction with EGFR inhibitors is a widespread papulopustular acneiform eruption consisting of erythematous follicle-based papules and pustules without comedones.

More than half of patients taking these drugs experience an acneiform eruption. It is usually mild or moderate but can be severe in a minority of cases. The acneiform eruption is often dose-dependent and begins within one week of treatment.17

The lesions commonly present on the face and trunk, spare the palms and soles, and are associated with pruritus.

While management depends on the severity, consultation with a dermatologist is recommended for most patients, particularly if the reaction lasts more than two weeks or is severe. Prevention can include medications, such as minocycline or doxycycline. Treatment can include topical and systemic corticosteroids, antibiotics and oral isotretinoin. If there is pruritus, oral histamine 1 (H1) antihistamines can be used. Gamma aminobutyric acid agonists such as gabapentin and pregabalin can be used as second-line treatments for itching.

Toenail inflammation

A study of 10 patients suggested paronychial inflammation, commonly with pyogenic granuloma-like lesions, as another cutaneous manifestation.18 Paronychia in the great toe often occurs first, and secondary bacterial infection (commonly Staphylococcus aureus) can occur as well.

Treatment with topical antibiotics, topical corticosteroids, electrodessication for larger lesions, and, more rarely, photodynamic therapy, can be effective.

Other reactions

EGFR inhibitors have also been associated with hair changes including development of brittle, fine and curly hair on the scalp and extremities.

Xerosis with desquamation, small aphthous ulcerations of the oral and nasal mucosa, photosensitivity and urticaria have also been noted.

Cases of Stevens-Johnson syndrome-toxic epidermal necrolysis have been associated with erlotinib therapy, but the incidence is low.19 Discontinuation is recommended if any sign of a bullous or exfoliative eruption occurs.

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