Cutaneous Eruptions Caused by Epidermal Growth Factor Receptor (EGFR) Inhibitors

How to Cite This Chapter: Lo VCK, Abu-Hilal M, Khalaf D, Krzakowski M, Krzemieniecki K. Cutaneous Eruptions Caused by Epidermal Growth Factor Receptor (EGFR) Inhibitors. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.22.2.3. Accessed April 24, 2024.
Last Updated: May 29, 2022
Last Reviewed: May 29, 2022
Chapter Information

Etiology, Pathogenesis, Clinical FeaturesTop

Monoclonal antibodies to epidermal growth factor receptor (EGFR) (eg, cetuximab, panitumumab) and tyrosine kinase inhibitors (TKIs) acting on the signaling pathways activated by the EGFR (eg, gefitinib, erlotinib, afatinib, osimertinib, and lapatinib) cause specific cutaneous toxicities in >80% of patients due to the abundant expression of the EGFR in the skin. The EGFR plays a critical role in the maintenance of skin homeostasis, as it is involved in regulating keratinocyte proliferation. EGFR inhibition leads to arrest of keratinocyte growth and subsequent apoptosis, resulting in skin toxicity.

Initial clinical manifestations include local erythema, edema, pruritus, and paresthesia (burning sensation), most commonly of the upper torso, neck, and face. Later, an acneiform rash characterized by sterile pustules and papules appears on the same erythematous areas (see Figure 1). The clinical presentation is similar to that of acne, but the lesions vary in size and lack the white and black comedones, which represent the hallmark of acne. Lesions can also be pruritic. Initial pustules are sterile, but superinfection with Staphylococcus aureus can occur. With prolonged exposure to EGFR inhibitors, the patient may develop severe xerosis, telangiectasia, and paronychia around the nails. In severe cases, the cutaneous lesions become more severe, with continuous exfoliation and desquamation. Other late manifestations may include hair loss, alopecia of the scalp, excessive facial hair growth (including excessive eyelash growth), and paronychia.

The cutaneous manifestations are generally mild to moderate. Severe cases can be seen in 8% to 17% of patients, warranting temporary or permanent discontinuation of the offending drug unless a severe, acneiform eruption is not a contraindication to continue anti-EGFR therapy.

TreatmentTop

1. Treatment of the skin manifestations depends on their severity (Table 1). Consider consultation with a dermatologist or oncologist.

2. Excessive growth of eyebrows, eyelashes, or other facial hair may be treated by different methods of epilation (eg, laser).

3. Patients who develop skin reactions to EGFR inhibitors generally have a better response to treatment and a higher survival rate than others.

Tables AND FIGURESTop

Table 13.1-1. Classification, clinical manifestations, and treatment of skin and nail lesions caused by EGFR inhibitors

Type

Clinical manifestations

Treatment

Papulopustular (acneiform) rash

Grade 1: Papulopustular eruption <10% of BSA

Topical treatment: Low-potency topical glucocorticoids (eg, 2.5% hydrocortisone cream bid ± topical 1% clindamycin gel or solution), moisturizer

Grade 2: Papulopustular eruption 10%-30% of BSA; limiting iADLs

Topical treatment: 2.5% hydrocortisone cream bid, moisturizer

Systemic treatment: Oral antibiotics with good anti-inflammatory properties, such as doxycycline or minocycline 100 mg PO bid for 7-14 days to assess response and treat for ≥4 weeks

Antipruritic treatment: Oral antihistamines (eg, hydroxyzine, cetirizine)

Analgesic treatment: Acetaminophen, ibuprofen

Grade 3:

– Papulopustular eruption >30% of BSA

– Limiting ADLs

Dose modification or discontinuation of EGFR inhibitors until severity of skin rash decreases ≤grade 2

Topical treatment: 2.5% hydrocortisone cream bid, moisturizer

Systemic treatment: Doxycycline or minocycline 100 mg PO bid for 7-14 days to assess response and treat for ≥4 weeks + prednisone 0.5 mg/kg for 7 days

Antipruritic and analgesic treatment: As above

Grade 4:

– Involvement of >30% BSA with serious consequences

– Erythroderma (skin desquamation and ulcerations)

– Discontinuation of EGFR inhibitors and transfer to specialized burn treatment facility

– Consider dermatology consultation for treatment with low doses of oral retinoids (eg, isotretinoin or acitretin)

Dry skin (xerosis)

Pruritus and dry skin

General recommendations: Avoid excessive skin exposure to water and soap

Emollients: 5%-10% urea and other preparations

Antipruritic treatment: Oral antihistamines (eg, hydroxyzine, cetirizine)

Fissures

Emollients: 5%-10% urea and other preparations

Inflammation of fingertips

Emollients: 5%-10% urea, intermittent topical treatment with medium-potency glucocorticoid (eg, fluticasone, betamethasone)

Paronychia

General recommendations: Preventive measures (loose footwear, antiseptic baths)

Topical treatment: Topical high-potency glucocorticoids (eg, clobetasol propionate for 2 weeks) ± topical antifungal agent (eg, ketoconazole cream bid for 2 weeks)

Treatment of infection: Cephalexin (500 mg PO qid) or cloxacillin 500 mg PO qid for 7 days

bid, 2 times a day; BSA, body surface area; ADL activities of daily living; EGFR, epidermal growth factor receptor; iADL, instrumental activities of daily living; PO, orally; qid, 4 times a day.

Figure 13.1-1. Diffuse acneiform papules and pustules on the face due to erlotinib treatment in a patient with non–small cell lung cancer.

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