*Dermatitis Caused by Epidermal Growth Factor Receptor Inhibitors

Chapter: Dermatitis Caused by Epidermal Growth Factor Receptor Inhibitors
Section Editor(s) in Interna Szczeklika: Jacek Łuczak
McMaster Author(s): Victor C. K. Lo
Author(s) in Interna Szczeklika: Maciej Krzakowski, Krzysztof Krzemieniecki†
† Deceased.
Additional Information

Etiology, Pathogenesis, Clinical FeaturesTop

Epidermal growth factor receptor (EGFR) inhibitors (eg, cetuximab, panitumumab, pertuzumab, and necitumumab) and tyrosine kinase inhibitors 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. Inhibition of the EGFR leads to arrest of keratinocyte growth and apoptosis.

Initial manifestations include local erythema, edema, and paresthesias (burning sensation) of the upper trunk and are followed by a facial maculopapular rash that often involves both cheeks and the chin. The clinical presentation is similar to acne, but the lesions are of a different nature and unusual location; the rash develops on the face, trunk, and extremities (sparing the palms and soles), comedones are absent, pruritus is present, and lesions resolve upon anti-inflammatory treatment (as opposed to conventional acne treatment). Initial pustules are sterile, but colonization with Staphylococcus aureus can occur.

After 1 to 3 months of EGFR-targeted treatment, the cutaneous lesions become more severe (xerosis, telangiectasia) and are accompanied by thinning and fragile hair on the scalp and limbs, excessive facial hair growth (including excessive eyelash growth), and paronychia. The cutaneous manifestations are generally mild to moderate, but in 8% to 17% of patients they are severe enough to warrant temporary or permanent discontinuation of the offending drug.

TreatmentTop

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

2. Excessive eyebrow or eyelash growth and excessive facial hair growth may be removed by epilation.

TablesTop

 

Table 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

– No pruritus

Topical treatment: 2.5% hydrocortisone cream bid ± 1% clindamycin gel

Grade 2:

– Papulopustular eruption

– Pruritus

– Involvement of <50% BSA

 

Topical treatment: 2.5% hydrocortisone cream bid

Systemic treatment: Doxycycline 100 mg once daily for 7-14 days

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

Analgesic treatment: Acetaminophen, ibuprofen

Grade 3:

– Papulopustular eruption

– Pruritus

– Involvement of >50% BSA

 

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

Topical treatment: 2.5% hydrocortisone cream bid + wet compresses (0.9% saline 2-4 × a day for 10 min)

Systemic treatment: Doxycycline 100 mg once daily for 7-14 days + prednisone 0.5 mg/kg for 7 days

Antipruritic and analgesic treatment: As above

Grade 4:

Erythroderma (skin desquamation and ulcerations)

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

– Consider expert consultation and treatment with isotretinoin

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: PO antihistamines (eg, hydroxyzine, cetirizine)

Fissures

Emollients: 5%-10% urea and other preparations

 

Dry pulpitis

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

Viral superinfection

Systemic treatment: Valacyclovir 500 mg bid for 5 days

Paronychia

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

Topical treatment: Topical high-potency glucocorticoids (eg, clobetasol)

Systemic treatment: Doxycycline 100 mg once daily for 7-14 days

Treatment of infection: Cloxacillin 500 mg qid for 7 days

bid, 2 times a day; BSA, body surface area; EGFR, epidermal growth factor receptor; qid, 4 times a day; PO, oral.

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