ReviewCutaneous side effects of epidermal growth factor receptor inhibitors: Clinical presentation, pathogenesis, and 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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EGFR inhibitors: clinical aspects, risk factors and biomarkers for acneiform eruptions and other mucosal and cutaneous adverse effects
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2022, Anais Brasileiros de DermatologiaCitation Excerpt :Also regarding EGFR inhibitors, involved in 18.9% of the total of AEs in this general series, they were responsible for 73.1% of the papulopustular eruptions in the present study. It is the most common AE of this oncologic therapy, occurring in 50%–100% of patients.11,13,14 Acneiform eruption, a very frequent adverse reaction after the use of corticosteroids, was reported in 24 of the patients in this series, secondary to the use of dexamethasone and prednisone, adjunct to antineoplastic regimens.
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Funding sources: None.
Conflicts of interest: None identified.