Staphylococcus Coagulase-Positive Skin Inflammation Associated with Epidermal Growth Factor Receptor-Targeted Therapy: An Early and a Late Phase of Papulopustular Eruptions

Abstract

Cutaneous eruptions, mainly papulopustular, are the most common associated side effects of epidermal growth factor receptor inhibitors (EGFRIs). This study investigated the possible role of bacterial infection in EGFRI-induced eruptions and its relation to clinical morphology. The study group consisted of all 29 patients referred for dermatologic evaluation of side effects of cetuximab or erlotinib from March 2008 to November 2009. Specimens were taken for bacterial culture from pustules in patients with grade >1 papulopustular rash and from periungual secretions in patients with paronychia. Twenty-four of 29 patients had a papulopustular reaction; five of 29 had paronychia/xerosis. Of the papulopustular eruption patients, time to rash appearance yielded two distinct groups: early-phase, median 8 days after drug initiation, located mainly on the face (n = 17) and late-phase, median ∼200 days after drug initiation, located mainly on the trunk (n = 7). Bacterial culture grew Staphylococcus aureus (SA) in seven of 13 early-phase patients tested and in all late-phase patients. Treatment consisted of topical steroids with or without topical/systemic antibiotics. All patients had a clear improvement in their cutaneous symptoms within a few days. Dose reduction or temporary discontinuation of the EGFRI was necessary in only four of 29 patients. As described in the literature, EGFRI-induced papulopustular eruption may appear early and probably is an inflammatory process with or without SA secondary infection. The papulopustular eruption may also appear as a late phase, described here for the first time, which is an infectious process with all patients being SA(+). The >50% overall incidence of SA infection in our study highlights the need for routine bacterial cultures from EGFRI-induced eruption.