This consists of follicular sterile selleck chem Brefeldin A pustules and papules usually involving the face, scalp, and upper trunk (Figures 1,,22,,3).3). Secondary infections are commonly observed, but must be confirmed by bacterial culture. Histopathology shows folliculitis with collections of neutrophils within the follicles and lymphocytes surrounding the follicles. It is essential to understand that this eruption resembles acne (hence the term
“acneiform”), but is actually not acne. This eruption lacks comedones and does not respond to topical retinoids, both of which are cornerstones of traditional acne vulgaris. The basic differential diagnosis for the acneiform eruption induced by EGFR Inhibitors,research,lifescience,medical inhibitors includes steroid induced acne and infectious folliculitis caused by bacteria or yeast. Positive correlations between the development of acneiform eruptions and clinical outcomes have been observed so it is important to treat through these reactions and
Inhibitors,research,lifescience,medical reserve discontinuation of medication as a last resort. Figure 1 Acneiform rash affecting the face during EGFR inhibitor treatment Figure 2 Acneiform rash affecting the back during EGFR inhibitor treatment Figure 3 Acneiform rash affecting the chest during EGFR inhibitor treatment Inhibitors,research,lifescience,medical The Common Terminology Criteria for Adverse Events established by the National Cancer Institute defines the severity of acneiform rash from grades Inhibitors,research,lifescience,medical one through five as shown in Table 1. Table 1 Common Terminology Criteria for Adverse Events-Acneiform rash Studies have been conducted to explore the pathogenesis of the acneiform eruption caused by EGFR inhibitors.
The EGF receptor is present in keratinocytes in the basal and suprabasal layers of the epidermis and the outer layers of hair follicles. Stimulation of the EGFR pathway promotes keratinocyte survival and proliferation. Han et al. found increased expression of cytokines such as interleukin-1 alpha, tumor necrosis factor-alpha, and interferon-gamma in acneiform lesions of patients when EGFR was inhibited by cetuximab. Inhibitors,research,lifescience,medical These increased cytokines may lead to inflammation in the dermis. This inflammation is characterized by neutrophilic inflammatory infiltrates GSK-3 followed by follicular proliferation and plugging that causes the papulopustular eruption. The mechanism is distinct from the etiology of acne vulgaris, where inflammation follows comedone formation. This explains why topical steroids are an effective treatment for the severe papulopustular eruption caused by cetuximab but may worsen acne vulgaris. Most patients receiving cetuximab or panitumumab (up to 90%) will develop the acneiform eruption within the first two weeks of therapy (2,3). Tol et al. reported a phase III study comparing toxicity of adding cetuximab to a combination treatment with capecitabine, oxaliplatin and bevacizumab (4). In the cohort not taking cetuximab only 7 of 197 experienced an acneiform skin rash.