Clinical features and treatment of epidermal growth factor inhibitor‐related late‐phase papulopustular rash

Abstract

Papulopustular rash, an acneiform rash, appears on the seborrheic region during the first to second week of treatment with an epidermal growth factor receptor inhibitor (EGFRi). The rash gradually disappears after the fourth week; however, it persists or newly develops in other regions during EGFRi treatment. Because Staphylococcus aureus is frequently isolated from late-phase papulopustular rash, we assessed the incidence of bacterial infection and treatment outcomes of patients with late-phase papulopustular rash. Sixty-four cases treated with an EGFRi over 4 weeks who presented with papulopustular rash were assessed retrospectively. The median duration of EGFR inhibitor treatment was 5 months. Grade 2 and 3 papulopustular rash was observed in 47 and eight cases, respectively. Bacterial culture was performed in 51 cases, 50 of which yielded positive results: methicillinsensitive S. aureus in 29, methicillin-resistant S. aureus in 14, Staphylococcus species in five, Pseudomonas aeruginosa in three, and other in four cases. Of the S. aureus isolates, 42% were resistant to minocycline and 40% to levofloxacin. After treatment with topical and/or oral antibiotics without topical corticosteroids, the papulopustular rash rapidly improved by an average of 2.9 AE 3.4 weeks. However, use of a combination of antibiotics and a topical corticosteroid prolonged the recovery period to an average of 18.9 AE 11.4 weeks. In conclusion, folliculitis that develops over 4 weeks after the initiation of EGFRi treatment is typically caused by staphylococcal infection. Bacterial culture is necessary due to the high rate of antibiotic resistance. It is important to distinguish late-from early-phase papulopustular rash and to treat using different approaches.

Exploring the human hair follicle microbiome*

“…We also need to characterize the constitutive HF microbiome differences in immunocompromised individuals, and how immunosuppressive therapies such as glucocorticosteroids, anti-IL-17 agents, 162 ciclosporin A, 163 UVB irradiation 161 as well as folliculitis-inducing oncological therapy (e.g. with epidermal growth factor receptor inhibitors) 164,165 alter the human HF microbiome.…”

EGFR inhibitor-induced folliculitis decalvans: a case series and management guidelines

“…Cutaneous toxicity of EGFR inhibitors originates from the interfered processes of proper maturation and differentiation of keratinocytes, mostly in the seborrheic areas of the skin [ 1 , 12 , 13 ]. Furthermore, the chemoattractant activity of EGFR inhibitors causes neutrophil chemotaxis and leads to sterile folliculitis [ 4 , 12 ]. A subsequent bacterial superinfection often co-occurs as EGFR inhibitors impair the antimicrobial defense of the skin [ 12 , 13 ].…”

“…Furthermore, the chemoattractant activity of EGFR inhibitors causes neutrophil chemotaxis and leads to sterile folliculitis [4,12]. A subsequent bacterial superinfection often co-occurs as EGFR inhibitors impair the antimicrobial defense of the skin [12,13]. In patients previously treated with radiation therapy, EGFR inhibitor-induced acne-like rash was found to spare the previously irradiated body regions due to radiation-induced follicular loss [14][15][16].…”

Facial Papulopustular Eruption during the COVID-19 Pandemic in Patients Treated with EGFR Inhibitors

“…The PPR mainly affects the sebaceous areas on the body; it is mostly located on the face (>80%), trunk (>50%), scalp (<20%), and extremities (>20%) [ 27 ]. The pathogenetic mechanism underlying the papulopustular manifestation has been related to the inhibition of the EGFR of the epidermal keratinocytes resulting in apoptosis and release of inflammatory cytokines [ 28 , 29 ].…”