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Clinical features and treatment of epidermal growth factor inhibitor-related late-phase papulopustular rash
Mikiko Tohyama1, Makoto Hamada2, Daijiro Harada3
1Department of Dermatology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
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: methicillin-sensitive 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 ± 3.4 weeks. However, use of a combination of antibiotics and a topical corticosteroid prolonged the recovery period to an average of 18.9 ± 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.
Insights
Late-phase papulopustular rash during epidermal growth factor receptor inhibitor (EGFRi) treatment is often a staphylococcal infection. Prompt antibiotic treatment without corticosteroids improves outcomes, unlike combination therapy which delays healing.
Area of Science:
- Oncology
- Dermatology
- Infectious Diseases
Background:
- Papulopustular rash is a common side effect of epidermal growth factor receptor inhibitors (EGFRi).
- Late-phase rash, developing after four weeks of EGFRi treatment, is often associated with Staphylococcus aureus.
- Understanding the etiology and optimal management of late-phase rash is crucial for patient care.
Purpose of the Study:
- To assess the incidence of bacterial infection in patients with late-phase papulopustular rash.
- To evaluate treatment outcomes based on different therapeutic approaches.
- To determine the necessity of bacterial culture due to rising antibiotic resistance.
Main Methods:
- Retrospective analysis of 64 patients treated with EGFRi for over four weeks presenting with papulopustular rash.
- Bacterial cultures were performed on 51 patients.
- Treatment outcomes were compared between patients receiving antibiotics alone versus antibiotics with topical corticosteroids.
Main Results:
- Bacterial cultures were positive in 50 out of 51 cases, predominantly identifying Staphylococcus aureus (methicillin-sensitive and methicillin-resistant strains).
- Significant antibiotic resistance was observed, with 42% of S. aureus isolates resistant to minocycline and 40% to levofloxacin.
- Treatment with antibiotics alone led to rapid rash improvement (average 2.9 weeks), while combination therapy with topical corticosteroids prolonged recovery (average 18.9 weeks).
Conclusions:
- Late-phase papulopustular rash developing after four weeks of EGFRi treatment is typically a staphylococcal infection.
- Bacterial culture is essential due to high rates of antibiotic resistance.
- Differentiating early-phase from late-phase rash and avoiding topical corticosteroids in late-phase treatment are critical for effective management.
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