Management of Treatment Resistant EGFR Inhibitor-Induced Papulopustular Exanthema With Isotretinoin and Dapsone

Epidermal growth factor receptor inhibitors (EGFRi) commonly cause papulopustular exanthemas that may compromise the success of cancer therapy. While tetracyclines are first-line treatment, data on alternative systemic agents for refractory cases remain limited. This study compares the effectiveness and tolerability of isotretinoin and dapsone for managing tetracycline-resistant EGFRi-induced papulopustular eruptions in a tertiary dermatology service.

A retrospective review was conducted of patients with EGFRi-induced papulopustular eruptions treated with isotretinoin or dapsone between 2018 and 2024. Clinical data included demographics, malignancy type, EGFRi agent, eruption severity, prior therapies, Physician's Global Assessment, treatment outcomes, time to best response, adverse events, and EGFRi dose modification. Group comparisons used one-way ANOVA and chi-square/Fisher's exact tests.

Sixteen patients were identified (8 isotretinoin, 8 dapsone). Baseline severity was higher in the isotretinoin group. Time to best response was shorter with isotretinoin (mean 14.9 weeks) than dapsone (21.0 weeks). Complete resolution occurred in 62.5% of isotretinoin-treated patients and 50% of dapsone-treated patients. Both agents were well tolerated, with only mild mucocutaneous effects in the isotretinoin group and mild anemia in one dapsone patient. Survival at follow-up was higher among patients who continued EGFRi (with or without dose reduction) than among those who ceased treatment. No significant differences were observed between isotretinoin and dapsone in EGFRi dose modification patterns or overall response rates.

Both isotretinoin and dapsone are effective, well-tolerated options for managing tetracycline-resistant EGFRi-induced papulopustular eruptions. Isotretinoin showed a trend toward faster improvement, while ultimate response rates were similar. Maintaining EGFRi therapy, even at reduced doses, in conjunction with dermatology treatment was associated with superior dermatological outcomes and higher survival at follow-up compared with cessation of EGFRi treatment, highlighting the importance of proactive dermatologic intervention to support oncologic treatment continuity.