Diffuse cutaneous aphthosis refers to a rare side effect due to the combination of an EGFR inhibitor with a MEK inhibitor, with or without a BRAF inhibitor. It was reported in a case series in 2023. Patients present with multiple diffuse red-to-petechial macules and papules that ulcerate and become painful approximately 1 week after starting therapy. The ulcers may heal with atrophic centers resembling malignant atrophic papulosis with porcelain-white, round scars with a fibrinous base surrounded by an erythematous rim.

Similar cutaneous ulcerations have also been reported as a side effect of amivantamab (a bispecific EGFR–mesenchymal-epithelial transition [MET] antibody) and, rarely, from EGFR inhibitors when given without a MEK inhibitor as well. Similar ulcerations with an ecthyma-like appearance have been reported after therapy with amivantamab and osimertinib (EGFR inhibitor).