Pemetrexed-Associated Eyelid Edema: Effective Treatment by Excision of Lymphedematous Eyelid Tissue

Pemetrexed is an antimetabolite agent that inhibits multiple folate-requiring enzymes and is used in the treatment of mesothelioma and non-small-cell lung cancer. One of its toxicities is isolated cutaneous swelling affecting the eyelids and/or orbit. The pathologic assessment or its management has not been addressed to date. Herein, the authors report a case of a 77-year-old woman treated with pemetrexed for non-small-cell lung adenocarcinoma who developed persistent, severe bilateral lower eyelid swelling for several months, despite compresses and oral diphenhydramine. Elective excision was performed with good results and no recurrence after 6 months' follow up. Histopathologically, the excised tissue showed changes typical of dermatochalasis with dissolution of collagen and elastic bundles and marked dilation of lymphatic vessels. The combination of pre-existing, localized lymphatic failure and capillary leakage secondary to pemetrexed therapy can explain the onset and worsening swelling with successive rounds of chemotherapy.