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A man in his late 70s with stage IV adenocarcinoma of the lung presented with acute onset of redness, pain, and swelling of both lower limbs. The patient had received 4 cycles of chemotherapy with carboplatin, pemetrexed, and pembrolizumab for progressive disease and was currently in maintenance with pemetrexed-pembrolizumab. The edema appeared 5 days after the patient’s 8th cycle of chemotherapy and evolved into sclerotic plaques. Physical examination revealed ill-defined, erythematoedematous plaques symmetrically distributed along the shins, with areas of induration (Figure, A). The patient remained afebrile and systemically well. Results of laboratory tests showed no elevation of inflammatory markers (normal white blood cell count and C-reactive protein level), with kidney, liver, and heart functions within the normal ranges. Results of venous Doppler ultrasonography imaging of the patient’s legs did not show evidence of deep vein thrombosis. A biopsy specimen was obtained for histopathologic analysis (Figure, B and C).
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C. Pemetrexed-induced inflammatory and sclerotic edema
Histopathologic examination showed a normal-appearing epidermis with edema in papillary dermis and perivascular infiltration of lymphocytes. In reticular dermis, a marked thickening of collagen with activated fibroblasts was observed. No signs of eccrine squamous syringometaplasia (ESS) or neutrophilic eccrine hidradenitis were detected (Figure, B and C). The patient was treated with a 7-day course of oral prednisone and topical clobetasol and showed substantial clinical improvement, including the disappearance of the lesions with only residual hyperpigmentation. Based on the findings and treatment response, the diagnosis was grade 3 pemetrexed-induced inflammatory and sclerotic edema. Pemetrexed treatment was subsequently discontinued, and the patient continued with pembrolizumab treatment alone.
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Corresponding Author: Mar Ramírez-Lluch, MD, Department of Dermatology, Fundación Instituto Valenciano de Oncología, Calle Profesor Beltrán Báguena, 4 Valencia, 46009 Spain (email@example.com).
Published Online: July 28, 2021. doi:10.1001/jamadermatol.2021.2576
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
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