Multiple lenvatinib‐associated skin ulcers: A case report and literature review

A 73-year-old man with metastatic papillary thyroid carcinoma presented to our dermatology clinic with a 1-year history of multiple proximal lower extremity ulcerative lesions, accompanied by stinging pain. Owing to tumour progression, oral lenvatinib (14 mg/day) was initiated 22 months before admission to our clinic. Physical examination revealed five well-demarcated ulcerative lesions on the left buttock and both thighs, with violaceous indurated borders and yellowish sloughing (Figure 1). The largest ulcer measured 5 × 3 cm. Pus cultures were positive for Morganella morganii and negative for fungal and mycobacterial infections. Complete blood count and comprehensive metabolic panel were normal. Topical mupirocin (twice/day), topical epidermal growth factor ointment (twice/day) and oral cefadroxil (500 mg twice/day) were administered for 14 weeks, but the ulceration worsened. We suspected an adverse reaction to lenvatinib, the recently initiated medication. After 13 weeks of lenvatinib discontinuation, a significant improvement was observed with granulation tissue growth and reduced ulcer size (Figure 2). However, due to the metastatic pulmonary nodule growth, lenvatinib was reinitiated at a lower dose (10 mg/day), following which the skin ulcer on the left buttock reappeared. However, treatment was continued because the recurring ulcer was less severe. Lenvatinib, an antiangiogenic tyrosine kinase inhibitor, is administered as a long-term treatment for various cancers, requiring effective management of its adverse effects. While palmar–plantar erythrodysesthesia and stomatitis are well-known dermatological toxicities of lenvatinib,1 cutaneous ulcers have been rarely reported, as summarized in Table S1. Kitamura et al.2 first reported a skin ulcer in the right subclavicular area following lenvatinib treatment, leading to its discontinuation before flap-reconstructive surgery. Dohmen3 and Cha et al.4 reported lenvatinib-associated ulcers on the left thigh and perineum, which resolved after lenvatinib discontinuation. Samal et al.5 reported development of multiple ulcers on the groin and perineum following lenvatinib therapy, which improved after its cessation. Considering the existing reports and the current case, lenvatinib-induced ulcers tend to preferentially involve the proximal lower extremities and perineal area, regardless of the primary cancer site or type. The pathophysiology of lenvatinib-induced skin ulcers is not completely understood, but the inhibition of vascular endothelial growth factors and platelet-derived growth factor receptors is believed to impede tissue healing.5 Currently, no specific guidelines are available for managing lenvatinib-associated cutaneous toxicities. Previous reports recommend permanent medication cessation when ulceration occurs, because ulcerations may worsen after reinitiation.2-4 However, our patient resumed lenvatinib after the near-complete resolution of ulcers, and continued it for 2.5 years, after assessing its potential risks and benefits. Due to the enlarged metastatic lung nodule lenvatinib was readministered at a relatively low dose. In summary, while immediate cessation of lenvatinib is advisable when cutaneous ulcers develop, lenvatinib reinitiation may be feasible if closely monitored. The authors declare no potential conflicts of interest. The patient provided informed consent for the publication of this report and its accompanying images. Table S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.