BI43 A high-risk squamous cell carcinoma developing in a patient with eczema treated with upadacitinib

Abstract

The treatment paradigm for atopic dermatitis has changed due to the advent of agents such as oral Janus kinase (JAK) inhibitors. However, there are limited long-term real-world safety data available for these medications. We present the case of a 45-year-old man with severe, refractory atopic dermatitis. He had previously not responded to one course of ultraviolet B phototherapy, methotrexate, ciclosporin and both dupilumab and tralokinumab. With a Dermatology Life Quality Index (DLQI) of 27.0 and an Eczema Area and Severity Index (EASI) of 27.1, he was commenced on upadacitinib 30 mg in October 2024. Within weeks, his eczema was much improved (EASI 9.5 and DLQI 5). Nine months later, he had developed a pink papule on the right nasal tip. He initially declined biopsy, and was subsequently seen again in September 2025. He now had a rapidly growing nodule on his nose, and biopsy confirmed a squamous cell carcinoma (SCC). Excisional biopsy demonstrated a poorly differentiated SCC 14 mm in diameter and 5 mm thick, with no perineural or lymphovascular invasion, and a 0.2-mm deep excision margin. Given the high-risk features and narrow deep excision margin, he was offered adjuvant radiotherapy. Due to patient concerns, his upadacitinib treatment was discontinued. There is a paucity of real-world data pertaining to the long-term side effects of JAK inhibitors in patients with atopic dermatitis, although current studies do not suggest any increased risk of nonmelanoma skin cancer. Our patient was at low risk for developing skin cancer. He was not a sun worshipper, never used a sunbed, worked as a teacher indoors, never lived in a sunny climate and had no evidence of actinic damage pretreatment. Despite his other immunosuppressant medications, it was only when he commenced upadacitinib that his aggressive, high-risk SCC developed. Although this could be coincidental, the rapid onset could suggest a tumour-promoting effect of the JAK inhibitor in certain susceptible older patients.