P037 Peripheral blood flow cytometry reveals heterogeneous but benign T-cell changes in patients with severe eczema undergoing dupilumab therapy
Authors: Grantham Henry , Best Katie , Weatherhead Sophie 
Published: June 2024

Abstract
The interleukin-4/13 receptor antagonist dupilumab dramatically changed the landscape of eczema treatment following NICE approval in 2018, and many patients now achieve remission or significant symptomatic improvement without notable side-effects. This has led to a rapid uptake in use; our department has &gt; 300 patients with eczema currently taking dupilumab. However, cutaneous T-cell lymphoma (CTCL) can mimic eczema and may respond to conventional systemic therapies; an unproven relationship with dupilumab exists (Park A, Wong L, Lang A et al. Cutaneous T-cell lymphoma following dupilumab use: a systematic review. Int J Dermatol 2023; 62: 962–76). Between 2019 and 2022, five dupilumab-treated patients with ‘eczema’ at our centre were found to have CTCL: three Sézary syndrome (one now deceased) and two atypical CTCL. Whether they had pre-existing CTCL or dupilumab had altered their phenotype was unknown; two of our patients with Sézary syndrome had lifelong eczema. We therefore introduced peripheral blood flow cytometric evaluation as part of our routine dupilumab examinations and 4 months after starting treatment. Furthermore, any patient with atypical eczema received a biopsy prior to starting dupilumab. From June to December 2023, 55 patients (29 female) from our complex eczema clinic started dupilumab. The mean age was 41 years (range 19–90). In total, 62% had atopy, 62% had a family history of eczema and 76% had had eczema since childhood. At baseline, 29% had abnormal peripheral blood flows, but none had Sézary syndrome. Abnormal findings included elevated and reduced CD4 : CD8 ratios (7% and 5%, respectively). Two had clonal changes. So far, in patients with a normal flow completing 4 months of treatment, 50% had normal levels when retested. Abnormal repeat flows in this group included reversed or elevated CD4 : CD8 ratio and new non-Sézary clonal change. Of patients with an abnormal baseline flow, 75% remained static when retested on treatment. One patient’s abnormal clonal population had changed phenotype. Nine patients with atypical eczema had pre-dupilumab biopsies, but none showed features of CTCL. Of the five previously identified patients with CTCL on dupilumab, one responded well to dupilumab and four did not respond. The two patients without Sézary syndrome were both biopsied 1–2 years prior to starting dupilumab, with no suggestion of CTCL. We advocate further investigation including biopsy and flow cytometry in atypical cases prior to dupilumab initiation, as dupilumab can cause CTCL progression in later stages. Flow cytometry is not typically carried out on patients with inflammatory disease, and almost one-third of our patients had an abnormal flow. Prescribers must remain vigilant for unrecognized severe side-effects with new medications. It is reassuring that we have not identified any cases of CTCL from our baseline screening so far, but we cannot exclude the possibility of CTCL developing after starting dupilumab, and we are continuing to monitor these patients.