Development of theragnostic approach to atopic dermatitis

Cutaneous T-cell lymphoma (CTCL), a cancer of white blood cells, can look like atopic dermatitis. This project from Larisa Geskin aims to develop and validate a screening test for patients with atopic dermatitis (AD) which will aid in identifying undiagnosed CTCL in these patients.

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are essential cytokines (i.e., signaling molecules released from cells to the environment in order to affect other cells), in the pathogenesis of AD. Targeting these cytokines with antibodies such as dupilumab or tralokinumab has proven to be highly effective for therapy of AD.

However, patients with AD may have an increased risk for lymphoma, especially CTCL. There are numerous reports of patients with AD who received dupilumab and later developed CTCL, lethal in some cases. Therefore, therapies targeting IL-4/IL-13 are currently contraindicated for patients with CTCL. However, differentiation between AD and CTCL is difficult because of similar manifestations in the skin and lack of specific markers (i.e., molecules that are uniquely present or expressed in a given condition) for these diseases.

In their preliminary studies Larisa and her team have screened the blood of patients with biopsy-confirmed CTCL and AD for 18 highly selected potential biomarkers using an efficient screening method. Of the 18 tested biomarkers, 9 demonstrated sensitivity and specificity potentially adequate to differentiate CTCL from benign dermatoses. These data serve as a proof of principle and justify further studies, as described in this proposed project, to test a broader set of biomarkers to find the most promising biomarker panel with the highest sensitivity and specificity to develop a simple, robust and inexpensive test, which may be widely accessible to all treating physicians before initiating therapy for AD.