Introduction

The chemokine receptor type 4 (CCR4) is involved in both Sézary syndrome (SS) and atopic dermatitis (AD) pathophysiology. Mogamulizumab (Moga), an anti-CCR4 monoclonal antibody, is labeled for the treatment of SS. We describe a patient for whom Moga had a benefit in both SS and AD.

Observations

A 45-year-old female patient had an atopic history with asthma, rhinitis and severe AD since childhood. Her face, folds, palms and soles were predominantly involved. She had been successively treated with UVB phototherapy, ciclosporin and methotrexate, with partial response.
She was referred to our unit because of the rapid onset of erythroderma, ectropion and alopecia. Skin biopsy, peripheral blood lymphocyte immunophenotyping, and T-cell clonality were consistent with the diagnosis of stage IVB2 SS. Extracorporeal photopheresis and bexarotene were introduced, with a blood partial response but no skin efficacy. Dupilumab was also administered, resulting in an aggravation of the erythroderma.
Moga was then initiated. After 3 months, we observed a complete response in both skin and blood compartments (CD4+ T-cell population included 1% of CD7+CD26-CD158k+ atypical T cells, versus 68% before Moga, and CD4:CD8 ratio was 1:1 versus 15:1). Interestingly, her eczema of the large folds, wrists, palms and soles that had been present since childhood had also decreased. In addition, the IgE level had normalized (11 versus 8952 kIU/L). To date, neither SS nor AD has recurred under Moga with a 24-month follow-up.

Discussion

CCR4 plays a role in T-cell adhesion and skin homing. It is expressed by tumor cells in SS, but also in a normal physiological state by regulatory T cells (Treg) and Th2 cells. In SS, Moga inhibits tumor lymphocytes both directly and via Treg inhibition.
In AD, CCR4 is highly expressed by Th2 cells in the skin and blood. Its expression is higher than in a psoriasis plaque or in normal skin. Moreover, the level of circulating CCR4+ lymphocytes correlates with the severity of AD. However, the role of Tregs in AD remains to be clarified. Finally, targeting CCR4 has been shown to be effective in mouse xenograft models of AD. To our knowledge, there are no studies on Moga in AD nor any reported cases of AD treated with Moga in humans, but a phase I trial is ongoing in asthma.

Conclusion

Our patient's observation reinforces the hypothesis that CCR4 is an attractive therapeutic target in AD. Human studies are needed to evaluate the efficacy and safety of anti-CCR4 in AD.