Unexpected systemic sclerosis in a patient with atopic dermatitis receiving dupilumab: a novel case report

Abstract Dupilumab, an interleukin (IL)-4 receptor alpha antagonist, is widely used in the treatment of atopic dermatitis and has shown potential benefit in certain fibrosing skin conditions. While blockade of IL-4 and IL-13 is generally considered to inhibit fibrosis, emerging reports of localized sclerosing dermatoses paradoxically arising during dupilumab therapy suggest a more complex immunological effect. We report a 37-year-old woman with the first case of systemic sclerosis developing in a patient with atopic dermatitis treated with dupilumab. After 2 years of treatment, she presented with new-onset dyspnoea, Raynaud phenomenon and digital puffiness. Serological tests revealed positive antinuclear and anticentromere antibodies; thoracic computed tomography showed interstitial lung disease. The modified Rodnan skin score was 4, and a skin biopsy from the fingertip demonstrated compact hyperkeratosis, irregular acanthosis and fibrosis extending to the superficial dermis. The patient met the American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 classification criteria for systemic sclerosis, with a total score of 10. Dupilumab was discontinued, and systemic treatments targeting vascular symptoms and pulmonary involvement were initiated, resulting in clinical improvement. This case highlights a significant potential paradoxical reaction associated with cytokine-targeted biologic therapy. It underscores the importance of monitoring for fibrotic and systemic symptoms even when using agents presumed to exert antifibrotic effects.