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

## TL;DR

A patient with atopic dermatitis developed systemic sclerosis after using dupilumab, highlighting unexpected immune effects of the drug.

## Contribution

First reported case of systemic sclerosis emerging during dupilumab therapy, revealing a paradoxical immune response.

## Key findings

- A 37-year-old woman developed systemic sclerosis with interstitial lung disease after 2 years of dupilumab treatment.
- The patient met classification criteria for systemic sclerosis with a score of 10.
- Discontinuation of dupilumab and targeted therapy improved clinical symptoms.

## 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.

Dupilumab is widely used for atopic dermatitis and is believed to reduce fibrosis by blocking interleukin (IL)-4/IL-13. We present the first reported case of systemic sclerosis emerging during dupilumab therapy. A 37-year-old woman developed Raynaud’s phenomenon, digital puffiness and interstitial lung disease 2 years after treatment began. Diagnostic investigations confirmed systemic sclerosis with an American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 score of 10. This unexpected outcome highlights the complex immunologic effects of cytokine blockade and the need for vigilance regarding fibrotic symptoms in treated patients. The case raises important questions about immune shifts and paradoxical responses in targeted biologic therapies.