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Rethinking immunosuppression in limited cutaneous systemic sclerosis. The lcSSc conundrum; pros and cons for a timely

Veronica Batani1, Francesco Del Galdo2, Marco Matucci-Cerinic3

  • 1Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UniRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy; Leeds Raynaud's and Scleroderma Program, NIHR Biomedical Research Centre Leeds, Leeds, UK.

Autoimmunity Reviews
|June 29, 2026
PubMed

The use of immunosuppressants (IS) has dramatically changed the management of autoimmune diseases. In systemic sclerosis (SSc), randomized controlled trials and international recommendations support IS use in patients with rapidly progressive diffuse disease or interstitial lung disease (ILD). However, their role in the limited cutaneous systemic sclerosis (lcSSc) subset remains controversial. This article discusses arguments both in favor of and against the use of IS in lcSSc, integrating clinical evidence, pathophysiological insights, and registry data, while acknowledging the limitations inherent to observational findings. Overall, the available evidence suggests that reliance on skin subset classification alone may be insufficient to guide treatment decisions, and highlights the potential value of more refined, biology-informed approaches. However, further prospective validation is required before such strategies can be translated into clinical practice.