Systemic Sclerosis: From Vasculopathy to CAR-T—Where Are We Now?
At the 2026 Masterclasses in Dermatology Annual Meeting, Scott Elman, MD, FAAD, delivered a forward-looking update on systemic sclerosis (SSc), emphasizing its biologic complexity and rapidly expanding therapeutic pipeline. He described SSc as “a widespread, multisystem disease.” It is “characterized by vascular dysfunction and progressive fibrosis, with heterogeneous presentations” that challenge even experienced clinicians.
Dr Elman reviewed the heterogeneity of SSc phenotypes. Limited cutaneous SSc (lcSSc, formerly CREST) often presents with distal sclerosis and late pulmonary arterial hypertension, whereas diffuse cutaneous SSc (dcSSc) features rapid proximal skin thickening and early interstitial lung disease (ILD). Raynaud phenomenon is “virtually always present,” and absence of Raynaud or nailfold capillary changes should prompt reconsideration of the diagnosis.
Pulmonary involvement occurs in more than 80% of patients. Early recognition and stabilization of lung function are critical. Cyclophosphamide has randomized trial support, and mycophenolate mofetil remains a mainstay. Nintedanib and tocilizumab have expanded options for SSc-related ILD.
Renal involvement remains “dreaded.” Scleroderma renal crisis (SRC) occurs in 10% to 15% of patients, particularly early in dcSSc. Dr Elman cautioned against “steroids in systemic sclerosis” because prednisone doses >15 mg daily may precipitate SRC.
“The sooner we identify these patients and treat them, the better they do.” In terms of treatments, for cutaneous disease, methotrexate and mycophenolate mofetil remain core immunomodulatory therapies. Rituximab (RTX) has the strongest evidence among biologics for improving skin fibrosis. In the European Scleroderma Trials and Research group cohort, skin improvement measured by modified Rodnan Skin Score (mRSS) was more frequent with RTX (OR 2.79; P=.002), with no overall decline in forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide and higher steroid tapering rates. In a head-to-head randomized controlled trial in early dcSSc-ILD, RTX led to significant FVC improvement vs cyclophosphamide and fewer serious adverse events. “RTX demonstrates skin benefit, lung stabilization/improvement, and superior tolerability compared with cyclophosphamide,” Dr Elman emphasized.
Intravenous immunoglobulin may benefit refractory inflammatory phenotypes. JAK inhibitors, including tofacitinib, target interferon and profibrotic pathways; early trials show good tolerability and trends toward mRSS improvement.
The type I interferon pathway is emerging as a key therapeutic target, with ongoing evaluation of interferon blockade strategies. CAR-T therapy represents a frontier approach under active investigation, with early reports suggesting potential immune reset strategies in severe disease.
Despite progress, SSc carries the highest mortality among rheumatic diseases, with approximately 50% disease-attributable mortality. “Our treatment doesn’t work really very well. We still need more treatment options,” Dr Elman noted, underscoring the need for continued innovation. “This remains a huge unmet need; we need better treatments for systemic sclerosis, and I think we'll get there.”
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Reference
Elman S. Emerging treatments for systemic sclerosis. Presented at: Masterclasses in Dermatology; February 19–22, 2026; Sarasota, FL.
