Intravenous immunoglobulin significantly improves skin involvement and gastrointestinal manifestations in systemic sclerosis patientsIntravenous immunoglobulin shows promise for systemic sclerosis symptoms

BackgroundSystemic sclerosis (SSc) is a complex autoimmune disease mainly characterized by progressive fibrosis affecting the skin and internal organs. Although several immunosuppressive and targeted therapies are currently available, many patients continue to experience refractory manifestations. Intravenous immunoglobulin (IVIG) has been increasingly used as an adjunctive treatment in selected cases; however, its efficacy across different disease manifestations remains incompletely defined.ObjectiveTo systematically evaluate the efficacy and safety of IVIG in patients with systemic sclerosis and to quantitatively synthesize available evidence regarding its effects on skin involvement, gastrointestinal manifestations, and inflammatory myopathy.MethodsA systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. MEDLINE/PubMed, Embase, LILACS, and the Cochrane Library were searched from January 1966 to May 2026. Studies evaluating IVIG in adult patients with systemic sclerosis were included. Randomized controlled trials, observational cohorts, pilot studies, and case series were eligible. Quantitative synthesis was performed using random-effects models and standardized mean differences (SMDs) with 95% confidence intervals (CIs).ResultsEleven studies were included in the systematic review. Six studies provided sufficient quantitative data for the meta-analysis of skin involvement, three for gastrointestinal outcomes, and two for muscle outcomes. The most common indications for IVIG therapy were cutaneous fibrosis, inflammatory myopathy, gastrointestinal involvement, and refractory musculoskeletal manifestations. Meta-analysis demonstrated a significant improvement in skin involvement assessed by the modified Rodnan Skin Score (SMD −0.59, 95% CI −0.95 to −0.22; p = 0.0019; I2 = 78.0%). Gastrointestinal manifestations also improved significantly (SMD −0.73, 95% CI −1.16 to −0.29; p = 0.0012; I2 = 0%). For inflammatory myopathies, a limited quantitative synthesis of two studies showed a significant reduction in creatinekinase levels (SMD −0.53, 95% CI −0.80 to −0.26; p < 0.001). Across studies, IVIG was well tolerated, and serious adverse events were uncommon.ConclusionIVIG was associated with improvements in several clinical outcomes, particularly in observational studies, including skin fibrosis, gastrointestinal manifestations, and inflammatory myopathies. However, the only randomized placebo-controlled trial did not demonstrate significant short-term improvement in skin involvement at its primary endpoint. The available evidence suggests a potential adjunctive role for IVIG in selected patients.